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BASICS

Description

  • Systemic viral infection involving the liver.

Epidemiology

  • Incidence of acute HCV has more than doubled since 2013.
  • IV drug use accounts for 60-70% of new cases.
  • HCV is the leading cause of chronic liver disease and transplantation in the US.
  • Eight genotypes with 86 subtypes; genotype 1 accounts for 75% in the US.
  • Genotype influences treatment response.

Special Populations

  • Geriatric: Patients >60 years may respond less to therapy due to advanced fibrosis/cirrhosis.
  • Pregnancy: Routine prenatal HCV testing recommended; retest RNA postpartum for clearance.
  • Pediatric: Test children born to HCV-positive mothers at 18 months; treatment starts at age ≥3 years.

DIAGNOSIS

History

  • Assess exposure risks: social, IV drug use, alcohol, psychiatric, coinfections.
  • Chronic HCV often asymptomatic or mild fatigue, depression.
  • Acute HCV usually asymptomatic or mild symptoms 2-12 weeks postexposure.

Physical Exam

  • RUQ tenderness, hepatomegaly, jaundice.
  • Signs of advanced liver disease: spider angioma, caput medusa, palmar erythema, gynecomastia, Terry nails.
  • HCV-associated extrahepatic manifestations: arthralgias, neuropathy, skin lesions (porphyria cutanea tarda, lichen planus).

Differential Diagnosis

  • Hepatitis A, B, D, E; EBV, CMV; alcoholic hepatitis; NASH; hemochromatosis; Wilson disease; autoimmune hepatitis.

Laboratory and Imaging

  • One-time routine HCV antibody (Ab) screening for adults 18-79 years.
  • If antibody reactive, confirm with HCV RNA testing.
  • Anti-HCV Ab detectable 4-10 weeks after infection; 97% develop antibodies by 6 months.
  • HCV RNA detectable 1-2 weeks after infection.
  • Pretreatment labs: CBC, liver function, INR, eGFR, HIV screening, hepatitis B status.
  • Assess hepatic fibrosis via FIB-4 score, US, CT, MRI, elastography, or liver biopsy.

TREATMENT

General Measures

  • Goal: achieve sustained virologic response (SVR), reduce liver disease progression and mortality.
  • Report acute HCV cases to health department.
  • Treat all with virologic evidence of infection except children <3 years, pregnancy, or short life expectancy.

Medications

First Line

  • Patients divided by presence of cirrhosis (none or compensated).
  • Simplified treatment: Does not require genotype testing in most cases.
  • Noncirrhotic: Glecaprevir/pibrentasvir (Mavyret) for 8 weeks or Sofosbuvir/velpatasvir (Epclusa) for 12 weeks.
  • Compensated cirrhosis: same as above with genotype-specific considerations.
  • Review all medications for drug interactions.
  • Screen for hepatitis B due to risk of reactivation with HCV treatment.

Second Line

  • For treatment-experienced or failure cases:
  • Sofosbuvir/velpatasvir/voxilaprevir ± ribavirin.
  • Glecaprevir/pibrentasvir + sofosbuvir + ribavirin.

ONGOING CARE

Follow-Up

  • SVR12: undetectable HCV RNA 12 weeks post-treatment indicates cure.
  • If no cirrhosis: no continued surveillance recommended after SVR.
  • If cirrhosis present: ultrasound ± α-fetoprotein every 6 months for HCC surveillance.
  • Endoscopic screening for varices:
  • Compensated cirrhosis without varices: every 2-3 years.
  • Known varices: every 1-2 years.

DIET AND PATIENT EDUCATION

  • Low-fat, high-fiber diet.
  • Exercise to address obesity and fatty liver.
  • Avoid alcohol, tobacco, illicit drugs.
  • Counsel on transmission risk and avoid hepatotoxic supplements.

PROGNOSIS

  • Approximately 50% of chronic HCV cases are diagnosed.
  • SVR rates with modern therapy >95%.
  • 5-25% develop cirrhosis within 10-20 years if untreated.
  • Cirrhosis increases risk for HCC (1-4% annually) and hepatic decompensation (3-6% annually).
  • Successful SVR reduces HCC risk by ~70% and liver-related mortality by 90%.

COMPLICATIONS

  • Progressive fibrosis and cirrhosis.
  • Hepatocellular carcinoma.
  • Risk factors for cirrhosis include age, race, hypertension, alcohol, anemia.
  • Risk factors for hepatic decompensation include diabetes, hypertension, anemia.

REFERENCES

  1. Schillie S, Wester C, Osborne M, et al. CDC recommendations for hepatitis C screening among adults —United States, 2020. MMWR Recomm Rep. 2020;69(2):1-17.

  2. Ghany MG, Morgan TR. Hepatitis C guidance 2019 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology. 2020;71(2):686-721.

CLINICAL PEARLS

  • HCV is the most common cause of HCC in the western world.
  • Genotype 1 is predominant in the US.
  • 10% of HCV patients have no identifiable risk factors.
  • One-time screening for adults 18-79 years recommended.
  • 15-25% clear infection spontaneously; half progress to chronic infection.
  • Early treatment prevents progression and improves outcomes.