Abstract
Seventy-five percent of the world’s population of approx 400 million hepatitis B virus (HBV) carriers are Asians (1,2). It is therefore not surprising that the majority of clinical studies of HBV infection is from Asian countries or consists of a large proportion of Asians. Because of the difference in the time of acquiring HBV between patients in the East and West, the profile of the HBV disease and treatment response are significantly different. In the East, nearly all HBV patients acquire the disease at birth or during the perinatal/early childhood period (3). The HBV infection is followed by a prolonged period of immunotolerance that can last for several decades. This is followed by another prolonged period of immune clearance that may result in severe damage to the liver and its architecture. As a consequence of this, hepatitis B e antigen (HBeAg) seroconversion does not necessarily prevent the development of cirrhosis-related complications and hepatocellular carcinoma (HCC) in Asians. In fact, the majority of cirrhosis-related complications and HCC develops after HBeAg seroconversion (4,5). Achieving a relatively low viremia state with HBeAg seroconversion is not enough to stop disease progression in Asians with chronic HBV infection.
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References
Lai, C.L.(1997) Chronic hepatitis B in Hong Kong: immunization strategies for the control of hepatitis B virus infection, in Hepatitis B in the Asian-Pacific Region, vol. 1: Screening, Diagnosis and Control (Zuckerman, ed.), Royal College of Physicians of London 79–87.
Lee, W.M.(1997) Hepatitis B infection. N. Engl. J. Med. 337, 1733–1745.
Derso, A., Boxall, E.H., Tarlow, M.J., and Flewett, T.H.(1978) Transmission of HBsAg from mother to infant in four ethnic groups. Br. Med. J. 1, 949–952.
Yuen, M.F., Wong, W.M., Cheng, C.C., Wu, C.H., Wu, P.C., and Lai C.L. (1997) Natural History of Chronic hepatitis in the Chinese: prognostic significance of HBeAg/anti-HBe positivity. Hepatology (Suppl) 26, 316A.
Yuen, M.F., and Lai, C.L. (2000) Natural history of chronic hepatitis B infection. J. Gastro. Hepatol. (Suppl) 15, 20–25.
Liaw, Y.F., Chu, C.M., Su, I.J., Huang, M.J., Lin, D.Y., and Chang-Chien, C.S. (1983) Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis. Gastroenterology 84, 216–219.
Liaw, Y.F., Pao, C.C., Chu, C.M., Sheen, I.S., and Huang, M.J. (1987) Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type B hepatitis. Hepatology 7, 1–3.
Yuen, M.F., Yuan, H.J., Hui, C.K., et al. (2003) A large population study of spontaneous HBeAg seroconversion and acute exacerbation of chronic hepatitis B infection: implications for antiviral therapy. Gut 53, 416–419.
Niederau, C., Heintges, T., Lange, S., et al. (1996) Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N. Engl. J. Med. 334, 1422–1427.
Lau, D.T., Everhart, J., Kleiner, D.E., et al. (1997) Long-term follow up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology 113, 1660–1667.
Yuen, M.F., Hui, C.K., Cheng, C.C., Wu, C.H., Lai, Y.P., and Lai, C.L. (2001) Long-term follow-up of interferon-alpha treatment in Chinese patients with chronic hepatitis B infection: the effect on HBeAg seroconversion and the development of cirrhosis-related complications. Hepatology 34, 139–145.
Yuen, M.F., Sablon, E., Yuan, H.J., et al. (2002) Relationship between the development of precore and core promoter mutations and hepatitis B e antigen seroconversion in patients with chronic hepatitis B virus. J. Infect. Dis. 186, 1335–1338.
Brunetto, M.R., Giarin, M., Saracco, G., et al. (1993) Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B. Gastroenterology 105, 845–850.
Lok, A.S., Heathcote, E.J., and Hoofnagle, J.H. (2001) Management of hepatitis B: 2000—summary of a workshop. Gastroenterology 120, 1828–1853.
Di Bisceglie, A.M., Waggoner, J.G., and Hoofnagle, J.H. (1987) Hepatitis B virus deoxyribonucleic acid in liver of chronic carriers: correlation with serum markers and changes associated with loss of hepatitis B e antigen after antiviral therapy. Gastroenterology 93, 1236–1241.
Lai, V.C.H., Guan, R., Wood, M.L., Lo, S.K., Yuen, M.F., and Lai, C.L. (1999) Nucleic acid-based crosslinking assay for the detection and quantification of hepatitis B virus DNA. J. Clin. Microbiol. 37, 161–164.
Ho, S.K., Chan, T.M., Cheng, I.K., and Lai, K.N. (1999) Comparison of the second-generation digene hybrid capture assay with the branched-DNA assay for measurement of hepatitis B virus DNA in serum. J. Clin. Microbiol. 37, 2461–2465.
Yuen, M.F. and Lai, C.L. (1999) Debates in hepatitis: how to assess HBV DNA reductions in association with therapy. Viral Hepat. Rev. 5, 159–175.
Heermann, K.H., Gerlich, W.H., Chudy, M., Schaefer, S., Thomssen, R., and Eurohep Pathobiology Group (1999) Quantitative detection of hepatitis B virus DNA in two international reference plasma preparations. J. Clin. Microbiol. 37, 68–73.
Averett, D.R., Mason, W.S. (1995) Evaluation of drugs for antiviral activity against hepatitis B virus. Viral Hepat. Rev. 1, 129–142.
Lai, C.L., Chien, R.N., Leung, N.W.Y., et al. (1998) A one-year trial of lamivudine for chronic hepatitis B. N. Engl. J. Med. 339, 61–68.
Van Ness, M.M., and Diehl, A.M. (1989) Is liver biopsy useful in the evaluation of patients with chronically elevated liver enzymes? Ann. Intern. Med. 111, 473–478.
Perrillo, R.P. (1997) The role of liver biopsy in hepatitis C. Hepatology (Suppl 1) 26, 57–61.
Yap, F.Y., Terrault, N.A., Freise, C., Maslow, I. and Bass, N.M. (2001) Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation: a comparative study using a matched, untreated cohort. Hepatology 34, 411–416.
Kapoor, D., Guptan, R.C., Wakil, S.M., et al. (2000) Beneficial effects of lamivudine in hepatitis B virus-related decompensated cirrhosis. J. Hepatol. 33, 308–312.
Yap, F.Y., and Bass, N.M. (2000) Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection. J. Hepatol. 33, 301–307.
Nowak, M.A., Bonhoeffer, S., Hill, A.M., Boehme, R., Thomas, H.C., and McDade, H. (1996) Viral dynamics in hepatitis B virus infection. Proc. Natl. Acad. Sci. USA 93, 4398–4402.
Tsiang, M., Rooney, J.F., Toole, J.J., and Gibbs, C.S.(1999) Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy. Hepatology 29, 1863–1869.
Yuen, M.F., Sablon, E., Hui, C.K., Yuan, H.J., Decraemer, H., Lai, C.L.(2001) Factors predicting hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy. Hepatology 34, 785–791.
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Yuen, MF., Lai, CL. (2004). Specific Considerations in the Design of Hepatitis B Virus Clinical Studies in the Far East. In: Hamatake, R.K., Lau, J.Y.N. (eds) Hepatitis B and D Protocols. Methods in Molecular Medicine™, vol 96. Humana Press. https://doi.org/10.1385/1-59259-670-3:457
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DOI: https://doi.org/10.1385/1-59259-670-3:457
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