exudates and Hepatitis-B--Chronic

In 2016 the World Health Organization (WHO) had adopted a global strategy to eliminate Hepatitis B (HBV) by 2030 through five core interventions. One of which is the "cascade of care", the continuum of services that persons with chronic Hepatitis B Virus (HBV) should receive as they progress from screening to diagnosis to treatment to chronic care. We determined the prevalence of the awareness and treatment of chronic HBV in Malaysia based on a large sample data from a screening campaign.. A total of 10,436 subjects participated in the HBV screening campaign organized by the Hepatitis Free Pahang Malaysia (HFP). Between in 2018 and 2019, HFP organized a total of 109 health fairs in partnership with local non-governmental organizations (NGO) to conduct HBV screening mostly in small towns and villages largely in the state of Pahang. All screen-positive subjects were recalled to undergo laboratory-based HBsAg and HBV DNA tests. Patients with confirmed chronic HBV were referred to local health services, while continued being monitored by HFP.. We estimated 13.1% of Malaysian adults aged 20 or older with chronic HBV were aware of their HBV status, and of those only 0.7% had received prior anti-viral treatment, but among those with baseline HBV DNA level > 20,000 IU/ml, 15.6% were subsequently treated. Tenofovir disoproxil fumarate was the only medicine used on all treated patients.. Few Malaysian adults with HBV were aware of their infection and even less received anti-viral therapy. Concerted public health efforts are urgently needed to improve HBV screening and care cascade in order to meet WHO's targets for HBV elimination.

Topics: Adult; Antiviral Agents; DNA, Viral; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Malaysia; Tenofovir

Asian countries account for almost three quarter of hepatocellular carcinoma (HCC) reported globally and chronic hepatitis B infection is one of the main contributors. Clinical observations show that Malay patients with chronic hepatitis B and HCC tend to have a worse outcome, when compared to other two major races in Malaysia. The objectives of this study was to determine the frequency of human leukocyte antigen (HLA) class II alleles in chronic hepatitis B patients with HCC among Malays compared to the general population to identify potential associations of HLA alleles with this disease. HLA class II typing was performed in chronic hepatitis B patients with hepatocellular carcinoma (n=12) by -polymerase chain reaction, sequence specific primer (PCR-SSP) method. There were higher allelic frequencies of certain HLA-DQB1 and HLA-DRB1 alleles; HLA-DQB1*03 (07) (41.7%), and HLA-DRB1*12 (41.7% vs 28.6%) and compared to controls (41.7% vs 29.7%). However, there was no significant statistical correlation found when compared with the normal healthy general population. This study provides an insight into the HLA Class II association with chronic hepatitis B and hepatocellular carcinoma in Malays. However, findings from this study should be validated with a larger number of samples using a high resolution HLA typing.

Topics: Carcinoma, Hepatocellular; Case-Control Studies; Female; Gene Frequency; Hepatitis B, Chronic; HLA-DQ Antigens; HLA-DRB1 Chains; Humans; Liver Neoplasms; Malaysia; Male; Middle Aged; Pilot Projects

Hepatitis B surface antigen is usually secreted by infected hepatocytes in the form of subviral particles rather than infectious virions, while the hepatitis B e antigen originates from the core gene and is modified and secreted by hepatocytes into the circulation and functions as a marker of active viral replication. This study aimed to study the relationship between HBV DNA and quantitative hepatitis B surface and e antigen in Malaysian patients.. A total of 82 chronic hepatitis B patients were recruited for this study from the Hepatology Department of Selayang Hospital. Quantitative hepatitis surface and e antigen was performed retrospectively on frozen plasma using enzyme linked immunosorbent assay according to the manufacturer's instructions. Hepatitis B viral DNA was extracted from all plasma samples and quantified using real-time PCR.. Quantitative hepatitis B surface and e antigens were found be high in 54.9% and 52.4% of the patients, respectively, while hepatitis B virus DNA level was high in 70.7%. The median of the viral load of HBV was 8,934.89 IU/mL and both hepatitis B surface and e antigens were also found to be high on average for qHBsAg (M = 5.19 IU/mL, SD ± 4. 33) and qHBeAg (M = 4.74IU/mL, SD ± 4.20), with qHBeAg being more strongly correlated to HBV DNA than qHBsAg (r = 0.893; p < 0.01).. This study revealed HBeAg to be the most appropriate marker that correlates well with HBV DNA, thus not completely novel but confirmative, and related to the Malaysian situation.

Topics: Adult; Biomarkers; Cross-Sectional Studies; DNA, Viral; Female; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Malaysia; Male; Middle Aged; Retrospective Studies

Hepatitis B virus co-infection with other strains of viral hepatitis is associated with increased risk of liver cirrhosis and hepatic decompensation.. This is a prevalence study that assessed the genetic diversity of chronic hepatitis B patients and coinfection.. Chronic hepatitis B patients enrolled in this study were tested for antibodies of other hepatitis viruses using ELISA kits. Patient clinical profiles were collected and partial genes of HBV, HCV, and HEV were amplified, sequenced, and analyzed using phylogenetic analysis. The associations between variables were determined using the chi-squared test.. Of the 82 patients recruited for this study, 53.7% were non-cirrhotic, 22.0% cirrhotic, 20.7% acute flare and 3.7% hepatocellular carcinoma. Majority (58%) of patients had a high level of ALT (≥34 U/L). Sequence analysis showed HBV (63.9%) belonged to genotype B, HEV belonged to genotype 4 while HCV belonged to genotype 3a and the genotypes were found to be significantly associated with the clinical stage of the patients (χ2=56.632; p<0.01). Similarly, Hepatitis B e antigen was also found to be significantly associated with the clinical stage of infection (χ2=51.952; p<0.01).. This study revealed that genetic diversity was found to have a significant impact on the severity of infection.

Topics: Adult; Antibodies, Viral; Carcinoma, Hepatocellular; Cross-Sectional Studies; DNA, Viral; Female; Genetic Variation; Genotype; Hepatitis B, Chronic; Hepatitis C; Hepatitis D; Hepatitis E; Humans; Liver Cirrhosis; Liver Function Tests; Liver Neoplasms; Malaysia; Male; Middle Aged; RNA, Viral; Severity of Illness Index

Up to 25% of chronic hepatitis B (CHB) patients eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood-based RNA biomarker panel for early HCC detection in CHB.. A genome-wide RNA expression study was performed using RNA extracted from blood samples from Malaysian patients (matched HCC, CHB, controls). Genes differentiating HCC from controls were selected for further testing using quantitative real-time polymerase chain reaction. Finally, a 6-gene biomarker panel was identified and characterized using a training set (cohort I = 126), and tested against 2 test sets (cohort II = 222; cohort III = 174). The total number of samples used for each group is: HCC + CHB = 143, CHB = 211, control = 168.. Our gene panel displays a consistent trend distinguishing HCC from controls in our test sets, with an area under receiver-operating characteristic curve of 0.9 in cohort III. Our independent test set (cohort III) showed that the gene panel had a sensitivity of 70% with a specificity of 92%. The biomarker profile for HCC was consistently detected in a small subgroup of CHB patients, thus potentially predicting early, preclinical cases of cancer that should be screened more intensively.. The biomarkers identified in this study can be used as the basis of a blood-based test for the detection of early HCC in CHB.

Topics: Adult; Area Under Curve; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Databases, Genetic; Early Detection of Cancer; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genetic Testing; Genome-Wide Association Study; Hepatitis B, Chronic; Humans; Liver Neoplasms; Malaysia; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Predictive Value of Tests; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; ROC Curve

Hepatitis B (HBV) is the leading cause of cirrhosis and hepatocellular carcinoma worldwide. This study assessed the knowledge, attitudes and practices of people with chronic HBV and the associated factors.. This cross-sectional study was conducted at an outpatient adult hepatology clinic at a tertiary hospital in Kuala Lumpur. A self-administered questionnaire was administered on a one-to-one basis to assess knowledge, attitudes, and lifestyle practices of people with chronic HBV.. The response rate was 89% (n = 483/543). Participants had a mean age of 46.3 (±14.7) years and the mean duration of HBV from time of diagnosis was 12.2 (±8.8) years. The mean knowledge score was 12.57/20 (standard deviation: ±4.4, range: 0-19). Participants aged 30-39 years, with higher educational attainment, employed in professional jobs, longer duration of diagnosis and those without cirrhosis had significantly higher knowledge scores. Age, education level and duration of diagnosis were significant predictors of the knowledge score on standard multiple regression analysis. More than half of the participants were worried of spreading HBV infection to family and friends and worried since the diagnosis. A third of the participants (33.5%) were embarrassed to reveal their diagnosis to the public but most of them (93.6%) would inform their family. Those who reported feeling worried since their diagnosis were more likely to be middle-aged, of Malay ethnicity, have shorter duration of diagnosis of less than 10 years and have received therapy. About half of the participants (50.6%) did not share dining utensils and the majority (93.2%) believed that HBV can be transmitted by sharing of eating and drinking utensils. Older patients were significantly less likely to share utensils. Those who felt worried since diagnosis had significant higher knowledge of HBV.. The findings highlight the stigma and misconceptions that still exist among the HBV patients. More patient and public education about HBV and its prevention are essential to increase awareness and to demystify the disease.

Topics: Adult; Ambulatory Care Facilities; Cross-Sectional Studies; Female; Health Knowledge, Attitudes, Practice; Hepatitis B, Chronic; Humans; Life Style; Malaysia; Male; Middle Aged; Surveys and Questionnaires; Tertiary Care Centers

To determine the etiology of liver cirrhosis and risk factors for hepatocellular carcinoma (HCC) in a multiracial Asian population.. Consecutive patients with liver cirrhosis presenting to outpatient clinics and inpatient service at the University of Malaya Medical Centre from 1 April 2006 to 31 May 2009 were included.. A total of 460 patients were included in the study: 317 male patients (68.9%) and 143 female patients (31.1%), with a mean age of 58.8years (range: 15-87years). The major causes of cirrhosis were: chronic hepatitis B, n=212, 46.1%; chronic hepatitis C, n=85, 18.5%; cryptogenic, n=71, 15.4%; alcohol, n=58, 12.6% and autoimmune, n=9, 2.0%. Alcohol was the main etiology in Indians (51.1%) compared to Malay (0%) and Chinese (4.4%) (both P<0.001). Hepatitis B was the predominant etiology in Malay (47.9%) and Chinese (58.8%) compared to Indians (5.6%) (both P<0.001). Hepatitis C cirrhosis was highest in Malays (25.0%). 136 patients (29.6%) had concurrent HCC. Male sex (P<0.001), age>60years (P=0.014), hepatitis B (P<0.001), hepatitis C (P=0.006) and cryptogenic cause (P=0.002) were found to be independent risk factors for HCC.. The etiology of cirrhosis has a peculiar pattern based on racial differences in alcohol intake and in the prevalence of hepatitis B.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alcohol Drinking; Asian People; Carcinoma, Hepatocellular; Chi-Square Distribution; China; Cross-Sectional Studies; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; India; Liver Cirrhosis; Liver Neoplasms; Malaysia; Male; Middle Aged; Odds Ratio; Prevalence; Risk Assessment; Risk Factors; Young Adult

Hepatitis B virus (HBV) has been classified into eight genotypes, designated A-H. These genotypes are known to have distinct geographic distributions. The clinical importance of genotype-related differences in the pathogenicity of HBV has been revealed recently. In Malaysia, the current distribution of HBV remains unclear. The aim of this study was to determine the genotypes and subtypes of HBV by using PCR, followed by DNA sequencing, as well as to analyse the mutations in the immunodominant region of preS and S proteins. The S gene sequence was determined from HBV DNA of four apparently healthy blood donors' sera and three sera from asymptomatic chronic hepatitis B carriers. Of this batch of sera, the preS gene sequence was obtained from HBV DNA from three out of the four blood donors and two out of the three chronic carriers. Due to insufficient sera, we had to resort to using sera from another blood donor to make up for the sixth DNA sequence of the preS gene. Based on the comparative analysis of the preS sequences with the reported sequences in the GenBank database, HBV DNA from two normal carriers was classified as genotype C. Genotype B was assigned to HBV from one blood donor and two hepatitis B chronic carriers, whereas HBV of one chronic carrier was of genotype D. Based on the S gene sequences, HBV from three blood donors was of genotype C, that of one blood donor and one chronic carrier was of genotype B, and the remaining, of genotype D. In the five cases where both preS and S gene sequences were determined, the genotypes assigned based on either the preS or S gene sequences were in concordance. The nature of the deduced amino acid (aa) sequences at positions 125, 127, 134, 143, 159, 161 and 168 of the S gene enabled the classification of these sequences into subtypes, namely, adrq+, adw2 and ayw2. The clustering of our DNA sequences into genotype groups corresponded to their respective subtype, that is, adw2 in genotype B, adrq in genotype C and ayw in genotype D. Analysis of the point mutations revealed that five of the sequences contained aa substitutions at immunodominant epitopes involved in B or/and T cell recognition. In conclusion, despite the low numbers of samples studied, due to budget constraints, these data are still worthwhile reporting, as it is important for the control of HBV infections. In addition, the genotype and mutational data obtained in this study may be useful for designing new treatment regimes for HBV patients.

Topics: Amino Acid Sequence; Carrier State; DNA, Viral; Genotype; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Malaysia; Molecular Sequence Data; Protein Precursors

A retrospective study was carried out to determine the frequency of the pre-core stop codon mutant virus in a group of chronic hepatitis B carriers: 81 cases were considered [33 hepatits B e antigen (HBe) positive and 48 HBe negative]. All of the HBe positive cases had detectable viral DNA by hybridization analysis; in the case of the HBe negative cases, one third had detectable viral DNA by hybridization analysis and two thirds had HBV DNA detectable by polymerase chain reaction (PCR) amplification. Pre-core stop codon mutant detection was carried out on all specimens using allele-specific oligonucleotide hybridization following PCR amplification of the target sequence. The pre-core mutant was detected in 13/33 (39.4%) of HBe positive cases and in 32/48 (66.7%) of HBe negative cases. Sequence analysis was carried out on 8 of the 16 HBe negative specimens that did not carry the pre-core mutant virus to determine the molecular basis for the HBe minus phenotype in these cases: the 1762/1764 TA paired mutation in the second AT rich region of the core promoter was detected in five cases; a start codon mutation was detected in one case. The predominant mutation resulting in the HBe minus phenotype in our isolates was the 1896A pre-core ("pre-core stop codon") mutation; other mutations responsible for the phenotype included the core promoter paired mutation and pre-core start codon mutation. In view of the high frequency of the pre-core mutant virus, sequence analysis was performed to determine the virus genotype on the basis of the nucleotide sequence of codon 15. The sequences of 21 wild type virus (14 HBe positive and 7 HBe negative cases) were examined: 15 were found to be codon 15 CCT variants (71.4%); the frequency in the HBe positive group was 12/14 (85.7%), while that in the HBe negative group was 3/7 (42.9%). The high frequency of the codon 15 CCT variant in association with the frequent occurrence of the pre-core mutant in our isolates concurs with the results of other studies.

Topics: Base Sequence; DNA Primers; DNA, Viral; Hepatitis B Core Antigens; Hepatitis B, Chronic; Humans; Malaysia; Mutation; Phenotype; Retrospective Studies

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).

Topics: Asian People; Carcinoma, Hepatocellular; Carrier State; China; Ethnicity; Female; Hepatitis B virus; Hepatitis B, Chronic; Humans; India; Liver Neoplasms; Malaysia; Male

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.

Topics: Carrier State; DNA, Viral; Hepatitis B Antibodies; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Malaysia; Serologic Tests