lamivudine therapy for advanced liver disease in patients with precore mutant.

liver411

Efficacy of lamivudine therapy for advanced liver disease in patients with precore mutant hepatitis B virus infection awaiting liver transplantation1
Date:  Tue, 5 Nov 2002 07:16:30 -0500
Transplantation 2002; 74(8):1119-1124

Efficacy of lamivudine therapy for advanced liver disease in patients with
precore mutant hepatitis B virus infection awaiting liver transplantation1

Pietro Andreone 2 4; Maurizio Biselli 2; Annagiulia Gramenzi 2; Carmela
Cursaro 2; Maria C. Morelli 3; Claudia Sama 3; Stefania Lorenzini 2; Giulio
Spinucci 3; Federica Porzio 2; Francesco Felline 2; Loriana Di Giammarino 2;
Mauro Bernardi 2

Background.
Orthotopic liver transplantation (OLT) for end-stage liver disease resulting
from hepatitis B virus (HBV) infection is associated with a high rate of
recurrence and reduced survival. Lamivudine is effective in inhibiting HBV
replication in patients with chronic hepatitis. This study evaluated the
impact of lamivudine on viral suppression, liver function, and disease
severity in patients awaiting OLT with HBV e-minus strain infection.

Methods.
Twenty-five patients received lamivudine (100 mg per day) from the day of
listing for OLT. All patients were positive for serum HBV-DNA by polymerase
chain reaction and all had a Child-Pugh score of 7 or higher.

Results.
Patients were followed for 12? months (mean ?SD). Eleven underwent OLT
within 13 months of treatment initiation, one died after 10 months, and one dropped out after 3 months. After 3, 6, and 9 months, HBV-DNA by polymerase chain reaction was undetectable in 14 of 25, 14 of 20, and 13 of 15 patients, respectively. Two patients developed lamivudine resistance after 9 and 18 months of treatment, respectively, without liver decompensation. Comparing baseline to last visit data, a significant improvement in prothrombin activity (43?5% vs. 52?9%; P=0.0014), serum bilirubin (3.4?.9 vs. 2.5?.2 mg/dL; P=0.0007), serum albumin (3.3?.3 vs. 3.6?.5 g/dL; P=0.0278), presence of ascites (15/25 vs. 7/25; P=0.0047), and Child-Pugh score (9 vs. 8; P=0.0003) was observed. Because of liver function improvement, four patients were placed on low priority status for OLT (United Network of Organ Sharing 3) and 9 on inactive status (United Network of Organ Sharing 7). The overall probability of survival at 6 and 12 months was 100% and 90.9%, respectively.

Conclusions.
Lamivudine has an important role in patients with end-stage liver disease
caused by HBV precore mutant strain. Not only does HBV-DNA suppression allow patients to be eligible for OLT, but the improvement of the patients'
clinical status may delay the need for OLT in an era of organ shortage.

1 This work was supported by "Associazione per la Ricerca sulle Malattie
Epatiche" and "Fondazione Carisbo, Progetto di Ricerca Clinica e Biologia
delle Gravi Insufficienze d'Organo," Bologna, Italy. M.B. was supported by a
grant from "Fondazione Carisbo, Progetto di Ricerca Clinica e Biologia delle
Gravi Insufficienze d'Organo."
2 Department of Internal Medicine, Cardioangiology, and Hepatology,
University of Bologna, "S. Orsola" Hospital, Bologna, Italy.
3 Department of Internal Medicine and Gastroenterology, University of
Bologna, "S. Orsola" Hospital, Bologna, Italy.
4 Address correspondence to: Dr P. Andreone, Semeiotica Medica, Policlinico
S. Orsola, Via Massarenti, 9-40138 Bologna, Italy.

Received 19 December 2001.
Revision Requested 28 March 2002.
Accepted 21 May 2002.