What tests are recommended for a patient with a remote history of Hepatitis C Virus (HCV) infection to evaluate liver function and detect potential complications?

Evaluation of Remote History of HCV

For a patient with remote history of HCV, start with HCV RNA testing to determine if active infection persists, followed by assessment of liver fibrosis and hepatic function to evaluate for cirrhosis and its complications.

Initial Virological Assessment

The first priority is determining whether the patient has cleared the virus or has chronic infection:

• Obtain quantitative HCV RNA testing using a sensitive assay (lower limit of detection ≤50 IU/ml, ideally real-time PCR) to confirm current infection status 1
• If HCV RNA is negative, the patient has spontaneously cleared the infection or achieved prior cure; no further HCV-specific treatment is needed 1
• If HCV RNA is positive, chronic infection persists and requires full evaluation for treatment 1
• Anti-HCV antibody testing alone is insufficient, as antibodies persist after viral clearance and cannot distinguish active from resolved infection 1

Assessment of Liver Damage and Fibrosis

Regardless of HCV RNA status, evaluate for existing liver damage since fibrosis can progress even after viral clearance:

Laboratory Testing

• Hepatic function panel including AST, ALT, total bilirubin, albumin, and INR to assess synthetic liver function 1, 2
• Complete blood count (CBC) with platelet count, as thrombocytopenia (platelets <150,000/mm³) suggests cirrhosis 1, 3
• Calculate FIB-4 score using: age (years) × AST (IU/L) / [platelet count (10⁹/L) × √ALT (IU/L)] 2, 4
  • FIB-4 <1.45 effectively rules out advanced fibrosis 2
  • FIB-4 >3.25 suggests cirrhosis 2, 4

Critical caveat: Do not rely on normal transaminases to exclude liver disease—approximately 50% of patients with chronic viral hepatitis have normal ALT/AST despite ongoing liver damage 1, 3.

Non-Invasive Fibrosis Assessment

• Transient elastography (FibroScan) if available, with stiffness >12.5 kPa indicating cirrhosis 1, 4
• Non-invasive serum markers (FibroSure, Enhanced Liver Fibrosis Test) can detect significant fibrosis (METAVIR F2-F4) 1, 4
• Liver biopsy remains the reference standard but is typically reserved for unclear cases 1

Evaluation for Cirrhosis and Decompensation

If cirrhosis is suspected (FIB-4 >3.25, elastography >12.5 kPa, platelets <150,000/mm³, or clinical evidence):

Calculate Child-Turcotte-Pugh (CTP) Score

Assess five parameters to differentiate compensated (CTP-A) from decompensated cirrhosis (CTP-B or C) 1, 3:

• Total bilirubin (>2.0 mg/dL indicates decompensation) 3
• Albumin (<3.5 g/dL indicates decompensation) 3
• INR (≥1.7 indicates decompensation) 3
• Presence of ascites 3
• Presence of hepatic encephalopathy 3

A CTP score ≥7 or any single criterion of decompensation (ascites, encephalopathy, bilirubin >2.0, albumin <3.5, or INR ≥1.7) confirms decompensated cirrhosis 3.

Imaging Studies

• Liver ultrasound (within prior 6 months) is mandatory for cirrhotic patients to screen for hepatocellular carcinoma (HCC) and detect subclinical ascites 1, 3, 4
• Evaluate for liver nodularity and splenomegaly as additional evidence of cirrhosis 1, 4

Common pitfall: Subclinical ascites may be present on ultrasound without obvious clinical signs, indicating more advanced disease than clinically apparent 3, 4.

Additional Testing for Active Infection

If HCV RNA is positive, obtain:

• HCV genotype/subtype to guide treatment selection if therapy is planned 1, 2
• Screening for extrahepatic manifestations including cryoglobulins if symptoms suggest mixed cryoglobulinemia syndrome 1

Surveillance Requirements

For Patients with Cirrhosis (Regardless of HCV RNA Status)

• Lifelong HCC surveillance with liver ultrasound every 6 months, as HCC risk persists even after viral clearance 1, 4
• Endoscopy to screen for esophageal varices if not previously performed 1
• Disease progression monitoring every 6-12 months with hepatic function panel, CBC, and INR 1, 2

For Patients Without Cirrhosis

• If HCV RNA negative and no advanced fibrosis (F0-F2), no additional HCV-specific follow-up is required 1
• If persistently elevated transaminases despite negative HCV RNA, assess for other causes of liver disease 1

Risk Factor Assessment

• Evaluate ongoing HCV exposure risk (injection drug use, men who have sex with men, incarceration, hemodialysis) 1
• For patients with ongoing risk factors, annual HCV RNA testing is recommended even if previously negative 1, 2

Key principle: The evaluation must be tailored to whether active infection persists and whether cirrhosis is present, as these two factors fundamentally determine prognosis, surveillance needs, and treatment urgency 1, 4.