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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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 Epidemiology of Non-Alcoholic Fatty Liver Disease (NAFLD) among adults in an urban Sri Lankan community(American Gastroenterological Association(AGA) Institute, Published by Elsevier Inc., 2008) Dassanayake, A.S.; Rajindrajith, S.; Kasturiratne, A.; Kalubowila, U.; de Silva, A.P.; Mizoue, T.; Makaya, M.; de Silva, H.J.BACKGROUND - Non-alcoholic fatty liver disease (NAFLD) is increasing in the Asia-Pacific region.NAFLD can progress from simple steatosis, through steatohepatitis to advanced hepatic fibrosis, cirrhosis and hepatoma. Its prevalence in Sri Lanka is not known. OBJECTIVE: To investigate community prevalence and risk factors associated with NAFLD among adults in an urban Sri Lankan population. DESIGN, SETTING AND METHODS: The sample consisted of 2985 randomly selected subjects, 35-65 years old, resident in the Ragama Medical Officer of Health area. NAFLD was diagnosed on ultrasound criteria (presence of 2 out of 3: increased hepatic echogenicity compared to spleen or kidney, blurring of hepatic vasculature, deep attenuation of ultrasound signal), when alcohol intake was <14 units/week for males and <7 units/week for females. Anthropometric and blood pressure (BP) measurements were made; fasting blood glucose and insulin, lipid profile and serum alanine transaminase (ALT) were estimated (normal cutoff values were based on revised ATP III criteria of metabolic syndrome for Asians). RESULTS: 974 (35%) individuals had NAFLD [mean age 52.8 years (SD 7.3), 605 (62.1%) females]. On multivariate analysis, male sex, presence of acanthosis nigricans, central obesity (BMI>25kg/m2 and/or waist circumference >90cm for males, >80cm females), elevated fasting plasma glucose (>100mg/dl),Insulin resistance(HOMA-IR>1), elevated diastolic BP (>85mmHg), elevated plasma triglycerides (>150mg/dl), elevated ALT (> twice the upper limit of normal), and low high density lipoprotein cholesterol (<40mg/dl for men, <50mg/dl for women) were significantly associated with NAFLD. CONCLUSIONS: The prevalence of NAFLD among adults in this urban Sri Lankan community is as high as in western populations. NAFLD is associated with factors that constitute the metabolic syndromeItem 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 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 Epidemiology of non- alcoholic fatty liver disease (NAFLD) in an urban Sri Lankan population(Sri Lanka Medical Association, 2008) Dassanayake, A.S.; Rajindrajith, S.; Kasturiratne, A.; Kalubowila, U.; de Silva, A.P.; Mizoue, T.; Makaya, M.; de Silva, H.J.BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasing in the Asia-Pacific region. NAFLD can progress from simple steatosis, through steatohepatitis to advanced hepatic fibrosis, cirrhosis and hepatoma. Its prevalence in Sri Lanka is not known. Objective: To investigate community prevalence and risk factors associated with NAFLD among adults in an urban Sri Lankan population. DESIGN, SETTING AND METHODS: The sample consisted of 2985 randomly selected subjects, 35-65 years old, resident in the Ragama Medical Officer of Health area. NAFLD was diagnosed on ultrasound criteria (presence of 2 out of 3: increased hepatic echogenicity compared to spleen or kidney, blurring of hepatic vasculature, deep attenuation of ultrasound signal), and when alcohol intake was <14 units/week for males and <7 units/week for females. Anthropometric and blood pressure (BP) measurements were made; fasting blood glucose, lipid profile and serum alanine transaminase (ALT) were estimated (normal cutoff values were based on revised ATP III criteria of metabolic syndrome for Asians). RESULTS: 974(35%) individuals had NAFLD [mean age 52.8 years (SD 7.3), 605 (62.1%) females]. On multivariate analysis, central obesity (BMI>25kg/m2 and/or waist circumference >90cm for males, >80cm females), elevated fasting plasma glucose (>100mg/dl), elevated diastolic BP (>85mmHg), elevated plasma triglycerides (>150mg/dl), elevated ALT (>twice the upper limit of normal), and low high density lipoprotein cholesterol (<40mg/dl for men, <50mg/dl for women) were significantly associated with NAFLD. CONCLUSIONS: The prevalence of NAFLD among adults in this urban Sri Lankan community is as high as in western populations. NAFLD is associated with factors that constitute the metabolic syndrome.Item 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.