What is the recommended treatment for hepatitis C?

Treatment for Hepatitis C

First-Line Treatment Recommendation

All patients with chronic hepatitis C should be treated with pangenotypic direct-acting antiviral (DAA) regimens: sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks (depending on cirrhosis status). 1, 2, 3

---

Treatment Selection Algorithm

For Patients WITHOUT Cirrhosis or WITH Compensated Cirrhosis (Child-Pugh A):

Preferred Option:

• Sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks - This achieves 98% SVR rates across all genotypes (1-6) and is the most straightforward regimen 4, 2, 5

Alternative Option:

• Glecaprevir/pibrentasvir for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis) 2, 3

For Patients WITH Decompensated Cirrhosis (Child-Pugh B or C):

• Sofosbuvir/velpatasvir PLUS weight-based ribavirin for 12 weeks 2, 5
• Ribavirin dosing: 1,000 mg/day if <75 kg; 1,200 mg/day if ≥75 kg, divided twice daily 5

---

Pre-Treatment Requirements (Mandatory Testing)

Before initiating any DAA therapy, you must obtain:

• HCV RNA quantitative testing using a sensitive assay (lower limit of detection <15 IU/ml) 4, 1, 2
• HCV genotype and subtype determination (particularly 1a vs 1b) 4, 1, 2
• Hepatitis B testing (HBsAg and anti-HBc) - This is critical as HBV reactivation can cause fulminant hepatitis and death 5
• Fibrosis staging to determine cirrhosis status 1, 2
• Comprehensive drug-drug interaction screening - P-glycoprotein inducers (rifampin, carbamazepine, phenytoin, St. John's wort) are absolute contraindications 4, 3

Note: IL28B genotyping is no longer needed with modern DAAs 4

---

Treatment Prioritization (Who Needs Immediate Treatment)

Treat these patients first:

• Advanced fibrosis (METAVIR F3-F4) or any cirrhosis 4, 1, 3
• Pre- and post-liver transplant recipients 3
• Severe extrahepatic manifestations 3
• Hepatocellular carcinoma patients 3

However, the current guideline position is that all treatment-naïve and treatment-experienced patients with compensated chronic liver disease who are willing to be treated and have no contraindications should be considered for therapy 4

---

Special Populations

HIV/HCV Coinfection:

• Use the same regimens as HCV monoinfected patients with identical expected outcomes 4, 3
• Sofosbuvir/velpatasvir achieved 95% SVR in HIV coinfected patients 4
• No significant drug-drug interactions with most antiretrovirals (emtricitabine, tenofovir, rilpivirine, efavirenz, darunavir/ritonavir, raltegravir) 4

Liver Transplant Recipients:

• Sofosbuvir/velpatasvir for 12 weeks (without cirrhosis or with compensated cirrhosis) 5
• For more complex cases, consider sofosbuvir/velpatasvir plus ribavirin for 12 weeks 3

Severe Renal Impairment (eGFR <30 ml/min):

• No dose recommendation available for sofosbuvir due to 20-fold higher metabolite exposure 4
• Glecaprevir/pibrentasvir may be considered as it does not require renal dose adjustment 6

---

Treatment Monitoring Protocol

During Treatment:

• HCV RNA at baseline, weeks 4 and 12, and end of treatment 3

Post-Treatment:

• SVR12 (HCV RNA at 12 weeks post-treatment) is the primary measure of cure - This represents viral eradication in >99% of patients who achieve it 1, 2, 3
• For most patients on modern DAA regimens with expected high SVR rates, checking SVR is optional except in patients at risk of reinfection 1

---

Treatment Outcomes and Long-Term Considerations

Expected Results:

• SVR rates exceed 95% in most patient populations with modern pangenotypic DAA regimens 2, 3, 6
• Successful eradication leads to improvement in liver histology, decreased risk of cirrhotic complications, reduced hepatocellular carcinoma occurrence, and improved survival 2, 3

Critical Caveat for Cirrhotic Patients:

• Patients with cirrhosis who achieve SVR still require ongoing monitoring as they remain at risk for hepatocellular carcinoma and other complications, though at significantly reduced rates 1, 2, 3
• Indefinite HCC surveillance via ultrasound every 6 months is required 1

---

Retreatment for DAA Failures

If initial DAA therapy fails (occurs in 1-5% of patients):

For patients who failed sofosbuvir alone or sofosbuvir + ribavirin:

• Retreat with sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, or sofosbuvir/daclatasvir with ribavirin for 12 weeks (F0-F2) or 24 weeks (F3-F4) 3

For patients who failed NS5A inhibitor-containing regimens:

• Use sofosbuvir with a protease inhibitor (grazoprevir/elbasvir or simeprevir) plus ribavirin for 12 weeks (genotype 1b or 4 without cirrhosis) or 24 weeks (genotype 1a or cirrhosis) 3
• Consider deferral of treatment if no cirrhosis or urgent need, as NS5A resistance-associated substitutions persist for >2 years 7

---

Critical Drug-Drug Interactions (Absolute Contraindications)

Do not use DAAs with:

• P-glycoprotein inducers: rifampin, carbamazepine, phenytoin, St. John's wort - These significantly decrease sofosbuvir concentrations and lead to treatment failure 4, 3

Older Contraindications (No Longer Relevant with Modern DAAs):

• The extensive contraindications for pegylated interferon-alpha/ribavirin (uncontrolled depression, psychosis, epilepsy, pregnancy, autoimmune disease, decompensated liver disease) do not apply to modern DAA regimens 4
• No absolute contraindications exist for DAAs themselves 4

---

Common Pitfalls to Avoid

1. Failing to test for hepatitis B before starting treatment - HBV reactivation can be fatal 5
2. Not screening for P-gp inducers - These drugs will cause treatment failure 4, 3
3. Assuming cirrhotic patients are "cured" after SVR - They still need HCC surveillance indefinitely 1
4. Using sofosbuvir in severe renal impairment - No safety data exists for eGFR <30 ml/min 4
5. Checking for baseline resistance-associated substitutions (RASs) - This is generally not necessary with modern pangenotypic regimens, though may affect treatment duration in specific scenarios 2