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.
A study has assessed the effects on fibrosis and cirrhosis of at least 5 years' treatment with Tenofovir disoproxil fumarate ( Tenofovir DF; Viread ) in chronic HBV infection.
After 48 weeks of randomised double-blind comparison of Tenofovir DF with Adefovir dipivoxil ( Hepsera ), 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.
Researchers have assessed histological improvement ( greater than or equal to 2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis ) and regression of fibrosis ( greater than or equal to 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 less than 0.0001 ).
Of the 96 ( 28% ) patients with cirrhosis ( Ishak score 5 or 6 ) at baseline, 71 ( 74% ) no longer had cirrhosis ( greater than or equal to 1 unit decrease in score ), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 ( p less than 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 disoproxil fumarate was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis. ( Xagena )
Marcellin P et al, The Lancet 2013; 381: 468-475