Hepatitis B
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《新英格兰医药杂志》
To the Editor: Ganem and Prince (March 11 issue)1 state that sustained remission of hepatitis B virus (HBV) infection is infrequently achieved by current treatment regimens. We recently showed that sustained remission is present after a response (loss of hepatitis B e antigen [HBeAg]) to interferon alfa.2 After long-term follow-up, patients who had a response to interferon alfa had a loss of hepatitis B surface antigen (HBsAg) and HBV DNA, as demonstrated by the polymerase chain reaction, significantly more often than those without a response (loss of HBsAg, 52 percent vs. 9 percent; loss of HBV DNA, 70 percent vs. 30 percent). In addition, our results indicated that, after correction for baseline factors, a response to interferon alfa significantly increased the rate of survival and reduced the risk of hepatocellular carcinoma.
Ganem and Prince also suggest that reducing the viral load with lamivudine therapy may allow the immune response to clear infected hepatocytes. Although a restored HBV-specific T-cell reactivity during treatment with lamivudine has been reported, hepatitis B core antigen–specific T-cell reactivity remained undetectable in another study.3,4 We found that an HBeAg response induced by lamivudine was significantly less durable than a response after therapy with interferon alfa.5 This difference with respect to relapse suggests a lack of efficient immune control after treatment with lamivudine. Both these arguments should encourage us to reconsider the rapid displacement of interferon from the roster of first-line therapies for HBV infection.
Harry L.A. Janssen, M.D., Ph.D.
Monika van Zonneveld, M.D.
Solko W. Schalm, M.D., Ph.D.
Erasmus Medical Center
3015 GD Rotterdam, the Netherlands
m.leeuwesteijn@erasmusmc.nl
References
Ganem D, Prince AM. Hepatitis B virus infection -- natural history and clinical consequences. N Engl J Med 2004;350:1118-1129.
van Zonneveld M, Honkoop P, Hansen BE, et al. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology 2004;39:804-810.
Boni C, Bertoletti A, Penna A, et al. Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B. J Clin Invest 1998;102:968-975.
Marinos G, Naoumov NV, Williams R. Impact of complete inhibition of viral replication on the cellular immune response in chronic hepatitis B virus infection. Hepatology 1996;24:991-995.
van Nunen AB, Hansen BE, Suh DJ, et al. Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase. Gut 2003;52:420-424.
To the Editor: Ganem and Prince state that HBeAg-negative chronic carriers with a viral load of less than 105 copies per milliliter and a normal alanine aminotransferase level have a low rate of disease progression and do not require treatment. Although HBV DNA levels of more than 105 copies per milliliter would exclude HBV carriers with inactive disease, nearly 30 percent of patients with chronic HBeAg-negative hepatitis B have an HBV DNA level that is persistently below this range.1 These patients have wide fluctuations in serum alanine aminotransferase levels, and 20 to 30 percent of patients with histologically documented chronic HBeAg-negative hepatitis B have normal serum alanine aminotransferase levels at the time of presentation.2 However, according to our experience (unpublished data), nearly all of them will have at least one episode of elevated alanine aminotransferase levels during two years of follow-up. Thus, a proportion of patients who are HBeAg-negative, have normal levels of alanine aminotransferase, and have HBV DNA levels below 105 copies per milliliter already have chronic HBeAg-negative disease and can be identified with frequent monitoring of alanine aminotransferase. Chronic HBeAg-negative hepatitis B is a severe and progressive liver disease with very rare spontaneous remissions and frequent development of cirrhosis if left untreated.2
Mehdi Mohamadnejad, M.D.
Iran University of Medical Sciences
Tehran 15937, Iran
Reza Malekzadeh, M.D.
Tehran University of Medical Sciences
Tehran 14114, Iran
malek@ams.ac.ir
References
Chu CJ, Hussain M, Lok AS. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology 2002;36:1408-1415.
Papatheodoridis GV, Hadziyannis SJ. Current management of chronic hepatitis B. Aliment Pharmacol Ther 2004;19:25-37.
Ganem and Prince also suggest that reducing the viral load with lamivudine therapy may allow the immune response to clear infected hepatocytes. Although a restored HBV-specific T-cell reactivity during treatment with lamivudine has been reported, hepatitis B core antigen–specific T-cell reactivity remained undetectable in another study.3,4 We found that an HBeAg response induced by lamivudine was significantly less durable than a response after therapy with interferon alfa.5 This difference with respect to relapse suggests a lack of efficient immune control after treatment with lamivudine. Both these arguments should encourage us to reconsider the rapid displacement of interferon from the roster of first-line therapies for HBV infection.
Harry L.A. Janssen, M.D., Ph.D.
Monika van Zonneveld, M.D.
Solko W. Schalm, M.D., Ph.D.
Erasmus Medical Center
3015 GD Rotterdam, the Netherlands
m.leeuwesteijn@erasmusmc.nl
References
Ganem D, Prince AM. Hepatitis B virus infection -- natural history and clinical consequences. N Engl J Med 2004;350:1118-1129.
van Zonneveld M, Honkoop P, Hansen BE, et al. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology 2004;39:804-810.
Boni C, Bertoletti A, Penna A, et al. Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B. J Clin Invest 1998;102:968-975.
Marinos G, Naoumov NV, Williams R. Impact of complete inhibition of viral replication on the cellular immune response in chronic hepatitis B virus infection. Hepatology 1996;24:991-995.
van Nunen AB, Hansen BE, Suh DJ, et al. Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase. Gut 2003;52:420-424.
To the Editor: Ganem and Prince state that HBeAg-negative chronic carriers with a viral load of less than 105 copies per milliliter and a normal alanine aminotransferase level have a low rate of disease progression and do not require treatment. Although HBV DNA levels of more than 105 copies per milliliter would exclude HBV carriers with inactive disease, nearly 30 percent of patients with chronic HBeAg-negative hepatitis B have an HBV DNA level that is persistently below this range.1 These patients have wide fluctuations in serum alanine aminotransferase levels, and 20 to 30 percent of patients with histologically documented chronic HBeAg-negative hepatitis B have normal serum alanine aminotransferase levels at the time of presentation.2 However, according to our experience (unpublished data), nearly all of them will have at least one episode of elevated alanine aminotransferase levels during two years of follow-up. Thus, a proportion of patients who are HBeAg-negative, have normal levels of alanine aminotransferase, and have HBV DNA levels below 105 copies per milliliter already have chronic HBeAg-negative disease and can be identified with frequent monitoring of alanine aminotransferase. Chronic HBeAg-negative hepatitis B is a severe and progressive liver disease with very rare spontaneous remissions and frequent development of cirrhosis if left untreated.2
Mehdi Mohamadnejad, M.D.
Iran University of Medical Sciences
Tehran 15937, Iran
Reza Malekzadeh, M.D.
Tehran University of Medical Sciences
Tehran 14114, Iran
malek@ams.ac.ir
References
Chu CJ, Hussain M, Lok AS. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology 2002;36:1408-1415.
Papatheodoridis GV, Hadziyannis SJ. Current management of chronic hepatitis B. Aliment Pharmacol Ther 2004;19:25-37.