"Long-term treatment with entecavir (Baraclude) at least partially reverses cirrhosis and fibrosis in most chronic hepatitis B patients, according to extended follow-up of a clinical trial.
In nucleoside-naive patients, liver biopsies taken at least six years after starting on three or more years of entecavir treatment revealed histologic improvement in 96% of patients.
Fibrosis score improved by at least one point in 88% of patients as well, found Ting-Tsung Chang, MD, of National Cheng Kung University Hospital in Tainan, Taiwan, and colleagues.
All 10 patients with advanced disease at baseline saw improvements in fibrosis and cirrhosis long term, the researchers reported in the September issue of Hepatology.
These results add to evidence challenging the idea that fibrosis is an irreversible and relentlessly progressive process, they noted.
The researchers analyzed outcomes from 69 patients who provided a long-term biopsy sample after having received entecavir for a total of at least three years as part of one of two identical phase III randomized trials, followed by rollover into an open-label study in which all patients got 1.0 mg entecavir daily.
The randomized phase of the trials showed entecavir superior to lamivudine (Epivir) for both patients with chronic e antigen-negative hepatitis B and those with e antigen-positive infections. All patients were nucleoside-naive before the trial.
Among the 57 patients who met criteria for the long-term efficacy analysis, the median time on entecavir was approximately six years (range three to seven).
The rate of histologic improvement compared with baseline rose to 96% at the long-term assessment, compared with 73% after just 48 weeks of therapy.
The same was true for the proportion with at least a one-point improvement in Ishak fibrosis score, rising from 32% at 48 weeks to 88% at the long-term assessment.
For those with necroinflammation by the Knodell classification at baseline, 75% dropped down to no or minimal necroinflammation long term. Among those with fibrosis at baseline, 72% had no or minimal fibrosis long term.
Only one of the 57 patients showed an increase in Ishak fibrosis score (1 at baseline versus 2 at long-term biopsy) despite undetectable HBV DNA, normal liver enzymes, and an improvement in necroinflammatory score long term.
Virologic suppression -- HBV DNA under 300 copies/mL -- was maintained for all patients at the time of long-term biopsy, while 86% had normalized alanine transaminase (ALT).
As expected from the sustained virologic response, there was no evidence of virologic rebound or development of antiviral drug resistance, the researchers noted.
Although 55% of patients lost e antigen and 33% had seroconversion during long-term treatment, those who didn't also showed improved liver histology and reversal of fibrosis, which Chang's group pointed to as evidence that "these outcomes are more closely associated with HBV DNA suppression than with immunologic response to therapy."
Moreover, the results confirm the value of long-term treatment for chronic hepatitis B, they concluded.
"The safety profile, potent suppression of HBV replication, and low potential for antiviral drug resistance in nucleoside-naive patients make long-term treatment of chronic hepatitis B with entecavir monotherapy possible," they wrote in the paper.
The study was sponsored by the Bristol-Myers Squibb Pharmaceutical Research Institute.
Chang reported having research funding from Gilead Sciences, Bristol-Myers Squibb, GlaxoSmithKline, Schering-Plough, and Pfizer, as well as receiving speech honoraria from Bristol-Myers Squibb and Schering-Plough.
Several co-authors reported being employees of Bristol-Myers Squibb."
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