Non-alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population-based study.

BACKGROUND: High intensity exercise improves metabolic status and may potentially mobilise hepatic fat. AIM: To assess the level of physical activity (PA) of subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: Data were obtained from NHANES (2003-2006). Activity counts obtained from accelerometer readings (ActiGraph, Fort Walton Beach, FL), from 7 consecutive days quantified total PA and time spent engaged in different levels of activity. All measures were counts/minutes/day: (sedentary <100; light 100-0027; moderate, 2020-5999 and vigorous, 6000+). NAFLD was defined as a fatty liver index >60 (FLI) in the absence of other chronic liver disease. Subjects with NAFLD were compared to controls using stratum-specific Chi-squared and t-tests. Simple linear regression analyses (with Taylor series linearised variance estimation and weighting) were used to determine the association between PA levels and NAFLD. P-values <0.05 were considered significant. Statistical analyses were conducted using sudaan version 10.1 and sas version 9.1. RESULTS: We included 3056 participants. NAFLD patients were older, had higher BMI, larger waist circumference, higher sum of skinfolds, more likely to have insulin resistance (HOMA > 3.0) and type-2 diabetes (all P-values <0.01). Average PA for NAFLD subjects was about 28.7 counts/minute/day less than controls (P < 0.01). Furthermore, NAFLD subjects spent less time participating in activity at any level (P < 0.01). Subjects with NAFLD and DM were in the lowest quartile of average PA as well as moderate-vigorous PA (P < 0.01). CONCLUSIONS: Data from this study show that non-alcoholic fatty liver disease patients have low level of physical activity and, when they have diabetes mellitus, they perform at the lowest quartile of physical activity and moderate-vigorous physical activity.

[Selection of reliable reference genes for qRT-PCR analysis in human non-cancerous gastric tissue].

UNLABELLED: Real-time PCR (qRT-PCR) is the standard method for studying changes in relative gene expression in complex diseases like obesity and gastritis. However, variations in amount of starting material, enzymatic efficiency and presence of amplification inhibitors can lead to quantification errors. Hence, the need for accurate data normalization is vital. Among several known strategies for data normalization, the use of reference genes as an internal control is the most common approach. Human gastric tissue has been the least investigated for stability of reference gene expression. In this study, three popular algorithms, GeNorm, NormFinder and BestKeeper were used to evaluate the reference gene stability. CONCLUSION: HPRT1 and GAPDH are the best performing pair of reference genes for qRT-PCR profiling experiments involving non-malignant gastric tissue samples.

Gene expression profiles associated with anaemia and ITPA genotypes in patients with chronic hepatitis C (CH-C).

Anaemia is a common side effect of ribavirin (RBV) which is used for the treatment of hepatitis C. Inosine triphosphatase gene polymorphism (C to A) protects against RBV-induced anaemia. The aim of our study was to genotype patients for inosine triphosphatase gene polymorphism rs1127354 SNP (CC or CA) and associate treatment-induced anaemia with gene expression profile and genotypes. We used 67 hepatitis C patients with available gene expression, clinical, laboratory data and whole-blood samples. Whole blood was used to determine inosine triphosphatase gene polymorphism rs1127354 genotypes (CC or CA). The cohort with inosine triphosphatase gene polymorphism CA genotype revealed a distinct pattern of protection against anaemia and a lower drop in haemoglobin. A variation in the propensity of CC carriers to develop anaemia prompted us to look for additional predictors of anaemia during pegylated interferon (PEG-IFN) and RBV. Pretreatment blood samples of patients receiving a full course of PEG-IFN and RBV were used to assess expression of 153 genes previously implicated in host response to viral infections. The gene expression data were analysed according to presence of anaemia and inosine triphosphatase gene polymorphism genotypes. Thirty-six genes were associated with treatment-related anaemia, six of which are involved in the response to hypoxia pathway (HIF1A, AIF1, RHOC, PTEN, LCK and PDGFB). There was a substantial overlap between sustained virological response (SVR)-predicting and anaemia-related genes; however, of the nine JAK-STAT pathway-related genes associated with SVR, none were implicated in anaemia. These observations exclude the direct involvement of antiviral response in the development of anaemia associated with PEG-IFN and RBV treatment, whereas another, distinct component within the SVR-associated gene expression response may predict anaemia. We have identified baseline gene expression signatures associated with RBV-induced anaemia and identified its functional pathways. In particular, we identified the hypoxia response pathway and the apoptosis/survival-related gene network, as differentially expressed in chronic hepatitis C patients with anaemia.

Caffeine is protective in patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is the most common cause of primary liver disease. Although recent studies have found that coffee drinking is protective against end stage chronic liver disease, there are scarce caffeine intake data in NAFLD specifically. AIM: To investigate the effects of dietary behaviour in NAFLD patients, using four continuous cycles of the National Health and Nutrition Examination Surveys (NHANES 2001-2008). METHODS: Using data from four continuous cycles of NHANES, dietary intake questionnaires that list 62 nutrition components. Logistic regression was used to identify independent predictors of NAFLD among nutrition components after adjustment for potential clinical confounders. All analyses were run using sas 9.1 and SUDAAN 10.0 (SAS Institute Inc., Cary, NC, USA). RESULTS: Of the 62 nutrient components used for the univariate analysis, 38% were significant (P-value <0.05) in NAFLD with caffeine consumption being higher in the control group (P-value <0.001). The multivariate analysis using demographics, clinical parameters and nutritional components found five factors independently associated with NAFLD [African American Race P-value <0.001); Male gender P-value <0.001); Obesity (BMI ≥ 30) P-value <0.001); Caffeine intake (mg) P-value <0.001) and total plain water consumption (g) P-value ≤ 0.02)]. CONCLUSIONS: Our analysis shows that caffeine intake is independently associated with a lower risk for NAFLD suggesting a potential protective effect. These data necessitate further research to elucidate the mechanism by which caffeine can protect against NAFLD.

Systematic review: association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common disorder for women of child-bearing age and is associated with metabolic syndrome (MS). AIM: To assess the literature for associations between polycystic ovary syndrome and non-alcoholic fatty liver disease (NAFLD). METHODS: We performed a systematic review using PubMed-search for peer-reviewed articles related to polycystic ovary syndrome and NAFLD. Articles were summarised and grouped according to different sections defining interactions of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease as well as risk factors, pathogenic pathways and treatment options. RESULTS: Obesity is a common factor involved in both polycystic ovary syndrome and non-alcoholic fatty liver disease. Obesity causes non-alcoholic fatty liver disease and aggravates hirsutism and menstrual disorders in polycystic ovary syndrome. Insulin resistance, a hallmark of metabolic syndrome is observed in 50-80% of women with polycystic ovary syndrome and patients with non-alcoholic fatty liver disease. Recent findings suggest that women with polycystic ovary syndrome may be at risk for developing non-alcoholic fatty liver disease and conversely, non-alcoholic fatty liver disease may be a risk for polycystic ovary syndrome. Based on the association of polycystic ovary syndrome and other metabolic abnormalities, such as insulin resistance, hyperandrogenism, obesity and non-alcoholic fatty liver disease, the candidate genes have been speculated for polycystic ovary syndrome. Closer scrutiny of these genes placed most of their proteins at the crossroads of three highly inter-related conditions: metabolic syndrome, obesity and non-alcoholic fatty liver disease. In most studies, the prevalence of both polycystic ovary syndrome and non-alcoholic fatty liver disease rises proportionally to the degree of insulin resistance and increases in the mass of adipose tissue. CONCLUSIONS: Non-alcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Similarly, it seems appropriate to consider polycystic ovary syndrome as the ovarian manifestation of metabolic syndrome. Both these conditions can co-exist and may respond to similar therapeutic strategies.

Non-invasive diagnostic tests for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Although simple or bland steatosis follows a relatively benign clinical course, NASH can potentially progress to cirrhosis (approximately 10 to 15 percent) and hepatocellular carcinoma. NAFLD occurs in an estimated 25 to 30 percent of the US general population, while NASH is reported in 2 to 3 percent of the population. Even though common explanation for the increased prevalence of NAFLD is the increased rate of obesity, the risk of developing NAFLD and NASH is not limited to overweight and obese individuals. Currently, the only way to diagnose NASH or to assess the stage of fibrosis is by obtaining a liver biopsy. Liver biopsy is invasive, expensive, and associated with potential risks, including post biopsy pain, bleeding, organ perforation, and even death; serious complications can occur in 0.3 percent of liver biopsies with 0.01 percent being fatal. This review examines the current strategies for development of the non-invasive techniques that will one day replace liver biopsy and serve as a non-invasive gold standard for the diagnosis and staging of NASH.

Functional pathway analysis of genes associated with response to treatment for chronic hepatitis C.

Chronic hepatitis C (CH-C) is among the most common causes of chronic liver disease. Approximately 50% of patients with CH-C treated with pegylated interferon-α and ribavirin (PEG-IFN-α + RBV) achieve a sustained virological response (SVR). Several factors such as genotype 1, African American (AA) race, obesity and the absence of an early virological response (EVR) are associated with low SVR. This study elucidates molecular pathways deregulated in patients with CH-C with negative predictors of response to antiviral therapy. Sixty-eight patients with CH-C who underwent a full course of treatment with PEG-IFN-α + RBV were included in the study. Pretreatment blood samples were collected in PAXgene™ RNA tubes. EVR, complete EVR (cEVR), and SVR rates were 76%, 57% and 41%, respectively. Total RNA was extracted from pretreatment peripheral blood mononuclear cells, quantified and used for one-step RT-PCR to profile 154 mRNAs. The expression of mRNAs was normalized with six 'housekeeping' genes. Differentially expressed genes were separated into up and downregulated gene lists according to the presence or absence of a risk factor and subjected to KEGG Pathway Painter which allows high-throughput visualization of the pathway-specific changes in expression profiles. The genes were consolidated into the networks associated with known predictors of response. Before treatment, various genes associated with core components of the JAK/STAT pathway were activated in the cohorts least likely to achieve SVR. Genes related to focal adhesion and TGF-ß pathways were activated in some patients with negative predictors of response. Pathway-centred analysis of gene expression profiles from treated patients with CH-C points to the Janus kinase-signal transducers and activators of transcription signalling cascade as the major pathogenetic component responsible for not achieving SVR. In addition, focal adhesion and TGF-ß pathways are associated with some predictors of response.