What is the treatment for a patient with hepatitis C, considering factors such as genotype, presence of cirrhosis, and previous treatment outcomes?

Treatment of Hepatitis C

All patients with chronic hepatitis C should be treated with interferon-free, direct-acting antiviral (DAA) regimens, with sofosbuvir/velpatasvir for 12 weeks being the preferred pangenotypic option for most patients regardless of genotype, cirrhosis status, or prior treatment history. 1, 2

First-Line Treatment Recommendations

Pangenotypic Regimens (Preferred for All Genotypes)

Sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks is the most broadly applicable first-line option, achieving 98% SVR rates across all genotypes and patient populations. 1, 2

• Treatment-naïve and treatment-experienced patients with or without compensated cirrhosis receive the same 12-week duration without ribavirin. 1
• This regimen achieved 98% SVR in genotype 1a (206/210 patients), 99% in genotype 1b (117/118), 100% in genotype 4 (116/116), 97% in genotype 5 (34/35), and 100% in genotype 6 (41/41). 1
• HIV-coinfected patients achieve similar SVR rates (95% in genotype 1a, 92% in genotype 1b) with the same regimen. 1

Glecaprevir/pibrentasvir is an equally effective alternative pangenotypic option. 2, 3

• Treatment-naïve patients without cirrhosis: 8 weeks. 2
• Patients with compensated cirrhosis or treatment-experienced: 12 weeks. 2
• SVR rates of 97-100% across genotypes 1,2,4,5, and 6. 1

Genotype-Specific Considerations

Genotype 1

For genotype 1a without cirrhosis: Sofosbuvir/ledipasvir for 12 weeks without ribavirin is an alternative option. 1

• Treatment can be shortened to 8 weeks in treatment-naïve patients without cirrhosis if baseline HCV RNA is below 6 million IU/ml, though this should be done with caution in F3 fibrosis. 1
• Treatment-experienced genotype 1a patients should receive ribavirin (1000-1200mg based on weight) added to sofosbuvir/ledipasvir for 12 weeks, OR extend to 24 weeks without ribavirin if ribavirin is contraindicated. 1

For genotype 1b: Sofosbuvir/ledipasvir for 12 weeks without ribavirin for both treatment-naïve and treatment-experienced patients. 1

Alternative for genotype 1a with cirrhosis: Ombitasvir/paritaprevir/ritonavir plus dasabuvir with ribavirin for 24 weeks. 1

Alternative for genotype 1b with cirrhosis: Ombitasvir/paritaprevir/ritonavir plus dasabuvir for 12 weeks without ribavirin. 1

Genotype 2

Sofosbuvir plus ribavirin for 12 weeks remains an acceptable option where newer pangenotypic regimens are unavailable. 1, 4

• Treatment-naïve patients without cirrhosis achieved 93% SVR with this regimen. 4
• Therapy should be prolonged to 16-20 weeks in patients with cirrhosis, especially if treatment-experienced. 1
• Treatment-experienced patients with cirrhosis achieved only 60% SVR with 12 weeks, supporting longer duration. 4

Genotype 3

Genotype 3 requires special attention as it has historically been more difficult to treat. 3

• Sofosbuvir/velpatasvir for 12 weeks is the preferred option. 1, 5
• Sofosbuvir/daclatasvir for 12 weeks is an alternative. 1, 5
• For treatment-experienced patients with cirrhosis who failed prior DAA therapy, consider sofosbuvir/velpatasvir/voxilaprevir for 12 weeks. 1, 3

Genotype 4

Multiple highly effective options exist for genotype 4. 1

• Sofosbuvir/velpatasvir for 12 weeks without ribavirin (100% SVR in clinical trials). 1
• Sofosbuvir/ledipasvir for 12 weeks: treatment-naïve patients without ribavirin; treatment-experienced patients with ribavirin or extend to 24 weeks without ribavirin. 1
• Ombitasvir/paritaprevir/ritonavir (without dasabuvir) for 12 weeks with ribavirin. 1

Genotypes 5 and 6

Treatment options mirror those for genotype 1. 1

• Sofosbuvir/velpatasvir for 12 weeks without ribavirin for all patients. 1
• Sofosbuvir/ledipasvir for 12 weeks: treatment-naïve without ribavirin; treatment-experienced with ribavirin or extend to 24 weeks without ribavirin. 1

Special Populations

Decompensated Cirrhosis (Child-Pugh B or C)

IFN-free regimens are the ONLY options for decompensated cirrhosis. 1, 6

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks is recommended. 5
• Standard DAA regimens without ribavirin may be contraindicated due to risk of severe complications. 6
• These patients require urgent treatment and should be evaluated for liver transplantation. 6

Post-Liver Transplant

The same IFN-free regimens used in non-transplant patients can be safely used post-transplant. 1

• Careful attention to drug-drug interactions with immunosuppressants is essential. 1

HIV-HCV Coinfection

The same HCV treatment regimens are used as in HCV monoinfection. 1, 5

• Treatment alterations or dose adjustments may be needed for interactions with antiretroviral drugs. 1
• Daclatasvir dose must be adjusted to 30mg with ritonavir/cobicistat-boosted regimens, and to 90mg with efavirenz. 5

Treatment-Experienced Patients Who Failed Prior DAA Therapy

This represents one of the most challenging scenarios. 1

• For genotype 1 patients who failed NS5A-containing regimens: sofosbuvir/velpatasvir/voxilaprevir for 12 weeks OR glecaprevir/pibrentasvir for 16 weeks. 1
• For genotype 1 patients who failed non-NS5A regimens: glecaprevir/pibrentasvir for 12 weeks OR sofosbuvir/velpatasvir for 12 weeks. 1
• Resistance testing may guide therapy, particularly for NS5A resistance-associated substitutions (RAS). 1
• Patients with both NS3 and NS5A RAS have limited efficacy with glecaprevir/pibrentasvir (SVR 25-80%). 1

Monitoring and Follow-Up

HCV RNA should be measured at baseline, weeks 4 and 12 during treatment, end of treatment, and 12 weeks post-treatment. 2

• SVR12 (undetectable HCV RNA 12 weeks after treatment completion) defines cure. 2, 7

Patients with cirrhosis or advanced fibrosis (F3-F4) require lifelong hepatocellular carcinoma surveillance with ultrasound every 6 months, even after achieving SVR. 6, 2

• The risk of HCC persists despite viral eradication in patients with established cirrhosis. 6

Screening for gastroesophageal varices with endoscopy should continue in cirrhotic patients. 6

Critical Drug Interactions

DAAs must not be used with P-glycoprotein inducers or moderate-to-strong CYP inducers, as these significantly decrease DAA concentrations and reduce efficacy. 2

• Common problematic medications include rifampin, carbamazepine, phenytoin, St. John's wort, and certain antiretrovirals. 2
• Verify all drug-drug interactions before prescribing, particularly with antiretrovirals, cardiac medications, and acid-suppressing agents. 2

Pre-Treatment Assessment

Essential baseline evaluations include: 2

• HCV genotype and subtype determination (genotype 1 that cannot be subtyped should be treated as 1a). 2
• Fibrosis staging using noninvasive methods or liver biopsy to determine treatment urgency and duration. 2
• Baseline HCV RNA level. 2
• Assessment for cirrhosis and decompensation (Child-Pugh score). 6

Common Pitfalls to Avoid

Do not defer treatment in patients with advanced fibrosis (F3-F4), as these patients have the most urgent need and greatest short-term benefit from viral eradication. 2

Do not use genotype 1a-specific regimens without confirming subtype. 2

Do not assume HCC risk disappears after SVR in cirrhotic patients—continue surveillance indefinitely. 6, 2

Cirrhotic patients often have hematological complications from portal hypertension and splenomegaly requiring careful monitoring during treatment. 6

In settings where modern DAA regimens are unavailable, pegylated interferon-alpha plus ribavirin or triple therapy with first-generation protease inhibitors (telaprevir, boceprevir) remain acceptable until newer DAAs become available. 1