Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: To evaluate the efficacy of empagliflozin compared to pioglitazone in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM). METHODS: In this prospective randomized, double-blind, placebo-controlled trial, we assigned 106 patients with NAFLD and T2DM to receive empagliflozin 10 mg (n = 35), pioglitazone 30 mg (n = 34), or placebo (n = 37) for 24 weeks. Liver fat content and liver stiffness were measured using fibroscans. Body composition assessment was performed by dual-energy x-ray absorptiometry (DEXA) scans. The primary end point was change from baseline in liver steatosis, using the controlled attenuation parameter (CAP) score. RESULTS: A borderline significant decrease in CAP score was observed with empagliflozin compared to placebo, mean difference: - 29.6 dB/m (- 39.5 to - 19.6) versus - 16.4 dB/m (- 25.0 to - 7.8), respectively; p = 0.05. Using multivariate analysis, we observed a significant reduction in the placebo-corrected change in liver stiffness measurement (LSM) with empagliflozin compared to pioglitazone: - 0.77 kPa (- 1.45, - 0.09), p = 0.02, versus 0.01 kPa (95% CI - 0.70, 0.71, p = 0.98), p for comparison = 0.03. Changes in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), HOMA2-IR, fibrosis-4 index (FIB4 index), NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index (APRI), android/gynecoid ratio (A/G ratio), and skeletal muscle index (SMI) were comparable between the two treatment groups, while significant reductions of the body weight and visceral fat area were observed only in the empagliflozin group (p < 0.001 and p = 0.01, respectively) and both were increased in the placebo and pioglitazone groups. There were no serious adverse events in either group. CONCLUSION: Treatment for 24 weeks with empagliflozin, in contrast to pioglitazone, was associated with improvement of liver steatosis and fibrosis in patients with NAFLD and T2DM. In addition, body weight and abdominal fat area were decreased in the empagliflozin group. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20190122042450N3.

Risk factor compositions of nonalcoholic fatty liver disease change with body mass index in males and females.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and correlated with obesity. To evaluate the role of body mass index (BMI) and gender difference in NAFLD, 8817 general adult subjects underwent physical examinations and were divided into four groups: underweight, normal, overweight and obese. The risk factor compositions for NAFLD were evaluated in each group by gender. The percentage of subjects with NAFLD increased sharply from 0.4% in the underweight group up to 81.9 % in the obese group. BMI stratification showed distinct risk factor compositions associated with NAFLD in males and females according to BMI and improved the performance of NAFLD prediction models in each group. Triglycerides (TG), alanine transaminase (ALT), aspartate transaminase (AST), and uric acid were steady risk factors for NAFLD in males. Total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), ALT, and uric acid were steady risk factors for NAFLD in females. TG, ALT and uric acid were common risk factors in both genders with high performance for NAFLD discrimination. Our data provide gender- and BMI-specific risk factor compositions that will facilitate individualised treatment and benefit NAFLD control and prevention.

"Hockey Stick" may Strike Back: Hepatocellular Carcinoma on Noncirrhotic Liver as a Late Toxicity of Lombo-Aortic Radiotherapy for Seminoma. A Review Triggered by an Unusual Case.

Most patients with testicular seminoma have been treated with a curative intent for decades. Second cancers after radiotherapy for testicular seminoma before 1990 are a growing issue, and are related to previous generation of dose planning and delineating strategies. Among those cancers, hepatocellular carcinoma is an extremely rare occurrence, especially when affecting patients with healthy, noncirrhotic liver. Here, we describe such a case in a patient of our institution, and subsequently review the relevant literature and large epidemiologic studies. Understanding those late and serious toxicity features may help cancer care teams to screen and treat those patients appropriately.

Effects of Telmisartan on Insulin Resistance and Oxidative Stress in Nonalcoholic Steatohepatitis Rats / 天津医药

Objective To investigate the effects of telmisartan on insulin resistance and oxidative stress in nonalco?holic steatohepatitis (NASH) rats. Methods Fifty male SD rats were randomly divided into five groups:control group, mod?el group, polyene phosphatidylcholine group, low-dose telmisartan group and high-dose telmisartan group by using random number table (n=10 in each group). Control group was given standard food,the other groups were given high fat diet for 12 weeks to establish NASH rat model. Then intervention groups were given either normal saline 1.0 mL/(kg·d) or polyene phos?phatidylcholine 8.4 mg/(kg·d), or telmisartan 4 mg/(kg·d) or telmisartan 8 mg/(kg·d) for 4 weeks by intragastric adminstra?tion. All rats were sacrificed at the end of the 16th week, the lever of plasma insulin resistance index (HOMA-IR), ALT, AST, TG, TC, MDA, SOD, T-AOC, CAT, GSH-PX and liver homogenate MDA, SOD, GSH-PX and liver NAS scores were tested. Results In polyene phosphatidylcholine treated group, the lever of plasma ALT, AST, HOMA-IR and liver NAS scores were degreased significantly compared with model group. The lever of plasma AST, SOD, T-AOC, CAT, GSH-PX and liver homogenate SOD, GSH-PX, liver NAS scores were improved in both low-dose and high-dose telmisartan groups com?pared with model group while plasma and liver homogenate MDA , HOMA-IR were reduced significantly in these two groups compared with model group. Besides, plasma ALT was significantly improved in high-dose telmisartan group compared with model group. Conclusion Telmisartan reduce plasma ALT, AST, oxidative stress, HOMA-IR and liver NAS scores in NASH rats. And high-does telmisartan is better than low-dose telmisartan and polyene phosphatidylcholine in treatment ef?fect.