Garcinia Cambogia attenuates diet-induced adiposity but exacerbates hepatic collagen accumulation and inflammation

AIM: To investigate long-term effects of Garcinia Cambogia (GC), weight-loss supplement, on adiposity and non-alcoholic fatty liver disease in obese mice. METHODS: Obesity-prone C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without GC (1%, w/w) for 16 wk. The HFD contained 45 kcal% fat, 20 kcal% protein and 35 kcal% carbohydrate. They were given free access to food and distilled water, and food consumption and body weight were measured daily and weekly, respectively. Data were expressed as the mean ± SE. Statistical analyses were performed using the statistical package for the social science software program. Student’s t test was used to assess the differences between the groups. Statistical significance was considered at P < 0.05. RESULTS: There were no significant changes in body weight and food intake between the groups. However, the supplementation of GC significantly lowered visceral fat accumulation and adipocyte size via inhibition of fatty acid synthase activity and its mRNA expression in visceral adipose tissue, along with enhanced enzymatic activity and gene expression involved in adipose fatty acid β-oxidation. Moreover, GC supplementation resulted in significant reductions in glucose intolerance and the plasma resistin level in the HFD-fed mice. However, we first demonstrated that it increased hepatic collagen accumulation, lipid peroxidation and mRNA levels of genes related to oxidative stress (superoxide dismutase and glutathione peroxidase) and inflammatory responses (tumor necrosis factor-α and monocyte chemoattractant protein-1) as well as plasma alanine transaminase and aspartate transaminase levels, although HFD-induced hepatic steatosis was not altered. CONCLUSION: GC protects against HFD-induced obesity by modulating adipose fatty acid synthesis and β-oxidation but induces hepatic fibrosis, inflammation and oxidative stress.     

Keishibukuryogan ameliorates glucose intolerance and hyperlipidemia in Otsuka Long-Evans Tokushima Fatty (OLETF) rats

Keishibukuryogan, one of the traditional herbal formulations, is used clinically to improve blood circulation. In this study, we examined the effects of keishibukuryogan on glucose and lipids metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. Forty-five-week-old male OLETF rats were divided into three groups: diabetic control rats given a standard chow; diabetic rats given keishibukuryogan (3%, w/w in chow); diabetic rats given pioglitazone (0.01%, w/w in chow). Oral administration of keishibukuryogan produced significant improvement against impaired glucose tolerance. On the other hand, fasting serum glucose and insulin levels, and the homeostasis index of insulin resistance did not change by keishibukuryogan treatment. Against lipid parameters, keishibukuryogan significantly lowered serum total cholesterol and triglyceride levels, and the hepatic total cholesterol level. Keishibukuryogan treatment also significantly reduced the serum leptin level, but it had no effect on the serum adiponectin level. Additionally, keishibukuryogan showed significant effects on epididymal adipose tissue by decreasing the size of fat cells and on skeletal muscle by reducing TNF-alpha protein content. From these results, it was suggested that keishibukuryogan exerts beneficial effects on the features associated with type 2 diabetes.     

No evidence demonstrating hepatotoxicity associated with hydroxycitric acid

Although a number of cases of hepatotoxicity are associated with the use of Hydroxycut weight management products, it has been alleged that their effects are primarily due to the presence of hydroxycitric acid （HCA, as Super CitriMax） in the formulations. However, while these products contain up to 20 different ingredients, some do not contain HCA. Case studies reported to date have not considered in depth the literature on the numerous animal and human studies that have been conducted on the safety and efficacy of HCA. No HCA- associated hepatotoxicity or treatment-related adverse effects have been reported in these studies, and thus it is premature to make the assumptions presented in the recent case studies regarding Hydroxycut. If it is established in well controlled studies that the use of these formulations with and/or without HCA can result in the occurrence or progression of hepatotoxicity, additional studies should be conducted to characterize the causative factor（s）.     

Amelioration of diet-induced diabetes mellitus by removal of visceral fat

The effect of visceral fat removal upon glucose homeostasis, insulin signal transduction, and serum adipokine levels in an animal model of diet-induced obesity and diabetes mellitus (DIO) was evaluated. Swiss mice were initially divided into two groups fed with regular rodent chow or with chow containing 24 g% saturated fat (DIO). DIO mice became obese and overtly diabetic after 8 weeks. DIO mice were then divided into three groups: control, sham, and visceral (epididymal and perinephric) fat removal. All groups were submitted to evaluation of basal glucose and insulin levels and i.p. insulin tolerance test. Insulin signal transduction in muscle was evaluated by immunoprecipitation and immunoblot, and serum adipokine levels were determined by ELISA. DIO mice became diabetic (228 versus 115 mg/dl), hyperinsulinemic (7.59 versus 3.15 ng/ml) and insulin resistant (K(itt) 2.88 versus 4.97%/min) as compared with control. Visceral fat removal partially reverted all parameters (147 mg/dl glucose; 3.82 ng/ml insulin; and 4.20%/min K(itt)). In addition, visceral fat removal completely reversed the impairment of insulin signal transduction through insulin receptor, insulin receptor substrate (IRS)-1, IRS-2 and Akt in muscle. Finally, serum levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6 were significantly increased, while adiponectin levels were significantly reduced in DIO mice. After visceral fat removal the levels of adipokines returned to near control levels. The present study shows that removal of visceral fat improves insulin signal transduction and glucose homeostasis in an animal model of diet-induced obesity and diabetes mellitus and these metabolic and molecular outcomes are accompanied by the restoration of adipokine levels.     

Novel risk markers for gastric cancer screening: Present status and future prospects

Initial identification of populations at high risk of gastric cancer (GC) is important for endoscopic screening of GC. As serum pepsinogen (PG) test-positive subjects with progression of chronic atrophic gastritis (CAG) show a high likelihood of future cancer development, this population warrants careful follow-up observation as a high-risk GC group. By combining the PG test with Helicobacter pylori (HP) antibody titers, the HP-related chronic gastritis stage can be classified, thus identifying not only a GC high-risk group but also a low-risk group. Among PG test-negative patients without CAG, those with high serum PG II levels and HP antibody titers are thought to have severe gastric mucosal inflammation and the risk of diffuse-type GC is also high. Meanwhile, in gastric mucosae obtained by endoscopic biopsy, HP infection induces aberrant DNA methylation in CpG islands in multiple gene regions and the extent of methylation clearly correlates with GC risk. By quantifying aberrant DNA methylation in suitable gene markers, we can determine the extent of the epigenetic field for cancerization. These novel concepts and risk markers will have many clinical applications in gastrointestinal endoscopy, including more efficient endoscopic GC screening and a strategic approach to metachronous multiple GCs after endoscopic treatment.     

Leptin in the Field of Hepatic Fibrosis: A Pivotal or an Incidental Player?

Leptin is a 16-kDa nonglycosylated protein primarily secreted from the adipocytes of white fat; minor levels of regulated leptin expression also occurs at other sites such as placenta, skeletal muscle, the stomach fundus, and culture-activated hepatic stellate cells (HSCs). Leptin is primarily involved in the regulation of food intake and body composition through a central feedback mechanism linking food ingestion, hypothalamus, and adipose tissue mass. In recent years, however, emerging evidence has suggested a critical role of leptin in hepatic inflammation and fibrogenesis and the influence of leptin on chronic liver disease has been an area of active research worldwide. In this review the data on the in vivo and in vitro actions of leptin on liver cells in experimental animal models of liver injury and the effects of leptin on human liver are discussed, with a focus on three distinct fields of chronic liver diseases: nonalcoholic steatohepatitis, alcoholic liver disease, chronic viral hepatitis, and, especially, hepatitis C.     

Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss

Aim: The efficacy of optimal doses of highly bioavailable (–)‐hydroxycitric acid (HCA‐SX) alone and in combination with niacin‐bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA‐SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. Methods: A randomized, double‐blind, placebo‐controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21–50, BMI >26 kg/m²). Subjects were randomly divided into three groups. Group A was administered HCA‐SX 4667 mg, group B was administered a combination of HCA‐SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30–60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. Results: At the end of 8 weeks, body weight and BMI decreased by 5–6% in both groups A and B. Food intake, total cholesterol, low‐density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high‐density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non‐significant effect was observed in all parameters in group C. Conclusion: The present study shows that optimal doses of HCA‐SX and, to a greater degree, the combination of HCA‐SX, NBC and GSE can serve as an effective and safe weight‐loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.     

Clinical implications of glucocorticoid metabolism by 11beta-hydroxysteroid dehydrogenases in target tissues

11beta-Hydroxysteroid dehydrogenases (11beta-HSD) are microsomal enzymes that catalyze the conversion of active glucocorticoids (GC) to their inactive 11-dehydro products and vice versa. Two isoenzymes of 11beta-HSD have been characterized and cloned in human tissues. The tissue-specific metabolism of GC by these enzymes is important for mineralocorticoid (MC) and GC receptor occupancy and seems to play a crucial role in the pathogenesis of diseases such as apparent MC excess syndrome, and may play roles in hypertension, obesity and impaired hepatic glucose homeostasis. This article reviews the literature and examines the role and importance of 11beta-HSD in humans.     

Normal adiponectin levels despite abnormal glucose tolerance (or diabetes) and inflammation in adult patients with cystic fibrosis

RATIONALE: Circulating adiponectin levels are negatively associated with glucose intolerance, inflammation and central adiposity. Since these conditions are common in cystic fibrosis (CF), we examined whether adiponectin values are altered in these patients. AIM: To determine if CF patients have altered adiponectin levels and if these levels correlate with glucose tolerance categories (normal, impaired glucose tolerance (IGT) and cystic fibrosis-related diabetes (CFRD)), insulin resistance or inflammatory markers such as fibrinogen and C-reactive protein (CRP). METHODS: Oral glucose tolerance tests (OGTTs) were performed and adiponectin levels were measured in 90 CF patients not known to be diabetic and 15 healthy controls matched for age, sex and body mass index (BMI). Inflammatory markers, serum albumin concentrations and the clinical status of CF patients (i.e. pulmonary function) were also examined. RESULTS: CF pathology was characterized by a high prevalence (43.5%) of glucose tolerance abnormalities: 26.5% of IGT and 17.0% of newly diagnosed CFRD. CF patients also presented systemic inflammation as revealed by a significant increase of fibrinogen (P=0.029) in all patients and higher CRP levels in CFRD patients compared to the controls (P<0.05). On the other hand, CF and control subjects had similar albumin serum concentration. While CF patients and controls had similar serum adiponectin values, women had significantly higher hormone levels than men (P<0.001). Adiponectin levels did not correlate with glucose tolerance, inflammatory markers or insulin resistance. On the other hand, they correlated positively with both total and HDL-cholesterol (P<0.001). CONCLUSION: CF patients did not show any alterations in adiponectin levels despite insulin resistance, glucose intolerance and sub clinical chronic inflammation. Thus, CF appears to be one of the rare conditions in which discordance between adiponectin values and insulin resistance or inflammation is evident.     

Alterations of hormonally active fibroblast growth factors after Roux-en-Y gastric bypass surgery

Thirty-five morbidly obese patients underwent Roux-en-Y gastric bypass surgery (RYGB). In addition to weight loss, these patients showed significant improvement of insulin resistance and a reduction of hepatic fat content. Three months after surgery, the serum bile salts were slightly but significantly elevated, and the levels of the endocrine-acting fibroblast growth factor 19 (FGF19) and FGF21 were increased. FGF19 and FGF21 play a role as regulators of hepatic lipid and glucose metabolism. These results show that RYGB surgery improves metabolism and that this improvement is still apparent 3 months after surgery. Bile salts may play a key role in the improvement of metabolism after RYGB. Why serum bile salt concentrations are elevated after RYGB needs to be investigated.     

Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity

Chemerin is a chemoattractant adipokine that regulates adipogenesis and may induce insulin resistance. Chemerin serum concentrations are elevated in obese, insulin-resistant, and inflammatory states in vivo. Here we investigate the role of omental (OM) and subcutaneous (SC) adipose tissue chemerin and CMKLR1 messenger RNA (mRNA) expression in human obesity. In addition, we test the hypothesis that changes in chemerin serum concentrations are primarily associated with reduced body fat mass in the context of 3 weight loss intervention studies. Chemerin serum concentration was measured in 740 individuals in a cross-sectional (n = 629) study including a subgroup (n = 161) for which OM and SC chemerin mRNA expression has been analyzed as well as in 3 interventions including 12 weeks of exercise (n = 60), 6 months of calorie-restricted diet (n = 19) studies, and 12 months after bariatric surgery (n = 32). Chemerin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes mellitus and correlates with circulating chemerin, body mass index (BMI), percentage body fat, C-reactive protein, homeostasis model assessment of insulin resistance, and glucose infusion rate in euglycemic-hyperinsulinemic clamps. CMKLR1 mRNA expression was not significantly different between the 2 fat depots. Obesity surgery-induced weight loss causes a significant reduction on both OM and SC chemerin expression. All interventions led to significantly reduced chemerin serum concentrations. Decreased chemerin serum concentrations significantly correlate with improved glucose infusion rate and reduced C-reactive protein levels independently of changes in BMI. Insulin resistance and inflammation are BMI-independent predictors of elevated chemerin serum concentrations. Reduced chemerin expression and serum concentration may contribute to improved insulin sensitivity and subclinical inflammation beyond significant weight loss.     

C-reactive protein is more strongly related to post-glucose load glucose than to fasting glucose in non-diabetic subjects; the Insulin Resistance Atherosclerosis Study.

AIMS: It has been suggested that cardiovascular disease may be more strongly related to post-challenge glycaemia than to fasting glucose concentrations. We hypothesized that subclinical inflammation, as indicated by elevated serum levels of C-reactive protein (CRP), may partially explain the association of cardiovascular disease with post-challenge glycaemia. METHODS: We studied the relationship of CRP (measured with a highly sensitive immunoassay) with fasting glucose and 2-h glucose concentrations during an oral glucose tolerance test in non-diabetic subjects from the Insulin Resistance Atherosclerosis Study. RESULTS: Spearman correlation analyses and multiple linear regression analyses showed a significant association of both fasting glucose and 2-h glucose concentrations with CRP levels, after adjusting for demographic covariates (age, sex, ethnicity, clinical centre; Spearman correlation coefficients: r = 0.18 for fasting glucose, r = 0.27 for 2-h glucose, both P < 0.0001). However, after additional adjustment for body mass index and waist-hip ratio only 2-h glucose (and not fasting glucose) was significantly related to CRP (r = 0.03 for fasting glucose, P = NS; r = 0.14 for 2-h glucose, P < 0.0001). Adding insulin sensitivity to the multivariate models further weakened the relationship of CRP to 2-h glucose (r = 0.07, P < 0.05). CRP mean values increased by 2-h glucose category (normal vs. impaired glucose tolerance vs. isolated post-challenge hyperglycaemia). CONCLUSIONS: Chronic, subclinical inflammation, as indicated by elevated circulating CRP levels, is more strongly associated with post-challenge glycaemia than with fasting glucose levels in non-diabetic subjects. This association is partially independent of body fat and insulin resistance.     

Overexpression of the A1 adenosine receptor in adipose tissue protects mice from obesity-related insulin resistance

In-vitro studies have implicated the A(1) adenosine receptor (A(1)AR) of adipocytes in inhibition of lipolysis, stimulation of lipogenesis and enhancement of the action of insulin on glucose metabolism. To determine whether any of these activities were physiologically relevant in an intact animal, A(1)AR was overexpressed in adipose tissue of transgenic mice. Lower plasma free fatty acid (FFA) levels were observed in the transgenic mice relative to the litter-matched controls, supporting a significant physiological role for adipocyte A(1)AR in the control of lipolysis. However, no differences were observed in body weights or body composition. On a high fat diet, both the transgenic mice and the litter matched controls, male and female, became equally obese. Unlike the control mice, however, the transgenic mice did not develop insulin resistance, as demonstrated by serum glucose and insulin levels and glucose and insulin tolerance tests. These findings demonstrate that adipocyte A(1)AR plays an important physiological role in the control of insulin sensitivity in an intact animal and therefore should be considered to be a potential therapeutic target for the treatment of obesity-related insulin resistance and type 2 diabetes.     

Subclinical inflammation and soleus muscle intramyocellular lipids in healthy Asian Indian males

OBJECTIVES: The relationship between C-reactive protein (CRP), a marker of subclinical inflammation, and intramyocellular lipid (IMCL) content, a novel correlate of insulin resistance, has not previously been investigated. METHOD AND DESIGN: We estimated IMCL content in soleus muscle in 30 healthy Asian Indian males using proton magnetic resonance spectroscopy ((1)H MRS), and correlated it with body mass index (BMI), measures of abdominal obesity, percentage of body fat (%BF), serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. RESULTS: Soleus muscle IMCL content was significantly correlated with age (rho=0.64, P<0.001), BMI (rho=0.41, P<0.05), %BF (rho=.53, P<= 0.01), waist circumference (rho=0.45, P<0.05) and waist-to-hip circumference ratio (rho=0.58, P<0.01) but did not correlate significantly with insulin resistance measured by the homeostasis model assessment (HOMA-IR) or CRP levels. CRP levels did not correlate with the HOMA-IR value. CONCLUSIONS: Soleus muscle IMCL content correlated significantly with measures of generalized and abdominal obesity but not with insulin sensitivity or CRP levels in healthy Asian Indian males. Studies are needed in other ethnic groups to corroborate these data.     

Serum procollagen-III-peptide in chronic hepatitis and schistosomiasis

Abstract Recent reports have suggested that the serum concentration of procollagen-III-peptide (PPCP III) reliably reflects the degree of hepatic fibrosis but the topic remains controversial. Serum PPCP III levels have been measured in 40 patients with chronic hepatitis or schistosomiasis. In five patients both diseases were present. The relationship between serum PPCP III levels, hepatic fibrosis and disease activity have been studied histologically and biochemically. The mean serum concentration of PPCP III in patients with chronic hepatitis and in those with active liver disease was significantly higher than that in patients with inactive liver disease. In patients with chronic hepatitis only, serum PPCP III levels correlated with fibrosis, inflammation, and necrosis and also with the combined histological scores. When patients with schistosomiasis as well as hepatitis were included, significant correlations were still observed. In patients with schistosomiasis only, the serum PPCP III levels varied widely and did not correlate with disease activity or with the degree of inflammation, necrosis and fibrosis, either separately or combined. Serum PPCP III concentrations only correlated with serum aspartate amino transferase levels when the patient groups were combined. Serial measurements in 21 patients showed that PPCP III levels varied widely over a short period of time, and that these fluctuations did not significantly correlate with the respective changes in serum AST levels.
In conclusion, serum PPCP III concentrations do not reliably reflect hepatic fibrosis, they are influenced by inflammation and activity of the disease, and they probably reflect the end result of the metabolic state of collagen in the liver, that is the combined effect of synthesis and degradation.     

MECHANISMS IN ENDOCRINOLOGY: Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21

Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.     

慢性乙型肝炎患者肝细胞脂肪变的发生率及其危险因素分析

目的 了解肝细胞脂肪变在慢性乙型肝炎(CHB)患者中的发生率及危险因素.方法 对2005年1月-2007年6月经肝活组织检查证实的CHB患者进行回顾性研究,剔除合并HCV和HW等病毒感染及其他慢性肝病.调查肝细胞脂肪变在CHB患者中的发生率及其变化趋势,分析肝脂肪变与相关的人口学特征、病毒学指标和生物化学指标、以及肝组织学改变之间的关系.结果 在1915例CHB患者中,男1497例,女418例,平均年龄(30.7±9.5)岁.肝组织病理显示肝细胞脂肪变发生率为13.6%(260/1915),并呈逐年增高趋势(2005-2007年分别为11.2%、14.30、17.9%).肝细胞脂肪变程度<30%(FI)的患者占90.4%;男性肝脂肪变(15.2%,228/1497)明显高于女性(7.7%,32/418).有肝脂肪变的CHB患者,其体重指数、年龄、空腹血糖和尿酸明显高于无肝脂肪变患者,t值分别为6.01,3.60,4.72,9.55,P值均<0.01.超重、肥胖、糖尿病,血脂异常和高尿酸血症患病率也明显高于无肝脂肪变患者,x2值分别为17.00,169.45,6.12,116.67,76.34,P值均<0.05.轻度CHB患者肝脂肪变发生率(17.8%)显著高于慢性HBsAg携带者(8.6%)以及CHB中度(9.4%)和重度(7.7%)患者;同样,炎症活动度G1患者肝脂肪变发生率(19.8%)和纤维化程度S1患者肝脂肪变发生率(19.1%)分别显著高于G0、G2、G3和G4(分别为10.3%、11.5%、9.3%和7.3%)和S0、S2、S3和S4(分别为10.8%、13.3%、7.1%、7.4%)患者;肝脂肪变发生率与HBeAg状态及HBV DNA水平无相关关系.多元回归分析显示:体重指数、甘油三酯、载脂蛋白B、尿酸和空腹血糖与CHB患者肝脂肪变的发生密切相关.结论 肝细胞脂肪变在CHB患者中并不少见,其发生主要由患者的代谢因素所致,而与HBV本身无关,肝细胞脂肪变发生与肝脏组织病理损伤程度之间也无明显相关.     

REVIEW: Hepatitis B and liver transplantation

Liver transplantation in hepatitis B virus (HBV)-infected patients is very commonly followed by recurrence of infection in the transplanted liver. Most recipients with HBV recurrence will develop chronic hepatitis that follows a more aggressive course than is seen in non-immuno-compromized subjects and this frequently results in graft failure. The presence of hepatitis B e antigen or significant levels of HBV-DNA in the serum is highly predictive of recurrence and this has led to the view that patients, whose serum is positive for these conventional markers of replication, should be excluded from transplantation. The key to improving the results of transplantation in patients with HBV infection lies in the development of effective strategies to prevent reinfection. High dose anti-HBs immunoglobulin is effective in patients who are coinfected with hepatitis D, those transplanted for fulminant hepatitis and cirrhotic patients who have very low levels of viral replication prior to transplantation. Unfortunately, immunoprophylaxis does not seem to influence the outcome in those patients with higher levels of replication. There are several new orally active nucleoside analogues that are potent inhibitors of hepatitis B replication that may be effective for both the prevention and treatment of recurrent disease. The most promising are lamivudine (2',3', dideoxy, 3', thiacytidine) and famciclovir (a guanosine analogue). Both agents have been extensively evaluated in animal models of HBV and have been shown to rapidly suppress viral replication. The initial experience with these agents in liver transplant recipients has been promising and a number of studies are currently underway to determine whether these drugs, used alone or in combination with immunoprophylaxis, are able to prevent recurrence in those patients at highest risk of post-transplant HBV recurrence.     

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。