Medicine
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Item Changing phenotype, early clinical course and clinical predictors of inflammatory bowel disease in Sri Lanka: a retrospective, tertiary care-based, multi-centre study(BioMed Central, 2021) Niriella, M.A.; Liyanage, I.K.; Kodisinghe, S.K.; de Silva, A.P.; Jayatissa, A.V.G.A.M.; Navarathne, N.M.M.; Peiris, R.K.; Kalubovila, U.P.; Kumarasena, S.R.; Jayasekara, R.W.; de Silva, H.J.BACKGROUND: Inflammatory bowel disease (IBD) is increasing in the Asia-Pacific region, with changes in disease phenotype and course. We aimed to assess the changing phenotypes of IBD over ten years, describe the early clinical course (ECC) and identify the clinical predictors (CP) of poor outcomes among a large, multi-centre, cohort of Sri Lankan IBD patients. METHODS: We included patients [diagnosed between June/2003-December/2009-Group-1(G1), January/2010-June/2016-Group-2(G2)] with ulcerative colitis (UC) and Crohn disease (CD) from five national-referral centres. Changing phenotype from G1 to G2, ECC (disease duration < 3-years) and CP of poor outcomes (disease duration ≥ 1-year) was assessed. Poor outcomes were complicated-disease (CompD-stricturing/penetrating-CD, extensive-UC/pancolitis, perforation/bleeding/colectomy/malignancy) and treatment-refractory disease (TRD-frequently-relapsing, steroid-dependent/refractory and biologic use). RESULTS: 375 (UC-227, CD-148) patients were recruited. Both G1/G2 had more UC than CD (77% vs 23%, 54.5 vs 45.5 respectively, p < 0.01). Increase of CD from G1-to-G2 was significant (23-45.4%, p < 0.001). In both groups, left-sided colitis (E2) and ileo-colonic (L3)/non-stricturing, non-penetrating disease behaviour (B1) CD predominated. Extensive-colitis (E3) (36.4% vs 22.7, p < 0.05) and stricturing-CD (B2) (26.1% vs 4.0%, p < 0.01) was commoner in G1. ECC was assessed in 173-patients (UC-94, CD-79). Aggressive disease behaviour and TRD were low among both UC and CD. Immunomodulator use was significantly higher among CD than UC (61.5% vs 29.0% respectively, p < 0.01). Anti-TNF use was low among both groups (UC-3.2%, CD-7.7%). Disease complications among UC [bleeding (2.1%), malignancy-(1.1%), surgery-(2.1%)] and CD [stricture-(3.9%), perforation-(1.3%), malignancy-(1.3%), surgery-(8.9%)] were generally low. CPs were assessed in 271-patients (UC-163, CD-108). Having a family history of IBD (for UC), extraintestinal manifestation (EIM), severe disease at presentation, being in younger age categories and severe disease at presentation, (for both UC and CD) predicted poor outcomes. CONCLUSION: There was an increase in CD over time without change in disease phenotype for both UC and CD. A relatively benign ECC was observed. Family history (UC), EIMs (UC/CD), severe disease at presentation (UC/CD), younger age (CD/UC) CPs of poor outcomes. KEYWORDS: Clinical course; Clinical predictors; Crohn disease; Inflammatory bowel disease; Phenotype; Sri Lanka; Ulcerative colitis.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 Non-resolution of non-alcoholic fatty liver disease (NAFLD) among urban, adult Sri Lankans in the general population: A prospective, cohort follow-up study.(Public Library of Science, 2019) Niriella, M.A.; Kasturiratne, A.; Beddage, T.; Ediriweera, D.S.; de Silva, S.T.; Perera, K.R.; Subasinghe, C.E.; Kodisinghe, S.K.; Piyaratna, T.C.; Rishikesawan, V.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.BACKGROUND: There are few studies investigating the natural course of non-alcoholic fatty liver disease (NAFLD) in the community. We assessed resolution of NAFLD in a general population cohort of urban Sri Lankans adults. METHODS: Participants were selected by age-stratified random sampling from electoral lists. They were initially screened in 2007 and re-evaluated in 2014. On both occasions structured interview, anthropometric-measurements, liver ultrasonography, and biochemical/serological tests were performed. NAFLD was diagnosed on ultrasound criteria for fatty liver, safe-alcohol consumption (<14-units/week for men, <7-units/week for women) and absence of hepatitis B/C markers. Non-NAFLD was diagnosed on absence of any ultrasound criteria for fatty liver and safe-alcohol consumption. Resolution of NAFLD was defined as absence of ultrasound criteria for fatty liver. Changes in anthropometric indices [Weight, Body-Mass-Index (BMI), waist-circumference (WC), waist-hip ratio (WHR)], clinical [systolic blood pressure (SBP), diastolic blood pressure (DBP)] and biochemical measurements [Triglycerides (TG), High Density Lipoprotein (HDL), Total Cholesterol (TC), HbA1c%] at baseline and follow-up were compared. RESULTS: Of the 2985 original study participants, 2148 (71.9%) attended follow-up after 7 years. This included 705 who had NAFLD in 2007 and 834 who did not have NAFLD in 2007. Out of 705 who had NAFLD in 2007, 11(1.6%) changed their NAFLD status due to excess alcohol consumption. After controlling for baseline values, NAFLD patients showed significant reduction in BMI, weight, WHR, HDL and TC levels and increase in HbA1c levels compared to non-NAFLD people. Despite this, none of them had complete resolution of NAFLD. CONCLUSION: We did not find resolution of NAFLD in this general population cohort. The observed improvements in anthropometric, clinical and biochemical measurements were inadequate for resolution of NAFLD.nal Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo, Japan.Item Percentage of small platelets on peripheral blood smear and Child-Turcott-Pugh class can predict the presence of oesophageal varices in newly diagnosed patients with cirrhosis: development of a prediction model for resource limited settings(BioMed Central, 2019) Perera, K.; Kodisinghe, S.K.; Ediriweera, D.S.; Moratuwagama, D.; Williams, S.; Pathmeswaran, A.; Niriella, M.A.; de Silva, H.J.BACKGROUND:In cirrhosis upper-gastrointestinal-endoscopy (UGIE) identifies oesophageal varices (OV). UGIE is unavailable in most resource-limited settings. Therefore, we assessed prediction of presence of 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, Sri Lanka from April 2014-April 2016. All patients had UGIE to evaluate presence and degree of OV, prior to appropriate therapy. HP (full blood count with indices using automated analyzer and peripheral blood smear using Leishmann stain) and CTP class were assessed on admission. 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 receiver operating characteristic (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.CONCLUSIONS:We constructed a model using %SP on peripheral blood smear and CTP class. This model may be used to predict the presence of OV, in newly diagnosed patients with cirrhosis, with acceptable sensitivity and specificity, to prioritize the patients who deserve early UGIE in limited resource settingsItem Genetic associations of inflammatory bowel disease in a South Asian population(Baishideng Publishing Group, 2018) Niriella, M.A.; Liyanage, I.K.; Kodisinghe, S.K.; Silva, A.P.; Rajapakshe, N.; Nanayakkara, S.D.; Luke, D.; Silva, T.; Nawarathne, M.; Peiris, R.K.; Kalubovila, U.P.; Kumarasena, S.R.; Dissanayake, V.H.W.; Jayasekara, R.W.; de Silva, H.J.AIM: To estimate prevalence and phenotypic associations of selected inflammatory bowel disease (IBD)-associated genetic variants among Sri Lankan patients. METHODS: A case study of histologically confirmed ulcerative colitis (UC) or Crohn's disease (CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12B:rs1045431, IL23R:rs11805303, ARPC2:rs12612347, IRGM:rs13361189, IL26/IL22:rs1558744, CDH1:rs1728785, IL10:rs3024505, FCGR2A:rs3737240, PTGER4:rs4613763, IL17REL/PIM3:rs5771069, HNF4a:rs6017342, STAT3:rs744166, SMURF1:rs7809799, LAMB1:rs886774, HLA-DRB5, DQA1, DRB1, DRA:rs9268853, MST1, UBA7, and APEH:rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium (P > 10-3). To account for multiple hypothesis testing, P-values < 0.003 were considered significant. RESULTS: A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms (SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774 (LAMB1-gene) and UC (odds ratio (OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease (OR = 1.66, P < 0.001) and remained in remission (OR = 1.48, P < 0.001). A positive association was noted between rs10045431 (IL 12B gene) and upper gastrointestinal involvement in CD (OR = 4.76, P = 0.002). CONCLUSION: This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.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 Ideal amount of exercise for a healthy life: have we solved the goldilocks problem? – review of the literature(Endocrine Society of Sri Lanka, 2016) Muthukuda, D.T.; Kodisinghe, S.K.; Niriella, M.A.There is an increasing interest in the place of physical activity to counter the increasing risk of non-communicable diseases and its complications in the community. Debate remains just how much exercise is too little, too much or just right to improve health and longevity. This article reviews the present evidence of physical activity on mortality and the possible ideal recommendations on physical activity.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.
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