Tenofovir Versus Entecavir for Tertiary Prevention of Hepatocellular Carcinoma in Chronic Hepatitis B Infection After Curative Therapy

A Systematic Review and Meta-analysis

Suprabhat Giri; Dhiraj Agrawal; Shivaraj Afzalpurkar; Amrit Gopan; Sumaswi Angadi; Sridhar Sundaram


J Viral Hepat. 2023;30(2):108-115. 

In This Article

Abstract and Introduction


Entecavir (ETV) and Tenofovir disoproxil fumarate (TDF) are the first-line drugs for the treatment of chronic hepatitis B virus (HBV). However, the impact of these two antiviral agents on the outcome of HBV-related hepatocellular carcinoma (HCC) after curative therapy remains to be explored. The purpose of the present study was to compare the effect of ETV and TDF on recurrence and mortality after curative treatment for HBV-related HCC. A comprehensive literature search of multiple electronic databases was conducted from 2000 to January 2022 for studies comparing ETV and TDF for HBV-related HCC patients after curative therapy. The adjusted hazard ratios (aHR) were pooled using a random-effects model. A total of nine studies with 5298 patients were included in the final meta-analysis. TDF was associated with a lower risk of HCC recurrence [aHR 0.73, 95% confidence interval (CI) 0.65–0.81] compared to HCC. TDF reduced the risk of late recurrence compared to ETV (aHR 0.58, 95% CI 0.45–0.76) but not early recurrence (aHR 0.88, 95% CI 0.76–1.02). The mortality risk was also lower with TDF compared to ETV (aHR 0.62, 95% CI 0.50–0.77). TDF was associated with a lower risk of recurrence and mortality than ETV after resection or ablation of HBV-related HCC. Further prospective randomized controlled studies are warranted to validate these results.


Chronic hepatitis B virus (HBV) infection is a global public health problem leading to liver failure, cirrhosis and hepatocellular carcinoma.[1–3] Chronic HBV infection and its complications contribute to approximately 780,000 deaths annually.[4,5] One of the most common causes of cancer-related deaths worldwide is hepatocellular carcinoma (HCC), with a high incidence in Asia compared to the rest of the world, mainly due to chronic HBV infection.[6,7] The development of these complications and mortality can be reduced by nucleos(t)ide analogues (NAs). Tenofovir disoproxil fumarate [TDF], Tenofovir alafenamide [TAF] and Entecavir (ETV) are the recommended first-line drugs for the management of chronic HBV infection due to their high barrier to resistance along with high antiviral potency.[8,9] The prevention of HCC in chronic HBV patients is essential to managing these patients. A meta-analysis by Cheung et al[10] reported a lower risk of HCC with TDF compared to ETV in chronic HBV infection, particularly in cirrhotic patients.

Hepatocellular carcinoma can develop in about 70% of patients within 5 years of curative resection, and the recurrence most commonly occurs in the first 2 years.[11] The most important and independent risk factor of recurrence in these patients is high HBV viral load.[12,13] Though antivirals prevent the recurrence of HCC after curative resection, they do not entirely eliminate the risk. The recurrence rate is shown to be 40%–60% in those patients who are on NAs after resection.[11,14] Choosing an appropriate antiviral drug is essential for the tertiary prevention of HCC. This meta-analysis aims to compare TDF with ETV for the tertiary prevention of HCC after curative therapy.