原发性胆汁性肝硬化患者免疫功能及肝功能损伤情况研究

目的研究原发性胆汁性肝硬化患者的免疫功能改变及肝功能损伤情况。方法选取2013年3月至2016年3月攀枝花市中西医结合医院收治的原发性胆汁性肝硬化患者30例作为观察组,肝功能轻度损伤者17例,肝功能严重损伤者13例;另外选取同期因其他肝脏疾病入院的30例患者作为其他肝病组,选取同期行健康体检的30例作为健康组,采用流式细胞术对3组研究对象的免疫细胞进行检测,比较3组外周血树突状细胞亚群及肝功能指标等。结果观察组患者CD4~+细胞(29.9%)、CD8~+细胞(28.8%)显著高于健康组,且差异有统计学意义(P0.05);而CD11c~+细胞(0.087%)、CD123~+细胞(0.035%)及NK细胞(13.333%)明显低于健康组,且差异具有统计学意义(P0.05)。观察组患者CD4~+细胞(29.9%)、CD8~+细胞(28.8%)、CD11c~+细胞(0.087%)、CD123~+细胞(0.035%)明显高于其他肝病组,但NK细胞(13.3%)显著低于其他肝病组,差异具有统计学意义(P0.05)。健康组CD4~+细胞,差异具有统计学意义(26.9%)、CD8~+细胞(23.6%)、CD11c~+细胞(0.169%)、CD123~+细胞(0.064%)及NK细胞(20.7%)均显著高于其他肝病组(P0.05)。肝功能严重损伤组CD4~+、CD8~+、CD123~+细胞显著高于肝功能一般损伤组,而CD11c~+、NK细胞则显著低于肝功能一般损伤组,差异均具有统计学意义(P0.05)。血清抗线粒体抗体(AMA)-M2阴性组CD4~+、CD8~+细胞显著低于AMA-M2阳性组,而CD123~+、CD11c~+、NK细胞则显著高于AMA-M2阳性组,差异均具有统计学意义(P0.05)。结论原发性胆汁性肝硬化患者的免疫功能与肝功能都与血清AMA-M2抗体的产生有关系,其中CD11c~+与CD123~+或为影响疾病发展及AMA-M2抗体产生的主要因素。     

Lipoprotein abnormalities in patients with early primary biliary cirrhosis

Abstract. In twelve females with early forms of primary biliary cirrhosis (PBC) serum lipoproteins, the intravenous fat tolerance test (IVFTT) and the lecithin: cholesterol acyl transferase (LCAT) rate were determined and compared to healthy controls. The cholestatic LDL (LP-X) test was negative in all cases. PBC patients had lower very low density lipoprotein TG concentrations than controls and had levels of (high-density lipoprotein) HDL-TG, -cholesterol and -phospholipids that were about 50% higher than in controls. In PBC the HDL₂-cholesterol concentration was double but the HDL₃-cholesterol concentration was 60% of control values ( P < 0·001 for both). The LCAT rate and the IVFTT value did not differ between the groups. A typical finding on agarose gel electrophoresis was the appearance of a slow-moving α-band. Several interpretations of these results are possible.
In PBC the hepatic lipase activity may be impaired leading to a shift of the HDL₂/HDL₃ relation. The transport of HDL₂ to the liver lipase site may also be affected and HDL₃ production reduced due to malabsorption in the intestine.     

Pituitary-testicular function in patients with alcoholic cirrhosis of the liver

In forty-two patients with alcoholic liver cirrhosis and without recent alcohol ingestion the pituitary-testicular function was studied in an effort to relate the endocrine abnormalities with the degree of liver cell dysfunction, evaluated on a quantitative basis. Compared with values in twenty-one healthy controls, we found significantly elevated serum oestrone, oestradiol, follicle-stimulating hormone, luteinizing hormone and prolactin (P less than 0.01). Serum dehydro-epiandrosterone and dehydroepiandrosterone sulphate were significantly reduced in the cirrhotics (P less than 0.01), whereas serum testosterone was not significantly different from that in the controls. Raised levels of sex-hormone binding globulin were found in 71% (22/31) of the patients (median 8 x 10(-18) mol/l, range 3-17 x 10(-8) mol/l). The incidence of gynaecomastia (38%), cutaneous spiders (67%), testicular atrophy (24%) and reduced axillary hair (71%) was without significant relation to raised levels of sex-hormone binding globulin or progressively reduced liver function. In the presence of clinical or hormonal hypo-gonadism we found evidence of a state of primary hypogonadism together with an inadequate secretion of gonadotropins. The state of hyperoestrogenaemia and the concentration of gonadotropins were significantly correlated to the hepatic synthesis of coagulation factors.     

Alpha1-antitrypsin phenotypes in chronic active liver disease and primary biliary cirrhosis.

Alpha1-antitrypsin concentrations and phenotypes were determined in groups of patients with chronic active liver disease and primary biliary cirrhosis. The concentrations of alpha1-antitrypsin were above normal values in both groups; the patients with primary biliary cirrhosis had higher concentrations than those with chronic active liver disease. The prevalence of common phenotypes in these two groups did not differ from that in a sample of healthy blood donors from this institution of from a large Norwegian sample. We interpret our data as disputing the view that alpha1-antitrypsin phenotypes, other than Z. significantly predispose adults to hepatic cirrhosis.     

Haemodynamic response to exercise in patients with alcoholic liver cirrhosis

Summary. Physical work capacity was evaluated by a multistage bicycle exercise test in 29 patients, 22 men and seven women aged 35–61 years (mean 49) with alcoholic liver cirrhosis and in a sex- and age-matched control group. The maximal work load was reduced in the patient group, mean 122 vs. 186 watts in men (P < 0·001), and 60 vs. 119 watts in women (P < 0·005). Resting heart rate was higher in patients (91 vs. 78 beats × min¹, (P < 0·005), and the maximal heart rate was lower (159 vs. 170 beats × min^-1, (P < 0·001) compared with controls. Thirteen of 29 (45%) patients compared with 5 of 29 (17%) control subjects had an increase in left ventricular ejection fraction of ≤5% during exercise (P < 0·05). The present results suggest that an impaired capacity of the cardiac function to respond adequately to physical stress may at times contribute to the reduced physical work capacity seen in patients with alcoholic liver cirrhosis.     

原发性胆汁性肝硬化患者自身抗体检测的临床意义

目的了解抗线粒体M2亚型抗体（AMA-M2）阳性原发性胆汁性肝硬化（PBC）患者自身抗体的种类和临床意义。方法92例AMA—M2阳性PBC患者,应用间接免疫荧光法,采用肝脏马赛克,包括猴肝和心肌、大鼠肝、胃、肾脏和人类上皮培养细胞（Hep2）为组织基质检测血清中的自身抗体;并用免疫印迹法检测AMA亚型（M2、M4和M9）、可提取的核抗原（ENA）抗体[核糖核蛋白／史密斯抗体（nRNP／Sm）、史密斯抗体（Sm）、干燥综合征抗原A抗体（SS-A）、干燥综合征抗原B抗体（SS-B）、硬皮病70抗体（Scl-70）、Jo-1抗体（Jo-1）、着丝点B蛋白抗体（CENPB）、双链DNA抗体（dsDNA）、组蛋白抗体（histones）和抗核糖核酸P蛋白抗体（rib-Pprotein）]和肝病相关自身抗体。结果92例PBC患者中有73例（79．35％）血清中存在抗核抗体（ANA）;其荧光模式分别为核膜型42例（45．65％）,着丝点型18例（19．57％）,核浆颗粒16例（17．39％）和核点型12例（13．02％）;ENA检测结果：CENPB阳性18例,SSIA阳性6例,SS-A＋SS-B阳性3例,组蛋白抗体和nRNP／Sm阳性各1例;AMA分型检测中单-AMA-M2阳性62例（67．39％）,AMA-M2＋M4阳性26例（28．26％）,AMA—M2＋M4＋M9阳性3例;还发现AMA-M2伴M4阳性的患者全部为疾病进展到肝硬化的阶段。结论大多数PBC患者血清中存在ANA,其荧光模式主要为核膜、着丝点、核浆颗粒和核点型;AMA-M2和M4亚型抗体为诊断PBC的重要血清免疫学标志,并且AMA—M4与疾病进程密切相关。     

Evaluation of rheumatic disorders in patients with primary biliary cirrhosis

Twenty-six consecutive patients with primary biliary cirrhosis (PBC) were subjected to clinical, radiological and serological assessment for evidence of rheumatic disease. Seven patients had asymptomatic liver disease, while the rest had symptoms indicating varying stages of advanced disease. Of the 18 patients with arthropathy, in 13 there was considered to be an association between the arthropathy and PBC as no other underlying causes could be discovered. In about half of the patients the symptoms were episodic, while the others had chronic pain. Usually both large and small joints were affected bilaterally. The joint symptoms had an average duration of 5 years, and had started in all patients after the onset of the liver disease. All 7 patients with arthritis fulfilled the criteria of the American Rheumatism Association for rheumatoid arthritis (RA). Five patients were classified as definite or classical RA. Circulating immune complexes were present in 35% of all patients, but there was no correlation with the presence of arthropathy. Seven patients were HLA-B27 positive, of whom 4 had arthritis. The investigation demonstrates that rheumatic disorders are common in PBC patients, whether or not they are symptomatic, and sometimes joint symptoms may even dominate the clinical picture.     

Abnormal vitamin D metabolism in patients with cirrhosis.

To assess the role of hepatic function and alcohol on vitamin D metabolism, serum 25-hydroxyvitamin D (25-OHD) levels were measured in 20 healthy nonalcoholic control subjects, 31 "inactive" cirrhotics whose alcoholism was in remission, 8 alcoholic cirrhotics, and 15 alcoholics with normal liver function. Cirrhosis but not alcoholism, was assoicated with low serum 25-OHD levels. The aminopyrine breath test (ABT) was performed because aminopyrine, like vitamin D3, is metabolized by hepatic microsomes; the ABT correlated highly (r = 0.74, rho less than 0.01) with serum 25-OHD in the inactive cirrhotics. After an intravenous injection of 120 mug vitamin D3, serum 25-OHD rose significantly within 24 hr in 6 healthy controls and 2 patients with celiac disease but not in 6 inactive cirrhotics. The data suggest impaired 25-hydroxylation of vitamin-D impaired in patients with cirrhosis, related predominantly to the degree of hepatic dysfunction.     

原发性胆汁性肝硬化85例实验室检测指标的分析

目的探讨原发性胆汁性肝硬化(PBC)的免疫学实验诊断特点。方法观察85例PBC患者的临床表现,并分析有关实验室检查资料。结果本组患者临床症状不典型。所有患者γ-谷氨酰转移酶(GGT)升高,98.8%(84/85)的患者碱性磷酸酶(ALP)升高,87.1%(74/85)的患者总胆红素(TB il)和结合胆红素(CB il)升高,81.2%(69/85)的患者丙氨酸转氨酶(ALT)、78.8%(67/85)的患者门冬氨酸转氨酶(AST)、52.9%(45/85)的患者球蛋白(GLB)、95.7%(22/23)的患者总胆汁酸(TBA)、84.0%(21/25)的患者高密度脂蛋白胆固醇(HDL-C)升高。自身抗体检测有59例抗核抗体(ANA)阳性(69%),其中32例为核膜型,20例为着丝点型;85例患者抗线粒体抗体(AMA)均为阳性,其中80例(94.1%)AMA M2阳性。结论PBC无典型性临床症状,医生可以通过临床表现结合AMA,尤其是AMA M2的检测结果获得诊断信息。     

Biochemical testing in patients with alcoholic liver disease

We evaluated physicians' laboratory utilization patterns for hospitalized patients with alcoholic liver disease and examined the relationship between the frequency of test ordering and certain variables in clinical outcome. During the study, 185 patients with alcoholic liver disease were hospitalized 378 times at the VA Medical Center, Long Beach, California. Physicians ordered liver panels (including serum albumin, alkaline phosphatase, total bilirubin, lactic dehydrogenase, glutamic pyruvate transaminase, and glutamic oxaloacetic transaminase) an average of 7.4 times per hospitalization. Increased biochemical testing did not decrease length of stay or improve clinical outcomes such as development of complications or survival of hospitalization. Since the treatment of alcoholic liver disease is largely supportive and not dependent upon frequent biochemical testing, we recommend that these tests be ordered only when patients are admitted to or discharged from the hospital, and when there has been a clinical change.     

原发性胆汁性肝硬化85例实验室检测指标的分析

目的探讨原发性胆汁性肝硬化（PBC）的免疫学实验诊断特点。方法观察85例PBC患者的临床表现,并分析有关实验室检查资料。结果本组患者临床症状不典型。所有患者γ-谷氨酰转移酶（GGT）升高,98．8％（84／85）的患者碱性磷酸酶（ALP）升高,87．1％（74／85）的患者总胆红素（TBil）和结合胆红素（CBil）升高,81．2％（69／85）的患者丙氨酸转氨酶（ALT）、78．8％（67／85）的患者门冬氨酸转氨酶（AST）、52．9％（45／85）的患者球蛋白（GLB）、95．7％（22／23）的患者总胆汁酸（TBA）、84．0％（21／25）的患者高密度脂蛋白胆固醇（HDL-C）升高。自身抗体检测有59例抗核抗体（ANA）阳性（69％）,其中32例为核膜型,20例为着丝点型;85例患者抗线粒体抗体（AMA）均为阳性,其中80例（94．1％）AMAM2阳性。结论PBC无典型性临床症状,医生可以通过临床表现结合AMA,尤其是AMAM2的检测结果获得诊断信息。     

Application of the Mayo primary biliary cirrhosis survival model to Mayo liver transplant patients

Liver transplantation is considered lifesaving for selected patients with end-stage primary biliary cirrhosis (PBC). A mathematical model to predict survival in the patient with PBC who has not undergone transplantation would be valuable for improving selection of patients for and timing of transplantation and for providing control information for assessment of the efficacy of transplantation. The Cox regression method and data from 312 Mayo Clinic patients with PBC were used to develop a model based on age, total serum bilirubin, serum albumin, prothrombin time, and severity of edema. When cross-validated on an independent set of 106 Mayo patients, the model accurately predicted their survival. It was similar to two other published survival models in terms of risk measurement but had the advantage of not necessitating liver biopsy. The model was used to assess the efficacy of liver transplantation by comparing the Kaplan-Meier survival of 32 Mayo patients after transplantation with the average model prediction of survival without transplantation. Beyond 3 months after transplantation, Kaplan-Meier survival probabilities were significantly greater than control survival predicted by the model (P less than 0.001). Examples of using the model for aiding in selection of patients for and timing of transplantation are provided.     

58例原发性胆汁性肝硬化患者抗线粒体抗体和抗核抗体的特征分析

目的 分析原发性胆汁性肝硬化（PBC）患者出现的抗线粒体抗体（AMA）和抗核抗体（ANA）及其特征。方法 对58例确诊的PBC患者采用间接免疫荧光法（IFA）检测AMA、ANA，进一步采用酶联免疫吸附试验（ELISA）和免疫条带法分别检测AMA和ANA的亚型抗体。结果 58例PBC患者AMA抗体均为阳性，89．2％的患者AMA的滴度≥1：320；AMA亚型M2、M4和M9的检出率分别为100％、75．9％和24．1％。M2≥200RU／L的患者丙氨酚转氨酶（ALT）、天冬氨酸转氨酶（AST）、γ-谷氨酰转氨酶（GGT）、碱性磷酸酶（ALP）、总胆红素（TBil）明显高于M2〈200RU／L的患者。M4阳性组ALT、AST明显高于M4阴性组。25．9％的患者出现了ANA，ANA的主要荧光模式为着丝点型11例、核膜型9例、核点型5例，集中出现在AMA高滴度以及M2≥200RU／L的患者。结论 PBC患者一般均有高水平的AMA和M2，且滴度和病情相关。M4、M9在PBC有一定的检出率。多数PBC患者还伴有高滴度的ANA并有主要的荧光模式。     

58例原发性胆汁性肝硬化患者抗线粒体抗体和抗核抗体的特征分析

目的分析原发性胆汁性肝硬化(PBC)患者出现的抗线粒体抗体(AMA)和抗核抗体(ANA)及其特征。方法对58例确诊的PBC患者采用间接免疫荧光法(IFA)检测AMA、ANA,进一步采用酶联免疫吸附试验(ELISA)和免疫条带法分别检测AMA和ANA的亚型抗体。结果58例PBC患者AMA抗体均为阳性,89.2%的患者AMA的滴度≥1∶320;AMA亚型M2、M4和M9的检出率分别为100%、75.9%和24.1%。M2≥200 RU/L的患者丙氨酚转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转氨酶(GGT)、碱性磷酸酶(ALP)、总胆红素(TB il)明显高于M2<200 RU/L的患者。M4阳性组ALT、AST明显高于M4阴性组。25.9%的患者出现了ANA,ANA的主要荧光模式为着丝点型11例、核膜型9例、核点型5例,集中出现在AMA高滴度以及M2≥200RU/L的患者。结论PBC患者一般均有高水平的AMA和M2,且滴度和病情相关。M4、M9在PBC有一定的检出率。多数PBC患者还伴有高滴度的ANA并有主要的荧光模式。     

Paraproteins in primary biliary cirrhosis

Paraproteins have rarely been described in primary biliary cirrhosis. Eighteen patients were identified as having both antimitochondrial antibodies, and a significant paraprotein by screening 950 patients with either a previously known paraprotein or documented antimitochondrial antibodies. The clinical spectrum included 11 patients with proven or probable primary biliary cirrhosis and five with a plasma dyscrasia, of whom two also had primary biliary cirrhosis Antimitochondrial antibody activity appeared polyclonal and unrelated to the paraprotein class. Whilst in patients with primary biliary cirrhosis antimitochondrial antibody activity was predominantly of IgG3 subclass with normal levels, there was no subclass restriction shown in the remainder and IgG3 levels were lowered.