Nonalcoholic fatty liver and the severity of acute pancreatitis

AimTo explore the effect of nonalcoholic fatty liver as a hepatic manifestation of metabolic syndrome on the severity of acute pancreatitis. We hypothesized that patients with nonalcoholic fatty liver would have a more severe form of acute pancreatitis.Patients and methodsWe retrospectively analyzed 822 patients hospitalized with acute pancreatitis. We diagnosed acute pancreatitis and determined its severity according the revised Atlanta classification criteria from 2012. We assessed nonalcoholic fatty liver with computed tomography.ResultsThere were 198 (24.1%) patients out of 822 analyzed who had nonalcoholic fatty liver. Patients with nonalcoholic fatty liver had statistically higher incidence of moderately severe (35.4% vs. 14.6%; p = 0.02) and severe acute pancreatitis (20.7% vs. 9.6%; p < 0.001) compared to patients without nonalcoholic fatty liver. At the admission patients with nonalcoholic fatty liver had higher values of C-reactive protein as well as at day three, higher APACHE II score at admission and significantly higher incidence of organ failure and local complications as well as higher values of computed tomography severity index compared to patients without nonalcoholic fatty liver. We found independent association between the occurrence of moderately severe and severe acute pancreatitis and nonalcoholic fatty liver (OR 2.13, 95%CI 1.236–3.689). Compared to patients without nonalcoholic fatty liver, patients with nonalcoholic fatty liver had a higher death rate, however not statistically significant (5.6% vs. 4.3%; p = NS).ConclusionPresence of nonalcoholic fatty liver at admission can indicate a higher risk for developing more severe forms of acute pancreatitis and could be used as an additional prognostic tool.     

Hepatic Circulation and Hepatic Oxygen Consumption in Alcoholic and Nonalcoholic Fatty Liver

The purpose of this study was to determine the differences in hepatic circulation and oxygen consumption in two groups: those with nonalcoholic obesity-related fatty live and those with alcoholic fatty liver. Although the histological degree of fatty infiltration was equal in the two groups, the delta Er569-650, as an index of the regional liver blood flow estimated by spectrophotometric method, was significantly lower in alcoholic fatty liver than in nonalcoholic fatty liver, and the in vivo hepatic oxygen consumption (VO2), also determined by hepatic reflectance spectrophotometry during peritoneoscopy, tended to be lower in alcoholic fatty liver than in nonalcoholic fatty liver. The oxygen saturation of hemoglobin in local liver blood (SO2) was, however, significantly higher in alcoholic fatty liver than in nonalcoholic fatty liver. These results suggest that an increase in oxygen extraction to maintain oxygen consumption, which was indicated by the lowering of the SO2, was not found in alcoholic fatty liver, in spite of a reduction of oxygen supply to the liver. It is concluded that the impairment of hepatic circulation and hepatic oxygen consumption was more serious in alcoholic fatty liver than in nonalcoholic fatty liver, possibly contributing to a different prognosis for the two forms of fatty liver.     

Serum Resistin as a Biomarker in Nonalcoholic Fatty Liver Disease: Is This a Road to be Taken?

Nonalcoholic fatty liver disease (NAFLD), which encompass-es a broad spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH...     

非酒精性脂肪性肝病相关心血管疾病的发病机制

非酒精性脂肪性肝病也称为代谢相关脂肪性肝病,是全球最为常见的慢性肝病。研究发现非酒精性脂肪性肝病与心血管疾病的风险增加有关,并且非酒精性脂肪性肝病本身是心血管疾病的独立危险因素。鉴于非酒精性脂肪性肝病与心血管疾病的密切关联,文章综述了连接非酒精性脂肪性肝病与心血管疾病的病理生理机制,为临床非酒精性脂肪性肝病患者心血管疾病的诊治提供了思路。     

Increased susceptibility to nonalcoholic fatty liver disease in heterozygotes for the mutation responsible for hereditary hemochromatosis

BACKGROUND: Insulin resistance is a key feature of nonalcoholic fatty liver disease. Patients with hereditary hemochromatosis, a disease characterized by progressive iron overload due, in most cases, to homozygosity for C282Y mutation in the HFE gene, have often decreased insulin sensitivity and release. AIMS: To determine whether increased iron parameters/heterozygosity for the mutations of the HFE gene confer susceptibility to nonalcoholic fatty liver disease. PATIENTS: One hundred and thirty-four consecutive Italian patients with clinical and ultrasonographic diagnosis of nonalcoholic fatty liver disease (82 with hyperferritinemia), half confirmed by liver biopsy. METHODS: Insulin was determined by radioimmunoassay. HFE gene mutations were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: (1) Prevalence of C282Y HFE mutation was significantly higher in patients with nonalcoholic fatty liver disease compared to controls, the difference being more striking in patients with hyperferritinemia than in those without. (2) The presence of mild iron overload was associated with a lower insulin release. (3) Carriers of C282Y mutation developed nonalcoholic fatty liver disease despite lower body mass index and triglycerides. CONCLUSION: The mild iron overload associated with heterozygosity for C282Y HFE mutation confers susceptibility to nonalcoholic fatty liver disease, causing relative insulin deficiency.     

Relationship between nonalcoholic fatty liver disease prevalence and visceral fat in obese adolescents

BACKGROUND: Visceral adiposity is the major risk factor for paediatric nonalcoholic fatty liver disease. AIMS: Determine the prevalence of nonalcoholic fatty liver disease according to the visceral fat quartile. SUBJECTS: 181 obese adolescents including 113 girls (16.58+/-1.56 years) and 68 boys (16.87+/-1.62 years) were evaluated. METHODS: The inclusion criteria were obesity and post-pubertal stage of Tanner. Visceral fat of obese adolescents was distributed in quartiles after ultrasound nonalcoholic fatty liver disease diagnosis. RESULTS: Nonalcoholic fatty liver disease prevalence was 45.30%. It was observed that 62.07% and 76.47% of girls and boys with nonalcoholic fatty liver disease were found in the 4th quartile. In a multivariate logistic analysis it was observed that only visceral fat remained statistically significant, every 1cm increase in visceral fat was associated with a 1.97 fold (95% CI 1.06-3.66) in boys and 2.08 fold (95% CI 1.38-3.13) in girls increased risk to develop nonalcoholic fatty liver disease. Indeed it was verified a positive correlation between visceral fat, body mass index, insulin levels, homeostasis model assessment insulin resistance index and steatosis degree. CONCLUSIONS: Our findings suggested that the expansion of visceral fat was a determinant factor to increase nonalcoholic fatty liver disease prevalence and the visceral fat measured by ultrasound might be a good predictor to identify risk for nonalcoholic fatty liver disease in obese adolescents. It was confirmed by a stronger correlation between visceral fat and body mass index.     

Hyperinsulinemia and the development of nonalcoholic Fatty liver disease in nondiabetic adults

Background

Insulin resistance is known to be the most important pathogenic factor in the development of nonalcoholic fatty liver disease. We performed a prospective study to analyze the associations of baseline and changes in fasting insulin levels with future development of nonalcoholic fatty liver disease in nondiabetic adults over a 5-year period.

Methods

This study was performed in 4954 subjects who did not have diabetes or nonalcoholic fatty liver disease and who participated in a health checkup program in both 2003 and 2008. The presence of nonalcoholic fatty liver disease was defined by ultrasonographic examination. Subjects were divided into 4 groups according to the baseline quartiles of fasting insulin and dichotomized fasting insulin levels at baseline and after 5 years: low-low, low-high, high-low, high-high.

Results

After 5 years, 644 subjects (13%) developed nonalcoholic fatty liver disease. The odds ratio (OR) for development of nonalcoholic fatty liver disease increased as the quartiles of the baseline fasting insulin levels increased from the first to the fourth quartile (1.00 vs. 0.99, 1.44, 1.65, respectively). The OR for nonalcoholic fatty liver disease was 2.5-fold higher in the high-high group and 1.6-fold higher in the low-high group compared with that of the low-low group. The OR for nonalcoholic fatty liver disease increased as the quartile of changes in fasting insulin level over the 5-year period increased.

Conclusion

High baseline and continuously increasing fasting insulin levels were the independent determinants for future development of nonalcoholic fatty liver disease during a 5-year follow-up in nondiabetic healthy adults.     

Ideal Cardiovascular Health Is Inversely Associated with Nonalcoholic Fatty Liver Disease: A Prospective Analysis

Background

Cardiovascular health has been proven to be associated with major cardiometabolic diseases. However, little is known of associations between cardiovascular health and nonalcoholic fatty liver disease.

Treatment of nonalcoholic fatty liver: present and emerging therapies

Treatment of patients with nonalcoholic fatty liver has typically been focused on the management of associated conditions such as obesity, diabetes mellitus, and hyperlipidemia as well as discontinuation of potentially hepatotoxic drugs. Nonalcoholic fatty liver associated with obesity may resolve with weight reduction, although the benefits of weight loss have been inconsistent. Appropriate metabolic control for patients with diabetes mellitus or hyperlipidemia is always recommended but not always effective in reversing nonalcoholic fatty liver. Promising results of pilot studies evaluating ursodeoxycholic acid, gemfibrozil, betaine, N-acetylcysteine, and alpha-tocopherol suggest that these medications may be of potential benefit in the treatment of patients with nonalcoholic fatty liver. These medications, however, need first to be tested in well-controlled trials with clinically relevant end points and extended follow-up. A better understanding of the pathogenesis and natural history of this condition will help to identify the subset of patients with nonalcoholic fatty liver at risk of progressing to advanced liver disease and, hence, the subgroup of patients who should derive the most benefit from medical therapy. In this article, we review (1) the existing medical therapy for patients with nonalcoholic fatty liver, (2) the emerging data from clinical trials evaluating potentially useful medications, and (3) the potential therapeutic implications of recent studies on the pathogenesis of this liver disease.     

大鼠非酒精性脂肪性肝纤维化形成过程中骨桥蛋白的表达及其意义

目的 通过观察非酒精性脂肪性肝纤维化形成过程中肝组织内骨桥蛋白(OPN)的变化规律,探讨OPN在非酒精性脂肪性肝纤维化形成过程中的作用. 方法选用纯系Wistar雄性大鼠56只,体质量180～200g,随机分为正常对照组和高脂饮食4、8、12,16、20、24周组(其中每组各8只).肝组织常规进行HE及Masson三色胶原染色,免疫组织化学染色检测肝组织α-平滑肌肌动蛋白的表达,RT-PeR、Western blot观察肝组织中OPN动态变化.结果 与正常对照组相比,高脂饲料组大鼠肝脏内OPN含量明显升高,随着脂肪肝程度的加重,OPN表达逐渐增强,mRNA及蛋白质表达比较,F值分别为7.30和7.15,尸值均<0.01;与α-平滑肌肌动蛋白表达及肝组织胶原纤维面积百分比呈显著正相关(r值分别为0.94和0.82,P值均<0.01).结论 在非酒精性脂肪性肝纤维化形成过程中,OPN在肝组织中表达显著上调,可能在非酒精性脂肪性肝纤维化的形成过程中发挥重要作用.     

Nonalcoholic fatty liver disease

The definition of nonalcoholic fatty liver disease has evolved in recent years. Today, it is considered a nonspecific term encompassing several clinicopathologic entities (steatosis alone, steatonecrosis, steatohepatitis and histologic alcoholiclike hepatitis) that are similar to alcoholic liver disease. Studies of nonalcoholic fatty liver disease have come to conflicting conclusions about the course of the disease. It can be argued that the disparate results are largely the result of nonuniform definitions. When histologic features such as hepatocyte ballooning, necrosis, and Mallory hyaline are seen, nonalcoholic fatty liver disease has been shown to be associated with an aggressive outcome. Steatosis alone, in contrast, appears to be benign. The current understanding of nonalcoholic fatty liver disease, the limited treatments available, and two theories of the pathogenesis of the disease are also reviewed here.     

血管内皮生长因子与非酒精性脂肪性肝病

非酒精性脂肪性肝病（NAFLD）是影响公共健康的全球性疾病,其病理变化可向非酒精性单纯性脂肪肝（NAFL）、脂肪性肝炎（NASH）甚至脂肪性肝硬化（FLC）发展。虽然NAFLD的这些病理进展机制尚未明确,但仍有一些实验研究提示了可能的诱发机制。其中血管内皮生长因子（VEGF）在促进NAFLD肝脏炎症、肝纤维化中发挥着重要的作用。本文就VEGF与NAFLD关系的研究进展予以综述。     

Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD)

BACKGROUND: Liver fibrosis is the main predictor of the progression of nonalcoholic fatty liver disease. Transient elastography (FibroScan), which measures liver stiffness, is a novel, noninvasive method to assess liver fibrosis. AIM: We investigated the usefulness of liver stiffness measurement in the evaluation of liver fibrosis in nonalcoholic fatty liver disease patients. STUDY POPULATION: A total of 97 nonalcoholic fatty liver disease patients. METHODS: Transient elastography was performed for liver stiffness measurement in 97 nonalcoholic fatty liver disease patients. And the relationship between histological parameters and liver stiffness measurement was studied by multivariate analysis. Moreover, we investigated the relationship between liver stiffness measurement and the serum levels of hyaluronic acid and type IV collagen 7s domain. RESULTS: The liver stiffness was well correlated with the stage of liver fibrosis (Kruskal-Wallis test p < 0.0001). The areas under the receiver-operating characteristic curves were 0.927 for > or = F1, 0.865 for > or = F2, 0.904 for > or = F3, 0.991 for > or = F4. Only fibrosis stage was correlated significantly with liver stiffness measurement by multiple regression analysis. Liver stiffness was also strongly correlated with the serum levels of type IV collagen 7s domain (r = 0.525, p < 0.0001) and hyaluronic acid (r = 0.457, p < 0.0001). CONCLUSIONS: Our results show a significant correlation between liver stiffness measurement and fibrosis stage in nonalcoholic fatty liver disease patients, as confirmed by the results of liver biopsy, which remains the gold standard for evaluation of the severity of liver fibrosis in patients with nonalcoholic steatohepatitis.     

中医药治疗非酒精性脂肪性肝病的重要靶位——肠道微生态

肠道微生态在非酒精性脂肪性肝病发病机制中具有重要意义。系统阐释非酒精性脂肪性肝病与肠道菌群、肠道菌代谢物和肠屏障功能关系,结合中医药调节肠道微生态与治疗非酒精性脂肪性肝病关系的研究概况,提出调节肠道微生态、维持肠道稳态是中医药治疗非酒精性脂肪性肝病的重要策略。     

细胞因子在非酒精性脂肪性肝炎发病机制中的作用

随着非酒精性脂肪性肝病发病率的逐年上升及其对健康的危害,包括3种类型:单纯性脂肪肝、脂肪性肝炎和脂肪性肝硬化已受到越来越多的重视,而非酒精性脂肪性肝炎是由单纯性脂肪肝发展为脂肪性肝硬化的必经阶段,了解其发病机制,探讨具有多种生物学效应的细胞因子在非酒精性脂肪性肝炎中的作用,对于弄清其发病机制的多样性有着深刻的意义。     

非酒精性脂肪性肝病与多囊卵巢综合征相关性研究

目的探讨非酒精性脂肪肝(NAFLD)与多囊卵巢综合征(PCOS)的相关性。方法选择PCOS患者47例和非PCOS患者47例,比较两组患者NAFLD、胰岛素抵抗(IR)、丙氨酸氨基转移酶(ALT)升高发生情况及一般临床参数。结果 PCOS组NAFLD、IR、ALT升高的发生率分别为42.6%、68.1%、34.0%,与对照组(分别为17.0%、10.6%、8.5%)比较显著增高,差异有统计学意义(P0.01);PCOS组伴NAFLD患者与不伴NALFD患者比较,ALT、睾酮(TESTO)显著增高,差异有统计学意义(P0.01)。体重指数(BMI)、促卵泡成熟激素(FSH),人促黄体生成激素(LH2)、睾酮(TESTO)两两相比较,差异有统计学意义(P0.05);PCOS伴NAFLD患者年龄小于不伴NAFLD的PCOS患者(P0.01);多因素Logisitc回归分析提示ALT的异常及胰岛素抵抗状态是PCOS伴发NAFLD的主要风险因素(ALTOR=1.12,P=0.01;HOMA-IROR=1.58,P=0.01)。结论 NAFLD在PCOS患者中患病率高,提示两种疾病有临床相关性,对年轻的PCOS患者有必要尽早进行肝脏疾病的相关检查。     

Bromocriptine reduces steatosis in obese rodent models

BACKGROUND/AIMS: Obesity is a risk factor for glucose intolerance, steatosis, and oxidative stress, characteristics of nonalcoholic fatty liver disease. Bromocriptine may have anti-obesity, insulin-sensitizing, lipolytic, and antioxidant properties. We, therefore, hypothesized that bromocriptine would improve markers of nonalcoholic fatty liver disease in obese rodent models. METHODS: We performed a randomized, controlled experiment in genetically obese fatty Zucker rats and diet-induced obese rats to assess for behavioral and peripheral anti-obesity actions of bromocriptine (10mg/kg) that would improve nonalcoholic fatty liver disease. RESULTS: Behaviorally, food intake decreased and locomotor activity increased in bromocriptine-treated fatty Zucker and dietary-induced obese rats. Peripherally, liver triglycerides were significantly reduced and hepatic manganese superoxide dismutase significantly increased in bromocriptine-treated fatty Zucker and diet-induced obese rats compared to controls. Blood glucose was significantly lower in bromocriptine-treated Zucker rats compared to fatty controls and was no different than that of lean controls. CONCLUSIONS: Improvements in obesigenic behaviors, glucose tolerance, hepatic lipid accumulation, and mitochondrial oxidative stress observed in genetically obese and diet-induced obese rodents indicate that bromocriptine may be promising as a broad-based therapy for nonalcoholic fatty liver disease.     

大鼠非酒精性脂肪肝中UCP2的动态表达

目的探讨解偶联蛋-2(uncoupling protein-2,UCP2)在大鼠非酒精性脂肪肝发病机理中的作用.方法Wistar大鼠64只,随机分为高脂饮食诱导脂肪肝组和正常对照组,用免疫组织化学和Western blot技术检测肝组织中UCP2表达变化,生化检测大鼠血清甘油三酯(TG)、游离脂肪酸(FAA)和丙氨酸氨基转移酶(ALT)含量.结果大鼠非酒精性脂肪形成过程中UCP2阳性细胞数和表达强度逐渐增加,血清TG、FAA和ALT含量较对照组增高,以高脂饮食喂养8、12周为著.结论随着非酒精性脂肪的形成和程度加重,UCP2表达逐渐增强,其介导的酶活性显著增高,启动脂质过氧化反应,促进脂肪肝的形成和发展.