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Effect of Alpha-Interferon Treatment in Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B: A Meta-Analysis

David K. H. Wong; Angela M. Cheung; Keith O'Rourke; C. David Naylor; Allan S. Detsky; and Jenny Heathcote
[+] Article and Author Information

From the Toronto Hospital and the Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario. Requests for Reprints: Jenny Heathcote, MD, 399 Bathurst Street, ECW 7-006, Toronto, Ontario M5T 2S8, Canada. Acknowledgments: The authors thank Dr. Edward Etchells and Dr. David Naimark for assessing the quality of the studies used in our meta-analysis and Drs. A. Lok, R. Muller, G. Pastore, M. Sabbour, and G. Saracco for providing additional information about their studies. Grant Support: Dr. Detsky is supported by a National Health Research Scholar Award from Health and Welfare Canada. Dr. Naylor is supported by a Career Scientist Award (02387) from the Ontario Ministry of Health.


Copyright 2004 by the American College of Physicians


Ann Intern Med. 1993;119(4):312-323. doi:10.7326/0003-4819-119-4-199308150-00011
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Purpose: To determine whether -interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic hepatitis B virus (HBV) infection.

Data Sources: Randomized controlled studies published in the English literature between January 1966 and June 1992 were identified through a MEDLINE computer search.

Study Selection: Fifteen randomized, controlled studies with a total of 837 adult chronic HBV carriers who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were identified. Studies were included if patients were treated for at least 3 months and followed for at least 6 months after cessation of therapy.

Results: Overall, the loss of HBsAg occurred 6% more often in interferon-treated patients than the natural seroconversion seen in controls (7.8% compared with 1.8%, P = 0.001), and the loss of viral replication occurred approximately 20% more often in treated patients than in controls (33% compared with 12% for loss of HBeAg and 37% compared with 17% for the loss of HBV DNA, P = 0.0001) if patients received interferon for 3 to 6 months and were followed for 6 to 12 months. Interferon also had a significant treatment effect on the development of antibodies to HBsAg (anti-HBs), antibodies to HBeAg (anti-HBe), and on the normalization of alanine aminotransferase levels.

Conclusions: Alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic HBV infection who are HBeAg positive when these patients are treated for 3 to 6 months and followed for 6 to 12 months after cessation of therapy. Follow-up studies are required to determine whether interferon reduces the risk for developing cirrhosis or hepatocellular carcinoma.

Figures

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Figure 1.
Natural history of chronic hepatitis B acquired in childhood.[19]

The initial phase of immune tolerance is followed by the phase of immune clearance of hepatitis B virus (HBV) and finally the cessation of HBV replication. The transition from the replicative to the nonreplicative phase may be rapid and smooth () or prolonged and fluctuating ( ). CPH = chronic persistent hepatitis; NSRH = nonspecific reactive hepatitis; CLH = chronic lobular hepatitis; CAH = chronic active hepatitis; HCC = hepatocellular carcinoma. From Lok and Lai , with permission.

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Figure 2.
Randomized controlled trials of -interferon treatment for patients with chronic hepatitis B infection and hepatitis B e antigen.leftright

The pooled and individual differences in proportions and their 95% CIs are shown for loss of hepatitis B surface antigen (HBsAg) ( ) and loss of hepatitis B e antigen (HBeAg) ( ). Values greater than 0 indicate a beneficial treatment effect.

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Figure 3.
The effect of high-dose compared with low-dose interferon therapy in patients with chronic hepatitis B and hepatitis B e antigen.leftright22

The pooled and individual differences in proportions and their 95% CIs are shown for loss of hepatitis B surface antigen (HBsAg) ( ) and loss of hepatitis B e antigen (HBeAg) ( ) for studies that randomized patients to different doses of interferon. A high dose was arbitrarily defined as greater than 15 MU/m per week (> 5 MU/m thrice weekly).

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Figure 4.
Sensitivity analyses by quality scores.leftright

The effect of quality scores on the pooled confidence intervals is shown for loss of hepatitis B surface antigen (HBsAg) ( ) and loss of hepatitis B e antigen (HBeAg) ( ). The trials of lower quality were sequentially eliminated.

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