Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese

Background and aims

It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.

De Novo Non-Alcoholic Fatty Liver Disease Following Orthotopic Liver Transplantation

Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized clinico-pathologic entity typically associated with obesity, type II diabetes and hyperlipidemia. It has been noted to recur after orthotopic liver transplantation (OLT). We report four patients who developed de novo NAFLD within 3 months of OLT without the typical predisposing factors of diabetes mellitus or obesity. Three of the four patients underwent OLT for hepatitis C-related cirrhosis, and the other for alcoholic cirrhosis. Examination of the liver explants revealed no evidence of steatosis. No surreptitious alcohol use or a drug-induced process could be identified in these patients. Treatment of recurrent hepatitis C infection in one patient with interferon and ribavirin led to sustained suppression of the viral RNA to undetectable levels, but no improvement in histology or liver enzymes. All four patients had histologic evidence of preservation injury on the initial post-OLT biopsies, but the significance of this finding in relationship to the development of NAFLD is unknown. NAFLD can develop without any of the known predisposing conditions after transplantation, and this raises further questions about the pathogenesis of this condition .     

Non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD), also referred to as metabolic associated fatty liver disease (MAFLD), is the commonest form of chronic liver disorder arising from metabolic dysregulation. It encompasses a wide spectrum of fatty liver phenotypes including isolated steatosis to non-alcoholic steatohepatitis (NASH). NASH is considered more likely to lead to grave clinical consequences such as cirrhosis and hepatocellular carcinoma, compared to simple steatosis. NASH is characterised by steatosis, inflammation, and damage to hepatocytes. Here, we present a case of a middle-aged gentleman with a background of infectious hepatitis who presented with NASH, with emphasis on terminology and histological assessment criteria of NAFLD and NASH. Reflection on and consistent effort to standardise terminology and assessment criteria will aid in addressing the scientific and clinical needs of NAFLD and NASH.     

Intrahepatic Fat Content and COVID-19 Lockdown in Adults with NAFLD and Metabolic Syndrome

Background: COVID-19 lockdowns had a significant impact on people’s health, triggering levels of anxiety, perceived stress, and changes in food and nutritional status. Objectives: To assess the changes in dietary habits, metabolic syndrome (MetS) and liver parameters before and after the COVID-19 lockdown according to changes in intrahepatic fat content in adults with non-alcoholic fatty liver disease (NAFLD) and MetS. Design: Pre- and post-lockdown observation of the COVID-19 lockdown on fifty-nine 40–60-year-old participants with MetS and NAFLD, in a parallel group, randomised experiment intended to treat NAFLD. Methods: Anthropometrics, liver and MetS biochemical parameters, intrahepatic fat content by abdominal magnetic resonance imaging, and dietary assessment using a validated 148-item Food Frequency Questionnaire were collected pre-COVID-19 lockdown and post-lockdown. Results: COVID-19 lockdown led to negative changes in the liver of patients with NAFLD and MetS, with weight gain and increases in glycemia, ALT and intrahepatic fat content post lockdown. Participants with worsened liver status had low consumption of fibre, cheese, nuts and coffee, and high consumption of sweets and pastries. Participants who improved liver status ameliorated ALT values, waist circumference, and intrahepatic fat content, assessed by magnetic resonance imaging post-lockdown. Conclusions: The maintenance of healthy lifestyle habits is vital, especially for populations with NAFLD and MetS, to reduce unhealthy lifestyle patterns displayed during lockdown.     

Berberine in Non-Alcoholic Fatty Liver Disease—A Review

The incidence of Non-Alcoholic Fatty Liver Disease (NAFLD) has been rapidly increasing during the last decade. It is a relevant health problem that affects 25% of the general population. NAFLD involves an extensive array of clinical conditions. So far, no approved pharmacological therapy for NAFLD has been developed. Multiple bioactive compounds have been proposed to treat NAFLD. One of the most promising is Berberine (BBR). Its pleiotropic effect positively impacts various cardiometabolic aspects. In this review, we summarize NAFLD, its metabolic and cardiovascular complications, the hepatoprotective effects of BBR due to its broad spectrum of pharmacological effects, and the potential role of BBR in NAFLD therapy. BBR ameliorates NAFLD by affecting numerous abnormalities. It inhibits lipogenesis and gluconeogenesis, improves insulin resistance and lipid profile, and modulates gut microbiota. The exact mechanism underlying these effects is not yet entirely explained. A growing amount of evidence confirming the positive effects of BBR on multiple metabolic pathways, such as lipids and glucose metabolism, energy homeostasis, or gut microbiota modulation, allows us to speculate about the importance of this natural bioactive substance for NAFLD therapy.     

Fatty Acids and Eicosanoids Change during High-Fiber Diet in NAFLD Patients—Randomized Control Trials (RCT)

Background: Non-alcoholic fatty liver disease (NAFLD) is a wide spectrum condition characterized by excessive liver fat accumulation in people who do not abuse alcohol. There is no effective medical treatment for NAFLD; therefore, most important recommendations to reduce liver steatosis are diet and lifestyle, including proper physical activity. The aim of our study was to analyze the fatty acids and eicosanoids changes in the serum of patients who consumed high-fiber rolls for 8 weeks. Materials and Methods: The group of 28 Caucasian participants was randomly divided into two groups, those who received 24 g of fiber/day—from 2 buns of 12 g each (n = 14), and those who received 12 g of fiber/day—from 2 buns of 6 g (n = 14). At the beginning and on the last visit of the 8-week intervention, all patients underwent NAFLD evaluation, biochemical parameter measurements, and fatty acids and eicosanoids evaluation. Results: Patients who received 12 g of fiber had significantly reduced liver steatosis and body mass index. In the group who received 24 g of fiber/day, we observed a trend to liver steatosis reduction (p = 0.07) and significant decrease in aspartate aminotransferase (p = 0.03) and total cholesterol (p = 0.03). All changes in fatty acid and eicosanoids profile were similar. Fatty acids analysis revealed that extra fiber intake was associated with a significant increase in monounsaturated fatty acids and decrease in saturated fatty acids. Moreover, both groups showed increased concentration of gamma linoleic acid and docosahexaenoic acid. We also observed reduction in prostaglandin E₂. Conclusions: Our study revealed that a high amount of fiber in the diet is associated with a reduction in fatty liver, although this effect was more pronounced in patients in the lower fiber group. However, regardless of the amount of fiber consumed, we observed significant changes in the profile of FAs, which may reflect the positive changes in the lipids liver metabolism. Regardless of the amount of fiber consumed, patients decreased the amount of PGE₂, which may indicate the lack of disease progression associated with the development of inflammation.     

Litchi-Derived Polyphenol Alleviates Liver Steatosis and Gut Dysbiosis in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Double-Blinded,Placebo-Controlled Study

Preclinical data suggest the role of litchi extract in alleviating non-alcoholic fatty liver disease (NAFLD) by modulating gut microbiota. We aimed at investigating whether oligonol, a litchi-derived polyphenol, could improve liver steatosis and gut dysbiosis in patients with NAFLD. Adults with grade ≥2 steatosis, defined by an MRI proton density fat fraction (MRI-PDFF) of ≥11%, were randomly assigned to receive either oligonol or placebo for 24 weeks. The alteration in the MRI-PDFF and gut microbiota composition assessed by 16S ribosomal RNA sequencing were examined. There were 38 patients enrolled (n = 19 in each group). A significant reduction in the MRI-PDFF between week 0 and week 24 was observed in the oligonol group, while there was a non-significant decrease in the placebo group. A significant improvement in alpha-diversity was demonstrated in both of the groups. The oligonol-induced microbiota changes were characterized by reduced abundance of pathogenic bacteria, including Dorea, Romboutsia, Erysipelotrichaceae UCG-003 and Agathobacter, as well as increased abundance of short-chain fatty acids (SCFAs)-producing bacteria, such as Akkermansia, Lachnospira, Dialister and Faecalibacterium. In summary, this study is the first to provide evidence that supports that oligonol improves steatosis through the modulation of gut bacterial composition. Our results also support the beneficial and complementary role of oligonol in treating NAFLD.     

CK18-M30和内毒素在大鼠非酒精性脂肪肝病中的促进作用

目的探讨细胞角蛋白18-M30片段(CK18-M30)、内毒素在大鼠非酒精性脂肪肝病(NAFLD)转化为非酒精性脂肪性肝炎(NASH)中的促进作用。方法 26只大鼠随机分为3组,对照组(NC组):普通饮食;NAFLD组:高脂饮食喂养8周;NASH组:高脂饮食喂养12周。生化仪测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST);光度法测定血清内毒素(ET);ELISA检测血清IL-18、CK18-M30,RT-PCR分析粪便肠道菌群;行苏木精伊红(HE)染色观察肝脏及末端回肠组织病理。结果 NAFLD及NASH组相比NC组,小肠黏膜结构由轻到重受到破坏。NAFLD组及NASH组大鼠血清ET、CK18-M30、肝脂肪变性程度及NAFLD活动度积分(NAS)、大肠杆菌属计数显著高于NC组,而双歧杆菌属、乳酸杆菌属计数显著低于NC组,差异有统计学意义(P<0.05);NASH组大鼠血清ET、CK18-M30、肝脂肪变性程度及NAS显著高于NAFLD组,差异有统计学意义(P<0.05);NASH组大鼠血清ALT、AST、IL-18显著高于NC组及NAFLD组,差异有统计学意义(P&l...     

活血与化痰基础方对大鼠非酒精性脂肪肝模型基本生化指标的影响

目的：观察活血与化痰基础方治疗大鼠非酒精性脂肪肝模型的疗效。方法：制备非酒精性脂肪肝大鼠动物模型,用二陈汤、桃红四物汤及其合方分别治疗。实验结束时,检测大鼠基本生化指标。结果：二陈汤可降低肝脏脏器系数、胆固醇、谷草转氨酶水平（P〈0.01）;二陈合桃红四物汤可降低谷草转氨酶、肝脏脏器系数水平（P〈0.01）。各中药治疗组能降低谷丙转氨酶、甘油三酯、空腹血糖和胰岛素、胰岛素抵抗指数,提高胰岛素敏感指数（P〈0.01）。结论：活血与化痰的基础方能从降脂、保肝、改善胰岛素抵抗等多个方面改善非酒精性脂肪肝的病理状态。     

强肝胶囊对非酒精性脂肪肝大鼠肝脏脂质的影响

目的观察强肝胶囊对非酒精性脂肪肝(NAFLD)大鼠模型肝脏脂质的影响。方法高脂饲料制备SD大鼠NAFLD模型,随机分为模型组、强肝胶囊组和辛伐他汀组。药物干预4周后行肝组织生化和病理学检测。结果强肝胶囊能明显降低NAFLD大鼠模型肝脂(TG、TC)的水平,改善脂肪变性,降低肝脏炎症反应,且效果优于辛伐他汀(P<0.05)。结论强肝胶囊对NAFLD大鼠肝脏脂质和炎症有较好的治疗作用。