Variation in hepatic estrogen receptor concentrations in patients with liver disease. A multivariate analysis.

Hepatic estrogen receptor concentrations were measured in liver biopsy specimens from 102 patients (58 women and 44 men) with liver disease and correlated to several clinical, biochemical, and histologic background variables by means of multiple regression analysis. Half of the tissue was processed for histologic evaluation with a semiquantitative registration of histologic characteristics, whereas the other part was used for receptor analysis by enzyme immunoassay. Fifteen patients with no or minimal histologic changes served as controls. The analysis shows that the reduced estrogen receptor concentrations observed in patients with chronic liver diseases reflect the degree of liver dysfunction and not the specific type of liver disease. Serum albumin, log serum bilirubin, log serum alkaline phosphatases, and the degree of parenchymal fibrosis were significantly related to hepatic estrogen receptor level in the final regression model, but only part of the variation can be explained by these variables, and other factors must be of importance.     

慢性乙型肝炎重度和慢加急性肝衰竭患者MELD评分与HBV DNA载量的变化

目的了解慢性乙型肝炎重度和肝衰竭患者极期与缓解期HBV DNA载量的变化。方法观察并比较51例慢性乙型肝炎重度和56例慢加急性肝衰竭患者病情极期和缓解期的MELD评分和HBV DNA载量变化。结果慢加急性乙型肝炎肝衰竭患者极期和缓解期MELD评分分别为20.5±4.4分和12.2±6.1分,HBV DNA载量为6.2±1.5log10 copies/ml和4.5±1.5log10 copies/ml,而慢性乙型肝炎重度患者极期和缓解期MELD评分则分别为11.9±3.2分和6.4±3.1分,HBV DNA载量为6.5±1.5log10 copies/ml和4.9±1.8log10 copies/ml。慢加急性乙型肝炎肝衰竭和慢性乙型肝炎重度患者极期和缓解期之间MELD评分和HBV DNA载量均存在差别(t=6.692～13.215,P均0.000)。结论不论慢加急性乙型肝炎肝衰竭还是慢性乙型肝炎重度患者,随着肝病的缓解,其MELD评分明显下降,HBV DNA载量出现显著的自发性下降。     

Baseline and salt-stimulated paraoxonase and arylesterase activities in patients with chronic liver disease: relation to disease severity

Background: It has been recently reported that serum paraoxonase (PON1) and arylesterase (ARE) activities may be significantly reduced in patients with chronic liver disease. The aim of the study was to investigate the relations between serum PON1 and ARE activities and the degree of liver damage in patients with chronic liver injury.
Methods: We studied a total of 75 patients with chronic liver disease (50 patients with cirrhosis and 25 patients with chronic hepatitis) and 25 healthy comparison subjects. Baseline and salt-stimulated PON1 and ARE activities were determined in all study participants.
Results: Baseline and stimulated PON1 and ARE activities were significantly lower in patients with chronic liver disease than in controls. Cirrhotic patients in Child–Pugh classes B and C subgroups had significantly reduced PON1 and ARE activities compared with Child–Pugh class A patients (both P -values <0.01). Receiver operating characteristic curve analysis showed that serum ARE activity was the most efficient test for identifying the presence and severity of chronic liver injury.
Conclusion: Baseline and stimulated PON1 and ARE activities are reduced in patients with chronic liver disease. Serum ARE activity could be a suitable biomarker for the evaluation of the presence and severity of chronic liver damage.     

Serum inhibition of complement derived leukocyte chemotaxis and levels of immunoglobulin A subclass in alcoholic liver disease

Serum inhibition of complement-derived leukocyte chemotaxis was examined in alcoholic liver disease with or without cirrhosis. Chemotactic inhibitory activity (CIA) was detected with higher frequency and degree in alcoholic liver disease, especially with liver cirrhosis compared with normal subjects and non-alcoholic liver cirrhosis. CIA was found in anti-IgA adsorbed fractions in the sera of patients with alcoholic liver cirrhosis. Serum concentrations of IgAl and IgA2 in alcoholic liver disease were statistically higher than in non-alcoholic liver cirrhosis. However, no correlation between CIA and the concentrations of IgA subclasses was demonstrated in alcoholic liver disease. This serum inhibitor may partly explain the high susceptibility to bacterial infection in alcoholic liver disease.     

The association between steatosis and liver damage in transfusion-dependent beta thalassaemia patients

Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Iron is the leading cause of liver damage in patients with transfusion-dependent thalassaemia (TDT), and data on the contribution of NAFLD to liver damage in TDT is lacking. Forty-five heavily transfused TDT patients who did not have biochemical or ultrasonic evidence of liver cirrhosis were evaluated for effects of iron overload, including the presence of diabetes mellitus, hypogonadism, serum ferritin, R2-MRI-liver, and liver enzymes alanine aminotransferase and aspartate aminotransferase. Liver fibrosis and steatosis were estimated using transient elastography (TE). Nine (20%) patients had significant steatosis (S1), and their body mass index (BMI) and liver fibrosis scores were higher than in patients without significant steatosis (S0) (p = 0.03 and p = 0.004, respectively). On regression analysis, the controlled attenuation parameter (CAP) score (i.e., degree of liver steatosis) was associated only with increasing BMI. The TE score (i.e., degree of liver fibrosis) was associated with increasing age, CAP score, male gender, and presence of diabetes. Neither liver steatosis nor fibrosis showed significant association with the liver iron concentration or iron-related organ damage (hypogonadism). In this cohort of TDT patients, steatosis of the liver, which is associated with increasing BMI, appeared to increase the risk of liver fibrosis.     

Fasting insulin and uric acid levels but not indices of iron metabolism are independent predictors of non-alcoholic fatty liver disease. A case-control study

BACKGROUND: Non-alcoholic fatty liver disease is a common reason for hepatological consultation and may herald severe hepatic and extra-hepatic disease. The aetiopathogenesis of this condition is an area of increasing interest. AIM: To evaluate anthropometric and biochemical factors associated to non-alcoholic fatty liver disease in a case-control study. Methods. Demographic and biochemical data of 60 consecutive patients with bright liver absent-to-low alcohol consumption, no evidence of viral, genetic and autoimmune diseases, were compared to those of 60 age- and gender-matched historical controls without fatty liver by univariate and multiple logistic regression analysis. RESULTS: Patients were more often hypertriglyceridaemic, obese and diabetic than controls (p<.01). Mean values of alanine transaminase, gammaglutamyltranspeptidase, triglycerides, uric acid, fasting and log insulin, transferrin percent saturation and ferritin were significantly higher in the patients, while transferrin and quantitative insulin sensitivity check index, a quantitative insulin sensitivity index, were lower. No iron storage was found in those who underwent liver biopsy At univariate analysis the relative risk for non-alcoholic fatty liver disease significantly increased (p<0. 05) with increasing body mass index, fasting insulin, alanine transaminase, uric acid, triglycerides and gammaglutamyltranspeptidase; it decreased with increasing transferrin and quantitative insulin sensitivity check index. Multiple logistic regression analysis disclosed only fasting insulin and uric acid to be independent predictors of non-alcoholic fatty liver disease (p<0.05). CONCLUSIONS: Fasting insulin and serum uric acid levels indicating insulin resistance, but not indices of iron overload, are independent predictors of non-alcoholic fatty liver disease.     

COMPARATIVE SENSITIVITY OF SERUM CHOLYLGLYCINE CONCENTRATION AND BROMSULPHALEIN RETENTION IN PATIENTS WITH EARLY AND LATE ALCOHOLIC LIVER DISEASE

Measurement of serum bile acids has been claimed to be a sensitive and specific biochemical test of hepatic function. We have prospectively measured post-prandial serum glycocholate (cholylglycine) concentrations in 31 patients with alcoholic liver disease and compared these measurements with those of bromsulphalein (BSP) retention, prothrombin time, and serum albumin. In the patients with early (non-cirrhotic) alcoholic liver disease (N = 14) BSP retention was abnormal significantly more frequently than was serum cholylglycine concentration (100% vs 29%, p < 0.001). In contrast, amongst patients with late (cirrhotic) alcoholic liver disease, BSP retention and serum cholylglycine were abnormal with equal frequency (94%). In both groups of patients BSP retention and serum cholylglycine were abnormal significantly more often than were prothrombin time and serum albumin concentrations. We conclude that moderately severe hepatocellular dysfunction is required before serum cholylglycine can become a reliable biochemical indicator of liver disease.     

肥胖人群血清尿酸水平与非酒精性脂肪性肝病严重程度的相关性分析

目的探究肥胖患者高尿酸血症发生的危险因素以及血清尿酸水平与非酒精性脂肪性肝病（NAFLD）严重程度的相关性。 方法回顾性分析2018年7月至2020年9月在南京鼓楼医院减重代谢中心拟行减重代谢手术的247例肥胖患者,收集患者术前临床资料及血清学数据及肝脏NAS评分。 结果221例患者进入肥胖患者高尿酸血症的危险因素分析,低尿酸组57（25.8%）人,高尿酸组164（74.2%）人,二组在性别、体质量指数（BMI）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、γ-谷氨酰转肽酶（γ-GT）、总胆红素（TBil）、甘油三酯（TG）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）、胰岛素（INS）、C肽（C-peptide）水平存在差异。141例患者拥有完善的病理学结果,其中40例可排除非酒精性脂肪性肝炎（NASH）,68例NASH可能,33例可诊断为NASH,三组高尿酸血症发生率分为别78.7%、76.5%、47.5%;多因素logistic回归分析提示三组在小叶内炎症、气球样变、ALT、UA水平存在差异（P<0.05）;而进一步研究发现血清尿酸水平与肝脏脂肪变性程度正相关（Spearman分析相关系数r=0.38,P<0.05）,而与气球样变及小叶内炎症无明显相关性（血清尿酸与气球样变：Spearman分析相关系数r=0.14,P=0.096;血清尿酸与炎症反应：Spearman分析相关系数r=0.058,P=0.493）。 结论随着肥胖患者BMI的增高,发生高尿酸血症以及非酒精性脂肪性肝炎的可能性增高;血清尿酸的增高也会促进肥胖患者非酒精性脂肪性肝病的发展,且血清尿酸水平与肝脏脂肪变性严重程度具有相关性。     

Serum Markers for Hepatic Fibrosis in Alcoholic Liver Disease: Which Is the Best Marker,Type III Procollagen,Type IV Collagen,Laminin, Tissue Inhibitor of Metalloproteinase,or Prolyl Hydroxylase?

Although various serum markers for the evaluation of hepatic fibrosis have been introduced, it remains unclear which is the best marker to evaluate the hepatic fibrosis observed in alcoholic liver disease (ALD). In this study, we measured serum concentrations of the immunoreactive β-subunit of prolyl hydroxylase, procollagen type III peptide, the 7s domain (7s-IV) and triple-helix domain (TH-IV) of type IV collagen, laminin, and tissue inhibitor of metalloproteinase (TIMP) in patients with and without ALD (non-ALD), and controls to evaluate the best serum marker reflecting the characteristic histologic features of ALD. Alter Azan-Mallory and silver-impregnated reticulin staining, histologic specimens were examined; and the degree of hepatic fibrosis was classified as mild, moderate, or severe. Although serum concentrations of all markers, except for TIMP, in patients with each type and stage of liver disease were higher than cut-off values and these concentrations increase with the progression of liver disease, statistical analyses indicate that serum TH-IV concentration is the best marker to distinguish ALD from non-ALD. A good correlation was also found between the hepatic type IV collagen content and serum TH-IV, but not serum 7s-IV concentration. Moreover, after abstinence from alcohol, serum concentrations of TH-IV decreased more quickly than other serum markers. These results clearly suggest that, compared with other markers, serum concentration of TH-IV may more strongly reflect the histologic features of ALD. However, other serum markers, except for TIMP, may be useful in evaluating the degree of hepatic fibrosis.     

Clinical significance of serum hyaluronan in patients with chronic viral liver disease

In order to elucidate the clinical significance of serum hyaluronan in chronic viral hepatitis, serum hyaluronan concentrations were measured using a sandwich enzyme binding assay in 115 patients with chronic viral hepatitis. These findings were examined in relation to the results of laboratory liver tests, levels of serum markers for fibrosis and liver histological findings. Serum hyaluronan levels increased with the progress of liver disease, particularly in liver cirrhosis. There were no significant differences in serum hyaluronan levels among the cirrhotic patients according to Child's grade. Multivariate analysis showed that the significant independent predictors of serum hyaluronan were serum aspartate aminotransferase (P= 0.020), serum alanine aminotransferase (P= 0.008), serum cholinesterase (P< 0.001), particularly serum type IV collagen 7S domain (P< 0.0001), and the histological degree of liver fibrosis (P< 0.0001). These findings suggest that elevated serum hyaluronan levels are closely related to the severity of liver fibrosis. We assessed the predictive value of serum hyaluronan in differentiating cirrhosis from chronic hepatitis, constructing receiver operating curves; we found that serum hyaluronan was a better test for diagnosing cirrhosis than serum type IV collagen 7S domain and laboratory liver tests.     

肝病血清丙二醛及超氧化物歧化酶测定的临床意义

目的:研究血清丙二醛及超氧化物歧化酶在肝病中的临床意义.方法:采用放免法和硫代巴比妥酸比色法测定53例肝病患者和26例正常对照组的血清丙二醛(MDA)和超氧化物歧化酶(SOD)水平.结果:急性肝炎组MDA高于正常对照组(P<0.01),差异显著,SOD低于正常对照组(P<0.01),差异显著.慢性肝炎组MDA明显高于正常对照组(P<0.002),差异非常显著.肝硬化组MDA显著高于正常组(P0.05),但均较正常组低.结论:肝病患者发病后均出现氧自由基代谢紊乱,而且随病变加重而自由基水平升高.因此,观察血清MDA和SOD水平的变化对临床上判断肝细胞的损害程度、病情发展、评估预后有一定的意义,同时为肝病的治疗提出了一条新途径及理论基础.     

瘦素及瘦素受体与非酒精性脂肪肝病的关系

目的 通过检测非酒精性脂肪肝病(NAFLD)患者血清瘦素、肝组织瘦素(Lp)及瘦素受体(OB-R)的水平,探讨瘦素及瘦素受体在NAFLD发病机制中的可能作用.方法 应用放免及免疫组织化学方法检测30例NAFLD患者及30例对照者血清Lp、肝组织中Lp及OB-R水平,并检测空腹血糖、总胆固醇、甘油三脂、C-肽、胰岛素、体...     

移植前终末期肝病模型评分与肝纤维化程度的相关性研究

目的 通过将临床终末期肝病模型(MELD)评分及Ishak病理学肝纤维化分级的相关性进行比较,探讨运用MELD评分评估肝移植患者肝纤维化程度的可行性.方法 采用计算机辅助图像分析法,定量评估华西医院2006年2至9月58例因终末期肝病接受肝移植手术者病肝标本的纤维化程度,同时运用改良Ishak肝纤维化分级法进行病理学诊断;收集入院当天的临床资料,计算MELD评分,利用Spearman等级相关分析法分析图像法、Ishak分级、MELD评分三者间的相关性,利用直线回归分析MELD评分与肝纤维化程度二者之间有无线性依存关系.按其结果 拟定参考标准.结果 图像分析法测定58例患者病肝标本的肝纤维化百分比为23.2%～88.4%,平均56.7%;入院当天的MELD评分为11～38分,平均22.85±9.32;Ishak分级0～6级者分别为0、2、7、12、18、12、7例,随着Ishak级数加大,肝纤维化百分比渐增,MELD评分逐步增高,Spearman等级相关分析表明其相关性有统计学意义(P＜0.01),利用直线回归分析MELD评分与肝纤维化程度二者之间也存在线性依存关系.结论 图像分析法能较准确地评估肝组织纤维化程度,与MELD评分有良好的相关性,运用MELD评分系统能对肝移植患者肝组织纤维化的严重程度进行评估.     

老年女性冠心病与血清性激素和尿酸的关系

目的　研究老年女性冠心病与血清性激素和尿酸之间的关系。方法　 115例绝经后女性根据冠状动脉造影结果分为冠心病组 (6 0例 )和对照组 (5 5例 ) ,比较两组血清性激素和尿酸水平及其与冠心病和冠状动脉病变支数的关系。应用逐步logistic回归分析危险因素与冠心病发病的关系。结果　冠心病组血清尿酸水平显著高于对照组 ,但两组雌二醇、孕激素及雄激素水平无显著差异。多因素分析显示 ,老年女性冠心病发病与年龄、血清尿酸及糖尿病显著相关。 3支冠状动脉病变患者血清尿酸浓度显著高于单支及 2支冠状动脉病变患者。结论　血清尿酸升高是老年女性冠心病发病的独立预测因素 ,并能够反映冠状动脉病变严重程度 ,而性激素无此作用。     

Serum testosterone concentrations in men with alcoholic cirrhosis: background for variation

Median serum testosterone concentration of men with alcoholic cirrhosis (n = 216) did not differ significantly from normal controls (n = 51), but serum testosterone concentrations varied by a factor 43.9 in patients compared to 3.2 in controls (P less than .001). Nineteen percent of the patients had serum testosterone concentrations above 30 nmol/L. Serum concentrations of sex-hormone-binding globulin (SHBG) were significantly (P less than .001) raised, and serum concentrations of calculated nonprotein-bound and non-SHBG-bound testosterone were significantly (P less than .001) decreased in patients compared to normal control values. A number of background variables were analyzed with reference to serum testosterone concentrations by means of multiple regression techniques after having divided the patients into groups (A, B, C) with decreasing liver function by a modification of the Child-Turcotte's criteria. The only significant (P less than .01) background variables associated with log serum testosterone concentrations were: group C (beta = -0.828), group B (beta = -0.222), age (years) (beta = -0.012), duration of hospitalization (days) (beta = -0.0077), and concentration of SHBG (nmol/L) (beta = 0.0044). Neither previous nor recent (within last six months) alcohol consumption influenced serum testosterone concentrations significantly, but about 50% of the patients had abstained from ethanol for two months or more. The same background variables as above were included as significantly (P less than .01) associated with log serum concentrations of calculated nonprotein-bound testosterone and calculated non SHBG-bound testosterone, except that SHBG was insignificantly associated to any of the two proportions and that testicular volume was significantly (P less than .05) associated with log non-SHBG bound testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)     

A non-invasive prediction model for non-alcoholic steatohepatitis in paediatric patients with non-alcoholic fatty liver disease

Background

Non-alcoholic fatty liver disease encompasses a spectrum of diseases that range from simple steatosis to the aggressive form of non-alcoholic steatohepatitis. Non-alcoholic steatohepatitis is currently diagnosed through liver biopsy.

Aim

To develop a non-invasive predictive model of non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease.

Methods

Anthropometric, laboratory, and histologic data were obtained in a cohort of children with biopsy-proven non-alcoholic fatty liver disease. Multivariable logistic regression analysis was employed to create a nomogram predicting the risk of non-alcoholic steatohepatitis. Internal validation was performed by bootstrapping.

Results

Three hundred and two children were included in this analysis with a mean age of 12.3 ± 3.1 years, a mean body mass index percentile of 94.3 ± 6.9, and non-alcoholic steatohepatitis was present in 67%. Following stepwise variable selection, total cholesterol, waist circumference percentile, and total bilirubin were included as variables in the model, with good discrimination with an area under the receiver operating characteristic curve of 0.737.

Conclusions

A nomogram was constructed with reasonable accuracy that can predict the risk of non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease. If validated externally, this tool could be utilized as a non-invasive method to diagnose non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease.     

雌激素在慢性肝病发生发展中的作用研究现状*

雌激素在各类慢性肝病患者均有不同程度的异常变化。雌激素水平的异常不仅是疾病进展的结果,同时可能还参与了各类慢性肝炎发生发展的全过程。本文重点介绍雌激素在病毒性肝炎、自身免疫性肝病、肝癌等慢性肝炎发病中的作用。     

Estrogen receptor levels in a murine model of systemic lupus erythematosus

Offspring of a cross between the NZB and NZW mice (F1) develop a disease similar to SLE in humans. Female mice of the F1 strain develop the disease at a younger age and die earlier than the males. In order to test the hypothesis that estrogen receptor concentrations in the lymphoid organs of these mice may correlate with increased female susceptibility, estrogen receptor assays were performed on cytosol from the uterus, thymus, spleen, and liver of affected animals and the parental stock using the dextran-charcoal method. Specific binding of the receptor was analysed by Scatchard analysis. There were no differences among receptor concentrations in the uterus, thymus, and spleen of NZB, NZW, and F1 mice. However, the estrogen receptor concentrations in the liver from NZW and F1 mice were twice that of NZB mice. This observation may be of importance since the liver is involved in steroid metabolism and abnormalities of estrogen metabolism have been reported in human SLE.     

Stability of HCV-RNA level and its lack of correlation with disease severity in asymptomatic chronic hepatitis C virus carriers

This study examines the relationship between HCV-RNA levels and disease severity in 60 individuals with chronic hepatitis C virus infection. HCV-RNA levels were quantified by the branched DNA (bDNA) assay in 445 samples (median: eight samples per patient) obtained over a median of 40.4 months (95% confidence interval (CI): 37.0–42.5). The median log HCV-RNA level was 6.77 (95% CI: 6.62–6.92) molecular equivalents/mL (MEQ/mL). The median log range of HCV-RNA levels in individual patients over the course of the study was 0.89 (95% CI: 0.69–1.16). HCV-RNA level varied over time by less than one log in 62% of patients, by 1–1.5 logs in 22% and by greater than 1.5 logs in only 17%. Univariate analysis, revealed an inverse association between HCV-RNA levels and ALT levels ( P =0.037). Univariate and logistic regression analysis showed no significant association between HCV-RNA levels and either the degree of inflammation or fibrosis. In contrast, there was a significant positive association between alanine aminotransferase (ALT) levels and histological activity especially in individuals with ALTs>  100 IU/L. Hence, HCV-RNA levels: (i) almost always fell within the dynamic range of the bDNA assay; (ii) were stable in asymptomatic chronically infected patients, with only a small proportion of patients exceeding a range of 1.5 logs; (iii) did not correlate with either the extent of inflammation or degree of fibrosis. In contrast, there was a strong association between ALT level and the histological severity of liver disease.