- Category: HBV Treatment
- Published on Thursday, 27 December 2012 00:00
- Written by Liz Highleyman
Treatment with tenofovir (Viread) remains safe and effective over 5 years, and people who achieve sustained viral load suppression experience improvement in liver histology, including regression of fibrosis and cirrhosis, according to study findings described in the December 7, 2012, advance online edition of The Lancet.
Over years or decades, chronic hepatitis B virus (HBV) infection can lead to serious liver disease including advanced fibrosis, cirrhosis (scarring), and hepatocellular carcinoma. Antiviral treatment with nucleoside/nucleotide analogs can suppress viral replication, but its long-term effects on liver health are not fully understood.
Patrick Marcellin from Hôpital Beaujon in Clichy, France, and colleagues analyzednearly 500 participants in Gilead Sciences' Study 102 (HBeAg negative) and Study 103 (HBeAg positive), which compared tenofovir disoproxil fumarate vs adefovir dipivoxil (Hepsera) for chronic hepatitis B.
After the 48-week randomized treatment period, patients had the option to remain on open-label tenofovir and undergo long-term follow-up including liver biopsies. Out of 641 patients who initially received randomized treatment, 585 (91%) entered the open-label phase, 489 (76%) completed 240 weeks of treatment, and 348 (54%) had biopsy results at baseline and week 240.
- 304 of the 348 participants with paired biopsies (87%) showed histological improvement at week 240, defined as at least a 2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis.
- 176 patients (51%) showed fibrosis regression, defined as at least a 1 unit decrease in Ishak fibrosis score.
- Among the 96 patients (28%) who had cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer did at week 240.
- Conversely, only 3 of 252 patients without cirrhosis at baseline progressed to cirrhosis by week 240.
- Virological breakthrough during treatment was uncommon and was not due to tenofovir resistance mutations.
- Tenofovir continued to be generally safe and well-tolerated over 5 years.
- 91 patients (16%) experienced adverse events, but only 9 had serious side effects related to the study drug.
Based on these findings, the study authors concluded, "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."
P Marcellin, E Gane, M Buti, et al. Regression of Cirrhosis during Treatment with Tenofovir Disoproxil Fumarate for Chronic Hepatitis B: a 5-Year Open-label Follow-up Study. The Lancet S0140-6736(12)61425-1. December 7, 2012 (Epub ahead of print).