Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.

Visceral fat and insulin resistance as predictors of non-alcoholic steatohepatitis

AIM： To examine whether visceral fat is associated with non-alcoholic steatohepatitis （NASH）, to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic severity in NASH. METHODS： Thirty NASH and 30 control subjects underwent biochemical tests, anthropometric assessment, bioelectrical impedance, dual energy X-ray absorptiometry and abdominal fat study by CT scan. Liver biopsies were graded according to the Brunt criteria. RESULTS： NASH subjects had elevated blood pressure, body mass index, waist circumference and waist-to-hip ratio. A greater number of diabetes rnellitus, impaired glucose tolerance test and HOMA-IR 〉 3.5 were found in NASH patients. HOMA-IR 〉 2.8 （OR 20.98, 95% CI 3.22-136.62; P 〈 0.001） and visceral fat area 〉 158 cm^2 （OR 18.55, 95% CI 1.60-214.67; P = 0.019） were independent predictors for NASH. Advanced stage of NASH was found in 15 （50%） patients. HOMA-IR 〉 3.5 （OR 23.12, 95% CI 2.00-266.23; P = 0.012） and grading of portal inflammation （OR 7.15, 95% CI 1.63-31.20; P = 0.009） were determined as independent risk factors for advanced stage of NASH. CONCLUSION： Obesity （especially central obesity） and metabolic syndrome are common in Thai NASH. Insulin resistance and elevated visceral fat are risk factors for the presence of NASH. The advanced stage of thedisease is related to insulin resistance.

Chronic liver disease questionnaire:Translation and validation in Thais

AIM:Quality of life (QOL) is a concept that incorporates many aspects of life beyond“health”.The chronic liver disease questionnaire (CLDQ) was developed to evaluate the impact of chronic liver diseases (CLD) on QOL.The objectives of this study were to translate and validate a liver specific questionnaire,the CLDQ. METHODS:The CLDQ was formally translated from the original version to Thai language with permission.The translation process included forward translation,back translation,cross-cultural adaptation and a pretest.Reliability and validity of the translated version was examined in CLD patients.Enrolled subjects included CLD and normal subjects with age- and sex-matched.Collected data were demography, physical findings and biochemical tests.All subjects were asked to complete the translated versions of CLDQ and SF- 36,which was previously validated.Cronbach's alpha and test-retest were performed for reliability analysis.One-way Anova or non-parametric method was used to determine discriminant validity.Speerman's rank correlation was used to assess convergent validity.P-value<0.05 was considered statistically significant. RESULTS:A total of 200 subjects were recruited into the study,with 150 CLD and 50 normal subjects.Mean ages (SD) were 47.3(11.7) and 49.1(8.5) years,respectively.The number of chronic hepatitis:cirrhosis was 76:74,and the ratio of cirrhotic patients classified as Child A:B:C was 37 (50%):26(35%):11(15%).Cronbach's alpha of the overall CLDQ scores was 0.96 and of all domains were higher than 0.93.Item-total correlation was>0.45.Test-retest reliability done at 1 to 4 wk apart was 0.88 for the average CLDQ score and from 0.68 to 0.90 for domain scores.The CLDQ was found to have discriminant validity.The highest scores of CLDQ domains were in the normal group,scores were lower in the compensated group and lowest in the decompensated group.The significant correlation between domains of the CLDQ and SF-36 was found.The average CLDQ score was strongly correlated with the general health domain of SF-36.(P=0.69:P=0.01). CONCLUSION:The translated CLDQ is valid and applicable in Thais with CLD.CLDQ reveals that QOL in these patients is lower than that in normal population.QOL is more impaired in advanced stage of CLD.

Improving quality of colonoscopy by adding simethicone to sodium phosphate bowel preparation

AIM： To evaluate the effectiveness of simethicone in enhancing visibility and efficacy during colonoscopy.METHODS： A prospective, double-blind, randomized, placebo-controlled study was conducted. One hundred and twenty-four patients were allocated to receive 2 doses of sodium phosphate plus 240 mg of tablet simethicone or placebo as bowel preparation. Visibility was blindly assessed for the amount of air bubbles and adequacy of colon preparation. Total colonoscopic time, side effects of the medication, endoscopist and patient satisfaction were also compared.RESULTS： Sodium phosphate plus simethicone, compared to sodium phosphate plus placebo, improved visibility by diminishing air bubbles （100.00% vs 42.37%, P 〈 0.0002） but simethicone failed to demonstrate improvement in adequacy of colon preparation （90.16% vs 81.36%, P = 0.17）. Endoscopist and patient satisfaction were increased significantly in the simethicone group. However, there was no difference in the total duration of colonoscopy and side effects of the medication.CONCLUSION： The addition of simethicone is of benefit for colonoscopic bowel preparation by diminishing air bubbles, which results in enhanced visibility. Endoscopist and patient satisfaction is also increased.

Factors influencing health-related quality of life in chronic liver disease

AIM： To investigate the factors contributing to healthrelated quality of life （HRQL） in chronic liver disease （CLD）.METHODS： Patients with CLD and age- and sexmatched normal subjects performed the validated Thai versions of the short-form 36 （SF-36） by health survey and chronic liver disease questionnaire （CLDQ）. Stepwise multiple regression analysis was used to assess the impact of disease severity, demography, causes of CLD, socioeconomic factors, and self-rating health perception on HRQL.RESULTS： Two-hundred and fifty patients with CLD and fifty normal subjects were enrolled into the study. Mean age and the numbers of low educated, unemployed, blue-collar career and poor health perception increased significantly from chronic hepatitis to Child＇s Classes A to B to C. Advanced stage of CLD was related to deterioration of HRQL. Increasing age and female reduced physical health area. Low socioeconomic factors and financial burden affected multiple areas of HRQL. In overall, the positive impact of self-rating health perception on HRQL was consistently showed.CONCLUSION： Advanced disease, old age, female sex, stages of chronic liver low socioeconomic status and financial burden are important factors reducing HRQL. Good health perception improves HRQL regardless of stages of liver disease.

Current position of vasoconstrictor and albumin infusion for type 1 hepatorenal syndrome

Spontaneous bacterial peritonitis(SBP),refractory ascites,hepatorenal syndrome(HRS),hyponatremia and hepatic encephalopathy are complicationswhich frequently happen during a clinical course of decompensated cirrhosis.Splanchnic and peripheral vasodilatation,increased intrarenal vasoconstriction and impaired cardiac responsive function are pathological changes causing systemic and hemodynamic derangement.Extreme renal vasoconstriction leads to severe reduction of renal blood flow and glomerular filtration rate,which finally evolves into the clinical feature of HRS.Clinical manifestations of type 1 and type 2 HRS come to medical attention differently.Patients with type1 HRS present as acute kidney injury whereas those with type 2 HRS will have refractory ascites as the leading problem.Prompt diagnosis of type 1 HRS can halt the progression of HRS to acute tubular necrosis if the combined treatment of albumin infusion and vasoconstrictors is started timely.HRS reversal was seen in 34%-60%of patients,followed with decreasing mortality.Baseline serum levels of creatinine less than5 mg/dL,bilirubin less than 10 mg/dL,and increased mean arterial pressure of over 5 mmHg by day 3 of the combined treatment of vasoconstrictor and albumin are the predictors of good response.Type 1 HRS can be prevented in some conditions such as albumin infusion in SBP,prophylactic antibiotics for upper gastrointestinal hemorrhage,albumin replacement after large volume paracentesis in cirrhotic patients with massive ascites.The benefit of albumin infusion in infection with primary source other than SBP requires more studies.

A prophylactic approach for bone marrow transplantation from a hepatitis B surface antigen-positive donor

It has been accepted that bone marrow transplantation （BMT） is the only curative therapeutic option for certain hematologic malignancies. The southeast Asia region is an endemic area of hepatitis B virus （HBV） infection; thus, BMT using a hepatitis B surface antigen （HBsAg）- positive donor is occasionally unavoidable. Organ transplantation using a HBsAg-positive donor can lead to post-transplantation de novo HBV infection and severe HBV-related hepatitis if no effective prophylactic measures are taken prior to and after transplantation. In this report, a four-level approach was designed for a patient with chronic myeloid leukemia, beginning with a booster HBV vaccination before performing BMT with a HBsAg-positive donor. Prior to BMT, the HBV viral load of the donor was reduced to an undetectable level by anUviral therapy. After BMT, hepatitis B immunoglobulin was administered intramuscularly for 1 wk together with a long-term antiviral drug, lamivudine. One year after discontinuation of lamivudine, the patient is still free of HBV infection.

Characteristics of Drug-induced Liver Injury in Chronic Liver Disease:Results from the Thai Association for the Study of the Liver(THASL)DILI Registry

Background and Aims:The impact of drug-induced liver injury(DILI)on patients with chronic liver disease(CLD)is unclear.There are few reports comparing DILI in CLD and non-CLD patients.In this study,we aimed to determine the incidence and outcomes of DILI in patients with and without CLD.Methods:We collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies,causes,and the severity of DILI.We compared the causative agents,clinical features,and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry.Subjects with definite,or highly likely DILI were included in the analysis.Results:A total of 200 subjects diagnosed with DILI were found in the registry.Of those,41 had CLD and 159 had no evidence of CLD in their background.Complementary and alternative medicine(CAM)products were identified as the most common class of DILI agents.Approximately 59%of DILI in the CLD and 40%in non-CLD group were associated with CAM use.Individuals with pre-existing CLD had similar severity including mortality.Twelve patients(6%)developed adverse outcomes related to DILI including seven(3.5%)deaths and five(2.5%)with liver failure.Mortality was 4.88%in CLD and 3.14%in non-CLD subjects over median periods of 58(8–106)days and 22(1–65)days,respectively.Conclusions:In this liver disease registry,the causes,clinical presentation,and outcomes of DILI in subjects with CLD and without CLD patients were not different.Further study is required to confirm our findings.