Tests tenofovir alafenamide in people with chronic hepatitis B and low virus levels

Trial details

Who runs it

Institute of Liver and Biliary Sciences, India

Trial code

NCT05195450

Record updated

28 February 2022

Original description

The main goal of therapy for patients with chronic HBV infection with no significant liver disease is to improve survival and quality of life by preventing disease progression, development of liver cirrhosis and consequently HCC development. The likelihood of achieving these goals depends on the timing of therapy during the natural course of the infection but also on the stage of the disease and the patients' age when treatment is started. The inhibition of viral replication and normalization of ALT by antiviral treatment has been shown to achieve the elimination of chronic HBV-induced necroinflammatory activity and progressive fibrotic liver progression in the vast majority of patients, in turn reducing the risk of HCC. Even in HBeAg positive patients, treatment-induced HBeAg loss and seroconversion to antiHBe characterizes the induction of a partial immune control often leading to a low replicative phase of the chronic HBV infection and good outcomes.Read full original descriptionShow less

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

The main goal of therapy for patients with chronic HBV infection with no significant liver disease is to improve survival and quality of life by preventing disease progression, development of liver cirrhosis and consequently HCC development. The likelihood of achieving these goals depends on the timing of therapy during the natural course of the infection but also on the stage of the disease and the patients' age when treatment is started. The inhibition of viral replication and normalization of ALT by antiviral treatment has been shown to achieve the elimination of chronic HBV-induced necroinflammatory activity and progressive fibrotic liver progression in the vast majority of patients, in turn reducing the risk of HCC. Even in HBeAg positive patients, treatment-induced HBeAg loss and seroconversion to antiHBe characterizes the induction of a partial immune control often leading to a low replicative phase of the chronic HBV infection and good outcomes.

Treatment in chronic HBV infection is indicated in - presence of advanced fibrosis/cirrhosis (LSM >11 KPA) or patients with significant fibrosis (LSM >8 or APRI >1.5 or >F2 on liver biopsy) with high viral load (>2000 IU/ml) or significantly elevated ALT (x2 ULN). Presence of any of these factors is known to increase the risk of development of cirrhosis and hepatocellular carcinoma. TAF in non-cirrhotic patients (LSM <8 KPA) with normal ALT and low viral load (HBV DNA <2000 IU/ml) (currently treatment ineligible) as compared to delayed initiation (on demand) might reduce HCC risk, progression of liver fibrosis and reduction in HBsAg levels. As TAF is known to have favorable effects on the overall long-term outcome, the main clinical challenge is to identify the patients at risk of HCC and cirrhosis who warrant early antiviral therapy.

Inclusion: 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: Prior NUC/IFN exposure; Post transplant, patients with advance malignancy or on chemotherapy; Co-infections - Hepatitis C, Hepatitis D, Human immunodeficiency virus; 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).

ClinicalTrials.gov NCT05195450