Validation of genetic variants associated with metabolic dysfunctionassociated fatty liver disease in an ethnic Chinese population

BACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To study the association of single nucleotide polymorphisms(SNPs),previously identified in Western populations,with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk factors.METHODS A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography,magnetic resonance imaging,or controlled attenuation parameter score.Subjects were recruited from two tertiary hospitals.Genetic alleles such as NCAN,GCKR,LYPLAL1,PNPLA3,PPP1R3B,FDFT1,COL13A1,EFCAB4B,PZP,and TM6SF2 were genotyped using the TaqMan®Predesigned SNP Genotyping Assay.RESULTS Weight and body mass index(BMI)were 1.2-times higher in patients(70.6 kg,95%confidence interval[CI]:57.1-84.1 vs 60.8 kg,95%CI:48.5-73.1,P<0.001 and 26.9 kg,95%CI:23-40.8 vs 23.3 kg 95%CI:19-27.6,P<0.001 respectively).The prevalence of diabetes mellitus in patients was 40.3%and 20.8%in controls(P=0.011).Patients had higher mean triglycerides than controls(P<0.001).PNPLA3 GG was more likely to be associated with MAFLD(43.4%CC vs 69.7%GG,P=0.017,and 44.8%CG vs 69.7%GG,P=0.022).In multivariable analysis,hypertriglyceridemia(odds ratio[OR]:2.0495%CI:1.3-3.1,P=0.001),BMI(OR:1.295%CI:1.1-1.4,P<0.001)and PNPLA3 GG(OR:3.495%CI:1.3-9.2,P=0.014)were associated with MAFLD(area under the receiver operating characteristic curve of 0.823).CONCLUSION Among the Chinese population of Singapore,PNPLA3 homozygous GG allele is a strong predictor of MAFLD,whereas LYPLAL1,GCKR,FDFT1,COL13A1,PZP,and TM6SF2 are not significantly associated.Hypertriglyceridemia,high BMI,and PNPLA3 GG are independent predictors of MAFLD.

Risk factors for ribavirin treatment failure in Asian organ transplant recipients with chronic hepatitis E infection

BACKGROUND Hepatitis E virus(HEV)infection is a cause of chronic hepatitis in immunosuppressed patients.Sustained virologic response rates to a 12-wk course of ribavirin therapy were reported to be>70%in the West.This study describes the outcome of HEV treatment in a transplant center in Singapore.AIM To study the outcome of ribavirin treatment in a series of chronic HEV patients,and the cause of treatment failure.METHODS We studied all of the transplant recipients who were diagnosed with HEV infection between 2012 to 2015.The outcome of therapy and virologic relapse are monitored for three years after the end of therapy.RESULTS Ten transplant recipients(4 liver,5 kidney,and 1 bone marrow transplantation)with positive HEV RNA were studied.Nine patients received at least 12 wk of ribavirin therapy,and the remaining patient resolved after reducing immunosuppression therapy.Two subjects had prolonged viremia that lasted more than one year,despite continuous ribavirin therapy.Four ribavirin-treated patients(44.4%)had HEV RNA relapse after achieving a virologic response by the end of treatment.The overall failure rate is 66.7%.Being a kidney transplant recipient is the strongest risk factor for not achieving an initial sustained virologic response(0/5 treated,Chi-Square test,P<0.05).The most common side effect of ribavirin is anemia(100%)(haemoglobin reduction of 3-6.2 g/dL).Seven patients required either a blood transfusion or erythropoietin therapy.CONCLUSION The sustained virologic response rate of 12-wk ribavirin therapy for HEV infection in this Asian series was lower than expected.Kidney transplant recipients had a higher rate of treatment failure due to higher immunosuppression requirements and adverse effects.