What is the primary treatment for recurrent viral hepatitis?

Treatment of Recurrent Viral Hepatitis Post-Liver Transplantation

For recurrent hepatitis C after liver transplantation, direct-acting antiviral (DAA) regimens—specifically sofosbuvir/ledipasvir plus ribavirin or sofosbuvir plus simeprevir—are the primary treatment, achieving SVR rates of 90-91% and should be initiated early in patients with significant graft damage (fibrosis ≥F2). 1

Hepatitis C Recurrence

When to Treat

• Antiviral therapy is recommended for all patients with hepatitis C recurrence 1
• Treatment should be initiated early in those with significant graft damage (F ≥2), as SVR is associated with improved outcomes including regression of liver fibrosis, improved hepatic venous pressure gradient values, and better patient survival compared to non-responders 1

Preferred Treatment Regimens

First-Line DAA Therapy:

• Sofosbuvir/ledipasvir plus ribavirin achieves 97% SVR in F0-F3 patients, 96% in Child-Pugh A patients, and 84% in Child-Pugh B patients 1
• Sofosbuvir plus simeprevir (with or without ribavirin) achieves 90-91% SVR rates in genotype 1 and 4-infected liver transplant recipients, including those with cirrhosis 1
• These regimens are safe and effective even in severe forms of recurrence such as fibrosing cholestatic hepatitis 1

Alternative for Specific Populations:

• In treatment-naïve patients with mild recurrence, the combination of ABT450/r, ombitasvir, dasabuvir plus ribavirin shows high efficacy, though cyclosporine and tacrolimus dose adjustments are necessary due to drug-drug interactions 1

Obsolete Treatments

• PegIFN and ribavirin therapy is no longer recommended due to low efficacy (SVR ~35%) and poor tolerability 1
• First-generation protease inhibitors (boceprevir, telaprevir) are no longer recommended in liver transplant recipients due to increased side effects despite modest efficacy improvements 1

Clinical Impact of Viral Clearance

The accelerated course of recurrent hepatitis C in the transplant setting makes viral eradication particularly impactful: liver fibrosis can regress, portal hypertension improves, and patient survival is significantly better in those achieving SVR versus non-responders 1, 2

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Hepatitis B Recurrence

Prevention Strategy (Primary Approach)

Standard Prophylaxis:

• Combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NUCs) is the most effective strategy, preventing HBV recurrence in >90% of patients 1
• Pre-transplant therapy with potent NUCs (entecavir or tenofovir) with high barrier to resistance is recommended for all HBsAg-positive patients to achieve the lowest possible HBV DNA level before transplantation 1

Risk-Stratified Prophylaxis:

• Patients with undetectable HBV DNA at transplant and no history of NUC resistance are candidates for low-dose HBIG or short-course HBIG (1-3 months) followed by NUC monotherapy 1
• Monotherapy with entecavir or tenofovir appears efficacious in controlling infection recurrence (0% virological relapse at 3 years with entecavir in one large study), but may not completely prevent HBV graft infection as some patients develop HBsAg reappearance without detectable HBV DNA 1

Treatment of Established HBV Recurrence

When HBV recurrence occurs (reappearance of HBsAg and quantifiable HBV DNA):

• Treatment should be initiated promptly with entecavir or tenofovir 1
• Entecavir may be preferred for individuals with renal failure 1
• Tenofovir is the best alternative for patients with lamivudine resistance 1
• The goal is to control HBV replication over time and prevent graft loss 1

Special Considerations

Anti-HBc Positive Donors:

• Prophylaxis should be initiated immediately post-transplant if recipients lack anti-HBs 1
• Lamivudine monotherapy is the most cost-effective treatment; HBIG should not be used in HBsAg-negative recipients who received anti-HBc positive donor livers 1

Resistance Monitoring

• For nucleoside-inhibitor-naïve patients on entecavir, the cumulative probability of developing resistance-associated substitutions is extremely low: 0.2% at 48 weeks, 0.5% at 96 weeks, and 1.2% at 240 weeks 3
• For lamivudine-refractory patients, resistance rates are substantially higher: 6.2% at 48 weeks, 15% at 96 weeks, and 51.5% at 240 weeks 3

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Common Pitfalls to Avoid

• Do not delay DAA therapy for HCV recurrence—early treatment in patients with F≥2 fibrosis prevents progression to cirrhosis and decompensation 1
• Do not use interferon-based regimens for post-transplant HCV recurrence given poor efficacy and high rates of serious adverse events including rejection 1
• Do not use HBIG monotherapy for HBV prophylaxis in high-risk patients (high viral load, HBeAg-positive)—combination with NUCs is essential 1
• Monitor for drug-drug interactions between DAAs and immunosuppressants, particularly with ABT450/r-based regimens requiring calcineurin inhibitor dose adjustments 1