Medicine
Permanent URI for this communityhttp://repository.kln.ac.lk/handle/123456789/12
This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
Browse
17 results
Search Results
Item Development of a model for a resource limited setting, to predict the presence of oesophageal varices among newly diagnosed patients with cirrhosis.(Sri Lanka Medical Association., 2019) Perera, K.; Kodisinghe, S.K.; Ediriweera, D.; Moratuwagama, H.M.D.; Williams, S.; Pathmeswaran, A.; Niriella, M.A.; de Silva, H.J.INTRODUCTION & OBJECTIVES: In cirrhosis upper-gastrointestinal-endoscopy (UGIE) identifies oesophageal varices (OV). UGIE is unavailable in most resource-limited settings. Therefore, we assessed prediction of presence OV using hematological parameters (HP) and Child-Turcott-Pugh (CTP) class. METHODS: A prospective study was carried out on consecutive, consenting, newly-diagnosed patients with cirrhosis, in the University Medical Unit, Colombo North Teaching Hospital, Ragama, from April 20 I 4-April 2016. All patients had UGIE to evaluate presence and degree of OV, prior to appropriate therapy. HP (FBC with indices using automated analyzer and peripheral blood smear using Leishmann stain) and CTP class were assessed. Linear logistic regression model was developed to predict OV using HP and CTP class. RESULTS: 54-patients with cirrhosis were included [14(26%), 24(44%) and 16(30%) belonged to CTP class A, B and C respectively]. 37 had varices [CTP-A 4/14(26.6%), CTP-B 19/24(79.2%), CTP-C 14/16(87.5%)] on UGIE. Generalized linear model fitting showed decreasing percentage of small platelets (%SP) (P=0.002), CTP-B (P=0.003) and CTP-C (P=0.003) compared to CTP-A had higher probability of having OV. The model predicts the log odds for having OV = - 0.189 - (0.046*%SP) + 2.9 [if CTP-B] + 3.7 [if CTP-C]. Based on ROC analysis, a model value >-0.19 was selected as the cutoff point to predict OV with 89%-sensitivity, 76%-specificity, 89% positive predictive value and 76%-negative predictive value. CONCLUSION: We constructed a model using %SP on peripheral blood smear and CTP class. This model can be used to predict the presence of OV, in newly diagnosed patients with cirrhosis, with high sensitivity and specificity, avoiding the need for initial UGIE.Item Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka(Springer, 2019) Niriella, M.A.; Kasturiratne, A.; Pathmeswaran, A.; de Silva, S.T.; 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.; Wickremasinghe, A.R.; Takeuchi, F.; Kato, N.; de Silva, H.J.INTRODUCTION: While patients with non-alcoholic fatty liver disease (NAFLD) are mostly overweight or obese, some are lean. METHODS: In a community-based follow-up study (baseline and follow-up surveys performed in 2007 and 2014), we investigated and compared the clinical characteristics, body composition, metabolic associations and outcomes, and other risk factors among individuals with lean (BMI < 23 kg/m2) NAFLD, non-lean (BMI ≥ 23 kg/m2) NAFLD and those without NAFLD. To investigate associations of selected genetic variants, we performed a case-control study between lean NAFLD cases and lean non-NAFLD controls.RESULTS: Of the 2985 participants in 2007, 120 (4.0%) had lean NAFLD and 816 (27.3%) had non-lean NAFLD. 1206 (40.4%) had no evidence of NAFLD (non-NAFLD). Compared to non-lean NAFLD, lean NAFLD was commoner among males (p < 0.001), and had a lower prevalence of hypertension (p < 0.001) and central obesity (WC < 90 cm for males, < 80 cm for females) (p < 0.001) without prominent differences in the prevalence of other metabolic comorbidities at baseline survey. Of 2142 individuals deemed as either NAFLD or non-NAFLD in 2007, 704 NAFLD individuals [84 lean NAFLD, 620 non-lean NAFLD] and 834 individuals with non-NAFLD in 2007 presented for follow-up in 2014. There was no difference in the occurrence of incident metabolic comorbidities between lean NAFLD and non-lean NAFLD. Of 294 individuals who were non-NAFLD in 2007 and lean in both 2007 and 2014, 84 (28.6%) had developed lean NAFLD, giving an annual incidence of 4.1%. Logistic regression identified the presence of diabetes at baseline, increase in weight from baseline to follow-up and a higher educational level as independent risk factors for the development of incident lean NAFLD. NAFLD association of PNPLA3 rs738409 was more pronounced among lean individuals (one-tailed p < 0.05) compared to the whole cohort sample. CONCLUSION: Although lean NAFLD constitutes a small proportion of NAFLD, the risk of developing incident metabolic comorbidities is similar to that of non-lean NAFLD. A PNPLA3 variant showed association with lean NAFLD in the studied population. Therefore, lean NAFLD also warrants careful evaluation and follow-up.Item Serious thiopurine adverse effects and discontinuation among inflammatory bowel disease patients in Sri Lanka(Sri Lanka Medical Association, 2017) Niriella, M.A.; Kodisinghe, S.K.; Dassanayake, S.U.B.; Rajapakshe, N.; Nanayakkara, S.D.; Luke, H.P.D.P.; Silva, K.T.M.; de Silva, A.P.; Navarathne, N.M.M.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Thiopurines such as azathioprine and 6-mercaptopurine use for long term is not uncommon for patients with inflammatory bowel disease (IBD). Severe thiopurine adverse effects are dependent on thiopurine methyltransferase (TPMT) activity. TPMT testing prior to commencing thiopurine has been suggested to identify individuals with low TPMT activity, so that thiopurine use can be avoided in such patients. There is very limited data on thiopurine adverse effects among IBD patients in South Asia. METHODS: Patients with histologically proven IBD [ulcerative colitis (UC), Crohn’s disease (CD)], diagnosed over a ten year period from May 2005 to April 2015, with at least one year of regular follow up, were included from Colombo North Teaching Hospital and National Hospital of Sri Lanka (two main IBD referral centers). Frequency of thiopurine use, thiopurine adverse effects (myelosuppression and hepatotoxicity), and drug discontinuation were noted. RESULTS: A total of 214 patients were eligible for inclusion [UC-148 (69.2%), 75 (50.7%) males, median follow up (IQR) 55.0 (30-81) months; CD-66 (30.8%), 31 (47.0%) males, median follow up (IQR) 41.5 (26.5-68) months]. Thiopurine was used in 74 (50.0%) and 60 (90.9%) of UC and CD patients, respectively. Very few had severe thiopurine adverse effects that led to discontinuation of treatment [UC-4 (2.7%); CD-4 (6%)]. These were myelosuppression (6 patients) and hepatotoxicity (2 patients). CONCLUSION: In this cohort of Sri Lankan IBD patients, severe thiopurine adverse effects resulting in discontinuation of treatment was uncommon. Routine TPMT testing prior to thiopurine use does not seem warranted in the Sri Lankan setting.Item Changing phenotype, early clinical course and clinical predictors of irritable bowel syndrome in Sri Lanka: a prospective, multi-centre descriptive study(Sri Lanka Medical Association, 2017) Niriella, M.A.; Kodisinghe, S.K.; Nanayakkara, S.D.; Silva, K.T.M.; Rajapakshe, N.; Luke, D.; de Silva, A.P.; Navarathne, N.M.M.; Dissanayake, V.H.W.; Jayasekara, R.W.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Incidence of inflammatory bowel disease (IBD) is increasing in the Asia Pacific, with changes in phenotype and disease course been reported. METHODS: Ulcerative colitis (UC) and Crohn disease (CD) cases from four national referral centres were included. Phenotype was compared for cases [Group-1/G1-diagnosed between June/2003-December/2009, Group-2/G2-January/2010-June/2016]. Early clinical course (ECC) [complicated disease (Comp D-stricturing/penetrating CD, extensive-UC/pancolitis), treatment refractory disease (TRD-frequently-relapsing, steroid-dependent/refractory, biologics), disease complications (DC-perforation/bleeding/colectomy/malignancy)] among disease duration <3 years, and clinical predictors (CP) of CompD/TRD/DC among disease duration >1 year were also assessed. RESULTS: A total of 452-cases [G1: UC-89 (78.8%), CD-24 (21.2%); G2: UC-197 (58.1%), CD-142 (41.9%)] were included. G2 had a higher proportion of CD (p<0.001). In both groups, leftsided colitis (E2) for UC, ileo-colonic (L3)/non-stricturing, non-penetrating (B1) for CD predominated. More penetrating-CD (B3) in G2 (p<0.01) and more stricturing-CD (B2) in G1 (p<0.05) were noted. ECC was assessed in 293 patients [UC-168 (57.3%), CD-125 (42.7%)]. Among UC: extensive/pan-colitis (E3)-40 (24.5%), severe (S3)-38 (42.2%); among CD:severe episodes-15 (25.9%), stricturing (B2)/penetrating(B3)-18 (14.7%), perianal-disease (P)-29 (23.4%). TRD was seen in 19 (11.3%)-UC and 17 (10.1%)-CD. Immunomodulator use was-70 (41.7%)/93 (74.4%), and anti-TNF use was 3 (1.8%)/12 (9.6%) respectively for UC and CD. Complications for UC: bleeding-6 (3.6%), malignancy-1 (0.6%), surgery-3 (1.8%); for CD: stricture-6 (4.9%), perforation-3 (2.4%), malignancy-1 (0.8%), surgery-2 (1.6%). CP were assessed in 373 [UC-266 (71.3%), CD 107 (28.7%)]. EIM of joints predicted CompD in UC/CD (OR-1.94/OR-2.28). Family history (OR=8.64) and EIM of joints (OR=10.07) predicted DC in UC. CONCLUSION: There was an increase in CD during the study period, but no changes in disease phenotype for UC or CD. Although admissions with CompD were common for UC (but not CD), few patients had TRD or DCs indicating a relatively benign early disease course. Family history, EIM of joints predicted poor outcomes in UC, EIM of joints predicted a poor outcome in CD.Item Influence of urban/rural and coastal/inland environment on the phenotype and clinical course of inflammatory bowel disease patients from Sri Lanka: a cross-sectional study(Sri Lanka Medical Association, 2017) Niriella, M.A.; Kodisinghe, S.K.; Dinamithra, N.P.; Rajapakshe, N.; Nanayakkara, S.D.; Luke, H.P.D.P.; Silva, K.T.M.; de Silva, A.P.; Navarathne, N.M.M.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Rural/urban and coastal/inland environmental influences on inflammatory bowel disease (IBD) is poorly studied. We investigated such environmental influences on IBD. METHODS: Patients with histologically proven IBD [ulcerative colitis (UC), Crohn disease (CD)] with a permanent residence and regular follow up, were included. Urban areas (UA) were defined as those administered by Municipal and Urban councils. Coastal areas (CA) were defined as areas with elevation <30 meters above sea level. Patients in different groups were compared with regard to phenotype of IBD [sex, age at diagnosis, Montreal subgroups, severity, extraintestinal manifestation (EIM) at diagnosis, and highest therapy during follow-up]. Fisher’s exact test was used to compare categorical variables. RESULTS: A total of 387 patients were included [UC-251 (64.8%), males-122 (48.6%), median followup (IQR)-22.5 (2-59) months; CD-136 (35.2%), males-65 (47.8%), median follow-up (IQR)- 63.0 (23-115) months; urban/rural distribution: UC-1.7:1, CD-1.5:1; coastal/inland distribution: both UC and CD-0.7:1]. Urban/rural or coastal/inland location did not affect the distribution of type of IBD, gender, age at diagnosis or presence of EIM. UC patients from rural areas had extensive disease (E3) (42.4% vs 24.5%, p=0.029) and used long term immunomodulator drugs more frequently (60.2% vs 47.3%; P=0.006) than UA patients. CD patients living in CA had more frequent ileo-colonic disease (L3) compared to inland patients (53.2% vs 38.0%, p=0.016). Patients with both UC and CD from inland areas needed immunomodulators or anti-TNF more frequently than coastal patients (56.7% vs 44.9%, p=0.026 and 82.1% vs 69.9%, p=0.023). CONCLUSION: IBD was more common among patients from inland, UA. Urban/rural or coastal/inland location did not affect gender, age at diagnosis or presence of EIM. However, UC patients from rural areas and CD patients from inland areas had more severe disease.Item 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.Item Early clinical course of IBD in Sri Lanka(Sri Lanka Medical Association, 2016) Niriella, M.A.; Kodisinghe, S.K.; Dinamithra, N.P.; Rajapakshe, N.; Nanayakkara, S.D.; Luke, H.P.D.P.; Silva, K.T.M.; Dassanayake, A.S.; de Silva, A.P.; Navarathne, N.M.M.; de Silva, H.J.INTRODUCTION: There is very limited data on the early clinical course of IBD from Sri Lanka. METHOD: Patients with histologically proven IBD [ulcerative colitis(UC), Crohn disease(CD)] of less than 3 years duration, were included from Colombo North Teaching Hospital and National Hospital of Sri Lanka (two main referral centers). Complicated disease behaviour (stricturing or penetrating CD, extensive or pancolitis for UC), treatment refractory disease (frequently relapsing, steroid dependent, steroid refractory, need for biologics) and complications (perforation, bleeding, colectomy and malignancy) were analysed. RESULTS: 177 patients were eligible for inclusion [UC-97(54.8%), 46(47.4%) males, median follow up (IQR) 17.0(5.5-28) months; CD 80(45.2%), 39(48.8%) males, median follow up (IQR) 7(2-21.5) months]. Admissions with severe episodes of extensive or pancolitis for UC were 26(26.8%) and 20(21.1%) respectively. Admissions with severe episodes, stricturing(B2), penetrating(B3) or perianal disease(P) for CD were 7(8.8%), 9(11.5%) and 16(20%) respectively. Treatment refractoriness (steroid dependency, steroid refractory or frequently relapsing) was 6(9.6%) for UC and 6(8.4%) for CD. Immunomodulator use was 35 (37.2%) and 56(72.7%), and Anti-TNF agent use 2(2.1%) and 2(2.6%) respectively for UC and CD. Few had complications [UC-bleeding 5(5.2%), malignancy 1(1%), surgery 2(2.1%); CD-stricture 3(3.8%), perforation 3(3.8%), malignancy 1(1.3%), surgery 3(3.8%)]. CONCLUSIONS: In the early clinical course of this cohort of IBD patients, admissions with complicated disease were common for UC but not CD. Few patients were treatment refractory. Immunomodulator use was more common for CD, but need for biologics was rare for both. Few IBD patients developed complications. This indicates a relatively benign early disease course.Item Changing phenotype of IBD in Sri Lanka(Sri Lanka Medical Association, 2016) Niriella, M.A.; Kodisinghe, S.K.; Dinamithra, N.P.; Rajapakshe, N.; Nanayakkara, S.D.; Luke, H.P.D.P.; Silva, K.T.M.; Dassanayake, A.S.; de Silva, A.P.; Navarathne, N.M.M.; de Silva, H.J.INTRODUCTION: Inflammatory bowel disease (IBD) is increasing in Asia Pacific, with recent changes in phenotype reported from some countries. METHOD: Patients with histologically proven IBD [ulcerative colitis(UC), Crohn’s disease(CD), unclassified(U)], diagnosed between January 2006-December 2010 (Group 1) and January 2011-December 2015 (Group 2), who had regular follow up, were included from Colombo North Teaching Hospital and National Hospital of Sri Lanka (two main referral centers). The two groups were compared with regard to phenotype of IBD (subgroups, severity, age at diagnosis, duration of symptoms, extra-intestinal manifestations (EIM) at diagnosis, cigarette smoking, family history, and highest therapy during follow up). RESULTS: 304 patients were included [Group 1: UC-72(74.2%), CD-25(25.8%); Group 2: UC-113(54.6%), CD-90(43.5%), U-4(1.9%)]. There were more females in Group 2 for UC and CD. Median age at diagnosis was similar for UC but higher for CD in Group 2 compared to Group 1.The median duration of symptoms to diagnosis was not different for UC and CD in the two groups. In both groups, left sided colitis (E2) predominated for UC and Ileo-colonic disease (L3) and non-stricturing, non-penetrating (B1) disease predominated for CD. There was no difference in degree of severity, rate of complications, pattern of EIM, smoking history at presentation, family history or highest therapy during follow up for either disease in the two groups (Table 1). CONCLUSIONS: During the 10 years, there seems to be a recent increase in the proportion of CD among IBD patients. However, there were no major changes in disease phenotype for UC or CD.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 in an urban, adult Sri Lankan population – a community cohort follow-up study(Sri Lanka Medical Association, 2016) Niriella, M.A.; Kasturiratne, A.; de Silva, S.T.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyarathna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.INTRODUCTION: In 2007, we reported a 33% prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with PNPLA3(rs738409) gene polymorphism in an urban, adult Sri Lankan population. OBJECTIVES: This study investigated incidence and risk factors for NAFLD 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 re-evaluated in 2014. On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. NAFLD was diagnosed on established 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 incident NAFLD was also performed. RESULTS: 2155/2985 (72.2%) of the original cohort attended follow-up [1244-women, 911-men; mean-age 59.2(SD, 7.7) years]. 1322 [839 women; mean-age 58.9 (SD, 7.6) years] had NAFLD. Out of 795 [466 women] who initially did not have NAFLD, 365 [226 women, mean-age 58.6(SD,7.9) years] had developed NAFLD after 7 years (annual incidence-6.6%). Increased waist circumference [p=0.001], BMI>23kg/m2 [p<0.001] and raised plasma triglycerides [p<0.05] independently predicted incident NAFLD. The updated genetic association study (1310 cases, 427 controls) showed borderline association with NAFLD at 2/10 candidate loci: PPP1R3B(rs4240624), PNPLA3(rs738409) (one-tailed p=0.044 and 0.033, respectively). CONCLUSIONS: In this community cohort follow-up study, the annual incidence of NAFLD was 6.6%. Incident NAFLD was associated with features of metabolic syndrome, and showed tendency of association with PNPLA3 and PPP1R3B gene polymorphisms.