Elsevier

Journal of Hepatology

Volume 46, Issue 1, January 2007, Pages 45-52
Journal of Hepatology

Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma,☆☆

https://doi.org/10.1016/j.jhep.2006.08.021Get rights and content

Background/Aims

The long-term outcomes of interferon-alpha (IFN-α) therapy in hepatitis B e antigen (HBeAg) seropositive patients remain controversial. This study was conducted to address this issue.

Methods

The long-term outcomes were compared in 233 IFN-treated patients and 233 well-matched untreated controls.

Results

The cumulative incidence at the end of 15 years of follow-up (median 6.8 years, range 1.1–16.5 years) in the IFN-treated patients and controls was: HBeAg seroconversion 74.6% vs. 51.7% (P = 0.031); hepatitis B surface antigen (HBsAg) seroclearance 3% vs. 0.4% (P = 0.03); cirrhosis 17.8% vs. 33.7% (P = 0.041); and hepatocellular carcinoma (HCC) 2.7% vs. 12.5% (P = 0.011). Significant reduction of HCC was only observed in patients with pre-existing cirrhosis (P < 0.01). Compared with untreated controls with persistent HBeAg, HBeAg seroconverters in untreated and IFN-treated group showed significantly lower incidence of cirrhosis and HCC (P = 0.003–0.031), while non-seroconverters of IFN-treated group had marginally significant lower incidence of cirrhosis (P = 0.065). Multivariate analysis showed that IFN therapy, HBeAg seroconversion and genotype B HBV infection are independent factors for better long-term outcomes.

Conclusions

IFN therapy reduces cirrhosis and HCC development.

Introduction

Studies on the natural history of chronic hepatitis B virus (HBV) infection have shown that active HBV replication contributes to the development of acute flare, hepatic decompensation, cirrhosis and hepatocellular carcinoma (HCC) [1]. Theoretically, cessation of HBV replication may reduce the complications and improve prognosis. Interferon alfa (IFN) has been used in the treatment of chronic hepatitis B for decades. Beneficial effects including hepatitis B e antigen (HBeAg)/HBV–DNA seroclearance, reduction of HCC development and better complication free survival have been documented [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. However, the effect on the prevention of cirrhosis and HCC development remains controversial [9], [10], [11]. The major reasons include relatively small sample size, low response rate, lack of adequate controls, short follow-up period and different age group at enrollment. To address these problems, the long-term outcomes were compared between 233 IFN-treated patients and 1:1 well-matched untreated controls. Considering the role of HBV genotype [12], it was also included in the analysis.

Section snippets

Study group

The study group (IFN-treated) consisted of 233 patients from 3 medical centers in Taiwan, including 176 patients from two randomized trials conducted in one center between 1986 and 1993, as described elsewhere [6], [9]. The remaining 57 were consecutive patients with active hepatitis who received IFN therapy as part of the clinical practice before end of 1995. All patients were HBeAg positive with active hepatitis demonstrated by a biopsy within 3 months before starting therapy, and no evidence

Results

During IFN treatment, 109 (46.8%) patients required dose reduction and two patients discontinued therapy because of severe malaise and psychosis, respectively. The long-term outcomes of IFN-treated and control group are compared in Table 2 based on intention to treat analysis.

Discussion

Although a variety of IFN regimens were used to treat patients in the present study, almost all were in the recommended range of 4–6 months [19], and the duration of IFN therapy was not a significant factor in multivariate analysis (Table 4). The results of these regimens as a group have confirmed our previous findings that IFN-therapy, particularly with corticosteroid priming, in HBeAg positive patients was associated with a higher cumulative rate of HBeAg/HBV–DNA seroclearance and reduced HCC

Acknowledgements

This work was supported by grants awarded to Y.-F. Liaw from the Department of Health (DOH90-HP-1004) and the Prosperous Foundation Taipei, Taiwan. The authors thank Ms. Ivy Cheng and SC Chu for excellent assistance.

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    Financial support: The authors have no financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work. YF Liaw has served as an advisory board member of Roche and Bristol Myers-Squibb.

    ☆☆

    The authors who have taken part in this study declared that they have no relationship with the manufactures of the drugs involved either in the past or present and they received funding from Wellcome and Roche to carry our their research.

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