A 48-year-old man with a 15-year history of intravenous drug use presents with progressive jaundice, ascites, and splenomegaly. He reports a single episode of acute hepatitis 12 years ago. Laboratory findings: ALT 120 IU/L, AST 240 IU/L, albumin 2.8 g/dL, total bilirubin 6.5 mg/dL, platelet count 85,000/μL, PT-INR 1.8. HBsAg is negative, anti-HBc is positive, anti-HCV is positive, HCV RNA is detectable. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Chronic Hepatitis C with Cirrhosis ### Key Diagnostic Features **Key Point:** This patient has chronic hepatitis C with established cirrhosis, evidenced by portal hypertension (ascites, splenomegaly, thrombocytopenia) and hepatic synthetic dysfunction (low albumin, coagulopathy). ### Serological Interpretation | Marker | Result | Interpretation | |--------|--------|----------------| | **HBsAg** | Negative | No active HBV infection | | **Anti-HBc** | Positive | Past HBV exposure/resolved infection | | **Anti-HCV** | Positive | HCV exposure (past or present) | | **HCV RNA** | Detectable | **Active HCV replication** — chronic infection | **High-Yield:** Detectable HCV RNA in the presence of anti-HCV confirms chronic hepatitis C. The negative HBsAg with positive anti-HBc indicates resolved hepatitis B (immunity or past infection), not active disease. ### Evidence of Cirrhosis **Mnemonic: ASPEN** — features of portal hypertension and liver failure: - **A**scites (present) - **S**plenomegaly (present) - **P**latelet count <100,000/μL (85,000 — present) - **E**levated PT-INR (1.8 — present) - **N**ormal/low albumin (2.8 — present) ### Pathophysiology of Chronic HCV 1. HCV establishes persistent infection in ~80% of acutely infected individuals 2. Chronic inflammation → hepatic fibrosis over 10–30 years 3. Progressive cirrhosis with portal hypertension and synthetic dysfunction 4. This patient's 15-year IVDU history with detectable HCV RNA confirms chronic infection **Clinical Pearl:** The combination of detectable HCV RNA, clinical signs of portal hypertension (ascites, splenomegaly), thrombocytopenia, and coagulopathy indicates cirrhosis. The negative HBsAg excludes active hepatitis B. ### Distinction from Other Diagnoses - **Occult HBV** would show detectable HBV DNA despite negative HBsAg — not present here - **Acute HCV superinfection** would show acute transaminitis (ALT/AST >1000) — not seen - **HBV reactivation** requires positive HBsAg — absent in this case [cite:Robbins 10e Ch 18]