While non-alcoholic fatty liver disease (NAFLD) is highly prevalent (15% to 45%) in modern societies, only 10% to 25% of cases develop hepatic fibrosis leading to cirrhosis, end-stage liver disease or hepatocellular carcinoma. Apart from pre-existing fibrosis, the strongest predictor of fibrotic progression in NAFLD is steatohepatitis or non-alcoholic steatohepatitis (NASH). The critical features other than steatosis are hepatocellular degeneration (ballooning, Mallory hyaline) and mixed inflammatory cell infiltration. While much is understood about the relationship of steatosis to metabolic factors (over-nutrition, insulin resistance, hyperglycemia, metabolic syndrome, hypoadiponectinemia), less is known about inflammatory recruitment, despite its importance for the perpetuation of liver injury and fibrogenesis. In this review, we present evidence that liver inflammation has prognostic significance in NAFLD. We then consider the origins and components of liver inflammation in NASH. Hepatocytes injured by toxic lipid molecules (lipotoxicity) play a central role in the recruitment of innate immunity involving Toll-like receptors (TLRs), Kupffer cells (KCs), lymphocytes and neutrophils and possibly inflammasome. The key pro-inflammatory signaling pathways in NASH are nuclear factor-kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK). The downstream effectors include adhesion molecules, chemokines, cytokines and the activation of cell death pathways leading to apoptosis. The upstream activators of NF-kappaB and JNK are more contentious and may depend on the experimental model used. TLRs are strong contenders. It remains possible that inflammation in NASH originates outside the liver and in the gut microbiota that prime KC/TLR responses, inflamed adipose tissue and circulating inflammatory cells. We briefly review these mechanistic considerations and project their implications for the effective treatment of NASH.
Adipose Tissue ; Apoptosis ; Carcinoma, Hepatocellular ; Cell Death ; Chemokines ; Cytokines ; Fatty Liver ; Fibrosis ; Hepatocytes ; Hyperglycemia ; Immunity, Innate ; Inflammation ; Insulin Resistance ; JNK Mitogen-Activated Protein Kinases ; Kupffer Cells ; Liver ; Liver Diseases ; Lymphocytes ; Metagenome ; Models, Theoretical ; Neutrophils ; NF-kappa B ; Toll-Like Receptors

INTRODUCTIONNot much is known regarding how primary care physicians (PCPs) in Singapore keep themselves healthy and mitigate ill health. This study aims to determine the health-seeking behaviour of local PCPs and to identify the predictors of local PCPs attaining the recommended level of exercise.

METHODSThis study was a cross-sectional questionnaire survey, which included questions on the demographic characteristics, practice profiles and health-seeking behaviour of PCPs. The sampling frame was the 1,400 listed members of the College of Family Physicians Singapore. The anonymised survey was executed in two phases: a postal survey, followed by a web-based survey on the College of Family Physicians Singapore website. The two data sets were collated; the categorical variables, summarised; and the differences between subgroups (based on exercise engagement), compared using Fisher's exact test. The effect of each risk factor on exercise duration was quantified using odds ratio (OR) estimate and 95% confidence interval (CI). Multivariate logistic regression analysis was performed to identify significant predictors of exercise engagement.

RESULTSA total of 631 PCPs participated in the survey--26% were ≤ 34 years old, 58% were male, 21% were single, 34% were singleton practitioners, and 56% were private practitioners. The percentage of PCPs who exercised ≥ 2.5 hours weekly was 29%, while 28% exercised < 0.5 hours weekly. Of the PCPs surveyed, 1% currently smoke, 0.8% drink more than 14 units of alcohol weekly, 60% undertook health screening, 65% had blood investigations done, and 64% had taken preventive measures such as getting influenza vaccination.

CONCLUSIONWhile local PCPs generally did not have undesirable habits such as smoking and alcohol abuse, they could further increase their exercise intensity and undertake more preventive measures such as getting vaccinated against various diseases.

Adult ; Aged ; Cross-Sectional Studies ; Exercise ; Female ; Health Behavior ; Health Surveys ; Humans ; Life Style ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Physicians, Primary Care ; Risk Factors ; Singapore ; Surveys and Questionnaires