Chronic hepatitis B virus infection in the Chinese : natural history, sequelae, treatment and prevention
Chronic Hepatitis B Virus Infection in the Chinese:
Natural History, Sequelae, Treatment and Prevention
Submitted by Yuen Man Fung for the degree of Doctor of Medicine
at The University of Hong Kong in August 2001
The aims of this thesis were 1) to delineate the natural history of Chinese patients with hepatitis B virus (HBV) infection; 2) to assess the two approved treatment, interferon - alpha (IFN-a) and lamivudine, of HBV; 3) to study the pathogenesis, immunology, screening program and treatment ofHCC; and 4) to evaluate HBV vaccines in preventing HBV infection.
In a study of 146 Chinese HBV patients, mannose binding lectin mutation was associated with increased chance of cirrhotic complications. The most important factor for the development of cirrhotic complications in a study of 3433 Chinese HBV patients was increasing age. The median age of development of cirrhotic complications was 55 60 years old. Though HBeAg seroconversion led to a low viraemic state, 60 - 70% of patients who had cirrhotic complications were anti-HBe positive. HBeAg seroconversion did not protect Chinese patients from the development of cirrhotic complications.
IFN-a treatment improves prognosis in Caucasian HBV patients. But, a nine-year follow-up study involving 411 Chinese patients showed that IFN-a treatment did not increase cumulative HBeAg seroconversion rate and more importantly, did not decrease cirrhotic complication.
Prolonged lamivudine treatment is associated with the emergence of YMDD variants. The factors associated with HBV DNA breakthrough were examined in 159 patients. Patients with higher baseline HBV DNA and alanine transaminase (ALT) levels were associated with earlier YMDD variants development. Patients with HBV DNA levels> 103 copies/ml at 6 months of therapy had 63% chance of developing YMDD variant within 29 months of follow-up. Patients with YMDD variants could still develop HBeAg seroconversion.
The pathogenic role of c-myc was examined in 150 patients. Though c-myc expression was high in HCC cell, its expression was reduced compared to that of nontumorous tissues. This indicates that apoptosis is impaired within the HCC cell since cmyc is an inducer of wide-type p53.
The immunobiology of HCC was investigated in three studies involving 50 patients. Though the level of transforming growth factor beta 1 (TGF-f31) was elevated in patients with HCC, TGF-f31 level was decreased as the tumour progressed, thus minimizing the apoptotic effect of TGF -f31. The growth of HCC was also facilitated by upregulating the Fas expression on the tumor infiltrating lymphocytes (TILs), hence
making TILs more vulnerable to apoptosis. The natural killer cells and natural T cell however enhanced the cytolytic activities against the HCC by downregulating the expression of killer inhibitory receptors.
A study recruiting 306 patients showed that screening for HCC by serum alphafetoprotein and ultrasonogram increased the chance of treatment. A pilot study using trans catheter arterial interferon embolisation showed that 30.8% and 38.5% patients achieved complete and partial response respectively.
Finally, a twelve-year follow-up study on the efficacy of HBV vaccines in 318 Chinese children showed that long-term protective immunity could be achieved without receiving a booster dose. Sixty-five subjects had at least one anamnestic response which was responsible for the continuing protection of vaccine recipients. Hepatitis B vaccination is the most cost-effective method to decrease the magnitude of the HBVrelated disease globally.
School:The University of Hong Kong
School Location:China - Hong Kong SAR
Source Type:Master's Thesis
Keywords:hepatitis b virus
Date of Publication:01/01/2001