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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 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 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 Genetic variants of NAFLD in an urban Sri Lankan community(Wiley Blackwell Scientific Publications, 2013) Niriella, M.A.; Kasturiratne, A.; Akiyama, K.; Takeuchi, F.; Isono, M.; Dassanayake, A.S.; de Silva, A.P.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.OBJECTIVE: Recently, genome-wide association studies (GWAS) have successfully identified loci associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in populations of European descent. No large-scale genetic studies have been performed thus far in South Asian populations. Therefore, as part of a community-based cohort study in an urban adult population of Sri Lankans, we investigated associations of genetic variants with NAFLD, diagnosed on established ultrasound criteria, and its related phenotypes. METHODS: We selected 10 single nucleotide polymorphisms (SNPs), all previously reported to be associated with NAFLD in populations of European and/or South Asian ancestry, for a case-control replication study. They included loci derived from GWAS [PNPLA3 (rs738409), LYPLAL1 (rs12137855), GCKR (rs780094), PPP1R3B (rs4240624) and NCAN (rs2228603)] plus those from candidate gene studies [APOC3 (rs2854117 and rs2854116), ADIPOR2 (rs767870) and STAT3 (rs6503695 and rs9891119)]. Genotype data of 2988 participants were used for the analysis. RESULTS: A significant NAFLD association was observed for PNPLA3 (rs738409) [OR = 1.25, 95% CI 1.08–1.44, P = 0.003)]; rs738409 was also associated with a trend towards lower serum triglycerides APOC3 variants were significantly (P = 7.3–7.5 × 10–8) associated with higher triglycerides, but not with NAFLD (OR = 0.86). Apart from SNP–lipid associations previously reported at the GCKR, PPP1R3B and NCAN loci, there were no other prominent associations. CONCLUSION: Our data confirm that the PNPLA3 gene variant is significantly associated with NAFLD in the general Sri Lankan population but could not replicate previously reported disease associations at other loci, reinforcing the importance of further large-scale study on genetic variants in diverse populations to better understand the pathophysiology of NAFLD.Item Is Acanthosis Nigricans a useful clinical screening test for non-alcoholic fatty liver disease(NAFLD) in resource poor settings(Elsevier, 2009) Niriella, M.A.; Dassanayake, A.S.; Kalubowila, K.V.U.; de Silva, A.P.; Wickremasinghe, A.R.; Kato, N.; Makaya, M.; de Silva, H.J.BACKGROUND: Acanthosis nigricans (AN) is an easily detectable papillomatosis and hyperkeratosis of the skin associated with insulin resistance. Insulin resistance is widely accepted as the underlying cause of Non- Alcoholic Fatty Liver Disease (NAFLD). Ultrasonography is the currently accepted tool to screen for NAFLD in the community, but is expensive and needs expertise. OBJECTIVES: To investigate whether AN would be an useful screening test for NAFLD in an adult Sri Lankan population. METHODS: This study was part of a community based investigation −Ragama Health Study (RHS). The study population consisted of 35−64 year old adults, selected using stratified random sampling. Consenting adults were screened by a structured interview, clinical examination, liver ultrasound and collection of 10 ml venous blood. NAFLD was diagnosed based on established ultrasound criteria for fatty liver, safe alcohol consumption and absence of serum markers for Hepatitis B and C. AN was identified by the presence of dark, thick, velvety skin in the neck, body folds and creases. Results: 3012 subjects participated in the study. AN was present significantly more frequently among NAFLD patients than normal individuals in both males (37.9% vs. 4.8%, p <0.001) and females (39.8% vs. 5.8%,p<0.001). The sensitivity, specificity, and positive predictive value of AN for NAFLD was 37.9%, 95.2%, 78.0% for males and 39.8%, 94.2%, and 81.3% for females respectively. CONCLUSION: AN is significantly more common in NAFLD than normal individuals. Although AN has a high specificity, it is not an useful test to screen for NAFLD in the community.Item Association of genetic variants with non-alcoholic fatty liver disease in an urban Sri Lankan community(Wiley-Blackwell, 2015) Kasturiratne, A.; Akiyama, K.; Niriella, M.A.; Takeuchi, F.; Isono, M.; Dassanayake, A.S.; de Silva, A.P.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.Item Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus(Wiley-Blackwell, 2013) Kasturiratne, A.; Weerasinghe, S.; Dassanayake, A.S.; Rajindrajith, S.; de Silva, A.P.; Kato, N.; Wickremasinghe, A.R.; de Silva, H.J.BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is linked to metabolic syndrome, and is known to be associated with impaired fasting glycemia and diabetes mellitus. This prospective community-based study was conducted to determine the association between NAFLD and incidence of diabetes mellitus in an urban adult population in Sri Lanka. METHODS: Participants of the Ragama Health Study cohort were assessed for NAFLD using established ultrasound criteria in 2007. Those who were free of diabetes at baseline were followed up for 3 years. Incidence rates of diabetes mellitus were compared between subjects with and without NAFLD at baseline. RESULTS: Out of 2984 subjects, 926 had NAFLD and 676 had diabetes in 2007. Of the 2276 subjects who were free of diabetes in 2007, 1914 were re-assessed in 2010. After 3 years, 104 out of 528 subjects with NAFLD and 138 out of 1314 subjects without NAFLD had developed diabetes mellitus de novo. Incidence rates of diabetes were respectively 64.2 and 34 per 1000 person-years of follow up for those with and without NAFLD. NAFLD was an independent predictor of developing diabetes mellitus. Other independent predictors were impaired fasting glycemia and dyslipidemia. CONCLUSIONS: Subjects with ultrasonically diagnosed NAFLD have an increased risk of developing diabetes mellitus. Intervention for NAFLD through lifestyle modification may prevent progression of the current diabetes epidemic. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.Item Prevalence and risk factors for non-alcoholic fatty liver disease among adults in an urban Sri Lankan population(Wiley-Blackwell, 2009) Dassanayake, A.S.; Kasturiratne, A.; Rajindrajith, S.; Kalubowila, U.; Chackrewarthy, S.; de Silva, A.P.; Makaya, M.; Mizoue, T.; Kato, N.; Wickremasinghe, A.R.; de Silva, H.J.BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in the Asia-Pacific region. However, its prevalence and risk factors in Asian (especially South Asian) communities is poorly studied. In this study, the aim was to determine the community prevalence and risk factors for NAFLD among adults in an urban Sri Lankan population. METHODS: The study population consisted of 35-64-year-old adults, 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. Blood pressure (BP) and anthropometric measurements were made, and fasting glucose, glycosylated hemoglobin, serum lipids, fasting serum insulin and serum alanine aminotransferase (ALT) were determined. RESULTS: Of the 2985 study participants, 974 (32.6%) had NAFLD (605 [62.1%] women, mean age 52.8 years [standard deviation, 7.3]). On multivariate analysis, obesity, acanthosis nigricans, insulin resistance, elevated diastolic BP, fasting plasma glucose, plasma triglycerides, and ALT twice the upper limit of the reference range or more were independently associated with NAFLD. CONCLUSION: The prevalence of NAFLD among adults in this urban Sri Lankan community is high and is strongly associated with constituent features of the metabolic syndrome.