What are the recommended labs and management for a patient with a remote history of positive Hepatitis C (HCV) infection?

Recommended Laboratory Testing and Management for Remote Positive Hepatitis C

For a patient with a remote history of positive HCV, immediately obtain HCV antibody testing with reflex HCV RNA PCR using a single blood draw to determine if the infection is active or resolved. 1

Initial Diagnostic Approach

The critical first step is distinguishing between active chronic infection versus spontaneously resolved past infection:

• Order anti-HCV antibody testing with automatic reflex to quantitative HCV RNA PCR if the antibody is reactive, using the same blood specimen without requiring a second draw 1, 2
• A reactive antibody with non-detectable HCV RNA indicates past resolved infection (most common scenario) or rarely a false-positive antibody test 3, 2
• A reactive antibody with detectable HCV RNA confirms active chronic HCV infection requiring further evaluation and treatment 2, 1

Management Based on Test Results

If HCV RNA is Non-Detectable (Past Resolved Infection)

No antiviral therapy or specific monitoring is needed for patients with negative HCV RNA. 3

• Inform the patient they do not have current HCV infection and are not infectious to others 3
• Counsel patients with ongoing risk factors (injection drug use, high-risk sexual practices, occupational exposures) about HCV transmission prevention 3
• Consider periodic HCV RNA retesting (annually or as clinically indicated) only in patients with continued high-risk exposures to detect potential reinfection 3
• Do not use antibody testing to detect reinfection, as antibodies remain positive indefinitely after clearance; only HCV RNA testing can identify new infection 1

If HCV RNA is Detectable (Active Chronic Infection)

Proceed with comprehensive pre-treatment laboratory evaluation:

Required Baseline Laboratory Tests 1, 2

• Quantitative HCV RNA viral load to establish baseline 1, 2
• HCV genotype determination (though less critical with pangenotypic direct-acting antivirals) 1, 2
• Complete blood count (CBC) 1
• Comprehensive metabolic panel including creatinine and calculated GFR 1
• Hepatic function panel (AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin) 1
• International normalized ratio (INR) 1
• Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) - mandatory before initiating any HCV treatment due to risk of HBV reactivation 4
• HIV antibody testing due to overlapping risk factors and impact on prognosis 1

Fibrosis Assessment 2, 1

Assess degree of liver fibrosis using non-invasive methods before treatment:

• Calculate FIB-4 score: age (years) × AST (IU/L) / [platelet count (10⁹/L) × √ALT (IU/L)] 2
  • FIB-4 <1.45 has 90% negative predictive value for advanced fibrosis 2
  • FIB-4 >3.25 has 65% positive predictive value for advanced fibrosis 2
• Calculate APRI score: (AST/upper limit of normal) × 100 / platelet count (10⁹/L) 2
  • APRI >1.5 suggests significant fibrosis (AUROC 0.8) 2
  • APRI >2.0 suggests cirrhosis (AUROC 0.89) 2
• If advanced fibrosis is suspected based on FIB-4 or APRI, obtain transient elastography (FibroScan) or alternative non-invasive testing 2, 1
  • Cutoff values for significant fibrosis (≥F2): 7.1-8.8 kPa 2
  • Cutoff values for cirrhosis: 12.5-14.6 kPa 2

Common pitfall: Do not rely on ALT levels alone to stage disease, as ALT fluctuates and does not correlate with fibrosis stage 1

Treatment Considerations

All patients with confirmed chronic HCV infection should be considered for treatment regardless of fibrosis stage, as the goal is to eradicate HCV and prevent progression to cirrhosis, hepatocellular carcinoma, and death. 2

Treatment Regimens for Non-Cirrhotic or Compensated Cirrhosis (Child-Pugh A) 4, 5

• Sofosbuvir/velpatasvir (Epclusa) 400mg/100mg once daily for 12 weeks - pangenotypic regimen for genotypes 1-6 4, 5
• Glecaprevir/pibrentasvir (Maviret) for 8 weeks - alternative pangenotypic option 5
• Both regimens achieve >90% sustained virologic response rates 4

Monitoring During Treatment 1

• Week 4 of treatment: CBC, creatinine, calculated GFR, hepatic function panel, quantitative HCV RNA 1
• Additional monitoring as clinically indicated for drug-related toxicity 1
• Discontinue therapy immediately if 10-fold increase in ALT at week 4, or any ALT increase <10-fold accompanied by weakness, nausea, vomiting, jaundice, increased bilirubin, alkaline phosphatase, or INR 1

Post-Treatment Assessment 1, 2

Measure quantitative HCV RNA at 12 weeks after completion of therapy (SVR12) to confirm virologic cure:

• Undetectable HCV RNA at ≥12 weeks post-treatment indicates sustained virologic response (SVR), which represents virologic cure with >99% durability 1, 2
• SVR corresponds to definitive cure of HCV infection in more than 99% of cases 2

Long-Term Follow-Up After Achieving SVR

Patients Without Advanced Fibrosis (F0-F2) 1

• No additional HCV-specific follow-up required 1
• Counsel on risk reduction if ongoing risk factors present 3

Patients With Advanced Fibrosis or Cirrhosis (F3-F4) 1

Despite achieving SVR, patients with cirrhosis remain at risk for hepatocellular carcinoma and require indefinite surveillance:

• Abdominal ultrasound every 6 months indefinitely for hepatocellular carcinoma surveillance 1
• Endoscopic surveillance for esophageal varices if cirrhosis is present 1
• Hepatic function panel, CBC, and INR every 6-12 months 1

Critical Safety Considerations

Hepatitis B Reactivation Risk 4

All patients must be tested for HBsAg and anti-HBc before initiating HCV treatment, as HBV reactivation during or after HCV treatment can cause fulminant hepatitis, hepatic failure, and death:

• HBV reactivation has been reported in both HBsAg-positive patients and those with resolved HBV infection (HBsAg-negative, anti-HBc-positive) 4
• Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up 4
• Initiate appropriate HBV antiviral therapy as clinically indicated 4

Referral Indications 5

Refer to hepatology/liver clinic if:

• Decompensated cirrhosis (Child-Pugh B or C) 4
• HIV or HBV coinfection 5
• Significant comorbidities affecting treatment selection 5
• Prior treatment failure with direct-acting antivirals 5

Patients without advanced fibrosis and without comorbidities can be treated by educated primary care physicians. 5