Serum bile acids in alcoholic liver disease. Comparison with histological features of the disease.

Fasting serum bile acids were measured by gas-liquid chromatography in 64 patients with alcoholic liver disease and compared with histological features in their percutaneous liver biopsy specimens. Total bile acid concentrations were normal (less than 2 mug/ml) or minimally increased in 6 patients in whom fatty infiltration was the only hepatic lesion. In the remaining 58 patients with more severe histological lesions, levels were increased in 93%, whereas serum bilirubins were elevated in only 43%. Chenodeoxycholic acid was usually the predominant serum bile acid, regardless of the degree of necrosis or connective tissue change in the biopsy specimen. Only small amounts of the secondary bile acids, deoxycholic acid and lithocholic acid, were detected. Levels of these secondary bile acids did not correlate with histological features.     

Lipoprotein-bound bile acids in serum from healthy men, postprandially and during fasting

Individual bile acids were determined by gas-liquid chromatography in, very low density, low density and high density lipoprotein fractions obtained by sequential ultracentrifugation of serum from normal adults, both postprandially and during fasting. The lipoproteins were found to contain 22-34% of fasting serum bile acids. The observed postprandial increase in bile acids did not exhibit any shift in the ratio between lipoprotein bound- and non-lipoprotein-bound bile acids. Bile acids were present in all isolated lipoprotein fractions, high density lipoproteins containing the highest amounts. In the lipoprotein fraction, a higher percentage of cholate than of chenodeoxycholate was found.     

血清天门冬氨酸氨基转移酶线粒体同工酶在酒精性肝病中的临床价值

目的探讨血清天门冬氨酸氨基转移酶线粒体同工酶(m-AST)活性在酒精性肝病(ALD)预后判断中的价值。方法采用免疫抑制法检测104例ALD患者[ALD组,包括酒精性脂肪肝(AFL)36例、酒精性肝炎(AH)52例和酒精性肝硬化(AC)16例]和100例病毒性肝炎患者[非酒精性肝病(NALD)组]治疗前(入院时)、治疗3周后及100名健康成人(对照组)血清m-AST活性,同时测定血清γ-谷氨酰基转移酶(GGT)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性;观察AFL、AH及AC患者治疗前、后GGT、ALT、AST、m-AST活性的变化。结果 ALD组、NALD组血清GGT、ALT、AST、m-AST活性均明显高于对照组(P<0.05),NALD组各项指标明显高于ALD组(P<0.05)。治疗后AFL、AH及AC组血清GGT、ALT、AST活性均明显下降(P<0.001),AFL和AH组下降幅度明显高于AC组;AFL组血清GGT、ALT、AST、m-AST活性基本降至正常水平;AH组血清m-AST活性有明显下降,但AC组下降不明显。结论血清m-AST对ALD的治疗监测具有一定的临床意义。     

Determination of 3 beta-hydroxylated bile acids in human serum and liver tissue

3 beta, 7 alpha-Dihydroxy-5 beta-cholanoic acid (3 beta, 7 alpha-diOH) was detected in serum of 3 patients with intrahepatic cholestasis. 3 beta, 7 beta-dihydroxy-5 beta-cholanoic acid (3 beta, 7 beta-diOH) appeared in serum of those patients after treatment with ursodeoxycholic acid (UDC). These bile acids were also detected in only unconjugated fractions of serum of another 7 patients with chronic liver diseases, but not in liver tissue of them. The liver does not seem to from these bile acids itself because they were absent in liver tissue.     

血清铁含量检测在酒精性脂肪性肝病和非酒精性脂肪性肝病中的临床意义

目的：探讨铁代谢相关血清学指标在酒精性脂肪性肝病(ALD)和非酒精性脂肪性肝病(NAFLD)中的意义及在肝损伤过程中的作用。方法脂肪性肝病患者406例,其中 ALD 组198例,NAFLD 组208例,另选健康对照组96例,检测血清铁(SF)、铁蛋白(Ferr)及转铁蛋白(TRF)。结果 NAFLD 组、ALD 组 SF、Ferr 水平均高于健康对照组(P <0.05);且 NAFLD 组 SF、Ferr 水平高于 ALD 组。NAFLD 组、ALD 组 TRF 水平均低于健康对照组(P <0.05);且 NAFLD 组 Ferr 水平低于 ALD 组。NAFLD、ALD 组肝硬化亚组血清 SF、Ferr 明显高于肝炎亚组(P <0.05),TRF 明显低于肝炎亚组,差异均有统计学意义(P <0.05)。结论 SF、Ferr 和 TRF 有助于了解脂肪性肝病患者肝损伤程度,特别是对 NAFLD 的预后有重要意义。     

Transport of serum bile acids in patients with liver cirrhosis and hyperbilirubinaemia

From 12 patients with liver cirrhosis and hyperbilirubinaemia, the different conjugates of bilirubin and bile acids in the serum were separated and determined. The serum of the patients contained varying amounts of unconjugated bilirubin, which was not correlated to total serum bilirubin. No correlation between bilirubin conjugates and different conjugates of bile acids could be found, indicating different elimination processes for these substances. To examine whether a changed plasma transport of bile acids, which may contribute to the different excretion pattern of bilirubin and bile acids, occurs in liver cirrhosis, the bile acids in the different serum lipoprotein fractions were determined in seven of the patients. It was found that 40% of serum bile acids were bound to serum lipoproteins, despite decreased serum lipoprotein levels. The degree of lipoprotein binding of bile acids was not correlated to total serum bile acid concentrations. Cholic acid conjugates were present to a higher extent in the lipoprotein fractions than those of chenodeoxycholic acid or of deoxycholic acid. Determination was made of the distribution of individual conjugates between different lipoproteins and it was found that most of the glycine conjugates were present in high density lipoprotein, whereas the main part of sulphates and taurine conjugates were present in low density lipoprotein. These results indicate that a higher fraction of bile acids in liver cirrhosis is transported by lipoproteins in plasma, which may be of importance for the hepatic elimination of bile acids in cases with this disease.     

Type IV collagen and laminin-related antigens in human serum in alcoholic liver disease

The two major constituents of basement membranes are type IV collagen and laminin. Specific radioimmunoassays are described here for two structural domains of these proteins (7-S collagen and the fragment P1, respectively) that allow the related antigens to be quantified in human serum. The serum 7-S collagen antigen was uniform in size, whereas the laminin P1 antigenicity was heterogeneous. These proteins were measured in sera from sixty-three alcoholics, divided on the basis of liver histology into four groups: normal light microscopy, fatty liver, alcoholic cirrhosis with hepatitis and inactive cirrhosis. The group with cirrhosis and hepatitis had clearly elevated values in both assays, differing significantly from the others. A few pathological results were also seen in the other groups. The increases noted in 7-S collagen concentration were larger than those in laminin P1. During follow-up of a patient with cirrhosis and hepatitis the 7-S collagen level in particular seemed to reflect the course of the disease. The elevated basement membrane protein concentrations in serum may be associated with the formation of real basement membranes in the perisinusoidal space, a process known as capillarization of the sinusoids which is found during the development of liver cirrhosis.     

酒精性肝病发病机制

酒精性肝病（alcoholic liver disease, ALD）是因长期过量饮酒引起的肝脏疾病,其中包括轻症ALD、酒精性脂肪肝、酒精性肝炎、酒精性肝纤维化和酒精性肝硬化,我们就氧化应激、内质网应激、硝化应激及调脂因子在酒精性肝病发病机制中的作用等进行阐述。     

糖缺乏转铁蛋白检测对酒精性肝病的诊断价值

目的　评价糖缺乏转铁蛋白 (CDT)对酒精性肝病的诊断价值。方法　选取 36例酒精性肝病、30例嗜酒者、30例非酒精性肝病和 30名健康者用离子交换色谱与免疫比浊法结合定量检测CDT ,同时检测γ 谷氨酰基转移酶 (GGT)等肝功能指标。结果　酒精性肝病组CDT为 (4.32± 1.2 2 ) % ,嗜酒者组为 (2 .87± 1.0 3) % ,非酒精性肝病组为 (2 .74± 0 .86 ) % ,正常对照组为 (2 .4 5± 0 .2 9) %。酒精性肝病组与正常组比较差异有显著性 (P<0 .0 0 1)。结论　CDT是诊断酒精性肝病较理想的辅助指标     

糖缺乏转铁蛋白检测对酒精性肝病的诊断价值

目的评价糖缺乏转铁蛋白(CDT)对酒精性肝病的诊断价值.方法选取36例酒精性肝病、30例嗜酒者、30例非酒精性肝病和30名健康者用离子交换色谱与免疫比浊法结合定量检测CDT,同时检测γ-谷氨酰基转移酶(GGT)等肝功能指标.结果酒精性肝病组CDT为(4.32±1.22)%,嗜酒者组为(2.87±1.03)%,非酒精性肝病组为(2.74±0.86)%,正常对照组为(2.45±0.29)%.酒精性肝病组与正常组比较差异有显著性(P<0.001).结论 CDT是诊断酒精性肝病较理想的辅助指标.     

Radioimmunoassay of bile acids in serum.

We developed four radioimmunoassay procedures for the determination of glycine-conjugated bile acids in serum. Antibodies to two primary bile acids, cholylgycine and chenodeoxycholylglycine, and to two secondary bile acids, sulfolithocholylglycine and deoxycholylglycine, were raised in rabbits after the acids were covalently linked to albumin by use of the carbodiimide reaction. Assay sensitivity for each of these bile acids is in the picomole range with the standard curve extending from 10-80 pmol. The concentration of bile acids in serum increased in various states of liver disease and its measurement appears to be an extremely sensitive indicator of liver function.     

Cardiac findings in alcoholic liver disease

In a prospective study 53 patients with alcohol-induced liver disease (fatty liver in 27, cirrhosis in 26) were studied clinically and with non-invasive techniques (electrocardiogram, systolic time intervals, M-mode echocardiography, upright bicycle stress test) to detect a possible cardiac involvement. Mean daily alcohol consumption was comparable in both groups (136 g/day over 16 years vs 124 g/day over 14 years). 15 to 41% of patients (more patients with fatty liver) complaint of angina pectoris and dyspnea at exercise or had palpitations. Echocardiography and systolic time intervals demonstrated in both groups (in patients with cirrhosis despite of a more intensive therapy with digitalis and diuretics) a marked enlargement of left ventricular dimensions with a significant (p less than 0.05) degree of dysfunction (PEP/LVET). Electrocardiography showed abnormalities in 26 to 44% of patients: signs of right ventricular enlargement in 26% of patients with fatty liver, and a prolongation of myocardial repolarisation (QTc) in 44% of patients with cirrhosis. Patients with alcohol-induced liver disease deserve more attention of their cardiac complaints, clinical and functional findings.     

酒精性肝病治疗研究进展

目前,长期过度摄入酒精而引发的酒精性肝病已经成为一个社会性的健康问题,给患者、家庭及社会带来了极大的经济负担。酒精性肝病包括酒精性脂肪肝、酒精性肝炎、肝硬化以及肝癌等。酒精性肝病的诊断一般基于临床上的症状,如饮酒史、肝病指标及临床化验指标等。目前酒精性肝病的治疗最重要的是戒酒,再根据病情采取相应的治疗措施,主要的治疗手段包括药物治疗、精神治疗及外科肝移植治疗等。严重的酒精性肝病临床上推荐使用皮质类固醇或己酮可可碱。干细胞治疗是肝硬化患者的一个可能的治疗措施。肝移植除了合适的肝脏供体,移植后使用的免疫抑制剂可能导致新的癌症的发生。新型的安全高效的病理生理主导的治疗方法是治疗酒精性肝病的必然趋势,可能的靶点包括CXC细胞因子、IL-22、TNF受体超家族、补体和脂多糖(LPS)等。     

Caput medusae in alcoholic liver disease

Caput medusae and palmar erythema are cardinal signs in cirrhosis of liver with portal hypertension. Palmar erythema is described more often as a marker for alcoholic etiology of chronic liver disease. The peripheral stigmata of chronic liver disease are not routinely seen now a days due to early diagnosis and better therapy. We recently encountered an interesting patient of alcoholic liver disease with two classical signs of the disease and report the same for this unusual presentation.