Conference Papers

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This collection contains abstracts of conference papers, presented at local and international conferences by the staff of the Faculty of Medicine

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    Prevalence, predictors and outcome of chronic kidney disease in a cohort of aging urban, adult Sri Lankans
    (Sri Lanka Medical Association, 2021) de Silva, S.T.; Ediriweera, D.D.; Niriella, M.A.; Kasturiratne, A.; Kato, N.; Wickremasinghe, A.R.; de Silva, H.J.
    Introduction and Objectives Chronic kidney disease (CKD) affects 700 million people worldwide. In 2017, deaths due to CKD accounted for 4.6% of mortality globally. Prevalence of CKD is increasing worldwide, with increasing diabetes and hypertension in aging populations. Our objective was to determine prevalence of CKD in an urban, adult cohort, since such data is scarce in Sri Lanka. Methods The study population was selected by stratified random sampling from Ragama MOH area initially in 2007 (aged 35-64 years) and re-assessed in 2014. On both occasions, participants were assessed by structured interview, anthropometric measurements and biochemical tests. CKD was assessed in 2014. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI formula. CKD was defined as eGFR<60ml/min/1.72m2, using KDIGO/KDOQI classification. The cohort was further followed up in 2017 when all-cause and cardiovascular (CV) mortality and CV morbidity were also assessed. Results Of 2985 individuals recruited in 2007, 2148(71.6%) attended follow-up in 2014. 2032/2148 (94.6%) had CKD data [57.0% women, mean age 52.3(SD 7.7) years]. Age adjusted prevalence of CKD was 3.03(1.98–4.11) per 100 population in 2014; 41/61(67.2%) were in CKD Stage-3A, 14/61(23%) in Stage-3B, 6/61(9.8%) in Stage-4 and none in end-stage. Independent predictors of CKD in 2014 were older age (p<0.001), male gender (P<0.05) and presence of diabetes (p<0.001) and hypertension (p<0,001) in 2007. CKD was not associated with all-cause mortality, CV mortality or morbidity (p>0.05) in 2017.Conclusion Diabetes and hypertension were associated with CKD. Most with CKD were in Stage 3, where early recognition and better control of co-morbidities retard progression of CKD.
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    Predictors of mortality in a cohort of adult Sri Lankans
    (Sri Lanka Medical Association., 2019) Kasturiratne, A.; Beddage, T.; de Silva, S.T.; Niriella, M.A.; Pathmeswaran, A.; Kato, N.; Wickremasinghe, A.R.; de Silva, H.J.
    INTRODUCTION & OBJECTIVES: There is limited knowledge on early predictors of mortality among Sri Lankans. We investigated predictors of mortality in the Ragama Health Study cohort 10 years after recruitment. METHODS: The study population (35-64-year-olds selected by age-stratified random sampling from the Ragama Medical Officer of Health area) was initially screened in 2007 for socio-demographic, lifestyle, anthropometric and clinical risk factors with informed written consent. Their vital status was assessed in 2017 and the causes of death of the deceased were retrieved from death certificates available with the next-of-kin or declaration of death records from the hospital where the death occurred. RESULTS: Of the 2986 enrolled in 2007, 169 [Males: 107 (63.3%)] had died over the 10-year period, giving an overall mortality rate of 5.7% (95% CI: 5.0 % - 6.4%). The number of deaths due to cardiovascular and cancer related causes were 73/169 and 31/169, respectively. On multivariate analysis using Cox's proportional hazards model, advancing age, male sex, lower educational level, unsafe alcohol consumption and the presence of metabolic syndrome at baseline were independent predictors of all-cause mortality. Advancing age, male sex, unsafe alcohol consumption and the presence of metabolic syndrome at baseline were independent predictors of cardiovascular mortality, while advancing age and unsafe alcohol consumption were the only independent predictors of cancer-related mortality. CONCLUSION: Unsafe alcohol consumption and the presence of metabolic syndrome were important modifiable risks for mortality in this population. Addressing these risks in early adulthood will help to improve longevity.
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    Incidence and predictors of Diabetes Mellitus: A 7- year community cohort follow-up of urban, adult Sri Lankans
    (Sri Lanka Medical Association., 2019) de Silva, S.T.; Ediriweera, D.; Beddage, T.; Kasturiratne, A.; Niriella, M.A.; de Silva, A.P.; Dassanayake, A.S.; Pathmeswaran, A.; Kato, N.; Wickremasinghe, A.R.
    INTRODUCTION & OBJECTIVES: There is limited data on incidence of type 2 diabetes mellitus (T2DM) from South Asia. We investigated incidence and predictors ofT2DM in an urban, adult population after seven-years of follow-up. METHODS: The study population (42-71 year-olds in 2014, selected by age-stratified random sampling from the Ragama MOH area) was initially screened in 2007 and re-evaluated in 2014 with informed written consent. On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. RESULTS: Of the 2986 enrolled in 2007, 737 had established T2DM giving a baseline prevalence of 24.7% (95% CI: 23.1%-26.2%). 2148/2984 (71.6%) of the original cohort attended follow-up [1237 (57.5%) women; median (IQR) 60 (54-66) years]. 1650 participants who did not have T2DM in 2007 presented for follow up; 436 (27.6%) of them had developed new T2DM by 2014, giving an annual incidence of 3.9% (95% CI: 3.0%-4.9%). Of 525 participants with pre-diabetes (HbA1c 5.7-6.4%) in 2007, 364 attended follow up and 201/364 (55.1%) had developed T2DM by 2014, giving an annual conversion rate of pre-diabetes to T2DM of 7.9%. On logistic regression, pre-diabetes (OR:4.4;95%CI:3.3%-6.0%), central obesity (OR: 1.8;95%CI: 1.3%-2.4%), dyslipidemia (OR: l.5;95%CI: 1.1 %-2.1 %) and non-alcoholic fatty liver disease (NAFLD) (OR:1.5;95%CI: 1.1 %-2.1%) showed significant association with incident T2DM. CONCLUSION: In this urban cohort, the annual incidence of T2DM was 3.9% and the annual conversion rate of pre-diabetes to T2DM was 7.9%. Our findings emphasize the need for targeted and intensive lifestyle interventions for individuals with high metabolic risk to prevent T2DM.
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    Incidence and predictors of metabolic syndrome among urban, adult Sri Lankans: a community cohort, 7-year follow-up study
    (European Association for the Study of Diabetes, 2017) de Silva, S.T.; Niriella, M.A.; Kasturiratne, A.; Kottahachchi, D.; Ranawaka, U.K.; Dassanayake, A.; de Silva, A.P.; Pathmeswaran, P.; Wickremasinghe, R.; Kato, N.; de Silva, H.J.
    BACKGROUND AND AIMS In 2007, we reported a 38.9% prevalence of metabolic syndrome (MetS) in an urban, adult population. Published data on incident MetS from South Asia is lacking. This study investigated the incidence and risk factors for MetS after a 7-year follow-up of the initial cohort. MATERIALS AND METHODS: The study population (selected by age-stratified random sampling from the Ragama MOH area) was screened in 2007 (aged 35-64 years) and re-evaluated in 2014 (aged 42-71 years). On both occasions, structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests were performed. MetS was diagnosed on established International Diabetes Federation (IDF 2012) criteria. Total body fat (TBF) and visceral fat percentage (VFP) were measured in 2014, using impedance. Abnormal TBF was defined as >32% for females and >25% for males. Abnormal VFP was defined as >10% for both sexes. Non-alcoholic fatty liver disease (NAFLD) was diagnosed on established ultrasound criteria, safe alcohol consumption (Asian standards: <14 units/week for men, <7 units/week for women) and absence of hepatitis B and C markers. RESULTS: 2137/2967 (72.0%) of the initial cohort attended follow-up [1229 (57.5%) women; mean-age 52.4 (SD-7.7) years]. 1000/2137 [548 (54.8%) women; mean age 57.5 years (SD-7.74)] had MetS (prevalence-46.8%). Out of 1246 individuals who initially did not have MetS in 2007, 318 [225 (70.8%) women; mean age 57.5 (SD 7.7) years] had developed incident MetS after 7 years (annual incidence-2.13%). Comparison of incident MetS with those with no MetS in 2014 is shown in Table 1. On logistic regression, female sex (OR 3.6, p<0.001), central obesity [OR 4.58, p<0.001], BMI >23kg/m2 [OR 4.84, p<0.001], increase in weight 2%-5% [OR 2.02, p<0.001], increase in weight >5% [OR 5.3, p<0.001), increase in waist circumference (WC) 5-10-cm [OR 3.68, p<0.001], increase in WC >10cm [OR 10.34, p<0.001] and NAFLD (OR 2.44, p<0.001) in 2007 were independently predictive of incident MetS in 2014. Abnormal VFP [OR 4.23, p<0.001] and abnormal TBF [OR 5.25, p<0.001] were also associated with incident MetS. CONCLUSION: In this prospective community study, the annual incidence of MetS was 2.13%. Female gender, increase in weight and WC from baseline and the presence of NAFLD predicted the development of incident MetS. Obesity at baseline was the only defining individual component of MetS that predicted future MetS.
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    Correlates of serum homocysteine in a Sri Lankan population
    (American Association For Clinical Chemistry, 2010) Chackrewarthy, S.; Wijayasinghe, Y.S.; Gunasekera, D.; Wickremasinghe, R.; Kato, N.
    Correlates of total serum homocysteine concentration in a Sri Lankan population BACKGROUND: Hyperhomocysteinemia, a possible risk factor for vascular disease occurs at a higher prevalence in South Asian countries. Serum homocysteine concentrations are influenced by genetic, nutritional and lifestyle factors. Correlates of total serum homocysteine concentration (tHcy) are not well characterized in the Sri Lankan population. Such information is important in developing therapeutic and preventative strategies. OBJECTIVE: To investigate the factors potentially associated with fasting levels of serum tHcy in a Sri Lankan population. METHODS: In a cross sectional study, 177 apparently healthy volunteers (91 men and 86 women) aged 38-65 years were selected from residents in an urban health administrative area. Individuals with a history of chronic disease and with any pharmacological treatment were excluded from the study. Information on diet, lifestyle factors and medical history were recorded. Anthropometric indices and blood pressure were measured according standard protocols. Fasting serum levels of tHcy, insulin, creatinine, folate and lipids were estimated using standard protocols. RESULTS: Fasting serum tHcy levels were higher in males than in females (geometric mean +/- SD, 13.75 mumol/l +/- 1.41 Vs. 9.58 mumol/l +/- 1.43, p<0.001) and were positively associated with age (r=0.204, p< 0.01) in both sexes. 32.3% of males and 10.3% of females had mild hyperhomocysteinemia (tHcy>15mumol/l). tHcy levels were significantly higher in smokers than in non-smokers (geometric mean +/- SD, 14.58 mumol/l +/- 1.44 Vs.12.71 mumol/l +/- 1.37, p<0.05) and in alcohol consumers than in non-consumers (geometric mean +/- SD, 14.53 mumol/l +/- 1.43 Vs.12.14 mumol/l +/- 1.32, p< 0.02). In males, tHcy levels were negatively related to serum insulin (r= -0.397, p<0.001) and BMI (r= -0.244, p <0.02) and positively related to serum creatinine (r=0.235, p<0.02). In females, there was a positive relationship between tHcy and systolic blood pressure (r= 0.239, p<0.02) but there was no significant correlation with serum insulin. In both sexes, serum tHcy levels strongly correlated with serum folate (r= -0.412, p<0.001). There were no significant associations between tHcy and serum lipids. Stepwise regression analysis confirmed the associations between tHcy and folate (p<0.001 in both sexes), insulin (p=0.026 in males) and creatinine (p=0.036 in males). CONCLUSION: Low intake of folate, alcohol consumption and smoking were associated with increased tHcy concentrations. Serum insulin and creatinine were independent correlates of tHcy in males, but not in females. Difference in tHcy levels between sexes may partly be attributed to differences in lean muscle mass and to a metabolic link between creatinine synthesis and homocysteine production. Insulin may regulate serum tHcy concentrations by homocysteine remethylation or by increasing homocysteine clearance.
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    Patterns of alcohol use and occurrence of alcoholic fatty liver disease: a prospective, community cohort, 7-year follow-up study
    (Sri Lanka Medical Association, 2017) 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 & OBJECTIVES: Data is limited on alcoholic fatty liver disease (AFLD). We investigated patterns of alcohol use and AFLD, among urban, adult, Sri Lankans. METHODS: Study population (selected by age-stratified random sampling from Ragama MOH-area) was screened initially in 2007 (35-64 years) and re-evaluated in 2014. On both occasions they were assessed by structured-interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. AFLD was diagnosed on ultrasound criteria, unsafe alcohol consumption (Asian standards: males>14units, females>7units per week) and absence of hepatitis B/C markers. Controls were individuals with unsafe alcohol consumption, but had no ultrasound criteria of AFLD. Case-control genetic-association for PNPLA3 (rs738409) polymorphism for AFLD was performed. RESULTS: A total of 2983/3012 (99%) had complete data. 272/2983(9.1%) were unsafe-drinkers [males- 70; mean-age 51.9 (SD-8.0) years]. 86/2983 (2.9%) of the cohort and 86/272 (31.6%) of unsafe-drinkers had AFLD [males-85; mean-age 50.2 (SD-8.6) years]. Males [p<0.001], increased waist circumference (WC) [p=0.001], BMI>23kg/m2 [p<0.001], raised triglycerides (TG) [p<0.001], low education level (LEL-not completed secondary-education) [p<0.01] and low monthly household-income (23kg/m2 [p<0.001], raised TG [p<0.001] and LEL [p<0.05] independently predicted incident-AFLD. The genetic association study [133-cases (combined 2007-2014), 97-controls] showed no association with AFLD at PNPLA3 (rs738409). CONCLUSION: The prevalence of AFLD was 2.9% in 2007 and annual incidence among heavy drinkers, after 7-year follow-up was 5.7%. Incident-AFLD was associated with males, obesity, raised TG and LEL.
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    Incidence, prevalence and demographic and life style risk factors for obesity among urban, adult Sri Lankans: a community cohort follow-up study
    (Sri Lanka Medical Association, 2017) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Kottachchi, D.; Ranasinghe, R.M.A.G.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.
    INTRODUCTION & OBJECTIVES: Obesity is a global problem. Data from the South Asian region is limited. METHODS: In a cohort follow-up study we investigated obesity among urban, adult, Sri Lankans (35-64y; selected by age-stratified random sampling from Ragama-MOH area; initial screening 2007; re-evaluation 2014). On both occasions structured interview, anthropometry, liver ultrasound, biochemical and serological tests were performed. Total body fat (TBF) and visceral fat percentage (VFP) were assessed by impedance in 2014. General-obesity (GO) was BMI>25kg/m2. Central-obesity (CO) was waist circumference (WC)>90cm males and WC>80cm females. Multinomial logistic regression was fitted to assess associations. RESULTS: In 2007 (n=2967), 614 (20.7%) were overweight [51.9%-women], 1161(39.1%) had GO [65.9%-women] and 1584(53.4%) had CO [71%-women]. Females (p<0.001), raised-TG (p<0.001), low-HDL (p<0.001), diabetes (p<0.001), hypertension (p<0.001), NAFLD (p<0.001), and low household income (p<0.001) were significantly associated with prevalent GO and CO respectively. Additionally, increased-age (p=0.05), low-educational level (p<0.001) and unhealthy eating (p<0.001) were associated with prevalent CO. Inadequate physical activity was not associated with either. 2137 (72%) attended follow-up in 2014. Of those who were initially non-obese who attended follow-up, 189/1270 (14.9%) [64% women] had developed GO (annual-incidence 2.13%) and 206/947 (21.9%) [56.3% women] had developed CO (annual incidence 3.12%) after 7 years. TBF and VFP significantly correlated with incident GO and CO (p<0.001). Female gender (OR-1.78, p<0.001; 2.81, p<0.001) and NAFLD (OR-2.93, p<0.001; OR-2.27, p<0.001) independently predicted incident GO and CO respectively. CONCLUSION: The prevalence and incidence of GO and CO were high in this cohort. Both incident GO and CO were strongly associated with female gender and NAFLD.
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    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.
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    Incidence and predictors of metabolic syndrome in an urban, adult Sri Lankan population – a community cohort follow-up study
    (Sri Lanka Medical Association, 2016) de Silva, S.T.; Niriella, M.A.; Kasturiratne, A.; Kottahachchi, D.; Ranawaka, U.K.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.
    INTRODUCTION: There is limited data on the incidence of metabolic syndrome (MetS) from the South Asian region. In 2007, we reported a 38.9% prevalence of MetS in an urban, adult Sri Lankan population. OBJECTIVES: This study investigated incidence and risk factors for MetS in this population cohort after seven years’ follow-up. METHOD: The study population (42-71-year-olds, selected by age-stratified random sampling from the Ragama MOH area) was screened initially in 2007 and invited for re-evaluation in 2014. On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, and biochemical and serological tests. MetS was diagnosed on established International Diabetes Federation (IDF 2006) criteria. RESULTS: 2155/2985 (72.2%) of the original cohort attended follow-up [1244 women, 911 men; mean-age 59.2 (SD 7.7) years]. 1227 fulfilled IDF criteria for MetS (prevalence 59.3%). Out of 1246 individuals who initially did not have MetS in 2007, 318 [225 women; mean age 57.5 (SD 7.7) years] had developed MetS after 7 years (annual incidence 3.65%). On logistical regression, female sex (OR 3.41; p<0.001), central obesity (OR=1.50, p=0.022), BMI >=23 (OR=3.82, p<0.001) and presence of non-alcoholic fatty liver disease (NAFLD) (OR=1.83, p=0.001) in 2007 were independently predictive of incident MetS. CONCLUSIONS: In this community cohort follow-up study, the annual incidence of MetS was 3.65%. Female gender, presence of NAFLD, central obesity and increased BMI predicted the development of future MetS.
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    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 declared