What is the recommended approach to hepatitis prevention and management in a patient with chronic kidney disease (CKD)?

Hepatitis Profile in CKD Patients

Screening and Initial Evaluation

All CKD patients must be screened for hepatitis C at initial CKD evaluation using immunoassay followed by nucleic acid testing (NAT) if positive, and all patients should be screened for hepatitis B prior to any antiviral therapy. 1

Hepatitis C Screening Protocol

• Screen at CKD diagnosis: Use immunoassay followed by NAT confirmation for all positive results 1
• In-center hemodialysis patients: Screen every 6 months with either immunoassay or NAT, with mandatory reporting of new infections to public health authorities 1
• Peritoneal dialysis/home hemodialysis: Screen at initiation of therapy 1
• Kidney transplant candidates: Mandatory screening at time of transplant evaluation 1
• Monitor ALT monthly in hemodialysis patients, as this can signal new infection even when levels appear normal (CKD patients may have significant fibrosis despite normal ALT) 1, 2

Hepatitis B Screening Protocol

• Test all HCV-positive patients for HBV before initiating direct-acting antiviral (DAA) therapy 1
• Screen for HBsAg, HBcAb, and HBsAb: If HBsAg positive, evaluate for HBV therapy; if markers of prior infection present, monitor for reactivation with HBV DNA testing if liver enzymes rise during DAA treatment 1
• Vaccinate against HAV and HBV if appropriate, and screen for HIV in all CKD patients with history of HCV infection 1

Liver Fibrosis Assessment

All HCV-infected CKD patients require noninvasive liver fibrosis assessment using FibroScan or serum biomarkers, with liver biopsy reserved for uncertain cases or discordant results. 1, 2

• Initial assessment: Use noninvasive methods (FibroScan, FIB-4, APRI scores) rather than biopsy as first-line 1, 2
• Advanced fibrosis (F3-4): Assess for portal hypertension with imaging and clinical evaluation 1
• Monitor for CKD progression: HCV accelerates kidney disease progression; follow kidney function regularly regardless of NAT status 1, 2

Treatment Approach by CKD Stage

All CKD patients with HCV (stages G1-G5, dialysis, and transplant recipients) should be evaluated for DAA therapy, with regimen selection based on GFR, prior treatment, drug interactions, and comorbidities. 1

CKD G1-G3b (GFR ≥30 mL/min)

• Use any licensed DAA regimen approved for general population 1
• Avoid ribavirin if creatinine clearance <50 mL/min due to contraindication 2

CKD G4-G5 (GFR <30 mL/min) and Non-Dialysis

Preferred regimens with high-quality evidence: 1

• Glecaprevir/Pibrentasvir 8 weeks (pangenotypic, 98% SVR, high-quality evidence with 132 patients) 1
• Grazoprevir/Elbasvir 12 weeks (genotypes 1a, 1b, 4; 99% SVR, high-quality evidence with 857 patients) 1
• Sofosbuvir/Daclatasvir 12-24 weeks (pangenotypic, high-quality evidence with 571 patients) 1

CKD G5D (Dialysis Patients)

Preferred regimens with highest quality evidence: 1

• Sofosbuvir/Velpatasvir 12 weeks (pangenotypic, high-quality evidence with 405 patients) 1
• Glecaprevir/Pibrentasvir 8 weeks (pangenotypic, moderate-quality evidence with 529 patients) 1
• Grazoprevir/Elbasvir 12 weeks (genotypes 1a, 1b, 4; moderate-quality evidence with 962 patients) 1

Critical caveat: Sofosbuvir-based regimens require careful consideration in dialysis due to 20-fold metabolite accumulation, though newer evidence supports their use 3

Kidney Transplant Recipients

For transplant recipients with GFR ≥30 mL/min: 1

• Sofosbuvir/Ledipasvir 12-24 weeks (pangenotypic, high-quality evidence with 300 patients) 1
• Sofosbuvir/Daclatasvir 12-24 weeks (pangenotypic, high-quality evidence with 290 patients) 1

For transplant recipients with GFR <30 mL/min: Use same regimens as CKD G4-G5 non-dialysis patients 1

Critical Drug-Drug Interactions

Monitor calcineurin inhibitor levels during and after DAA treatment in kidney transplant recipients, as DAA therapy can significantly alter immunosuppressant concentrations. 1

• Pre-treatment assessment mandatory: Check all concomitant medications for interactions, especially immunosuppressants 1
• Avoid OATP1B1/3 inhibitors with grazoprevir (risk of hyperbilirubinemia) 3
• Contraindicated: CYP3A4 inducers reduce antiviral activity 3
• Nephrotoxic agents: Avoid combination when possible to reduce acute kidney injury risk 3

Hepatitis B Management in CKD

For HBsAg-positive CKD patients, entecavir is preferred due to high potency, high genetic barrier to resistance, and favorable renal safety profile, with dose adjustment required for creatinine clearance <50 mL/min. 4, 5

Entecavir Dosing by Renal Function

• CrCl ≥50 mL/min: 0.5 mg once daily (1 mg for lamivudine-refractory) 4
• CrCl 30-49 mL/min: 0.5 mg every 48 hours (0.5 mg daily or 1 mg every 48 hours for lamivudine-refractory) 4
• CrCl 10-29 mL/min: 0.5 mg every 72 hours (1 mg every 72 hours for lamivudine-refractory) 4
• CrCl <10 or hemodialysis/CAPD: 0.5 mg every 7 days (1 mg every 7 days for lamivudine-refractory); administer after hemodialysis session 4

Alternative: Tenofovir may be preferred in lamivudine or telbivudine resistance settings 5

Timing of Treatment

Treat all kidney transplant candidates before transplantation to maintain undetectable HCV RNA, reduce liver fibrosis, and prevent hepatic decompensation post-transplant. 1, 2, 5

• Coordinate with transplant center to optimize treatment timing 1
• Achieving SVR before transplant reduces liver-related mortality, cardiovascular mortality, and improves quality of life 3
• Do not delay treatment unless life expectancy <12 months 1

Monitoring During and After Treatment

Monitor liver function tests regularly during DAA therapy, as viral eradication may improve hepatic function and alter drug metabolism. 1, 3

• During treatment: Check ALT, AST, and kidney function regularly 2
• Post-treatment: Continue monitoring kidney disease progression for at least several months after completing therapy 1
• Hemodialysis patients with resolved HCV: Repeat NAT testing every 6 months to detect reinfection 1

Common Pitfalls to Avoid

• Never assume normal ALT excludes significant liver disease in CKD patients—significant fibrosis can exist despite normal transaminases 2
• Do not use entecavir for HIV/HBV co-infection without concurrent HAART due to HIV resistance risk; offer HIV testing before initiating entecavir 4
• Recognize intermittent HCV viremia in hemodialysis patients requires sequential RNA monitoring 6
• Monitor for lactic acidosis in patients with decompensated liver disease receiving nucleoside analogs, as they are at higher risk 4
• Continue DAA therapy to completion (typically 12 weeks) even with mild-moderate symptoms unless serious adverse events occur, as achieving SVR dramatically improves outcomes 3