Outcome of Hepatitis B e Antigen–Negative Chronic Hepatitis ... : Hepatology (original) (raw)

Viral Hepatitis

Outcome of Hepatitis B e Antigen–Negative Chronic Hepatitis B on Long-Term Nucleos(t)ide Analog Therapy Starting With Lamivudine*

Papatheodoridis, George V.1; Dimou, Evangelini2; Dimakopoulos, Konstantinos3; Manolakopoulos, Spilios4; Rapti, Irene2; Kitis, George3; Tzourmakliotis, Dimitrios4; Manesis, Emanuel1; Hadziyannis, Stephanos J.2†‡

1 2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Greece

2 Department of Medicine & Hepatology, Henry Dunant Hospital of Athens, Greece

3 Department of Gastroenterology, George Papanikolaou General Hospital of Thessaloniki, Greece

4 Department of Gastroenterology, Polyclinic General Hospital of Athens, Greece

† Department of Medicine & Hepatology, Henry Dunant Hospital, 107 Messogion Ave., 11526 Athens, Greece

Email:[email protected]

Received 8 February 2005; Accepted 19 April 2005

Published online in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: Gilead; Grant sponsor: Schering-Plough; Grant sponsor: Roche.

*Potential conflict of interest: Dr. Manolakopoulos is a consultant for Gilead. Dr. Kitis is a consultant for and has received a research grant from Gilead. Dr. Papatheodoridis is on the advisory board for Roche and is the principal investigator in clinical trials for Idenix. Dr. Manesis has received a research grant from Schering-Plough. Dr. Hadziyannis is a consultant, on the speakers' bureau, and on the advisory board for Gilead, Roche, and Bristol-Myers Squibb and has received research grants from Gilead and Roche.

‡fax: (30) 210-6972974

Abstract

**We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients treated for 3.8 ± 1.4 years and 2 historical similar cohorts: 1 treated with interferon-alfa (n = 209) and 1 untreated (n = 195). Virological or biochemical remission rate at 48 months under lamivudine was 34% or 36%, respectively, whereas adefovir was administered in 79 patients with virological–biochemical breakthroughs or no response. Of the lamivudine-treated patients, 4 died, 1 underwent a transplantation, and another 8 developed major events, all having advanced fibrosis at baseline and all but 1 having experienced breakthroughs or no response. At 5 years, survival was 96%, and major event–free survival was 93%. The major event–free survival was significantly better in patients with than in those without virological remission under lamivudine. At the end of follow-up, both survival and major event–free survival were independently associated with type of and response to treatment, being significantly better in patients under long-term antiviral therapy or interferon sustained responders than in interferon non-sustained responders or untreated cases (5-year survival: 96% or 98% vs. 88% or 90%, respectively).**In conclusion,in HBeAg-negative chronic hepatitis B, long-term nucleos(t)ide analog therapy starting with lamivudine significantly improves survival and reduces the risk of major complications, compared with interferon non-sustained responders or untreated patients. In such patients with advanced fibrosis, close follow-up for lamivudine resistance and prompt onset of additional antiviral therapy is required or the ab initio use of agent(s) with low resistance rates should be considered. (Hepatology 2005;42:121–129.)