Dataset Information

Cohort profile: the Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort.

ABSTRACT: PURPOSE:The Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort is a population-based study designed to examine the interaction between genetic and lifestyle factors and their association with increased risk of NAFLD within the Indian population. PARTICIPANTS:Between 2013 and 2016, a total of 2222 participants were recruited to this cohort through multistage cluster sampling across the whole population of Trivandrum-a district within the state of Kerala, South India. Data were collected from all inhabitants of randomly selected households over the age of 25. FINDINGS TO DATE:Full baseline clinical and pathological data were collected from 2158 participants. This included detailed demographic profiles, anthropometric measures and lifestyle data (food frequency, physical activity and anxiety and depression questionnaires). Biochemical profile and ultrasound assessment of the liver were performed and whole blood aliquots were collected for DNA analysis.The NAFLD prevalence within this population was 49.8% which is significantly higher than the global pooled prevalence of 25%. This highlights the importance of robust, prospective studies like this to enable collection of longitudinal data on risk factors, disease progression and to facilitate future interventional studies. FUTURE PLANS:The complete analysis of data collected from this cohort will give valuable insights into the interaction of the phenotypic and genotypic profiles that result in such a dramatic increased risk of NAFLD within the Indian population. The cohort will also form the basis of future lifestyle interventional studies, aimed at improving liver and metabolic health.

SUBMITTER: Chalmers J

PROVIDER: S-EPMC6502065 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Cohort profile: the Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort.

Chalmers Jane J Ban Lu L Leena Kondarapassery B KB Edwards Kimberley L KL Grove Jane L JL Aithal Guruprasad P GP Shenoy Kotacherry T KT

BMJ open 20190505 5

<h4>Purpose</h4>The Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort is a population-based study designed to examine the interaction between genetic and lifestyle factors and their association with increased risk of NAFLD within the Indian population.<h4>Participants</h4>Between 2013 and 2016, a total of 2222 participants were recruited to this cohort through multistage cluster sampling across the whole population of Trivandrum-a district within the state of Kerala, South India. Data ...[more]

PMID: 31061050

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Project description:Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A's functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central role in vitamin A metabolism: (1) it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2) it produces retinol binding protein 4 (RBP4) that distributes vitamin A, as retinol, to peripheral tissues; and (3) it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs). In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 ?mol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH); it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M) is the most prominent heritable factor associated with NAFLD. Interestingly, PNPLA3 harbors retinyl ester hydrolase activity and PNPLA3-I148M is associated with low serum retinol level, but enhanced retinyl esters in the liver of NAFLD patients. Low circulating retinol in NAFLD may therefore not reflect true "vitamin A deficiency", but rather disturbed vitamin A metabolism. Here, we summarize current knowledge about vitamin A metabolism in NAFLD and its putative role in the progression of liver disease, as well as the therapeutic potential of vitamin A metabolites.

Project description:Covid-19 disease causes significant morbidity and mortality through increase inflammation and thrombosis. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are states of chronic inflammation and indicate advanced metabolic disease. We sought to understand the risk of hospitalization for Covid-19 associated with NAFLD/NASH. Retrospective analysis of electronic medical record data of 6,700 adults with a positive SARS-CoV-2 PCR from March 1, 2020 to Aug 25, 2020. Logistic regression and competing risk were used to assess odds of being hospitalized. Additional adjustment was added to assess risk of hospitalization among patients with a prescription for metformin use within the 3 months prior to the SARS-CoV-2 PCR result, history of home glucagon-like-peptide 1 receptor agonist (GLP-1 RA) use, and history of metabolic and bariatric surgery (MBS). Interactions were assessed by gender and race. A history of NAFLD/NASH was associated with increased odds of admission for Covid-19: logistic regression OR 2.04 (1.55, 2.96, p<0.01), competing risks OR 1.43 (1.09-1.88, p<0.01); and each additional year of having NAFLD/NASH was associated with a significant increased risk of being hospitalized for Covid-19, OR 1.86 (1.43-2.42, p<0.01). After controlling for NAFLD/NASH, persons with obesity had decreased odds of hospitalization for Covid-19, OR 0.41 (0.34-0.49, p<0.01). NAFLD/NASH increased risk of hospitalization in men and women, and in all racial/ethnic subgroups. Mediation treatments for metabolic syndrome were associated with non-significant reduced risk of admission: OR 0.42 (0.18-1.01, p=0.05) for home metformin use and OR 0.40 (0.14-1.17, p=0.10) for home GLP-1RA use. MBS was associated with a significant decreased risk of admission: OR 0.22 (0.05-0.98, p<0.05). NAFLD/NASH is a significant risk factor for hospitalization for Covid-19, and appears to account for risk attributed to obesity. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm risk associated with visceral adiposity, and patients should be screened for and informed of treatments for metabolic syndrome.

Dataset Information

Cohort profile: the Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort.

Publications

Cohort profile: the Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort.

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