A.S. Dassanayake

Prevalence and risk factors for non-alcoholic fatty liver disease among adults in an urban Sri Lankan population

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.

Iron overload in the Asian community

Hereditary hemochromatosis is an iron overload disorder that can lead to the impairment of multiple organs and is caused by mutations in one or more different genes. Type 1 hemochromatosis is the most common form of the disease and results from mutations in the HFE gene. Juvenile hemochromatosis (JH) is the most severe form, usually caused by mutations in hemojuvelin (HJV) or hepcidin (HAMP). The autosomal dominant form of the disease, type 4, is due to mutations in the SLC40A1 gene, which encodes for ferroportin (FPN). Hereditary hemochromatosis is commonly found in populations of European origin. By contrast, hemochromatosis in Asia is rare and less well understood and can be masked by the presence of iron deficiency and secondary iron overload from thalassemia. Here, we provide a comprehensive report of hemochromatosis in a group of patients of Asian origin. We have identified novel mutations in HJV, HAMP, and SLC40A1 in countries not normally associated with hereditary hemochromatosis (Pakistan, Bangladesh, Sri Lanka, and Thailand). Our family studies show a high degree of consanguinity, highlighting the increased risk of iron overload in many countries of the developing world and in countries in which there are large immigrant populations from these regions.

Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus

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.

Prevalence of inflammatory bowel disease in two districts of Sri Lanka: a hospital based survey

BackgroundInflammatory bowel disease (IBD) is being increasingly diagnosed in Asia. However there are few epidemiological data from the region.MethodsTo determine prevalence and clinical characteristics of IBD, a hospital-based survey was performed in the Colombo and Gampaha districts (combined population 4.5 million) in Sri Lanka. Patients with established ulcerative colitis (UC) and Crohns disease (CD), who were permanent residents of these adjoining districts, were recruited from hospital registries and out-patient clinics. Clinical information was obtained from medical records and patient interviews.ResultsThere were 295 cases of IBD (UC = 240, CD = 55), of which 34 (UC = 30, CD = 4) were newly diagnosed during the study year. The prevalence rate for UC was 5.3/100,000 (95% CI 5.0-5.6/100,000), and CD was 1.2/100,000 (95% CI 1.0-1.4/100,000). The incidence rates were 0.69/100,000 (95% CI 0.44-0.94/100,000) for UC and 0.09/100,000 (95% CI 0.002-0.18/100,000) for CD. Female:male ratios were 1.5 for UC and 1.0 for CD. Mean age at diagnosis was (males and females) 36.6 and 38.1y for UC and 33.4 and 36.2y for CD. Among UC patients, 51.1% had proctitis and at presentation 58.4% had mild disease. 80% of CD patients had only large bowel involvement. Few patients had undergone surgery.ConclusionsThe prevalence of IBD in this population was low compared to Western populations, but similar to some in Asia. There was a female preponderance for UC. UC was mainly mild, distal or left-sided, while CD mainly involved the large bowel.

Non-alcoholic fatty liver disease in a rural, physically active, low income population in Sri Lanka

BackgroundNon-alcoholic fatty liver disease (NAFLD) is recognized as a metabolic disorder largely seen in urbanized populations. The purpose of this study was to assess prevalence and risk factors for NAFLD in a rural, physically active, economically deprived population in Sri Lanka.MethodsBy visiting individual households in the community, 35-64 year old adults resident in two selected estates in the Nuwara Eliya District of Sri Lanka, were invited to participate in the study. Blood pressure and anthropometric measurements were made on all participants. Blood samples were obtained for the assay of fasting glucose, serum lipids, serum insulin and alanine aminotransferase. NAFLD was diagnosed on established ultrasound criteria for fatty liver in the absence of hepatitis B and C markers and high alcohol consumption.ResultsOf those invited, 403 (65%) participated in the study. Almost all participants were either Indian or Sri Lankan Tamils and 53% were females. Prevalence of NAFLD was 18% in this population. Twice as many males were diagnosed as having NAFLD compared to females. Male sex, high BMI, high waist circumference, high diastolic blood pressure and high plasma glucose levels were significant predictors of NAFLD.ConclusionNearly one in five people in this predominantly Indian Tamil, rural, physically active, economically deprived population had NAFLD. The condition was associated with constituent features of the metabolic syndrome. These results support studies reporting ethnic variations in disease susceptibility and suggest that genetic factors may also play a role in determining disease risk.

Intravenous N-acetylcysteine in dengue-associated acute liver failure

We read with interest the article by Mumtaz et al. [1] on the role of oral N-acetylcysteine (NAC) in adults with non-acetaminophen-induced acute liver failure. We agree that their findings are of particular relevance to many developing countries, where liver transplantation is neither available nor affordable. There has been another recent study in which intravenous NAC has been shown to improve transplant-free survival in early-stage non-acetaminophen-induced acute liver failure in adults [2]. We report our initial experience in treating acute liver failure caused by dengue infection with NAC. Use of NAC in this situation has not been previously described.

Subclinical mucosal inflammation in diarrhea-predominant irritable bowel syndrome (IBS) in a tropical setting

Abstract Background and aims. There is evidence for low-grade inflammation in the pathophysiology of post-infectious irritable bowel syndrome (IBS). We assessed the degree of subclinical intestinal mucosal inflammation in diarrhea-predominant IBS (IBS-D) in a tropical setting. Material and methods. In a prospective study over 1 year, we investigated 49 patients with IBS-D (cases; median age 34 years (range 18–59); M:F 36:13), diagnosed on Rome III criteria. 14 individuals with a family history of colon cancer (median age 46.5 years (range 23–56); M:F 6:8) were selected as controls. Stools of cases and controls were tested for calprotectin. During colonoileoscopy, serial biopsies were obtained. Mucosal mast cells, neutrophils, eosinophils and lymphocytes/plasma cell infiltrate were quantified. Tissue expression of IL-8 and IL-10 was assessed in biopsies by semi-quantitative RT-PCR. Results. A history suggestive of an episode of infectious diarrhea (ID) was present in 16/49 cases and 0/14 controls (p = 0.013). In cases, there were significantly more mucosal mast cells in the ileum and all segments of colon and significantly more eosinophils in the cecum. Tissue expression of IL-8 was significantly higher and IL-10 significantly lower in cases compared with controls (target/standard cDNA ratio, median (range) IL-8: 1.25 (0.75–2) vs. 0.85 (0.63–1.3), p < 0.0001, Mann–Whitney U test; IL-10: 0.33 (0–0.63) vs. 0.55 (0.5–0.7), p < 0.0001). There was a significant inverse correlation between IL-8 and IL-10 expression (Pearson correlation, (-) 0.509; p < 0.01). Conclusion. There was evidence of subclinical intestinal mucosal inflammation in patients with IBS-D. The finding of increased eosinophils is novel, and may be of special relevance to IBS-D in the tropics.

Survival of patients with alcoholic and cryptogenic cirrhosis without liver transplantation: a single center retrospective study.

BackgroundThere is no recent data addressing the long term survival of cirrhosis patients without transplantation, but with the availability of optimal pharmacological and endoscopic therapies. We compared the long term transplant free survival of alcoholic (AC) and cryptogenic (CC) cirrhosis patients in a setting where liver transplantation was, until very recently, not available. AC and CC patient details were extracted from our database, maintained since 1995. For those who had not attended clinics within the past 4 weeks, the patient or families were contacted to obtain survival status. If deceased, cause of death was ascertained from death certificates and patient records. Survival was compared using Kaplan-Meier curves.ResultsComplete details were available in 549/651 (84.3%) patients (AC 306, CC 243). Mean follow up duration (SD) (months) was 29.9 (32.6). 82/96 deaths (85.4%) among AC and 80/94 deaths (85.1%) among CC were liver related. Multivariate analysis showed age at diagnosis and Child’s class predicted overall survival among all groups. The median survival in Child’s class B and C were 53.5 and 25.3 months respectively. Survival was similar among AC and CC. Among AC survival was improved by abstinence [HR = 0.63 (95% CI: 0.40-1.00)] and was worse with diabetes [HR=1.59 (95% CI: 1.02- 2.48)] irrespective of alcohol status.ConclusionsThe overall survival of AC was similar to CC. Death in both groups were predominantly liver related, and was predicated by age at diagnosis and Child class. Among AC, presence of diabetes and non-abstinence from alcohol were independent predictors for poor survival.

Prevalence of Acanthosis Nigricans in an urban population in Sri Lanka and its utility to detect metabolic syndrome

BackgroundInsulin resistance (IR) plays a major role in the pathogenesis of metabolic syndrome. Acanthosis nigricans (AN) is an easily detectable skin condition that is strongly associated with IR. The aims of this study were, firstly, to investigate the prevalence of AN among adults in an urban Sri Lankan community and secondly, to describe its utility to detect metabolic syndrome.FindingsIn a community based investigation, 35-64 year adults who were selected using stratified random sampling, underwent interview, clinical examination, liver ultrasound scanning, and biochemical and serological tests. Metabolic syndrome was diagnosed on revised ATP III criteria for Asian populations. AN was identified by the presence of dark, thick, velvety skin in the neck.2957 subjects were included in this analysis. The prevalence of AN, metabolic syndrome and type 2 diabetes mellitus were 17.4%, 34.8% and 19.6%, respectively. There was a strong association between AN and metabolic syndrome. The sensitivity, specificity, positive predictive value and negative predictive value of AN to detect metabolic syndrome were 28.2%, 89.0%, 45.9% and 79.0% for males, and 29.2%, 88.4%, 65.6% and 62.3% for females, respectively.ConclusionsAN was common in our study population, and although it did not have a high enough sensitivity to be utilized as a screening test for metabolic syndrome, the presence of AN strongly predicts metabolic syndrome.

Esophageal motility, vagal function and gastroesophageal reflux in a cohort of adult asthmatics

BackgroundAsthmatics are known to have esophageal hypomotility. Vagal hypofunction and prolonged intra-esophageal acidification cause esophageal hypomotility. The contribution of gastroesophageal reflux (GER) and vagal function to esophageal motility in asthmatics is unclear. We studied the relationship between esophageal motility, GER and vagal function in a cohort of adult asthmatics.MethodsThirty mild, stable asthmatics (ATS criteria) and 30 healthy volunteers underwent 24-hour ambulatory esophageal monitoring, manometry, autonomic function testing and GER symptom assessment. 27 asthmatics underwent gastroscopy. A vagal function score calculated from 3 tests (valsalva maneuver, heart rate response to deep breathing and to standing from supine position) was correlated with esophageal function parameters.ResultsAsthmatics (mean age 34.8 (SD 8.4), 60% female) had more frequent GERD symptoms than controls (mean age 30.9 (SD 7.7), 50% female). 10/27 asthmatics had esophageal mucosal damage, 22 showed hypervagal response, none had a hyperadrenergic response. 14 asthmatics had ineffective esophageal motility. Higher GERD-score asthmatics had significantly fewer peristaltic and more simultaneous contractions than controls, and higher esophageal acid contact times than those with lower scores. All reflux parameters were significantly higher and acid clearance time prolonged in asthmatics than controls (p < 0.001, Mann–Whitney U test). There was no correlation between vagal function score and esophageal function parameters.ConclusionsA cohort of adult asthmatics was found to have peristaltic dysfunction and pathological GER, but otherwise normal esophageal motility. The peristaltic dysfunction seems to be associated with vagal hyperreactivity rather than vagal hypofunction.