View source for Hepatitis C

{{Short description|Human viral infection}}
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{{Infobox medical condition (new)
| name          = Hepatitis C
| image         = HCV EM picture 2.png
| caption       = [[Electron micrograph]] of [[hepatitis C virus]] from cell culture (scale = 50&nbsp;[[nanometers]])
| field         = [[Gastroenterology]], [[Infectious disease (medical specialty)|infectious disease]]
| symptoms      = Typically none<ref name=CDC2016 />
| complications = [[Liver failure]], [[hepatocellular carcinoma|liver cancer]], [[esophageal varices|esophageal]] and [[gastric varices]]<ref name=Sherris2004 />
| onset         = 
| duration      = Long term (80%)<ref name=CDC2016 />
| causes        = [[Hepatitis C virus]] usually spread by blood-to-blood contact<ref name=CDC2016 /><ref name=Mah2010/>
| risks         = 
| diagnosis     = Blood testing for [[antibodies]] or viral [[RNA]]<ref name=CDC2016 />
| differential  = 
| prevention    = Sterile needles, testing donated blood<ref name=whofactsheet/>
| treatment     = Medications, [[liver transplant]]<ref name=NEJM2011 />
| medication    = Antivirals ([[sofosbuvir]], [[simeprevir]], others)<ref name=CDC2016 /><ref name=whofactsheet/>
| prognosis     = 
| frequency     = 58 million (2019)<ref name=whofactsheet/>
| deaths        = 290,000 (2019)<ref name=whofactsheet/>
| alt           = 
}}

'''Hepatitis C''' is an [[infectious disease]] caused by the [[hepatitis C virus]] (HCV) that primarily affects the [[liver]];<ref name=Sherris2004>{{cite book | title = Sherris Medical Microbiology | url = https://archive.org/details/sherrismedicalmi00ryan | url-access = limited | edition = 4th | publisher = McGraw Hill | year = 2004 | pages=[https://archive.org/details/sherrismedicalmi00ryan/page/n568 551]–52 | isbn = 978-0-8385-8529-0 |veditors=Ryan KJ, Ray CG }}</ref> it is a type of [[viral hepatitis]].<ref>{{Cite web |title=Hepatitis MedlinePlus |url=https://medlineplus.gov/hepatitis.html |access-date=2020-06-19 |website=U.S. National Library of Medicine}}</ref> During the initial infection period, people often have mild or no symptoms.<ref name="CDC2016">{{cite web |title=Q&A for Health Professionals |url=https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm#section1 |website=Viral Hepatitis |publisher=Centers for Disease Control and Prevention |access-date=28 September 2020}}</ref> Early symptoms can include fever, dark urine, abdominal pain, and [[jaundice|yellow tinged skin]].<ref name=CDC2016 /> The virus persists in the liver, becoming [[Chronic condition|chronic]], in about 70% of those initially infected.<ref name=whofactsheet/> Early on, chronic infection typically has no symptoms.<ref name=CDC2016 /> Over many years however, it often leads to [[liver disease]] and occasionally [[cirrhosis]].<ref name=CDC2016 /> In some cases, those with cirrhosis will develop serious complications such as [[liver failure]], [[hepatocellular carcinoma|liver cancer]], or [[esophageal varices|dilated blood vessels in the esophagus]] and [[gastric varices|stomach]].<ref name=Sherris2004 />

HCV is spread primarily by blood-to-blood contact associated with [[injection drug use]], poorly sterilized medical equipment, [[needlestick injuries]] in healthcare, and [[blood transfusions|transfusions]].<ref name=CDC2016 /><ref name=Mah2010>{{cite journal | vauthors = Maheshwari A, Thuluvath PJ | title = Management of acute hepatitis C | journal = Clinics in Liver Disease | volume = 14 | issue = 1 | pages = 169–76; x | date = February 2010 | pmid = 20123448 | doi = 10.1016/j.cld.2009.11.007 }}</ref> In regions where blood screening has been implemented, the risk of contracting HCV from a transfusion has dropped substantially to less than one per two million.<ref name=CDC2016 /> HCV may also be spread from an infected mother to her baby during birth.<ref name=CDC2016 /> It is not spread through breast milk, food, water, or casual contact such as hugging, kissing, and sharing food or drinks with an infected person.<ref name=whofactsheet>{{cite web|date=24 June 2022|title=Hepatitis C Fact sheet|url=https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-c|url-status=live|archive-url=https://web.archive.org/web/20160131041006/http://www.who.int/mediacentre/factsheets/fs164/en/|archive-date=31 January 2016|website=WHO}} Updated as required.</ref> It is one of five known hepatitis viruses: [[hepatitis A|A]], [[hepatitis B|B]], C, [[hepatitis D|D]], and [[hepatitis E|E]].<ref>{{cite web|title=Viral Hepatitis: A through E and Beyond|url=http://www.niddk.nih.gov/health-information/health-topics/liver-disease/viral-hepatitis-a-through-e/Pages/facts.aspx|website=National Institute of Diabetes and Digestive and Kidney Diseases|access-date=4 February 2016|date=April 2012|url-status=dead|archive-url=https://web.archive.org/web/20160202083731/http://www.niddk.nih.gov/health-information/health-topics/liver-disease/viral-hepatitis-a-through-e/Pages/facts.aspx|archive-date=2 February 2016}}</ref>
Diagnosis is by blood testing to look for either [[antibodies]] to the virus or viral [[RNA]].<ref name=CDC2016 /> In the [[United States]], screening for HCV infection is recommended in all adults age 18 to 79 years old.<ref name=USPSTF />
There is no [[vaccine]] against hepatitis C.<ref name=CDC2016 /><ref name=Web2015>{{cite journal | vauthors = Webster DP, Klenerman P, Dusheiko GM | title = Hepatitis C | journal = Lancet | volume = 385 | issue = 9973 | pages = 1124–35 | date = March 2015 | pmid = 25687730 | pmc = 4878852 | doi = 10.1016/S0140-6736(14)62401-6 }}</ref> Prevention includes [[harm reduction]] efforts among people who inject drugs, testing donated blood, and treatment of people with chronic infection.<ref name=whofactsheet/><ref name="TA">{{cite journal | vauthors = Zelenev A, Li J, Mazhnaya A, Basu S, Altice FL | title = Hepatitis C virus treatment as prevention in an extended network of people who inject drugs in the USA: a modelling study | journal = The Lancet. Infectious Diseases | volume = 18 | issue = 2 | pages = 215–224 | date = February 2018 | pmid = 29153265 | pmc = 5860640 | doi = 10.1016/S1473-3099(17)30676-X }}</ref> Chronic infection can be cured more than 95% of the time with [[antiviral medications]] such as [[sofosbuvir]] or [[simeprevir]].<ref name=CDC2016 /><ref name=whofactsheet/> [[Peginterferon]] and [[ribavirin]] were earlier generation treatments that proved successful in <50% of cases and caused greater side effects.<ref name=whofactsheet/>{{rp|2015 version}}<ref name=Kim2016/> While access to the newer treatments was expensive,  by 2022 prices had dropped dramatically in many countries (primarily low-income and lower-middle-income countries) due to the introduction of generic versions of medicines.<ref name=whofactsheet/> Those who develop cirrhosis or liver cancer may require a [[liver transplant]].<ref name=NEJM2011 /> Hepatitis C is one of the leading reasons for liver transplantation. However, the virus usually recurs after transplantation.<ref name=NEJM2011>{{cite journal | vauthors = Rosen HR | title = Clinical practice. Chronic hepatitis C infection | journal = The New England Journal of Medicine | volume = 364 | issue = 25 | pages = 2429–38 | date = June 2011 | pmid = 21696309 | doi = 10.1056/NEJMcp1006613 | s2cid = 19755395 }}</ref>

An estimated 58 million people worldwide were infected with hepatitis C in 2019. Approximately 290,000 deaths from the virus, mainly from liver cancer and cirrhosis attributed to hepatitis C, also occurred in 2019.<ref name=":1">{{Cite web|title=Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021|url=https://www.who.int/publications-detail-redirect/9789240027077|access-date=2022-01-19|website=www.who.int|language=en}}</ref> The existence of hepatitis C – originally identifiable only as a type of non-[[Hepatitis A|A]] non-[[Hepatitis B|B]] [[hepatitis]] – was suggested in the 1970s and proven in 1989.<ref name="pmid19781804">{{cite journal | vauthors = Houghton M | title = The long and winding road leading to the identification of the hepatitis C virus | journal = Journal of Hepatology | volume = 51 | issue = 5 | pages = 939–48 | date = November 2009 | pmid = 19781804 | doi = 10.1016/j.jhep.2009.08.004 | url = http://www.journal-of-hepatology.eu/article/S0168-8278%2809%2900535-2/fulltext | doi-access = free }}</ref> Hepatitis C infects only humans and [[Common chimpanzee|chimpanzees]].<ref>{{cite book| vauthors = Shors T |title=Understanding viruses|publisher=Jones & Bartlett Learning|location=Burlington, MA|isbn=978-0-7637-8553-6|pages=535|url=https://books.google.com/books?id=Uk8xP5LRHr4C&pg=PA535|edition=2nd|year=2011|url-status=live|archive-url=https://web.archive.org/web/20160515225439/https://books.google.com/books?id=Uk8xP5LRHr4C&pg=PA535|archive-date=2016-05-15}}</ref>
[[File:En.Wikipedia-VideoWiki-Hepatitis C.webm|thumb|thumbtime=0:28|upright=1.3|Video summary ([[Wikipedia:VideoWiki/Hepatitis C|script]])]]

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== Signs and symptoms ==

=== Acute infection ===
[[Acute (medicine)|Acute]] symptoms develop in some 20% of those infected.<ref name=whofactsheet /><ref name=CDC2016/> When this occurs, it is generally 4–12 weeks following infection (but it may take from 2 weeks to 6 months for acute symptoms to appear).<ref name=CDC2016/><ref name=whofactsheet />

Symptoms are generally mild and vague, and may include fatigue, [[nausea]] and vomiting, fever, [[myalgia|muscle]] or [[Arthralgia|joint pains]], abdominal pain, [[Anorexia (symptom)|decreased appetite]] and weight loss, jaundice (occurs in ~25% of those infected), dark urine, and clay-coloured stools.<ref name=CDC2016/><ref name="Book2011p4">{{cite book|url=https://books.google.com/books?id=6G7mff5DnBQC&pg=PA4|title=Chronic Hepatitis C Virus Advances in Treatment, Promise for the Future|publisher=Springer Verlag|year=2011|isbn=978-1-4614-1191-8|page=14|archive-url=https://web.archive.org/web/20160617181023/https://books.google.com/books?id=6G7mff5DnBQC&pg=PA4|archive-date=2016-06-17|url-status=live}}</ref><ref name="AFP2010">{{cite journal | vauthors = Wilkins T, Malcolm JK, Raina D, Schade RR | title = Hepatitis C: diagnosis and treatment | journal = American Family Physician | volume = 81 | issue = 11 | pages = 1351–1357 | date = June 2010 | pmid = 20521755 | url = http://www.aafp.org/afp/2010/0601/p1351.pdf | url-status = live | archive-url = https://web.archive.org/web/20130521071850/http://www.aafp.org/afp/2010/0601/p1351.pdf | archive-date = 2013-05-21 }}</ref> Acute liver failure due to acute hepatitis C is exceedingly rare.<ref name="Rao2022">{{cite journal | vauthors = Rao A, Rule JA, Cerro-Chiang G, Stravitz RT, McGuire BM, Lee G, Fontana RJ, Lee WM | display-authors = 6 | title = Role of Hepatitis C Infection in Acute Liver Injury/Acute Liver Failure in North America | journal = Digestive Diseases and Sciences | volume = 68 | issue = 1 | pages = 304–311 | date = January 2023 | pmid = 35546205 | pmc = 9094131 | doi = 10.1007/s10620-022-07524-6 }}</ref> Symptoms and laboratory findings suggestive of liver disease should prompt further tests and can thus help establish a diagnosis of hepatitis C infection early on.<ref name=AFP2010/>

Following the acute phase, the infection may resolve spontaneously in 10–50% of affected people; this occurs more frequently in young people and females.<ref name="Book2011p4" />

=== Chronic infection ===
About 70% of those exposed to the virus develop a chronic infection.<ref name=whofactsheet/> This is defined as the presence of detectable viral replication for at least six months. Though most experience minimal or no symptoms during the initial few decades of a chronic infection,<ref name=Book2011 /> chronic {{nowrap|hepatitis C}} can be associated with fatigue<ref name=ID2010 /> and mild cognitive problems.<ref>{{cite journal | vauthors = Forton DM, Allsop JM, Cox IJ, Hamilton G, Wesnes K, Thomas HC, Taylor-Robinson SD | title = A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection | journal = AIDS | volume = 19 | issue = Suppl 3 | pages = S53-63 | date = October 2005 | pmid = 16251829 | doi = 10.1097/01.aids.0000192071.72948.77 | doi-access = free }}</ref> After several years, chronic infection may cause [[cirrhosis]] or [[liver cancer]].<ref name=NEJM2011 /> The liver enzymes measured from blood samples are normal in 7–53%.<ref name=Nicot2011 /> (Elevated levels indicate the virus or other disease is damaging liver cells). Late relapses after apparent cure have been reported, but these can be difficult to distinguish from reinfection.<ref name=Nicot2011 />

[[Steatohepatitis|Fatty changes to the liver]] occur in about half of those infected and are usually present before cirrhosis develops.<ref name="El-Zayadi2008" /><ref>{{cite journal | vauthors = Paradis V, Bedossa P | title = Definition and natural history of metabolic steatosis: histology and cellular aspects | journal = Diabetes & Metabolism | volume = 34 | issue = 6 Pt 2 | pages = 638–42 | date = December 2008 | pmid = 19195624 | doi = 10.1016/S1262-3636(08)74598-1 }}</ref> Usually (80% of the time) this change affects less than a third of the liver.<ref name="El-Zayadi2008">{{cite journal | vauthors = El-Zayadi AR | title = Hepatic steatosis: a benign disease or a silent killer | journal = World Journal of Gastroenterology | volume = 14 | issue = 26 | pages = 4120–6 | date = July 2008 | pmid = 18636654 | pmc = 2725370 | doi = 10.3748/wjg.14.4120 | doi-access = free }}</ref> Worldwide hepatitis C is the cause of 27% of cirrhosis cases and 25% of hepatocellular carcinoma.<ref name=World2007>{{cite journal | vauthors = Alter MJ | title = Epidemiology of hepatitis C virus infection | journal = World Journal of Gastroenterology | volume = 13 | issue = 17 | pages = 2436–41 | date = May 2007 | pmid = 17552026 | pmc = 4146761 | doi = 10.3748/wjg.v13.i17.2436 | doi-broken-date = 2024-11-14 | doi-access = free }}</ref> About 10–30% of those infected develop cirrhosis over 30 years.<ref name=NEJM2011 /><ref name=AFP2010 /> Cirrhosis is more common in those also infected with [[hepatitis B]], [[schistosoma]], or HIV, in [[alcoholic]]s, and in those of male sex.<ref name=AFP2010 /> In those with hepatitis C, excess alcohol increases the risk of developing cirrhosis 5-fold.<ref>{{cite journal | vauthors = Mueller S, Millonig G, Seitz HK | title = Alcoholic liver disease and hepatitis C: a frequently underestimated combination | journal = World Journal of Gastroenterology | volume = 15 | issue = 28 | pages = 3462–71 | date = July 2009 | pmid = 19630099 | pmc = 2715970 | doi = 10.3748/wjg.15.3462 | doi-access = free }}</ref> Those who develop cirrhosis have a 20-fold greater risk of [[hepatocellular carcinoma]]. This transformation occurs at a rate of 1–3% per year.<ref name=NEJM2011 /><ref name=AFP2010 /> Being infected with hepatitis B in addition to hepatitis C increases this risk further.<ref>{{cite journal | vauthors = Fattovich G, Stroffolini T, Zagni I, Donato F | title = Hepatocellular carcinoma in cirrhosis: incidence and risk factors | journal = Gastroenterology | volume = 127 | issue = 5 Suppl 1 | pages = S35-50 | date = November 2004 | pmid = 15508101 | doi = 10.1053/j.gastro.2004.09.014 | doi-access = free }}</ref>

Liver cirrhosis may lead to [[portal hypertension]], [[ascites]] (accumulation of fluid in the abdomen), [[coagulopathy|easy bruising or bleeding]], varices (enlarged veins, especially in the stomach and esophagus), [[jaundice]], and a syndrome of cognitive impairment known as [[hepatic encephalopathy]].<ref name=Tah2009 /> Ascites occurs at some stage in more than half of those who have a chronic infection.<ref name=Zaltron2012>{{cite journal | vauthors = Zaltron S, Spinetti A, Biasi L, Baiguera C, Castelli F | title = Chronic HCV infection: epidemiological and clinical relevance | journal = BMC Infectious Diseases | volume = 12 | pages = S2 | year = 2012 | issue = Suppl 2 | pmid = 23173556 | pmc = 3495628 | doi = 10.1186/1471-2334-12-S2-S2 | doi-access = free }}</ref>

=== Extrahepatic complications ===
The most common problem due to {{nowrap|hepatitis C}} but not involving the liver is mixed [[cryoglobulinemia]] (usually the type II form) – an [[vasculitis|inflammation of small and medium-sized blood vessels]].<ref name=Cryo2013>{{cite journal | vauthors = Dammacco F, Sansonno D | title = Therapy for hepatitis C virus-related cryoglobulinemic vasculitis | journal = The New England Journal of Medicine | volume = 369 | issue = 11 | pages = 1035–45 | date = September 2013 | pmid = 24024840 | doi = 10.1056/NEJMra1208642 | s2cid = 205116488 }}</ref><ref>{{cite journal | vauthors = Iannuzzella F, Vaglio A, Garini G | title = Management of hepatitis C virus-related mixed cryoglobulinemia | journal = The American Journal of Medicine | volume = 123 | issue = 5 | pages = 400–8 | date = May 2010 | pmid = 20399313 | doi = 10.1016/j.amjmed.2009.09.038 }}</ref> {{nowrap|Hepatitis C}} is also associated with autoimmune disorders such as [[Sjögren's syndrome]], [[lichen planus]], [[thrombocytopenia|a low platelet count]], [[porphyria cutanea tarda]], [[necrolytic acral erythema]], [[insulin resistance]], [[diabetes mellitus]], [[diabetic nephropathy]], autoimmune [[thyroiditis]], and B-cell [[lymphoproliferative disorder]]s.<ref name=Extrahepatic>{{cite journal | vauthors = Zignego AL, Ferri C, Pileri SA, Caini P, Bianchi FB | title = Extrahepatic manifestations of Hepatitis C Virus infection: a general overview and guidelines for a clinical approach | journal = Digestive and Liver Disease | volume = 39 | issue = 1 | pages = 2–17 | date = January 2007 | pmid = 16884964 | doi = 10.1016/j.dld.2006.06.008 }}</ref><ref name=Ko2012>{{cite journal | vauthors = Ko HM, Hernandez-Prera JC, Zhu H, Dikman SH, Sidhu HK, Ward SC, Thung SN | title = Morphologic features of extrahepatic manifestations of hepatitis C virus infection | journal = Clinical & Developmental Immunology | volume = 2012 | pages = 740138 | year = 2012 | pmid = 22919404 | pmc = 3420144 | doi = 10.1155/2012/740138 | doi-access = free }}</ref> 20–30% of people infected have [[rheumatoid factor]] – a type of antibody.<ref name=Dammacco2000>{{cite journal | vauthors = Dammacco F, Sansonno D, Piccoli C, Racanelli V, D'Amore FP, Lauletta G | title = The lymphoid system in hepatitis C virus infection: autoimmunity, mixed cryoglobulinemia, and Overt B-cell malignancy | journal = Seminars in Liver Disease | volume = 20 | issue = 2 | pages = 143–57 | year = 2000 | pmid = 10946420 | doi = 10.1055/s-2000-9613 | s2cid = 260318352 }}</ref> Possible associations include [[prurigo nodularis|Hyde's prurigo nodularis]]<ref>{{cite journal | vauthors = Lee MR, Shumack S | title = Prurigo nodularis: a review | journal = The Australasian Journal of Dermatology | volume = 46 | issue = 4 | pages = 211–18; quiz 219–20 | date = November 2005 | pmid = 16197418 | doi = 10.1111/j.1440-0960.2005.00187.x | s2cid = 30087432 }}</ref> and [[membranoproliferative glomerulonephritis]].<ref name=ID2010 /> [[Cardiomyopathy]] with associated [[Heart arrhythmia|abnormal heart rhythms]] has also been reported.<ref name=Matsumori2006>{{cite book| vauthors = Matsumori A | chapter = Role of hepatitis C virus in cardiomyopathies.| title = Ernst Schering Research Foundation Workshop|volume=55|year=2006|issue=55|pages=99–120|pmid=16329660|doi=10.1007/3-540-30822-9_7|isbn=978-3-540-23971-0}}</ref> A variety of central and peripheral nervous system disorders has been reported.<ref>{{cite journal | vauthors = Moretti R, Giuffrè M, Merli N, Caruso P, Di Bella S, Tiribelli C, Crocè LS | title = Hepatitis C Virus-Related Central and Peripheral Nervous System Disorders | journal = Brain Sciences | volume = 11 | issue = 12 | pages = 1569 | date = November 2021 | pmid = 34942871 | pmc = 8699483 | doi = 10.3390/brainsci11121569 | doi-access = free }}</ref><ref name=Monaco2012>{{cite journal | vauthors = Monaco S, Ferrari S, Gajofatto A, Zanusso G, Mariotto S | title = HCV-related nervous system disorders | journal = Clinical & Developmental Immunology | volume = 2012 | pages = 236148 | year = 2012 | pmid = 22899946 | pmc = 3414089 | doi = 10.1155/2012/236148 | doi-access = free }}</ref> Chronic infection seems to be associated with an increased risk of [[pancreatic cancer]].<ref name=Web2015 /><ref name=Xu2013>{{cite journal | vauthors = Xu JH, Fu JJ, Wang XL, Zhu JY, Ye XH, Chen SD | title = Hepatitis B or C viral infection and risk of pancreatic cancer: a meta-analysis of observational studies | journal = World Journal of Gastroenterology | volume = 19 | issue = 26 | pages = 4234–41 | date = July 2013 | pmid = 23864789 | pmc = 3710428 | doi = 10.3748/wjg.v19.i26.4234 | doi-access = free }}</ref> People may experience other issues in the mouth such as [[xerostomia|dryness]], [[sialadenitis|salivary duct stones]], and crusted lesions around the mouth.<ref>{{cite journal | vauthors = Lodi G, Porter SR, Scully C | title = Hepatitis C virus infection: Review and implications for the dentist | journal = Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics | volume = 86 | issue = 1 | pages = 8–22 | date = July 1998 | pmid = 9690239 | doi = 10.1016/S1079-2104(98)90143-3 | citeseerx = 10.1.1.852.7880 }}</ref><ref>{{cite journal | vauthors = Carrozzo M, Gandolfo S | title = Oral diseases possibly associated with hepatitis C virus | journal = Critical Reviews in Oral Biology and Medicine | volume = 14 | issue = 2 | pages = 115–27 | date = 2003-03-01 | pmid = 12764074 | doi = 10.1177/154411130301400205 | doi-access =  }}</ref><ref>{{Cite book|title=Dental Management of the Medically Compromised Patient|url=https://archive.org/details/littlefalacesden00msja_927|url-access=limited|year=2013|isbn=978-0323080286|page=[https://archive.org/details/littlefalacesden00msja_927/page/n267 151]| vauthors = Little JW, Falace DA, Miller C, Rhodus NL|publisher=Elsevier Science Health Science Division }}</ref>

=== Occult infection ===
Persons who have been infected with hepatitis C may appear to clear the virus but remain infected.<ref name=Sugden2012>{{cite journal | vauthors = Sugden PB, Cameron B, Bull R, White PA, Lloyd AR | title = Occult infection with hepatitis C virus: friend or foe? | journal = Immunology and Cell Biology | volume = 90 | issue = 8 | pages = 763–73 | date = September 2012 | pmid = 22546735 | doi = 10.1038/icb.2012.20 | s2cid = 23845868 }}</ref> The virus is not detectable with conventional testing but can be found with ultra-sensitive tests.<ref name="Carreño2006">{{cite journal | vauthors = Carreño V | title = Occult hepatitis C virus infection: a new form of hepatitis C | journal = World Journal of Gastroenterology | volume = 12 | issue = 43 | pages = 6922–5 | date = November 2006 | pmid = 17109511 | pmc = 4087333 | doi = 10.3748/wjg.12.6922 | doi-access = free }}</ref> The original method of detection was by demonstrating the viral [[genome]] within liver biopsies. Still, newer methods include an antibody test for the virus' core protein and the detection of the viral genome after first concentrating the viral particles by [[ultracentrifugation]].<ref name="CarreñoGarcía2011">{{cite journal | vauthors = Carreño García V, Nebreda JB, Aguilar IC, Quiroga Estévez JA | title = [Occult hepatitis C virus infection] | journal = Enfermedades Infecciosas y Microbiologia Clinica | volume = 29 | pages = 14–9 | date = March 2011 | issue = Suppl 3 | pmid = 21458706 | doi = 10.1016/S0213-005X(11)70022-2 }}</ref> A form of infection with persistently moderately elevated serum liver enzymes but without antibodies to hepatitis C has also been reported.<ref name=Pham2010>{{cite journal | vauthors = Pham TN, Coffin CS, Michalak TI | title = Occult hepatitis C virus infection: what does it mean? | journal = Liver International | volume = 30 | issue = 4 | pages = 502–11 | date = April 2010 | pmid = 20070513 | doi = 10.1111/j.1478-3231.2009.02193.x | s2cid = 205651069 }}</ref> This form is known as cryptogenic occult infection.

Several clinical pictures have been associated with this type of infection.<ref name="Carreño2012">{{cite journal | vauthors = Carreño V, Bartolomé J, Castillo I, Quiroga JA | title = New perspectives in occult hepatitis C virus infection | journal = World Journal of Gastroenterology | volume = 18 | issue = 23 | pages = 2887–94 | date = June 2012 | pmid = 22736911 | pmc = 3380315 | doi = 10.3748/wjg.v18.i23.2887 | doi-access = free }}</ref> It may be found in people with anti-hepatitis-C antibodies but with normal serum levels of liver enzymes; in antibody-negative people with ongoing elevated liver enzymes of unknown cause; in healthy populations without evidence of liver disease; and in groups at risk for HCV infection including those on hemodialysis or family members of people with occult HCV. The clinical relevance of this form of infection is under investigation.<ref name="Carreño2008">{{cite journal | vauthors = Carreño V, Bartolomé J, Castillo I, Quiroga JA | title = Occult hepatitis B virus and hepatitis C virus infections | journal = Reviews in Medical Virology | volume = 18 | issue = 3 | pages = 139–57 | date = May–June 2008 | pmid = 18265423 | doi = 10.1002/rmv.569 | s2cid = 12331754 }}</ref> The consequences of occult infection appear to be less severe than with chronic infection but can vary from minimal to hepatocellular carcinoma.<ref name="CarreñoGarcía2011" />

The rate of occult infection in those apparently cured is controversial but appears to be low.<ref name=Nicot2011>{{cite book| vauthors = Nicot F |title=Occult hepatitis C virus infection: Where are we now?|year=2004|isbn=978-953-307-883-0|chapter=Chapter 19. Liver biopsy in modern medicine.|publisher=BoD – Books on Demand }}</ref> 40% of those with hepatitis but with both negative hepatitis C serology and the absence of detectable viral genome in the serum have hepatitis C virus in the liver on biopsy.<ref name=Scott2007>{{cite journal | vauthors = Scott JD, Gretch DR | title = Molecular diagnostics of hepatitis C virus infection: a systematic review | journal = JAMA | volume = 297 | issue = 7 | pages = 724–732 | date = February 2007 | pmid = 17312292 | doi = 10.1001/jama.297.7.724 | doi-access =  }}</ref> How commonly this occurs in children is unknown.<ref name=Robinson2008>{{cite journal | title = Vertical transmission of the hepatitis C virus: Current knowledge and issues | journal = Paediatrics & Child Health | volume = 13 | issue = 6 | pages = 529–541 | date = July 2008 | pmid = 19436425 | pmc = 2532905 | doi = 10.1093/pch/13.6.529 | last1 = Robinson | first1 = JL }}</ref>

== Virology ==
{{Main|Hepatitis C virus}}

The [[hepatitis C virus]] (HCV) is a small, enveloped, single-stranded, positive-sense [[RNA virus]].<ref name=NEJM2011 /> It is a member of the genus ''[[Hepacivirus]]'' in the family ''[[Flaviviridae]]''.<ref name=ID2010>{{cite book | vauthors = Ray SC, Thomas DL | veditors = Mandell GL, Bennett, Dolin R |title=Mandell, Douglas, and Bennett's principles and practice of infectious diseases|year=2009|publisher=Churchill Livingstone |location=Philadelphia, PA|isbn=978-0-443-06839-3|chapter=Chapter 154: Hepatitis C |edition=7th}}</ref> There are seven major genotypes of HCV, which are known as genotypes one to seven.<ref name=Nakano2011>{{cite journal | vauthors = Nakano T, Lau GM, Lau GM, Sugiyama M, Mizokami M | title = An updated analysis of hepatitis C virus genotypes and subtypes based on the complete coding region | journal = Liver International | volume = 32 | issue = 2 | pages = 339–45 | date = February 2012 | pmid = 22142261 | doi = 10.1111/j.1478-3231.2011.02684.x | s2cid = 23271017 }}</ref> The genotypes are divided into several subtypes with the number of subtypes depending on the genotype. In the United States, about 70% of cases are caused by genotype 1, 20% by genotype 2, and about 1% by each of the other genotypes.<ref name=AFP2010 /> Genotype 1 is also the most common in South America and Europe.<ref name=NEJM2011 />

The half-life of the virus particles in the serum is around 3 hours and may be as short as 45 minutes.<ref name=Lerat2004 /><ref>{{cite book| vauthors = Pockros P |title=Novel and Combination Therapies for Hepatitis C Virus, An Issue of Clinics in Liver Disease|year=2011|isbn=978-1-4557-7198-1|page=47|publisher=Elsevier Health Sciences |url=https://books.google.com/books?id=Gm6aXv8A8cUC&pg=PT47|url-status=live|archive-url=https://web.archive.org/web/20160521235637/https://books.google.com/books?id=Gm6aXv8A8cUC&pg=PT47|archive-date=2016-05-21}}</ref> In an infected person, about 10<sup>12</sup> virus particles are produced each day.<ref name=Lerat2004>{{cite journal | vauthors = Lerat H, Hollinger FB | title = Hepatitis C virus (HCV) occult infection or occult HCV RNA detection? | journal = The Journal of Infectious Diseases | volume = 189 | issue = 1 | pages = 3–6 | date = January 2004 | pmid = 14702146 | doi = 10.1086/380203 | doi-access = free }}</ref> In addition to replicating in the liver the virus can multiply in lymphocytes.<ref name=Zignego2012>{{cite journal | vauthors = Zignego AL, Giannini C, Gragnani L, Piluso A, Fognani E | title = Hepatitis C virus infection in the immunocompromised host: a complex scenario with variable clinical impact | journal = Journal of Translational Medicine | volume = 10 | issue = 1 | pages = 158 | date = August 2012 | pmid = 22863056 | pmc = 3441205 | doi = 10.1186/1479-5876-10-158 | doi-access = free }}</ref>

== Transmission ==
[[File:Hepatitis C infection by source (CDC) - en.svg|thumb|upright=1.4|Hepatitis C infection in the United States by source]]

[[Percutaneous]] contact with contaminated blood is responsible for most infections; however, the method of transmission is strongly dependent on both geographic region and economic status.<ref>{{cite journal | vauthors = Hagan LM, Schinazi RF | title = Best strategies for global HCV eradication | journal = Liver International | volume = 33 | issue = s1 | pages = 68–79 | date = February 2013 | pmid = 23286849 | pmc = 4110680 | doi = 10.1111/liv.12063 | url = }}</ref> Indeed, the primary route of transmission in the [[developed world]] is [[injection drug use]], while in the [[developing world]] the main methods are [[blood transfusions]] and unsafe medical procedures.<ref name=Mah2010 /> The cause of transmission remains unknown in 20% of cases;<ref name=Pon2011>{{cite journal | vauthors = Pondé RA | title = Hidden hazards of HCV transmission | journal = Medical Microbiology and Immunology | volume = 200 | issue = 1 | pages = 7–11 | date = February 2011 | pmid = 20461405 | doi = 10.1007/s00430-010-0159-9 | s2cid = 664199 }}</ref> however, many of these are believed to be accounted for by injection drug use.<ref name=Book2011p4 />

=== Body modification ===
[[Tattooing]] is associated with two- to threefold increased risk of {{nowrap|hepatitis C}}.<ref name=Tato2010>{{cite journal | vauthors = Jafari S, Copes R, Baharlou S, Etminan M, Buxton J | title = Tattooing and the risk of transmission of hepatitis C: a systematic review and meta-analysis | journal = International Journal of Infectious Diseases | volume = 14 | issue = 11 | pages = e928-40 | date = November 2010 | pmid = 20678951 | doi = 10.1016/j.ijid.2010.03.019 | doi-access = free }}</ref> This could be due to improperly sterilized equipment or contamination of the dyes used.<ref name=Tato2010 /> Tattoos or [[Body piercing|piercings]] performed either before the mid-1980s, "underground", or nonprofessionally are of particular concern, since sterile techniques in such settings may be lacking. The risk also appears to be greater for larger tattoos.<ref name=Tato2010 /> It is estimated that nearly half of prison inmates share unsterilized tattooing equipment.<ref name=Tato2010 /> It is rare for tattoos in a licensed facility to be directly associated with HCV infection.<ref>{{cite web|title=Hepatitis C|url=https://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf|publisher=Centers for Disease Control and Prevention (CDC)|access-date=2 January 2012|url-status=live|archive-url=https://web.archive.org/web/20120105131937/http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf|archive-date=5 January 2012}}</ref>

=== Drug use ===
[[File:Cocaine lines 2.jpg|thumb|left|Lines of cocaine prepared for snorting. [[Contaminated currency]] such as banknotes might serve as a [[fomite]] of diseases like hepatitis C<ref name="LV">{{cite web |url=http://cocaine.org/cokemoney/banknotes.html |title='Shared banknote' health warning to cocaine users |accessdate=2008-07-26 |author=Laureen Veevers |date=1 October 2006 |work=The Observer }}</ref>]]
{{see also|Needle sharing}}

[[Injection drug use]] (IDU) is a major risk factor for {{nowrap|hepatitis C}} in many parts of the world.<ref name=China2008>{{cite journal | vauthors = Xia X, Luo J, Bai J, Yu R | title = Epidemiology of hepatitis C virus infection among injection drug users in China: systematic review and meta-analysis | journal = Public Health | volume = 122 | issue = 10 | pages = 990–1003 | date = October 2008 | pmid = 18486955 | doi = 10.1016/j.puhe.2008.01.014 }}</ref> Of 77 countries reviewed, 25 (including the United States) were found to have a prevalence of {{nowrap|hepatitis C}} of 60–80% among people who use injection drugs.<ref name=Lancet2011>{{cite journal | vauthors = Nelson PK, Mathers BM, Cowie B, Hagan H, Des Jarlais D, Horyniak D, Degenhardt L | title = Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews | journal = Lancet | volume = 378 | issue = 9791 | pages = 571–83 | date = August 2011 | pmid = 21802134 | pmc = 3285467 | doi = 10.1016/S0140-6736(11)61097-0 }}</ref><ref name=China2008 /> Twelve countries had rates greater than 80%.<ref name=Lancet2011 /> It is believed that ten million people who use intravenous drug are infected with {{nowrap|hepatitis C}}; China (1.6 million), the United States (1.5 million), and Russia (1.3 million) have the highest absolute totals.<ref name=Lancet2011 /> [[Infectious diseases within American prisons#Hepatitis C|Occurrence of {{nowrap|hepatitis C}} among prison inmates in the United States]] is 10 to 20 times that of the occurrence observed in the general population; this has been attributed to high-risk behavior in prisons such as IDU and tattooing with non-sterile equipment.<ref name=Jail2010>{{cite journal | vauthors = Imperial JC | title = Chronic hepatitis C in the state prison system: insights into the problems and possible solutions | journal = Expert Review of Gastroenterology & Hepatology | volume = 4 | issue = 3 | pages = 355–64 | date = June 2010 | pmid = 20528122 | doi = 10.1586/egh.10.26 | s2cid = 7931472 }}</ref><ref>{{cite journal | vauthors = Vescio MF, Longo B, Babudieri S, Starnini G, Carbonara S, Rezza G, Monarca R | title = Correlates of hepatitis C virus seropositivity in prison inmates: a meta-analysis | journal = Journal of Epidemiology and Community Health | volume = 62 | issue = 4 | pages = 305–13 | date = April 2008 | pmid = 18339822 | doi = 10.1136/jech.2006.051599 | s2cid = 206989111 }}</ref> Shared intranasal drug use may also be a risk factor.<ref name="Moyer2013"/>

=== Fomites ===
A [[fomite]] ({{IPAc-en|ˈ|f|oʊ|m|aɪ|t}}) or fomes ({{IPAc-en|ˈ|f|oʊ|m|iː|z}}) is any [[inanimate object]] that, when contaminated with or exposed to [[infectious agents]] (such as [[pathogenic bacteria]], [[viruses]] or [[fungi]]), can transfer [[disease]] to a new [[host (biology)|host]].<ref name=Cramer2019>{{Cite web |url=http://microblogology.com/fomites-fomites-fomites/ |title=Fomites, fomites, fomites! |work=Microblogology |last=Cramer |first=Lorraine |date=1 September 2011 |language=en-US |access-date=8 March 2019 |archive-date=23 September 2020 |archive-url=https://web.archive.org/web/20200923101811/http://microblogology.com/fomites-fomites-fomites/ |url-status=dead }}</ref>

Personal-care items such as razors, toothbrushes, and manicuring or pedicuring equipment can be contaminated with blood. Sharing such items can potentially lead to exposure to HCV.<ref name="pmid16907842">{{cite journal | vauthors = Lock G, Dirscherl M, Obermeier F, Gelbmann CM, Hellerbrand C, Knöll A, Schölmerich J, Jilg W | display-authors = 6 | title = Hepatitis C - contamination of toothbrushes: myth or reality? | journal = Journal of Viral Hepatitis | volume = 13 | issue = 9 | pages = 571–3 | date = September 2006 | pmid = 16907842 | doi = 10.1111/j.1365-2893.2006.00735.x | s2cid = 24264376 }}</ref><ref name=CDC12 /> Appropriate caution should be taken regarding any medical condition that results in [[bleeding]], such as cuts and sores.<ref name=CDC12 /> HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils,<ref name=CDC12>{{cite web |url= https://www.cdc.gov/hepatitis/HCV/HCVfaq.htm |title= Hepatitis C FAQs for Health Professionals |publisher= Centers for Disease Control and Prevention (CDC) |access-date= 2 January 2012 |url-status= live |archive-url= https://web.archive.org/web/20120104063744/http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm |archive-date= 4 January 2012 }}</ref> nor is it transmitted through food or water.<ref>{{cite journal | vauthors = Wong T, Lee SS | title = Hepatitis C: a review for primary care physicians | journal = CMAJ | volume = 174 | issue = 5 | pages = 649–59 | date = February 2006 | pmid = 16505462 | pmc = 1389829 | doi = 10.1503/cmaj.1030034 }}</ref>

=== Healthcare exposure ===
[[Blood transfusion]], transfusion of blood products, or [[organ transplants]] without HCV screening carry significant risks of infection.<ref name=AFP2010 /> The United States instituted universal screening in 1992,<ref name=Rosen2011 /> and Canada instituted universal screening in 1990.<ref>{{cite book|vauthors=Day RA, Paul P, Williams B|title=Brunner & Suddarth's textbook of Canadian medical-surgical nursing|date=2009|publisher=Lippincott Williams & Wilkins|location=Philadelphia, PA|isbn=978-0-7817-9989-8|page=1237|url=https://books.google.com/books?id=SB_-CRXvZPYC&pg=PA1237|edition=Canadian 2nd |url-status=live|archive-url=https://web.archive.org/web/20160425134413/https://books.google.com/books?id=SB_-CRXvZPYC&pg=PA1237|archive-date=2016-04-25}}</ref> This decreased the risk from one in 200 units<ref name=Rosen2011>{{cite book|title=Rosen's emergency medicine: concepts and clinical practice | edition = 7th | vauthors = Marx J |year=2010|publisher=Mosby/Elsevier |location=Philadelphia, PA |isbn=978-0-323-05472-0 |page=[https://archive.org/details/rosensemergencym00mdjo/page/n1176 1154] |url=https://archive.org/details/rosensemergencym00mdjo|url-access=limited }}</ref> to between one in 10,000 to one in 10,000,000 per unit of blood.<ref name=Book2011p4 /><ref name=Pon2011 /> This low risk remains as there is a period of about 11–70 days between the potential [[blood donor]]'s acquiring {{nowrap|hepatitis C}} and the blood's testing positive depending on the method.<ref name=Pon2011 /> Some countries do not screen for {{nowrap|hepatitis C}} due to the cost.<ref name=World2007 />

Those who have experienced a [[needle stick injury]] from someone who was HCV positive have about a 1.8% chance of subsequently contracting the disease themselves.<ref name=AFP2010 /> The risk is greater if the needle is hollow and the puncture wound is deep.<ref name=World2007 /> There is a risk from mucosal exposure to blood, but this risk is low, and there is no risk if blood exposure occurs on intact skin.<ref name=World2007 />

Hospital equipment has also been documented as a method of transmission of {{nowrap|hepatitis C}}, including the reuse of needles and syringes, multiple-use medication vials, infusion bags, and improperly sterilized surgical equipment, among others.<ref name=World2007 /> Limitations in the implementation and enforcement of stringent standard precautions in public and private medical and dental facilities are known to have been the primary cause of the spread of HCV in [[Egypt]], the country which had the highest rate of infection in the world in 2012. In 2023, Egypt became the first country to achieve WHO validation on the path to elimination of hepatitis C.<ref>{{cite web|author=WHO Eastern Mediterranean Region|title=Egypt becomes the first country to achieve WHO validation on the path to elimination of hepatitis C|url=https://www.emro.who.int/media/news/egypt-becomes-the-first-country-to-achieve-who-validation-on-the-path-to-elimination-of-hepatitis-c.html|date=9 October 2023|access-date=18 May 2023}}<!-- auto-translated by Module:CS1 translator --></ref>

For further information, see [[HONOReform|HONOReform (Hepatitis Outbreaks National Organization for Reform)]].

=== Mother-to-child transmission ===
[[Mother-to-child transmission]] of {{nowrap|hepatitis C}} occurs in fewer than 10% of pregnancies.<ref name=Preg10>{{cite journal | vauthors = Lam NC, Gotsch PB, Langan RC | title = Caring for pregnant women and newborns with hepatitis B or C | journal = American Family Physician | volume = 82 | issue = 10 | pages = 1225–9 | date = November 2010 | pmid = 21121533 | url = http://www.aafp.org/afp/2010/1115/p1225.pdf | url-status = live | archive-url = https://web.archive.org/web/20130521080102/http://www.aafp.org/afp/2010/1115/p1225.pdf | archive-date = 2013-05-21 }}</ref> There are no measures that alter this risk.<ref name=Preg10 /> It is not clear when transmission occurs during pregnancy, but it may occur both during gestation and at delivery.<ref name=Pon2011 /> A long labor is associated with a greater risk of transmission.<ref name=World2007 /> There is no evidence that [[breastfeeding]] spreads HCV; however, to be cautious, an infected mother is advised to avoid breastfeeding if her nipples are cracked and bleeding,<ref>{{cite book | vauthors = Mast EE |chapter=Mother-to-Infant Hepatitis C Virus Transmission and Breastfeeding |series=Advances in Experimental Medicine and Biology |title=Protecting Infants through Human Milk |volume=554 |pages=211–16|year=2004 |pmid=15384578 |doi=10.1007/978-1-4757-4242-8_18|isbn=978-1-4419-3461-1 }}</ref> or if her viral loads are high.<ref name=Pon2011 />

=== Sexual intercourse ===
Sexual transmission of hepatitis C is uncommon.<ref name=Kim2016/> Studies examining the risk of HCV transmission between [[heterosexual]] partners, when one is infected and the other is not, have found very low risks.<ref name=Kim2016/> Sexual practices that involve higher levels of trauma to the [[anogenital area|anogenital]] mucosa, such as [[anal penetration|anal penetrative sex]], or that occur when there is a concurrent [[sexually transmitted infection]], including [[HIV]] or [[genital ulcer]]ation, present greater risks.<ref name=Kim2016/><ref name=Sex2010>{{cite journal | vauthors = Tohme RA, Holmberg SD | title = Is sexual contact a major mode of hepatitis C virus transmission? | journal = Hepatology | volume = 52 | issue = 4 | pages = 1497–505 | date = October 2010 | pmid = 20635398 | doi = 10.1002/hep.23808 | s2cid = 5592006 | doi-access =  }}</ref> The [[United States Department of Veterans Affairs]] recommends [[condom]] use to prevent {{nowrap|hepatitis C}} transmission in those with multiple partners, but not those in relationships that involve only a single partner.<ref>{{cite web|title=Hepatitis C Group Education Class|url=http://www.hepatitis.va.gov/products/HCV-education-class-script.asp|publisher=United States Department of Veteran Affairs|url-status=dead|archive-url=https://web.archive.org/web/20111109105344/http://www.hepatitis.va.gov/products/HCV-education-class-script.asp|archive-date=2011-11-09|access-date=2011-11-20}}</ref>

== Diagnosis ==
[[File:Hepatitis C serology.png|thumb|upright=1.4|Serologic profile of hepatitis C infection]]

There are several diagnostic tests for {{nowrap|hepatitis C}}, including HCV [[antibody]] [[ELISA|enzyme immunoassay]] (ELISA), [[Western blot|recombinant immunoblot assay]], and quantitative HCV [[RNA]] [[polymerase chain reaction]] (PCR).<ref name=AFP2010 /> HCV [[RNA]] can be detected by PCR typically one to two weeks after infection. In contrast, antibodies can take substantially longer to form and thus be detected.<ref name=Tah2009 />

Diagnosing patients is generally a challenge as patients with acute illness often present with mild, non-specific flu-like symptoms,<ref>{{cite journal | vauthors = Westbrook RH, Dusheiko G | title = Natural history of hepatitis C | journal = Journal of Hepatology | volume = 61 | issue = 1 Suppl | pages = S58-68 | date = November 2014 | pmid = 25443346 | doi = 10.1016/j.jhep.2014.07.012 | doi-access = free }}</ref> while the transition from acute to chronic is sub-clinical.<ref>{{cite journal | vauthors = Patel K, Muir AJ, McHutchison JG | title = Diagnosis and treatment of chronic hepatitis C infection | journal = BMJ | volume = 332 | issue = 7548 | pages = 1013–7 | date = April 2006 | pmid = 16644828 | pmc = 1450048 | doi = 10.1136/bmj.332.7548.1013 | url = }}</ref> Chronic {{nowrap|hepatitis C}} is defined as infection with the {{nowrap|hepatitis C}} virus persisting for more than six months based on the presence of its RNA.<ref name=Book2011>{{cite book | vauthors = Kanwal F, Bacon BR | chapter = Does Treatment Alter the Natural History of Chronic HCV? | veditors = Schiffman ML |title=Chronic Hepatitis C Virus Advances in Treatment, Promise for the Future|year=2011|publisher=Springer Verlag|isbn=978-1-4614-1191-8|pages=103–04|chapter-url=https://books.google.com/books?id=6G7mff5DnBQC&pg=PA104 }}</ref> Chronic infections are typically asymptomatic during the first few decades,<ref name=Book2011 /> and thus are most commonly discovered following the investigation of [[Liver function tests|elevated liver enzyme levels]] or during a routine screening of high-risk individuals. Testing is not able to distinguish between acute and chronic infections.<ref name=World2007 /> Diagnosis in infants is difficult as maternal antibodies may persist for up to 18 months.<ref name=Robinson2008 />

=== Serology ===
{{nowrap|Hepatitis C}} testing typically begins with [[serology|blood testing]] to detect the presence of antibodies to the HCV, using an enzyme immunoassay.<ref name=AFP2010 /> If this test is positive, a confirmatory test is then performed to verify the immunoassay and to determine the [[viral load]].<ref name=AFP2010 /> A recombinant immunoblot assay is used to verify the immunoassay and the viral load is determined by an HCV RNA polymerase chain reaction.<ref name=AFP2010 /> If there is no RNA and the immunoblot is positive, it means that the person tested had a previous infection but cleared it either with treatment or spontaneously; if the immunoblot is negative, it means that the immunoassay was wrong.<ref name=AFP2010 /> It takes about 6–8 weeks following infection before the immunoassay will test positive.<ref name=ID2010 /> Several tests are available as [[point of care testing|point-of-care testing]] (POCT), which can provide results within 30 minutes.<ref>{{cite journal | vauthors = Shivkumar S, Peeling R, Jafari Y, Joseph L, Pant Pai N | title = Accuracy of rapid and point-of-care screening tests for hepatitis C: a systematic review and meta-analysis | journal = Annals of Internal Medicine | volume = 157 | issue = 8 | pages = 558–66 | date = October 2012 | pmid = 23070489 | doi = 10.7326/0003-4819-157-8-201210160-00006 | s2cid = 5650682 }}</ref>

Liver enzymes are variable during the initial part of the infection<ref name=Book2011 /> and on average begin to rise seven weeks after infection.<ref name=ID2010 /> The elevation of liver enzymes does not closely follow disease severity.<ref name=ID2010 />

=== Biopsy ===
[[Liver biopsy|Liver biopsies]] are used to determine the degree of liver damage present; however, there are risks from the procedure.<ref name=NEJM2011 /> The typical changes seen are [[lymphocyte]]s within the parenchyma, [[lymphoid follicles]] in [[portal triad]], and changes to the bile ducts.<ref name=NEJM2011 /> There are many blood tests available that try to determine the degree of [[hepatic fibrosis]] and alleviate the need for biopsy.<ref name=NEJM2011 />

=== Screening ===
It is believed that only 5–50% of those infected in the United States and Canada are aware of their status.<ref name=Tato2010 /> Routine screening for those between the ages of 18 and 79 was recommended by the [[United States Preventive Services Task Force]] in 2020.<ref name=USPSTF>{{cite journal | vauthors = Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Donahue K, Doubeni CA, Epling JW, Kubik M, Ogedegbe G, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB | display-authors = 6 | title = Screening for Hepatitis C Virus Infection in Adolescents and Adults: US Preventive Services Task Force Recommendation Statement | journal = JAMA | volume = 323 | issue = 10 | pages = 970–975 | date = March 2020 | pmid = 32119076 | doi = 10.1001/jama.2020.1123 | doi-access = free }}</ref> Previously, testing was recommended for those at high risk, including injection drug users, those who have received blood transfusions before 1992,<ref name="Moyer2013"/> those who have been incarcerated, those on long-term [[hemodialysis]],<ref name=Moyer2013>{{cite journal | vauthors = Moyer VA | title = Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement | journal = Annals of Internal Medicine | volume = 159 | issue = 5 | pages = 349–57 | date = September 2013 | pmid = 23798026 | doi = 10.7326/0003-4819-159-5-201309030-00672 | url = https://semanticscholar.org/paper/cc502bd0e6ef93d2c52e48d32c1923eb1f32d8de | s2cid = 8563203 }}</ref> and those with tattoos.<ref name=Tato2010 /> Screening is also recommended for those with elevated liver enzymes, as this is frequently the only sign of chronic hepatitis.<ref>{{cite journal | vauthors = Senadhi V | title = A paradigm shift in the outpatient approach to liver function tests | journal = Southern Medical Journal | volume = 104 | issue = 7 | pages = 521–5 | date = July 2011 | pmid = 21886053 | doi = 10.1097/SMJ.0b013e31821e8ff5 | s2cid = 26462106 }}</ref> {{As of|2012}}, the U.S. [[Centers for Disease Control and Prevention]] (CDC) recommends a single screening test for those born between 1945 and 1965.<ref>{{cite journal | vauthors = Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Teo CG, Jewett A, Baack B, Rein DB, Patel N, Alter M, Yartel A, Ward JW | display-authors = 6 | title = Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965 | journal = MMWR. Recommendations and Reports | volume = 61 | issue = RR-4 | pages = 1–32 | date = August 2012 | pmid = 22895429 | url = https://www.cdc.gov/mmwr/pdf/rr/rr6104.pdf }}</ref><ref>{{cite web | title=Testing Recommendations for Hepatitis C Virus Infection – HCV – Division of Viral Hepatitis | website=U.S. [[Centers for Disease Control and Prevention]] (CDC) | date=12 June 2019 | url=https://www.cdc.gov/hepatitis/hcv/guidelinesc.htm | access-date=11 January 2020 }}</ref><ref>{{cite web | title=People Born 1945–1965 (Baby Boomers) – Populations and Settings – Division of Viral Hepatitis | website=U.S. [[Centers for Disease Control and Prevention]] (CDC) | date=26 July 2019 | url=https://www.cdc.gov/hepatitis/populations/1945-1965.htm | access-date=11 January 2020 | archive-url=https://web.archive.org/web/20191022221926/https://www.cdc.gov/hepatitis/populations/1945-1965.htm | archive-date=22 October 2019 | url-status=dead }}</ref><ref>{{cite web | title=Final Update Summary: Hepatitis C: Screening | website=US Preventive Services Task Force | url=https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/hepatitis-c-screening | access-date=11 January 2020}}</ref> In Canada, a one-time screening is recommended for those born between 1945 and 1975.<ref>{{cite journal | vauthors = Shah H, Bilodeau M, Burak KW, Cooper C, Klein M, Ramji A, Smyth D, Feld JJ | display-authors = 6 | title = The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver | journal = CMAJ | volume = 190 | issue = 22 | pages = E677–E687 | date = June 2018 | pmid = 29866893 | pmc = 5988519 | doi = 10.1503/cmaj.170453 }}</ref>

== Prevention ==
{{See also|Hepatitis C vaccine}}
As of 2022, no approved [[vaccine]] protects against contracting {{nowrap|hepatitis C}}.<ref>{{Cite web |last=CDC |date=2021-06-14 |title=Hepatitis C {{!}} CDC |url=https://www.cdc.gov/hepatitis/hcv/index.htm |access-date=2023-03-27 |website=Centers for Disease Control and Prevention |language=en-us}}</ref> A combination of [[harm reduction]] strategies, such as the [[needle exchange programs|provision of new needles and syringes]] and treatment of [[substance abuse|substance use]], decreases the risk of {{nowrap|hepatitis C}} in people using injection drugs by about 75%.<ref>{{cite journal | vauthors = Hagan H, Pouget ER, Des Jarlais DC | title = A systematic review and meta-analysis of interventions to prevent hepatitis C virus infection in people who inject drugs | journal = The Journal of Infectious Diseases | volume = 204 | issue = 1 | pages = 74–83 | date = July 2011 | pmid = 21628661 | pmc = 3105033 | doi = 10.1093/infdis/jir196 }}</ref> The screening of blood donors is important at a national level, as is adhering to [[universal precautions]] within healthcare facilities.<ref name=ID2010 /> In countries where there is an insufficient supply of sterile [[syringes]], medications should be given orally rather than via injection (when possible).<ref name=World2007 /> Recent research also suggests that treating people with active infection, thereby reducing the potential for transmission, may be an effective preventive measure.<ref name="TA" />

Hepatitis C vaccine phase 1 clinical trials are set to begin in the summer of 2023.<ref>{{cite web|url=https://www.contagionlive.com/view/biden-administration-others-working-towards-eliminating-hepatitis-c|title=Biden Administration, Others Working Towards Eliminating Hepatitis C|date=13 March 2023 }}</ref>

== Treatment ==
Those with chronic {{nowrap|hepatitis C}} are advised to avoid [[alcohol (drug)|alcohol]] and medications that are [[Hepatotoxicity|toxic to the liver]].<ref name=AFP2010 /> They should also be [[vaccinated]] against [[hepatitis A]] and [[hepatitis B]] due to the increased risk if also infected.<ref name=AFP2010 /> Use of [[acetaminophen]] is generally considered safe at reduced doses.<ref name=Kim2016>{{cite journal | vauthors = Kim A | title = Hepatitis C Virus | journal = Annals of Internal Medicine | volume = 165 | issue = 5 | pages = ITC33–ITC48 | date = September 2016 | pmid = 27595226 | doi = 10.7326/AITC201609060 | type = Review | s2cid = 95756 }}</ref> [[Nonsteroidal anti-inflammatory drug]]s (NSAIDs) are not recommended in those with advanced liver disease due to an increased risk of bleeding.<ref name=Kim2016/> [[Ultrasound]] surveillance for [[hepatocellular carcinoma]] is recommended in those with accompanying cirrhosis.<ref name=AFP2010 /> Regular, moderate [[coffee]] consumption, especially [[Caffeine|caffeinated]], has been associated with a slower rate of liver [[fibrosis|scarring]] in those infected with HCV.<ref name=Kim2016/><ref>{{cite journal|vauthors=Ruiz-Margáin A, Román-Calleja BM, Moreno-Guillén P, González-Regueiro JA, Kúsulas-Delint D, Campos-Murguía A, Flores-García NC, Macías-Rodríguez RU|date=15 October 2021|title=Nutritional therapy for hepatocellular carcinoma|journal=World J Gastrointest Oncol|volume=13|issue=10|pages=1440–1452|doi=10.4251/wjgo.v13.i10.1440|pmc=8529929|pmid=34721776|doi-access=free}}</ref><ref>{{cite journal|vauthors=Shan L, Zhao N, Wang F, Zhai D, Liu J, Lv X|date=11 March 2024|title=Caffeine in Hepatocellular Carcinoma: Cellular Assays, Animal Experiments, and Epidemiological Investigation|journal=J Inflamm Res|volume=17|issue=|pages=1589–1605|doi=10.2147/JIR.S424384|pmc=10941793|pmid=38495344|doi-access=free}}</ref>

=== Medications ===
[[File:Ribavirin.svg|thumb|right|[[Ribavirin]]]]
More than 95% of chronic cases are resolved with treatment.<ref name=whofactsheet/> Treatment with [[antiviral medication]] is recommended for all people with proven chronic hepatitis C who are not at high risk of death from other causes.<ref name=IDSA2015>{{cite journal | title = Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus | journal = Hepatology | volume = 62 | issue = 3 | pages = 932–54 | date = September 2015 | pmid = 26111063 | doi = 10.1002/hep.27950 | doi-access = free | author1 = AASLD/IDSA HCV Guidance Panel }}</ref> People with the highest complication risk, based on the degree of liver scarring, should be treated first.<ref name=IDSA2015 /> The initial recommended treatment depends on the type of hepatitis C virus, if the person has received previous hepatitis C treatment, and whether the person has cirrhosis.<ref name=IDSA2017/> [[Direct-acting antivirals]] are the preferred treatment and have been validated by testing for virus particles in patients' blood.<ref>{{cite journal | vauthors = Jakobsen JC, Nielsen EE, Feinberg J, Katakam KK, Fobian K, Hauser G, Poropat G, Djurisic S, Weiss KH, Bjelakovic M, Bjelakovic G, Klingenberg SL, Liu JP, Nikolova D, Koretz RL, Gluud C | display-authors = 6 | title = Direct-acting antivirals for chronic hepatitis C | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD012143 | date = September 2017 | issue = 9 | pmid = 28922704 | pmc = 6484376 | doi = 10.1002/14651858.CD012143.pub3 }}</ref>

====No prior treatment====
* HCV genotype 1a (no cirrhosis): 8 weeks of [[glecaprevir/pibrentasvir]] or [[ledipasvir/sofosbuvir]] (the latter for people who do not have [[HIV/AIDS]], are not [[African-American]], and have less than 6 million HCV viral copies per milliliter of blood) or 12 weeks of [[elbasvir/grazoprevir]], ledipasvir/sofosbuvir, or [[sofosbuvir/velpatasvir]].<ref name="HCVGuidelinesGenotype1a">{{cite book | title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | chapter = Treatment: Naive Genotype 1a Without Cirrhosis | chapter-url=https://www.hcvguidelines.org/treatment-naive/gt1a/no-cirrhosis| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref> [[Sofosbuvir]] with either [[daclatasvir]] or [[simeprevir]] may also be used.<ref name=IDSA2017>{{cite web | title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C |url=http://hcvguidelines.org/sites/default/files/full-guidance-pdf/HCVGuidance_April_12_2017_b.pdf|access-date=28 July 2017|date=12 April 2017|url-status=dead|archive-url=https://web.archive.org/web/20170710035751/http://hcvguidelines.org/sites/default/files/full-guidance-pdf/HCVGuidance_April_12_2017_b.pdf|archive-date=2017-07-10}}</ref>
* HCV genotype 1a (with compensated [[cirrhosis]]): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. An alternative treatment regimen of elbasvir/grazoprevir with weight-based ribavirin for 16 weeks can be used if the HCV is found to have antiviral resistance mutations against NS5A protease inhibitors.<ref name="HCVGuidelinesGenotype1acompensated">{{cite book |title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C| chapter = Treatment: Naive Genotype 1a With Compensated Cirrhosis | chapter-url= https://www.hcvguidelines.org/treatment-naive/gt1a/compensated-cirrhosis| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>
* HCV genotype 1b (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or ledipasvir/sofosbuvir (with the aforementioned limitations for the latter as above) or 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. Alternative regimens include 12 weeks of [[ombitasvir/paritaprevir/ritonavir]] with [[dasabuvir]] or 12 weeks of [[sofosbuvir]] with either [[daclatasvir]] or [[simeprevir]].<ref name="HCVGuidelinesGenotype1b">{{cite book |title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | chapter = Treatment: Naive Genotype 1b Without Cirrhosis| chapter-url=https://www.hcvguidelines.org/treatment-naive/gt1b/no-cirrhosis | via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>
* HCV genotype 1b (with compensated cirrhosis): 8 weeks of [[Glecaprevir/pibrentasvir|glecaprevir]]/pibrentasvir or 12 weeks of [[elbasvir/grazoprevir]], ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. A 12-week course of paritaprevir/ritonavir/ombitasvir with dasabuvir may also be used.<ref name="HCVGuidelinesGenotype1bcompensated">{{cite book |title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | chapter = Treatment: Naive Genotype 1b With Compensated Cirrhosis| chapter-url=https://www.hcvguidelines.org/treatment-naive/gt1b/compensated-cirrhosis| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>
* HCV genotype 2 (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir. Alternatively, 12 weeks of sofosbuvir/daclatasvir can be used.<ref name="HCVGuidelinesGenotype2">{{cite book |title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | chapter = Treatment; Naive Genotype 2 Without Cirrhosis| chapter-url=https://www.hcvguidelines.org/treatment-naive/gt2/no-cirrhosis| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>
* HCV genotype 2 (with compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/[[velpatasvir]]. An alternative regimen of sofosbuvir/daclatasvir can be used for 16–24 weeks.<ref name="HCVGuidelinesGenotype2compensated">{{cite book |title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | chapter = Treatment – Naive Genotype 2 With Compensated Cirrhosis| chapter-url=https://www.hcvguidelines.org/treatment-naive/gt2/compensated-cirrhosis| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>
* HCV genotype 3 (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir or sofosbuvir and daclatasvir.<ref name="HCVGuidelinesGenotype3">{{cite book |title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C |chapter = Treatment: Naive Genotype 3 Without Cirrhosis| chapter-url=https://www.hcvguidelines.org/treatment-naive/gt3/no-cirrhosis| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>
* HCV genotype 3 (with compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir, or if certain antiviral mutations are present 12 weeks of sofosbuvir/velpatasvir/[[voxilaprevir]] (when certain antiviral mutations are present), or 24 weeks of sofosbuvir and daclatasvir.<ref name="HCVGuidelinesGenotype3compensated">{{cite book |title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | chapter = Treatment: Naive Genotype 3 With Compensated Cirrhosis| chapter-url=https://www.hcvguidelines.org/treatment-naive/gt3/compensated-cirrhosis| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>
* HCV genotype 4 (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir, elbasvir/grazoprevir, or ledipasvir/sofosbuvir. A 12-week [[ombitasvir/paritaprevir/ritonavir]] regimen is also acceptable in combination with weight-based [[ribavirin]].<ref name="HCVGuidelinesGenotype4">{{cite book|title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | chapter = Treatment: Naive Genotype 4 Without Cirrhosis| chapter-url = https://www.hcvguidelines.org/treatment-naive/gt4/no-cirrhosis| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>
* HCV genotype 4 (with compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir, elbasvir/grazoprevir, or ledipasvir/sofosbuvir is recommended. A 12-week course of ombitasvir/paritaprevir/ritonavir with weight-based [[ribavirin]] is an acceptable alternative.<ref name="HCVGuidelinesGenotype4compensated">{{cite book |title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | chapter = Treatment: Naive Genotype 4 With Compensated Cirrhosis| chapter-url=https://www.hcvguidelines.org/treatment-naive/gt4/compensated-cirrhosis| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>
* HCV genotype 5 or 6 (with or without compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir is recommended. If cirrhosis is present, then a 12-week course of sofosbuvir/velpatasvir, or [[ledipasvir/sofosbuvir]] is an alternative option.<ref name="HCVGuidelinesGenotypes5and6">{{cite book |title=HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | chapter = Treatment: Naive Genotype 5 or 6| chapter-url=https://www.hcvguidelines.org/treatment-naive/gt5-6| via = www.hcvguidelines.org|publisher=American Association for the Study of Liver Diseases|access-date=26 April 2017}}</ref>

More than 95% of people with chronic infection can be cured when treated with medications;<ref name=CDC2019>{{cite web |title=Hepatitis C Questions and Answers for Health Professionals |url=https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm |website=www.cdc.gov |access-date=23 July 2019 |language=en-us |date=2 July 2019}}</ref><!-- Quote = Over 90% of HCV-infected persons can be cured of HCV infection regardless of HCV genotype, with 8-12 weeks of oral therapy --> this could be expensive, but by 2022 prices had dropped dramatically.<ref name=whofactsheet/> The combination of [[Sofosbuvir/velpatasvir/voxilaprevir|sofosbuvir, velpatasvir, and voxilaprevir]] may be used in those who have previously been treated with sofosbuvir or other drugs that inhibit [[Hepatitis C virus nonstructural protein 5A|NS5A]] and were not cured.<ref>{{cite press release | title=FDA approves Vosevi for Hepatitis C|url=https://www.fda.gov/news-events/press-announcements/fda-approves-vosevi-hepatitis-c |website=U.S. [[Food and Drug Administration]] (FDA) |access-date=27 July 2017|date=18 July 2017|url-status=dead|archive-url=https://web.archive.org/web/20170723062106/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm567467.htm|archive-date=23 July 2017}}</ref>

Before 2011, treatments consisted of a combination of [[pegylated interferon]] alpha and [[ribavirin]] for a period of 24 or 48 weeks, depending on HCV [[genotype]].<ref name=AFP2010 /> This treatment produces cure rates of 70–80% for genotype 2 and 3, respectively, and 45–70% for genotypes 1 and 4.<ref name=NEJM2013>{{cite journal | vauthors = Liang TJ, Ghany MG | title = Current and future therapies for hepatitis C virus infection | journal = The New England Journal of Medicine | volume = 368 | issue = 20 | pages = 1907–17 | date = May 2013 | pmid = 23675659 | pmc = 3893124 | doi = 10.1056/NEJMra1213651 }}</ref> Adverse effects with these treatments were common, with 50–60% of those being treated experiencing [[Influenza-like illness|flu-like symptoms]] and nearly a third experiencing depression or other emotional issues.<ref name=AFP2010 /> Treatment during the first six months of infection (the acute stage) is more effective than when {{nowrap|hepatitis C}} has entered the chronic stage.<ref name=Tah2009 /> In those with chronic hepatitis B, treatment for hepatitis C results in reactivation of hepatitis B about 25% of the time.<ref name="Mücke2018">{{cite journal | vauthors = Mücke MM, Backus LI, Mücke VT, Coppola N, Preda CM, Yeh ML, Tang LS, Belperio PS, Wilson EM, Yu ML, Zeuzem S, Herrmann E, Vermehren J | display-authors = 6 | title = Hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C: a systematic review and meta-analysis | journal = The Lancet. Gastroenterology & Hepatology | volume = 3 | issue = 3 | pages = 172–180 | date = March 2018 | pmid = 29371017 | doi = 10.1016/S2468-1253(18)30002-5 }}</ref>

=== Surgery ===
Cirrhosis due to hepatitis C is a common reason for [[liver transplant]]ation,<ref name=Tah2009>{{cite journal | vauthors = Ozaras R, Tahan V | title = Acute hepatitis C: prevention and treatment | journal = Expert Review of Anti-Infective Therapy | volume = 7 | issue = 3 | pages = 351–61 | date = April 2009 | pmid = 19344247 | doi = 10.1586/eri.09.8 | s2cid = 25574917 }}</ref> though the virus usually (80–90% of cases) recurs afterwards.<ref name=NEJM2011 /><ref>{{cite book| vauthors  = Sanders M |title=Mosby's Paramedic Textbook|year=2011|publisher=Jones & Bartlett Publishers|isbn=978-0-323-07275-5|page=839|url=https://books.google.com/books?id=PJyhIH8N8qgC&pg=PA839|url-status=live|archive-url=https://web.archive.org/web/20160511134533/https://books.google.com/books?id=PJyhIH8N8qgC&pg=PA839|archive-date=2016-05-11}}</ref> Infection of the graft leads to 10–30% of people developing cirrhosis within five years.<ref name=Ciria2013>{{cite journal | vauthors = Ciria R, Pleguezuelo M, Khorsandi SE, Davila D, Suddle A, Vilca-Melendez H, Rufian S, de la Mata M, Briceño J, Cillero PL, Heaton N | display-authors = 6 | title = Strategies to reduce hepatitis C virus recurrence after liver transplantation | journal = World Journal of Hepatology | volume = 5 | issue = 5 | pages = 237–50 | date = May 2013 | pmid = 23717735 | pmc = 3664282 | doi = 10.4254/wjh.v5.i5.237 | doi-access = free }}</ref> Treatment with pegylated interferon and ribavirin post-transplant decreases the risk of recurrence to 70%.<ref name=Coilly2013>{{cite journal | vauthors = Coilly A, Roche B, Samuel D | title = Current management and perspectives for HCV recurrence after liver transplantation | journal = Liver International | volume = 33 | pages = 56–62 | date = February 2013 | issue = Suppl 1 | pmid = 23286847 | doi = 10.1111/liv.12062 | s2cid = 23601091 | doi-access = free }}</ref> A 2013 review found no clear evidence as to whether antiviral medication is useful if the graft became reinfected.<ref>{{cite journal | vauthors = Gurusamy KS, Tsochatzis E, Toon CD, Xirouchakis E, Burroughs AK, Davidson BR | title = Antiviral interventions for liver transplant patients with recurrent graft infection due to hepatitis C virus | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD006803 | date = December 2013 | volume = 2014 | pmid = 24307460 | doi = 10.1002/14651858.CD006803.pub4 | pmc = 8930021 }}</ref>

=== Alternative medicine ===
Several [[alternative medicine|alternative therapies]] are claimed by their proponents to be helpful for {{nowrap|hepatitis C}}, including [[Silybum marianum|milk thistle]], [[ginseng]], and [[colloidal silver]].<ref name=NCCAM>[http://nccam.nih.gov/health/providers/digest/hepatitisC-science.htm Hepatitis C and CAM: What the Science Says] {{webarchive|url=https://web.archive.org/web/20110320175202/http://nccam.nih.gov/health/providers/digest/hepatitisC-science.htm |date=2011-03-20 }}. [[National Center for Complementary and Alternative Medicine]] (NCCAM). March 2011. (Retrieved 7 March 2011)</ref> However, no alternative therapy has been shown to improve outcomes for {{nowrap|hepatitis C}} patients, and no evidence exists that alternative therapies have any effect on the virus.<ref name=NCCAM /><ref>{{cite journal | vauthors = Liu J, Manheimer E, Tsutani K, Gluud C | title = Medicinal herbs for hepatitis C virus infection: a Cochrane hepatobiliary systematic review of randomized trials | journal = The American Journal of Gastroenterology | volume = 98 | issue = 3 | pages = 538–44 | date = March 2003 | doi = 10.1111/j.1572-0241.2003.07298.x | pmid = 12650784 | s2cid = 20014583 }}</ref><ref>{{cite journal | vauthors = Rambaldi A, Jacobs BP, Gluud C | title = Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD003620 | date = October 2007 | volume = 2009 | pmid = 17943794 | doi = 10.1002/14651858.CD003620.pub3 | pmc = 8724782 }}</ref>

== Prognosis ==
{{anchor|Sustained viral response}}
[[File:Hepatitis C world map - DALY - WHO2004.svg|thumb|left|upright=1.3|[[Disability-adjusted life year]] for hepatitis C in 2004 per 100,000&nbsp;inhabitants
{{Col-begin}}
{{Col-break}}
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|<10}}
{{legend|#fff200|10–15}}
{{legend|#ffdc00|15–20}}
{{legend|#ffc600|20–25}}
{{legend|#ffb000|25–30}}
{{legend|#ff9a00|30–35}}
{{Col-break}}
{{legend|#ff8400|35–40}}
{{legend|#ff6e00|40–45}}
{{legend|#ff5800|45–50}}
{{legend|#ff4200|50–75}}
{{legend|#ff2c00|75–100}}
{{legend|#cb0000|>100}}
{{col-end}}]]
The response to treatment is measured by ''sustained viral response'' (SVR), defined as the absence of detectable [[RNA]] of the [[hepatitis C virus]] in [[serum (blood)|blood serum]] for at least 24 weeks after discontinuing treatment,<ref>{{cite book| veditors = Helms RA, Quan DJ |title=Textbook of Therapeutics: Drug and Disease Management|date=2006|publisher=Lippincott Williams & Wilkins|location=Philadelphia, PA [u.a.]|isbn=978-0-7817-5734-8|page=1340|edition=8th |url=https://books.google.com/books?id=YjrQla7JPD0C|access-date=7 November 2014|url-status=live|archive-url=https://web.archive.org/web/20151205070808/https://books.google.com/books?id=YjrQla7JPD0C|archive-date=5 December 2015}}</ref> and rapid virological response (RVR), defined as undetectable levels achieved within four weeks of treatment. Successful treatment decreases the future risk of hepatocellular carcinoma by 75%.<ref>{{cite journal | vauthors = Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y | title = Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies | journal = Annals of Internal Medicine | volume = 158 | issue = 5 Pt 1 | pages = 329–37 | date = March 2013 | pmid = 23460056 | doi = 10.7326/0003-4819-158-5-201303050-00005 | doi-access =  | s2cid = 15553488 }}</ref>

Before 2012, sustained response occurred in about 40–50% of those with HCV genotype 1 who received 48 weeks of treatment.<ref name=NEJM2011 /> A sustained response was seen in 70–80% of people with HCV genotypes 2 and 3 following 24 weeks of treatment.<ref name=NEJM2011 /> A sustained response occurs for about 65% of those with genotype 4 after 48 weeks of treatment. For those with HCV genotype 6, a 48-week treatment protocol of pegylated interferon and ribavirin results in a higher rate of sustained responses than for genotype 1 (86% vs. 52%). Further studies are needed to determine results for shorter 24-week treatments and those given at lower dosages.<ref>{{cite journal | vauthors = Fung J, Lai CL, Hung I, Young J, Cheng C, Wong D, Yuen MF | title = Chronic hepatitis C virus genotype 6 infection: response to pegylated interferon and ribavirin | journal = The Journal of Infectious Diseases | volume = 198 | issue = 6 | pages = 808–12 | date = September 2008 | pmid = 18657036 | doi = 10.1086/591252 | doi-access = free }}</ref>

=== Spontaneous resolution ===
Around 30% (15–45%) of those with acute HCV infections will spontaneously clear the virus within six months before the infection is considered chronic.<ref name=whofactsheet /> Spontaneous resolution following acute infection appears more common in females and younger patients and may be influenced by certain genetic factors.<ref name=Book2011p4/> Chronic HCV infection may also resolve spontaneously months or years after the acute phase has passed, though this is unusual.<ref name="Book2011p4" />

== Epidemiology ==

{{Update|section|date=July 2020}}
[[File:Countries Most Affected by Hepatitis C in 2019.png|alt=World map showing hepatitis C infection rate by country in 2019|thumb|Percentage of people infected with hepatitis C by country in 2019]]
The [[World Health Organization]] estimated in a 2021 report that 58 million people globally were living with chronic hepatitis C as of 2019.<ref name=":1" /> About 1.5 million people are infected per year, and about 290,000 people die yearly from hepatitis C–related diseases, mainly from liver cancer and cirrhosis.<ref name=whofactsheet/>

Hepatitis C infection rates increased substantially in the 20th century due to a combination of intravenous drug abuse and the reuse of poorly sterilized medical equipment.<ref name="World2007" /> However, advancements in treatment have led to notable declines in chronic infections and deaths from the virus. As a result, the number of chronic patients receiving treatment worldwide has grown from about 950,000 in 2015 to 9.4 million in 2019. During the same period, hepatitis C deaths declined from about 400,000 to 290,000.<ref name=whofactsheet /><ref name=":1" />

Previously, a 2013 study found high infection rates (>3.5% population infected) in [[Central Asia|Central]] and [[East Asia]], [[Middle East and North Africa|North Africa and the Middle East]], intermediate infection rates (1.5–3.5%) in South and [[Southeast Asia]], [[sub-Saharan Africa]], [[Andean civilizations|Andean]], Central and Southern Latin America, Caribbean, Oceania, Australasia and Central, Eastern and Western Europe; and low infection rates (<1.5%) in Asia-Pacific, Tropical Latin America and North America.<ref name="Mohd2013">{{cite journal | vauthors = Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST | title = Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence | journal = Hepatology | volume = 57 | issue = 4 | pages = 1333–42 | date = April 2013 | pmid = 23172780 | doi = 10.1002/hep.26141 | s2cid = 16265266 | doi-access = free }}</ref>

Among those chronically infected, the risk of [[cirrhosis]] after 20 years varies between studies but has been estimated at ~10–15% for men and ~1–5% for women. The reason for this difference is not known. Once cirrhosis is established, the rate of developing [[hepatocellular carcinoma]] is ~1–4% per year.<ref name=Yu2009>{{cite journal | vauthors = Yu ML, Chuang WL | title = Treatment of chronic hepatitis C in Asia: when East meets West | journal = Journal of Gastroenterology and Hepatology | volume = 24 | issue = 3 | pages = 336–45 | date = March 2009 | pmid = 19335784 | doi = 10.1111/j.1440-1746.2009.05789.x | s2cid = 27333980 | doi-access = free }}</ref> Rates of new infections have decreased in the Western world since the 1990s due to improved screening of blood before transfusion.<ref name=Tah2009 />

In Egypt, following [[Egypt Vision 2030|Egypt's 2030 Vision]], the country managed to bring down the infection rates of hepatitis C from 22% in 2011 to just 2% in 2021.<ref name="egypttoday.com">{{Cite web |date=2021-02-06 |title=Hepatitis C prevalence in Egypt drops from 7% to 2% thanks to Sisi's initiative |url=https://www.egypttoday.com/Article/1/98273/Hepatitis-C-prevalence-in-Egypt-drops-from-7-to-2 |access-date=2021-03-06 |website=EgyptToday}}</ref> It was believed that the high prevalence in Egypt was linked to a discontinued mass-treatment campaign for [[schistosomiasis]], using improperly sterilized glass syringes.<ref name="World2007" />

In the United States, about 2% of people have chronic {{nowrap|hepatitis C}}.<ref name=AFP2010 /> In 2014, an estimated 30,500 new acute hepatitis C cases occurred (0.7 per 100,000 population), an increase from 2010 to 2012.<ref>{{cite web |title =Surveillance for Viral Hepatitis – United States, 2014  |publisher = CDC |url = https://www.cdc.gov/hepatitis/statistics/2014surveillance/commentary.htm#bkgrndC |date=May 17, 2016 |access-date = 2016-08-04 |url-status = live |archive-url = https://web.archive.org/web/20160808042215/http://www.cdc.gov/hepatitis/statistics/2014surveillance/commentary.htm#bkgrndC |archive-date = 2016-08-08 }}</ref> The number of deaths from hepatitis C rose to 15,800 in 2008<ref>{{cite web |title=Table 4.5. Number and rate* of deaths with hepatitis C listed as a cause of death†, by demographic characteristic and year — the United States, 2004–2008 |date=June 7, 2012 |url=https://www.cdc.gov/hepatitis/Statistics/2010Surveillance/Table4.5.htm|work=Viral Hepatitis Statistics & Surveillance |publisher=Centers for Disease Control and Prevention |location= Atlanta, GA|access-date=28 July 2013|url-status=dead |archive-url=https://web.archive.org/web/20140309141408/http://www.cdc.gov/hepatitis/Statistics/2010Surveillance/Table4.5.htm|archive-date=9 March 2014}}</ref> having overtaken HIV/AIDS as a cause of death in the US in 2007.<ref>{{cite news|title=Hepatitis C Deaths Creep Past AIDS, Study Finds |first1=Nicholas |last1=Bakalar |url=https://www.nytimes.com/2012/02/28/health/research/hepatitis-c-deaths-creep-past-aids-study-finds.html |url-access=subscription |access-date=28 July 2013|newspaper=New York Times|date=27 February 2012|url-status=live|archive-url=https://web.archive.org/web/20170630112442/http://www.nytimes.com/2012/02/28/health/research/hepatitis-c-deaths-creep-past-aids-study-finds.html?_r=0|archive-date=30 June 2017}}</ref> In 2014, it was the single greatest cause of infectious death in the United States.<ref name="CDC2016a">{{cite web|title=Hepatitis C Kills More Americans than Any Other Infectious Disease|url=https://www.cdc.gov/media/releases/2016/p0504-hepc-mortality.html|publisher=Centers for Disease Control and Prevention|access-date=3 August 2016|date=May 4, 2016|url-status=live|archive-url=https://web.archive.org/web/20160809080556/http://www.cdc.gov/media/releases/2016/p0504-hepc-mortality.html|archive-date=9 August 2016}}</ref> This mortality rate is expected to increase, as those infected by transfusion before HCV testing become apparent.<ref name=Cola2004>{{cite book | veditors = Colacino JM, Heinz BA | vauthors = Blatt LM, Tong M |title=Hepatitis prevention and treatment |year=2004 |publisher=Birkhäuser |location=Basel |isbn=978-3-7643-5956-0 |page=32 |url=https://books.google.com/books?id=KwSWN_QtVLUC&pg=PA32 |url-status=live |archive-url=https://web.archive.org/web/20160624071639/https://books.google.com/books?id=KwSWN_QtVLUC&pg=PA32 |archive-date=2016-06-24 }}</ref> In Europe, the percentage of people with chronic infections has been estimated to be between 0.13 and 3.26%.<ref>{{cite journal | vauthors = Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F | title = The burden of liver disease in Europe: a review of available epidemiological data | journal = Journal of Hepatology | volume = 58 | issue = 3 | pages = 593–608 | date = March 2013 | pmid = 23419824 | doi = 10.1016/j.jhep.2012.12.005 | doi-access = free }}</ref>

In the United Kingdom, about 118,000 people were chronically infected in 2019.<ref>{{cite web | title=Hepatitis C |publisher=NHS UK| date=27 October 2021 | url=https://www.nhs.uk/conditions/hepatitis-c/}}</ref> About half of people using a needle exchange in London in 2017–18 tested positive for hepatitis C of which half were unaware that they had it.<ref>{{cite journal| title=More than half of patients using needle exchange pilot tested positive for Hepatitis C| vauthors = Burns C | website=The Pharmaceutical Journal | date=17 May 2018| url=https://pharmaceutical-journal.com/article/news/more-than-half-of-patients-using-needle-exchange-pilot-tested-positive-for-hepatitis-c}}</ref> As part of a bid to eradicate hepatitis C by 2025, [[NHS England]] conducted a large procurement exercise in 2019. [[Merck Sharp & Dohme]], [[Gilead Sciences]], and [[Abbvie]] were awarded contracts, which, together, are worth up to £1 billion over five years.<ref>{{cite news |title=Legal action firm among winners for largest medicines procurement |url=https://www.hsj.co.uk/quality-and-performance/legal-action-firm-among-winners-for-largest-medicines-procurement/7024966.article |access-date=9 June 2019 |publisher=Health Service Journal |date=30 April 2019}}</ref>

The total number of people with this infection is higher in some countries in Africa and Asia.<ref>{{cite book | vauthors = Holmberg S| veditors = Brunette GW, Kozarsky PE, Magill AJ, Shlim DR, Whatley AD |title=CDC Health Information for International Travel 2012 |publisher=Oxford University Press |location=New York |isbn=978-0-19-976901-8 |page=[https://archive.org/details/cdchealthinforma0000unse/page/231 231] |url=https://archive.org/details/cdchealthinforma0000unse/page/231 |date=2011-05-12 |url-access=registration }}</ref> Countries with particularly high rates of infection include Pakistan (4.8%) and China (3.2%).<ref name=WHO2011>{{cite web |title=Hepatitis C |publisher=World Health Organization (WHO) |url=https://www.who.int/mediacentre/factsheets/fs164/en/index.html |date=June 2011 |access-date=2011-07-13 |url-status=live |archive-url=https://web.archive.org/web/20110712194903/http://www.who.int/mediacentre/factsheets/fs164/en/index.html |archive-date=2011-07-12 }}</ref>

Since 2014, extremely effective treatments have been available to eradicate the disease within 8–12 weeks in most people.<ref name=":0">{{cite journal | vauthors = Lombardi A, Mondelli MU | title = Hepatitis C: Is eradication possible? | journal = Liver International | volume = 39 | issue = 3 | pages = 416–426 | date = March 2019 | pmid = 30472772 | doi = 10.1111/liv.14011 | doi-access = free | hdl = 2434/870308 | hdl-access = free }}</ref> In 2015, about 950,000 people were treated while 1.7 million new infections occurred, meaning that overall the number of people with HCV increased.<ref name=":0" /> These numbers differ by country and improved in 2016, with some countries achieving higher cure rates than new infection rates (mostly high-income countries).<ref name=":0" /> By 2018, twelve countries are on track to achieve HCV elimination.<ref name=":0" /> While antiviral agents will curb new infections, it is less clear whether they impact overall deaths and morbidity.<ref name=":0" /> Furthermore, for them to be effective, people need to be aware of their infection – it is estimated that worldwide only 20% of infected people are aware of their infection (in the US, fewer than half were aware).<ref name=":0" />

== History ==
[[File:15 Hegasy Nobel Prize 2020 HepC.jpg|thumb|upright=1.5|Nobel Prize in Physiology or Medicine 2020: Seminal experiments by HJ Alter, M Houghton and CM Rice leading to the discovery of HCV as the causative agent of non-A, non-B hepatitis]]
In the mid-1970s, [[Harvey J. Alter]], Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the [[National Institutes of Health]], and his research team demonstrated how most post-[[blood transfusion|transfusion]] hepatitis cases were not due to [[hepatitis A]] or [[Hepatitis B|B]] viruses. Despite this discovery, international research efforts to identify the virus, initially called ''non-A, non-B hepatitis'' (NANBH), failed for the next decade. In 1987, [[Michael Houghton (virologist)|Michael Houghton]], [[Qui-Lim Choo]], and [[George Kuo]] at [[Chiron Corporation]], collaborating with [[Daniel W. Bradley]] at the [[Centers for Disease Control and Prevention]], used a novel [[molecular cloning]] approach to identify the unknown organism and develop a diagnostic test.<ref name = Boyer>{{cite book | isbn = 978-0-7923-8760-2 | vauthors = Boyer JL | title = Liver cirrhosis and its development: proceedings of the Falk Symposium 115 | pages = [https://books.google.com/books?id=n5P696E7T0wC&pg=PA344 344] | publisher = [[Springer Science+Business Media|Springer]] | year = 2001 }}</ref> In 1988, Alter confirmed the virus by verifying its presence in a panel of NANBH specimens, and Chiron announced its discovery at a Washington, D.C. press conference in May 1988.

At the time, Chiron was in talks with the Japanese health ministry to sell a biotech version of the hepatitis B vaccine. Simultaneously, [[Hirohito|Emperor Hirohito]] had developed cancer and required numerous blood transfusions. The Japanese health ministry placed a screening order for Chiron's experimental NANBH test. Chiron's Japanese marketing subsidiary, Diagnostic Systems KK, introduced the term "Hepatitis C" in November 1988 in Tokyo news reports publicizing the testing of the emperor's blood.<ref>{{cite news |vauthors=Barnum A |title=US Biotech is Thriving in Japan: Chiron got its start by using blood test on Emperor Hirohito |url=https://www.prepispoison.com/_files/ugd/f29443_600c5edfcea64f47ba3e0a303ce51d05.pdf |archive-url=https://web.archive.org/web/20220811053205/https://www.prepispoison.com/_files/ugd/f29443_600c5edfcea64f47ba3e0a303ce51d05.pdf |url-status=dead |archive-date=August 11, 2022 |work=San Francisco Chronicle |date=May 12, 1992 }}</ref> Chiron sold a screening order to the Japanese health ministry in November 1988, earning the company [[US$]]60 million a year. However, because Chiron had not published any of its research and did not make a culture model available to other researchers to verify Chiron's discovery, hepatitis C earned the nickname "The Emperor's New Virus."

In April 1989, the "discovery" of HCV was published in two articles in the journal ''[[Science (journal)|Science]]''.<ref name="choo">{{cite journal | vauthors = Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M | title = Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome | journal = Science | volume = 244 | issue = 4902 | pages = 359–62 | date = April 1989 | pmid = 2523562 | doi = 10.1126/science.2523562 | url = http://courses.washington.edu/conj504/readings/polyak_reading1.pdf | citeseerx = 10.1.1.469.3592 | bibcode = 1989Sci...244..359C | author-link4 = Lacy Overby }}</ref><ref name="kuo">{{cite journal | vauthors = Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE | display-authors = 6 | title = An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis | journal = Science | volume = 244 | issue = 4902 | pages = 362–4 | date = April 1989 | pmid = 2496467 | doi = 10.1126/science.2496467 | bibcode = 1989Sci...244..362K }}</ref> Chiron filed for several patents on the virus and its diagnosis.<ref name="houghton">{{cite patent | country = EP | number = 0318216 | status = patent | title = NANBV diagnostics | gdate = 1989-05-31 | inventor = Houghton M, Choo QL, Kuo G | assign1 = Chiron }}</ref> A competing patent application by the CDC was dropped in 1990 after Chiron paid $1.9 million to the CDC and $337,500 to Bradley. In 1994, Bradley sued Chiron, seeking to invalidate the patent, have himself included as a co-inventor, and receive damages and royalty income. The court ruled against him, which was sustained on appeal in 1998.<ref>{{cite web|last=Wilken |title=United States Court of Appeals for the Federal Circuit |url=https://caselaw.findlaw.com/court/us-federal-circuit/1200071.html|url-status=live|publisher=United States Court of Appeals for the Federal Circuit |date=20 February 1998|archive-url=https://web.archive.org/web/20091119144520/http://www.ll.georgetown.edu/federal/judicial/fed/opinions/96opinions/96-1536.html |archive-date=19 November 2009}}</ref>
Because of the unique molecular "isolation" of the hepatitis C virus, although Houghton and Kuo's team at Chiron had discovered strong biochemical markers for the virus and the test proved effective at reducing cases of post-transfusion hepatitis, the existence of a hepatitis C virus was essentially inferred.<ref>{{cite web |title=Hepatitis C Investigative guidelines |url=https://www.oregon.gov/oha/PH/DISEASESCONDITIONS/COMMUNICABLEDISEASE/REPORTINGCOMMUNICABLEDISEASE/REPORTINGGUIDELINES/Documents/hepc.pdf |publisher=[[Oregon Health Authority]] |date=January 2020}}</ref> In 1992, the ''San Francisco Chronicle'' reported that the virus had never been observed under an electron microscope.<ref>{{cite news |vauthors=Barnum A |title=US Biotech is Thriving in Japan: Chiron got its start by using blood test on Emperor Hirohito |url=https://www.prepispoison.com/_files/ugd/f29443_600c5edfcea64f47ba3e0a303ce51d05.pdf |work=San Francisco Chronicle |date=May 12, 1992 |access-date=July 24, 2022 |archive-date=August 11, 2022 |archive-url=https://web.archive.org/web/20220811053205/https://www.prepispoison.com/_files/ugd/f29443_600c5edfcea64f47ba3e0a303ce51d05.pdf |url-status=dead }}</ref> In 1997, the American FDA approved the first hepatitis C drug on the basis of a [[surrogate marker]] called "Sustained Virological Response." In response, the pharmaceutical industry established a nationwide network of "[[Astroturfing|Astro-Turf]]" patient advocacy groups to raise awareness (and fear) of the disease.<ref>{{cite news | vauthors = O'Harrow R |title=Grass Roots seeded by Drugmaker |newspaper=Washington Post |date=September 12, 2000}}</ref>

Hepatitis C was finally "discovered" in 2005 when a Japanese team was able to propagate a molecular clone in a cell culture called [[Huh7]].<ref>{{cite journal | vauthors = Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Kräusslich HG, Mizokami M, Bartenschlager R, Liang TJ | display-authors = 6 | title = Production of infectious hepatitis C virus in tissue culture from a cloned viral genome | journal = Nature Medicine | volume = 11 | issue = 7 | pages = 791–796 | date = July 2005 | pmid = 15951748 | pmc = 2918402 | doi = 10.1038/nm1268 }}</ref> This discovery enabled proper characterization of the viral particle and rapid research into the development of protease inhibitors replacing early interferon treatments. The first of these, [[sofosbuvir]], was approved on December 6, 2013. These drugs are marketed as "cures;" however, because they were approved on the basis of surrogate markers and not clinical endpoints such as prolonging life or improving liver health, many experts question their value.<ref>{{cite journal | vauthors = Jakobsen JC, Nielsen EE, Feinberg J, Katakam KK, Fobian K, Hauser G, Poropat G, Djurisic S, Weiss KH, Bjelakovic M, Bjelakovic G, Klingenberg SL, Liu JP, Nikolova D, Koretz RL, Gluud C | display-authors = 6 | title = Direct-acting antivirals for chronic hepatitis C | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 9 | pages = CD012143 | date = September 2017 | pmid = 28922704 | pmc = 6484376 | doi = 10.1002/14651858.CD012143.pub3 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Koretz RL, Lin KW, Ioannidis JP, Lenzer J | title = Is widespread screening for hepatitis C justified? | journal = BMJ | volume = 350 | pages = g7809 | date = January 2015 | pmid = 25587052 | doi = 10.1136/bmj.g7809 | s2cid = 36816304 }}</ref>

After blood screening began, a notable hepatitis C prevalence was discovered in Egypt, which claimed six million individuals were infected by unsterile needles in a late 1970s mass chemotherapy campaign to eliminate [[schistosomiasis]] (snail fever).<ref>{{cite news | vauthors = McNeil D |title=Curing Hepatitis C, in an Experiment the Size of Egypt |newspaper=The New York Times |url=https://www.nytimes.com/2015/12/16/health/hepatitis-c-treatment-egypt.html |date=December 15, 2015}}</ref>

On October 5, 2020, Houghton and Alter, together with [[Charles M. Rice]], were awarded the [[Nobel Prize in Physiology or Medicine]] for their work.<ref>{{Cite news| vauthors = Gallagher J |date=2020-10-05|title=Hepatitis C discovery wins the Nobel Prize|language=en-GB|work=BBC News|url=https://www.bbc.com/news/health-54418463|access-date=2020-10-05}}</ref><ref>{{cite journal |title=The unsung heroes of the Nobel-winning hepatitis C discovery |url=https://www.nature.com/articles/d41586-020-02932-y |journal=Nature |access-date=20 October 2020 |date=19 October 2020|doi=10.1038/d41586-020-02932-y | vauthors = Ledford H |volume=586 |issue=7830 |page=485 |pmid=33082542 |bibcode=2020Natur.586..485L |s2cid=224822368 |url-access=subscription }}</ref>

== Society and culture ==

{{Update|section|date=July 2020}}

{{See also|List of people with hepatitis C}}
[[World Hepatitis Day]], held on July 28, is coordinated by the World Hepatitis Alliance.<ref>{{cite journal | author = Eurosurveillance editorial team | title = World Hepatitis Day 2011 | journal = Euro Surveillance | volume = 16 | issue = 30 | date = July 2011 | pmid = 21813077 | url = http://www.eurosurveillance.org/images/dynamic/EE/V16N30/art19926.pdf | url-status = live | archive-url = https://web.archive.org/web/20111125163506/http://eurosurveillance.org/images/dynamic/EE/V16N30/art19926.pdf | archive-date = 2011-11-25 }}</ref> The economic costs of hepatitis C are significant both to the individual and to society. In the United States, the average lifetime cost of the disease was estimated at US$33,407 in 2003<ref name=Cost2006>{{cite journal | vauthors = Wong JB | title = Hepatitis C: cost of illness and considerations for the economic evaluation of antiviral therapies | journal = PharmacoEconomics | volume = 24 | issue = 7 | pages = 661–72 | year = 2006 | pmid = 16802842 | doi = 10.2165/00019053-200624070-00005 | s2cid = 6713508 }}</ref> with the cost of a liver transplant {{as of|2011|lc=y}} costing approximately US$200,000.<ref name=Cost2011 /> In Canada, the cost of a course of antiviral treatment is as high as 30,000 CAD in 2003,<ref>{{cite web|title=Hepatitis C Prevention, Support and Research ProgramHealth Canada|url=http://www.phac-aspc.gc.ca/hepc/pubs/psrpmideval-ppsrevalinter/i_problem-eng.php|publisher=Public Health Agency of Canada|access-date=10 January 2012|date=Nov 2003|archive-url=https://web.archive.org/web/20110322182718/http://www.phac-aspc.gc.ca/hepc/pubs/psrpmideval-ppsrevalinter/i_problem-eng.php|archive-date=22 March 2011}}</ref> while the United States costs are between 9,200 and US$17,600 in 1998.<ref name=Cost2006 /> In many areas of the world, people cannot afford treatment with antivirals as they either lack insurance coverage or their insurance will not pay for antivirals.<ref>{{cite book| veditors = Thomas H, Lemon S, Zuckerman A |title=Viral Hepatitis|year=2008|publisher=John Wiley & Sons|location=Oxford|isbn=978-1-4051-4388-2|pages=532|url=https://books.google.com/books?id=nT2dauLXoYAC&pg=PA532|edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20160617164927/https://books.google.com/books?id=nT2dauLXoYAC&pg=PA532|archive-date=2016-06-17}}</ref> In the [[National Health Service (England)|English National Health Service]] treatment rates for hepatitis C were higher among less deprived groups in 2010–2012.<ref name=UK2015>{{cite news|title=Commissioning supplement: Health inequalities tell a tale of data neglect| vauthors = Blackledge C |url=http://www.hsj.co.uk/resource-centre/supplements/commissioning-supplement-health-inequalities-tell-a-tale-of-data-neglect/5083351.article|publisher=Health Service Journal|date=19 March 2015|url-status=live|archive-url=https://web.archive.org/web/20150728084950/http://www.hsj.co.uk/resource-centre/supplements/commissioning-supplement-health-inequalities-tell-a-tale-of-data-neglect/5083351.article|archive-date=28 July 2015}}</ref>

Hepatitis C–infected Spanish anaesthetist [[Juan Maeso]] was jailed for the maximum possible period of 20 years for infecting 275 patients between 1988 and 1997, as he used the same needles to give both himself and the patients opioids.<ref>{{cite news|title=Spanish Anesthetist Infected Patients|url=https://www.washingtonpost.com/wp-dyn/content/article/2007/05/15/AR2007051500921.html|newspaper=The Washington Post|date=15 May 2007|agency=Associated Press|url-status=live|archive-url=https://web.archive.org/web/20160822072146/http://www.washingtonpost.com/wp-dyn/content/article/2007/05/15/AR2007051500921.html|archive-date=22 August 2016}}</ref><ref>{{cite news|title=Spanish Hep C anaesthetist jailed|url=http://news.bbc.co.uk/1/hi/world/europe/6657509.stm|work=BBC|date=15 May 2007|url-status=live|archive-url=https://web.archive.org/web/20071023220711/http://news.bbc.co.uk/1/hi/world/europe/6657509.stm|archive-date=23 October 2007}}</ref>

== Special populations ==

=== Children and pregnancy ===
{{Main|HCV in children and pregnancy}}
Compared with adults, infection in children is much less understood. Worldwide the prevalence of {{nowrap|hepatitis C}} virus infection in pregnant women and children has been estimated to be 1–8% and 0.05–5% respectively.<ref name=Arshad2011>{{cite journal | vauthors = Arshad M, El-Kamary SS, Jhaveri R | title = Hepatitis C virus infection during pregnancy and the newborn period--are they opportunities for treatment? | journal = Journal of Viral Hepatitis | volume = 18 | issue = 4 | pages = 229–36 | date = April 2011 | pmid = 21392169 | doi = 10.1111/j.1365-2893.2010.01413.x | s2cid = 35515919 }}</ref> The [[Vertically transmitted infection|vertical transmission]] rate has been estimated to be 3–5% and there is a high rate of spontaneous clearance (25–50%) in the children. Higher rates have been reported for both vertical transmission (18%, 6–36%, and 41%)<ref name=Hunt1997>{{cite journal | vauthors = Hunt CM, Carson KL, Sharara AI | title = Hepatitis C in pregnancy | journal = Obstetrics and Gynecology | volume = 89 | issue = 5 Pt 2 | pages = 883–90 | date = May 1997 | pmid = 9166361 | doi = 10.1016/S0029-7844(97)81434-2 | s2cid = 23182340 }}</ref><ref name=Thomas1998>{{cite journal | vauthors = Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ | title = A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection | journal = International Journal of Epidemiology | volume = 27 | issue = 1 | pages = 108–17 | date = February 1998 | pmid = 9563703 | doi = 10.1093/ije/27.1.108 | doi-access =  }}</ref> and prevalence in children (15%).<ref name=Fischler2007>{{cite journal | vauthors = Fischler B | title = Hepatitis C virus infection | journal = Seminars in Fetal & Neonatal Medicine | volume = 12 | issue = 3 | pages = 168–73 | date = June 2007 | pmid = 17320495 | doi = 10.1016/j.siny.2007.01.008 | citeseerx = 10.1.1.852.7880 }}</ref>

In developed countries, transmission around the time of birth is now the leading cause of HCV infection. In the absence of the Hepatitis C virus in the mother's blood, transmission is rare.<ref name=Thomas1998 /> Factors associated with an increased rate of infection include membrane rupture of longer than 6 hours before delivery and procedures exposing the infant to maternal blood.<ref name=Indolfi2009>{{cite journal | vauthors = Indolfi G, Resti M | title = Perinatal transmission of hepatitis C virus infection | journal = Journal of Medical Virology | volume = 81 | issue = 5 | pages = 836–43 | date = May 2009 | pmid = 19319981 | doi = 10.1002/jmv.21437 | s2cid = 21207996 }}</ref> Cesarean sections are not recommended. Breastfeeding is considered safe if the nipples are not damaged. Infection around the time of birth in one child does not increase the risk in a subsequent pregnancy. All genotypes appear to have the same risk of transmission.

HCV infection is frequently found in children who have previously been presumed to have non-A, non-B hepatitis, and cryptogenic liver disease.<ref name="González-Peralta1997">{{cite journal | vauthors = González-Peralta RP | title = Hepatitis C virus infection in pediatric patients | journal = Clinics in Liver Disease | volume = 1 | issue = 3 | pages = 691–705, ix | date = November 1997 | pmid = 15560066 | doi = 10.1016/s1089-3261(05)70329-9 }}</ref> The presentation in childhood may be asymptomatic or with elevated liver function tests.<ref name=Suskind2004>{{cite journal | vauthors = Suskind DL, Rosenthal P | title = Chronic viral hepatitis | journal = Adolescent Medicine Clinics | volume = 15 | issue = 1 | pages = 145–58, x-xi | date = February 2004 | pmid = 15272262 | doi = 10.1016/j.admecli.2003.11.001 }}</ref> While the infection is commonly asymptomatic, both cirrhosis with liver failure and hepatocellular carcinoma may occur in childhood.

=== Immunosuppressed ===
{{See also|Hepatitis C and HIV coinfection}}
The rate of {{nowrap|hepatitis C}} in immunosuppressed people is higher. This is particularly true in those with [[human immunodeficiency virus]] infection, recipients of [[organ transplant]]s, and those with [[hypogammaglobulinemia]].<ref name=Einav2002>{{cite journal | vauthors = Einav S, Koziel MJ | title = Immunopathogenesis of hepatitis C virus in the immunosuppressed host | journal = Transplant Infectious Disease | volume = 4 | issue = 2 | pages = 85–92 | date = June 2002 | pmid = 12220245 | doi = 10.1034/j.1399-3062.2002.t01-2-02001.x | s2cid = 27843061 }}</ref> Infection in these people is associated with an unusually rapid progression to cirrhosis. People with stable HIV who never received medication for HCV may be treated with a combination of [[peginterferon]] plus [[ribavirin]] with caution to the possible side effects.<ref>{{cite journal | vauthors = Iorio A, Marchesini E, Awad T, Gluud LL | title = Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD004888 | date = January 2010 | pmid = 20091566 | doi = 10.1002/14651858.CD004888.pub2 }}</ref>

== Research ==
{{As of|2011}}, there are about one hundred medications in development for {{nowrap|hepatitis C}}.<ref name=Cost2011>{{cite journal | vauthors = El Khoury AC, Klimack WK, Wallace C, Razavi H | title = Economic burden of hepatitis C-associated diseases in the United States | journal = Journal of Viral Hepatitis | volume = 19 | issue = 3 | pages = 153–60 | date = March 2012 | pmid = 22329369 | doi = 10.1111/j.1365-2893.2011.01563.x | s2cid = 27409621 | doi-access = free }}</ref> These include vaccines to treat hepatitis, [[immunomodulators]], and [[cyclophilin]] inhibitors, among others.<ref>{{cite journal | vauthors = Ahn J, Flamm SL | title = Hepatitis C therapy: other players in the game | journal = Clinics in Liver Disease | volume = 15 | issue = 3 | pages = 641–56 | date = August 2011 | pmid = 21867942 | doi = 10.1016/j.cld.2011.05.008 }}</ref> These potential new treatments have come about due to a better understanding of the {{nowrap|hepatitis C}} virus.<ref>{{cite journal | vauthors = Vermehren J, Sarrazin C | title = New HCV therapies on the horizon | journal = Clinical Microbiology and Infection | volume = 17 | issue = 2 | pages = 122–34 | date = February 2011 | pmid = 21087349 | doi = 10.1111/j.1469-0691.2010.03430.x | doi-access = free }}</ref> There are several vaccines under development and some have shown encouraging results.<ref name=Vac2016>{{cite journal | vauthors = Abdelwahab KS, Ahmed Said ZN | title = Status of hepatitis C virus vaccination: Recent update | journal = World Journal of Gastroenterology | volume = 22 | issue = 2 | pages = 862–73 | date = January 2016 | pmid = 26811632 | pmc = 4716084 | doi = 10.3748/wjg.v22.i2.862 | doi-access = free }}</ref>

The combination of [[sofosbuvir]] and [[velpatasvir]] in one trial (reported in 2015) resulted in cure rates of 99%.<ref>{{cite journal | vauthors = Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S | display-authors = 6 | title = Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection | journal = The New England Journal of Medicine | volume = 373 | issue = 27 | pages = 2599–607 | date = December 2015 | pmid = 26571066 | doi = 10.1056/NEJMoa1512610 | url = http://qmro.qmul.ac.uk/xmlui/handle/123456789/17933 | doi-access = free | hdl = 10722/226358 | hdl-access = free }}</ref> More studies are needed to investigate the role of the preventive antiviral medication against HCV recurrence after transplantation.<ref>{{cite journal | vauthors = Gurusamy KS, Tsochatzis E, Toon CD, Davidson BR, Burroughs AK | title = Antiviral prophylaxis for the prevention of chronic hepatitis C virus in patients undergoing liver transplantation | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD006573 | date = December 2013 | volume = 2013 | pmid = 24297303 | pmc = 6599865 | doi = 10.1002/14651858.CD006573.pub3 }}</ref>

=== Animal models ===
One barrier to finding treatments for {{nowrap|hepatitis C}} is the lack of a suitable animal model. Despite moderate success, research highlights the need for pre-clinical testing in mammalian systems such as [[mouse]], particularly to develop vaccines in poorer communities. [[Common chimpanzee|Chimpanzees]] remain the only living system to study, yet their use has ethical concerns and regulatory restrictions. While scientists have used human cell culture systems such as hepatocytes, questions have been raised about their accuracy in reflecting the body's response to infection.<ref name=Sand2013>{{cite journal | vauthors = Sandmann L, Ploss A | title = Barriers of hepatitis C virus interspecies transmission | journal = Virology | volume = 435 | issue = 1 | pages = 70–80 | date = January 2013 | pmid = 23217617 | pmc = 3523278 | doi = 10.1016/j.virol.2012.09.044 }}</ref>

One aspect of hepatitis research is to reproduce infections in mammalian models. A strategy is to introduce liver tissues from humans into mice, a technique known as xenotransplantation. This is done by generating chimeric mice and exposing the mice to HCV infection. This engineering process is known to create humanized mice and provide opportunities to study hepatitis C within the 3D architectural design of the liver and evaluate antiviral compounds.<ref name=Sand2013 /> Alternatively, generating inbred mice with susceptibility to HCV would simplify the process of studying mouse models.

== See also ==
*[[PSI-6130]], an experimental drug treatment

== References ==
{{Reflist}}

== External links ==
{{Commons}}
{{Spoken Wikipedia|Hep C en.ogg|date=2014-07-26}}
* {{cite web|title=Recommendations for Testing, Managing, and Treating Hepatitis C|url=http://www.hcvguidelines.org/| via = www.hcvguidelines.org|publisher=IDSA/AASLD|access-date=28 July 2017}}
* {{cite web | url = https://medlineplus.gov/hepatitisc.html | publisher = U.S. National Library of Medicine | work = MedlinePlus | title = Hepatitis C }}

{{Medical condition classification and resources
| DiseasesDB      = 5783
| ICD10           = {{ICD10|B|17|1|b|15}}, {{ICD10|B|18|2|b|15}}
| ICD9            = {{ICD9|070.70}},{{ICD9|070.4}}, {{ICD9|070.5}}
| OMIM            = 609532
| MedlinePlus     = 000284
| eMedicineSubj   = med
| eMedicineTopic  = 993
| eMedicine_mult  = {{EMedicine2|ped|979}}
| MeshID          = D006526
| SNOMED CT       = 186643004
}}
{{Portal bar|Medicine|Viruses}}
{{Viral diseases}}
{{Gastroenterology}}
{{Authority control}}

[[Category:Hepatitis C| ]]
[[Category:Healthcare-associated infections]]
[[Category:Infectious causes of cancer]]
[[Category:Wikipedia medicine articles ready to translate (full)]]
[[Category:Wikipedia emergency medicine articles ready to translate]]
[[Category:Hepatitis|+C]]