Identifying potential biomarkers of nonalcoholic fatty liver disease via genome-wide analysis of copy number variation.

BACKGROUND: The prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing and emerging as a global health burden. In addition to environmental factors, numerous studies have shown that genetic factors play an important role in the development of NAFLD. Copy number variation (CNV) as a genetic variation plays an important role in the evaluation of disease susceptibility and genetic differences. The aim of the present study was to assess the contribution of CNV to the evaluation of NAFLD in a Chinese population. METHODS: Genome-wide analysis of CNV was performed using high-density comparative genomic hybridisation microarrays (ACGH). To validate the CNV regions, TaqMan real-time quantitative PCR (qPCR) was utilized. RESULTS: A total of 441 CNVs were identified, including 381 autosomal CNVs and 60 sex chromosome CNVs. By merging overlapping CNVs, a genomic CNV map of NAFLD patients was constructed. A total of 338 autosomal CNVRs were identified, including 275 CNVRs with consistent trends (197 losses and 78 gains) and 63 CNVRs with inconsistent trends. The length of the 338 CNVRs ranged from 5.7 kb to 2.23 Mb, with an average size of 117.44 kb. These CNVRs spanned 39.70 Mb of the genome and accounted for ~ 1.32% of the genome sequence. Through Gene Ontology and genetic pathway analysis, we found evidence that CNVs involving nine genes may be associated with the pathogenesis of NAFLD progression. One of the genes (NLRP4 gene) was selected and verified by quantitative PCR (qPCR) method with large sample size. We found the copy number deletion of NLRP4 was related to the risk of NAFLD. CONCLUSIONS: This study indicate the copy number variation is associated with NAFLD. The copy number deletion of NLRP4 was related to the risk of NAFLD. These results could prove valuable for predicting patients at risk of developing NAFLD.

Physical activity intervention for non-diabetic patients with non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease nowadays. Changes in diet and lifestyle have led to a dramatic increase in the prevalence of NAFLD around the world. This meta-analysis is to investigate the efficacy of physical activity intervention on liver-specific endpoints in the population with NAFLD, including hepatic enzyme, serum lipid, glucose metabolism and intra-hepatic lipid. METHODS: PubMed and China National Knowledge Infrastructure (CNKI) databases were searched for randomized clinical trials of physical activity intervention on NAFLD patients through April 20th, 2019. Effect sizes were reported as standardized mean difference (SMD) and 95% confidence intervals (CI). Quality of included studies was assessed according to the Cochrane risk of bias tool. Meta-analyses were conducted using random-effect or fixed-effect models depending on the significance of heterogeneity. Subgroup analyses according to types and duration of physical activity were conducted to investigate clinical variability. RESULTS: Nine studies with a cumulative total of 951 participants met selection criteria. Physical activity was found associated with small reductions in hepatic enzyme parameters: ALT (SMD -0.17, 95% CI:-0.30 to - 0.05), AST (SMD -0.25, 95% CI: - 0.38, - 0.13) and GGT (SMD -0.22, 95% CI: - 0.36, - 0.08). Significant small improvements were also found in serum lipid parameters including TC (SMD = - 0.22, 95% CI: - 0.34, - 0.09), TG (SMD = - 0.18, 95% CI: - 0.31 to - 0.06) and LDL-C (SMD = - 0.26, 95% CI: - 0.39 to - 0.13). Significant improvement was also found in intra-hepatic lipid content (SMD = - 0.21, 95% CI: - 0.36 to - 0.06) There was no difference between physical intervention group and control group in HDL and three glucose metabolism parameters. Subgroup analysis suggested both aerobic exercise alone and resistance exercise alone can improve most liver function and longer period of exercise generally had better improvement effect. CONCLUSIONS: Our findings suggest that physical activity alone can only slightly improve hepatic enzyme levels, most serum lipid levels and intra-hepatic lipid content in non-diabetic patients with NAFLD.

The role of hepatitis B infection in anti-tuberculosis drug-induced liver injury: a meta-analysis of cohort studies.

Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13-3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95-5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66-3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80-24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87-2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.

Association of food intake with a risk of metabolic dysfunction-associated fatty liver disease: a cross-sectional study.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease, the risk of which can be increased by poor diet. The objective of this study was to evaluate the associations between food items and MAFLD, and to propose reasonable dietary recommendations for the prevention of MAFLD. Methods: Physical examination data were collected from April 2015 through August 2017 at Nanping First Hospital (n = 3,563). Dietary intakes were assessed using a semi-quantitative food frequency questionnaire. The association between food intake and the risk of MAFLD was assessed by using the inverse probability weighted propensity score. Results: Beverages (soft drinks and sugar-sweetened beverages) and instant noodles were positively associated with MAFLD risk, adjusting for smoking, drinking, tea intake, and weekly hours of physical activity [adjusted odds ratio (ORadjusted): 1.568; P = 0.044; ORadjusted: 4.363; P = 0.001]. Milk, tubers, and vegetables were negatively associated with MAFLD risk (ORadjusted: 0.912; P = 0.002; ORadjusted: 0.633; P = 0.007; ORadjusted: 0.962; P = 0.028). In subgroup analysis, the results showed that women [odds ratio (OR): 0.341, 95% confidence interval (CI): 0.172-0.676] had a significantly lower risk of MAFLD through consuming more tubers than men (OR: 0.732, 95% CI: 0.564-0.951). Conclusions: These findings suggest that reducing consumption of beverages (soft drinks and sugar-sweetened beverages) and instant noodles, and consuming more milk, vegetables, and tubers may reduce the risk of MAFLD.

Copy number variation in the CES1 gene and the risk of non-alcoholic fatty liver in a Chinese Han population.

A recent genome-wide copy number variations (CNVs) scan identified a 16q12.2 deletion that included the carboxylesterase 1 (CES1) gene, which is important in the metabolism of fatty acids and cholesterol. We aimed to investigate whether CES1 CNVs was associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in a Chinese Han population. A case-control study was conducted among 303 patients diagnosed with NAFLD and 303 age (± 5) and sex-matched controls from the Affiliated Nanping First Hospital of Fujian Medical University in China. The copy numbers of CES1 were measured using TaqMan quantitative real-time polymerase chain reaction (qPCR) and serum CES1 was measured using enzyme-linked immunosorbent assays. The Chi-squared test and a logistic regression model were used to evaluate the association between CES1 CNVs and NAFLD susceptibility. The distribution of CES1 CNVs showed a higher frequency of CNVs loss (< 2) among patients; however, the difference was not significant (P = 0.05). After controlling for other known or suspected risk factors for NAFLD, CES1 CNVs loss was significantly associated with greater risk of NAFLD (adjusted OR = 2.75, 95% CI 1.30-5.85, P = 0.01); while CES1 CNVs gain (> 2) was not. There was a suggestion of an association between increased CES1 serum protein levels and CNVs losses among cases, although this was not statistically significant (P = 0.07). Copy number losses (< 2) of CES1 contribute to susceptibility to NAFLD in the Chinese Han population.