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Key Features

Essentials of Diagnosis

  • Chronic inflammatory reaction of the liver of more than 3–6 months' duration

  • Persistently abnormal serum aminotransferase levels and antibody to hepatitis C virus (HCV) in serum

General Considerations

  • Chronic hepatitis is characterized on

    • The basis of the etiology

    • The grade of portal, periportal, and lobular inflammation (minimal, mild, moderate, or severe)

    • The stage of fibrosis (none, mild, moderate, severe, cirrhosis)

  • HCV may be the most common etiology of chronic hepatitis

  • HCV coinfection is found in 30% of persons infected with HIV

  • Anti-HCV is not protective; in chronic hepatitis its presence in serum signifies that HCV is the cause


  • Chronic hepatitis C develops in up to 85% of patients with acute hepatitis C

  • The number of cases of chronic HCV infections in the United States decreased from 3.2 million in 2001 to 2.3 million in 2013, although estimates of at least 4.6 million persons exposed and 3.5 million currently infected have also been reported

  • HCV was responsible for over 90% of cases of posttransfusion hepatitis; yet only 4% of cases of hepatitis C were attributable to blood transfusions

  • Over 50% of cases are transmitted by injection drug use

  • The risk of sexual and maternal-neonatal transmission is low and may be greatest in those with high circulating levels of HCV RNA

  • Multiple sexual partners may increase the risk of HCV infection

Clinical Findings

Symptoms and Signs

  • Clinically indistinguishable from chronic hepatitis due to other causes

Differential Diagnosis

  • Hepatitis B and D (delta agent)

  • Autoimmune hepatitis

  • Alcoholic and nonalcoholic steatohepatitis

  • α1-Antiprotease deficiency

  • Drug-induced hepatitis

  • Hemochromatosis

  • Wilson disease

  • Gluten enteropathy (rarely)


Laboratory Tests

  • Serum anti-HCV by enzyme immunoassay (EIA) is present (Figure 16–3)

  • In approximately 40% of cases, serum aminotransferase levels are persistently normal

  • In rare cases of negative anti-HCV EIA, HCV RNA is detected by polymerase chain reaction (PCR)

Diagnostic Procedures

  • Liver biopsy is indicated in patients offered treatment for diagnosis, staging, and predicting response to therapy



  • Peginterferon and ribavirin

    • Combination of these agents was standard therapy from the late 1990s to the early 2010s

    • Ribavirin continues to be used in some all-oral regimens but use is declining

  • Because of high discontinuation rates and distressing side effects, peginterferon-based is being supplanted by new oral direct-acting antiviral agents (Table 16–6)

    • Nonstructural (NS)3/4A protease inhibitors

      • Higher rates of response were achieved in persons infected with HCV genotype 1 when a NS3/4A serine protease inhibitor was added to peginterferon plus ribavirin

    • NS5A inhibitors

      • Characterized by high antiviral potency at picomolar doses

    • NS5B nucleos(t)ide polymerase inhibitors

      • Active against all HCV ...

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