itle FACTORS ASSOCIATED WITH REGRESSION OF CIRRHOSIS IN PATIENTS WITH CHORNIC HEPATITIS B (CHB) INFECTION TREATED WITH TENOFOVIR DISOPROXIL FUMARATE (TDF)
Speaker: Nezam Afdhal
Author: N. Afdhal1*, M. Buti2, S. Fung3, E. Gane4, J. Flaherty5, E. Martins5, N. Bekele5, J. Bornstein5, P. Marcellin6
Affiliation: 1Harvard Medical School, Boston, MA, USA, 2Servei de Medicina Interna-Hepatologia, Vall d'Hebron Hospital General, Barcelona, Spain, 3Univeristy of Toronto, Toronto, ON, Canada, 4Auckland City Hospital, Auckland, New Zealand, 5Gilead Sciences, Foster City, CA, USA, 6Hopital Beaujon, Clichy, France. ****@****
Regression of fibrosis is an important clinical outcome for patients with CHB who achieve long term viral suppression with nucleos(t)ide therapy. It has been previously reported that up to 5 years of TDF therapy results in a regression of cirrhosis in 74% of patients. The clinical and pathophysiologic differences between those that had reversal and those that did not has not been described.
Methods: A retrospective analysis was conducted on 96 cirrhotic patients (Ishak fibrosis stage ≥ 5) who had liver biopsies at baseline and at year 5 in 2 studies that compared the safety and efficacy of TDF to adefovir for 48 weeks in HBeAg negative (Study 0102) and HBeAg positive (Study 0103) patients, followed by open-label TDF treatment for an additional 7 years.
Results: 96 patients with cirrhosis at baseline had follow-up biopsies at year 5. 71 of the 96 (74%) were no longer cirrhotic (Ishak fibrosis stage ≤ 4). Among the different baseline covariates assessed, elevated body weight (87.4 kg vs. 76.8 kg, p=0.013) and body mass index (BMI) (29.0 kg/m2 vs 25.7 kg/m2, p< 0.001) were the only variables that were significantly correlated with persistent cirrhosis. Age, gender, race, viral genotype, inflammation, platelet count, albumin, ALT, and DNA and HBsAg titers did not correlate. There was a trend showing that patients with a shorter time since diagnosis and those with Ishak fibrosis stage 5 were more likely regress than those with longer duration of infection and Ishak stage 6 fibrosis. Subjects who were no longer cirrhotic were more likely than those with persistent cirrhosis to have a normal ALT at year 5, but no other differences were noted in outcomes for those that resolved cirrhosis vs. those that did not. Both groups had similar increases in platelet counts and albumin levels, similar rates of HBeAg loss, viral suppression, and HCC rates. No patient in either group had ascites, variceal bleeding or hepatic encephalopathy.
Conclusion: TDF therapy results in a high rate of cirrhosis reversal. Persistence of cirrhosis is most likely when risk factors for a 2nd disease such as obesity induced liver disease co-exists.