Long-Term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy

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HEPATOLOGY

April 2003 . Volume 37 . Number 4

Original Articles: Viral Hepatitis

Long-Term suppression of hepatitis B e antigen-negative chronic hepatitis B

by 24-month interferon therapy

Pietro Lampertico1 ,Ersilio Del Ninno1 ,Mauro Viganò1

Raffaella Romeo1 , Francesca Donato1

Erwin Sablon2 ,Alberto Morabito3, Massimo Colombo1

Abstract

To assess whether extended treatment with interferon improves the outcome of

hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 101 consecutive

patients were treated with 6 MU of interferon alfa 2b 3 times weekly for 24

months. During the 68-month study, 30 patients (30%) had a sustained

response (i.e., normal serum transaminase levels and undetectable hepatitis

B virus DNA by non-polymerase chain reaction [PCR] assays), and 15 cleared

serum surface antigen. Twenty-five nonresponders, 16 relapsers, and 30 who

discontinued treatment were considered treatment failures. Multivariate

analysis predicted a sustained response for young age (odds ratio, 0.94; 95%

confidence interval, 0.89-0.99; P = .041) and high pretreatment serum levels

of immunoglobulin M (IgM) anti-hepatitis B core antigen (HBc) (odds ratio,

4.52; 95% confidence interval, 1.63-12.5; P = .004). Liver disease

progressed in none of the sustained responders but in 16 with treatment

failure (0% vs. 22%, P = .002); hepatocellular carcinoma (HCC) developed

with similar frequency in both groups (7%). Overall, estimated 8-year

complication-free survival was longer for the 30 sustained responders than

the 71 patients with treatment failure (90% vs. 60%, P < .001), but 8-year

patient survival was similar in the 2 groups (100% and 90%). Short

complication-free survival was predicted by failure to respond to interferon

(hazard ratio, 7.8; 95% confidence interval, 1.8-34.0; P = .006) and high

scores for liver fibrosis (hazard ratio, 1.71; 95% confidence interval,

1.17-2.50; P = .005). In conclusion, 24 months of treatment with interferon

alfa 2b led to sustained disease suppression in a significant proportion of

patients with HBeAg-negative chronic hepatitis B. (HEPATOLOGY

2003;37:756-763.)

Abbreviations

HBeAg hepatitis B e antigen

HBV hepatitis B virus

HCC hepatocellular carcinoma

HBsAg hepatitis B surface antigen

anti-HBe antibody to hepatitis B e antigen

ALT alanine aminotransferase

PCR polymerase chain reaction

HIV human immunodeficiency virus

anti-HBs antibody to hepatitis B surface antigen

IgM immunoglobulin M

anti-HBc antibody to hepatitis B core antigen

Publishing and Reprint Information

From the 1Division of Hepatology and Fondazione Italiana Ricerca Cancro

Liver Cancer Unit, Istituto di Ricovero e Cura a Carattere Scientifico

(IRCCS) Maggiore Policlinico Hospital, University of Milan, Milan, Italy;2

Innogenetics N.V., Ghent, Belgium;3 Division of Statistics, Department of

Medicine, Surgery and Dentistry, University of Milan, Milan, Italy.

Received August 9, 2002.

Accepted January 14, 2003.

Supported in part by the Fondazione Italiana Ricerca Cancro and the

Consorzio Interuniversitario Trapianti d'Organo, Rome.

Address reprint requests to: Massimo Colombo, M.D., Division of Hepatology,

IRCCS Maggiore Hospital, Via Pace 9, 20122 Milan, Italy. E-mail:

massimo.colombo@... ; fax: (39) 0250320700.

Copyright © 2003 by the American Association for the Study of Liver

Diseases.

0270-9139/03/3704-0008$30.00/0

doi:10.1053/jhep.2003.50148