Non-alcoholic fatty liver disease and thyroid dysfunction:A systematic review

Thyroid hormones are totally involved in the regulation of body weight, lipid metabolism, and insulin resistance. Therefore it is anticipated that thyroid hormones may have a role in the pathogenesis of non alcoholic fatty liver disease(NAFLD) and non alcoholic steatohepatitis(NASH). In this study, we reviewed the current literature on the association between thyroid dysfunction and NAFLD/NASH. A search for English language medical literature reporting an association between thyroid dysfunction and NAFLD/NASH in humans was conducted across PubMed, ISI Web of Science, and Scopus in August, 2013. Out of 140 studies initially identified through the search, 11 relevant articles were included in the final review. Thyroid dysfunctions in the form of overt or subclinical hypothyroidism are prevalent among patients with NAFLD/NASH. Hypothyroidism appears to be an independent risk factor for NAFLD/NASH in some studies; however, other newly published studies failed to find such anassociation. The results of the studies on the role of thyroid abnormalities in NAFLD/NASH are inconsistent, and further research is recommended to determine the relationship between hypothyroidism and NAFLD/NASH and the underlying mechanisms.

Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians

AIM： To evaluate the clinical and biochemical profile of patients with non alcoholic fatty liver disease （NAFLD） and to assess their histological severity at presentation.METHODS： Consecutive patients presenting to the liver clinic of All India Institute of Medical Sciences （AIIMS） with raised transaminases to at least 1.5 times upper limit of normal, and histologically confirmed non-alcoholic fatty liver disease were included. Patients who had significant alcohol intake or positive markers of other liver diseases or who were taking drugs known to produce fatty liver were excluded. The clinical, biochemical and histological profile of this group was studied. RESULTS： Fifty-one patients with NAFLD formed the study population. Their median age and BMI were 34（17-58） years and 26.7（21.3-32.5） kg/m^2 respectively and 46 （90.1%） were males. The majority of the patients had mild inflammation, either grade 1 [32 （63%）] or grade 2 [16 （31%）] and only 3 （6%） patients had severe （grade 3） inflammation. Twenty-three （45%）, 19 （37%）, 8（16%） and 1（2%） patient had stage 0, 1, 2 and 3 fibrosis respectively on index biopsy and none had cirrhosis. On univariate analysis, triglyceride levels more than 150 mg % （OR = 7.1; 95% CI： 1.6-31.5, P = 0.002） and AST ALT ratio 〉 1 （OR = 14.3; 95% CI： 1.4-678.5, P = 0.008） were associated with high grades of inflammation and none was associated with advanced fibrosis. On multivariate logistic regression analysis, hypertriglyceridemia 〉150 mg% was the only factor independently associated with presence of high grade of inflammation （OR = 1.6; 95% CI： 1.3-22.7, P =0.02）, while none was associated with advanced fibrosis. Triglyceride levels correlated positively with inflammatory grade （r = 0.412; P = 0.003）. CONCLUSION： NAFLD in North Indian patients is a disease of young over-weight males, most of whom are insulin resistant and they tend to have a mild histological disease at presentation.

Surgically induced weight loss by gastric bypass improves non alcoholic fatty liver disease in morbid obese patients

AIM: To evaluate the effects of surgical weight loss (Roux-en-Y gastric bypass with a modified Fobi-Capella technique) on non alcoholic fatty liver disease in obese patients.

Mechanism of Qishen Decoction inhibition of macrophage M1 type polarization by targeting TGR5-mediated NLRP3 inflammasome

Objective:To observe the effect of Qishen decoction on TGR5-mediated activation of NLRP3 inflammasome,so as to clarify the molecular mechanism of its inhibition of macrophage M1-type polarisation to ameliorate non-alcoholic steatohepatitis;Methods:Mouse macrophage cell line RAW264.7 was randomly divided into a control group,model group,Qishen decoction group,TGR5 agonist group and Qishen decoction+TGR5 agonist group.Except for the control group,the remaining groups were constructed the macrophage NLRP3 activation model by palmitic acid induction,and the corresponding drugs were given to intervene.ELISA was used to detect the levels of TNF-α,IL-6,IL-1βand CXCL2 in macrophage supernatants,flow cytometry was used to detect the expression levels of macrophage polarisation marker molecules CD86 and iNOS,and Western blot was used to detect the expression of the TGR5/STAT1/STAT6 signaling pathway and the expression of NLRP3 inflammasome-associated proteins,respectively.Results:Compared with the control group,the contents of macrophages TNF-α,IL-6,IL-1β,CXCL2 and the proportion of macrophages with positive expression of CD86 and iNOS were significantly increased in the model group,and the differences were all statistically significant(P<0.01).Compared with the model group,the contents of TNF-α,IL-6,IL-1β,CXCL2 and the proportion of macrophages with positive expression of CD86 and iNOS were significantly decreased in the Qishen decoction group,and the differences were all statistically significant(P<0.01).In addition,the expression of NLRP3 and Pro-IL-1βproteins in the macrophage lysate and the expression of Caspase-1 p10,Caspase-1 p20 and IL-1βp17 proteins in the cell supernatant of the model group were significantly increased when compared with the control group,and the differences were all statistically significant(P<0.01).Compared with the model group,the expression of NLRP3 and Pro-IL-1βproteins in macrophage lysate and the expression of Caspase-1 p10,Caspase-1 p20 and IL-1βp17 proteins in cell supernatant of the Qishen decoction were significantly reduced,and the differences were all statistically significant(P<0.01);Conclusion:Qishen decoction can inhibit the activation of NLRP3 inflammasome in macrophages by inhibiting the TGR5/STAT1/STAT6 signaling pathway,thereby inhibiting macrophage M1 polarization and improving inflammatory response.

Is transient elastography a useful tool for screening liver disease?

Transient elastography(TE)is a new non invasive tool for measuring liver stiffness,which is correlated to the histologic stage of liver fibrosis.Several studies in chronic liver disease(CLD)have determined a good accuracy of TE in predicting significant fibrosis and an optimal accuracy in predicting cirrhosis.Normal liver stiffness ranges between 3.3-7.8 KPa and using a cut off of 7.1 KPa,significant fibrosis and cirrhosis can be excluded with a very high negative predictive value(NPV).Positive predictive value(PPV)for the diagnosis of cirrhosis is lower using just a single scan but increases to 90% if high stiffness values are confirmed by a second independent scan.However the presence of fatty liver and metabolic syndrome slightly increases the readings and may reduce the accuracy of the test.It is uncertain if this increase is related to the presence of steatofibrosis or ifit is caused by steatosis itself.TE can be used in screening patients attending the liver clinics to identify those with signifi cant fi brosis or cirrhosis and may be particularly useful in discriminating HBV inactive carriers from chronic hepatitis B patients.TE,however,is not reliable in predicting the presence of esophageal varices in cirrhotics.Another potential indication for TE is the systematic screening of populations at high risk for CLD,such as intravenous drug users and alcoholics,but further studies are needed to determine its diagnostic accuracy in these settings.

Obese children with fatty liver: Between reality and disease mongering

Following the current epidemic of obesity, the worldwide prevalence of nonalcoholic fatty liver disease(NAFLD)has increased with potential serious health implications. While it is established that in adults NAFLD can progress to end-stage liver disease in many cases, the risk of progression during childhood is less well defined. Since most obese children are not adherent to lifestyle modifications and hypocaloric diets, there is a growing number of studies on pharmacological interventions with the risk of disease mongering, the practice of widening the boundaries of illness in order to expand the markets for treatment. Here, we propose a critical appraisal of the best available evidence about long-term course of pediatric NAFLD and efficacy of treatments other than hypocaloric diet and physical exercise. As a result, the number of NAFLD children with a poor outcome is small in spite of the alarming tones used in some papers; large-scale longitudinal studies with longterm follow-up of pediatric NAFLD patients are lacking; the studies on ancillary pharmacological interventions have been performed in few patients with inconclusive and conflicting results.