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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Nonalcoholic Fatty Liver Disease: identifying the disease burden in Sri Lanka(Jaypee Prothers Medical Publishers, 2018) Dassanayake, A.S.Nonalcoholic fatty liver disease (NAFLD) is becoming one of the most important causes for chronic liver disease and also hepatocellular carcinoma (HCC) in Sri Lanka. This tendency is also recognized worldwide. More than half of the middle-aged and elderly adults in urban Sri Lanka have ultrasonic evidence of NAFLD. The NAFLD is also identified in population from rural areas of Sri Lanka and also in children. Nonalcoholic steatohepatitis (NASH) cirrhosis is the most common cause of referral for liver transplantation in Sri Lankans. The NASH is also the most common cause for rejecting potential donors for liver transplantation in Sri Lanka. Patients who underwent liver transplantation for cryptogenic cirrhosis developed evidence of NASH following liver transplantation. Recent evidence suggests that there is a genetic component to NAFLD. PNPLA3, a single gene polymorphism linked to the short arm of chromosome 22, is associated with the severity of NAFLD. The presence of this genetic polymorphism appears to carry higher risk of patients with NAFLD developing NASH with fibrosis cirrhosis and hepatocellular carcinoma. In a large population-based study from Sri Lanka, there was a tendency to develop NAFLD associated with this genetic polymorphism. In a population-based study, NAFLD was identified as an independent risk factor for development of diabetes. This association is recognized worldwide now. Most patients with HHC in Sri Lanka developed it on a back ground of cryptogenic cirrhosis. At the same time, the prevalence of the markers for hepatitis B and C was rare in Sri Lankan patients with HCC.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 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 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 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.