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For further information, see CMDT Part 16-06: Chronic Viral Hepatitis

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

Demographics

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

  • Worldwide, 170 million people are infected with HCV, with 1.8% of the US population infected

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)

Diagnosis

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

Treatment

Medications

  • 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 treatment 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 genotypes

      • Have a high barrier to resistance

    • NS5B non-nucleos(t)ide polymerase inhibitors

      • Non-nucleoside polymerase inhibitors are the weakest class of compounds against HCV because of a low barrier to resistance

      • Most drugs in this class are more active against HCV genotype 1b than HCV genotype 1a

      • Being developed to be used only in combination with the other direct-acting antiviral agents, mainly protease inhibitors and NS5A inhibitors

  • Simeprevir

    • Effective for genotypes 1 and 4

    • Dosage: 150 mg orally once daily

      ...

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