Treatment of Chronic Hepatitis C in Blacks and Non-Hispanic Whites
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Muir et al. (May 27 issue)1 state that black race is an independent risk factor for a low rate of response to treatment of infection with hepatitis C virus (HCV) infection with peginterferon alfa-2b and ribavirin. There is a further point in their study that merits attention.
Black and non-Hispanic white patients were similar in their baseline characteristics except for a significant difference in weight (89.0 kg vs. 81.6 kg), incidence of hypertension (46 percent vs. 12 percent), and incidence of diabetes mellitus (23 percent vs. 6 percent). Higher body weight has previously been identified as an independent risk factor for a low response to treatment of HCV,2 whereas nonobese patients showed a stronger biologic response on exposure to exogenous interferon alfa.3 An increase in body weight and in the incidence of hypertension and diabetes mellitus are all part of the insulin-resistance syndrome or the metabolic syndrome.
Recently, Shintani et al. showed that HCV infection contributes to the pathogenesis of insulin resistance and diabetes mellitus.4 The data presented suggest that the inverse relation is there as well — namely, that a preexisting insulin-resistance syndrome influences the course of HCV infection by decreasing the rate of response to current standard HCV therapy.
Elmar S. Aigner, M.D.
Paracelsus Medical University Salzburg
5020 Salzburg, Austria
elmar.aigner@gmx.net
References
Muir AJ, Bornstein JD, Killenberg PG. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 2004;350:2265-2271.
Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-965.
Lam NP, Pitrak D, Speralakis R, Lau AM, Wiley TE, Layden TJ. Effect of obesity on pharmacokinetics and biologic effect of interferon-alpha in hepatitis C. Dig Dis Sci 1997;42:178-185.
Shintani Y, Fujie H, Miyoshi H, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 2004;126:840-848.
To the Editor: A recent meta-analysis has confirmed a close correlation between the number of mutations in an interferon-sensitivity–determining region (ISDR) of the HCV protein NS5A (2209–2248) and the outcome of interferon monotherapy for hepatitis C virus type 1b infection worldwide.1 This phenomenon has also been confirmed in our study in the case of therapy with standard or pegylated interferon plus ribavirin.2 However, the geographic distribution of ISDR mutations is reportedly different.1 For example, isolates obtained in Japan have significantly more mutations in the ISDR than isolates from Northern Europe (Germany, the United Kingdom, the Netherlands, and Sweden; P=0.004).1 Therefore, the differences in the response rate between blacks and non-Hispanic whites given pegylated interferon plus ribavirin for HCV type 1b infection, as reported by Muir et al., may be explained by the distribution of the number of ISDR mutations among these populations.
Hisashi Moriguchi, M.P.H.
University of Tokyo
Tokyo 153-8904, Japan
hisashi@ip.rcast.u-tokyo.ac.jp
Chifumi Sato, M.D.
Tokyo Medical and Dental University
Tokyo 113-8519, Japan
References
Schinkel J, Spaan WJ, Kroes AC. Meta-analysis of mutations in the NS5A gene and hepatitis C virus resistance to interferon therapy: uniting discordant conclusions. Antivir Ther 2004;9:275-286.
Moriguchi H, Sato C. Statistical analysis of combined substitutions in NS5A 2209-2248 of hepatitis C virus 1b infection and standard or pegylated interferon plus ribavirin therapy response. Gastroenterology 2004;126:Suppl 2:A-719. abstract.
Dr. Muir replies: Aigner and Moriguchi and Sato have raised interesting issues concerning the etiology of the reduced response to treatment of chronic hepatitis C in blacks. Although the presence of diabetes mellitus was not an independent predictor of a lack of response to treatment for hepatitis C, the increased prevalence of diabetes mellitus among the black patients was curious and supports the need for further investigation of the role of insulin resistance. My colleagues and I also agree that further analysis of mutations in the ISDR would add to our understanding of this important question.
Andrew J. Muir, M.D., M.H.S.
Duke University Medical Center
Durham, NC 27710
muir0002@mc.duke.edu
Black and non-Hispanic white patients were similar in their baseline characteristics except for a significant difference in weight (89.0 kg vs. 81.6 kg), incidence of hypertension (46 percent vs. 12 percent), and incidence of diabetes mellitus (23 percent vs. 6 percent). Higher body weight has previously been identified as an independent risk factor for a low response to treatment of HCV,2 whereas nonobese patients showed a stronger biologic response on exposure to exogenous interferon alfa.3 An increase in body weight and in the incidence of hypertension and diabetes mellitus are all part of the insulin-resistance syndrome or the metabolic syndrome.
Recently, Shintani et al. showed that HCV infection contributes to the pathogenesis of insulin resistance and diabetes mellitus.4 The data presented suggest that the inverse relation is there as well — namely, that a preexisting insulin-resistance syndrome influences the course of HCV infection by decreasing the rate of response to current standard HCV therapy.
Elmar S. Aigner, M.D.
Paracelsus Medical University Salzburg
5020 Salzburg, Austria
elmar.aigner@gmx.net
References
Muir AJ, Bornstein JD, Killenberg PG. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 2004;350:2265-2271.
Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-965.
Lam NP, Pitrak D, Speralakis R, Lau AM, Wiley TE, Layden TJ. Effect of obesity on pharmacokinetics and biologic effect of interferon-alpha in hepatitis C. Dig Dis Sci 1997;42:178-185.
Shintani Y, Fujie H, Miyoshi H, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 2004;126:840-848.
To the Editor: A recent meta-analysis has confirmed a close correlation between the number of mutations in an interferon-sensitivity–determining region (ISDR) of the HCV protein NS5A (2209–2248) and the outcome of interferon monotherapy for hepatitis C virus type 1b infection worldwide.1 This phenomenon has also been confirmed in our study in the case of therapy with standard or pegylated interferon plus ribavirin.2 However, the geographic distribution of ISDR mutations is reportedly different.1 For example, isolates obtained in Japan have significantly more mutations in the ISDR than isolates from Northern Europe (Germany, the United Kingdom, the Netherlands, and Sweden; P=0.004).1 Therefore, the differences in the response rate between blacks and non-Hispanic whites given pegylated interferon plus ribavirin for HCV type 1b infection, as reported by Muir et al., may be explained by the distribution of the number of ISDR mutations among these populations.
Hisashi Moriguchi, M.P.H.
University of Tokyo
Tokyo 153-8904, Japan
hisashi@ip.rcast.u-tokyo.ac.jp
Chifumi Sato, M.D.
Tokyo Medical and Dental University
Tokyo 113-8519, Japan
References
Schinkel J, Spaan WJ, Kroes AC. Meta-analysis of mutations in the NS5A gene and hepatitis C virus resistance to interferon therapy: uniting discordant conclusions. Antivir Ther 2004;9:275-286.
Moriguchi H, Sato C. Statistical analysis of combined substitutions in NS5A 2209-2248 of hepatitis C virus 1b infection and standard or pegylated interferon plus ribavirin therapy response. Gastroenterology 2004;126:Suppl 2:A-719. abstract.
Dr. Muir replies: Aigner and Moriguchi and Sato have raised interesting issues concerning the etiology of the reduced response to treatment of chronic hepatitis C in blacks. Although the presence of diabetes mellitus was not an independent predictor of a lack of response to treatment for hepatitis C, the increased prevalence of diabetes mellitus among the black patients was curious and supports the need for further investigation of the role of insulin resistance. My colleagues and I also agree that further analysis of mutations in the ISDR would add to our understanding of this important question.
Andrew J. Muir, M.D., M.H.S.
Duke University Medical Center
Durham, NC 27710
muir0002@mc.duke.edu