Impact of Adefovir (Hepsera) on Liver Fibrosis and Histological Activity Assessed Using FibroTest-ActiTest in Hepatitis B Patients

Although liver biopsy remains the gold standard for assessing the degree of liver fibrosis and/or cirrhosis in chronic hepatitis B patients, many individuals find its invasiveness problematic. Therefore, researchers have explored several non-invasive methods for assessing liver damage.

The aim of the current study, presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston (November 2-6, 2007), was to evaluate the usefulness of the non-invasive FibroTest-ActiTest (FT-AT) as surrogate markers of histological features in people with chronic hepatitis B.

Chronic hepatitis B patients were randomized in 2 pivotal trials of adefovir (Hepsera) versus placebo. Paired liver biopsies and FT-AT scores at baseline and after 48 weeks of treatment were analysed

Fibrosis and histological activity were assessed blindly according to the Ishak scoring system. The diagnostic value of FT-AT was assessed using the area under the receiver operating characteristics curves (AUROCs) for the diagnosis of bridging fibrosis, cirrhosis, and moderate-to-severe necro-inflammatory activity. Sensitivity analyses took into account race, length of biopsy, HBeAg status, and sample date.

The impact of treatment versus placebo was assessed on liver injury according to baseline stage and virological response at 48 weeks. For baseline discordant patients, 48-week repeated estimates in adefovir virological responders and placebo non-responders were permitted to estimate the ratio due to FT-AT or biopsy failures.

Results

• 462 patients with paired biopsies and FT-AT were included (304 treated with adefovir and 158 receiving placebo).

• Analysis of 924 estimates showed very significant FT-AT AUROCs:

• 0.76 ± 0.02 for the diagnosis of bridging fibrosis;

• 0.81 ± 0.02 for cirrhosis;

• 0.80 ± 0.01 for moderate-to-severe necro-inflammatory activity.

• Similar impacts on liver fibrosis and activity were observed both with biopsy and FT-AT, with greater efficacy in patients with baseline advanced fibrosis, those treated with adefovir, and virological responders.

• The discordance analyses suggested that 66% of discordances were attributable to biopsy failure and 34% to FT-AT failure.

Conclusion

These findings led the authors to conclude, "In patients with chronic hepatitis B, FibroTest-ActiTest is a simple and non-invasive quantitative estimate of liver fibrosis and necrotico-inflammatory activity, which could be used as a surrogate marker to reduce the need for liver biopsy."

These results add to a growing body of data that suggest these tests and other, similar non-invasive assays have a significant role to play in improving the quality of life for patients who require reliable information concerning liver fibrosis and necrotic activity and who do not wish to undergo repeated liver biopsies.

APHP GHPS, Paris, France; Gilead, Foster City, CA, USA; APHP Beaujon, Paris, France; Henri Dunant Hospital, Athens, Greece.

12/07/07

Reference
T Poynard, Y Ngo, P Marcellin, and others. Impact of adefovir dipivoxil on liver fibrosis and activity assessed with FibroTest-ActiTest in patients infected by Hepatitis B Virus. 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA, November 2-6, 2007. Abstract 996.