Hepatitis C, Chronic

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

  ...