IF: 1.578
Cite Score:
1.45
THOMSON REUTERS - SCOPUS

Commentaries and points of view 2

AUTHORS

Kamran chairman@hepmon.ir 1 , * , Seyed Moayed Alavian 2

1 Namazi hospital, Shiraz, Fars, IR.Iran

2 Associate professor of gastroenterology and hepatology, Baqiyatallah University of Medical Sciences, Tehran, Tehran, IR.Iran

How to Cite: chairman@hepmon.ir K, Alavian S M. Commentaries and points of view 2, Hepat Mon. 2004 ; 4(8):e93016.

ARTICLE INFORMATION

Hepatitis Monthly: 4 (8); e93016
Published Online: September 30, 2004
Article Type: Commentaries
Received: May 06, 2019
Accepted: September 30, 2004

Crossmark

CHEKING

READ FULL TEXT
Abstract

Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B.

N Engl J Med. 2004 Sep 16;351(12):1206-17.

Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, Lu ZM, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Button P, Pluck N; Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group

Service d'Hepatologie, INSERM Unite 481 and Centre de Recherches Claude Bernard sur les Hepatites Virales, Hopital Beaujon, Clichy, France. patrick.marcellin@bjn.ap-hop-paris.fr

Background: Available treatments for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are associated with poor sustained responses. As a result, nucleoside and nucleotide analogues are typically continued indefinitely, a strategy associated with the risk of resistance and unknown long-term safety implications.

Methods: We compared the efficacy and safety of peginterferon alfa-2a (180 microg once weekly) plus placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), and lamivudine alone in 177, 179, and 181 patients with HBeAgnegative chronic hepatitis B, respectively. Patients were treated for 48 weeks and followed for an additional 24 weeks.

Results: After 24 weeks of follow-up, the percentage of patients with normalization of alanine aminotransferase levels or hepatitis B virus (HBV) DNA levels below 20,000 copies per milliliter was significantly higher with peginterferon alfa-2a monotherapy (59 percent and 43 percent, respectively) and peginterferon alfa-2a plus lamivudine (60 percent and 44 percent) than with lamivudine monotherapy (44 percent, P=0.004 and P=0.003, respectively; and 29 percent, P=0.007 and P=0.003, respectively). Rates of sustained suppression of HBV DNA to below 400 copies per milliliter were 19 percent with peginterferon alfa-2a monotherapy, 20 percent with combination therapy, and 7 percent with lamivudine alone (P<0.001 for both comparisons with lamivudine alone). Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups, as compared with 0 patients in the group given lamivudine alone. Adverse events, including pyrexia, fatigue, myalgia, and headache, were less frequent with lamivudine monotherapy than with peginterferon alfa-2a monotherapy or combination therapy.

Conclusions: Patients with HBeAg-negative chronic hepatitis B had significantly higher rates of response, sustained for 24 weeks after the cessation of therapy, with peginterferon alfa-2a than with lamivudine. The addition of lamivudine to peginterferon alfa-2a did not improve posttherapy response rates.

Keywords

hepatitis b treatment

© 2004, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

Fulltext

Hepatitis Monthly Editorial Board Comment 2

Kamran Bagheri Lankarani 1, Seyed-Moayed Alavian 2

1.Associate professor of gastroenterology and hepatology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, I.R.Iran

2.Associate professor of gastroenterology and hepatology, Baqiyatallah University of Medical Sciences, Tehran, I.R.Iran

We read with interest the article titled" Peginterferon Alfa-2a Alone, Lamivudine Alone, and the Two in Combination in Patients with HBeAg-Negative Chronic Hepatitis B" by Marcellin et al. (N Engl J Med. 2004; 351:1206-17). It was very interesting for us to understand the efficacy of new drugs in chronic hepatitis B (CHB) patients, especially in CHB with HBeAg negative. Treatment of chronic hepatic B infection in the absence of HBe antigen is very challenging. Marcellin and his colleagues in their recent study used pegylated interferon alfa (PEG IFN) in these patients (1), but several points in their study need more clarification. First of all, there is no comparison with standard interferon. Available data indicate prolonged course of standard interferon for ³12 months has 20-30% sustained virologic response which is almost the same as what is reported with PEG IFN in this study with a much lower cost (1, 2, 3). It seems that we need a protocol to compare between the standard interferon alfa with pegylated interferon in HBeAg negative CHB by considering the costs. The second point is that there was one death in PEG IFN group which needs more consideration. While it was claimed that all treated patients had elevated ALT before treatment, the baseline data in table one indicate ALT level in all treatment groups included normal values!?. If this is the case then indication of treatment in these cases with normal ALT level is not clear (4). As mentioned in the article, rate of HBsAg loss and HBsAg seroconversion at week 72 occurred in seven and five patients who received peginterferon alfa-2a monotherapy respectively and; in five and three patients who received peginterferon alfa-2a plus lamivudine, respectively and in no patients in lamivudine group. However, the authors concluded the importance of dual immunomodulatory and antiviral effects of interferon-based therapies in the treatment of HBeAg negative CHB. We think this benefit belongs to interferon alfa and not to lamivudine, which is in accordance with what the authors mentioned in another part of discussion. The results with peginterferon alfa-2a monotherapy were better than combination therapy. The best conclusion is that response rate to lamivudine is lower than that of interferon-based therapy. Several studies suggests that HBV genotypes may influence response to anti-viral therapy and genotypes A and B have been reported to be associated with higher rates of response to interferon alfa than genotypes D and C, respectively (5).There are also no data on genotypes in this article which may affect response to treatment. By considering these points, we believe that while this is an excellent response rate with peginterferon alfa-based therapy in comparison with lamivudine, it is still a long way to conclude that peginterferon alfa is the first-line therapy for HBeAg negative CHB and it needs more studies.

References

  • 1.

    Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, Lu ZM, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Button P, Pluck N; Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004; 351:1206-17.

  • 2.

    Lampertico P, Del Ninno E, Manzin A, Donato MF, Rumi MG, Lunghi G, et al. A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum. Hepatology 1997; 26:1621-5.

  • 3.

    Lampertico P, Del Ninno E, Vigano M, et al.: Long term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy. Hepatology 2003, 37:756-763.

  • 4.

    Papatheodoridis GV, Hadziyannis SJ. Review article: current management of chronic hepatitis B. Aliment Pharmacol Ther. 2004; 19:25-37.

  • 5.

    Kao JH; Wu NH; Chen PJ; Lai MY; Chen DS. Hepatitis B genotypes and the response to interferon therapy. J Hepatol 2000; 33:998-1002.

  • COMMENTS

    LEAVE A COMMENT HERE: