What antiviral treatment is recommended for a patient with viral hepatitis, considering their liver function, kidney function, and overall health status?

Antiviral Treatment for Viral Hepatitis

For chronic hepatitis B, initiate treatment with entecavir 0.5 mg daily, tenofovir disoproxil fumarate (TDF) 300 mg daily, or tenofovir alafenamide (TAF) 25 mg daily as first-line monotherapy, as these agents achieve >90% virologic suppression with minimal resistance. 1

Hepatitis B Treatment Selection

First-Line Agent Selection

Choose tenofovir (TDF or TAF) or entecavir as initial therapy based on patient-specific risk factors:

• For patients with renal dysfunction risk factors (eGFR <60 mL/min, proteinuria >0.5 mg/dL, hypophosphatemia <2.5 mg/dL, uncontrolled diabetes/hypertension, osteopenia/osteoporosis, chronic steroid use, or advanced age), prefer TAF 25 mg daily, entecavir 0.5 mg daily, or besifovir over TDF. 2

• For patients with normal renal function and no bone disease risk, TDF 300 mg daily remains an excellent first-line option with proven long-term efficacy (93% virologic suppression at 48 weeks). 1

• For lamivudine-experienced patients, use tenofovir (TDF or TAF) exclusively—never use entecavir due to archived resistance mutations, even with brief prior lamivudine exposure. 1

Treatment Indications by Clinical Scenario

Compensated cirrhosis:

• Treat if HBV DNA ≥2,000 IU/mL regardless of ALT level 3, 1
• Use oral antivirals (tenofovir or entecavir) as monotherapy 3
• Avoid peginterferon due to risk of hepatic decompensation 3

Decompensated cirrhosis:

• Initiate prompt oral antiviral therapy if HBV DNA is detectable by PCR, regardless of ALT 3
• Prefer tenofovir or entecavir monotherapy 3
• Peginterferon is absolutely contraindicated due to risk of hepatic failure 3
• Coordinate with transplant centers and consider liver transplantation 3

HBeAg-positive chronic hepatitis:

• Treat when HBV DNA >20,000 IU/mL AND ALT ≥2× upper limit of normal (ULN) 1
• Continue treatment for minimum 1 year after HBeAg seroconversion, then additional 3-6 months 1

HBeAg-negative chronic hepatitis:

• Treat when HBV DNA >2,000 IU/mL AND ALT ≥2× ULN 1
• Plan for lifelong therapy, as relapse rates reach 80-90% if stopped within 1-2 years 1

Dosing Specifications

Standard adult dosing:

• Entecavir: 0.5 mg once daily (normal renal function, no HIV coinfection) 1
• TDF: 300 mg once daily 2, 4
• TAF: 25 mg once daily 1, 4

Renal impairment adjustments for TDF:

• CrCl ≥50 mL/min: 300 mg every 24 hours 2
• CrCl 30-49 mL/min: 300 mg every 48 hours 2
• CrCl 10-29 mL/min: 300 mg every 72-96 hours 2
• Hemodialysis: 300 mg every 7 days or after ~12 hours of dialysis 2

Pediatric dosing (≥12 years, ≥35 kg):

• TDF 300 mg once daily or 8 mg/kg daily (maximum 300 mg) 3, 2
• TAF and entecavir also approved for this age group 3

Critical Monitoring Requirements

Before initiating tenofovir:

• Assess baseline creatinine clearance, serum phosphorus, urine glucose, and urine protein 4
• Monitor renal function (BUN, creatinine) every 1-3 months during therapy 3, 2
• Monitor bone density in patients with osteoporosis risk factors 2

During treatment:

• Test liver function every 2-6 months in compensated cirrhosis 3
• Test liver function every 1-3 months in decompensated cirrhosis 3
• Measure HBV DNA by real-time PCR every 2-6 months 3
• Check HBeAg status every 2-6 months 3

After discontinuation:

• Monitor hepatic function closely with clinical and laboratory follow-up for at least several months due to risk of severe acute exacerbations 2, 4

Hepatitis C Treatment Selection

For chronic hepatitis C, use interferon-free direct-acting antiviral (DAA) regimens, as they achieve cure rates approaching 100% with minimal side effects. 3, 5

Treatment Indications

Prioritize treatment for:

• Advanced fibrosis (≥F3) including compensated and decompensated cirrhosis 3
• Pre- and post-liver transplant patients 3
• Severe extrahepatic manifestations (HCV-related mixed cryoglobulinemia, glomerulonephritis) 3
• All patients with no contraindications should be considered for treatment 3

DAA Regimen Selection by Genotype

Genotype 1 or 4:

• Sofosbuvir 400 mg + simeprevir 150 mg daily for 12-24 weeks, with or without weight-based ribavirin 3
• Sofosbuvir 400 mg + daclatasvir 60 mg daily for 12-24 weeks, with or without weight-based ribavirin 3
• Ledipasvir 90 mg/sofosbuvir 400 mg fixed-dose combination once daily 6

Genotype 2:

• Sofosbuvir 400 mg daily + weight-based ribavirin (1000 mg if <75 kg or 1200 mg if ≥75 kg) for 12-24 weeks 3

Genotype 3,5, or 6:

• Sofosbuvir 400 mg + daclatasvir 60 mg daily for 12-24 weeks, with or without weight-based ribavirin 3

Special Populations

Decompensated cirrhosis (pre- or post-transplant):

• Ledipasvir/sofosbuvir + ribavirin for 12 weeks achieved 87-95% SVR12 in Child-Pugh B patients and 88% in pre-transplant Child-Pugh C patients 6
• Post-transplant patients without cirrhosis or with compensated cirrhosis achieved 95-98% SVR12 6

Severe renal impairment/ESRD requiring dialysis:

• Ledipasvir/sofosbuvir can be used in dialysis patients 6
• 8-week regimen achieved 93% SVR12, 12-week regimen achieved 100% SVR12 in dialysis patients 6
• Sofosbuvir is contraindicated in patients with eGFR <30 mL/min who are not on dialysis 3

Pediatric patients (≥3 years):

• Ledipasvir/sofosbuvir for 12 weeks achieved 98-99% SVR12 in treatment-naïve and treatment-experienced children 6

Treatment Response Definition

Sustained virologic response (SVR) is defined as undetectable HCV RNA (<50 IU/mL) at 12 weeks after treatment completion, with 98% concordance between SVR12 and SVR24. 3

Critical Pitfalls to Avoid

Never use entecavir in any patient with prior lamivudine exposure, even if brief, due to risk of archived resistance mutations that compromise efficacy. 1

Never discontinue hepatitis B therapy prematurely in HBeAg-negative patients or those with cirrhosis, as this causes severe hepatitis flares. 1

Never use peginterferon in decompensated cirrhosis due to risk of life-threatening hepatic failure. 3

Never use sofosbuvir in patients with eGFR <30 mL/min who are not on dialysis. 3