Metabolic syndrome, but not non-alcoholic fatty liver disease, increases 10-year mortality: A prospective, community-cohort study.

BACKGROUND: Data on outcomes of non-alcoholic fatty liver disease (NAFLD) from South Asia are lacking. We compared mortality, among those with- and without-NAFLD, after 10-years follow-up among urban, adult Sri Lankans. METHOD: Participants (aged 35-64 years), selected by age-stratified random sampling, were screened by structured-interview in 2007. Anthropometric measurements, liver ultrasonography and biochemical/serological tests were done. NAFLD was diagnosed on ultrasound criteria, safe-alcohol consumption (Asian-standards) and absence of hepatitis B/C. Subjects without NAFLD were those without any ultrasound criteria of fatty liver, safe-alcohol consumption and absence of hepatitis B/C. The cohort was re-evaluated to assess mortality in 2017. Participants or their households were contacted by telephone/post, and deaths confirmed by home-visits and death certificate review. Cox-regression was used to determine predictors of all-cause mortality (ACM) and cardiovascular mortality (CVM) in those with- and without-NAFLD. RESULTS: 2724 (91.2%) of 2985 original participants were contacted (851-with NAFLD and 1072-without NAFLD). Overall there were 169 (6.2%) deaths [41-deaths among NAFLD (17-cardiovascular; 9-cancer-related; 4-liver-specific; 11-other) and 79-deaths among no-NAFLD (28-cardiovascular; 17-cancer-related; 1-liver-specific; 33-other)]. Metabolic syndrome (MetS), low-education level, higher age and male-gender independently predicted ACM. MetS, increasing age and male-gender independently predicted CVM. NAFLD did not predict either ACM or CVM. In those with NAFLD, MetS and age >55-years were independently associated with ACM, while MetS and male-gender were associated with CVM. CONCLUSION: In this community-based study, increasing age, male-gender and MetS, but not NAFLD, predicted 10-year ACM and CVM. Among those with NAFLD, only those metabolically abnormal were at a higher risk for mortality.

Non-alcoholic fatty liver disease and its associations among adolescents in an urban, Sri Lankan community.

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.

Clinical characteristics and outcome of hepatocellular carcinoma in alcohol related and cryptogenic cirrhosis: a prospective study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease. Hepatocellular carcinoma (HCC) is one of its complications. Although the pathophysiology is unclear, it is reasonable to expect that cryptogenic cirrhosis related HCC (cryptogenic HCC) behaves differently to other types of HCC. This study prospectively compared patients with cryptogenic HCC and those with HCC related to alcoholic cirrhosis. METHODS: A total of 150 consecutive patients with HCC (89 cryptogenic HCC and 61 alcohol related HCC) referred to our unit over a 23-month period were studied. Their demographic data, liver function, tumor characteristics and outcomes were compared. RESULTS: Alcohol related HCC was seen only in males. Compared with cryptogenic HCC, alcohol related HCC had significantly higher aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (1.7 vs 1.4, P=0.002), model for end-stage liver disease score (13 vs 11, P=0.018) and Child's score (7 vs 6, P=0.037). No significant difference was seen in platelet counts, serum sodium and AST to platelet ratio index. Single nodular tumors were more common in cryptogenic HCC, while diffuse type tumors and macroscopic vascular invasion were common in alcohol related HCC. In patients who could not be offered any treatment because of advanced tumors or poor liver function, alcohol related HCC had a significantly lower median survival (5.3 months) compared with cryptogenic HCC (9.3 months, P=0.034). CONCLUSIONS: Compared with cryptogenic HCC, alcohol related HCC had worse liver function and aggressive tumor morphology at presentation, and a higher proportion was untreatable. In patients who could not be treated, median survival was lower in patients with alcohol related HCC than in those with cryptogenic HCC.

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

BACKGROUND AND AIM: 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. METHODS: Participants of the Ragama Health Study cohort were assessed for NAFLD using established ultrasound criteria in 2007. Those who were free of diabetes at baseline were followed up for 3 years. Incidence rates of diabetes mellitus were compared between subjects with and without NAFLD at baseline. RESULTS: Out of 2984 subjects, 926 had NAFLD and 676 had diabetes in 2007. Of the 2276 subjects who were free of diabetes in 2007, 1914 were re-assessed in 2010. After 3 years, 104 out of 528 subjects with NAFLD and 138 out of 1314 subjects without NAFLD had developed diabetes mellitus de novo. Incidence rates of diabetes were respectively 64.2 and 34 per 1000 person-years of follow up for those with and without NAFLD. NAFLD was an independent predictor of developing diabetes mellitus. Other independent predictors were impaired fasting glycemia and dyslipidemia. CONCLUSIONS: Subjects with ultrasonically diagnosed NAFLD have an increased risk of developing diabetes mellitus. Intervention for NAFLD through lifestyle modification may prevent progression of the current diabetes epidemic.

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

BACKGROUND: Asthmatics 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. METHODS: Thirty 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. RESULTS: Asthmatics (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. CONCLUSIONS: A 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.

NAFLD vs MAFLD: South Asian NAFLD Patients don't Favor Name Change.

Aim: There have been vociferous attempts to change the name of Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Associated Fatty Liver Disease (MAFLD). Of the many arguments put forth in support of this, an important one is the presumed demand by patient groups insisting on the change. However, this claim does not have credible evidence to support it. Therefore, we decided to conduct a survey among South Asian NAFLD patients to understand their perspectives with regard to the change in nomenclature. Materials and Methods: The study was conducted at multiple centers across South Asia from January 2021 to June 2021. Patients were surveyed using an 8-question survey questionnaire and responses were categorized by multiple-choice format. Results: Of 218 patients surveyed, 80.3% of the patients were not aware of the entity "NAFLD" before they were first diagnosed. Although 74.3% of patients admitted to being questioned about alcohol intake at the time of the first diagnosis, 75.9% of female patients were not questioned regarding this. After being labelled NAFLD, 92.1% of patients were never questioned again about alcohol intake. While 86.3% of patients found the term "NAFLD" consoling, 83% did not feel that "Non" in NAFLD trivialized their problem. In addition, only 6.9% of patients were scared of developing cardiovascular disease. Conclusion: The term "NAFLD" destigmatizes patients of the taboo associated with alcohol use. It was found to be consoling to most patients and they did not feel it trivialized their problem. A change of name without considering patients' perspectives and peculiarities specific to different populations will have enormous ramifications for both patients and physicians. Clinical significance: Our survey clearly shows that patients are happy with the term "NAFLD" and it effectively destigmatizes them from the taboo of alcohol. This would lead to higher compliance with management and greater patient participation in future studies and trials. How to cite this article: Singh SP, Anirvan P, Butt AS, et al. NAFLD vs MAFLD: South Asian NAFLD Patients don't Favor Name Change. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S1-S4.

The prone 12 o'clock position reduces ileal intubation time during colonoscopy compared to the left lateral 6 o'clock (standard) position.

BACKGROUND: Ileal intubation is the gold standard for a complete colonoscopy. However, despite evidence of clinical benefit ileoscopy is not always attempted due to perceived technical difficulty. Our aim was to compare time taken for ileal intubation using a new position-the prone 12 o'clock position (PP) with the standard method (left lateral 6 o'clock position-LLP). METHODS: We performed a pilot study using fluoroscopy to determine the best patient position for ileal intubation. This was the prone 12 o'clock position. Patients were colonoscoped in the left lateral position and then randomized to ileal intubation in the 6 o'clock position(LL) or the 12 o'clock (PP) position. RESULTS: 202 consecutive patients were referred for colonoscopy. Colonoscopy was performed on 150 patients [82 females, mean (SD) age 53 (16) years]. 75 patients were randomized for ileal intubation in the PP and 75 patients in the LLP. Overall, the ileum was successfully intubated in 145 (96%) patients [74 (98.7%) in the PP and 71 (94.7%) in the LLP]. The median (Interquartile Range) ileal intubation time was 12 (10) seconds in the PP and 87 (82) seconds in the LLP (p < 0.0001; Mann-Whitney U test). The ileum was abnormal in 11 (7.5%) patients. CONCLUSIONS: During colonoscopy, the prone 12 o'clock position gives a more direct approach to the ileo-caecal valve and significantly reduces ileal intubation time. TRIAL REGISTRY: Sri Lanka Clinical Trial Registry Clinical trial registry number: SLCTR/2009/002.

Non-alcoholic fatty liver disease in diabetes: When to refer to the hepatologist?

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide. A strong relationship exists between NAFLD and diabetes mellitus. There is growing evidence of a mechanistically complex and strong association between the two diseases. Current data also shows that one disease actually leads to worsening of the other and vice versa. Understanding of the various pathophysiological mechanisms involved, natural history and spectrum of these two diseases is essential not only for early diagnosis and management but also for prevention of severe disease forms. Despite the tremendous progress made in recent times in acquiring knowledge about these highly prevalent diseases, the guidelines and recommendations for screening and management of diabetics with NAFLD remain ambiguous. An interdisciplinary approach is required to not only raise awareness of the prevalence of NAFLD in diabetics but also for better patient management. This can help attenuate the development of significant complications, such as cirrhosis, decompensation and hepatocellular carcinoma in these patients, thereby halting NAFLD in its tracks. This review focuses on the pivotal role of primary care physicians and endocrinologists in identification of NAFLD in diabetics in early stages and the role of proactive screening for prompt referral to hepatologist.

Physical Activity Tracking Among Sri Lankan Adults: Findings From a 7-Year Follow-up of the Ragama Health Study.

Limited data are available on physical activity tracking among adults in low- and middle-income countries. Using a longitudinal design, we assessed trends and correlates of physical activity among Sri Lankan adults. Individuals selected through age-stratified random sampling, were screened initially in 2007 (n = 2986) and reevaluated in 2014 (n = 2148). On both occasions, structured interviews and clinical measurements were completed. Approximately 40% of the participants engaged in recommended levels of physical activity both at baseline and follow-up. One-fifth reported increased physical activity at follow-up, a similar proportion reported being persistently inactive or a reduction in physical activity. In the adjusted analysis, being persistently active was associated with male sex, a lower educational level and income, being free of any chronic disease conditions, better self-rated health, and sitting time <8 hours. Our findings support public health interventions to help maintain recommended physical activity levels over time, particularly for subgroups at high-risk of physical inactivity.

Is a six hour fast after a rice meal sufficient before upper gastrointestinal endoscopy?

OBJECTIVE: Rice is the staple diet in many Asian countries. Current endoscopic guidelines advice a 6 h fast for solids and a 4 h fast for liquids before the procedure. However, these guidelines focus on a Western type diet. The aim of the study was to determine if a 6 h fast for rice is sufficient prior to upper gastrointestinal endoscopy (UGIE). PATIENTS AND METHODS: After informed consent, 212 patients referred for UGIE, who had no alarm symptoms, were randomized into two groups in preparation for UGIE. Fasting 6 h after a rice meal (R6) or fasting 10 h after a rice meal (R10). All meals contained lentils and an egg, and were isocaloric. Endoscopic vision was graded as poor, average, or good. RESULTS: In the R10 group (n = 107) vision was poor in 2 (1.9%), average in 7 (6.5%), and good in 98 (91.6%). While in the R6 group (n = 105) vision was poor in 30 (28.6%), average in 19 (18.1%), good in 56 (53.3%). The observed difference of percentages among the two groups for endoscopic vision was significant (M-H Chi-Square for trend = 25.67; df = 1; p < 0.001). CONCLUSIONS: Fasting for 6 h after a rice based meal seems inadequate for UGIE. Fasting for 10 h significantly improves endoscopic vision. Current guidelines need to be re-evaluated for populations where rice is the staple diet.

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

BACKGROUND: Inflammatory bowel disease (IBD) is being increasingly diagnosed in Asia. However there are few epidemiological data from the region. METHODS: To 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 Crohn's 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. RESULTS: There 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. CONCLUSIONS: The 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.

One-hour fast for water and six-hour fast for solids prior to endoscopy provides good endoscopic vision and results in minimum patient discomfort.

BACKGROUND AND AIM: Current guidelines for upper gastrointestinal endoscopy (UGIE) advise at least 6-8 h fasting for solids and 4-h fasting for liquids. We aimed to determine whether a 6-h fast for solids and one-hour fast for water prior to UGIE gives good endoscopic vision and less patient discomfort. METHODS: 128 patients referred for UGIE were given a standard meal 6 h before endoscopy, and then randomized to either nil by mouth for 6 h (group A, n = 65) or allowed to drink water for up to one hour prior to endoscopy (group B, n = 63). Before endoscopy patients were requested to indicate discomfort due to fasting on a visual analog scale. Fluid in the gastric fundus was aspirated, when present, for volume and pH measurements, and endoscopic vision was graded. RESULTS: 53 patients in group A and 43 patients in group B completed the study. Discomfort was significantly lower in group B than group A (P < 0.0001). Endoscopic vision was good in all 53 patients in group A and 40 in group B, and average in 3 patients in group B. Fluid in the gastric fundus was noted in 11 patients in group A and 16 in group B, but there were no significant differences in volume or pH between groups. There were no complications attributable to endoscopy in either group. CONCLUSIONS: A 6-h fast for solids and a 1-h fast for water prior to UGIE gives good endoscopic vision, and causes minimum patient discomfort.

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. METHODS: The study population consisted of 35-64-year-old adults, 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. Blood pressure (BP) and anthropometric measurements were made, and fasting glucose, glycosylated hemoglobin, serum lipids, fasting serum insulin and serum alanine aminotransferase (ALT) were determined. RESULTS: Of the 2985 study participants, 974 (32.6%) had NAFLD (605 [62.1%] women, mean age 52.8 years [standard deviation, 7.3]). On multivariate analysis, obesity, acanthosis nigricans, insulin resistance, elevated diastolic BP, fasting plasma glucose, plasma triglycerides, and ALT twice the upper limit of the reference range or more were independently associated with NAFLD. CONCLUSION: The prevalence of NAFLD among adults in this urban Sri Lankan community is high and is strongly associated with constituent features of the metabolic syndrome.

Nonalcoholic Fatty Liver Disease: Identifying the Disease Burden in Sri Lanka.

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. How to cite this article: Dassanayake AS. Nonalcoholic Fatty Liver Disease: Identifying the Disease Burden in Sri Lanka. Euroasian J Hepato-Gastroenterol 2018;8(1):69-72.

Diffuse-Type Hepatoma: A Grave Prognostic Marker.

BACKGROUND: Data on diffuse-type hepatocellular carcinoma (HCC) are rare. HCC in Sri Lanka is rising, and the majority is related to nonalcoholic fatty liver disease. This study was planned to compare nodular- and diffuse-type HCC in this cohort. METHODS: CT scans of 227 patients with HCC negative for infective hepatitis were analyzed and grouped as nodular and diffuse from July 2011 to July 2014. Diffuse-type cancer was defined as a tumor without convex/distinct margin, diffusely infiltrating the hepatic parenchyma. There were 45 (20%) cases. The baseline liver functions, etiology, treatment, and the outcome were compared with nodular-type cancers. Stage III diffuse cancers were matched with 2 stage III nodular cancers looking at the T stage and background liver. RESULTS: There was no difference in the age (63 vs. 62 years, p = 0.937) and gender. Diffuse cancers had a low BMI (24 vs. 22, p = 0.009), a higher alpha fetoprotein (AFP) level (p < 0.001), a higher incidence of major vascular invasion (14 vs. 80%, p < 0.001), and a history of significant alcohol consumption (39 vs. 67%, p = 0.001). The baseline liver functions were similar in diffuse and nodular cancers. A large proportion (27 vs.77%, p < 0.001) of diffuse cancers were not candidates for active treatment. Overall survival was poor in the diffuse type (4.7 vs. 25 months, p < 0.001). Diffuse-type stage III cancers had a poor survival compared to matched nodular cancers (2.5 vs. 15.8 months, p = 0.001). CONCLUSION: HCC without a background of infective hepatitis were common in our cohort. These tumors are associated with high AFP levels, major vascular invasion, and a poor prognosis.

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

BACKGROUND: Non-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. METHODS: By 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. RESULTS: Of 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. CONCLUSION: Nearly 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.