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  1. 2018 Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C in Chronic Kidney Disease Guideline Implementation: Asia Summit Conference Report
    Li PK, Bavanandan S, Mohamed R, Szeto CC, Wong VW, Chow KM, et al.
    Kidney Int Rep, 2020 Aug;5(8):1129-1138.
    PMID: 32775812 DOI: 10.1016/j.ekir.2020.05.001
    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.
  2. Fulltext Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
    Martin P, Awan AA, Berenguer MC, Bruchfeld A, Fabrizi F, Goldberg DS, et al.
    Kidney Int, 2022 Dec;102(6):1228-1237.
    PMID: 36411019 DOI: 10.1016/j.kint.2022.07.012
    Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.
  3. The Role of Isocitrate Lyase (ICL1) in the Metabolic Adaptation of Candida albicans Biofilms
    Ishola OA, Ting SY, Tabana YM, Ahmed MA, Yunus MA, Mohamed R, et al.
    Jundishapur J Microbiol, 2016 Sep;9(9):e38031.
    PMID: 27800147
    A major characteristic of Candida biofilm cells that differentiates them from free-floating cells is their high tolerance to antifungal drugs. This high resistance is attributed to particular biofilm properties, including the accumulation of extrapolymeric substances, morphogenetic switching, and metabolic flexibility.
  4. Reduction of microbial risk associated with greywater by disinfection processes for irrigation
    Al-Gheethi AA, Radin Mohamed RM, Efaq AN, Amir Hashim MK
    J Water Health, 2016 Jun;14(3):379-98.
    PMID: 27280605 DOI: 10.2166/wh.2015.220
    Greywater is one of the most important alternative sources for irrigation in arid and semi-arid countries. However, the health risk associated with the microbial contents of these waters limits their utilization. Many techniques have been developed and used to generate a high microbiological quality of greywater. The main problem in the treatment of greywater lies in the nature of pathogenic bacteria in terms of their ability to survive during/after the treatment process. The present review focused on the health risk associated with the presence of pathogenic bacteria in greywater and the treatment technologies used for the disinfection processes.
  5. Bioaugmentation process of secondary effluents for reduction of pathogens, heavy metals and antibiotics
    Al-Gheethi AA, Mohamed RM, Efaq AN, Norli I, Abd Halid A, Amir HK, et al.
    J Water Health, 2016 Oct;14(5):780-795.
    PMID: 27740544
    The study probed into reducing faecal indicators and pathogenic bacteria, heavy metals and β-lactam antibiotics, from four types of secondary effluents by bioaugmentation process, which was conducted with Bacillus subtilis strain at 45 °C. As a result, faecal indicators and pathogenic bacteria were reduced due to the effect of thermal treatment process (45 °C), while the removal of heavy metals and β-lactam antibiotics was performed through the functions of bioaccumulation and biodegradation processes of B. subtilis. Faecal coliform met the guidelines outlined by WHO and US EPA standards after 4 and 16 days, respectively. Salmonella spp. and Staphylococcus aureus were reduced to below the detection limits without renewed growth in the final effluents determined by using a culture-based method. Furthermore, 13.5% and 56.1% of cephalexin had been removed, respectively, from secondary effluents containing 1 g of cephalexin L(-1) (secondary effluent 3), as well as 1 g of cephalexin L(-1) and 10 mg of Ni(2+) L(-1) (secondary effluent 4) after 16 days. The treatment process, eventually, successfully removed 96.6% and 66.3% of Ni(2+) ions from the secondary effluents containing 10 mg of Ni(2+) L(-1) (secondary effluent 2) and E4, respectively. The bioaugmentation process improved the quality of secondary effluents.
  6. A review of potential factors contributing to epidemic cholera in Yemen
    Al-Gheethi A, Noman E, Jeremiah David B, Mohamed R, Abdullah AH, Nagapan S, et al.
    J Water Health, 2018 Oct;16(5):667-680.
    PMID: 30285950 DOI: 10.2166/wh.2018.113
    The menace of cholera epidemic occurrence in Yemen was reported in early 2017. Recent reports revealed that an estimated 500,000 people are infected with cholera whereas 2,000 deaths have been reported in Yemen. Cholera is transmitted through contaminated water and food. Yemen is the least developed country among the Middle East countries in terms of wastewater and solid waste management. The population of Yemen is about 24.5 million and generates about 70-100 million m3 of sewage. An estimated 7% of the population has sewerage systems. It has been revealed that 31.2 million m3 of untreated sewage is used for irrigation purposes especially for vegetables and Khat trees. In addition, more than 70% of the population in Yemen has no potable water. They depend on water wells as a water source which are located close to sewage disposal sites. The present review focuses on the current status of water, wastewater as well as solid waste management in Yemen and their roles in the outbreak of cholera. Future prospects for waste management have been proposed.
  7. Influence of pathogenic bacterial activity on growth of Scenedesmus sp. and removal of nutrients from public market wastewater
    Al-Gheethi AA, Mohamed RM, Jais NM, Efaq AN, Abd Halid A, Wurochekke AA, et al.
    J Water Health, 2017 Oct;15(5):741-756.
    PMID: 29040077 DOI: 10.2166/wh.2017.080
    The present study aims to investigate the influence of Staphylococcus aureus, Escherichia coli and Enterococcus faecalis in public market wastewater on the removal of nutrients in terms of ammonium (NH4-) and orthophosphate (PO43) using Scenedesmus sp. The removal rates of NH4- and orthophosphate PO43- and batch kinetic coefficient of Scenedesmus sp. were investigated. The phycoremediation process was carried out at ambient temperature for 6 days. The results revealed that the pathogenic bacteria exhibited survival potential in the presence of microalgae but they were reduced by 3-4 log at the end of the treatment process. The specific removal rates of NH4- and PO43- have a strong relationship with initial concentration in the public market wastewater (R2 = 0.86 and 0.80, respectively). The kinetic coefficient of NH4- removal by Scenedesmus sp. was determined as k = 4.28 mg NH4- 1 log10 cell mL-1 d-1 and km = 52.01 mg L-1 (R2 = 0.94) while the coefficient of PO43- removal was noted as k = 1.09 mg NH4- 1 log10 cell mL-1 d-1 and km = 85.56 mg L-1 (R2 = 0.92). It can be concluded that Scenedesmus sp. has high competition from indigenous bacteria in the public market wastewater to remove nutrients, with a higher coefficient of removal of NH4- than PO43.
  8. Household greywater treatment methods using natural materials and their hybrid system
    Wurochekke AA, Mohamed RM, Al-Gheethi AA, Atiku H, Amir HM, Matias-Peralta HM
    J Water Health, 2016 Dec;14(6):914-928.
    PMID: 27959870
    Discharge of household greywater into water bodies can lead to an increase in contamination levels in terms of the reduction in dissolved oxygen resources and rapid bacterial growth. Therefore, the quality of greywater has to be improved before the disposal process. The present review aimed to present a hybrid treatment system for the greywater generated from households. The hybrid system comprised a primary stage (a natural filtration unit) with a bioreactor system as the secondary treatment combined with microalgae for greywater treatment, as well as the natural flocculation process. The review discussed the efficiency of each stage in the removal of elements and nutrients. The hybrid system reviewed here represented an effective solution for the remediation of household greywater.
  9. Hepatitis C elimination by 2030 in Malaysia: an achievable goal?
    Mohamed R, Shabaruddin FH, Azzeri A, McDonald SA, Dahlui M
    Journal of virus eradication, 2019 Nov 04;5(4):253.
    PMID: 31754450
  10. Asian consensus recommendations on optimizing the diagnosis and initiation of treatment of hepatitis B virus infection in resource-limited settings
    Gane EJ, Charlton MR, Mohamed R, Sollano JD, Tun KS, Pham TTT, et al.
    J Viral Hepat, 2020 05;27(5):466-475.
    PMID: 31785182 DOI: 10.1111/jvh.13244
    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.
  11. Fatty liver is associated with advanced fibrosis but does not predict adverse outcomes in patients with chronic hepatitis B
    Wong SW, Chan WK, Mohamed R
    J Viral Hepat, 2020 12;27(12):1297-1305.
    PMID: 32668489 DOI: 10.1111/jvh.13361
    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.
  12. Findings from a large Asian chronic hepatitis C real-life study
    Lim SG, Phyo WW, Shah SR, Win KM, Hamid S, Piratvisuth T, et al.
    J Viral Hepat, 2018 12;25(12):1533-1542.
    PMID: 30141214 DOI: 10.1111/jvh.12989
    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.
  13. Contextual and individual factors associated with knowledge, awareness and attitude on liver diseases: A large-scale Asian study
    Lee MH, Ahn SH, Chan HLY, Choudhry A, Alvani Gani R, Mohamed R, et al.
    J Viral Hepat, 2022 02;29(2):156-170.
    PMID: 34817896 DOI: 10.1111/jvh.13636
    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.
  14. Historical epidemiology of hepatitis C virus in select countries-volume 4
    Maaroufi A, Vince A, Himatt SM, Mohamed R, Fung J, Opare-Sem O, et al.
    J Viral Hepat, 2017 10;24 Suppl 2:8-24.
    PMID: 29105285 DOI: 10.1111/jvh.12762
    Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.
  15. The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4
    Chan HLY, Chen CJ, Omede O, Al Qamish J, Al Naamani K, Bane A, et al.
    J Viral Hepat, 2017 10;24 Suppl 2:25-43.
    PMID: 29105283 DOI: 10.1111/jvh.12760
    Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.
  16. Strategies to manage hepatitis C virus infection disease burden-Volume 4
    Chen DS, Hamoudi W, Mustapha B, Layden J, Nersesov A, Reic T, et al.
    J Viral Hepat, 2017 10;24 Suppl 2:44-63.
    PMID: 29105286 DOI: 10.1111/jvh.12759
    The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.
  17. Comparative Evaluation of Surface Detail Reproduction and Dimensional Stability of Poly Ether, Vinyl Siloxane, and Vinyl Siloxane Ether Impression Materials: An In vitro Study
    Rose S, Aravindakshan S, Mohamed Usman JA, Mohamed R, Menon S, Shafiullah RS, et al.
    J Pharm Bioallied Sci, 2021 Jun;13(Suppl 1):S851-S856.
    PMID: 34447214 DOI: 10.4103/jpbs.JPBS_819_20
    Introduction: Impression making is an integral part of prosthetic dentistry. Development of material science has allowed integrating qualities of hydrophilic polyether and hydrophobic polyvinyl siloxane into a newer hybrid material, vinyl polysiloxane (VPS) ether. This study was aimed to compare the VPS ether with the polyether and polyvinyl siloxane in terms of accuracy and dimensional stability.

    Materials and Methods: Stainless steel dies with the American Dental Association specification 19 were made. Die has three horizontal and two vertical lines which are used for taking the impression. Two cross-points at the junction of the vertical lines with line 2 were marked as x and x' and served as beginning and end points of measurements for dimensional accuracy. Accuracy was evaluated 30 min after making each impression. If at least two of the three horizontal lines were reproduced continuously between cross-points, this impression was considered satisfactory. The specimens are poured with Type IV gypsum product and allowed to set completely for 24 h. Then, dimensional stability was measured in the model by measuring the distance between the two lines and comparing the distance with the measurement of line on metal die, which was used to make the impression.

    Results: The mean value obtained for light- and medium-bodied VPS ether was 0.05370 and 0.05330 and for light and medium-bodied polyvinyl siloxane was 0.06370 and 0.07150, respectively. The mean value for polyether monophase was 0.06430. Two-way ANOVA and post hoc test showed statistical significance.

    Conclusion: The newer VPS ether material showed good surface detail reproduction and dimensional stability when compared with polyvinyl siloxane and polyether.

  18. Fulltext Dermatopathology of Orf Virus (Malaysian Isolates) in Mice Experimentally Inoculated at Different Sites with and without Dexamethasone Administration
    Bala JA, Balakrishnan KN, Abdullah AA, Kimmy T, Abba Y, Bin Mohamed R, et al.
    J Pathog, 2018;2018:9207576.
    PMID: 30155311 DOI: 10.1155/2018/9207576
    Orf is a clinical manifestation of parapoxvirus infection often fatal in goats and sheep especially when they are under stress or influenced by unfavorable environment. This study investigated the pathogenicity of two Orf virus isolates (ORFV UPM1/14 and UPM2/14) and host response in mouse model by using different inoculation sites with/without prior exposure to dexamethasone. Treatments with dexamethasone served as an immunosuppressant that may mimic stress situation in affected animals. Groups of five mice were given intradermal injection of 0.2 mL of tissue culture infective dose 50 (TCID50) of UPM1/14 (Group 1) and UPM2/14 (Group 2) at the dorsum (Group 1A; Group 2A), ear pinna (Group 1B; Group 2B), and labial commissure (Group 1C; Group 2C). An inoculum 0.2 mL of UPM1/14 was administered to animals treated with dexamethasone (n=5; 5 mg/kg/day intraperitoneally) and nondexamethasone (n=5) groups at the dorsum, ear pinna, and labial commissure. No significant difference (p>0.05) was observed in the mean lesion scores among the groups of different inoculation sites or between dexamethasone-treated and nontreated groups. However, there was a significant difference (p<0.05) in the mean stratum thickness of affected skin following inoculation with UPM2/14 isolate at the ear pinna and labial commissure. Histopathology examination revealed keratosis, acanthosis, and ballooning degeneration in the skin of affected mice. Orf virus DNA was detected in the skin samples by targeting F1L and B2L virus-specific genes in polymerase chain reaction (PCR) assay. Intradermal inoculation with UPM1/14 or UPM2/14 isolate produced a mild skin lesion in mice, and there was no significant difference in orf disease manifestation despite variation of inoculation sites. Similarly, short-term dexamethasone administration gave no adverse effects on pathogenicity of orf virus isolates.
  19. Fulltext Novel Genetic Variants of Hepatitis B Virus in Fulminant Hepatitis
    Chook JB, Ngeow YF, Tee KK, Peh SC, Mohamed R
    J Pathog, 2017;2017:1231204.
    PMID: 29410920 DOI: 10.1155/2017/1231204
    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.
  20. Combined use of wild-type HBV precore and high serum iron marker as a potential tool for the prediction of cirrhosis in chronic hepatitis B infection
    Chook JB, Ngeow YF, Yap SF, Tan TC, Mohamed R
    J Med Virol, 2011 Apr;83(4):594-601.
    PMID: 21328372 DOI: 10.1002/jmv.22016
    Hepatitis B virus (HBV) and high liver iron deposits have both been associated with the development of cirrhosis. Among HBV factors, genotype and mutations in the basal core promoter (BCP) and precore regions have been most frequently studied but the evidence for a positive association with cirrhosis has been inconsistent. In this study, sera from persons with chronic HBV infection with and without cirrhosis were used for whole HBV genome analysis and for the estimation of serum iron marker (serum iron or ferritin) levels. Single codon analysis showed that the precore wild-type, TGG (nt 1,895-1,897), gave the highest accuracy (77.5%) for the identification of cirrhosis compared to other codons. When TGG was analyzed together with the precore start codon wild-type, ATG (nt 1,814-1,816), the accuracy was improved to 80.0% (odds ratio=35.29; 95% confidence interval=3.87-321.93; Phi=0.629; P<0.001). When the serum iron marker was included for analysis, it was clear that a combination of a precore wild-type and high serum iron marker gave a better accuracy (90.0%) (odds ratio=107.67; 95% confidence interval=10.21-1,135.59; Phi=0.804; P<0.001) for the identification of cirrhosis than either biomarker alone. It appeared that a combined use of both these biomarkers might help to predict the development of cirrhosis in a person with chronic HBV infection, but longitudinal studies are required to test this hypothesis.
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