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Hepatitis C virus infection
Other Resources UpToDate PubMed

Hepatitis C virus infection

Contributors: Yoshihiko Murata MD, PhD, Suk Chul Kim MD, William Bonnez MD, Zaw Min MD, FACP, Peter Mariuz MD, Paritosh Prasad MD
Other Resources UpToDate PubMed


Hepatitis C is an infection of the liver with the hepatitis C virus (HCV), an RNA virus related to the flaviviruses. Seven genotypes are recognized and have therapeutic implications. HCV can cause acute or chronic hepatitis and very uncommonly fulminant hepatitis. HCV is transmitted through percutaneous or mucosal contact with infectious body fluids. Intravenous drug use is the main mode of transmission in developed countries. Needle stick injuries, tattooing, body piercing, and ritual circumcision are lesser risk factors. Sexual transmission and perinatal transmission have been reported but are thought to be far less frequent than parenteral transmission. Blood transfusion was a leading cause of HCV transmission but is extremely rare since blood screening for HCV became available in 1992.

Following exposure to HCV, the incubation time for acute hepatitis C is 2-24 weeks (average 4-12 weeks), thus intermediate between incubation times for hepatitis A and B. In 70%-80% of cases, acute HCV infection is asymptomatic or leads to mild disease. Approximately 15%-25% of patients clear HCV infection following acute hepatitis. However, in 75%-85% of cases of acute HCV infection, the host immune response fails to prevent a chronic HCV infection. It is estimated that of 100 patients infected with HCV, cirrhosis will develop over a period of 20 years in approximately 5-20, and approximately 1-5 patients will die from consequences of chronic infection.

HCV-related liver disease is usually exacerbated and more rapidly evolving in immunocompromised patients such as transplant patients, HIV-coinfected patients, and patients with hypogammaglobulinemia. For liver transplant patients, it takes an average of 2 years after transplantation with an HCV-infected liver to develop cirrhosis, whereas the average is 20 years in immunocompetent hosts. Patients with HIV-HCV coinfection have a threefold higher rate of progression to cirrhosis than in HCV-monoinfected patients. New therapies for management of HCV infection have significantly changed the outlook for these patients. 

Signs and symptoms of acute hepatitis C include low-grade fever, fatigue, dark urine, clay-colored stool, right upper quadrant pain, hepatomegaly, loss of appetite, nausea, vomiting, arthralgia, and jaundice. Such symptoms are clinically indistinguishable in the individual patient from other types of acute viral hepatitis.

Fulminant hepatitis caused by acute HCV infection is very uncommon, but its risk is higher in HIV-infected men who have sex with men (MSM).

Symptoms of chronic hepatitis C vary from absent to severely debilitating and life-threatening. Individuals with mild to moderate chronic hepatitis C infection are generally asymptomatic, while decompensated cirrhosis may be associated with fatigue, jaundice, loss of muscle mass (weight loss), ascites, edema, bruising (coagulopathy), gastrointestinal bleeding, and hepatic encephalopathy.
More than patients with other viral hepatitides, those with chronic HCV infection are likely to experience extrahepatic manifestations, including essential mixed cryoglobulinemia and associated membranoproliferative glomerulonephritis, palpable purpura / leukocytoclastic vasculitis, Raynaud phenomenon, pruritus, psoriasis, porphyria cutanea tarda, lichen planus, necrolytic acral erythema, membranous glomerulonephritis, chronic kidney disease, cardiovascular disease, B-cell non-Hodgkin lymphoma, Sjögren syndrome, type 2 diabetes mellitus, and autoimmune thyroiditis. These extrahepatic manifestations are considered secondary to immune-mediated mechanisms, either lymphoproliferative or autoimmune in nature, although direct infection of extrahepatic tissue cells by HCV has been documented.


B19.20 – Unspecified viral hepatitis C without hepatic coma

50711007 – Viral hepatitis type C

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Differential Diagnosis & Pitfalls

  • Drug-induced hepatotoxicity (eg, chlorpromazine) – Relevant exposure history.
  • Viral hepatitis (Hepatitis A virus infection, Hepatitis B virus infection, and Hepatitis E virus infection viruses, Cytomegalovirus infection, Epstein-Barr virus infection, Herpes simplex virus, Adenovirus infection, Coxsackie viral infection, Yellow fever) – Consider relevant clinical findings and epidemiological history.
  • Autoimmune hepatitis
  • Acute fatty liver of pregnancy – Consider clinical context.
  • Alcoholic hepatitis
  • Liver cirrhosis
  • Metabolic dysfunction-associated steatotic liver disease (NASH) / metabolic dysfunction-associated steatotic liver disease (MASLD)
  • Toxin exposure (eg, Acetaminophen poisoning, hydrocarbons, halothane) – Review exposure history.
  • Bacterial infections (Tick-borne relapsing fever, Leptospirosis) – Relevant exposure history.
  • Acute circulatory collapse and hypoperfusion (ie, "shock liver") due to cardiovascular and/or Bacterial sepsis – Should be considered in the appropriate clinical context.

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Last Reviewed:11/09/2021
Last Updated:07/13/2023
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Hepatitis C virus infection
A medical illustration showing key findings of Hepatitis C virus infection (Acute) : Dark urine, Fever, Jaundice, Nausea/vomiting, Anorexia, Arthralgia, RUQ pain
Clinical image of Hepatitis C virus infection - imageId=330635. Click to open in gallery.  caption: 'Deep red palmar erythema in an HIV-infected patient.'
Deep red palmar erythema in an HIV-infected patient.
Copyright © 2024 VisualDx®. All rights reserved.