Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Identification of patients with type 2 diabetes with non-alcoholic fatty liver disease who are at increased risk of progressing to advanced fibrosis: a cross-sectional study(BMJ Publishing Group Ltd, 2023) Mettananda, C.; Egodage, T.; Dantanarayana, C.; Fernando, R.; Ranaweera, L.; Luke, N.; Ranawaka, C.; Kottahachchi, D.; Pathmeswaran, A.; de Silva, H.J.; Dassanayake, A.S.INTRODUCTION: Identification of advanced hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) is important as this may progress to cirrhosis and hepatocellular carcinoma. The risk of hepatic fibrosis is especially high among patients with diabetes with NAFLD. Annual screening of patients with diabetes for fatty liver and calculation of Fibrosis-4 (FIB-4) score and exclusion of significant fibrosis with vibration-controlled transient elastography (VCTE) have been recommended. However, VCTE is expensive and may not be freely available in resource-limited settings. We aim to identify predictors of significant liver fibrosis who are at increased risk of progression to advanced liver fibrosis and to develop a prediction model to prioritise referral of patients with diabetes and NAFLD for VCTE. METHODS AND ANALYSIS: This cross-sectional study is conducted among all consenting adults with type 2 diabetes mellitus with NAFLD at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All patients get the FIB-4 score calculated. Those with FIB-4 ≥1.3 undergo VCTE (with FibroScan by Echosens). Risk associations for progression to advanced liver fibrosis/cirrhosis will be identified by comparing patients with significant fibrosis (liver stiffness measure (LSM) ≥8 kPa) and without significant fibrosis (LSM <8 kPa). A model to predict significant liver fibrosis will be developed using logistic regression. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (P/66/07/2021). Results of the study will be disseminated as scientific publications in reputable journals.Item Non-alcoholic fatty liver disease and its associations among adolescents in an urban, Sri Lankan community(BioMed Central, 2017) Rajindrajith, S.; Pathmeswaran, A.; Jayasinghe, C.; Kottahachchi, D.; Kasturiratne, A.; de Silva, S.T.; Niriella, M.A.; Dassanayake, A.S.; de Silva, A.P.; de Silva, H.J.BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common problem across the world. We aimed to determine the prevalence of NAFLD and its associations in Sri Lankan adolescents living in an urban Sri Lankan community. METHOD: The study population consisted of the birth cohort of the year 2000, residing in the Ragama Medical Officer of Health area. Socio-demographic and anthropometric data [anthropometric measurements, blood pressure and total body fat distribution] of these adolescents were collected by trained data collectors. Fasting blood sugar, serum insulin, fasting serum lipids and serum alanine aminotransferase (ALT) levels were measured and an abdominal ultrasound was performed. NAFLD was diagnosed on established ultrasound criteria for fatty liver and absent alcohol consumption. RESULTS: The study sample consisted of 499 adolescents [263 (51.8%) girls]. Forty two (8.4%) had NAFLD. NAFLD was significantly associated with being breast fed for less than 4 months (33.3% vs. 17.1 in controls, p = 0.02), higher waist circumference (prevalence risk ratio 83.3/20.3, 4.1, p < 0.0001), higher body mass index (prevalence risk ratio 40.5/4.8, 8.4, p < 0/0001),higher HOMA-IR (3.7 vs. 1.9, p < 0.0001) and high triglycerides (prevalence risk ratio 14.3/5.8, 2.5, p = 0.033). Adolescents with NAFLD also had a higher amount of total body fat (p < 0.001) and subcutaneous fat (p < 0.001) than those without NAFLD. The number of children with metabolic derangements was higher among adolescents with NAFLD than those without (85.8 vs 26.3 in controls, p < 0.0001), but a family history of hypertension, diabetes, myocardial infarction or dyslipidaemia were not. CONCLUSION: Prevalence of NAFLD was high in Sri Lankan adolescents, and was associated with metabolic derangements, especially obesity, insulin resistance and early cessation of breast feeding.Item Lean non-alcoholic fatty liver disease (Lean-NAFLD): characteristics and risk factors from a community cohort follow up study(Sri Lanka Medical Association, 2016) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyaratna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is usually associated with obesity. However, some NAFLD patients are lean. We assessed the characteristics and risk factors for lean-NAFLD. METHOD: In a community cohort follow up study (initial screening-2007, re-evaluation-2014), NAFLD was established on USS criteria and exclusion of alcohol overuse and secondary causes. Lean (BMI <23 kg/m2) and non-lean (BMI ≥23 kg/m2) NAFLD were compared. The two groups were compared for differences in gender, diabetes, hypertension, hypertriglyceridemia, low-HDL, weight and waist circumference (WC) at baseline. They were also compared for differences in development of incident diabetes, hypertension, hypertriglyceridemia, low-HDL, and change in weight and WC. RESULTS: 678 (69.6%) individuals with NAFLD detected in 2007 presented for follow up in 2014. 78(11.5%) [males-32(41%); mean-age 53.7(SD-7.1) years] were lean and 600(88.5%) [males-191(31.8%); mean-age 52.3(SD-7.5) years] were non-lean. Hypertension (p=0.007) and a smaller WC (<90cm for males, <80cm for females) (p<0.001) were associated with lean-NAFLD. After 7 years, change in BMI was less (p=0.022) among lean-NAFLD. There were no differences in change in WC or incident metabolic co-morbidities. Of those who did not have NAFLD in 2007, 746 developed incident NAFLD in 2014; lean-NAFLD 193/746 (25.9%) [males-100(51.8%); mean age 59.6(SD-7.5)], non-lean-NAFLD 553/746 (74.1%) [males-201(36.3%); mean age 58.2(SD-7.7)]. On logistic regression analysis, presence of diabetes (p=0.002, OR 2.1) and raised WC (p=0.003, OR 1.7) were associated with incident lean-NAFLD. CONCLUSIONS: Among individuals with NAFLD, lean-NAFLD is associated with hypertension and smaller WC. In the community, diabetes and bigger WC predict incident lean-NAFLD.Item Incidence and risk factors for non-alcoholic fatty liver disease: A 7-year follow-up study among urban, adult Sri Lankans(Blackwell Munksgaard, 2017) Niriella, M.A.; Pathmeswaran, A.; de Silva, S.T.; Kasturiratne, A.; Perera, R.; Subasinghe, C.E.; Kodisinghe, K.; Piyaratna, C.; Rishikesawan, V.; Dassanayake, A.S.; de Silva, A.P.; Wickremasinghe, R.; Takeuchi, F.; Kato, N.; de Silva, H.J.BACKGROUND: This study investigated incidence and risk factors for NAFLD among an adult cohort with 7-year follow-up. METHODS: The study population (age-stratified random sampling, Ragama MOH area) was screened initially in 2007 (aged 35-64 years) and re-evaluated in 2014 (aged 42-71 years). On both occasions assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. NAFLD was diagnosed on ultrasound criteria, safe alcohol consumption and absence of hepatitis B/C markers. Non-NAFLD controls did not have any ultrasound criteria for NAFLD. An updated case-control genetic association study for 10 selected genetic variants and NAFLD was also performed. RESULTS: Out of 2985 of the original cohort, 2148 (72.0%) attended follow-up (1238 [57.6%] women; mean-age 59.2 [SD-7.6] years) in 2014, when 1320 (61.5%) were deemed NAFLD subjects. Out of 778 who initially did not have NAFLD and were not heavy drinkers throughout follow-up, 338 (43.4%) (221 [65.4%] women, mean-age 57.8 [SD-8.0] years) had developed NAFLD after 7-years (annual incidence-6.2%). Central obesity (OR=3.82 [95%-CI 2.09-6.99]), waist increase >5% (OR=2.46 [95%-CI 1.20-5.05]) overweight (OR=3.26 [95%-CI 1.90-5.60]), weight gain 5%-10% (OR=5.70 [95%-CI 2.61-12.47]), weight gain >10% (OR=16.94 [95%-CI 6.88-41.73]), raised plasma triglycerides (OR=1.96 [95%-CI 1.16-3.29]) and diabetes (OR=2.14 [95%-CI 1.13-4.06]), independently predicted the development of incident NAFLD in multivariate analysis. The updated genetic association study (1362-cases, 392-controls) showed replicated association (P=.045, 1-tailed) with NAFLD at a candidate locus: PNPLA3 (rs738409). CONCLUSIONS: In this community cohort study, the annual incidence of NAFLD was 6.2%. Incident NAFLD was associated with general and central obesity, raised triglycerides and diabetes, and showed a tendency of association with PNPLA3 gene polymorphisms.Item The value of brunt scoring in predicting the short term outcome of non-alcohlic steatohepatitis(Wiley Blackwell Scientific Publications, 2004) Hewavisenthi, S.J.de S.; Pathmeswaran, A.; de Silva, H.J.BACKGROUND: Brunt scoring is currently used in the grading and staging of liver biopsies in non-alcoholic steatohepatitis (NASH). Its value in predicting the outcome of patients following modifications in lifestyle, the cornerstone of management in NASH, needs evaluation. OBJECTIVES: To determine whether Brunt grades correlate with Aspartate transaminase (AST) and Alanine transaminase (ALT) levels, and outcome following lifestyle modifications in NASH. METHOD: In a prospective study from May 1999 to May 2003 the biopsies of 79 patients diagnosed as having NASH were assigned 3 necroinflammatory grades based on the Brunt system. The mean serum transaminase values at presentation for each necroinflammatory grade were compared using ANOVA. 77/79 patients were given advice on lifestyle modifications and then followed up for a median 2.5 years. The time taken for serum transaminases to return to normal was correlated with the necroinflammatory grades, AST and ALT values at presentation using Kendall tau b. RESULTS : The mean AST and ALT values (IU/L) in the three necroinflammatory grades were - grade 1:62.4 and 102:1, grade 2: 87.6 and 139.4 and grade 3: 90.9 and 164.5. There was a significant difference in the AST and ALT values between grades 1 and 2, and grades 1 and 3, but not between grades 2 and 3. In 51/77 patients serum transaminases returned to normal levels after a median 6 months (range 3– 14 months). There was no significant correlation between the time taken for serum transaminases to return to normal and the transaminase values or necroinflammatory grades at presentation. CONCLUSION: Brunt grading correlates with both AST and ALT levels. However, neither necroinflammatory grades nor serum transaminase values at first presentation are predictors of the duration to normalization of liver enzymes in NASH patients managed with life style modificationsItem Incidence and risk factors for Non-Alcoholic Fatty Liver Disease in an urban, adult Sri Lankan population – a community cohort follow-up study(Sage Publishing, 2015) Niriella, M.; Kasturiratne, A.; de Silva, S.; Perera, R.; Subasinghe, C.; Kodisinghe, K.; Priyantha, C.; Rishikeshavan, V.; Dassanayake, A.; de Silva, A.; Pathmeswaran, A.; Kato, N.; de Silva, H.J.INTRODUCTION: We previously reported a community prevalence of 33% for NAFLD in an urban, adult Sri Lankan population. We also found a significant association between patatin-like phospholipase domain containing 3 (PNPLA3) gene rs738409 polymorphism, and susceptibility to NAFLD in the same population, after testing 10 selected single nucleotide polymorphisms (SNPs) in a case control study. AIMS & METHODS: The aim of this study was to assess the incidence and risk factors for NAFLD in this population after seven years of follow-up. The study population consisted of 42-71-year-old adults, originally selected by age stratified random sampling from electoral lists from Ragama, Sri Lanka. The target population was screened initially in 2007 and subsequently invited back for re-evaluation in 2014. On both occasions they were assessed using a structured interview, clinical and anthropometric measurements, liver ultrasound, and biochemical and serological tests. NAFLD was diagnosed on established ultrasound criteria for fatty liver (two out of three criteria: increased echogenecity of the liver compared to kidney and spleen, obliteration of the vascular architecture of the liver and deep attenuation of the ultrasonic signal), safe alcohol consumption (Asian standards: 514 units/week for men, 57 units/week for females) and absence of hepatitis B and C markers. Non-NAFLD controls were defined as subjects who did not have any of the ultrasound criteria for NAFLD. We also performed an updated case-control study to investigate associations of selected genetic variants with incident NAFLD [SNPs: PNPLA3 (rs738409), LYPLAL1 (rs12137855), GCKR (rs780094), PPP1R3B (rs4240624) and NCAN (rs2228603), APOC3 (rs2854117 and rs2854116), ADIPOR2 (rs767870) and STAT3 (rs6503695 and rs9891119)]. RESULTS: Of the 2985 original study participants, 2155 (72.2%) (1244 women and 911 men; mean age 59.2 years [SD, 7.7]) participated in the follow-up assessment. 1322 [mean age 58.9 years (SD, 7.6), 483 (53.0%) men and 839 (67.4%) women] had NAFLD. Out of 795 [466 (58.6%) women] participants who did not have NAFLD in the original study, 365 [226 (61.9%) women, mean age 58.6 years (SD, 7.9)] had developed NAFLD after 7 years, giving an annual incidence rate 6.6%. On multivariate analysis, increased waist circumference [OR 1.96(1.30 – 2.97), p=0.001], BMI4 23 kg/m2 [OR 2.93(1.99 – 4.30), p50.001] and raised plasma triglycerides (TG) [OR 1.49(1.03 – 2.13), p=0.03] were independently predictive of incident NAFLD in this cohort, while raised BP and reduced HDL, were not. In the updated association study involving 1310 cases and 427 controls, we found borderline association with NAFLD at two of the 10 candidate loci: rs4240624 at PPP1R3B and rs738409 at PNPLA3 (one-tailed P=0.044 and 0.033, respectively). CONCLUSION: In this community cohort follow-up study in an urban, adult population in Sri Lanka, the annual incidence of NAFLD was 6.6%. Incident NAFLD was associated with features of the metabolic syndrome, and showed tendency of association at PNPLA3 and PPP1R3B gene polymorphisms. Disclosure of Interest: None declaredItem Prevalence and risk factors for Non-Alcoholic Fatty Liver Disease among an urban aging adult Sri Lankan population – Ragama Health Study 7-year follow up(Sri Lanka Medical Association, 2015) Niriella, M.A.; Kasturiratne, A.; de Silva, S.T.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Priyantha, T.A.C.L.; Vithiya, K.; Kottachchi, D.; Ranawaka, U.K.; Jayasinghe, Y.C.; Rajindrajith, S.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: A previous community based study reported a prevalence of 33% for non-alcoholic fatty liver disease (NAFLD) among and urban adult Sri Lankan population. In this follow up study of the same population after 7 years, e reassessed the prevalence and risk factors for NAFLD. METHODS: The study population consisted of 42-71 year old adults, originally selected by stratified random sampling. NAFLD was diagnosed on established ultrasound criteria for fatty liver, safe alcohol consumption (<14 units/week for men, <7 units/week for females) and absence of hepatitis B and C markers. Anthropometric measurements, blood pressure (BP) and body fat distribution estimates were made. HbA1c, fasting serum lipids, serum alanine aminotransferase (ALT) and serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) were determined. CKD was defined as eGFR<60ml/min/1.72m2 (KDIGO/KDOQI classification). RESULTS: of the 2985 original study participants, 2155(72.2%) (1244[57.7%] women, mean age 59.2 years [SD, 7.7]) participated in the present study. 1322 [mean age 58.9 years (SD, 7.6), 483(53.0%) men and 839(67.4%) women] had NAFLD. On multivariate analysis, obesity, abnormal body fat distribution, elevated systolic BP, raised plasma triglycerides, and low HDL were independently associated wth NAFLD. Raised diastolic BP, raised HbA1c, raised ALT and presence of CKD were not associated with NAFLD. CONCLUSION: The prevalence of NAFLD among adults in this aging urban Sri Lankan community has increased over 7 years and is independently associated with constituent features of the metabolic syndrome.Item Prevalence of non-alcoholic fatty liver disease and its risk factors in an urban adolescent cohort in Sri Lanka(Sri Lanka Medical Association, 2015) Jayasinghe, Y.C.; Rajindrajith, S.; Kasturiratne, A.; de Silva, S.T.; Niriella, M.A.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Priyantha, T.A.C.L.; Vithiya, K.; Pathmeswaran, A.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: High prevalence of non-alcoholic fatty liver disease (NAFLD) is reported among adults in Sri Lanka. Although limited data on childhood obesity is available, community prevalence of NAFLD and its risk factors among adolescents is unknown. We investigated the prevalence and risk factors for NAFLD in an urban adolescent birth cohort in Sri Lanka. METHODS: The study population consisted 14 year-olds, belonging to the birth cohort born in 2000, residing in the Ragama Medical Officer of Health area. NAFLD was diagnosed based on established ultrasound criteria. Anthropometric measurements, blood pressure (BP) and total body fat distribution (TBF) estimates were made. Fasting blood sugar, serum insulin, fasting serum lipid and serum alanine aminotransferase (ALT) levels were measured. Independent predictors of NAFLD were determined by multivariate analysis. RESULTS: 508 adolescents [263 (51.8%) girls] participated in the study. Overall 44 (8.7%) had NAFLD [22 (8.4%) girls]. 46 (18.8%) boys and 54 (20.5%) girls had a BMI above the equivalent of 23 kgm2in adults. 44 (17.1%) boys and 77 (29.3%) girls had elevated TBF. On multivariate analysis, having an elevated BMI [OR=10.1 (95% confidence interval: 3.9-29.2) and elevated TBF [OR=4.4 (95% confidence interval: 1.5-12.8)] were independently associated with NAFLD. CONCLUSION: The prevalence of NAFLD among adolescents in this urban Sri Lankan community is high, and is strongly associated with obesity and abnormal TBF. Despite elevated TBF being commoner in girls, we found no gender differences in prevalence of NAFLD among adolescents in this urban Sri Lankan community is strongly associated with obesity and abnormal TBF. Our findings emphasize the needs to access these risk factors through preventive and screening programs.