Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver conditions that are characterized by excess accumulation of fat in the liver, and is diagnosed after exclusion of significant alcohol intake and other causes of chronic liver disease. In the majority of cases, NAFLD is associated with overnutrition and obesity, although it may be also found in lean or non-obese individuals. It has been estimated that 19.2% of NAFLD patients are lean and 40.8% are non-obese. The proportion of patients with more severe liver disease and the incidence of all-cause mortality, liver-related mortality, and cardiovascular mortality among non-obese and obese NAFLD patients varies across studies and may be confounded by selection bias, underestimation of alcohol intake, and unaccounted weight changes over time. Genetic factors may have a greater effect towards the development of NAFLD in lean or non-obese individuals, but the effect may be less pronounced in the presence of strong environmental factors, such as poor dietary choices and a sedentary lifestyle, as body mass index increases in the obese state. Overall, non-invasive tests, such as the Fibrosis-4 index, NAFLD fibrosis score, and liver stiffness measurement, perform better in lean or non-obese patients compared to obese patients. Lifestyle intervention works in non-obese patients, and less amount of weight loss may be required to achieve similar results compared to obese patients. Pharmacological therapy in non-obese NAFLD patients may require special consideration and a different approach compared to obese patients.

Chronic diarrhoea in tropical countries may be due to a myriad of causes from infective to non-infective. This case report illustrates the challenges faced in the investigation of a middle-age Chinese gentleman who presented with chronic diarrhoea and weight loss. The diagnosis of type II enteropathy-associated T-cell lymphoma (EATL) was finally made. The diagnosis of EATL was least suspected as the condition is almost unheard of in this part of the world. The epidemiology, presentation, diagnosis, management and prognosis of this rare condition are discussed.

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.

transmission of hepatitis B virus (HBV) infection amongchildren of hepatitis B surface antigen (HBsAg) positivemothers in Malaysia. Methods: This is a cross-sectional study of all the childrenof HBsAg-positive mothers who delivered at the Universityof Malaya Medical Centre between 1993 and 2000. Results: A total of 60 HBsAg-positive mothers and their 154children participated in the study. HBsAg was detected infour children (2.6%) while IgG antibody to the hepatitis Bcore antigen (anti-HBc IgG) was detected in seventeenchildren (11.0%). The mother’s age at childbirth wassignificantly lower in the children with detectable HBsAg(22.5±6.1 years vs. 29.7±4.5 years, p=0.043) and anti-HBc IgG(26.6±6.1 years vs. 30.0±4.3 years, p=0.004). Children born inthe 1980s were significantly more likely to have detectableHBsAg (18.8% vs. 0.7%, p=0.004) and anti-HBc IgG (37.5%vs. 8.0%, p=0.000) compared with those born later. Allchildren with detectable HBsAg were born via spontaneousvaginal delivery, and hepatitis B immunoglobulin was eithernot given or the administration status was unknown. Themajority of mothers with chronic HBV infection (70.4%) werenot under any regular follow-up for their chronic HBVinfection and the main reason was the lack of awareness ofthe need to do so (47.4%). Conclusion: Transmission of HBV infection among childrenof HBsAg-positive mothers in Malaysia is low. However,attention needs to be given to the high rate of HBsAg-positive mothers who are not on any regular follow-up.

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.

Introduction: We aimed to compare the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) staging systems. Materials and Methods: This is a retrospective study on patients with newly diagnosed hepatocellular carcinoma (HCC) at the University Malaya Medical Centre between 2011 and 2014. Survival times were analysed using the KaplanMeier procedure and comparison between groups was done using the log rank test. Results: The data of 190 patients was analysed. Chronic hepatitis B was the most common aetiology for HCC (43.7%), but a large proportion was cryptogenic or non-alcoholic steatohepatitis-related (41.6%). Only 11.1% were diagnosed early (BCLC Stage 0-A) while majority were diagnosed at an intermediate stage (BCLC Stage B, 53.7%). The median survival rate was significantly different between the different groups when either of the staging systems was used (p<0.05 for all comparisons). However, the two staging systems lacked agreement (weighted kappa 0.519, 95%CI: 0.449, 0.589) with significant difference in median survival rates between BCLC Stage A and HKLC Stage 2, and between BCLC Stage C and HKLC Stage 4. Conclusion: Both staging systems were able to stratify patients according to survival, but they only had moderate agreement with significant differences observed in two groups of the staging systems.

INTRODUCTION: The diagnosis of Wilson disease (WD) is plagued by biochemical and clinical uncertainties. Thus, calculated parameters have been proposed. This study aimed to: (a) compare the diagnostic values of non-caeruloplasmin copper (NCC), NCC percentage (NCC%), copper-caeruloplasmin ratio (CCR) and adjusted copper in WD; and (b) derive and evaluate a discriminant function in diagnosing WD. METHODS: A total of 213 subjects across all ages who were investigated for WD were recruited. WD was confirmed in 55 patients, and the rest were WD free. Based on serum copper and caeruloplasmin values, NCC, NCC%, CCR and adjusted copper were calculated for each subject. A function was derived using discriminant analysis, and the cut-off value was determined through receiver operating characteristic analysis. Classification accuracy was found by cross-tabulation. RESULTS: Caeruloplasmin, total copper, NCC, NCC%, CCR, adjusted copper and discriminant function were significantly lower in WD compared to non-WD. Discriminant function showed the best diagnostic specificity (99.4%), sensitivity (98.2%) and classification accuracy (99.1%). Caeruloplasmin levels <0.14 g/L showed higher accuracy than the recommended 0.20 g/L cut-off value (97.7% vs. 87.8%). Similarly, molar NCC below the European cut-off of 1.6 umol/L showed higher accuracy than the American cut-off of 3.9 umol/L (80.3% vs. 59.6%) (P < 0.001). NCC%, mass NCC, CCR and adjusted copper showed poorer performances. CONCLUSION Discriminant function differentiates WD from non-WD with excellent specificity, sensitivity and accuracy. Performance of serum caeruloplasmin <0.14 g/L was better than that of <0.20 g/L. NCC, NCC%, CCR and adjusted copper are not helpful in diagnosing WD.
Humans ; Hepatolenticular Degeneration/diagnosis* ; Copper/analysis* ; Ceruloplasmin/metabolism* ; Repressor Proteins

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*