Much of hepatology relies on surrogate markers to convey whether treatments are effective. For hepatitis B virus (HBV), some of these markers include serology (eg. development of HBV e antibody), improvements in biochemistry (eg. transaminases) as well as histology. Of these, improved histology is likely to have the most bearing on clinical outcomes like progression to end-stage liver disease and hepatocellular carcinoma. A previous study of lamivudine has indicated that regression of fibrosis can reduce the rate of hepatocellular carcinoma (NEJM 2004; 351: 1521-31).
As such, the results of long-term use of agents like tenofovir have been awaited. Since tenofovir along with entecavir are considered 1st line agents, their use has become commonplace for the treatment of HBV. Now 5-year data are available in a large cohort (Lancet 2013; 381: 468-75).
The data from this study was derived from an open-label cohort that followed 48-week double-blind comparison trials. 489 patients completed 240 weeks of treatment. 348 patients had biopsy results available at baseline and at week 240.
- 304 (87%) of those with biopsies at study completion had histologic improvement.
- 176 (51%) had regression of fibrosis
- 71 of 96 (74%) who had cirrhosis at baseline no longer had cirrhosis (≥1 unit decrease in Ishak fibrosis score)
- 3 of 252 without cirrhosis at baseline progressed to cirrhosis at week 240
- No evidence of resistance to tenofovir was evident. Nearly all patients on tenofovir had undetectable HBV DNA
- Adverse safery events were rare
As with all studies looking at liver histology, there were limiting factors including potential sampling errors and variable interpretation. The authors sought to minimize this by using an independent pathologist. Another strength of the study was the broad range of patients to make these findings broadly applicable.
Take-home message: Tenofovir treatment for 5 years is safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and reversal of cirrhosis.
Related blog posts:
- Extended data with entecavir & annotated HBV … – gutsandgrowth
- More on entecavir and tenofovir | gutsandgrowth
- Lessons about HBV in NYC | gutsandgrowth
- “Immune-tolerant” — a misnomer for HBV infection | gutsandgrowth
- HBV: translating advances from adults to pediatrics | gutsandgrowth
- Drink Up! | gutsandgrowth
- Live longer –drink more coffee | gutsandgrowth