Increased incidence of menstrual abnormalities and hysterectomy preceding primary biliary cirrhosis.

A study was performed to assess the incidence of previous hysterectomy and dilatation and curettage among women with primary biliary cirrhosis. In 87 patients with primary biliary cirrhosis hysterectomy or dilatation and curettage had been performed significantly more often than among 100 age matched normal controls and 80 age matched patients with chronic active hepatitis or alcoholic liver disease. Among the 47 patients with primary biliary cirrhosis who had undergone hysterectomy or dilatation and curettage operations had been performed at a mean of 10.7 years and 13.2 years, respectively, before the onset of disease. The main indication for hysterectomy among patients with primary biliary cirrhosis and controls was menorrhagia. These menstrual disorders may be a consequence of high concentrations of oestrogens in patients with primary biliary cirrhosis.     

Breast cancer in women with primary biliary cirrhosis.

The occurrence of extrahepatic malignancy was studied in 195 unselected patients who satisfied predetermined biochemical, immunological, and histological criteria for the diagnosis of primary biliary cirrhosis. The incidence of breast cancer in women with primary biliary cirrhosis was found to be significantly higher than in an age and sex matched control population from the same well defined geographical area (p less than 0.0015). The association of breast cancer and primary biliary cirrhosis remains unexplained, though diminished immunological surveillance, fat soluble vitamin deficiency, or endocrine dysfunction may play a part.     

Cell-mediated Immune Response in Primary Biliary Cirrhosis to a Protein Fraction from Human Bile

Cell-mediated immune responses to a protein fraction of human bile have been demonstrated, using the leucocyte migration test, in eight out of 10 patients with primary biliary cirrhosis but in only three out of nine with active chronic hepatitis. In the latter condition sensitization to a liver-specific hepatocellular antigen was found more frequently (five out of nine patients) than in primary biliary cirrhosis (two out of 10). These results, as well as the granuloma formation observed histologically, suggest that the initial bile duct lesion in primary biliary cirrhosis may be associated with a cell-mediated response to antigens—perhaps derived from bile duct epithelial cells—which may be normal constituents of hepatic bile.     

Detection of Helicobacter in the liver of patients with chronic cholestatic liver diseases.

Helicobacter species were identified in human liver tissues by PCR. Biopsies were obtained from patients with primary sclerosing cholangitis, primary biliary cirrhosis and noncholestatic liver cirrhosis. One set of Helicobacter genus-specific primers and two different primer sets for Helicobacter pylori were used in the PCR-assays. Using Helicobacter genus-specific primers 80% (8/10) of patients with primary sclerosing cholangitis and 90% (9/10) of patients with primary biliary cirrhosis were positive. Seven of these 17 samples were positive using two different primers for H. pylori and Southern blot hybridization. Among the non-cholestatic liver cirrhosis controls, only one sample was positive in the Helicobacter genus-specific PCR-assay. Significantly higher values of alkaline phosphatases and prothrombin complex was found for the patients positive for Helicobacter genus. In conclusion, gene sequences of Helicobacter species and H. pylori were detected in human liver tissue using PCR and DNA hybridization in patients with a cholestatic liver disease, but rarely in noncholestatic liver cirrhosis.     

“Sicca Complex” in Liver Disease

Sixty-three patients with liver disease were studied for the presence of the components of Sjögren''s syndrome. The “sicca complex” (that is, patients without arthritis) was detected in 42% of patients with active chronic hepatitis, 72% with primary biliary cirrhosis, and 38% with cryptogenic cirrhosis. One patient with active chronic hepatitis and one with primary biliary cirrhosis had rheumatoid arthritis. No evidence of Sjögren''s syndrome was detected in seven patients with alcoholic cirrhosis. It is suggested that the sicca complex and autoimmune liver disease may be part of a systemic disorder in which immunological mechanisms are concerned in the pathogenesis.     

Fibrinolysis in Cholestatic Jaundice

The fibrinolytic system was studied in primary biliary cirrhosis (16 patients) and large bile duct obstruction (10 patients, nine of whom had carcinoma). Plasma fibrinolysis (plasminogen activator activity) was decreased and fibrinogen increased in both groups of patients, particularly in those with large duct obstruction. These changes were related to the degree of cholestasis. Plasminogen activator activity was inversely related to serum triglyceride levels in patients with primary biliary cirrhosis. Urokinase inhibitors were decreased in both groups and antiplasmins increased in patients with large duct obstruction; fibrin/fibrinogen degradation products were normal in primary biliary cirrhosis and moderately increased in large duct obstruction. None of these fibrinolytic indices was related to the degree of cholestasis. Fibrinolytic activity and fibrinogen returned almost to normal levels after palliative surgery in the three patients with large duct obstruction who were studied. The decreased plasma fibrinolysis and increased fibrinogen may be due to altered lipid metabolism in cholestatic jaundice. In patients undergoing surgery for large duct obstruction there may be an increased risk of thrombosis.     

肝纤维化程度及自身抗体表达对熊去氧胆酸单药治疗自身免疫性肝病重 叠综合征患者临床疗效的影响

目的:肝纤维化程度及自身抗体表达对熊去氧胆酸单药治疗自身免疫性肝病重叠综合征患者临床疗效的影响。方法:回顾性收集2007年-2011年住院的20例做过肝穿活检的经熊去氧胆酸单药治疗达到满意效果的自身免疫性肝炎和原发性胆汁性肝硬化重叠综合征患者的临床资料。结果:20例患者中,12例患者(60%)的肝穿标本活检评估处于肝纤维化S3或S4期,其初诊时基线特征与肝纤维化处于S0-S2期的患者基线特征无统计学差异。此外,该20例患者的血清抗平滑肌抗体的阳性率较低(1/20)。结论:肝脏纤维化程度不会引起熊去氧胆酸治疗效果的下降。     

Antimitochondrial antibodies (AMA) in primary biliary cirrhosis. I. Separation of the PBC antigen activity from mitochondrial ATPase activity

Antimitochondrial antibodies are found in a variety of autoimmune liver diseases, particularly primary biliary cirrhosis. The antigen against which these antibodies are directed is localized on the inner mitochondrial membrane. Earlier work suggested that this antigen was associated with the mitochondrial ATPase. However, we have succeeded in separating the enzyme activity from the antigenic activity using gel filtration and ion-exchange chromatography. Furthermore, the antigenic activity is not affected by modulators of ATPase enzymatic activity like aurovertin or oligomycin. The antigenic activity is, however, very susceptible to reagents which block thiol groups. The mitochondrial antigen, in contrast to the ATPase enzyme, is found in high amounts in brown fat mitochondria. Identification of this antigen may help to explain why specific antimitochondrial antibodies arise in the sera of patients with primary biliary cirrhosis.Abbreviations ATPase adenosine triphosphatase - PBC primary biliary cirrhosis - AMA antimitochondrial antibodies - SMPs submitochondrial particles - CFT complement fixation test - SDS sodium dodecyl sulfate - BSA bovine serum albumin - BAT brown adipose tissue     

Use of Computer-assisted Model in Diagnosis of Drug Hypersensitivity Jaundice

Of 374 patients with jaundice seen in the liver unit over a four-year period 21 were finally thought to be hypersensitive to one of seven different drugs. The clinical, laboratory, and histological features were often difficult to distinguish from those of viral hepatitis, tumour of the extrahepatic biliary tree, or primary biliary cirrhosis. A computer-assisted diagnostic model made use of minor differences, and made a correct diagnosis in all patients. Even when information about drug ingestion was left out it was still correct in 81% of patients. Sixty-four other patients gave a history of ingestion of potentially hepatotoxic drugs of whom 62 were correctly diagnosed by the computer. In the complete series of 374 patients only two were incorrectly computed to have drug jaundice when there was no history of drug ingestion.Two additional patients became jaundiced after exposure to drugs, but were found to have primary biliary cirrhosis.     

Primary biliary cirrhosis--an attempt to evaluate the usefulness of selected tests in differential diagnosis]

Seven cases of the primary biliary cirrhosis are presented. The diagnostic problems in early stages of the primary biliary cirrhosis as well as the value of both biochemical and serologic test have been discussed with particular attention to the value of liver biopsy.     

Scleroderma and Primary Biliary Cirrhosis

Two cases of scleroderma and primary biliary cirrhosis are described. One had systemic sclerosis with primary biliary cirrhosis of six years'' duration at the stage of ductular proliferation. The other had the C.R.S.T. syndrome (calcinosis, Raynaud''s phenomenon, sclerodactyly, and telangiectases) with primary biliary cirrhosis at the florid stage. Several similar cases were found in a review of other reports, and it is suggested that the association may be due to a common “autoimmune” process.     

An association between α1-antitrypsin phenotype and chronic liver disease

Summary The phenotypes of alpha-1-antitrypsin have been analyzed by isoelectric focusing on polyacrylamide gels in 232 healthy Japanese blood donors and in 240 Japanese patients with chronic liver diseases: 69 with chronic active hepatitis, 122 with liver cirrhosis, 41 with hepatocellular carcinoma and 8 with primary biliary cirrhosis. The liver cirrhosis patients had a gene frequency of 0.07 forPI ^* M3, which was significantly higher (P<0.01) than that (0.03) in blood donors. The gene frequency of PI ^* M3 was significantly increased in cryptogenic liver cirrhosis (P<0.05), and there was a tendency toward an increased frequency of PI ^* M3 in post-transfusion groups, and in primary biliary cirrhosis. There were also tendenciestoward increased frequencies of PI ^* M3 in cryptogenic and post-transfusion groups of patients with chronic active hepatitis. The present study indicates that PI ^* M3 is a genetic or predisposing factor for chronic liver diseases, especially for cryptogenic and/or non A-non B viral chronic liver disease and also for primary biliary cirrhosis.     

Primary biliary cirrhosis,dark adaptometry,electro-oculography,and vitamin A state.

Twenty five patients with primary biliary cirrhosis were studied for vitamin A state. In nine patients found to have low circulating vitamin A concentrations no abnormality was found on electro-oculography or in dark adaptation. A positive correlation was found between retinol binding protein and vitamin A values (r = +0.88; p less than 0.001) and between serum albumin and vitamin A values (r = +0.75; p less than 0.001). A weaker and negative correlation was found between serum bilirubin (r = -0.47; p less than 0.05) and vitamin A values. Patients with primary biliary cirrhosis should not receive regular parenteral or even oral vitamin A supplementation unless dark adaptometry or electrooculography yields an abnormal result.     

Vitamin A treatment for night blindness in primary biliary cirrhosis.

Three patients with late stage primary biliary cirrhosis were found to have appreciable night blindness. Serum vitamin A concentrations were low in all three patients despite regular intramuscular supplementation in two. All patients responded dramatically to high dose oral supplementation, with full recovery of adaptation to dark and visual fields. Oral rather than intramuscular vitamin A supplementation seems appropriate in the prevention of ocular complications of vitamin A deficiency in biliary cirrhosis.     

Copper and Manganese Concentrations in Biliary Cirrhosis of Liver

The presence of large amounts of copper in the liver in primary biliary cirrhosis has been confirmed; a similar increase is not found in cases of long-standing extrahepatic biliary obstruction. The serum caeruloplasmin levels are raised in primary and secondary biliary cirrhosis, but this increase does not appear to be related to the degree of increase of hepatic copper. The manganese content of the liver is slightly raised in both these conditions.The reason for the increased metal content in these circumstances cannot yet be determined, and the effects are not yet understood.     

原发性胆汁性肝硬化患者临床指标变化与肝脏病理分期的回顾性分析

目的通过肝活检检测原发性胆汁性肝硬化（PBC）患者的病理分期,并对比血生化、自身抗体等指标进一步明确各期的生化特点,便于指导临床。方法所有患者采静脉血检查肝功,自身抗体,免疫球蛋白,所有患者进行肝脏活检,分析其肝脏病理分期。结果 43例患者血清抗线粒体抗体（AMA）及AMA-M2阳性为31例（72.1%）。27例（62.8%）ANA阳性,37例（86.1%）患者血清IgM水平升高。均有肝功能指标的明显异常,以GGT及ALP升高最明显。结论对胆酶增高而原因未明的肝病患者,早期自身免疫抗体及肝脏病理检查对原发性胆汁性肝硬化的诊断及治疗具有临床指导意义。     

Cell-mediated Immune Responses in Chronic Liver Diseases

Studies of the cell-mediated response to liver antigens, using the leucocyte migration test, in 163 patients with various liver disorders showed that abnormal responses were almost confined to active chronic hepatitis (53% abnormal), primary biliary cirrhosis (64%), and cryptogenic cirrhosis (29%). The test was also abnormal in five out of seven patients with jaundice due to drug hypersensitivity and in one patient with acute infectious hepatitis at a time when mitochondrial antibodies were present in the serum. More of those with active chronic hepatitis on prednisone or azathioprine had normal tests than of those who were untreated, and in 8 out of 10 examined serially during therapy there was an accompanying improvement in leucocyte migration. Abnormal responses to salivary gland or kidney antigens were also found in nearly half of those with features of Sjögren''s syndrome or renal tubular acidosis as part of a multisystem involvement—this, though occurring in cryptogenic cirrhosis, was found with greater frequency in active chronic hepatitis and primary biliary cirrhosis. These cell-mediated immune responses, perhaps triggered by the initial damage to the liver from viral or other agents, may be responsible both for the perpetuation of the liver disease and, because of common surface antigens, for the damage to other organs.     

超声对原发性胆汁性肝硬化合并自身免疫性甲状腺炎的诊断价值和相关性分析

摘要 目的：探讨超声对原发性胆汁性肝硬化合并自身免疫性甲状腺炎的诊断价值以及相关性。方法：选取2017年1月~2019年12月我院收治的90例原发性胆汁性肝硬化合并自身免疫性甲状腺炎患者为研究组,根据患者病情的不同将其分为早期组（n=48）和晚期组（n=42）。另选取50例健康志愿者为对照组,对所有患者进行超声诊断,比较两组患者的门静脉血流参数、肝动脉血流参数、肝中静脉血流参数以及脾静脉血流参数。结果：晚期组的门静脉主干内径（portal vein diameter,PVD）明显高于早期组和对照组（P<0.05）,晚期组的平均流速（portal vein velocity,PVV）明显低于早期组和对照组（P<0.05）,三组患者的门静脉血流量（perceptual video quality,PVQ）差异无统计学意义（P>0.05）。晚期组的肝动脉内径（hepatic artery inner diameter,HAD）、阻力指数（resistance index,RI）、收缩期峰值流速（peak systolic velocity/end diastolic velocity,HAVmax）、血流量（blood flow,HAQ）均明显大于对照组（P<0.05）。晚期组的肝中静脉内径（middle hepatic vein diameter,MHAD）、最高平均流速（maximum average flow rate ,MHV Vm）、最大血流量（maximum blood flow,MHVQ）均较早期组和对照组减少（P<0.05）。晚期组的脾静脉内径（splenic vein diameter,SVD）明显高于对照组和早期组（P<0.05）,晚期组的脾静脉平均流速（splenic vein mean flow rate,SVm）、脾静脉血流量 (splenicveinflow, SVF)与对照组、早期组相比差异无统计学意义（P>0.05）;经过相关性分析肝脏超声指标与甲状腺超声指标均呈现正相关关系（P＜0.05）。结论：超声在原发性胆汁性肝硬化合并自身免疫性甲状腺炎患者中应用具有很高的价值,通过对原发性胆汁性肝硬化超声指标推测自身免疫性甲状腺炎病情程度,患者的超声图像具有一定的特征性,可以用以患者的诊断和病因分析,值得在临床中应用推广。     

Primary biliary cirrhosis: an epidemiological study.

A three-year study (1977-9) of primary biliary cirrhosis in the city of Sheffield disclosed 34 cases, a point prevalence of 54 per million population. Closer inspection showed an apparent clustering of cases, and the prevalence in relation to one water reservoir appeared to be more than ten times that of the other reservoirs. Nevertheless, analyses of the water showed no significant relevant differences between the reservoir serving areas with a high prevalence of cirrhosis and other reservoirs. Despite the inconclusive results of the water analyses, these findings do suggest that an environmental agent may be a cause of primary biliary cirrhosis and that further epidemiological studies may help to elucidate the cause.     

Increased prevalence of CFTR mutations and variants and decreased chloride secretion in primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) and cystic fibrosis (CF) are both slowly progressive cholestatic liver diseases characterized by fibro-obliterative inflammation of the biliary tract. We hypothesized that dysfunction of the CF gene product, cystic fibrosis transmembrane conductance regulator (CFTR), may explain why a subset of patients with inflammatory bowel disease develop PSC. We prospectively evaluated CFTR genotype and phenotype in patients with PSC ( n=19) compared with patients with inflammatory bowel disease and no liver disease ( n=18), primary biliary cirrhosis ( n=17), CF ( n=81), and healthy controls ( n=51). Genetic analysis of the CFTR gene in PSC patients compared with disease controls (primary biliary cirrhosis and inflammatory bowel disease) demonstrated a significantly increased number of mutations/variants in the PSC group (37% vs 8.6% of disease controls, P=0.02). None of the PSC patients carried two mutations/variants. Of PSC patients, 89% carried the 1540G-variant-containing genotypes (resulting in decreased functional CFTR) compared with 57% of disease controls ( P=0.03). Only one of 19 PSC patients had neither a CFTR mutation nor the 1540G variant. CFTR chloride channel function assessed by nasal potential difference testing demonstrated a reduced median isoproterenol response of 14 mV in PSC patients compared with 19 mV in disease controls ( P=0.04) and 21 mV in healthy controls ( P=0.003). These data indicate that there is an increased prevalence of CFTR abnormalities in PSC as demonstrated by molecular and functional analyses and that these abnormalities may contribute to the development of PSC in a subset of patients with inflammatory bowel disease.