The association of hepatitis B virus (HBV) infection and liver cancer is well documented in epidemiological study. Patients with chronic hepatitis B have increased risk of hepatocelluar carcinoma (HCC), in particular those with active liver disease and cirrhosis. The incidence of HCC increases with age and is more common among male patients. The introduction of universal HBV vaccination program for the newborn in endemic regions has started to show beneficial impact. Taiwan introduced this program two decades ago and the incidence of liver cancer among infants and young children have declined significantly. The carcinogenic events leading to HCC are under intense research. A number of hypotheses have been proposed. HBV is not directly hepatotoxic but its interaction with the host immune system creates opportunity for HBV DNA integration into the host genome. One of the main foci of research is the HBX-encoded X protein. Its integration and protein expression impose alteration in cell proliferation cycle and apoptosis process. Many other factors may be involved including viral-induced alterations in p53 and telemerase, HBV genotypes, co-infection with HCV or delta agents, patient's lifestyle such as smoking, alcohol excesses, and genetic factors of the host patient. The processes of necroinflammation, cell proliferation and fibrosis facilitate the initial carcinogenic development. HCC surveillance with tumor markers such as alpha-foetal protein, decarboxylated prothrombin, in conjunction with imaging techniques has identified early small HCC that is amenable to curative therapy. Viral load has been correlated with increase risk of HCC. The available anti-viral agents have demonstrated clinical benefit among those with maintained and sustained response. Interferon and lamivudine therapy have demonstrated reduction of HCC among responders. However, they only constitute a minority proportion of treated patients. The mainstay of prevention should lie in prevention of HBV infection and early effective therapy of chronic hepatitis B infection.
The implementation of the Expanded Program of Immunization (EPI) in 1989 has dramatic impact on hepatitis B virus (HBV) infection in school children in Malaysia. A cross-sectional seroprevalence study of HBV infection in 190,077 school children aged 7-12 years from 1997 to 2003 showed a steady decline of HBV surface antigen (HBsAg) prevalence rate from 2.5% for children born in 1985 to 0.4% among school children born in 1996. The overall prevalence of HBsAg was 0.6%, 0.7% in males and 0.6% in females. Over 92.7% of school children had been vaccinated with HBV vaccine, in which 93.7% were vaccinated under the EPI and 6.3% on voluntary basis. The school children vaccinated under EPI had a 0.4% HBsAg carrier rate, which was significantly lower than school children vaccinated on a voluntary basis (HBsAg carrier rate 1.3%) and non-vaccinated school children (HBsAg carrier rate 2.7%), suggesting that HBV vaccination of infants was the most effective measure in preventing vertical transmission of HBV in the hyperendemic region.
The Asia-Pacific Expert Committee on Hepatitis B Management recently reviewed the impact of hepatitis B in the region and assessed the differences and similarities observed in the practical management of the disease in individual Asia-Pacific countries. Hepatitis B is a major health concern in the Asia-Pacific region, and of all chronically infected carriers worldwide, approximately 75% are found in Asia. The disease poses a considerable burden on healthcare systems, and is likely to remain a cause of substantial morbidity and mortality for several decades. Disease prevention activities, including screening and vaccination programs, have been implemented successfully in some Asia-Pacific countries and similar measures are being established in other parts of the region. The management of hepatitis B in the Asia-Pacific varies throughout the region, with each country confronting different issues related to treatment options, disease monitoring and duration of therapy. The influence of cost, availability of diagnostic equipment, and patient awareness and compliance are of additional concern. Although guidelines such as those developed by the Asian Pacific Association for the Study of the Liver have been created to address problems encountered in the management of hepatitis B, many physicians in the region still find it difficult to make satisfactory management decisions because of the treatment choices available. This article examines the different approaches to hepatitis B management in a number of Asia-Pacific countries, and highlights the difficulties that can arise when adhering to treatment guidelines and disease prevention solutions that have proved to be successful in the region.
"Parenteral" or "serum" hepatitis is known to have afflicted man for centuries. However, it was not until the mid-1960s that the causative agent of this infection, the hepatitis B virus, was discovered. Since then, the biology and the replication strategy of the virus, and the clinical features and the epidemiology of the hepatitis B infection have been determined. Knowledge about the virus and the infection it causes led to the development of firstly, a plasma-derived vaccine and later a recombinant vaccine for the prevention of the infection. Integration of the hepatitis B vaccine into newborn vaccination programmes on a worldwide basis represents a major step in the effort to eliminate this infectious disease and its complications. Laboratory tests are available for the diagnosis and monitoring of the disease. Therapies have been developed to halt the progress of the chronic infection in affected individuals. While these developments have resulted in a decrease of the frequency of infection in many countries, particularly those that have implemented universal immunization of newborns, the chronic infection remains a significant global problem. Worldwide, over 300 million individuals are infected and each year, an estimated 1 million persons die from chronic complications of the disease including hepatocellular carcinoma and hepatic failure. The therapies currently available result in elimination of the virus in only a relatively small proportion of subjects and carry with it serious side effects. Geopolitical, economic and other factors hinder the vision of elimination of the infection through immunization programmes. Nevertheless, work continues to clarify further the underlying pathological mechanism of the infection, the host and viral factors that promote elimination or persistence of the virus in the human host. It is hoped that such investigations will reveal viral targets for the design of newer and potentially more effective drugs to treat the infection.
The MLF since its inception in 1996 has endeavored to develop a coordinated approach towards the improved care and treatment of liver diseases in Malaysia. Its close liaison with the Malaysian MOH, local medical associations, and corporate bodies has contributed to the success of its many programs. Educating the public, research, and training have been important elements of successful hepatitis disease control programs. Hepatitis Days have been proven to be very successful in raising the awareness of the general public to hepatitis disease. Rapid screening and vaccination has also helped to remove the social stigma associated with the disease, eliminated the need for numerous clinic appointments, and rendered vaccination more accessible to the public. The MLF perspective emphasizes the need for collaborative effort between Government bodies and other agencies, such as non-governmental organizations, laboratories, and the medical fraternity, to ensure the overall success of hepatitis disease management programs.
Asia and Africa have previously been classified as areas of high endemicity for hepatitis B virus (HBV), but in some countries highly effective vaccination programmes have shifted this pattern towards intermediate or low endemicity. Thus, China is now the only country in Asia where HBV endemicity is high. Countries with intermediate endemicity include India, Korea, the Philippines, Taiwan and Thailand, and those with low endemicity include Japan, Pakistan, Bangladesh, Singapore, Sri Lanka and Malaysia. Most countries in Africa have high HBV endemicity, with the exceptions of Tunisia and Morocco, which have intermediate endemicity. Zambia has borderline intermediate/high endemicity. In the Middle East, Bahrain, Iran, Israel and Kuwait are areas of low endemicity, Cyprus, Iraq and the United Arab Emirates have intermediate endemicity, and Egypt, Jordan, Oman, Palestine, Yemen and Saudi Arabia have high endemicity. All of these Middle East countries reach a large proportion of their population with hepatitis B vaccination, which is reducing the infection rate, particularly in Saudi Arabia. The vaccination programme in Taiwan has also greatly reduced the HBV infection rate. Future vaccination programmes must take into account the mode of transmission of HBV, the healthcare infrastructure to deliver vaccination, and the socioeconomic and political factors in each individual country, to determine the most cost-effective way of infection control.
Regular blood transfusions for patients with thalassemia have improved their overall survival although these transfusions carry a definite risk of the transmission of certain viruses. Infection with hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) leads to complications which contribute to the morbidity and mortality of patients with thalassemia. We analyzed the blood samples taken from 85 transfusion dependent thalassemics receiving treatment at the day care center in Hospital Universiti Kebangsaan Malaysia and found that the seroprevalence rates for HBV, HCV and CMV were 2.4%, 22.4% and 91.8% respectively. None of the patients tested positive for HIV. Those positive for HBV and HCV will require further tests and treatment if chronic hepatitis is confirmed.
The percentage of lymphocyte subsets from the peripheral blood of healthy adults and hepatitis B surface antigen (HBsAg) carriers were analyzed by flow cytometry. The five lymphocyte subsets studied were:- T (CD3) cells, B (CD19) cells, CD4 cells, CD8 cells, Natural Killer (CD3- CD16+/CD56+) cells (NK cells) and the CD4/CD8 ratio. The percentage (mean +/- SD) for the five lymphocyte subsets from the healthy adults were (67.5 +/- 8.5)%, (12.4 +/- 4.5)%, (35.5 +/- 7.8)%, (36.8 +/- 8.5)%, (17.9 +/- 8.1)% and 1.1 +/- 0.6, respectively. HBsAg carriers positive for HBV-DNA had a lower CD4/CD8 ratio than the healthy population (P = 0.030). The percentage of CD8 cells in HBsAg carriers increased significantly (r = 0.28; P = 0.019) with an increase in ALT levels but the values remained within normal range. The percentage of NK cells and CD4/CD8 ratio in HBsAg carriers positive for anti-HBe were higher than HBsAg carriers negative for anti-HBe (92% of which are HBeAg positive) (P = 0.045 and P = 0.035, respectively). The CD4/CD8 ratio in HBsAg carriers negative for anti-HBe (92% positive for HBeAg) was also lower than in the healthy population (P = 0.042). HBsAg carriers positive for HBV-DNA, HBeAg and raised ALT levels had a lower CD4/ CD8 ratio than did the healthy population. The lower ratio was due to an increase in the percentage of CD8 cells. This suggests an activated immune response triggered by the infection in an attempt to clear the virus. HBsAg carriers with normal ALT levels and who are negative for HBV-DNA may be in a state of tolerance.
HBV-DNA were analysed in 330 HBsAg-positive carriers in Malaysia by dot-blot hybridization and polymerase chain reaction. Seventy-three (22.12%) were positive for the virus. Of these, 65 (89%) were males and 8 (11%) were females. Statistically, there was no significant difference (P = 0.13). No significant decline in HBV-DNA with age in the Malay and Chinese males was observed (P = 0.2). Prevalence of HBV-DNA was higher in the Chinese carriers than in the Malay carriers for most age groups in both sexes. Sixty-one HBV-DNA-positive carriers were also positive for HBeAg. However, three individuals were positive only for anti-HBe, one was positive for both HBeAg and anti-HBe, and eight were negative for both HBeAg and anti-HBe. Fifty-seven were positive for HBeAg but negative for HBV-DNA. No relation was observed between raised alanine aminotransaminase and aspartate aminotransaminase levels and the presence of HBV-DNA (P = 0.4).
Dental employees in government institutions in a State in Peninsular Malaysia were screened for exposure to hepatitis B virus (HBV) in 1989. Almost all (96.8%) of the 217 employees responded. One quarter (24.8%) was positive for at least one serological markers to HBV; 2.4% had hepatitis B surface antigen (HBsAg) and 22.4% had anti-body to HBsAg (anti-HBs). The presence of HBsAg was unrelated to age, sex, ethnicity, geographical locality and occupations of the subjects. The prevalence of anti-HBs increased with age and was highest for ethnic Chinese (53.6%), followed by Indians (25%), compared to Malays (14.9%) (p less than 0.001) and were increased among dentists (53.1%) and assistant nurses (33.3%). The overall prevalence of HBsAg and anti-HBs were similar to the situation in the community. However, dentists and their chairside assistant nurses, with a higher proportion of Chinese, had higher anti-HBs prevalences compared with that of the general population.
This study was based on a hepatitis B screening program conducted in one of the states in Malaysia in 1989. The majority (84.6%) of the 2986 health employees were screened. One quarter (25%) was found to have serological markers for the Hepatitis B Virus (HBV); 2.1% had Hepatitis B surface Antigen (HBsAg) and 22.8% had antibody to the Hepatitis B surface Antigen (anti-HBs). The occurrence of HBsAg was higher in ethnic Chinese (6.3%) compared to Malays (1.8%) and Indians (0.9%), even when analyzed by sex, but not with age, type of institution and geographical locality. The distribution of anti-HBs was higher with ethnic Chinese (41.6%), male sex (27.2%) and age. There was a wide variation of the prevalence of serological markers among occupations and increased relative risks of HBsAg were found among medical assistants (RR3.7; 95% CI 1.4-9.1) and laboratory staff (RR 3.2; 95% CI 1-8.8), and that of anti-HBs among medical assistants (RR 2.8; 95% CI 1.8-3.7). The variations of HBsAg among occupations by type of institutions was marginal while that of anti-HBs was higher among attendants and midwives in hospitals, medical assistants in health departments, and assistant nurses and dentists in dental centers. The patterns of distribution of serological markers of HBV among health staff reflect the situation in the community with high endemicity and resemble specific occupational factors noted in previous studies in the West.
Publication year is 1992-1993
This study documents the prevalence of Hepatitis B serological markers among STD patients who have had multiple sexual partners in Kuala Lumpur, Malaysia, and compares the rates with those of a sample of the population with single or no sexual partners. A total of 336 Chinese STD patients (multiple partners group) and 234 Chinese control subjects (non-multiple partner group) were screened. Those with a history of blood transfusion or parenteral drug abuse had been excluded from the study, and all study subjects were heterosexuals. The overall carrier rate was 9.2% for the multiple partner group (MP group) and 6.8% for the non-multiple partner group (NMP group). Infection rates were 64.3% for the MP-group and 38.9% for the NMP group. After adjustments for age and sex, there was no significant difference in carrier rates between the two groups, but infection rates were significantly different with the MP group, being 3.2 times more likely to acquire infection than the NMP group. The study concludes that in heterosexuals, those with multiple sexual partners have increased chances of acquiring HBV infection.
The prevalence of sexually transmitted diseases was determined among 370 prostitutes in Kuala Lumpur, Malaysia. Chlamydial cervicitis (26.5%) was detected more frequently than gonorrhoea (14.25%) and was associated more often with pelvic inflammatory disease. Concurrent infections and asymptomatic infections were common. Seropositivity to hepatitis B and syphilis were 66.3% and 13.6% respectively. Women under 20 years of age had significantly higher rates of infection with Chlamydia trachomatis and hepatitis B virus than older women.
Study site: private clinic, Kuala Lumpur, Malaysia
Brunei Darussalam has a mixed population with entirely different cultures and religions. The overall incidence of Hepatitis B virus (HBV) infection is 6%. A racial analysis of the incidence of HBV infection in Brunei shows a significantly higher incidence in Chinese compared to the other races. This is consistent with the incidence in the neighbouring countries.
Sera were obtained from 494 non-icteric patients admitted with illnesses other than overt hepatitis into the medical wards of the rural and urban hospitals in Malaysia. They were tested for HBsAg, HBeAg, and anti-HBs by enzyme immunoassay. The overall HBsAg carrier rate was 18.0% ranging from 9.6% in children, (10 years and under), to a maximum of 23.5% in the adolescents (11 to 20 years), the rates decreasing subsequently to 16.5% and 20.8% in the adult and middle-age groups, respectively. The Chinese (18.6%) and Malays (19.9%) had similar HBsAg carrier rates but the rate in the Indians (9.0%) was distinctly lower. Similar rates were observed in the males (16.5%) and the females (19.8%). The carrier rate was 17.1% in rural patients compared with 21.4% in the urban ones. The 'e' antigen was found in 14 of the 89 HBsAg carriers (15.7%). The overall prevalence was 14/494 (2.8%) rising sharply from childhood (2.9%) to adolescence (5.3%), subsequently declining with advancing age. The Chinese had the highest rate (6.2%) followed by the Indians (1.5%) and the Malays (1.1%). Males had a rate of 3.3% compared to the females with 2.3%. Anti-HBs was found in 33.8% of the patients, increasing steadily from childhood (18.3%) to middle-age (46.4%). The Chinese had a higher prevalence rate (41.6%) than the Indians (32.8%) and the Malays (29.3%). The rates were similar for the males (35.6%) and the females (31.5%). Rural patients (46.1%) had a higher rate than urban patients (35.7%). Both areas showed rising prevalence with increasing age.(ABSTRACT TRUNCATED AT 250 WORDS)
Sera from 200 Malaysian male drug abusers were tested for markers of Hepatitis B virus (HBV) infection, viz. HBsAg, HBeAg, anti-HBs and anti-HBc using commercially available enzyme immunoassay (EIA) kits supplied by Abbot Laboratories, Chicago. Of these, 103 (51.5%) were positive for at least one HBV marker, 11 (5.5%) were positive for HBsAg; 4 (2%) for HBeAg, 74 (37%) for anti-HBs and 85 (42.5%) for anti-HBc. The HBsAg carrier rate was roughly the same as the carrier rate in the general population of Malaysia. The majority of drug abusers (95%) have had subclinical, asymptomatic HBV infection. Racially the Malay drug abusers had the highest exposure rate (54.2%). The HBsAg carrier rate was highest in the Chinese drug abusers (15.3%) and lowest in the Indians (0%). The mean age for the HBsAg carriers was found to be 26 years with a mean duration of drug abuse of 72 months. The Malaysian Anti-Narcotics Task Force of the National Security Council reported in the Malay Mail (July 13, 1985) that there were about 106,000 identified drug abusers in Malaysia and that 63% of these were in the 20-29 age groups. It appears from our study that this age group also coincides with the period of high HBsAg carrier rate. Age wise, those less than 21 years old had the highest HBsAg (11%) and HBeAg (5.6%) prevalence rates indicating high infectivity. After the age of 30 years, nearly 50% of the drug abusers appear to be immune with the HBe prevalence of 0%.(ABSTRACT TRUNCATED AT 250 WORDS)
Serological markers were used to determine the infective agents causing acute viral hepatitis in 246 patients. The frequencies of the five viral infections investigated were: non-A, non-B hepatitis - 99 patients (40.2%); hepatitis A - 98 patients (39.8%); hepatitis B - 43 patients (17.5%); cytomegalovirus - 4 patients (1.6%); and Epstein-Barr virus - 2 patients (0.8%). The log mean ages of presentation for the three predominant infections were: hepatitis A - 18 years; hepatitis B - 25 years; and non-A, non-B hepatitis - 30 years (F = 18.8, p =< 0.001). 52% of all cases were Malays (expected 32. 7%); 32% Chinese (expected 54.6%); and 16% Indians (expected 1l.5%) (X2 = 53, p = < 0.001). Hepatitis A virus infection was more common amongst Malays whilst non-A, non-B hepatitis was more frequent amongst Chinese and Indians. 28% of children <16 years) and 50% of adults had serological markers of previous hepatitis B infection. The variation in frequency for the different forms of hepatitis amongst the three main ethnic groups would suggest that socioeconomic and/or cultural factors are important in the propagation of acute viral hepatitis in Malaysia. HBsAg-negative chronic liver disease in our community may be a product of the high incidence of non-A, non-B hepatitis.
Naturally occurring malaria, arbovirus infection and hepatitis in monkeys can be a hazard for the investigator and might interfere with the outcome of experiments. 63 young adult Macaca fascicularis from Malaysia were screened for these infections. About 1 year after their arrival in France, parasitaemia due to Plasmodium spp., was present in 6.4% of the animals and specific antibodies in 55.5%. 19 of 35 initially positive monkeys were tested again 2 years later. Parasitaemia was found in 1 of 4 monkeys and antibodies in 11 of 19 monkeys which were initially positive. 9 of the monkeys initially tested had low titres of antibodies to the Flavivirus genus. All animals were negative for the hepatitis B surface antigen and anti-HBc. The prevalence of IgG antibodies against hepatitis A was 46.0%. The implications in terms of control are discussed.