Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial
effect on regression of advanced liver fibrosis associated with chronic HBV infection
remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least
5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection.
After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805)
of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg)
were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a
pre-specified repeat liver biopsy at week 240. We assessed histological improvement
(≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis)
and regression of fibrosis (≥1 unit decrease by Ishak scoring system).
Of 641 patients who received randomised treatment, 585 (91%) entered the open-label
phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at
both baseline and week 240. 304 (87%) of the 348 had histological improvement, and
176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients
with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis
(≥1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline
progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently
and was not due to resistance to tenofovir DF. The safety profile was favourable:
91 (16%) patients had adverse events but only nine patients had serious events related
to the study drug.
In patients with chronic HBV infection, up to 5 years of treatment with tenofovir
DF was safe and effective. Long-term suppression of HBV can lead to regression of
fibrosis and cirrhosis.
Copyright © 2013 Elsevier Ltd. All rights reserved.