The Question
A 62-year-old man with type 2 diabetes and longstanding chronic hepatitis C is evaluated for antiviral therapy. He reports mild fatigue but no jaundice, ascites, or encephalopathy. Vitals are stable. Exam shows small non-tender hepatomegaly and no stigmata of chronic liver disease. Labs: ALT 85 U/L, AST 110 U/L, total bilirubin 0.9 mg/dL, albumin 3.8 g/dL, INR 1.1, platelets 130,000/microL, serum creatinine 2.2 mg/dL (eGFR ~25 mL/min/1.73 m2). HCV RNA 3.2 million IU/mL, genotype 1a. Hepatitis B surface antigen negative, HIV antibody negative. Abdominal ultrasound shows a nodular liver consistent with cirrhosis but no portal vein thrombosis; he has compensated cirrhosis (Child-Pugh A). He is treatment-naïve. Which of the following is the most appropriate antiviral regimen for this patient?
See the answer and explanation below:
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View on AmazonThe Correct Answer
B
Explanation
High-Yield Pearl: In patients with chronic HCV and severe renal impairment or dialysis-dependent kidney disease, the protease inhibitor–NS5A combination glecaprevir/pibrentasvir is the guideline-preferred pan-genotypic regimen; for treatment-naïve patients with compensated cirrhosis the usual duration is 12 weeks.
Detailed Reasoning: This patient has genotype 1a chronic HCV with compensated cirrhosis and advanced CKD (eGFR ~25), making choice of antiviral guided by renal function and cirrhosis status; AASLD-IDSA guidance favors glecaprevir/pibrentasvir in patients with eGFR <30 including those on dialysis. Sofosbuvir-containing regimens (sofosbuvir-velpatasvir or ledipasvir-sofosbuvir) were initially avoided in severe renal impairment because the predominant sofosbuvir metabolite is renally excreted and early trials excluded eGFR <30, so they are less preferred in this setting despite emerging data. Pegylated interferon plus ribavirin is outdated, poorly tolerated, and ribavirin poses significant toxicity and dosing challenges in severe CKD, so it is not appropriate. Deferring therapy until after kidney transplantation is unnecessary and delays viral cure and risks hepatic progression; treating now is recommended when a safe, effective regimen exists. Finally, note that protease inhibitor–containing regimens like glecaprevir are contraindicated in decompensated cirrhosis (Child-Pugh B/C), but this patient is Child-Pugh A, so glecaprevir-pibrentasvir for 12 weeks is the most appropriate choice per current AASLD-IDSA guidance.
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