How should I screen, diagnose, and treat an adult with chronic hepatitis C (no decompensated cirrhosis), including preferred pan‑genotypic direct‑acting antiviral regimens and adjustments for cirrhosis, renal impairment, HIV co‑infection, or prior DAA failure?

Hepatitis C: Screening, Diagnosis, and Treatment in Adults

Screening

All adults aged 18 years and older should be screened for hepatitis C at least once in their lifetime, and during each pregnancy. 1, 2

• Begin with an HCV antibody test that automatically reflexes to HCV RNA PCR testing if positive—this single blood draw approach avoids the major barrier of requiring patients to return for confirmatory testing 1
• Persons with ongoing risk factors (particularly injection drug users) require periodic screening as long as risk behavior continues 1
• One-time screening is recommended for patients younger than 18 years who have risk factors 2

Diagnosis

Confirm active infection with quantitative or qualitative HCV RNA testing (detection level ≤25 IU/mL) following a positive antibody test. 1

Key Diagnostic Steps:

• HCV RNA positive = current active infection requiring treatment 1
• HCV antibody positive but RNA negative = either past resolved infection or false positive; no current infection 1
• For immunocompromised patients or those with exposure within the past 6 months, proceed directly to HCV RNA testing as antibody may be falsely negative 1

Essential Pre-Treatment Assessment:

• Assess fibrosis stage using FIB-4 score (preferred initial test); cirrhosis is presumed if FIB-4 >3.25, transient elastography >12.5 kPa, platelet count <150,000/mm³, or clinical evidence of liver nodularity/splenomegaly 1
• Screen for HIV and hepatitis B (HBsAg) in all patients—coinfection worsens prognosis and affects treatment selection 1, 3
• Genotyping is no longer required for treatment-naive patients without cirrhosis when using pangenotypic regimens 1
• Genotyping IS required for patients with prior DAA treatment failure 1

Treatment: Treatment-Naive Adults WITHOUT Cirrhosis

For treatment-naive adults without cirrhosis, use simplified pangenotypic regimens that achieve >95% cure rates. 1, 2

Recommended First-Line Regimens:

• Glecaprevir 300 mg/pibrentasvir 120 mg taken with food for 8 weeks 1, 4, 2
• Sofosbuvir 400 mg/velpatasvir 100 mg for 12 weeks 1, 4, 2

Patients NOT Eligible for Simplified Treatment (Require Specialist Referral):

• Prior hepatitis C treatment failure 1
• End-stage renal disease (eGFR <30 mL/min) 1
• HIV or HBsAg positive 1
• Current pregnancy 1
• Known or suspected hepatocellular carcinoma 1
• Prior liver transplantation 1

Treatment: Treatment-Naive Adults WITH Compensated Cirrhosis (Child-Pugh A)

Patients with compensated cirrhosis can use the same pangenotypic regimens but require additional monitoring. 1

Recommended Regimens:

• Glecaprevir 300 mg/pibrentasvir 120 mg with food for 8 weeks 1, 4
• Sofosbuvir 400 mg/velpatasvir 100 mg for 12 weeks 1, 4

Additional Pre-Treatment Requirements for Cirrhosis:

• Calculate Child-Pugh score—patients with Child-Pugh B or C (score ≥7) have decompensated cirrhosis and are NOT eligible for simplified treatment 1
• Obtain liver ultrasound within prior 6 months to exclude hepatocellular carcinoma and subclinical ascites 1
• Providers may order periodic blood tests during treatment to monitor for rare hepatic decompensation 1

Special Populations

Decompensated Cirrhosis (Child-Pugh B/C):

Sofosbuvir combined with an NS5A inhibitor (ledipasvir, velpatasvir, or daclatasvir) with or without ribavirin is the treatment of choice. 5, 6

• Protease inhibitor combinations are specifically NOT recommended due to safety concerns 6
• SVR rates exceed 80% but are lower than in compensated cirrhosis 6
• Risk factors for further decompensation: albumin <3.5 g/dL, MELD >14, or genotype 3 infection 6

Renal Impairment:

• All DAAs may be used safely down to eGFR 30 mL/min 5
• Simeprevir, paritaprevir, ombitasvir, and dasabuvir may be given down to eGFR 15 mL/min 5
• Daclatasvir requires no dose adjustment in any degree of renal impairment 5

HIV Coinfection:

• Requires specialist management due to drug-drug interactions with antiretroviral therapy 1, 7, 8
• DAA therapy is highly effective in HIV-coinfected patients 8

Prior DAA Failure:

• Requires genotyping to guide retreatment regimen selection 1
• Must be managed by a specialist 1

On-Treatment Monitoring

No routine laboratory monitoring is required for most patients on modern DAA regimens. 1

Specific Monitoring Requirements:

• Patients on diabetes medications: Monitor for symptomatic hypoglycemia 1
• Patients on warfarin: Monitor INR for subtherapeutic anticoagulation 1
• Patients with cirrhosis: Consider periodic monitoring for hepatic decompensation (rare) 1
• Assess for drug-drug interactions using AASLD/IDSA guidance or University of Liverpool checker 1

Assessment of Cure

Test for sustained virologic response (SVR) with quantitative HCV RNA at 12 weeks or later after completing therapy. 1, 2

• Undetectable HCV RNA at 12 weeks post-treatment = virologic cure 1, 2
• Also obtain hepatic function panel to confirm transaminase normalization 1
• Continue monitoring for hypoglycemia (diabetes patients) and INR (warfarin patients) 1

Post-SVR Follow-Up

Patients WITH Cirrhosis (Even After SVR):

• Hepatocellular carcinoma surveillance: Abdominal ultrasound ± alpha-fetoprotein every 6 months indefinitely 3, 2
• Variceal screening: Upper endoscopy every 2-3 years 2

Patients WITHOUT Cirrhosis After SVR:

• No liver-related follow-up is required 2
• Assess for other causes of liver disease if transaminases remain elevated 1

Patient Education and Counseling

All patients with HCV infection must receive comprehensive counseling at diagnosis. 1

• Alcohol abstinence is mandatory—no safe level of alcohol exists for HCV patients, and alcohol accelerates fibrosis and hepatocellular carcinoma development 1
• Educate about HCV transmission prevention to protect others 1
• Vaccinate against hepatitis A and hepatitis B if susceptible 1
• Vaccinate against pneumococcal infection if cirrhosis present 1
• Avoid hepatotoxic drugs (acetaminophen >2 g/day, certain herbal supplements) and nephrotoxic drugs (NSAIDs) in cirrhotic patients 1

Critical Pitfalls to Avoid

• Do NOT delay treatment in any patient, including those with ongoing substance use—active drug or alcohol use is NOT a contraindication to DAA therapy 1, 3
• Do NOT skip HIV and HBV screening—coinfection dramatically affects prognosis and treatment approach 1, 3, 7
• Do NOT use protease inhibitor combinations in decompensated cirrhosis due to safety concerns 6
• Do NOT forget HBV reactivation risk—patients positive for HBsAg require additional monitoring during HCV treatment 1
• Do NOT discontinue HCC surveillance after SVR in cirrhotic patients—cancer risk persists despite viral cure 3, 2