Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis?

Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis.     

Correlations of Hepatic Hemodynamics,Liver Function,and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.     

The Natural Course of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death.     

米糠甾醇对非酒精性脂肪性肝炎大鼠的治疗作用

目的：研究米糠植物甾醇对非酒精性脂肪性肝炎（non-alcoholic steatohepatitis,NASH）大鼠的干预治疗作用。方法：实验选用50只健康SD雄性大鼠,随机分为正常对照组、NASH模型组和米糠甾醇低、中、高3个剂量组（65、130、195 mg/kg）。高脂饲料饲喂造模,各实验组同时进行米糠甾醇溶液灌胃干预。13周后观察各组大鼠肝组织病理学特点,测定血清中血脂总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇含量和谷丙转氨酶、谷草转氨酶、一氧化氮合酶和超氧化物歧化酶活性,并比较各组肝脏指数和脾脏指数。结果：肝脏组织切片观察到NASH模型组有明显的肝细胞脂肪变性和炎症聚集浸润,米糠甾醇各治疗组肝组织病变呈现不同程度减轻。NASH模型组血清高密度脂蛋白胆固醇含量、超氧化物歧化酶、一氧化氮合酶、谷丙转氨酶和谷草转氨酶活性与正常对照组相比,均表现出明显异常;米糠甾醇各剂量组与NASH模型组比较,血清谷丙转氨酶显著降低（P＜0.001）、谷草转氨酶/谷丙转氨酶比值显著升高（P＜0.01）;低剂量组血清超氧化物歧化酶（P＜0.05）和一氧化氮合酶（P＜0.001）显著降低;中剂量组血清高密度脂蛋白胆固醇显著升高（P＜0.05）。结论：米糠甾醇对大鼠非酒精性脂肪性肝炎有预防与治疗作用。     

Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.