What is the recommended treatment and management plan for a patient with a confirmed Hepatitis C (HCV) infection?

Hepatitis C Infection: Treatment and Management

All patients with confirmed chronic Hepatitis C infection should be treated with direct-acting antiviral (DAA) regimens to achieve cure and prevent progression to cirrhosis, hepatocellular carcinoma, and death. 1

Initial Diagnostic Confirmation

• Confirm active HCV infection with HCV RNA testing using a sensitive molecular method (lower limit of detection <15 IU/mL) in all patients who test positive for anti-HCV antibodies 2, 1
• For suspected acute hepatitis C or immunocompromised patients, include HCV RNA testing in the initial evaluation even before antibody results 2, 1
• Retest HCV RNA 3 months later in anti-HCV positive, HCV RNA negative individuals to confirm true viral clearance 1

Pre-Treatment Assessment

Before initiating therapy, obtain the following:

• HCV genotype determination to guide treatment selection 2, 1
• Liver disease severity assessment using non-invasive methods or liver biopsy to determine presence of advanced fibrosis or cirrhosis 1
• Test for HBV coinfection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before starting any HCV treatment, as HBV reactivation can cause fulminant hepatitis, hepatic failure, and death 3, 4
• Screen for HIV, syphilis, gonorrhea, chlamydia due to overlapping risk factors 5
• Assess for other causes of liver disease including alcohol use and metabolic factors 1

Treatment Recommendations by Genotype

Genotype 1a (Treatment-Naive)

Choose one of the following regimens: 2

• Ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis) 2, 3
• Paritaprevir/ritonavir/ombitasvir plus dasabuvir with weight-based ribavirin for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis) 2
• Sofosbuvir plus simeprevir for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis), only if Q80K variant testing is negative in patients with cirrhosis 2

Genotype 1b (Treatment-Naive)

Choose one of the following regimens: 2

• Ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks 2, 3
• Paritaprevir/ritonavir/ombitasvir plus dasabuvir for 12 weeks (without ribavirin) 2
• Sofosbuvir plus simeprevir for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis) 2

Genotype 2

• Sofosbuvir plus weight-based ribavirin for 12 weeks (no cirrhosis) or 16 weeks (cirrhosis) 2, 4

Genotype 3

• Sofosbuvir plus weight-based ribavirin for 24 weeks 2, 4

Genotype 4,5, or 6

• Ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks 2, 3

Special Populations

Decompensated Cirrhosis (Child-Pugh B or C)

• Ledipasvir/sofosbuvir plus ribavirin for 12 weeks 3
• Starting ribavirin dose is 600 mg daily, titrated up to weight-based dosing (1000 mg if <75 kg, 1200 mg if ≥75 kg) 3

Liver Transplant Recipients

• Ledipasvir/sofosbuvir plus ribavirin for 12 weeks for genotype 1 or 4 infection without cirrhosis or with compensated cirrhosis 3

Acute Hepatitis C

• Monitor for spontaneous clearance for at least 12-16 weeks before initiating treatment 1
• If treatment is indicated, immediate DAA therapy achieves 95.9% cure rates with minimal adverse events 6

Treatment Contraindications and Precautions

Defer or avoid treatment in: 2

• Patients currently drinking excessive alcohol or injecting drugs (delay until abstinent ≥6 months) 2
• Pregnant women (if using ribavirin-containing regimens) 2
• Patients with major depressive illness, severe cytopenias, or uncontrolled autoimmune disease 2
• Advanced cirrhosis at risk for decompensation requires specialist consultation 2

Critical drug interaction: Never coadminister with amiodarone due to risk of fatal bradycardia and cardiac arrest 3

Essential Vaccinations

All HCV-positive patients require: 5

• Hepatitis A vaccination if lacking immunity, as HAV superinfection causes fulminant hepatitis and higher mortality 5
• Hepatitis B vaccination using double-dose regimen (40 µg) in patients with cirrhosis, as HBV coinfection accelerates progression to cirrhosis and hepatocellular carcinoma 5
• Pneumococcal vaccination (PCV13 followed by PPSV23 at least 8 weeks later) for all patients with cirrhosis 5
• Annual influenza vaccination for all HCV patients 5
• COVID-19 vaccination without discontinuing HCV therapy 5

Post-Treatment Monitoring

• Confirm cure with HCV RNA testing 12 weeks after treatment completion (SVR12), which corresponds to definitive cure in >99% of cases 2, 1
• Patients with cirrhosis who achieve SVR require lifelong hepatocellular carcinoma surveillance every 6 months by ultrasound, as cure reduces but does not eliminate HCC risk 2, 1, 7
• Monitor liver enzymes post-SVR, as persistently elevated levels may indicate ongoing inflammation from other causes 7

Patient Counseling

• Alcohol abstinence is mandatory, as even modest amounts accelerate liver disease progression 5
• HCV is not spread by casual contact, sneezing, hugging, coughing, food, water, or sharing eating utensils 2
• Avoid sharing personal hygiene items (razors, nail clippers, toothbrushes), needles, or drug paraphernalia 5
• Patients should not be excluded from work, school, or childcare based on HCV status 2
• Breastfeeding is acceptable unless nipples are cracked or bleeding 2