TAF (Tenofovir Alafenamide) for Preventing Progression of Liver Disease in Non-cirrhotic Chronic HBV Infection With Normal ALT and Low Viral Load.

Aim and Objective - To study the safety and efficacy of TAF as compared to initiation based on current criteria in patients with non-cirrhotic chronic HBV infection and normal ALT and low viral load.

Methodology:

Study population: The study will be conducted on the treatment naïve consecutive patients having non-cirrhotic chronic HBV infection and normal ALT and low viral load seen at the outpatient clinics/wards of Department of Hepatology, ILBS, New Delhi.

Study design:

• A prospective, randomized, single center open label study.

Study period: 5 years from the last patient enrollment

Sample size with justification: All consecutive cases consenting to be a participant in this study and meeting inclusion and exclusion criteria will be enrolled. Considering the incidence of 20% for the composite end-point in patients without TAF and 5% for patients on TAF, with power of 80% and alpha error of 5%, 176 patients (88 patients in each arm) need to be enrolled. Considering the attrition rate of ~15%, we decide to enroll 100 patients in each arm.

Intervention

• TAF 25 mg OD vs no treatment x 5 years and beyond
• Tests - Baseline - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant), Fibroscan
• 6 monthly - ALT
• 1 yearly - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant), Fibroscan
• No liver biopsy

Statistical Analysis:

Data will be reported as mean + SD. Categorical variables will be compared using the chi-square test or Fisher exact test. Normal continuous variables will be compared using the Student's t test Non normal continuous variables will be compared using the Mann Whitney rank-sum test (unpaired data) or the Wilcoxon test (paired data). The actuarial probability of survival will be calculated by the Kaplan-Meier method and compared using the log-rank test. A Cox regression analysis will be performed to identify independent prognostic factors for survival. Univariate and multivariate analysis will be used whenever applicable.

Adverse effects:

Most common- headache, nausea, and fatigue; (1% to 10%): Abdominal pain, nausea, diarrhea, dyspepsia, elevated serum amylase, vomiting, flatulence, abdominal distension; Common (1% to 10%): Rash, pruritus, elevated ALT; Uncommon (0.1% to 1%): Treatment ALT flares.

Inclusion criteria

• HBsAg+

• Persistent normal ALT 3-6m apart (<30 IU/ml in male and <20 IU/ml in female)
• HBV DNA < 2000 IU/ml
• LSM <8 Kpa

Exclusion criteria

• Prior NUC/IFN exposure
• Renal dysfunction (Serum Creatinine >1.5 mg/dl)
• Known liver cirrhosis/ esophageal varices
• Any clinical decompensation (CD)
• Pre-existing hepatocellular carcinoma
• Pregnancy
• Healthcare workers (HCW)
• Post transplant, patients with advance malignancy or on chemotherapy
• Co-infections - Hepatitis C, Hepatitis D, Human immunodeficiency virus