Editing Hepatitis C (section)

== 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>