TAF (Tenofovir Alafenamide) for preventing progression of liver disease in non-cirrhotic chronic HBV infection with normal ALT and low viral load – a randomized controlled trial.

Aim and Objective –

To study the safety and efficacyof TAF as compared to initiation based on current criteria in patients withnon-cirrhotic chronic HBV infection and normal ALT and low viral load.

Methodology:

Study population: The study willbe conducted on the treatment naïve consecutive patients having non-cirrhoticchronic HBV infection and normal ALT and low viral load seen at the outpatientclinics/wards of Department of Hepatology, ILBS, New Delhi.

Study Design: A Prospective,Randomized, Single Center Open Labelled Study.

Study Period: 5 years from thelast patient enrollment

Sample Size with justification:All consecutive cases consenting to be a participant in this study and meetinginclusion and exclusion criteria will be enrolled. Considering the incidence of20% for the composite end-point in patients without TAF and 5% for patients onTAF, with power of 80% and alpha error of 5%, 176 patients (88 patients in eacharm) need to be enrolled. Considering the attrition rate of ~15%, we decide toenroll 100 patients in each arm.

Intervention

1.       TAF25 mg OD vs no treatment x 5 years and beyond

2.       Tests– Baseline – USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant),Fibroscan

3.       6monthly – ALT

4.       1yearly - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant),Fibroscan

5.       Noliver biopsy

Statistical Analysis: Data willbe reported as mean + SD. Categorical variables will be compared using thechi-square test or Fisher exact test. Normal continuous variables will becompared using the Student’s t test Non normal continuous variables will becompared using the Mann Whitney rank-sum test (unpaired data) or the Wilcoxontest (paired data). The actuarial probability of survival will be calculated bythe Kaplan-Meier method and compared using the log-rank test. A Cox regressionanalysis will be performed to identify independent prognostic factors forsurvival. 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.