What is the recommended treatment protocol for acute hepatitis C?

Acute Hepatitis C Treatment Protocol

Patients with acute hepatitis C should be treated with sofosbuvir/velpatasvir (400/100 mg) once daily for 8 weeks, which achieves sustained virologic response rates exceeding 90% across all genotypes. 1, 2

Initial Assessment and Timing

Baseline Testing Requirements:

• Confirm HCV RNA positivity with quantitative viral load measurement 1, 2
• Test for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating treatment to identify HBV coinfection 3, 4
• Determine HCV genotype if resources permit, though pangenotypic regimens eliminate this necessity for treatment selection 1, 2
• Assess for HIV coinfection status, as this may influence treatment duration 1, 2

Treatment Timing Strategy:

• Consider delaying treatment for 8-12 weeks after symptom onset or ALT elevation to allow for spontaneous viral clearance, which occurs in 20-50% of cases 2
• Monitor HCV RNA levels every 4 weeks during this observation period 2
• Spontaneous clearance is more likely in symptomatic patients, females, younger individuals, and those with favorable IL28B (IFNL3) genetic polymorphisms 1, 2
• If HCV RNA remains detectable at 12 weeks, initiate antiviral therapy immediately 2

First-Line Treatment Regimens

Standard Treatment (All Genotypes):

• Sofosbuvir/velpatasvir (400/100 mg): One tablet once daily for 8 weeks without ribavirin 1, 2
• Alternative option - Sofosbuvir/ledipasvir: For genotypes 1,4,5, and 6 only, one tablet once daily for 8 weeks 1, 2
• Alternative option - Sofosbuvir/daclatasvir: For all genotypes, once daily for 8 weeks 1, 2

The EASL guidelines specifically recommend 8 weeks based on high SVR rates (>90%) observed in clinical trials, though the optimal duration remains somewhat uncertain given limited data 1, 2. A recent 2023 study confirmed 100% SVR12 in adherent patients with acute HCV monoinfection treated with sofosbuvir/velpatasvir for 8 weeks 5.

Extended Treatment Duration (12 Weeks) - Consider for:

• HIV coinfection 1, 2
• Baseline HCV RNA >1 million IU/ml (6.0 log IU/ml) 1, 2

Administration Details

Dosing Instructions:

• Take sofosbuvir/velpatasvir with or without food 3
• No ribavirin required for acute hepatitis C in most patients 1, 2
• Ensure medication adherence throughout the entire treatment course, as loss to follow-up represents the primary cause of treatment failure 5

Post-Treatment Monitoring

SVR Assessment:

• Measure HCV RNA at 12 weeks post-treatment (SVR12) 1, 2
• Critical: Also assess at 24 weeks post-treatment, as late relapses have been documented in acute hepatitis C 1, 2
• Both timepoints are necessary given the unique relapse pattern observed in acute infection 1

Special Populations and Considerations

HIV Coinfection:

• Extend treatment duration to 12 weeks with the same DAA regimens 1, 2
• Review antiretroviral medications for drug-drug interactions before initiating HCV therapy 3, 4
• Sofosbuvir/velpatasvir achieves 92-100% SVR rates in HIV/HCV coinfected patients 6, 7

People Who Inject Drugs:

• Offer treatment without delay, as early treatment prevents HCV transmission in high-risk groups 5
• Both sofosbuvir/velpatasvir and glecaprevir/pibrentasvir achieve >94% cure rates in this population 8
• Provide treatment within comprehensive harm reduction programs 8

Common Pitfalls and Caveats

Diagnostic Challenges:

• Anti-HCV antibodies may be negative early in acute infection; HCV RNA testing is essential when acute hepatitis C is suspected 1, 2
• Differentiating acute hepatitis C from acute exacerbation of chronic hepatitis C can be difficult; when uncertain, treat as chronic infection 1
• Most patients with acute hepatitis C are asymptomatic, making diagnosis challenging 1, 2

Treatment Contraindications:

• No indication exists for post-exposure prophylaxis in the absence of documented HCV transmission 1, 2
• Do not use glecaprevir/pibrentasvir in patients with decompensated cirrhosis (though rare in acute infection) 6

Drug Interactions:

• Screen for concomitant medications that may interact with DAAs, particularly antiretrovirals, proton pump inhibitors, and antiarrhythmics 3, 4
• Sofosbuvir/velpatasvir has fewer drug interactions than protease inhibitor-based regimens 7

Historical Context

Prior to DAA availability, pegylated interferon alpha monotherapy for 24 weeks was standard treatment, achieving 80-90% SVR rates 1, 2. The shift to 8-week DAA regimens represents a dramatic improvement in tolerability, efficacy, and treatment duration 1, 5.