Antivirals After Liver Resection for HBV-Associated Hepatocellular Carcinoma: Which Is Better, Tenofovir vs. Entecavir?

Tenofovir disoproxil was associated with better long-term results than entecavir in a retrospective cohort study comparing the two antivirals in patients with hepatitis B virus (HBV)-associated hepatocellular cancer who had been surgically treated with liver resection, according to results reported today in JAMA Network Open.

Meta-analyses and randomized trials have shown that antiviral therapy after surgical treatment for HBV-associated hepatocellular cancer is associated with reduced risks of reoccurrence of cancer and improved survival rates, although there is some question about how much of a difference antiviral treatment will make in people without active infections or a high viral load.

This study used propensity score-matching to compare 989 patients who were treated with tenofovir disoproxil with a like number of patients treated with entecavir at the Eastern Hepatobiliary Surgery Hospital in Shanghai, China. After one year, the overall survival rate of the patients treated with entecavir was a slightly better than those treated with entecavir (92.2% vs. 90.9%). But after that, after three years and five years the rates were better for the patients treated with tenofovir disoproxil: 75.2% at three years compared with 70.9% for those who were treated entecavir and at five years, 64% compared with 54.2% for those who were treated with entecavir.

A side-by-side comparison of recurrence-free survival produce the same pattern of early superiority for entecavir but then better results for tenofovir disoproxil at three and five years.

“This cohort study found that among patients with HBV-related HCC (hepatocellular carcinoma) who underwent liver resections with curative intent, tenofovir disoproxil was associated with significantly better OS (overall survival) and RFS (recurrence-free survival) rates compared with entecavir on long-term follow-up but not in short-term follow-up,” wrote corresponding authors Gang Huang, M.D., and Weiping Zhou, M.D., of the Eastern Hepatobiliary Surgery Hospital and their colleagues. “Tenofovir disoproxil could be considered the preferred long-term antiviral treatment for these patients.”

This study was not designed to identify reasons for one antiviral being superior to another. But in the discussion section of the paper, Huang and Zhou referenced a study published in 2018 in the journal Gut that showed that tenofovir disoproxil triggered expression of interferon-lambda3 and inhibited production of HBV antigen.

They also said that the early advantage of entecavir over tenofovir disoproxil might be explained by the “widely accepted theory” that early recurrences of hepatocellular carcinoma after surgery are the result of existing cancer cells spreading into the remaining part of the liver rather than being the result hepatitis B infection.