Jordan J. Feld, MD; Marc G. Ghany, MD
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Istanbul University, Cerrahpasa Medical School, Infectious Dis. Dept.
December 20, 2007
More on "Evolution of therapy for chronic hepatitis B: progressing from the simple to the complex"
TO THE EDITOR: We read with great interest the editorial of Feld and Ghany (1). They summarized the complexity of the issue of hepatitis B treatment. They simply compared the response to approved antiviral agents among hepatitis B e antigen-positive patients in the Table. Also they mentioned that response definitions are imperfect. However there are several differences between these studies by many aspects (Table) (1-6). Different methods were used in these studies for detection and quantification HBV DNA. Also sensitivity, detection limit and dynamic range of quantification of these tests make them difficult to compare (7). For example, baseline HBV level which is lower more than 1 log (corresponds to several folds) in adefovir study, for example, makes it almost impossible to compare. Combined data of three studies were given for lamivudine, however virological response criterion differed among these studies. ALT is another issue: Baseline mean ALT levels may not be comparable. Additionally, ALT level as an inclusion criterion varied: greater than 1 time the upper limit of the normal range for pegylated interferon (3), 1.3 times for entecavir (4) and telbivudine (5), and 1.2 times for adefovir (6). Patient numbers, genotype distributions, treatment durations, previous treatment, and probably many other differences exist among the studies compared, discouraging to make a head-to-head comparison. Asian race for example, is associated with poor response to interferon treatment (8), and the rate of this race is highest in pegylated interferon study. Considering the role of high ALT and low DNA on treatment response, a comparison of efficacy of any two drugs should include the details of distribution of these parameters in the study population. Only the telbivudine study described the stratification of the patients according to DNA levels. A simple comparison of several drugs in differing study characteristics may not give robust information to the reader. Unless randomizing the patients in the same study design, it seems difficult to compare the efficacies of any given drugs. When giving such tables, the reader should be warned against the difference among study characteristics and better, the main differences should also be included.
1. Feld JJ, Ghany MG. Evolution of therapy for chronic hepatitis B: progressing from the simple to the complex. Ann Intern Med 2007;147:806-8. [PMID: 18056667]
2. Wong DK, Cheung AM, O'Rourke K, Naylor CD, Detsky AS, Heathcote J. Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med. 1993;119:312-23. [PMID: 8328741]
3. Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, et al.; Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study Group. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg- positive chronic hepatitis B. N Engl J Med. 2005;352:2682-95. [PMID: 15987917]
4. Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, et al.; BEHoLD AI463022 Study Group. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001-10. [PMID: 16525137].
5. Lai CL, Gane E, Liaw YF, Thongsawat S, Wang Y, et al. Telbivudine vs. lamivudine for chronic hepatitis B: first-year results from the international phase III Globe trial [Abstract]. Hepatology. 2005;42:748A.
6. Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al.; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003;348:808-16. [PMID: 12606735]
7. Valsamakis A. Molecular Testing in the Diagnosis and Management of Chronic Hepatitis B. Clin Microbiol Rev. 2007;20:426-39. [PMID: 17630333]
8. Lai CL. Antiviral therapy for hepatitis B and C in Asians. J Gastroenterol Hepatol. 1999;14 Suppl:S19-21. [PMID: 10382633]
Feld JJ, Ghany MG. Evolution of Therapy for Chronic Hepatitis B: Progressing from the Simple to the Complex. Ann Intern Med. 2007;147:806-808. doi: 10.7326/0003-4819-147-11-200712040-00014
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Published: Ann Intern Med. 2007;147(11):806-808.
Gastroenterology/Hepatology, Infectious Disease, Liver Disease.
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