Impact of non-alcoholic fatty liver disease on chronic hepatitis B.

BACKGROUND: The impact of superimposed non-alcoholic fatty liver disease (NAFLD) is well established in patients with chronic hepatitis C (CH-C), but the impact in patients with chronic hepatitis B (CH-B) is less clear. Aim: This study aims to evaluate the prevalence of NAFLD in patients with CH-B and the association with viral and host factors, particularly in patients with metabolic syndrome (MS). DESIGN: Data from patients with CH-B was obtained from our databases. Patients with excessive alcohol use were excluded. Hepatitis B virus (HBV) genotyping by INNO-LIPA was available for some patients. The presence of MS was defined according to the Adult Treatment Panel III (ATP III). All biopsies were read by two hepatopathologists using Metavir, modified histologic activity index (MHAI), as well as a NAFLD pathologic protocol. Patients were classified as (1) those without NAFLD; (2) those with simple hepatic steatosis; (3) and those with superimposed non-alcoholic steatohepatitis (NASH). Factors associated with superimposed NAFLD, its subtypes, and hepatic fibrosis were also analysed. RESULTS: Subjects included 153 HBV patients [66% male, age 50.5+/-27.5 years, body mass index 24.7+/-3.7 kg/m(2), waist 83.2+/-10.9 cm; 8.5% Caucasian, 67% Asian, aspartate aminotransferase (AST) 63.2+/-88.2 IU/l, alanine aminotransferase (ALT) 98.6+/-164.6 IU/l, glucose 111.6+/-50.5 mg/dl, HBV-DNA 1.8 x 10(8)+/-1.9 x 10(6) copies/ml, 7% with MS, 13% with diabetes, 20% with arterial hypertension and 8.5% with dyslipidaemia]. Liver biopsy was available for 64 subjects [19% had superimposed NAFLD, 13% had superimposed NASH, 86% had some degree of fibrosis, and 39% had advanced fibrosis (Ishak >3)]. Patients with HBV and superimposed NASH were significantly older (55 vs. 42 years, P=0.008), more likely to have hypertension (63% vs. 15%, P=0.006) and dyslipidaemia (50% vs. 8%, P=0.006), and had a larger waist circumference (92 vs. 83 cm, P=0.03). The presence of fibrosis was associated with higher waist circumference (84 vs. 80 cm, P=0.03), higher HBV-DNA (1.9 x 10(8) vs. 5 x 10(6) copies/ml, P=0.005), and elevated ALT >40 IU/l (73.6% vs. 33.3%, P=0.02). CONCLUSIONS: The components of MS (obesity, hypertension, and dyslipidaemia) are associated with the presence of NASH in patients with CH-B. The presence of hepatic fibrosis seems to be associated with known host and viral factors as well as the presence of abdominal obesity.     

慢性乙型肝炎合并非酒精性脂肪肝的研究动态

近年来,随着我国非酒精性脂肪肝发病率不断攀升,慢性乙型肝炎合并非酒精性脂肪肝的患者日益增多。本文回顾近几年的文献,就目前慢性乙型肝炎合并非酒精性脂肪肝的流行病学情况、发病机制、诊断和预后等问题进行综述。希望有助于广大临床医师更充分地认识此类疾病。     

Difference in malignancies of chronic liver disease due to non-alcoholic fatty liver disease or hepatitis C in Japanese elderly patients

Aim: Malignancies that include hepatocellular carcinoma often occurred in patients with chronic liver disease. The aim of this retrospective match control study was to assess the cumulative development incidence and predictive factors for total malignancies in elderly Japanese patients with non‐alcoholic hepatic diseases (NAFLD) or hepatitis C virus (HCV). Methods: A total of 1600 NAFLD patients with age of ≥60 years were enrolled, and 1600 HCV patients with age of ≥60 years were selected as control by matching 1:1 with NAFLD group for age, sex, and follow‐up period. The primary goal is the first development of malignancies. Evaluation was performed by the use of the Wilcoxon rank sum test, the Kaplan–Meier method, and Cox proportional hazard model. The mean observation period is 8.2 years in both NAFLD and HCV group, respectively. Results: The number of patients with the development of malignancies was 167 in the NAFLD group and 395 in the HCV group. The 10th development rate of malignancies was 13.9% in the NAFLD group and 28.2% in the HCV group (risk ratio 2.27; P < 0.001). The incident rates of hepatocellular carcinoma in all the malignancies were 6.0% (10/167) in the NAFLD group and 67.6% (267/395) in the HCV group (P < 0.001). The malignancies in the NAFLD group were observed in the following order: gastric cancer 34 cases (20.4%) > colon cancer 31 cases (18.6%) > prostate cancer 21 cases (12.6%). Conclusions: The incident rates of hepatocellular carcinoma in all the malignancies were approximately 6% in the NAFLD group and two‐thirds in the HCV group.     

代谢综合征、非酒精性脂肪性肝病与慢性乙型病毒性肝炎

非酒精性脂肪性肝病(nonalcoholic falty liver disease,NAFLD)是一种胰岛素抵抗和遗传易感性相关的代谢应激性肝损伤,为肥胖和代谢综合征累及肝脏的病理表现.肥胖和代谢综合征除可导致NAFLD外,还可促进慢性丙型病毒性肝炎(丙肝)、慢性乙型病毒性肝炎(乙肝)等其他肝病的进展并影响其疗效.本文主要综述代谢综合征、NAFLD和慢性乙肝之间关系及其机制.     

慢性乙型肝炎病毒感染合并非酒精性脂肪性肝病动物模型的建立与鉴定

目的 采用高脂饮食喂饲HBV转基因小鼠,建立慢性HBV感染合并非酒精性脂肪性肝病(NAFLD)的动物模型。 方法 将携带HBV全基因组的小鼠随机分为雄性对照组、雄性模型组、雌性对照组、雌性模型组。各模型组给予高脂饮食(含胆固醇2％、猪油l0％、基础饲料88％),对照组则喂饲基础饲料。分批于第8、16、24周末处死小鼠,检测体质学指标、肝肾功能、糖脂代谢等NAFLD相关指标;血清HBV分型、HBeAg、HBV DNA,以及肝组织HBsAg免疫组织化学染色等病毒学指标;并通过HE、Mason及油红O染色评价肝脏组织的病理学改变。组间均数的比较采用t检验,P＜0.05为差异有统计学意义。结果 与对照组相比,不同造模时间的雌性和雄性模型组小鼠体质量、肝脏质量、肝指数均明显升高;ALT、AST、碱性磷酸酶、γ-谷氨酰转移酶、总胆红素、胆汁酸等肝功能指标受损;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和空腹血糖等糖脂代谢指标也有不同程度升高。然而,各组间血清HBV DNA、HBeAg水平和肝细胞HBsAg阳性率无明显差异。组织病理学检查结果提示,造模第8周时,雌、雄模型组小鼠均可见不同程度的肝细胞脂肪变,伴小叶内散在的点状坏死及炎症细胞浸润;第24周时肝脏脂肪变及炎症虽未明显加重,但有窦周纤维化和中央静脉周围纤维化。结论 成功建立慢性HBV感染合并NAFLD动物模型,为进一步研究慢性乙型肝炎合并NAFLD发病机制、药物筛选及疗效评价等提供了可靠的实验平台。     

慢性乙型肝炎合并脂肪肝临床与肝组织病理学分析*

目的 探讨慢性乙型肝炎（chronic hepatitis B,CHB）合并非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）患者临床特点及脂肪肝对CHB的影响。方法 收集118例经肝穿刺活检诊断的患者,其中脂肪肝患者37例,CHB合并脂肪肝患者41例,CHB患者40例,对三组临床资料包括性别、年龄、血清学、病毒学指标及肝组织学变化进行对比分析。结果 三组患者Alb、ALT、AST、血糖之间无显著性差异（P>0.05）,而非酒精性脂肪肝组GGT和CHOL水平明显高于其他两组（P<0.01）,慢性乙型肝炎合并脂肪肝组TG水平高于非酒精性脂肪肝和慢性乙型肝炎组患者,差异显著（P<0.01）;慢性乙型肝炎患者肝组织中重度炎症的比例（72.5%）显著重于慢性乙型肝炎合并脂肪肝患者（63.4%）和非酒精性脂肪肝患者（24.3%）,差异有统计学意义（P<0.01）;与非酒精性脂肪肝组（8.1%）和慢性乙型肝炎组（27.5%）相比,乙型肝炎合并脂肪肝组肝组织中重度肝纤维化比例更高（39%）,且有显著性差异（P<0.01）。结论 脂肪肝能加重慢性乙型肝炎患者肝组织纤维化和肝损伤程度。     

Obesity and non-alcoholic fatty liver disease: Disparate associations among asian populations

obesity is a global epidemic contributing to an increas-ing prevalence of obesity-related systemic disorders, including nonalcoholic fatty liver disease. The rising prevalence of nonalcoholic steatohepatitis(NASh) will in the near future lead to end-stage liver disease in a large cohort of patients with NASh-related cirrhosis and NASh is predicted to be a leading indication for liver transplantation in the coming decade. however, the prevalence of obesity and the progression of hepatic histological damage associated with NASh exhibit sig-nificant ethnic disparities. Despite a significantly lower body mass index and lower rates of obesity compared to other ethnic groups, Asians continue to demonstrate a significant prevalence of hypertension, diabetes, met-abolic syndrome and NASh. Ethnic disparities in central adiposity and visceral fat distribution have been hy-pothesized to contribute to these ethnic disparities. The current review focuses on the epidemiology of obesity and NASh among Asian populations.     

Post-load insulin resistance is an independent predictor of hepatic fibrosis in virus C chronic hepatitis and in non-alcoholic fatty liver disease

BACKGROUND: Insulin resistance is a significant risk factor for hepatic fibrosis in patients with both non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), either directly or by favouring hepatic steatosis. Several methods are available to assess insulin resistance, but their impact on this issue has never been evaluated. AIMS: To determine the relative contribution of steatosis, metabolic abnormalities and insulin resistance, measured by different basal and post-load parameters, to hepatic fibrosis in CHC and in NAFLD patients. METHODS: In 90 patients with CHC and 90 pair-matched patients with NAFLD, the degree of basal insulin resistance (by the homeostasis model assessment, (HOMA)) and post-load insulin sensitivity (by the oral glucose insulin sensitivity (OGIS) index) was assessed, together with the features of the metabolic syndrome according to Adult Treatment Panel III definition. Data were correlated with hepatic histopathology. RESULTS: The prevalence of basal insulin resistance (HOMA values >75th percentile of normal) was 23.3% in CHC patients and 57.8% in NAFLD, but it increased to 28.8 and 67.8% when measured by post-load insulin resistance (OGIS <25th percentile). In a multivariate model, after adjustment for age, gender and body mass index, OGIS was a predictor of severe fibrosis in CHC and in NAFLD patients, independently of steatosis. An OGIS value below the cut-off of the 25th percentile increased the likelihood ratio of severe fibrosis by a factor of 1.5-2 and proved to be a more sensitive and generally more specific test than HOMA-R for the identification of subjects with severe fibrosis both in NAFLD and in CHC. CONCLUSIONS: Post-load insulin resistance (OGIS <9.8 mg/kg/min) is associated with severe hepatic fibrosis in both NAFLD and CHC patients, and may help identify subjects at risk of progressive disease.     

Inflammation and fibrosis in chronic liver diseases including nonalcoholic fatty liver disease and hepatitis C

At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy.     

阿德福韦酯治疗慢性乙型肝炎合并非酒精性脂肪性肝病的疗效观察

近年来,慢性乙型肝炎(CHB)合并非酒精性脂肪性肝病(NAFLD)的患者在临床上越来越常见。有报道显示27%~76%的CHB患者合并NAFLD[1]。NAFLD常促进原有基础肝病的进展,影响原有肝病治疗的疗效,如HBV感染者合并NAFLD,NAFLD可促进其肝硬化和肝细胞癌的发生[2];慢性丙型肝炎(CHC)患者合并NAFLD,NAFLD可降低非基因3型     

恩替卡韦治疗非酒精性脂肪性肝病合并慢性乙型肝炎的疗效及对胰岛素抵抗的影响

目的探讨恩替卡韦治疗非酒精性脂肪性肝病合并慢性乙型肝炎的疗效及对胰岛素抵抗的影响。方法对2012-08~2015-08该院诊治的65例非酒精性脂肪性肝病合并慢性乙型肝炎患者应用恩替卡韦治疗(观察组),将同期接受相同治疗方式的58例单纯慢性乙型肝炎患者作为对照(对照组),分析两组治疗12个月后血清谷丙转氨酶(ALT)复常率、病毒学应答以及胰岛素抵抗情况。结果治疗后,两组ALT水平显著下降,且对照组下降幅度显著高于观察组(P0.01);观察组ALT复常率(52.31%)低于对照组(72.41%)(P0.05)。观察组乙肝病毒定链(HBV-DNA)拷贝量显著高于对照组(P0.01),HBV-DNA阴转率显著低于对照组(P0.05)。两组空腹血糖(FPG)、空腹胰岛素(FINS)和胰岛素抵抗(HOMA-IR)均显著下降,且对照组下降幅度显著高于观察组(P0.05或P0.01)。结论非酒精性脂肪性肝病可影响恩替卡韦治疗慢性乙型肝炎疗效,乙肝治疗过程应注重脂肪肝对症治疗。     

Hepatic lipogranulomas in patients with chronic liver disease: association with hepatitis C and fatty liver disease

AIM: To study the significance and clinical implication of hepatic lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 pati...     

Lipidomics in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disorder in Western countries, comprises steatosis to nonalcoholic steatohepatitis (NASH), with the latter having the potential to progress to cirrhosis. The transition from isolated steatosis to NASH is still poorly understood, but lipidomics approach revealed that the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis and these alterations correlate with disease progression. Recent data suggest that both quantity and quality of the accumulated lipids are involved in pathogenesis of NAFLD. Changes in glycerophospholipid, sphingolipid, and fatty acid composition have been described in both liver biopsies and plasma of patients with NAFLD, implicating that specific lipid species are involved in oxidative stress, inflammation, and cell death. In this article, we summarize the findings of main human lipidomics studies in NAFLD and delineate the currently available information on the pathogenetic role of each lipid class in lipotoxicity and disease progression.     

Glycosyltransferases and non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases(GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized.     

抵抗素与非酒精性脂肪性肝病

抵抗素是存在于血浆中的富含半胱氨酸的分泌性蛋白,属于抵抗素样分子家族,又称脂肪组织特异性分泌因子.其与胰岛素抵抗及炎症等关系密切.非酒精性脂肪性肝病(NAFLD)代表了一组以甘油三酯在肝内过度贮积而引起的临床病理综合征,目前认为其属于代谢综合征的范畴,胰岛素抵抗及炎症因子的参与是其发病的重要环节.深入研究抵抗素与胰岛素抵抗及炎症的关系将有助于进一步了解NAFLD的发病机制,为寻求合理的治疗方案提供理论依据.     

脂肪因子与非酒精性脂肪肝

非酒精性脂肪性肝病的发病机制目前尚不十分清楚,脂代谢异常(尤其是TG)与胰岛素抵抗(IR)可能是其病因的关键环节,瘦素、脂联素、抵抗素、肿瘤坏死因子等多种脂肪因子在非酒精性脂肪肝的形成、炎性改变及纤维化的过程中发挥了重要作用.     

Visfatin与非酒精性脂肪肝

Visfatin是一新发现主要由内脏脂肪组织分泌的脂肪细胞因子,通过与胰岛素受体上不同于胰岛素结合部位的位点结合,可发挥拟胰岛素作用,进而参与调节糖脂代谢及炎症反应。非酒精性脂肪性肝病作为常见肝病,因其发病核心事件为胰岛素抵抗而常伴有代谢紊乱、炎症、氧化应激的发生。故在发病机制和病理生理上,Visfatin密切关联于非酒精性脂肪性肝病,探究两者关系或能为非酒精性脂肪性肝病防治提供新靶点。