Splenic Stiffness Measurement Combined With Liver Stiffness Measurement Compared With Baveno VII Criteria in Predicting the Presence of Oesophageal and Gastric Varices in Patients With Compensated Advanced Liver Cell Disease (cALCD).

INTRODUCTION: Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) is being increasingly used as a screening tool to predict varices. Our aim was to test the utility of Baveno VII criteria and other combinations of LSM, platelet count (PC), and splenic stiffness measurement (SSM) to predict the presence of varices in a cohort of Sri Lankan patients with compensated advanced liver cell disease (cALCD). METHODS: Consecutive patients with newly diagnosed Child-Pugh class A cALCD (non-viral, BMI<30) were recruited prospectively. They underwent gastroscopy. LSM and SSM were taken using vibration-controlled transient elastography (VCTE) (Echosens FibroScan 502 Touch; Echosens SA, Paris, France) by a single operator who was unaware of endoscopy findings. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of different Baveno VII criteria to predict the varices and different combinations of LSM, SSM, and PC were also explored. RESULTS: One hundred and seventy-four individuals were recruited. The mean age was 61.4 ((95% CI: 59.7-62.8) years. A total of 110 individuals were males, and 106 had varices. Our results indicated that the three Baveno VII criteria had sensitivities of 61%, 63%, and 42%, and specificities of 79%, 77%, and 87% to predict varices. SSM>30kPa alone and in combination with LSM>15kPa had sensitivities of 81 and 75%, specificities of 72 and 83%, PPVs of 82 and 87%, NPVs of 71% and 67%, and accuracies of 78 and 78%, respectively, to predict varices. CONCLUSION: Baveno VII criteria had a low sensitivity but high specificity in predicting the presence of varices. However, SSM>30kPa alone or in combination with LSM>15kPa had better sensitivity, specificity, PPV, NPV, and accuracy in predicting varices.

Characteristics and survival of advanced untreated hepatocellular carcinoma of non-viral etiology.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is an aggressive tumor and presents late. The underlying etiology of HCC is changing rapidly. HCC in Sri Lanka is unique due to its predominant non-viral etiology (nvHCC) but lacks survival data. METHOD: Data was collected from patients who presented with HCC from 2011 to 2018. There were 560/568 (98.6%) nvHCC. The patients who were not candidates for tumor-specific treatment (149/560 [26.7%]) were selected. Population characteristics, demographic data, tumor characteristics, survival and factors affecting survival were analyzed. RESULTS: The median age was 64 years (range 30-88) and 86% (n = 129) were males. As many as 124 (83%) were cirrhotic. The overall performance score was 80%. Nearly 21/124 tumors were detected in cirrhotic screening. Tumors were single nodular in 32 (21%), up to three nodules in 28 (18%), more than three nodules in 33 (22%) and diffusely infiltrating in 56 (37%). The major venous invasions were present in 78 (52.3%). Extra-hepatic tumor spread was seen in 19 (12.7%) (lungs 13 [72.2%], bones 2 [11.1%]). The median survival of patients receiving palliative care was three months (1-43 months). Tumor size and cirrhotic status were significant predictors in univariate analysis. CONCLUSION: A quarter of nvHCCs were not amenable to treatment at presentation as they had dismal survival. CLINICAL TRIAL REGISTRY NUMBER: P/126/09/2021.

AARC score determines outcomes in patients with alcohol-associated hepatitis: a multinational study.

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients. METHODS: Prospectively collected data from the AARC database were analyzed. RESULTS: Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p < 0.001); extrahepatic organ failure [66.9% vs. 41.8% vs. 35.4%; p < 0.001] respectively. The AARC score better discriminated 90-day mortality. Harrell's C-index was 0.72 compared to other scores. CONCLUSION: Nearly 4 of 5 patients with AH present with ACLF. Such patients have a higher risk of infections, organ failures, lower response to CS, and higher mortality. Patients with AH and ACLF with AARC grade 3 should be considered for an early liver transplant.

'Mistakes in managing non-alcoholic fatty liver disease and how to avoid them'.

Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease. NAFLD is estimated to affect 25% of the global population. Therefore, it is widely encountered in primary care. A proportion of patients with NAFLD need a specialist referral, evaluation and follow-up.There have been many updated guidelines on the management of NAFLD in the past few years. Given the burden of NAFLD in the community and its cardiovascular and liver-related adverse outcomes, knowledge of evidence-based standards of care for these patients is essential for any practitioner managing patients with NAFLD. As an asymptomatic disease in the early stages, NAFLD can lead to many mistakes in its management.We aim to highlight some common mistakes in managing NAFLD and attempt to provide evidence-based recommendations.

Chronic nausea and vomiting: a diagnostic approach.

INTRODUCTION: Chronic nausea and vomiting (CNV) are commonly encountered symptoms in medical practice. CNV is the presenting symptom in a variety of gastrointestinal and non-gastrointestinal disorders. However, in a significant percentage of patients without an obvious underlying cause, CNV poses a significant diagnostic challenge to the evaluating physician. AREAS COVERED: A comprehensive clinical history and physical examination form the foundation for further diagnostic work-up. In the present review, we discuss the diagnostic approach to CNV, highlighting the epidemiology, pathophysiology, causes, and modes of evaluation of this condition. Specific investigations, carefully guided by clinical assessment and tailored for each patient, would be more beneficial in diagnosing CNV than empirically performing a blanket of investigations. EXPERT OPINION: Whilst CNV remains a historically challenging diagnostic and therapeutic dilemma, research into this topic is limited. Hence, there is a growing call for more research into diagnostic modalities for CNV. With scientific advancement and further research, it is hoped that easy-to-use, cheap, noninvasive novel diagnostic modalities for CNV will be available soon.

Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: Preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.

Masks in COVID-19: let's unmask the evidence.

INTRODUCTION: One of the main issues in the novel coronavirus 2019 (COVID-19) pandemic has been the lack of uniformity of recommendations for the usage of face masks. AREAS COVERED: While Asian countries started using masks early during the epidemic, most Western countries were slow to do so. To avoid such situations, clear guidelines, need to be established, not only regarding the use of masks but also the type of mask to suit different situations. In this article, we will examine the types of masks and review the recommendations for their use based on the available evidence for each type of mask. EXPERT OPINION: We explore future needs in research-related mask use in COVID-19 pandemic, improvements to be made in mask design, adopting guidelines for the use of masks and the psycho-social aspects of widespread and prolonged mask use.

Low-dose melatonin for sleep disturbances in early-stage cirrhosis: A randomized, placebo-controlled, cross-over trial.

BACKGROUND AND AIM: Melatonin is used to treat sleep disturbances (SDs). The aim of this study was to investigate the safety and efficacy of low-dose melatonin for SDs in early-stage cirrhosis. METHODS: In a single-center, randomized, double-blind, placebo-controlled, cross-over clinical trial, patients with early-stage (Child-Turcotte-Pugh [CTP] class A or B) cirrhosis with SDs, without hepatic encephalopathy, were randomized to placebo or 3 mg of melatonin for 2 weeks. After 2 weeks, the patients were given a washout period of 1 week and crossed over to melatonin or placebo for a further 2 weeks. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to measure sleep quality and daytime sleepiness, respectively. Analysis of results was based on intention to treat, and linear mixed-effect models were used to evaluate the effect of melatonin. Analysis was conducted using R-programming language 3.5.1. RESULTS: Seventy one patients were recruited (mean age: 61.9 ± 8.7 years, males: 46 [64.8%], and CTP Class A = 52 [73.2%] and Class B = 19 [26.8%]). Sixty patients completed the study (mean age: 61.7 ± 8.8 years, males: 40 [66.6%], and CTP Class A = 45 [75.0%] and Class-B = 15 [25.0%]). Two patients dropped out due to adverse events. Nine patients were lost to follow up. Patients given melatonin had a significantly lower PSQI and ESS compared to both pretreatment (P < 0.001) and postplacebo scores (P < 0.001). Incidence of adverse events was similar (two each of abdominal pain, one each of headache, one each of dizziness) in both groups. CONCLUSION: Melatonin seems safe and effective for use in patients with SDs in early-stage cirrhosis in the short term. However, larger and longer-term studies to assess efficacy and safety are required before its clinical use can be recommended.

Hydroxychloroquine for post-exposure prophylaxis of COVID-19 among naval personnel in Sri Lanka: study protocol for a randomized, controlled trial.

BACKGROUND: The first case of a coronavirus 2019 (COVID-19) infection in a Sri Lankan was reported on March 11, 2020. The situation in Sri Lanka changed with the rapid increase of personnel contracting COVID-19 in a naval base camp that housed more than 4000 people. This provided a unique opportunity to study the effectiveness of hydroxychloroquine (HCQ) for post-exposure prophylaxis (PEP), while taking stringent, non-pharmacologic, public health measures to prevent spread. Our aim is to study the effectiveness and safety of HCQ for PEP among naval personnel with exposure to COVID-19-positive patients. METHODS/DESIGN: This is a placebo-controlled, randomized, clinical trial carried out in the naval base camp and quarantine centers of the Sri Lanka Navy, Ministry of Defense, Sri Lanka. Navy personnel who are exposed to a patient with confirmed COVID-19 infection but test negative for the virus on reverse real-time polymerase chain reaction (rRT-PCR) at recruitment will be randomized, 200 to each arm, to receive HCQ or placebo and monitored for the development of symptoms or rRT-PCR positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus for 14 days. DISCUSSION: This trial will provide high-quality evidence of the effectiveness and safety of HCQ as PEP for COVID-19. The study design is unique due to the circumstances of the outbreak in a confined area among otherwise healthy adults, at a relatively early stage of its spread. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry (SLCTR) SLCTR/2020/011 . Registered on 04 May 2020.

Identification of dengue patients with high risk of severe disease, using early clinical and laboratory features, in a resource-limited setting.

Only a minority of dengue infections lead to plasma leakage (critical phase [CP]). Early identification of the risk for CP is helpful for triage of patients. This study aimed to identify early clinical predictors of CP that will aid in patient triage during early illness. A retrospective, case-record-based analysis was performed on all microbiologically confirmed (NS1-antigen- or dengue-IgM-antibody-positive), dengue patients (n = 697), admitted to our unit from 01.01.2017 to 30.06.2017. Bivariate analysis was performed to identify clinical and laboratory parameters that predicted CP. Stepwise multivariate logistic regression with backward elimination (p < 0.05) was used to identify independent risk factors for CP. CP developed in 226 (32.4%) patients. Mortality was 1.0%. Predictors for CP (p < 0.05) within the first three days included age category 41-50 years (OR = 1.96), females (OR = 2.09), diabetes (OR = 1.30), persistent vomiting (OR = 2.18), platelet count < 120,000/mm-3 (OR = 1.91) and AST > 60 IU/L (OR = 3.72). On multivariate analysis, other variables except diabetes remained significant. Elevated transaminase levels remained the strongest independent predictor of CP (OR 2.83). The absence of all five risk factors excluded CP (negative predictive value: 97.2%). Age 41-50 years, female gender, persistent vomiting, thrombocytopenia, and elevated transaminases were early predictors of CP in dengue fever. The absence of these can be used to identify patients who may not require hospital admission. Elevated transaminase was the strongest predictor of CP during early illness.

Transfusion-transmitted hepatitis C: A cluster of cases in transfusion-dependent thalassaemia patients in Sri Lanka.

OBJECTIVES: To report the clinical and virologic epidemiology of a recent epidemic of hepatitis C in thalassaemia patients in Sri Lanka. BACKGROUND: Transfusion-dependent thalassaemia patients remain at risk for hepatitis C virus (HCV). Here, we report a cluster of recent HCV infections in Sri Lankan thalassaemia patients and examine the phylogenetic relationship of viral sequences. METHODS: We conducted two prospective cross-sectional surveys of 513 patients in four Sri Lankan thalassaemia centres in 2014/2015 and re-surveyed one centre in 2016. We screened for anti-HCV antibodies using the CTK Biotech enzyme-linked immunosorbent assay (ELISA) kits and confirmed active infection by reverse transcription-polymerase chain reaction (RT-PCR) for HCV-RNA. HCV genomes were sequenced by unbiased target enrichment. RESULTS: Anti-HCV antibodies were found in 116/513 (22.6%) of patients initially tested. Active hepatitis C infection was found in 26 patients with no cases of active hepatitis B infection. Of 26 patients with HCV, two were infected with genotype 1(a), and the rest had 3(a). In a single centre (Ragama), 122 patients (120 new cases and two previously tested, but negative) were retested for anti-HCV antibodies. 32/122 (26.2%) patients were seropositive. Twenty-three (23/122; 18.8%) of these new cases were confirmed by HCV PCR (all genotype 3[a]). CONCLUSION: There is a significant cluster of recent HCV cases in multiply transfused thalassaemia patients in several centres in Sri Lanka. Most of the viruses shared a close phylogenetic relationship. The results are consistent with recent continuing transfusion-transmitted HCV infection. Routine surveillance for HCV of chronically transfused patients is required irrespective of screening of blood products.

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.

Incidence and risk factors for metabolic syndrome among urban, adult Sri Lankans: a prospective, 7-year community cohort, follow-up study.

BACKGROUND: The metabolic syndrome (MetS) is a clustering of abdominal obesity, diabetes and prediabetes, high cholesterol and high blood pressure, that confers an increased risk of cardiovascular disease. There is limited data on incidence of MetS from South Asia. This study investigated incidence and risk factors for new onset MetS in an urban adult Sri Lankan population. METHODS: Subjects (selected by age-stratified random sampling from the Ragama Medical Officer of Health area) were screened initially in 2007 (35-64 years) and re-evaluated in 2014 (42-71 years). On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, and biochemical/serological tests. MetS was diagnosed on International Diabetes Federation (IDF-2006) criteria. Total body fat (TBF) and visceral fat percentage (VFP) were measured in 2014, using body impedance method. Incidence and factors at baseline, associated with new onset MetS, were investigated among those who presented for re-evaluation. RESULTS: 2985 (99.1%) [1636 (54.8%) women (54.8%); median age (IQR) 53 (47-59) years] from the initial cohort in 2007 had complete data. 2148 (71.9%) [1237 (57.6%) women; median age (IQR) 60 (54-66) years] attended follow-up. 949 of them [701 (73.9%) women; median age (IQR) 60 (54-65) years] had MetS (prevalence 47.2%, 95% CI 45.0-49.4%). Of 1246 who did not have MetS in 2007, 265 [178 (67.1%) women, median age (IQR) 57 (51-64) years] had developed MetS after 7 years (annual incidence 3.5% (95% CI 2.4-4.5%). Females (OR = 4.9, 95% CI 3.4-7.4), BMI > 23 kg/m2 in 2007 (OR = 1.6 per unit increase, 95% CI 1.5-1.7), weight gain (by 2-5% OR = 2.0, 95% CI 1.1-3.5; by > 5% OR = 2.2, 95% CI 1.4-3.4), and increase in waist circumference (by 2-5% OR = 7.0, 95% CI 4.0-12.2; by > 5% OR = 13.4, 95% CI 8.3-22.4) from baseline and presence of non-alcoholic fatty liver disease (NAFLD) in 2007 (OR = 1.70, 95% CI 1.04-2.76) were associated new onset MetS. Those with MetS had abnormal VFP and TBF in 2014 [P < 0.001]. CONCLUSION: In this study, annual incidence of MetS was 3.5%. Female gender, BMI > 23 kg/m2 and NAFLD in 2007 and increase in weight and waist circumference from baseline were significantly associated with new onset MetS. Obesity was the best predictor of future MetS.

Association of Serum Ferritin with Diabetes and Alcohol in Patients with Non-Viral Liver Disease-Related Hepatocellular Carcinoma.

INTRODUCTION: Non-alcoholic fatty liver disease is a leading cause for hepatocellular carcinoma (HCC) in Sri Lanka. Diabetes mellitus, alcohol abuse, and liver inflammation are known to increase the risk of HCC. The present study evaluates serum ferritin levels in a cohort of patients with non-viral HCC (nvHCC). METHODOLOGY: Consecutive patients with nvHCC presenting to the Colombo North Liver transplant Service, Ragama, from January 2012 to July 2013 were investigated. All were negative for hepatitis B and C. At registration, 5 mL of serum was separated into plain tubes, stored at -80°C and analysed for ferritin using an enzyme-linked immunosorbent assay. Correlation between the serum ferritin and patient risk factors, liver status, and tumour characteristics were analysed. RESULTS: There were 93 patients with nvHCC (median age 65 [12-82] years; 82 [88.2%] males). The median ferritin level was 246.2 µg/L, and 38 (40.86%) patients had elevated ferritin. Non-diabetics (median 363.5 mg/L, p = 0.003) and alcohol abusers (median 261.2 mg/L, p = 0.018) had higher ferritin levels. On multiple-variable analysis, being non-diabetic (p = 0.013) and alcoholic (p = 0.046) was significantly associated with high serum ferritin. No association was found with body mass index, tumour stage, size, macrovascular invasion, number of nodules, alpha-fetoprotein, bilirubin, international normalized ratio, and survival. CONCLUSION: In patients with nvHCC, serum ferritin levels are higher in non-diabetics and alcoholics.

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.

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.

Incidence and risk factors for non-alcoholic fatty liver disease: A 7-year follow-up study among urban, adult Sri Lankans.

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.