Acute Hepatitis C Infection

Background

• Hepatitis C virus (HCV) is an RNA virus of the Flaviviridae family with 6 primary genotypes.
• Most patients with acute HCV infection are asymptomatic, but symptoms are reported to occur in 20%-33% of patients. Symptoms are usually nonspecific but can include fatigue, myalgia, nausea, vomiting, low-grade fever, dark urine, and/or abdominal pain.
• The disease onset can occur 2-12 weeks after exposure (mean time of 7 weeks).
• Approximately 80% of people with acute HCV infection do not clear the virus and progress to chronic hepatitis C infection. The reported range typically varies from 50% to 90%. Persons with icteric illness caused by acute HCV infection are more likely to have spontaneous and complete clearance of the virus.
• Risk factors for acute hepatitis C include substance use (highest risk for IV drug use but intranasal drug use, such as cocaine use also linked to infection); anal sex, particularly among men who have sex with men; and parenteral exposure to blood and blood products.
• Acute hepatitis C is considered a reportable infection in 49 of the 50 states in the United States. Matching this and other viral hepatitis with HIV surveillance registries facilitates early detection of "social networks of HCV transmission", as among men with HIV infection who have sex with men or other contacts.

Evaluation

• Clinical concern for acute HCV may be prompted by clinical presentation or elevated aminotransferase levels, particularly in patients with a history of exposure, injection or intranasal drug use, anal intercourse, or a history of incarceration.
• Elevation of alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) may be the first indication of acute HCV.
• Hepatitis C antibodies (anti-HCV testing) and HCV RNA testing are recommended as initial tests when there is a concern for acute HCV (Strong recommendation).
• Evaluation of increased liver enzymes should include other potential causes such as acute hepatitis A, hepatitis B (HBV) with or without hepatitis D, hepatitis E, autoimmune hepatitis, drug-induced liver injury, ischemic liver injury, and biliary disease
• The presence of HCV RNA without detectable antibodies is suggestive of early acute infection, especially when followed by seroconversion.
• In patients with suspected acute HCV infection, the diagnosis may be made based on any of the following:
  • a patient tests negative for HCV antibodies and positive for HCV RNA
  • documented seroconversion of anti-HCV antibodies, where a patient tests positive for anti-HCV antibodies with a recent record of a prior negative anti-HCV test, with confirmation by a positive HCV RNA test.
  • documented positive HCV RNA, with a recent record of prior negative HCV RNA test (an anti-HCV test may be either negative in case of new infection or positive in case of reinfection)
  • patient has no prior record of HCV RNA testing, a current positive HCV RNA test (anti-HCV test result not contributive), and all of the following:
    • recent high-risk exposure
    • marked new elevation of liver enzymes that may often include notable patterns of rapid fluctuation
    • acute hepatitis symptoms with exclusion of other potential causes
• As part of the initial evaluation, consider standard liver biochemical tests, prothrombin, INR, and complete blood count to determine the liver disease severity.
• In patients with discrete exposure, conduct baseline testing within 48 hours.
  • If baseline testing is negative, repeat testing is recommended at 1 month and 3 months at a minimum.
  • If earlier identification is desired, repeat HCV RNA and ALT testing every 4-8 weeks for 6 months.

Management

• For persons with active HCV infection, implement the following interventions with the goals of reducing progression of liver disease.
  • Counsel patients to avoid alcohol consumption and hepatotoxic drugs including acetaminophen; also counsel on how to avoid spreading HCV to others (Strong recommendation).
  • Refer all patients with acute HCV related to substance use to an addiction specialist (Strong recommendation).
  • American Association for the Study of Liver Diseases/Infectious Diseases Society of America (AASLD/IDSA) recommends vaccination against hepatitis A and hepatitis B for all susceptible persons with HCV infection.
• Optimal time for starting treatment in patients with acute HCV infection is uncertain.
  • For patients with acute hepatitis C not at an increased risk, guidelines differ regarding when to initiate therapy.
    • AASLD/IDSA recommends monitoring HCV RNA for ≥ 12-16 weeks before starting treatment to allow opportunity for spontaneous resolution before treatment consideration.
    • The European Association for Study of the Liver guidelines recommend considering antiviral therapy for patients who are HCV RNA positive in order to prevent progression to chronic hepatitis C.
  • Clinical situations which may favor early treatment over waiting for spontaneous clearance include:
    • an increased risk for transmitting infection such as a surgeon or other physician, persons who inject drugs, and/or men who have sex with men, particularly who are HIV positive
    • a risk of severe clinical consequences, such as a patient with cirrhosis and acute superinfection of HCV
    • higher likelihood of loss to follow-up, such as patients who may not be engaged in care for 3-6 months
  • If a delay in treatment initiation is considered and acceptable to practitioner and patient, monitor for spontaneous clearance at 3 months. When a decision is made to initiate treatment after this time, then treat as for chronic hepatitis C (Weak recommendation).
• For treatment and follow-up management details for both treated and untreated patients, see
  • Chronic hepatitis C infection
  • Hepatitis C - treatment of genotype 1
  • Hepatitis C - treatment of genotypes 2-6
• Note that patients coinfected with HBV require monitoring of HBV viral load and assessment for potential interventions with anti-HBV treatment using direct acting antivirals (DAAs). FDA Safety Communication 2016 Oct 4 lists DAAs associated with hepatitis B reactivation.
• For those who are not treated with antiviral medication at an early time, for whatever reason:
  • Regular lab monitoring of patients with acute HCV infection for 6-12 months with serial HCV measurements is recommended in order to determine whether there is persistence of infection. (Strong recommendation).
  • Follow up visits and monitoring of liver chemistries with provision of therapy in patients who do not spontaneously clear virus is recommended according to chronic HCV guidelines.