Displaying publications 1 - 20 of 198 in total

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  1. Zeti AM, Shamsir MS, Tajul-Arifin K, Merican AF, Mohamed R, Nathan S, et al.
    PLoS Comput Biol, 2009 Aug;5(8):e1000457.
    PMID: 19714208 DOI: 10.1371/journal.pcbi.1000457
  2. Zangrillo A, Lomivorotov VV, Pasyuga VV, Belletti A, Gazivoda G, Monaco F, et al.
    PMID: 35168907 DOI: 10.1053/j.jvca.2022.01.001
    OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG).

    DESIGN: A post hoc analysis of a randomized trial.

    SETTING: Cardiac surgical operating rooms.

    PARTICIPANTS: Patients undergoing elective, isolated CABG.

    INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes.

    MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03).

    CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

  3. Zainudin BH, Salleh S, Mohamed R, Yap KC, Muhamad H
    Food Chem, 2015 Apr 1;172:585-95.
    PMID: 25442595 DOI: 10.1016/j.foodchem.2014.09.123
    An efficient and rapid method for the analysis of pesticide residues in cocoa beans using gas and liquid chromatography-tandem mass spectrometry was developed, validated and applied to imported and domestic cocoa beans samples collected over 2 years from smallholders and Malaysian ports. The method was based on solvent extraction method and covers 26 pesticides (insecticides, fungicides, and herbicides) of different chemical classes. The recoveries for all pesticides at 10 and 50 μg/kg were in the range of 70-120% with relative standard deviations of less than 20%. Good selectivity and sensitivity were obtained with method limit of quantification of 10 μg/kg. The expanded uncertainty measurements were in the range of 4-25%. Finally, the proposed method was successfully applied for the routine analysis of pesticide residues in cocoa beans via a monitoring study where 10% of them was found positive for chlorpyrifos, ametryn and metalaxyl.
  4. Zainudin BH, Salleh S, Yaakob AS, Mohamed R
    Food Chem, 2021 Aug 06;368:130778.
    PMID: 34391100 DOI: 10.1016/j.foodchem.2021.130778
    Multiresidue quantitative and qualitative screening method for the analysis of pesticide residues in dried cocoa beans was validated and applied to imported and domestic cocoa beans samples. The quantitative method comprises of 15 pesticides while the screening method covers 110 pesticides of different chemical classes. The method was based on modified QuEChERS (Quick Easy Cheap Efficient Rugged Safe) extraction and detection using triple quadrupole (QQQ-MS) and ion mobility quadrupole time of flight mass spectrometry (IMS-QTOF). The method was quantitatively validated in terms of linearity, limit of quantification (LOQ), specificity, selectivity, accuracy, and precision. On the other hand, screening detection limits were established for 110 pesticides. Finally, the optimized strategy was successfully applied for the routine analysis of pesticide residues in 137 cocoa bean samples and 32% of the total samples were found positive for ametryn, chlorpyrifos, isoprocarb, and metalaxyl.
  5. Zain SM, Mohamed Z, Mohamed R
    J Gastroenterol Hepatol, 2015 Jan;30(1):21-7.
    PMID: 25167786 DOI: 10.1111/jgh.12714
    BACKGROUND AND AIM: Although studies have suggested that rs780094, a common variant in the glucokinase regulatory (GCKR) gene to be associated with type 2 diabetes, obesity, and their related traits, the genetic basis of the association between GCKR rs780094 and nonalcoholic fatty liver disease (NAFLD) is still being examined. This meta-analysis was performed to evaluate the effect strength caused by GCKR rs780094 on NAFLD.
    METHODS: We searched Medline, PubMed, Scopus, and Embase for relevant articles published up to April 2014. Data were extracted, and summary estimates of the association between GCKR rs780094 and NAFLD were examined. Heterogeneity and publication bias were also examined.
    RESULTS: This meta-analysis incorporated a total of 2091 NAFLD cases and 3003 controls from five studies. Overall, the pooled result indicated that the GCKR rs780094 was significantly associated with increased risk of NAFLD (additive: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.14-1.36, P 
  6. Zain SM, Mohamed R, Cooper DN, Razali R, Rampal S, Mahadeva S, et al.
    PLoS One, 2014;9(4):e95604.
    PMID: 24743702 DOI: 10.1371/journal.pone.0095604
    Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD) develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC). To investigate the molecular basis of disease progression, we performed a genome-wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD [10 simple steatosis and 39 non-alcoholic steatohepatitis (NASH)] and 49 matched controls using high-density comparative genomic hybridization (CGH) microarrays. A total of 11 CNVs were found to be unique to individuals with simple steatosis, whilst 22 were common between simple steatosis and NASH, and 224 were unique to NASH. We postulated that these CNVs could be involved in the pathogenesis of NAFLD progression. After stringent filtering, we identified four rare and/or novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs, located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (XPO4) and phosphodiesterase 1B (PDE1B) genes which are already known to be involved in the etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at these four CNV loci with genes already known to be associated with NAFLD yielded a set of genes associated with shared biological processes including cell death, the key process involved in 'second hit' hepatic injury. To our knowledge, this pilot study is the first to provide CNV information of potential relevance to the NAFLD spectrum. These data could prove invaluable in predicting patients at risk of developing NAFLD and more importantly, those who will subsequently progress to NASH.
  7. Zain SM, Mohamed Z, Mahadeva S, Rampal S, Basu RC, Cheah PL, et al.
    PLoS One, 2013;8(3):e58538.
    PMID: 23484035 DOI: 10.1371/journal.pone.0058538
    Angiotensin II type 1 receptor (AGTR1) has been reported to play a fibrogenic role in non-alcoholic fatty liver disease (NAFLD). In this study, five variants of the AGTR1 gene (rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were examined for their association with susceptibility to NAFLD. Subjects made up of 144 biopsy-proven NAFLD patients and 198 controls were genotyped using TaqMan assays. The liver biopsy specimens were histologically graded and scored according to the method of Brunt. Single locus analysis in pooled subjects revealed no association between each of the five variants with susceptibility to NAFLD. In the Indian ethnic group, the rs2276736, rs3772630 and rs3772627 appear to be protective against NAFLD (p = 0.010, p = 0.016 and p = 0.026, respectively). Haplotype ACGCA is shown to be protective against NAFLD for the Indian ethnic subgroup (p = 0.03). Gene-gene interaction between the AGTR1 gene and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, which we previously reported as associated with NAFLD in this sample, showed a strong interaction between AGTR1 (rs3772627), AGTRI (rs3772630) and PNPLA3 (rs738409) polymorphisms on NAFLD susceptibility (p = 0.007). Further analysis of the NAFLD patients revealed that the G allele of the AGTR1 rs3772622 is associated with increased fibrosis score (p = 0.003). This is the first study that replicates an association between AGTR1 polymorphism and NAFLD, with further details in histological features of NAFLD. There is lack of evidence to suggest an association between any of the five variants of the AGTR1 gene and NAFLD in the Malays and Chinese. In the Indians, the rs2276736, rs3772630 and rs3772627 appear to protect against NAFLD. We report novel findings of an association between the G allele of the rs3772622 with occurrence of fibrosis and of the gene-gene interaction between AGTR1gene and the much-studied PNPLA3 gene.
  8. Zain SM, Mohamed Z, Mahadeva S, Cheah PL, Rampal S, Chin KF, et al.
    J Gastroenterol Hepatol, 2013 May;28(5):873-9.
    PMID: 23278404 DOI: 10.1111/jgh.12104
    Genetic polymorphism has been implicated as a factor for the occurrence of non-alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD.
  9. Zain SM, Mohamed Z, Pirmohamed M, Tan HL, Alshawsh MA, Mahadeva S, et al.
    Sci Rep, 2015 Aug 21;5:13306.
    PMID: 26293807 DOI: 10.1038/srep13306
    A recent genome-wide copy number (CNV) scan identified a 13q12.11 duplication in the exportin-4 (XPO4) gene to be associated with non-alcoholic steatohepatitis (NASH). We sought to confirm the finding in a larger cohort and to assess the serum XPO4 pattern in a broad spectrum of non-alcoholic fatty liver disease (NAFLD) cases. We analysed 249 NAFLD patients and 232 matched controls using TaqMan assay and serum XPO4 was measured. Copy number distribution was as follows: copy number neutral (NAFLD: 53.8%, controls: 68.6%), copy number losses (NAFLD: 13.3%, controls: 12.9%), copy number gains (NAFLD: 32.9%, controls: 18.5%). CNV gain was significantly associated with a greater risk of NAFLD (adjusted OR 2.22, 95% CI 1.42-3.46, P = 0.0004) and NASH (adjusted OR 2.33, 95% CI 1.47-3.68, P = 0.0003). Interestingly, subjects carrying extra copy number showed significantly higher serum ALT and triglyceride (P 
  10. Zain SM, Mohamed R, Mahadeva S, Cheah PL, Rampal S, Basu RC, et al.
    Hum Genet, 2012 Jul;131(7):1145-52.
    PMID: 22258181 DOI: 10.1007/s00439-012-1141-y
    The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12-3.37, p = 0.018; OR 3.51, 95% CI 1.69-7.26, p = 0.001 and OR 2.05, 95% CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurrence of fibrosis in patients with NAFLD.
  11. Zain SM, Tan HL, Mohamed Z, Chan WK, Mahadeva S, Basu RC, et al.
    JGH Open, 2020 Dec;4(6):1155-1161.
    PMID: 33319051 DOI: 10.1002/jgh3.12414
    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 

  12. Zain SM, Pung YF, Mohamed R
    J Diabetes Metab Disord, 2023 Jun;22(1):237-243.
    PMID: 37255815 DOI: 10.1007/s40200-022-01119-8
    BACKGROUND: Elevated circulating vaspin levels is linked with type 2 diabetes mellitus (T2DM) and obesity. The genetic basis of the association between vaspin rs2236242 and T2DM and obesity is still being investigated. We executed a meta-analysis to evaluate the magnitude of effect caused by vaspin rs2236242 on T2DM and obesity.

    METHODS: We searched Pubmed, Embase, MEDLINE, Scopus, Web of Science, and Google Scholar for relevant articles published up to 19 February 2022. Data were extracted and summary estimates of the association between vaspin rs2236242 and T2DM and obesity were assessed. Odds ratios (ORs) and confidence intervals (CIs) were used to measure the effect.

    RESULTS: This meta-analysis included 2206 cases and 2715 controls in the T2DM cohort, meanwhile 271 cases and 444 controls in the obesity cohort. The pooled estimates revealed no link between vaspin rs2236242 and T2DM, but allele-A was significantly higher in the controls of the obesity cohort, showing that this single nucleotide polymorphism (SNP) has a reduced obesity risk effect. Sensitivity analysis revealed no studies that would modify the estimates or the heterogeneity. Begg and Mazumdar's and Egger's tests indicated no substantial publication bias.

    CONCLUSION: Our meta-analysis provides evidence of significant association between vaspin rs2236242 and reduced risk of obesity but not T2DM.

    SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-022-01119-8.

  13. Yunus MA, Ramli MM, Osman NH, Mohamed R
    Arch Immunol Ther Exp (Warsz), 2021 Jul 29;69(1):20.
    PMID: 34327598 DOI: 10.1007/s00005-021-00625-6
    Sole nanomaterials or nanomaterials bound to specific biomolecules have been proposed to regulate the immune system. These materials have now emerged as new tools for eliciting immune-based therapies to treat various cancers. Graphene, graphene oxide (GO) and reduced GO (rGO) are the latest nanomaterials among other carbon nanotubes that have attracted wide interest among medical industry players due to their extraordinary properties, inert-state, non-toxic and stable dispersion in a various solvent. Currently, GO and rGO are utilized in various biomedical application including cancer immunotherapy. This review will highlight studies that have been carried out in elucidating the stimulation of GO and rGO on selected innate and adaptive immune cells and their effect on cancer progression to shed some insights for researchers in the development of various GO- and rGO-based immune therapies against various cancers.
  14. 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.
  15. Wong XZ, Gan CC, Mohamed R, Yahya R, Ganapathy S, Tan SS, et al.
    BMC Nephrol, 2020 11 13;21(1):480.
    PMID: 33187498 DOI: 10.1186/s12882-020-02154-4
    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  3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p 

  16. Wong XZ, Amirah A, Gan CC, Fatiha S, Maznah D, Yahya R, et al.
    Nephrology (Carlton), 2021 May;26(5):463-470.
    PMID: 33580732 DOI: 10.1111/nep.13862
    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 

  17. Wong SW, Ting YW, Yong YK, Tan HY, Barathan M, Riazalhosseini B, et al.
    Scand J Clin Lab Invest, 2021 Apr;81(2):147-159.
    PMID: 33528280 DOI: 10.1080/00365513.2021.1876245
    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.
  18. 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.
  19. Wickramatilake CM, Mohideen MR, Pathirana C
    Ann Endocrinol (Paris), 2015 Jul;76(3):260-3.
    PMID: 26142486 DOI: 10.1016/j.ando.2015.04.008
    OBJECTIVE: There is limited data on the assessment of relationship between sex hormones, metabolic syndrome (MS) and inflammation. Therefore, our objective was to examine the relationship between metabolic syndrome, testosterone and inflammation.
    PATIENTS AND METHODS: It was a cross-sectional study which included 309 subjects in the age range of 30-70years. Blood was analyzed for plasma glucose, serum lipids, total testosterone (TT) and high-sensitivity C-reactive protein (hs-CRP).
    RESULTS: There were 153 patients with metabolic syndrome and 156 without MS according to modified NCEP guidelines. Age, BMI, obesity, dyslipidaemia, smoking (OR=2.35, CI=1.35-4.09), LDL-Ch, low TT (OR=0.76, CI=0.38-1.52) and elevated hs-CRP (OR=1.56, CI=0.87-2.80) were significant independent predictors of MS (all P<0.05).
    CONCLUSIONS: The low testosterone and high hs-CRP levels are independent predictors of metabolic syndrome.
    KEYWORDS: Hommes; Inflammation; Men; Metabolic syndrome; Syndrome métabolique; Testosterone; Testostérone
  20. Wei L, Lim SG, Xie Q, Văn KN, Piratvisuth T, Huang Y, et al.
    Lancet Gastroenterol Hepatol, 2019 02;4(2):127-134.
    PMID: 30555048 DOI: 10.1016/S2468-1253(18)30343-1
    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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