What is the recommended treatment for a patient with hepatitis secondary to infection?

Treatment of Hepatitis Secondary to Infection

Hepatitis C Virus (HCV) Infection

All patients with confirmed active HCV infection should be treated with pangenotypic direct-acting antiviral (DAA) regimens, specifically sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status, achieving cure rates exceeding 95-97%. 1, 2

Pre-Treatment Assessment

Before initiating DAA therapy, the following assessments are mandatory:

• HBV screening: Test all patients for HBsAg and anti-HBc to prevent potentially fatal HBV reactivation during HCV treatment 3, 2
• HCV RNA quantitative testing: Required to confirm active viremia 1, 2
• Fibrosis staging: Use non-invasive methods (FIB-4 score, transient elastography) to determine presence of cirrhosis 2
• Drug-drug interaction screening: Comprehensive review of all medications, including over-the-counter drugs and supplements 2, 1
• HIV testing: Mandatory as co-infection affects treatment selection 4

First-Line Treatment Regimens

For treatment-naïve patients without cirrhosis:

• Sofosbuvir/velpatasvir 400mg/100mg: Single tablet once daily for 12 weeks (all genotypes 1-6) 1, 2
• Glecaprevir/pibrentasvir 300mg/120mg: For 8 weeks (without cirrhosis) 1, 2

For patients with compensated cirrhosis (Child-Pugh A):

• Sofosbuvir/velpatasvir: 12 weeks 1, 2
• Glecaprevir/pibrentasvir: Extended to 12 weeks 1, 2

Genotype-Specific Considerations

Genotype 1a:

• Ledipasvir/sofosbuvir 90mg/400mg daily for 12 weeks (without cirrhosis) or 24 weeks (with cirrhosis) 1, 2
• For cirrhotic patients with NS3 Q80K polymorphism, avoid simeprevir-based regimens 2

Genotype 1b:

• Ledipasvir/sofosbuvir 90mg/400mg daily for 12 weeks 1, 2
• Paritaprevir/ritonavir/ombitasvir plus dasabuvir for 12 weeks 2

Genotype 2:

• Sofosbuvir/velpatasvir for 12 weeks 2
• Extend to 16 weeks in patients with cirrhosis 2

Genotype 3:

• Sofosbuvir/velpatasvir for 12 weeks (treatment-naïve without cirrhosis) 1
• For decompensated cirrhosis: sofosbuvir/velpatasvir or sofosbuvir/daclatasvir for 24 weeks with ribavirin 2

Genotypes 4,5, or 6:

• Ledipasvir/sofosbuvir for 12 weeks 2, 1

Decompensated Cirrhosis (Child-Pugh B or C)

Critical management principles:

• MELD score <18-20: Treat prior to transplantation with sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, or sofosbuvir/daclatasvir plus weight-based ribavirin for 12 weeks 2
• MELD score ≥18-20: Transplant first, treat HCV after transplantation 2
• Protease inhibitors are absolutely contraindicated in Child-Pugh B or C cirrhosis 2
• Ribavirin dosing: Start at 600mg daily and titrate based on tolerance (target 1000mg if <75kg, 1200mg if ≥75kg) 2

Special Populations

HIV/HCV co-infection:

• Use same HCV treatment regimens as HCV mono-infected patients 1
• Verify antiretroviral drug interactions before prescribing 1, 5

Post-liver transplant recipients:

• Genotype 1 or 4: Ledipasvir/sofosbuvir plus ribavirin for 12 weeks 2
• High SVR rates (>90%) achieved with sofosbuvir-based regimens 2

Acute hepatitis C:

• Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, or sofosbuvir/daclatasvir for 8 weeks without ribavirin 2
• Patients with HIV co-infection or baseline HCV RNA >1 million IU/ml may require 12 weeks 2

Critical Drug-Drug Interactions

Absolute contraindications:

• P-glycoprotein inducers (rifampin, St. John's wort) 2, 1
• Moderate-to-strong CYP3A4 inducers 1
• Efavirenz-containing antiretroviral regimens 1

Amiodarone warning:

• Coadministration with ledipasvir/sofosbuvir can cause fatal cardiac arrest and symptomatic bradycardia 3
• If no alternative exists, require 48-hour inpatient cardiac monitoring followed by daily heart rate monitoring for 2 weeks 3

Monitoring Protocol

During treatment:

• HCV RNA at baseline, weeks 4 and 12, and end of treatment 1, 4
• If HCV RNA detectable at week 4, repeat at week 6; discontinue if viral load increases >10-fold 2
• Monitor for hypoglycemia in diabetic patients 2
• Monitor INR in patients taking warfarin 2

Post-treatment:

• HCV RNA at 12 weeks post-treatment (SVR12) confirms cure in >99% of cases 1, 4
• Patients with cirrhosis or advanced fibrosis require lifelong HCC surveillance with ultrasound every 6 months, even after achieving SVR 4, 2

Common Pitfalls to Avoid

• Do not withhold treatment based on high viral load: Modern DAAs achieve SVR rates of 95-97% regardless of baseline HCV RNA levels 4, 1
• Do not use protease inhibitors in decompensated cirrhosis: This is associated with severe adverse events and is absolutely contraindicated 2
• Do not delay HBV screening: HBV reactivation during HCV treatment can cause fulminant hepatitis, hepatic failure, and death 3
• Do not assume normal transaminases are required: Elevated liver enzymes indicate active inflammation but are not required to initiate therapy 4

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Hepatitis B Virus (HBV) Infection

HBsAg-positive patients should receive high-potency nucleos(t)ide analogues (entecavir or tenofovir) as first-line treatment, with long-term therapy significantly reducing disease progression to cirrhosis and HCC incidence. 2, 6

Treatment Indications

• Patients with decompensated cirrhosis (any HBV DNA level) 2
• Patients with compensated cirrhosis and detectable HBV DNA 2
• Patients undergoing immunosuppression or chemotherapy 2
• Patients with acute liver failure 2
• Patients with extrahepatic manifestations and active viral replication 2

Preferred Agents

• Entecavir or tenofovir (disoproxil fumarate or alafenamide): High genetic barrier to resistance 2
• Long-term therapy reduces cirrhosis progression and HCC incidence, particularly in HBe antigen-positive patients 6

Liver Transplantation Setting

• HBsAg-positive recipients: High-potency nucleos(t)ide analogues with or without HBIG, depending on HBV DNA levels at transplant 2
• HBsAg-negative recipients receiving anti-HBc-positive donor livers: Long-term nucleos(t)ide analogue prophylaxis 2

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Other Viral Hepatitis

Dengue hepatitis requires supportive care with acetaminophen for fever/pain, adequate oral hydration (>2500ml daily), and avoidance of NSAIDs and aspirin due to bleeding risk. 7 Monitor daily complete blood counts for thrombocytopenia and rising hematocrit indicating capillary leak syndrome. 7