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.

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.

Predicting acute liver failure in dengue infection.

In a retrospective study involving 240 patients with dengue infection, we attempted to identify early predictors of acute liver failure (ALF). Sixteen out of 41 patients with serum AST more than 1000 IU/ml developed ALF compared to none with serum AST less than 1000 IU/ml. Among patients with serum AST more than 1000 IU/ml, presence of two of the three following phenomena, within the first 5 days of illness: elevated serum bilirubin, elevated alkaline phosphatise or persistent nausea and vomiting, predicted development of ALF (93.8% sensitivity, 98.7% specificity, 83.3% positive predictive and 99% negative predictive value). The presence of elevated serum bilirubin, alkaline phosphatase and persistent nausea and vomiting in patients with very high serum AST during the early phase of dengue infection should alert the physician of impending ALF.

Clinical, biochemical and histological characteristics of a Sri Lankan population of non-alcoholic steatohepatitis (NASH) patients.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is common and can progress to cirrhosis. It has been regarded as a 'disease of affluence' and there are only a few reports from developing countries. OBJECTIVE: To describe the clinical, biochemical, and histological characteristics of a cohort of NASH patients in Sri Lanka, and to determine their short term outcome following modifications of lifestyle. METHOD: Patients who had a liver biopsy for investigation of raised hepatic enzymes were assessed during the period May 1999 - May 2003. Patients who had an alcohol intake of over 40 g/week were excluded. Detailed clinical and biochemical data of patients with histologically confirmed NASH were compiled. Histological grading and staging was done using the Brunt system. The patients were advised on lifestyle modifications and the control of diseases known to be associated with NASH. They were followed up at 3 -monthly intervals. RESULTS: During the study period liver biopsies were performed on 296 patients and 100 ( 35.1%) were diagnosed as having NASH. (Men = 79, Mean age 37.2 years, SD 10.6). Risk factors for NASH included diabetes mellitus (55%), obesity (52%), hyperlipidaemia (54%), a family history of risk factors (66%) and a high dietary fat intake (66%). However, 44.3% of men and 33.3% of women were not overweight. The histological grading and staging of 80 biopsies showed Grade 1 in 31 (38.8%), Grade 2 in 29 (36.3%), Grade 3 in 20 (25%), Stage 1 in 57 (71.3%) Stage 2 in 13 (16.3%), Stage 3 in 2 (2.5%) and Stage 4 in 8 (10%). In 55/91 (60.4%) patients who were followed up for a median of 2.5 years (range 1-4 years) the serum transaminases returned to normal in a median of 7 months (range 3-14 months). CONCLUSION: The clinical, biochemical and histological features of NASH patients in our series are similar to that reported in western countries. However "lean males" accounted for a significant proportion. In the short term a majority of patients showed improvement in serum transaminases with lifestyle modification.