Chronic Hepatitis C Infection

Background

• Hepatitis C virus (HCV) may cause a chronic, usually asymptomatic infection primarily affecting the liver. If left untreated, 55%-85% of adults with HCV develop persistent viremia; over about 25 years, about 20%-30% of patients will develop cirrhosis and the associated increased risk for hepatocellular cancer.
• HCV is the most common chronic blood borne infection in the United States and is most prevalent in adults born between 1945 and 1965.
• Transmission occurs primarily through percutaneous exposure to HCV-infected blood.
  • Sexual transmission of HCV among heterosexual monogamous couples is possible but occurs at exceedingly low rates.
  • Risk of vertical transmission of HCV from mother to baby appears low. Breastfeeding is not contraindicated.
• Risk factors associated with HCV transmission include
  • illicit injection and intranasal drug use.
  • exposure to percutaneous/parenteral needlesticks in unregulated or healthcare setting.
  • history of transfusions or organ transplants in selected prior recipients (mainly in countries with inconsistent or no HCV screening of donors).
  • unregulated tattooing or tattooing with non-sterile equipment.
  • current of history of long-term hemodialysis.
  • HIV-positive status (based on finding of significant rates of HCV co-infection).
  • sexual activity with HCV or HIV infected persons.
  • maternal HCV infection during pregnancy/birth.
  • incarceration.
• Prevention of HCV transmission includes blood and tissue bank monitoring, needle exchange programs, and educating the public on safe sex practices.
• Chronic hepatitis C infection is associated with an increased risk of liver-related mortality, but the absolute risk is low.
  • Coinfection with HIV or hepatitis B virus and HCV is associated with a greater prevalence of fibrosis, cirrhosis, and hepatocellular carcinoma. Alcohol consumption is associated with an increased risk of progression to fibrosis.
  • Chronic HCV is associated with extrahepatic manifestations particularly cryoglobulinemia, vasculitis, and renal disease.

Evaluation

Screening and Diagnosis

• Universal screening for hepatitis C virus (HCV) is recommended at least once for all adults aged up to 79 years (Strong recommendation).
  • Screening is also recommended in all pregnant women (Strong recommendation), and in persons with a history of certain high-risk behaviors (Strong recommendation).
  • Repeat testing should be considered in patients with ongoing behaviors associated with increased risk for HCV infection.
• Diagnosis of acute or chronic HCV infection usually requires both a serologic test of antibody to HCV (anti-HCV) and molecular assay for HCV RNA (viral load) (Strong recommendation).
  • Serum transaminase levels, in particular alanine aminotransferase (ALT) levels, fluctuate but can be normal or mildly elevated at any stage of chronic HCV infection.
  • Anti-HCV serology is recommended as the initial test for HCV infection.
    • If anti-HCV positive, current infection should be confirmed by sensitive quantitative HCV RNA test.
    • If anti-HCV negative, consider performing HCV RNA in patients with suspected liver disease and potential HCV exposure within prior 6 months, or in immunocompromised patients (such as those on chronic hemodialysis).
  • HCV RNA levels usually range from 10⁵-10⁷ units/L but may fluctuate widely; levels usually remain relatively stable within an individual patient and have no bearing on symptoms or fibrosis progression. There is no indication for repeat HCV RNA testing in a viremic patient outside of the antiviral treatment context.
  • Interpretation of diagnostic tests for HCV

Table 1. Test Interpretation

Testing and Evaluation

• Once diagnosed, HCV genotyping is useful for selecting an antiviral therapy and in certain genotypes, predicting response to antiviral therapy. (Strong recommendation).
• Inquire about co-morbidities, social history and medications. Most patients with chronic hepatitis C virus (HCV) infection are asymptomatic, though some may have non-specific symptoms and evidence of chronic liver disease on exam.
• Laboratory testing within 12 weeks of HCV antiviral testing includes complete blood count, hepatic function panel (albumin, total and direct bilirubin, ALT, aspartate aminotransferase (AST) and alkaline phosphatase levels), international normalized ratio (INR) and calculated glomerular filtration rate(eGFR); also test patients for HIV, hepatitis A, hepatitis B, and consider evaluation for extrahepatic manifestations, particularly cryoglobulinemia and other autoantibodies, vasculitis, and renal disease.
• Assessment for advanced fibrosis in patients with hepatitis C infection using noninvasive testing or liver biopsy is recommended to guide treatment strategy and define the need for additional screening measures, such as screening for hepatocellular carcinoma and esophageal varices (Strong recommendation).
  • If cirrhosis is clinically evident, staging tests are not necessary.
  • Fibrosis stage and presence of cirrhosis may be assessed noninvasively through a combination of direct serum biomarkers and vibration-controlled transient liver elastography.
    • Noninvasive alternatives to liver biopsy are preferred because of diagnostic accuracy, lack of procedural discomfort and biopsy risks.
    • If direct serum marker testing or liver elastography is not available, consider using aspartate aminotransferase-to-platelet ratio index (APRI) or fibrosis-4 (FIB-4) index to identify patients with advanced fibrosis or cirrhosis (Metavir stage F3-F4).
    • Consider liver biopsy if results from biomarkers and elastography are sufficiently discordant to affect clinical decision-making.
  • Ultrasound has limited utility for detecting the extent of liver steatosis in patients with chronic hepatitis C.
• All persons with HCV who, based on serologic testing, are susceptible to hepatitis A virus and hepatitis B virus should be vaccinated against hepatitis A and hepatitis B (Strong recommendation).
• Advise abstinence from alcohol, marijuana, and smoking. Each are associated with increased development of fibrosis (Strong recommendation).
• Perform a thorough review of a patient’s medications prior to HCV antiviral selection to avoid drug-drug interactions. (Strong recommendation). Common medications that interact with HCV direct-acting antiviral medications include amiodarone, statins, proton pump inhibitors and anticonvulsants.

Management

• Recommend treatment for all patients with chronic HCV infection, except those with short life expectancies that cannot be remediated by HCV therapy.
• Share decision-making for antiviral treatment regardless of signs of progression of liver fibrosis; treating early can optimally preserve liver function and avoid complications, particularly as methods to determine degree of fibrosis can underestimate the actual condition of the liver.
• Recommendations for antiviral treatment regimens vary by hepatitis C virus (HCV) genotype, prior treatment history, presence or absence of cirrhosis, and if cirrhosis present, the presence of hepatic decompensation.
• 72% of Americans with HCV have genotype 1a or 1b infection
  • Recommended Treatment Options for Treatment-naive Genotype 1a Patients

• • Recommended Treatment Options for Treatment-naive Genotype 1b Patients

• Retreatment regimens for patients who failed previous treatment vary by prior regimen and genotype.
• Patients with chronic kidney disease, including those on hemodialysis, may be treated with HCV antivirals approved for use in this setting.
• Patients with decompensated HCV-cirrhosis should be referred for consideration of liver transplant.
  • Pretransplant HCV treatment resulting in an sustained virologic response (virologic cure) prevents HCV recurrence posttransplantation.
  • It is important that HCV treatment in a potential liver transplant candidate be planned in coordination with a transplant hepatologist, and in some cases HCV treatment post-transplant may be preferable.
  • Regimens containing protease inhibitors are not recommended in patients with decompensated cirrhosis.
• See Hepatitis C - treatment of genotype 1 for additional information.
• See Hepatitis C - treatment of genotypes 2-6 for information related to other genotypes.
• For treatment of acute hepatitis C, delay in treatment to wait for spontaneous clearance is an option. If a delay in treating a new infection is acceptable, monitor for spontaneous clearance for at least 6 months and if treatment is initiated after 6 months, treat as chronic hepatitis C. If delay in treatment is not acceptable, the same regimens appropriate for patients with chronic HCV based on genotype also apply to patients with acute HCV.
• Monitoring and follow-up of patients receiving treatment for HCV infection
  • During treatment, perform clinic visits or telephone contacts to ensure adherence and to evaluate for adverse effects and drug-drug interactions. Recommended laboratory testing during antiviral therapy includes complete blood count, creatinine, eGFR, and a hepatic function panel after 4 weeks of treatment and as clinically indicated subsequently. Certain subgroups of patients may need more frequent monitoring (for example those taking ribavirin or with decompensated cirrhosis) . (Strong recommendation)
  • Quantitative HCV RNA testing is recommended after 4 weeks of therapy and 12 weeks after the completion of therapy. Undetectable HCV RNA 12 weeks after the completion of therapy is known as sustained virologic response (SVR12) and equates with cure.(Strong recommendation)
  • After successful treatment, for those without advanced fibrosis, follow up is identical to those who never had HCV infection (Strong recommendation).
  • If initial treatment is unsuccessful, monitor for disease progression every 6-12 months and evaluate for re-treatment as effective alternative treatments become available (Strong recommendation).
  • In patients with advanced fibrosis, perform surveillance for hepatocellular carcinoma with liver ultrasound with or without serum alpha fetoprotein every 6 months (Strong recommendation), regardless of treatment outcome.