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Hepatitis B: review of development from the discovery of the "Australia Antigen" to end of the twentieth Century

Yap SF

Malays J Pathol, 2004 Jun;26(1):1-12.
PMID: 16190102

"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.
Chronic hepatitis B infection in Malaysians

Yap SF

Malays J Pathol, 1994 Jun;16(1):3-6.
PMID: 16329567

Chronic hepatitis B virus (HBV) infection constitutes a major public health problem particularly in developing countries in East Asia, South-East Asia, the Pacific Basin and Africa. In Malaysia, a developing nation in the South East Asian region, the chronic HBV carrier rate varies between < 1% to about 10% depending on the ethnic group studied. The highest frequency is seen among the Chinese, followed by the Malays and lastly the Indians, with a male preponderance of between 2 : 1 and 3 : 1. Exposure to the virus among the adult population is estimated to be about 15%, 26% and 36% among the Indians, Malays and Chinese respectively. Serological study of adult chronic HBV carriers showed a frequency of HBe antigenemia of about 35%, with a significant decreasing trend with age. HBV DNA status generally correlated with the HBe status. An atypical profile of anti-HBe associated with serum HBV DNA is found in some carriers; in most instances, this is related to seroconversion from HBe antigenemia to anti-HBe. Chronic complications of HBV infection include the development of hepatocellular carcinoma (HCC), the occurrence of which closely parallel that of HBsAg carrier rate. In Malaysia, HCC is the third most common malignant neoplasm and among the 10 leading causes of death. About 80% of our HCC cases are HBV associated. All 3 ethnic groups are afflicted, the highest frequency being among the Chinese. Males show a disproportionate risk with an odds ratio of 3.93 (p < 0.0001).
Fulltext The clinical use of leucocyte--depleting filters in the multiply transfused patients--a case report

Yap S, Duraisamy G

Med J Malaysia, 1992 Jun;47(2):150-3.
PMID: 1494336
The immunology laboratory services in Malaysia

Yap SF

Malays J Pathol, 1982 Aug;5:11-3.
PMID: 7187453
Fulltext The surgical repair of ruptured sinus of valsalva aneurysms

Yap S, Jeyamalar R

Med J Malaysia, 1987 Sep;42(3):182-5.
PMID: 3506641

Over a period of nine years, from June 1976 through May 1985, 18 cases of ruptured sinus of Valsalva aneurysms were seen at the University Hospital, Kuala Lumpur (UK KL). Seven of these cases were treated surgically. The majority of patients were males, with a mean age of 26.6 years. All cases were symptomatic. The site of aneurysm was the right coronary sinus in five patients and the non-coronary sinus in two patients. All aneurysms ruptured into the right ventricle. The fistula was closed via a transaortic approach. In addition, repair of the right heart chamber was necessary in six patients. There were no deaths. Clinically significant morbidity included aortic regurgitation in one patient and residual fistula requiring reoperation in another. The long term follow-up at two years was excellent.
Fulltext The clinical significance of elevated levels of serum CA 19-9

Pavai S, Yap SF

Med J Malaysia, 2003 Dec;58(5):667-72.
PMID: 15190651

The tumour marker CA19-9 is a sensitive marker for pancreatic, gastric and hepatobiliary malignancies. High CA 19-9 level indicates unresectable lesions and a poor prognosis. The objective of the study was to determine the significance and implications of elevated CA 19-9 levels in the serum. A one-year retrospective review of all patients who had CA19-9 measured in our Medical Centre was undertaken; 69 patients were found to have CA 19-9 level above the cut-off value (37 U/ml). Thirty-six patients had malignant and the remaining 33 had benign lesions. CA 19-9 was found to be elevated in malignancies of pancreas, colorectum, lung, liver and ovary. Benign conditions associated with elevation of CA 19-9 included disease of the hepatobiliary system, pneumonia, pleural effusion, renal failure and SLE. In two individuals, there was no obvious cause for the elevation of this marker. CA 19-9 levels were significantly lower in benign than in malignant conditions. In conclusion, elevated CA 19-9 may be found in patients with benign as well as malignant disease. Therefore, it is important (1) that elevated levels of CA 19-9 are interpreted in the light of the clinical presentation of the patient and (2) to be aware of the benign conditions that can be associated with increased levels of this marker. With these factors in mind, CA 19-9 can be used to assist in the diagnosis of pancreatic cancer and assessment of resection adequacy post-operatively.
Serum complement (C3 and C4) levels in the Malaysian adult population

Yap SF, Pang T

Asian J Infect Dis, 1979 Jun;3(2):85-7.
PMID: 120736

Serum C3 and C4 values were determined in 236 normal adults of three racial groups, using the single radial immunodiffusion techniques. The C3 levels varied from 47 to 119 mg/dl and C4 levels from 16 to 66 ml/dl (mean +/- 2SD). The values were found to be comparable to the normals reported in some Western series. No significant differences in the levels related to sex and race were found.
Lansium domesticum: skin and leaf extracts of this fruit tree interrupt the lifecycle of Plasmodium falciparum, and are active towards a chloroquine-resistant strain of the parasite (T9) in vitro

Yapp DT, Yap SY

J Ethnopharmacol, 2003 Mar;85(1):145-50.
PMID: 12576213

Malaria remains a global problem in the light of chloroquine-resistant strains of Plasmodium falciparum. New compounds are needed for the development of novel antimalarial drugs. Seed, leaf, and fruit skin extracts of Lansium domesticum, a common fruit tree in South-East Asia, are used by indigenous tribes in Sabah, Malaysia for treating malaria. The skin and aqueous leaf extracts of the tree were found to reduce parasite populations of the drug sensitive strain (3D7) and the chloroquine-resistant strain (T9) of P. falciparum equally well. The skin extracts were also found to interrupt the lifecycle of the parasite. The data reported here indicate that extracts of L. domesticum are a potential source for compounds with activity towards chloroquine-resistant strains of P. falciparum.
The prevalence of recurrent abdominal pain in 11- to 16-year-old Malaysian schoolchildren

Boey C, Yap S, Goh KL

J Paediatr Child Health, 2000 Apr;36(2):114-6.
PMID: 10760006

OBJECTIVE: To determine the prevalence of recurrent abdominal pain (RAP) among Malaysian school children aged from 11 to 16 years.
METHODOLOGY: A preliminary cross-sectional survey in which three urban schools and three rural schools were selected randomly. Two classes were selected randomly from each year. A questionnaire was given to each child asking him or her about whether they had experienced abdominal pain occurring at least three times over a period of at least 3 months, interfering with normal daily activity. 1 Interfering with normal daily activity was defined as missing school and/or having to stop doing a routine daily activity on account of the pain. Girls whose pains were related to periods were excluded. After the forms had been completed, each child was again interviewed to ensure that Apley's criteria1 was fulfilled in cases of RAP.
RESULTS: The overall prevalence of RAP among 1549 schoolchildren (764 boys; 785 girls) was 10.2% (95% confidence interval (CI), 8.8-11.8). There appeared to be a higher prevalence in rural schoolchildren (P = 0.008; odds ratio (OR) 1.58), in those with a lower family income (P < 0.001; OR 2.02) and in children whose fathers have a lower educational attainment (P = 0.002; OR 1. 92). There were no significant differences in the prevalence of RAP among children of different sex, age, ethnic group and family size.
CONCLUSION: : In spite of differences in time and culture, the overall prevalence of 10.2% found in this study is similar to that determined by Apley.1 There are significant differences in the prevalence of RAP between children from rural and urban schools, among children with different family incomes and among children whose parents have different educational backgrounds.
An epidemiological survey of recurrent abdominal pain in a rural Malay school

Boey CC, Yap SB

J Paediatr Child Health, 1999 Jun;35(3):303-5.
PMID: 10404456

OBJECTIVE: To study the prevalence of complaints of recurrent abdominal pain (RAP) among school children aged 11-12 years in a rural setting in Malaysia.
METHODOLOGY: Questionnaires were distributed to all parents and teachers of children aged 11-12 years who attended a small rural school in which all the children were Malays. Complaints of RAP were defined as at least three such complaints occurring over a period of at least 3 months.
RESULTS: One hundred and sixty questionnaires were distributed, of which 148 were returned, giving a response rate of 92.5%. Sixty-one children (41.2%) had RAP. Approximately 45.2% of girls and 35.9% of boys reported having RAP. Compared with children without RAP, there was a significantly larger number of children with RAP (85.2%) who had at least one stress factor (P = 0.0109). There were no significant associations between RAP and total family income (P = 0.0573), a history of abdominal pain in at least one parent (P = 0.1686), a history of abdominal pain in at least one sibling (P = 0.0617), academic performance (P = 0.9967) or the degree of sports participation (P = 0.8469). There was an increased incidence of other systemic complaints in children with RAP when compared with children without RAP.
CONCLUSION: Recurrent abdominal pain was found to be common among 11- to 12-year-old children in a rural Malay school. There was a significant association found between RAP and the presence of stressful events, as well as with the presence of other systemic complaints.
Fulltext The prevalence of endemic goitre among Penans of the Baram

Chen PC, Yap SB

Med J Malaysia, 1988 Jun;43(2):159-61.
PMID: 3266288
Alpha-fetoprotein in hepatocellular carcinoma: a serological and histochemical study in Malaysian patients

Yap SF, Peh SC

Malays J Pathol, 1991 Dec;13(2):115-8.
PMID: 1726642

Serum alpha-fetoprotein (AFP) levels and its expression in liver tissue was studied in 50 cases of histologically confirmed hepatocellular carcinoma (HCC). Serum AFP levels were elevated (greater than 20iu/ml) in 35/50 (70%) of the cases, 28 of whom had levels greater than 500 iu/ml, which is highly suggestive of HCC. These results indicate that serum AFP, by itself, is a relatively insensitive diagnostic test for HCC. Although elevated levels in high risk patients provide a specific clue, a negative result does not exclude the diagnosis of HCC. Expression of AFP by tumour cells paralleled that of serum in the majority of cases. However, tissue AFP was negative in 7 patients who had markedly elevated serum AFP. This observation may be a reflection of preferential excretion of the tumour antigen or differential expression of the antigen by the tumour cells. None of the patients with normal serum AFP demonstrated a reaction for tissue AFP. There was no correlation between AFP production and tumour differentiation.
The nutritional status of children in an urban squatter community in Malaysia

Yap SB, Teoh ST

Asia Pac J Public Health, 1989;3(4):297-300.
PMID: 2517875

An anthropometric assessment was conducted on a sample of 309 children, aged twelve years and below, from an urban squatter community in Kuala Lumpur, Malaysia. The community consists mainly of Malays and Indians and is fairly established with a mean length of residence of about fifteen years. There was not much difference between the two ethnic groups with regard to educational status or income. Most of the residents were unskilled or semiskilled workers employed in factories and government agencies. About 40 percent of the infants and toddlers were found to be wasted, while about one-third of the older children were stunted. There appears to be some association between income per capita and nutritional status.
Primary cardiac amyloidosis

Jeyamalar R, Pathmanathan R, Yap SF, Kannan P

Ann Acad Med Singap, 1991 Nov;20(6):795-7.
PMID: 1803972

Cardiac amyloidosis is an uncommon and often unrecognised cause of cardiac failure. It is an infiltrative disease that may mimic either a restrictive or hypertrophic cardiomyopathy, constrictive pericarditis, coronary artery disease or valvular heart disease. The diagnosis should be suspected in a patient with cardiac failure who has low voltage complexes on the electrocardiogram, in association with increased myocardial mass and echogenicity on the echocardiogram. The definitive diagnosis, however, can only be made by endomyocardial biopsy or biopsy of any involved organ in systemic amyloidosis. Prognosis is poor and treatment ineffective.
Human T- and B-lymphocyte populations in blood: local population studies

Pang T, Parasakthi N, Yap SF

Med J Malaysia, 1979 Mar;33(3):243-6.
PMID: 316496
Hybridisation analysis for serum hepatitis B virus DNA

Yap SF, Wong PW, Kenneth-Raj

Br J Biomed Sci, 1994 Dec;51(4):336-40.
PMID: 7756940

A study was carried out to determine optimal assay conditions for an in-house hybridisation assay for detection of hepatitis B virus (HBV) genome in serum samples. Pre-treatment of samples, blot treatment and hybridisation conditions were found to affect assay performance. The indirect serum blot procedure was more robust and reliable than direct serum blotting. In the former, viral particles were isolated from the sample, lysed and then extracted. In comparison, no approaches to the direct serum spot method performed adequately. Sensitivity studies showed that labelling of the nucleic acid probe with dCTP was more efficient than with dATP. Using probes labelled to a specific activity of > 1 x 10(8) and an autoradiography period of about 48 h we could achieve a detection limit of < 1 pg. Specificity was achieved by use of a highly purified probe and moderately stringent hybridisation and wash conditions. Background binding was minimal and there was no non-specific binding of probe to negative control samples. Factors affecting speed of the assay were studied to identify steps that could be modified to shorten assay time without sacrificing performance. A shorter centrifugation step and the use of a high specific-activity probe permitted completion of an assay within four days.
Fulltext Management and Clinical Outcome of Children with Transfusion-Dependent Thalassaemia in Hospital Tuanku Ja'afar Seremban

Aina Mariana AM, Yap SH

Med J Malaysia, 2014 Aug;69(4):178-83.
PMID: 25500846 MyJurnal

The aim of this study was to evaluate the management and clinical outcome of transfusion-dependent thalassaemia children receiving care in the Paediatric Ambulatory Care Centre, Hospital Tuanku Ja'afar Seremban in comparison to The Malaysian Clinical Practice Guidelines. The demography, management and clinical outcome of the patients were documented using a checklist. Information on compliance to chelation agents was obtained through interview. There were twenty-six patients recruited in this study out of thirty seven patients registered in the centre. This study showed that more effort and vigilance should be given to ensure that the management of these patients adheres to the guidelines and clinical outcome of these patients monitored closely.

Study site: Paediatric Ambulatory Care Centre, Hospital Tunku Ja'afar, Seremban.
Correlation between oestrogen receptor protein expression in infiltrating ductal carcinoma of the breast by immunohistochemistry and cytosol measurements

Looi LM, Yap SF, Cheah PL

Ann Acad Med Singap, 1997 Nov;26(6):750-3.
PMID: 9522973

Fresh frozen neoplastic tissues from 70 infiltrating ductal breast carcinomas were analysed for cytosolic oestrogen receptor (ER) protein content using a solid phase enzyme immunoassay (EIA) method based on a "sandwich" principle (Abbott ER-EIA monoclonal). Formalin-fixed, paraffin-embedded sections from the same carcinomas were examined for nuclear immunoreactivity against a monoclonal antibody for ER protein (Dako) using the standard avidin-biotin complex immunoperoxidase (IP) method after microwave antigen retrieval. The degree of ER positivity by IP was also scored according to a visual estimation of the percentage of cells expressing immunopositivity and the intensity of staining. Twenty-eight (40%) of the carcinomas were ER-positive by EIA and 34 (48.6%) were positive by IP. Twenty-five (35.7%) were ER-positive and 33 (47.1%) were ER-negative by both methods. Nine (12.9%) were ER-negative by EIA but were positive by IP, this discrepancy being ascribed to sampling inadequacy for EIA. However, 3 (4.3%) tumours were ER-positive by EIA and negative by IP. This discrepancy may be variously due to inadequate antigen retrieval, faulty technique and the possibility that the two methods do not measure identical ER proteins. IP appears to have an advantage over EIA in that it has a higher pick-up rate, does not require fresh tissue and can be applied to archival material. However, to reduce false negative estimations, it may be necessary to run IP staining using more than one ER antibody. Standardisation of the IP method for ER is desirable before this method is to be widely adopted in Malaysian laboratories. Quantitation of ER positivity by IP scoring correlated poorly with actual cytosolic levels. Caution should be exercised in attaching patient management value to visual IP scoring.
Correlation between histological grade and c-erbB2 oncoprotein overexpression in infiltrating ductal carcinoma of breast

Looi LM, Cheah PL, Yap SF

Malays J Pathol, 1997 Jun;19(1):35-9.
PMID: 10879240

One hundred and twelve infiltrating ductal carcinoma of breast were studied by the standard avidinbiotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, using a monoclonal antibody to c-erbB-2 oncoprotein. The same tumours were assessed and scored according to the Bloom and Richardson criteria into three histological grades. The distribution of tumours according to grade were: 8 Grade I, 34 Grade II and 70 Grade III. Forty-three (38.4%) tumours showed positive membrane staining for c-erbB-2 oncoprotein. These comprised 7 Grade II and 36 Grade III tumours with c-erbB-2 immunopositivity rates of 20.6% and 51.4% respectively. The oncoprotein was not expressed by Grade I tumours. This study shows a good correlation between c-erbB-2 expression and histological grade, a known prognostic indicator of invasive breast carcinoma. Because the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor gene, its overexpression can be expected to result in more aggressive tumour behaviour. While it may be regarded as another indicator of poor prognosis breast cancers, its value in the selection of carcinomas less responsive to hormonal therapy and those more suitable for immunotherapy than chemotherapy has been mooted but remains to be clarified.
Serum hepatitis B virus DNA: relationship with the e-antigen and anti-e status in chronic carriers

Yap SF, Wong NW, Goh KL

Malays J Pathol, 1994 Jun;16(1):57-62.
PMID: 16329577

The relationship between serum Hepatitis B virus DNA (HBV-DNA) and the Hepatitis B e-antigen/ anti-Hepatitis Be (HBeAg/anti-HBe) serological status in Malaysians was studied. 212 cases of asymptomatic HBV carriers were recruited for this study. 92 cases were positive for the HBeAg at the point of recruitment. 85 (92.4%) of these patients tested positive for HBV-DNA, of whom 55 (64.7%) had levels over 100pg/ml of serum. Three of the remaining 7 HBeAg positive cases who were negative for HBV-DNA subsequently seroconverted. The other 4 cases remained negative for HBV-DNA for periods of 6-12 months. Out of 113 cases who were anti-HBe positive, 12 (10.6%) gave a positive HBV-DNA result. 2 of these 12 patients were recent seroconverters; the remaining cases had transiently increased viral replicative activity which later subsided. 7 out of the 212 carriers were in the e-window period; all 7 tested negative for HBV-DNA. Our data confirm a high frequency of HBV-DNA in HBeAg positive carriers and a negative correlation between HBV-DNA and anti-HBe. An atypical profile of anti-HBe associated with HBV-DNA was observed in 10.6% of the carriers. An inverse relationship between serum HBV-DNA levels and age was also observed.

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