Publications by authors named "Rosmawati Mohamed"

71 Publications

Contextual and individual factors associated with knowledge, awareness and attitude on liver diseases: A large-scale Asian study.

J Viral Hepat 2021 Nov 24. Epub 2021 Nov 24.

Kantar Health, Singapore, Singapore.

There are limited data to provide better understanding of the knowledge/awareness of general population towards liver health in Asia. We sought to identify the knowledge gaps and attitudes towards liver health and liver diseases as well as evaluate associated individual-level and macro-level factors based on contextual analysis. An online survey assessing knowledge, awareness and attitudes towards liver health and disease was conducted among 7500 respondents across 11 countries/territories in Asia. A liver index was created to measure the respondents' knowledge level and the degree of awareness and attitudes. Multilevel logistic regression was performed to identify individual factors and contextual effects that were associated with liver index. The overall liver index (0-100-point scale) was 62.4 with 6 countries/territories' liver indices greater than this. In the multilevel model, the inclusion of geographical information could explain for 9.6% of the variation. Residing in a country/territory with higher HBV prevalence (80% IOR: 1.20-2.79) or higher HCV death rate (80% IOR: 1.35-3.13) increased the individual probability of obtaining a high overall liver index. Individual factors like age, gender, education, household income, disease history and health screening behaviour were also associated with liver index (all p-values<0.001). The overall liver index was positively associated with the two macro-level factors viz. HBV prevalence and HCV death rate. There is a need to formulate policies especially in regions of lower HBV prevalence and HCV death rate to further improve the knowledge, awareness and attitudes of the general public towards liver diseases.
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http://dx.doi.org/10.1111/jvh.13636DOI Listing
November 2021

Risk factors of nonalcoholic fatty liver disease in lean body mass population: A systematic review and meta-analysis.

JGH Open 2021 Nov 4;5(11):1236-1249. Epub 2021 Oct 4.

Department of Medicine University Malaya Medical Centre Kuala Lumpur Malaysia.

The pathophysiology and risk factors of nonalcoholic fatty liver disease (NAFLD) among lean patients is poorly understood and therefore investigated. We performed a meta-analysis of observational studies. Of 1175 articles found through searching from Medline/PubMed, Banglajol, and Google Scholar by two independent investigators, 22 were selected. Data from lean ( = 6768) and obese ( = 9253) patients with NAFLD were analyzed; lean ( = 43 398) and obese ( = 9619) subjects without NAFLD served as controls. Age, body mass index, waist circumference, systolic blood pressure, and diastolic blood pressure (DBP) had significantly higher estimates in lean NAFLD patients than in lean non-NAFLD controls. Fasting blood sugar [MD(mean difference) 5.17 mg/dl, 95% CI(confidence interval) 4.14-6.16], HbA1c [MD 0.29%, 95% CI 0.11-0.48], and insulin resistance [HOMA-IR] [MD 0.49 U, 95% CI 0.29-0.68]) were higher in lean NAFLD patients than in lean non-NAFLD controls. All components of the lipid profile were raised significantly in the former group except high-density lipoprotein. An increased uric acid (UA) level was found to be associated with the presence of NAFLD among lean. Cardio-metabolic profiles of nonlean NAFLD patients significantly differs from the counter group. However, the magnitude of the difference of lipid and glycemic profile barely reached statistical significance when subjects were grouped according to lean and nonlean NAFLD. But DBP (slope: 0.19,  < 0.037), HOMA-IR (slope: 0.58,  < 0.001), and UA (slope: 0.36,  = 0.022) were significantly higher if NAFLD was present compared to that of non-NAFLD group. Lean and nonlean NAFLD patients are metabolically similar and share common risk factors.
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http://dx.doi.org/10.1002/jgh3.12658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593777PMC
November 2021

Comparative expression of pro-inflammatory and apoptotic biosignatures in chronic HBV-infected patients with and without liver cirrhosis.

Microb Pathog 2021 Oct 5;161(Pt A):105231. Epub 2021 Oct 5.

Department of Medicine, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, 50603, Malaysia. Electronic address:

The interplay of immune mediators is paramount to optimal host anti-viral immune responses, especially against chronic hepatitis B virus (HBV) infection. Here, we investigated the dynamic changes in host immune responses in chronic HBV-infected individuals with and without liver cirrhosis by examining the signatures of apoptosis and plasma levels of pro-inflammatory cytokines, chemokines, and cytotoxic proteins. A total of 40 chronic HBV patients with and without liver cirrhosis were studied for plasma levels of immune mediators, and signatures of apoptosis in peripheral blood mononuclear cells (PBMCs). The intracellular concentrations of reactive oxygen species (ROS) in patients with chronic HBV with liver cirrhosis was relatively higher as compared to chronic HBV patients. The onset of apoptosis was sustained due to ongoing liver inflammation in concert with plasma TNF-α and IL-6 levels. Plasma VEGF was upregulated among chronic HBV patients with liver cirrhosis, whereas CCL2, CCL5 and granzyme B levels were down-regulated. High levels of ROS, IL-6 and TNF-α correlated with ongoing inflammation among chronic HBV patients with liver cirrhosis, which likely attributed to the expression of biosignatures of apoptosis and activation in immune cells.
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http://dx.doi.org/10.1016/j.micpath.2021.105231DOI Listing
October 2021

Association of deleted in liver cancer-1 gene polymorphism with increased risk of chronicity of disease among Malaysian patients with hepatitis B infection.

Pharmacogenet Genomics 2021 12;31(9):185-190

The Pharmacogenomics Laboratory, Department of Pharmacology.

Objective: The aim of this study is to examine the association between genetic variations in deleted in liver cancer 1 (DLC1) gene with progression of the hepatitis B virus (HBV) infection.

Methods: A total of 623 subjects were included in this study, of whom, 423 were chronic hepatitis B (CHB) patients without liver cirrhosis or hepatocellular carcinoma (HCC), 103 CHB with either liver cirrhosis ± HCC and 97 individuals who had resolved HBV. Two single-nucleotide polymorphisms rs3739298 and rs532841 of DLC1 gene were genotyped using the Sequenom MassARRAY platform.

Results: Our results indicated significant differences between the chronic HBV and resolved HBV groups in genotype and allele frequencies of DLC1-rs3739298 [odds ratio (OR) = 2.23; 95% confidence interval (CI): 1.24-3.99; P = 0.007] and (OR = 1.54; 95% CI: 1.07-2.22; P = 0.021), respectively. Moreover, haplotype analysis revealed significant associations between chronicity of HBV with TG and GA haplotypes (P = 0.041 and P = 0.042), respectively.

Conclusion: A significant association exists between the rs3739298 variant and susceptibility to CHB infection.
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http://dx.doi.org/10.1097/FPC.0000000000000439DOI Listing
December 2021

Loss-of-function HSD17B13 variants, non-alcoholic steatohepatitis and adverse liver outcomes: Results from a multi-ethnic Asian cohort.

Clin Mol Hepatol 2021 Jul 23;27(3):486-498. Epub 2021 Feb 23.

Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Background/aims: 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients.

Methods: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded.

Results: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P<0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR], 0.004; 95% confidence interval [CI], 0.00-0.64; P=0.033 and HR, 0.01; 95% CI, 0.00-0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese.

Conclusion: HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.
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http://dx.doi.org/10.3350/cmh.2020.0162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273635PMC
July 2021

Hepatitis C virus core antigen as alternative diagnostic algorithm for active hepatitis C virus infection among haemodialysis population: Cost implications.

Nephrology (Carlton) 2021 May 23;26(5):463-470. Epub 2021 Feb 23.

Department of Medicine, Faculty of Medicine, University of Malaya, Jalan University, Kuala Lumpur, Malaysia.

Aims: In Malaysia, majority anti-HCV positive haemodialysis patients do not undergo hepatitis C confirmation due to the high cost of HCV RNA. HCV Core Antigen might be a cost-effective diagnostic test to identify HD patients who have active HCV infection eligible for Direct Acting Anti-viral therapy.

Methods: A cross-sectional study was conducted to assess the correlation between HCV Ag and HCV RNA and the cost implications of different diagnostic algorithms to diagnose active HCV infection using Anti-HCV, HCV Ag, and HCV RNA. Pre-dialysis blood was tested for both HCV Ag and HCV RNA. HCV Ag was tested with Abbott ARCHITECT HCV Ag test.

Results: Two-hundred twenty-seven haemodialysis patients were recruited from 20 centres with mean age of 57.68 ± 12.48 years, and male constitutes 56.8% (129) of the study population. HCV Ag correlated well with HCV RNA (Spearman test coefficient 0.943, p < .001) with sensitivity of 93.9%, specificity 99.3%, and the accuracy was 97.36%. Cost analysis indicated that a sequential test involving Anti-HCV antibody as initial screening, followed by HCV Ag on Anti-HCV positive and HCV RNA on HCV Ag negative cases translated to a modest cost-saving algorithm compared to standard diagnostic algorithm.

Conclusion: HCV Ag correlated well with HCV RNA and can potentially be fused in an alternative diagnostic algorithm to generate cost savings methods to diagnose active HCV infection among haemodialysis patients. This alternative algorithm is especially relevant in low to middle-income countries such as Malaysia to optimize the use of the healthcare resource and gains in clinical outcomes.
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http://dx.doi.org/10.1111/nep.13862DOI Listing
May 2021

Chronic inflammation involves CCL11 and IL-13 to facilitate the development of liver cirrhosis and fibrosis in chronic hepatitis B virus infection.

Scand J Clin Lab Invest 2021 Apr 2;81(2):147-159. Epub 2021 Feb 2.

Gastroenterology Unit, Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.

The pathogenesis involving non-alcoholic fatty liver disease (NAFLD) in the context of chronic HBV (CHB) virus infection requires to be understood for developing improved modalities of diagnosis and treatment. We retrospectively investigated the association between NAFLD and CHB virus infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between years 2013 and 2016, we studied 455 subjects in the current investigation. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the hepatitis B virus (HBV) viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. We found that there was a high concurrence of NAFLD among patients with CHB virus infection. The presence of metabolic syndrome and chronic inflammation in CHB virus-infected patients were two independent factors that led to the progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components.
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http://dx.doi.org/10.1080/00365513.2021.1876245DOI Listing
April 2021

Use of simple scoring systems for a public health approach in the management of non-alcoholic fatty liver disease patients.

JGH Open 2020 Dec 12;4(6):1155-1161. Epub 2020 Sep 12.

Department of Medicine, Faculty of Medicine University of Malaya Kuala Lumpur Malaysia.

Background And Aim: Advanced fibrosis is the most important predictor of liver-related mortality in non-alcoholic fatty liver disease (NAFLD). The aim of this study was to compare the diagnostic performance of noninvasive scoring systems in identifying advanced fibrosis in a Malaysian NAFLD cohort and propose a simplified strategy for the management of NAFLD in a primary care setting.

Methods: We enrolled and reviewed 122 biopsy-proven NAFLD patients. Advanced fibrosis was defined as fibrosis stages 3-4. Noninvasive assessments included aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), AST/ALT ratio, diabetes (BARD) score, fibrosis-4 (FIB-4) score, and NAFLD fibrosis score.

Results: FIB-4 score had the highest area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) of 0.86 and 94.3%, respectively, for the diagnosis of advanced fibrosis. FIB-4 score < 1.3 ruled out advanced fibrosis in 72% of the patients, with 6% being understaged. Further stratification of the indeterminate group patients by other non-alcoholic steatohepatitis (NASH) clinical predictors, such as abnormal gamma-glutamyl transpeptidase (GGT) level and presence diabetes mellitus (DM), could further reduce the number of patients who are unlikely to have advanced fibrosis by 52% and 35%, respectively.

Conclusion: We found that FIB-4 score outperforms other scoring systems based on AUROC and NPV. The use of a simple scoring system such as FIB-4 as first-line triage to risk-stratify NAFLD patients in the primary care setting, with further stratification of those in the indeterminate group using clinical predictors of NASH, can help in the development of a simplified strategy for a public health approach in the management of NAFLD.
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http://dx.doi.org/10.1002/jgh3.12414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731808PMC
December 2020

Hepatitis C core antigen testing to diagnose active hepatitis C infection among haemodialysis patients.

BMC Nephrol 2020 11 13;21(1):480. Epub 2020 Nov 13.

Department of Medicine, Faculty of Medicine, University of Malaya, Jalan University, 50603, Kuala Lumpur, Malaysia.

Background: Hepatitis C virus (HCV) infects more than 71 million people worldwide and chronic HCV infection increases the risk of liver cirrhosis and failure. Haemodialysis (HD) is one of the renal replacement therapies with risk of HCV transmission. Anti-HCV antibodies are the serological screening test for HCV infection that does not detect active phase of infection. Majority HCV infected HD patients in Malaysia do not have further HCV RNA performed due to high cost and thus HCV treatment is less frequently offered. HCV Core Antigen (HCV Ag) can potentially be used to diagnose active HCV infection in HD population in comparison to HCV RNA, at lower cost.

Methods: We conducted a cross-sectional study to assess the correlation between HCV Ag and HCV RNA and to identify the prevalence of active HCV infection among HCV seropositive HD patients from dialysis centres across West Malaysia from July 2019 to May 2020. Pre-dialysis blood was taken and tested for both HCV Ag and HCV RNA tests. HCV Ag was tested with Abbott ARCHITECT HCV Ag test.

Results: We recruited 112 seropositive HD patients from 17 centres with mean age of 54.04 ± 11.62 years, HD vintage of 14.1 ± 9.7 years, and male constitute 59.8% (67) of the study population. HCV Ag correlates well with HCV RNA (Spearman test coefficient 0.833, p < 0.001). The sensitivity was 90.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 76.5%, and accuracy 92.9%. For HCV RNA level > 3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p < 0.001). The prevalence of active HCV infection was 76.8% among HCV seropositive HD patients.

Conclusions: Although HCV Ag is less sensitive, it shows an excellent correlation with HCV RNA and has 100% PPV. HCV Ag can be considered as an alternative diagnostic tool for chronic active HCV infection among HD cohort, who can then be considered for HCV treatment. For seropositive HD patient with negative HCV Ag, we recommend to follow-up with HCV RNA test.
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http://dx.doi.org/10.1186/s12882-020-02154-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666439PMC
November 2020

2018 Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C in Chronic Kidney Disease Guideline Implementation: Asia Summit Conference Report.

Kidney Int Rep 2020 Aug 21;5(8):1129-1138. Epub 2020 May 21.

Kidney Disease: Improving Global Outcomes (KDIGO), Brussels, Belgium.

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.
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http://dx.doi.org/10.1016/j.ekir.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403514PMC
August 2020

Fatty liver is associated with advanced fibrosis but does not predict adverse outcomes in patients with chronic hepatitis B.

J Viral Hepat 2020 12 27;27(12):1297-1305. Epub 2020 Aug 27.

Department of Medicine, Gastroenterology and Hepatology Unit, University Malaya Medical Centre, Kuala Lumpur, Malaysia.

Hepatic steatosis is increasingly common and has been implicated in progression of liver fibrosis in chronic hepatitis B (CHB) patients. We aimed to investigate the impact of hepatic steatosis on liver fibrosis and clinical outcomes in CHB patients. Consecutive CHB patients who underwent transient elastography between 2013 and 2017 at a tertiary hospital were included in this longitudinal cohort study. Presence of hepatic steatosis was defined as controlled attenuation parameter, CAP ≥ 248 dB/m, while advanced liver fibrosis was defined as liver stiffness measurement, LSM ≥ 9.4 kPa. Cardiovascular events, liver-related complications, malignancy and mortality and a composite of these outcomes were evaluated with Kaplan-Meier analysis and Cox proportional hazards regression. Our study cohort included 614 patients with median follow-up of 45 (32-63) months. Hepatic steatosis was present in 294 patients (47.9%), and advanced liver fibrosis was present in 127 patients (21.0%). Presence of hepatic steatosis (OR: 1.956, 95% CI: 1.250-3.060) and diabetes mellitus (OR: 3.507, 95% CI: 2.069-5.944) was independently associated with advanced fibrosis. Advanced fibrosis was independently associated with composite outcome (HR: 2.496, 95% CI: 1.352-4.606), liver-related complications (HR: 3.765, 95% CI: 1.380-10.271) and mortality (HR: 3.632, 95% CI: 1.342-9.826), but not cardiovascular events and malignancy. Hepatic steatosis was not associated with any adverse outcomes. We conclude that hepatic steatosis is common and associated with advanced fibrosis in CHB patients. Unlike advanced fibrosis, hepatic steatosis does not predict adverse outcomes in CHB patients.
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http://dx.doi.org/10.1111/jvh.13361DOI Listing
December 2020

An expert review on the use of tenofovir alafenamide for the treatment of chronic hepatitis B virus infection in Asia.

J Gastroenterol 2020 Sep 14;55(9):811-823. Epub 2020 Jul 14.

PMC, Allied and DHQ Hospital, Faisalabad, Pakistan.

Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for curbing HBV infection and associated morbidity in Asia. However, there are some challenges to the use of ETV and TDF; while ETV is associated with high resistance in lamivudine (LAM)-exposed (especially LAM-refractory) patients; bone and renal safety issues are a major concern with TDF. Hence, a panel of twenty-eight expert hepatologists from Asia convened, reviewed the literature, and developed the current expert opinion-based review article for the use of TAF in the resource-constrained settings in Asia. This article provides a comprehensive review of two large, phase 3, double-blind, randomized controlled trials of TAF versus TDF in HBeAg-negative (study 0108) and HBeAg-positive (study 0110) chronic HBV patients (> 70% Asians). These studies revealed as follows: (1) non-inferiority for the proportion of patients who had HBV DNA < 29 IU/mL; (2) significantly high rate of normalization of alanine aminotransferase levels; (3) no incidence of resistance; and (4) significantly better bone and renal safety, with TAF vs. TDF up to 144 weeks. Considering the benefits of TAF, the expert panel proposed recommendations for optimizing the use of TAF in Asia, along with guidance on specific patient groups at risk of renal or bone disease suitable for TAF therapy. The guidance provided in this article may help clinicians optimize the use of TAF in Asia.
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http://dx.doi.org/10.1007/s00535-020-01698-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452871PMC
September 2020

Increased Proinflammatory Cytokine Production by Chronic Hepatitis B Patients with Mutant Hepatitis B Virus: Plausible Mechanisms Underlying Severe Liver Diseases in These Patients.

Viral Immunol 2020 09 8;33(7):530-534. Epub 2020 Jun 8.

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Hepatitis B virus (HBV) is a noncytopathic virus and billions of HBV-infected patients live uneventful lives and do not suffer from notable liver damage. However, HBV also causes progressive liver diseases characterized by hepatic inflammation, hepatic fibrosis, and liver cancer in millions of HBV-infected patients. The goal of this study was to evaluate the role of mutant HBV in HBV pathogenesis. In a cohort of 360 chronic HBV-infected patients, mutations at T1762/A1764 of HBV genome were detected in most of the patients with HBV-induced liver cirrhosis and hepatocellular carcinoma. To explore if mutations at T1762/A1764 of HBV genome has any role in progressive liver disease, peripheral blood mononuclear cells (PBMCs) and antigen-presenting dendritic cells (DCs) were isolated from five chronic hepatitis B (CHB) patients with mutations at T1762/A1764 and five comparable patients of CHB without mutations at T1762/A1764. DCs were pulsed with hepatitis B surface antigen (HBsAg). The levels of cytokines produced by PBMCs and DCs as well as nitrite production by DCs were evaluated. Significantly higher levels of interleukin-12, tumor necrosis factor-alpha, interferon-gamma, and transforming growth factor-beta were detected in cultures of PBMCs, DCs, and HBsAg-pulsed DCs from CHB patients with mutations at T1762/A1764 compared with those without mutations ( < 0.05). DCs of all CHB patients with mutations produced significantly higher levels of nitrite compared with those without mutation at T1762/A1764 ( < 0.001). This study discusses the inflammatory potential of mutant HBV that may be responsible for diverse levels of pathogenicity of HBV. Further studies involving larger cohorts would provide more insight into these unresolved issues about HBV pathogenesis and these insights may aid in developing immune therapy for CHB patients.
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http://dx.doi.org/10.1089/vim.2019.0198DOI Listing
September 2020

Allele HLA-DQB1*06 reduces fibrosis score in patients with non-alcoholic fatty liver disease.

Hepatol Res 2020 Aug 8;50(8):947-954. Epub 2020 Jun 8.

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Aim: Human leukocyte antigen (HLA) regions were highlighted as important genetic markers for various liver diseases by hepatology-related genome-wide association studies. Replication studies in non-alcoholic fatty liver disease (NAFLD) are limited and none has investigated the association of HLA alleles with non-alcoholic steatohepatitis (NASH) and other histological characteristics. In the current study, we examined the association of HLA-DQA1 and HLA-DQB1 alleles with NAFLD spectrum and its histological characteristics.

Methods: Consecutive biopsy-proven NAFLD patients (n = 191) and healthy controls (n = 188) were enrolled and genotyped for HLA-DQA1 and HLA-DQB1 alleles using the sequence-specific oligonucleotide-polymerase chain reaction method.

Results: No association was found between the HLA alleles and NAFLD or NASH in a case-control setting. Nevertheless, among NAFLD patients, the frequency of HLA-DQB1*06 allele was significantly the lowest in NASH with significant fibrosis (10.4%) and approximately similar for NASH without significant fibrosis (22.9%) and NAFL (22.5%) (P = 0.004). It is noteworthy that the association remains significant after correction for multiple comparisons (P  = 0.04). Multivariate analysis revealed that HLA-DQB1*06 allele is also associated with fibrosis score (P = 0.001); the result remains significant after correction for multiple comparisons.

Conclusion: These findings suggest that HLA-DQB1*06 is associated with lower fibrosis score in NAFLD patients.
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http://dx.doi.org/10.1111/hepr.13525DOI Listing
August 2020

Estimating the Population Size of People Who Inject Drugs in Malaysia for 2014 and 2017 Using the Benchmark-Multiplier Method.

Subst Use Misuse 2020 14;55(6):871-877. Epub 2020 Jan 14.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands.

: As hepatitis C elimination efforts are launched, national strategies for screening and treatment scale-up in countries, such as Malaysia, must be designed and implemented. Strategic information, including estimates of the total number of patients chronically-infected with hepatitis C virus (HCV) and the size of key populations, such as people who inject drugs (PWID), is critical to informing these efforts. For Malaysia, the estimate of the PWID population size most frequently reported in global systematic reviews is for the year 2009. : To support ongoing national HCV planning efforts, we aimed to estimate the national population size of active PWID in Malaysia, for the years 2014 and 2017. : To estimate the PWID population size, we applied standard benchmark-multiplier methodology, frequently used for PWID population size estimation, and extended it by adjusting for cessation of injecting drug use within the benchmark and calculating statistical uncertainty intervals. : The estimated active PWID population size was 153,000 (95% uncertainty interval (UI): 136,000-172,000) for 2014 and 156,000 (95% UI: 137,000-188,000) for 2017. /: This updated estimate of the active PWID population size in Malaysia will help inform effective planning for the scale-up of HCV screening and treatment services. The proposed methodology is applicable to other countries that maintain national HIV registries and have conducted Integrated Biological and Behavioral Surveys among active PWID.
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http://dx.doi.org/10.1080/10826084.2019.1708943DOI Listing
June 2021

Metabolic Syndrome Is Associated With Advanced Liver Fibrosis Among Pediatric Patients With Non-alcoholic Fatty Liver Disease.

Front Pediatr 2019 26;7:491. Epub 2019 Nov 26.

Endocrinology Unit, Department of Pediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Non-alcoholic fatty liver disease (NAFLD) among children is a growing concern with potential significant outcome. This study aims to investigate the relationship between hepatic steatosis, metabolic syndrome, and liver fibrosis among children with obesity and diabetes mellitus. Children aged 6-18 years old were recruited from pediatric obesity and diabetes clinic in University Malaya Medical Center (UMMC) between year 2016 and 2019. Data on basic demographics, anthropometric measurements and clinical components of metabolic syndrome were collected. Transient elastography was performed with hepatic steatosis and liver fibrosis assessed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) respectively. Mild, moderate and severe steatosis were defined as >248, >268, and >280 dB/m respectively, and LSM above 7.0 kPa for fibrosis stage F ≥ 2, 8.7 kPa for F ≥ 3, and 10.3 kPa for F4 (cirrhosis). A total of 57 children (60% male) with median age of 13 years old were recruited. Fifty (87.7%) of the children are obese and 27 (54%) out of 50 are morbidly obese. Among 44 (77.2%) patients with steatosis, 40 (70.2%) had severe steatosis and 18 (40.9%) had developed liver fibrosis of stage 2 and above. Advanced fibrosis or cirrhosis was detected in 8 (18.2%) children with presence of steatosis. Twenty-three out of 57 (40.4%) was diagnosed with metabolic syndrome. Fibrosis is three times more likely to occur in the presence of metabolic syndrome (OR = 3.545, 95% CI: 1.135-11.075, = 0.026). Waist circumference is a significant predictor of fibrosis after multiple regression analysis. Obese children with metabolic syndrome are more likely to have advanced liver fibrosis compared to those without metabolic syndrome. Waist circumference predicts development of liver fibrosis.
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http://dx.doi.org/10.3389/fped.2019.00491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901954PMC
November 2019

Asian consensus recommendations on optimizing the diagnosis and initiation of treatment of hepatitis B virus infection in resource-limited settings.

J Viral Hepat 2020 05 23;27(5):466-475. Epub 2019 Dec 23.

Medical Affairs, Mylan Pharmaceuticals Private Limited, Bangalore, India.

Asia has an intermediate-to-high prevalence of and high morbidity and mortality from hepatitis B virus (HBV) infection. Optimization of diagnosis and initiation of treatment is one of the crucial strategies for lowering disease burden in this region. Therefore, a panel of 24 experts from 10 Asian countries convened, and reviewed the literature, to develop consensus guidance on diagnosis and initiation of treatment of HBV infection in resource-limited Asian settings. The panel proposed 11 recommendations related to diagnosis, pre-treatment assessment, and indications of therapy of HBV infection, and management of HBV-infected patients with co-infections. In resource-limited Asian settings, testing for hepatitis B surface antigen may be considered as the primary test for diagnosis of HBV infection. Pre-treatment assessments should include tests for complete blood count, liver and renal function, hepatitis B e-antigen (HBeAg), anti-HBe, HBV DNA, co-infection markers and assessment of severity of liver disease. Noninvasive tests such as AST-to-platelet ratio index, fibrosis score 4 or transient elastography may be used as alternatives to liver biopsy for assessing disease severity. Considering the high burden of HBV infection in Asia, the panel adopted an aggressive approach, and recommended initiation of antiviral therapy in all HBV-infected, compensated or decompensated cirrhotic individuals with detectable HBV DNA levels, regardless of HBeAg status or alanine transaminase levels. The panel also developed a simple algorithm for guiding the initiation of treatment in noncirrhotic, HBV-infected individuals. The recommendations proposed herein, may help guide clinicians, to optimize the diagnosis and improvise the treatment rates for HBV infection in Asia.
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http://dx.doi.org/10.1111/jvh.13244DOI Listing
May 2020

Hepatitis C elimination by 2030 in Malaysia: an achievable goal?

J Virus Erad 2019 Nov 4;5(4):253. Epub 2019 Nov 4.

Centre of Population Health, Department of Social and Preventative Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844403PMC
November 2019

Increased Coffee Intake Reduces Circulating HBV DNA and HBsAg Levels in HBeAg-Negative Infection: A Cohort Study.

Viruses 2019 09 1;11(9). Epub 2019 Sep 1.

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.

Coffee is hepatoprotective and potentially antiviral; however, its anti-hepatitis B virus (anti-HBV) property is not known in humans. This study investigated the influence of coffee drinking behaviour as well as clinical and biochemical profiles of hepatitis B e antigen (HBeAg) negative participants on circulating HBV DNA and hepatitis B surface antigen (HBsAg) levels at a 24-week interval. Exactly 114 chronically HBV-infected adult participants were enrolled from the University of Malaya Medical Centre (UMMC), Malaysia. A significant reduction of HBV DNA level was observed in those drinking three or more cups of coffee per day, with a median reduction of 523 IU/mL ( = 0.003). Reduction of HBsAg level was observed in those drinking two cups per day, with a median reduction of 37 IU/mL ( < 0.001). Multivariate analysis showed that increased coffee intake ( = 0.015) and lower ALT level ( = 0.033) were the significant predictors for a lower HBV DNA level, whereas increased coffee intake ( = 0.002) and having a family history of HBV infection ( = 0.021) were the significant predictors for a lower HBsAg level. These data suggest that drinking three cups or more coffee per day reduces circulating HBV DNA and HBsAg levels.
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http://dx.doi.org/10.3390/v11090808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783832PMC
September 2019

A Stepwise Approach to a National Hepatitis C Screening Strategy in Malaysia to Meet the WHO 2030 Targets: Proposed Strategy, Coverage, and Costs.

Value Health Reg Issues 2019 May 25;18:112-120. Epub 2019 Mar 25.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, Scotland.

Background: In Malaysia, more than 330 000 individuals are estimated to be chronically infected with hepatitis C virus (HCV), but less than 2% have been treated to date.

Objectives: To estimate the required coverage and costs of a national screening strategy to inform the launch of an HCV elimination program.

Methods: We designed an HCV screening strategy based on a "stepwise" approach. This approach relied on targeting of people who inject drugs in the early years, with delayed onset of widespread general population screening. Annual coverage requirements and associated costs were estimated to ensure that the World Health Organization elimination treatment targets were met.

Results: In total, 6 million individuals would have to be screened between 2018 and 2030. Targeting of people who inject drugs in the early years would limit annual screening coverage to less than 1 million individuals from 2018 to 2026. General population screening would have to be launched by 2026. Total costs were estimated at MYR 222 million ($58 million). Proportional to coverage targets, 60% of program costs would fall from 2026 to 2030.

Conclusions: This exercise was one of the first attempts to conduct a detailed analysis of the required screening coverage and costs of a national HCV elimination strategy. These findings suggest that the stepwise approach could delay the onset of general population screening by more than 5 years after the program's launch. This delay would allow additional time to mobilize investments required for a successful general population screening program and also minimize program costs. This strategy prototype could inform the design of effective screening strategies in other countries.
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http://dx.doi.org/10.1016/j.vhri.2018.12.005DOI Listing
May 2019

Hepatitis Screening and Treatment Campaign in Malaysia-Validation of Low-cost Point of Care Screening Tests and Nucleic Acid Tests for Hepatitis B and C.

Euroasian J Hepatogastroenterol 2018 Jul-Dec;8(2):101-107. Epub 2019 Feb 1.

Hepatitis Free Pahang Society, Pahang Malaysia.

Background: Two major challenges in implementing budget-constrained Hepatitis screening and treatment campaign in Malaysia are the availability of low-cost point of care tests (POCT) and nucleic acid tests (NAT) for hepatitis C virus ribonucleic acid (HCV RNA) and hepatitis B virus dioxyribo nucleic acid (HBV DNA). We evaluated the performance of these tests in this study.

Methods: We conducted a cross-sectional study to evaluate the diagnostic performance of four POCT brands at 12 sites in Malaysia. We assessed the sensitivity and specificity of the POCTs for the detection of HBsAg and anti-HCV in a finger-stick capillary or venepuncture whole-blood samples compared with test results from lab-based enzyme immunoassay (EIA) or chemi-luminescence immunoassay (CLIA) assay as the reference standard. We also conducted a cross-sectional study on 30 to 139 serum specimen panel to evaluate the diagnostic performance of a low-cost in-house Applied BiosystemTaqMan real-time polymerase chain reaction (PCR) assay (ABS) for the detection of HCV RNA and HBV DNA, compare with Roche Cobas Ampliprep/TaqMan assay (COBAS).

Results: Between March and December 2017, we enroll 295 participants for the evaluation of POCT for HBsAg and another 307 participants for POCT anti-HCV evaluation. Three of the four POCT brands dropped out of evaluation early on account of sub-optimal sensitivity. The sensitivity of the remaining POCT for HBsAg was 95.2%and specificity 100%, while the POCT for anti-HCV has a sensitivity of 98.1% and specificity 100%.Hepatitis B virus dioxyribo nucleic acid and HCV RNA concentrations detected by the ABS were systematically higher than those measured by COBAS (mean bias +0.10 and +0.17 log10 IU/mL respectively). The 95% limits of agreement between the two assays are -1.28 to 1.47 log10 IU/mL for HBV DNA and -0.41 to 0.75 log10 IU/mL for HCV RNA.

Conclusion: We found adequate evidence for the diagnostic validity of a low-cost POCT for anti-HCV and HBsAg, as well as for an in-house nucleic acid tests (NAT), to provide support for their broader use in our Hepatitis screening and treatment campaign.

Abbreviations: ABS: Applied BiosystemTaqMan real-time PCR assay, CI: Confidence interval, CLD: Chronic liver disease, CLIA: Chemi-luminescence immunoassay, COBAS: Roche Cobas Ampliprep/ TaqMan assay, DAA: Direct Acting Anti-Viral drugs, EIA: Enzyme immunoassay, HBV: Hepatitis B virus, HCV: Hepatitis C virus, HFPM: Hepatitis Free Pahang Malaysia, LOA: Limits of agreement, LOD: Limit of detection, MOH: Ministry of Health, Malaysia, NAT: Nucleic Acid Tests, POCT: Point of Care Tests, SD: Standard deviation, WHO: World Health Organization Radzi AHM, Tan SS, Mohamed R, Jaya F, Senamjit K, Aun AC, Kutty GA, Wong HS, Abdullah R, Seman MR, Mahtab MA, Morad Z, Lim TO. Hepatitis Screening and Treatment Campaign in Malaysia-Validation of Low-cost Point of Care Screening Tests and Nucleic Acid Tests for Hepatitis B and C. Euroasian J Hepatogastroenterol, 2018;8(2):101-107.
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http://dx.doi.org/10.5005/jp-journals-10018-1273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395483PMC
February 2019

Sofosbuvir-velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial.

Lancet Gastroenterol Hepatol 2019 02 14;4(2):127-134. Epub 2018 Dec 14.

Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Treatment with combined sofosbuvir and velpatasvir has resulted in high sustained virological response rates in patients chronically infected with hepatitis C virus (HCV) with genotypes 1-6 in clinical trials and real-world settings, but its efficacy and safety has not been assessed in Asia, a region with diverse HCV genotypes.

Methods: In this single-arm, open-label, phase 3 trial, we recruited patients from 38 sites across China, Thailand, Vietnam, Singapore, and Malaysia, who were chronically infected with HCV genotypes 1-6, and were HCV treatment-naive or treatment-experienced, either without cirrhosis or with compensated cirrhosis. Patients self-administered a combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks. The primary efficacy endpoint was sustained virological response, defined as HCV RNA less than 15 IU/mL at 12 weeks after completion of treatment (SVR12), assessed in all patients who received at least one dose of study drug. The primary safety endpoint was the proportion of adverse events leading to premature discontinuation of study drug. This trial is registered with ClinicalTrials.gov, number NCT02671500, and is completed.

Findings: Between April 14, 2016, and June 30, 2017, 375 patients were enrolled in the study, of whom 374 completed the full treatment course and one discontinued treatment. Overall, 362 (97% [95% CI 94-98]) of 375 patients achieved SVR12. Among 42 patients with HCV genotype 3b, all of whom had baseline resistance-associated substitutions in NS5A, 25 (89% [95% CI 72-98]) of 28 patients without cirrhosis and seven (50% [23-77]) of 14 patients with cirrhosis achieved SVR12. The most common adverse events were upper respiratory tract infection (36 [10%] patients) and headache (18 [5%] patients). There were no discontinuations due to adverse events. Serious adverse events were reported in three (1%) patients, none of which was judged to be related to sofosbuvir-velpatasvir treatment.

Interpretation: Consistent with data from other phase 3 studies, single-tablet sofosbuvir-velpatasvir for 12 weeks is an efficacious and safe treatment for Asian patients with chronic HCV infection, but might have lower efficacy in those infected with HCV genotype 3b and with cirrhosis.

Funding: Gilead Sciences.
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http://dx.doi.org/10.1016/S2468-1253(18)30343-1DOI Listing
February 2019

Viral Persistence and Chronicity in Hepatitis C Virus Infection: Role of T-Cell Apoptosis, Senescence and Exhaustion.

Cells 2018 Oct 12;7(10). Epub 2018 Oct 12.

Division of Infection Biology and Medical Microbiology, Department of Life Sciences, Central University of Tamil Nadu (CUTN), Thiruvarur 610005, India.

Hepatitis C virus (HCV) represents a challenging global health threat to ~200 million infected individuals. Clinical data suggest that only ~10⁻15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence, which includes, but is not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here we discuss a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.
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http://dx.doi.org/10.3390/cells7100165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210370PMC
October 2018

Interleukin-6 gene variants are associated with reduced risk of chronicity in hepatitis B virus infection in a Malaysian population.

Biomed Rep 2018 Sep 9;9(3):213-220. Epub 2018 Jul 9.

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.

Interleukin-6 (IL-6) is a cytokine with a critical role in regulating the immune response to infectious disease. Studies have indicated that polymorphisms in the gene may be linked to hepatitis B virus (HBV) infection. The purpose of the present study was to examine the association among SNPs and haplotypes with HBV infection risk in a Malaysian population. A total of 1,246 Malaysian subjects with and without chronic hepatitis B were recruited for this study. Three polymorphisms (rs2069837, rs1800796 and rs2066992) were genotyped using a Sequenom MassARRAY platform. The results suggested that GC and CC genotypes of rs1800796 as well as GT and TT genotypes of rs2066992 were associated with protection against HBV infection (P<0.001). Furthermore, haplotypes GG and CT exhibited a significant association with protection against HBV (P=0.003 and =0.005, respectively); and haplotypes GG and CT exhibited a significant association with clearance of HBV infection (P=0.035 and =0.037, respectively). The present study indicates that two SNPs (rs1800796 and rs2066992) are associated with clearance of chronic HBV or protection against HBV infection at allelic, genotypic and haplotypic levels.
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http://dx.doi.org/10.3892/br.2018.1126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158402PMC
September 2018

Projections of the Healthcare Costs and Disease Burden due to Hepatitis C Infection under Different Treatment Policies in Malaysia, 2018-2040.

Appl Health Econ Health Policy 2018 12;16(6):847-857

Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Introduction: The World Health Organisation (WHO) has set ambitious goals to reduce the global disease burden associated with, and eventually eliminate, viral hepatitis.

Objective: To assist with achieving these goals and to inform the development of a national strategic plan for Malaysia, we estimated the long-term burden incurred by the care and management of patients with chronic hepatitis C virus (HCV) infection. We compared cumulative healthcare costs and disease burden under different treatment cascade scenarios.

Methods: We attached direct costs for the management/care of chronically HCV-infected patients to a previously developed clinical disease progression model. Under assumptions regarding disease stage-specific proportions of model-predicted HCV patients within care, annual numbers of patients initiated on antiviral treatment and distribution of treatments over stage, we projected the healthcare costs and disease burden [in disability-adjusted life-years (DALY)] in 2018-2040 under four treatment scenarios: (A) no treatment/baseline; (B) pre-2018 standard of care (pegylated interferon/ribavirin); (C) gradual scale-up in direct-acting antiviral (DAA) treatment uptake that does not meet the WHO 2030 treatment uptake target; (D) scale-up in DAA treatment uptake that meets the WHO 2030 target.

Results: Scenario D, while achieving the WHO 2030 target and averting 253,500 DALYs compared with the pre-2018 standard of care B, incurred the highest direct patient costs over the period 2018-2030: US$890 million (95% uncertainty interval 653-1271). When including screening programme costs, the total cost was estimated at US$952 million, which was 12% higher than the estimated total cost of scenario C.

Conclusions: The scale-up to meet the WHO 2030 target may be achievable with appropriately high governmental commitment to the expansion of HCV screening to bring sufficient undiagnosed chronically infected patients into the treatment pathway.
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http://dx.doi.org/10.1007/s40258-018-0425-3DOI Listing
December 2018

Findings from a large Asian chronic hepatitis C real-life study.

J Viral Hepat 2018 12 27;25(12):1533-1542. Epub 2018 Sep 27.

Hospital Ampang, Selangor, Malaysia.

There is a paucity of information on chronic hepatitis C (CHC) patients treated with direct antiviral agents (DAAs) in Asia. We invited Asia-Pacific physicians to collate databases of patients enrolled for CHC treatment, recording baseline clinical, virologic and biochemical characteristics, sustained virologic response at week 12 (SVR12) and virologic failure. SVR12 outcome was based on intention to treat (ITT). Multivariate analysis was used to assess independent risk factors for SVR12 using SPSS version 20. A total of 2171 patients from India (n = 977), Myanmar (n = 552), Pakistan (n = 406), Thailand (n = 139), Singapore (n = 72) and Malaysia (n = 25) were collected. At baseline, mean age was 49 years, 50.2% were males, and 41.8% had cirrhosis. Overall, SVR12 was 89.5% and by genotype (GT) based on ITT and treatment completion, respectively, was 91% and 92% for GT1, 100% and 100% for GT2, 91% and 97% for GT3, 64% and 95% for GT4, 87% and 87% for GT6 and 79% and 91% for GT untested. Patients with cirrhosis had SVR12 of 85% vs 93% for noncirrhosis (P < 0.001) (RR 2.1, 95% CI 1.4-3.1, P = 0.0002). Patients with GT1 and GT3 treated with sofosbuvir/ribavirin (SR) had 88% and 89% SVR12, respectively, but those GT6 treated with sofosbuvir/ledipasvir (SL) had only 77.6% SVR12. Multivariate analysis showed absence of cirrhosis was associated with higher SVR12 (OR 2.0, 95% CI 1.3-3.1, P = 0.002). In conclusion, patients with GT1 and GT3 with/without cirrhosis had surprisingly high efficacy using SR, suggesting that Asians may respond better to some DAAs. However, poor GT6 response to SL suggests this regimen is suboptimal for this genotype.
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http://dx.doi.org/10.1111/jvh.12989DOI Listing
December 2018

Hepatocellular Carcinoma in Malaysia and Its Changing Trend.

Euroasian J Hepatogastroenterol 2018 Jan-Jun;8(1):54-56. Epub 2018 May 1.

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Hepatocellular carcinoma (HCC) is one of the leading causes of death globally. In Malaysia liver cancer is the eighth most common cause of cancer for both gender and fifth most common cause of cancer for males. Liver cancer is a cause of premature death in Malaysia: The trend from 1990 to 2010 was observed upward. Since 1990, the annual years of life lost (YLLs) from liver cancer have increased by 31.5%. Older persons are at higher risk and there is male predominance observed. Curative surgical resection, liver transplantation, and supportive symptomatic care, including percutaneous ethanol injection and radiofrequency ablation (RFA), and noncurative transarterial chemoembolization (TACE) are among available treatment facilities. Yet the survival rate is very poor as majority of patients present at very advanced stage. Hepatitis B virus (HBV) remained the leading cause of HCC in Malaysia. Several studies showed cryptogenic causes, which are mainly nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) among the predominant causes of HCC in Malaysia than hepatitis C virus (HCV), alcohol, or any other reason. This mainly correlates with the increasing incidence of diabetes and obesity in Malaysia. Raihan R, Azzeri A, Shabaruddin FH, Mohamed R. Hepatocellular Carcinoma in Malaysia and Its Changing Trend. Euroasian J Hepato-Gastroenterol 2018;8(1):54-56.
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http://dx.doi.org/10.5005/jp-journals-10018-1259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024046PMC
May 2018

Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161TCR iVα7.2 Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection.

Front Immunol 2018 19;9:472. Epub 2018 Mar 19.

Center of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia.

Mucosal-associated invariant T (MAIT) cells, defined as CD161TCR iVα7.2 T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3CD161TCR iVα7.2 MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2 CD161 MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4 T cells and MAIT cells and with CD57 on CD8 T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2 MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.
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http://dx.doi.org/10.3389/fimmu.2018.00472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868455PMC
April 2019

Novel Genetic Variants of Hepatitis B Virus in Fulminant Hepatitis.

J Pathog 2017 19;2017:1231204. Epub 2017 Dec 19.

Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%), K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%). We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH.
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http://dx.doi.org/10.1155/2017/1231204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749291PMC
December 2017

Chronic Viral Hepatitis in Malaysia: "Where are we now?"

Euroasian J Hepatogastroenterol 2017 Jan-Jun;7(1):65-67. Epub 2017 May 5.

Department of Medicine, Hospital Ampang, Ministry of Health, Kuala Lumpur, Malaysia.

Malaysia is a country where an estimated 1 million people are chronically infected with hepatitis B virus (HBV) and an estimated 2.5% of the adult population are positive for antibody to hepatitis C virus (HCV). Effective nationwide vaccine coverage seems to be a highly effective measure to prevent new HBV infection. Treatment of HCV infection is also a regular practice in Malaysia. These measures highlight the possibility to reach the World Health Organization elimination target by 2030. To achieve this target, the Health Ministry and other nongovernmental organizations, such as My Commitment to Cure (MyC2C) are working together to develop a strategic road map to reach the global elimination target in Malaysia by 2030. Raihan R, Mohamed R, Hasan MRA, Rosaida MS. Chronic Viral Hepatitis in Malaysia: "Where are we now?" Euroasian J Hepato-Gastroenterol 2017;7(1):65-67.
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http://dx.doi.org/10.5005/jp-journals-10018-1214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663777PMC
May 2017
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