Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic(type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease

AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.

Have guidelines addressing physical activity been established in nonalcoholic fatty liver disease?

The purpose of this review was to highlight, in relation to the currently accepted pathophysiology of non-alcoholic fatty liver disease (NAFLD), the known exercise habits of patients with NAFLD and to detail the benefits of lifestyle modification with exercise (and/or physical activity) on parameters of metabolic syndrome. More rigorous, controlled studies of longer duration and defined histopathological end-points comparing exercise alone and other treatment are needed before better, evidence-based physical activity modification guidelines can be established, since several questions remain unanswered.

Efficacy of Sitagliptin on Nonalcoholic Fatty Liver Disease in High-fat-diet-fed Diabetic Mice

Objective Nonalcoholic fatty liver disease(NAFLD)is a common cause of clinical liver dysfunction and an important prepathological change of liver cirrhosis.Central obesity,type 2 diabetes mellitus,dyslipidemia,and metabolic syndrome are the major risk factors for NAFLD.Sitagliptin(Sig)is a novel hypoglycemic agent that improves blood glucose levels by increasing the level of active incretin.Sig has been shown to prevent the development of fatty livers in mice on a fructose-rich diet.The purpose of this study was to observe the efficacy of Sig on NAFLD in type 2 diabetic mice.Methods The diet-induced obesity mouse model was established,and the diabetic mice were screened by an intraperitoneal glucose tolerance trial.The mice were randomly divided into four groups for 8 weeks of intervention:high-fat diet(HFD)group,Sig group,metformin(Met)group,and Sig+Met group.After the intervention,the liver function indexes as well as the blood glucose and blood lipid levels of the mice were measured.In addition,the wet weight of the liver was measured;the pathological sections of the liver tissues were stained to observe the hepatocyte fatty degeneration,inflammation,necrosis,and fibrosis;and the hepatic histological injury was recorded as the NAFLD activity score(NAS).Results Compared with the normal control group,the body weight,liver weight,blood glucose level,insulin resistance(IR),blood lipid level,and transaminase level of the mice in the HFD group were significantly increased,showing typical metabolic syndrome.After treatment with Sig and/or Met,the mice gained less weight,had lower levels of blood glucose,triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and transaminase,and had improved IR compared with the HFD group.The liver pathological NASs in the Sig group(P=0.01),Met group(P=0.028),and Sig+Met group(P<0.001)were lower than those in the HFD group(P<0.05),suggesting that the use of the two drugs alone or in combination can improve the state of liver inflammation.In terms of fibrosis,there was no fibrosis in the control group but there was significant fibrosis in the HFD group(P<0.001).There was no significant difference between the drug intervention groups and the HFD group,indicating that the drug therapy(Sig and/or Met)did not significantly improve the pre-existing fibrosis.Conclusion Our experiment proved that Sig can improve NAFLD,including improvement of the serum transaminase level,hepatic pathological inflammation level,and hepatocyte adiposis,suggesting that Sig may play a role by improving glucose and lipid metabolism,reducing the body weight and liver weight,improving insulin sensitivity,and inhibiting fatty liver inflammation.Sig may be a new direction for the treatment of patients with a nonalcoholic fatty liver and diabetes,delaying the progression of NAFLD.

FXR agonist GW4064 alleviates endotoxin-induced hepatic inflammation by repressing macrophage activation

AIM: To examine the effect of farnesoid X receptor (FXR) activation by GW4064 on endotoxin-induced hepatic inflammation in nonalcoholic fatty liver disease (NAFLD) and the underlying mechanism.