A 45-year-old man from Mumbai is found to have chronic hepatitis C infection (HCV RNA positive, genotype 1b) with compensated cirrhosis (Child-Pugh A). He has no prior treatment for HCV. What is the drug of choice for treatment of chronic hepatitis C?

Question

Accepted Answer

A. Sofosbuvir + velpatasvir. ## Treatment of Chronic Hepatitis C **Key Point:** Direct-acting antivirals (DAAs), particularly sofosbuvir-based regimens, are now the gold standard for all genotypes of chronic hepatitis C, including genotype 1b with cirrhosis. ### Why Sofosbuvir + Velpatasvir? 1. **Pan-genotypic coverage**: Effective against all HCV genotypes (1–6), including genotype 1b 2. **High SVR rates**: >95% sustained virological response (SVR12) across all populations, including those with cirrhosis 3. **Oral, fixed-dose combination**: Convenient 12-week regimen; no injections 4. **Minimal drug interactions**: Unlike older regimens 5. **Tolerability**: Well-tolerated with minimal side effects ### Sofosbuvir + Velpatasvir Mechanism ```mermaid flowchart TD A[HCV RNA]:::outcome --> B[NS5B polymerase inhibition]:::action A --> C[NS5A inhibition]:::action B --> D[Viral replication blocked]:::outcome C --> D D --> E[Undetectable HCV RNA
SVR achieved]:::outcome ``` **High-Yield:** Sofosbuvir (NS5B inhibitor) + velpatasvir (NS5A inhibitor) = synergistic viral suppression. ### Comparison with Older Regimens | Regimen | Genotype Coverage | SVR Rate | Duration | Route | Tolerability | |---|---|---|---|---|---| | **Sofosbuvir + Velpatasvir** | Pan-genotypic (1–6) | >95% | 12 weeks | Oral | Excellent | | **Peg-IFN + Ribavirin** | Genotype-dependent | 40–50% (Gt 1) | 24–48 weeks | Injection + oral | Poor (flu-like, cytopenias) | | **Ribavirin alone** | None | <10% | — | Oral | Teratogenic, haemolytic anaemia | **Clinical Pearl:** Even patients with cirrhosis (Child-Pugh A or B) achieve excellent SVR with DAAs. Liver transplant is no longer required solely for HCV treatment. **Warning:** Pegylated interferon-alpha + ribavirin is now **obsolete** for HCV treatment. It has been replaced by DAAs due to superior efficacy, shorter duration, and better tolerability. [cite:Harrison 21e Ch 298]

Answer

B. Interferon-alpha + lamivudine

Answer

C. Ribavirin monotherapy

Answer

D. Pegylated interferon-alpha + ribavirin

A 45-year-old man from Mumbai is found to have chronic hepatitis C infection (HCV RNA positive, genotype 1b) with compensated cirrhosis (Child-Pugh A). He has no prior treatment for HCV. What is the drug of choice for treatment of chronic hepatitis C?

Explanation

Treatment of Chronic Hepatitis C

Why Sofosbuvir + Velpatasvir?

Sofosbuvir + Velpatasvir Mechanism

Comparison with Older Regimens

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Regimen	Genotype Coverage	SVR Rate	Duration	Route	Tolerability
Sofosbuvir + Velpatasvir	Pan-genotypic (1–6)	>95%	12 weeks	Oral	Excellent
Peg-IFN + Ribavirin	Genotype-dependent	40–50% (Gt 1)	24–48 weeks	Injection + oral	Poor (flu-like, cytopenias)
Ribavirin alone	None	<10%	—	Oral	Teratogenic, haemolytic anaemia