Primary biliary cirrhosis associated with idiopathic thrombocytopenic purpura

A case of primary biliary cirrhosis (PBC) associated with idiopathic thrombocytopenic purpura (ITP) is reported. The patient is a 59-year-old man. When he was 49 years old, he was diagnosed with ITP and received steroid therapy that successfully increased platelet numbers. However, the steroid therapy failed to normalize the elevated gamma-glutamyl transpeptidase. Ten years after this episode, he suffered from general itching and malaise and exhibited a gradual increase of serum biliary enzyme levels. Immunologically, IgM was increased and anti-mitochondrial antibody was positive. Histological findings of liver needle biopsy showed chronic non-suppurative destructive cholangitis, confirming the diagnosis of PBC. To date, very few PBC cases associated with ITP have been reported. Our case is the second one in Japan. PBC and ITP in our patient seemed to develop simultaneously, but the effect of steroid therapy on the two conditions was different. This result suggests that the autoimmune process may have been different in PBC and ITP in the present patient.     

Laparoscopic Findings in Senescent Patients with Primary Biliary Cirrhosis

Abstract: Fifty -two patients with primary biliary cirrhosis (PBC), 10 of whom were 65 years or older at the time of diagnosis, were investigated by laparo-scopy. Laparoscopic findings in these 10 patients were evaluated and compared with those in younger patients. The 10 cases were composed of nine females and one male, and two had been diagnosed as having symptomatic PBC with skin itching, while the remaining eight had asymptomatic PBC. Two, seven and one case were in Scheuer's stage I, II and III, respectively, and eight had chronic non-suppurative destructive cholangitis (CNSDC) on liver biopsy specimens. The majority of senescent PBC patients had typical findings of the early stage of PBC on the liver surface; mild undulations in nine and reddish patches in eight. The laparoscopic findings in senescent PBC were relatively mild.     

A female with asymptomatic primary biliary cirrhosis associated with pernicious anemia

We experienced a female case with asymptomatic primary biliary cirrhosis that was associated with pernicious anemia after 16 years from the onset. She was 52 years old when she first visited a clinic in 1981 for liver dysfunction treatment. Antimitochondrial antibody was negative and antipyruvate dehydrogenase complex antibody was positive in a low titer in its immunoglobulin (Ig)M type. Histological examination of her liver revealed a presence of definite chronic non-suppurative destructive cholangitis with numerous epithelioid cell granuloma. She had been given 600 mg of the oral daily dose of ursodeoxycholic acid since 1992. Macrocytic anemia incidiously appeared in September 1999. An immunological examination detected negative antiparietal cell antibodies and positive anti-intrinsic factor antibodies. Her bone marrow smear showed numerous megaloblasts and serum vitamin B12 in her blood was low at 99 pg/mL. Severe reversed atrophic-type gastritis (type A gastritis) was demonstrated by the use of dye-endoscopy with Congo red. Her macrocytic anemia dramatically improved after intramuscular administration of vitamin B12. In conclusion, attention should be given to the association of pernicious anemia during the follow up of primary biliary cirrhosis.     

Coexistence of primary biliary cirrhosis and myasthenia gravis: a case study

We present a case that suggests a relationship between primary biliary cirrhosis and myasthenia gravis. A 43-year-old Japanese woman was admitted to the Nagoya City University Medical School, First Department of Internal Medicine with abnormal liver function in August 1991. She had had ptosis of the right eye since 1990. She had not been treated for liver disease. Ptosis of the right eye and hepatomegaly were present. Serum laboratory examinations revealed elevated biliary enzymes and IgM levels; tests were positive for antimitochondrial antibody and antiacetylcholine antibody. Liver histology revealed chronic non-suppurative destructive cholangitis and led to a diagnosis of primary biliary cirrhosis. The tensilon test was positive. Electromyography with repetitive motor nerve stimulation revealed a neuromuscular junction defect; i.e., the primary characteristic of myasthenia gravis. The patient was diagnosed with myasthenia gravis. Although the development of myasthenia gravis has previously been reported in patients with primary biliary cirrhosis during D-penicillamine administration, this is a very rare case of the coexistence of both diseases before such treatment.     

Diagnosis of primary biliary cirrhosis

Primary biliary cirrhosis is the archetypal autoimmune liver disease, with the disease label describing a chronic granulomatous lymphocytic small bile duct cholangitis, which now most commonly presents asymptomatically and at an early pre-cirrhotic stage. Disease is more common than thought, with 1 in 1000 women over the age of 40 affected. Characteristic immunologic features of the disease assist clinicians in ready non-invasive diagnosis of patients, even if asymptomatic with only anicteric/cholestatic liver biochemical profiles. Over 90% of patients are anti-mitochondrial antibody positive, and for those negative, a significant proportion have highly specific anti-nuclear antibody profiles. Liver biopsy remains useful in certain settings where clarity is needed to confirm diagnosis, exclude alternative disease, and assess the relative contribution of PBC to other co-existent liver injury, and seeks to demonstrate in particular the classic bile duct lesions, as well as the degree of interface activity.     

Autoimmune cholangitis in a patient with thymoma

Autoimmune cholangitis is characterized biochemically by chronic cholestasis and histopathologically by chronic non-suppurative destructive cholangitis. It is associated with positive antinuclear antibody test and negative antimitochondrial antibody test results. Recently, we experienced a case of a 35-year-old woman with autoimmune cholangitis associated with thymoma who presented with pruritis, jaundice, chronic fatigue and anterior chest discomfort. Her laboratory examinations revealed marked increases in levels of serum alkaline phosphatase and gamma-glutamyl transpeptidase. In serological tests, antinuclear antibody was found, but antimitochondrial antibody was not. Liver biopsy findings were compatible with chronic non-suppurative destructive cholangitis. On computed tomography (CT) of the chest, a large anterior mediastinal mass was found. The mass was totally resected and the patient was treated with ursodeoxy cholic acid. Thereafter, her clinical symptoms improved and liver functions completely returned to the normal range. We describe here an uncommon association of autoimmune cholangitis with thymoma, which has not been reported previously in the English-written literature.     

Value of laparoscopy in the diagnosis of chronic nonsuppurative destructive cholangitis

39 female and 5 male patients with chronic non-suppurative destructive cholangitis (CNDC), excluding cases with the complete picture of a primary biliary cirrhosis, were examined. Besides clinical and immunological investigations in all patients laparoscopy was performed, in 18 cases repeatedly in order to control the course. As typical laparoscopic appearance in 43 of the cases we saw geographically outlined and generally communicating areas on the liver surface within somewhat brighter surroundings ("map-like-phenomenon"). Besides this a darker coloration in the center of the liver lobules was significant ("leopard skin-phenomenon"). Regarding the size, the consistency, the shape of the edge, and the structure of the surface of the liver we determined different stages of the disease. Our scale showed a good correlation to the copper-content of the liver, but did not always correlate to Scheuer's histological scheme. The significant uncertainties of histopathological interpretations of the findings in early stages of CNDC as well as differential diagnostic considerations are discussed. According to our results we believe that laparoscopy can significantly contribute to solve the diagnostic problems.     

Is mitochondrial antibody diagnostic of primary biliary cirrhosis?

In a series of 218 patients diagnosed as having primary biliary cirrhosis only nine exhibited a negative serum mitochondrial antibody. On examining additional specimens from these patients, seven were found to be positive, giving a final incidence of greater than 99%. The two patients whose sera remained negative for the mitochondrial antibody had liver histology compatible with the diagnosis of primary biliary cirrhosis, but a firm diagnosis could not be reached. Three additional mitochondrial antibody positive subjects who were asymptomatic and exhibited normal serum alkaline phosphatase were shown on liver biopsy to have stage I primary biliary cirrhosis. The presence of a positive serum mitochondrial antibody in a patient with or without abnormalities in liver function tests strongly suggests the diagnosis of primary biliary cirrhosis.     

临床病理学在自身免疫性肝病诊治中的重要性

肝脏组织学在自身免疫性肝病的诊断中起着重要作用,尤其是临床表现非特异、自身抗体阴性的患者。介绍了几种自身免疫性肝病在组织学上的特征性表现。自身免疫性肝炎(AIH)的特征性表现包括界面性肝炎伴淋巴-浆细胞浸润、玫瑰花环及穿入现象,而慢性非化脓性胆管炎、上皮样肉芽肿常提示原发性胆汁性肝硬化(PBC)。胆管周围洋葱皮样纤维化是原发性硬化性胆管炎(PSC)特征性表现,席纹状纤维化伴IgG4阳性浆细胞浸润常须考虑为IgG4相关硬化性胆管炎。最后指出,在日常工作中,临床医生和病理医生加强沟通有利于提高自身免疫性肝病的诊治。     

Primary and secondary autoimmunity in hepatology

Primary autoimmune liver diseases can be hepatitic or cholestatic in nature. Autoimmune hepatitis, more often diagnosed in women, is characterized by biochemical and histological activity, with polyclonal hypergammaglobulinemia as a frequent feature. Antinuclear and anti-smooth muscle antibodies are the serological hallmarks of type 1 autoimmune hepatitis, whereas liver-kidney microsomal antibody type 1 and liver cytosol antibody type 1 designate the type 2 form. Response to immunosuppression is usually excellent. The most frequent cholestatic autoimmune disease is primary biliary cirrhosis, characterized by anti-mitochondrial antibody positivity and typical bile duct lesions observed on liver biopsy. Treatment with biliary acids improves the biochemical picture, may alleviate pruritus, and delays the development of end-stage liver disease. Primary sclerosing cholangitis occurs more frequently in men and affects both the intra- and extrahepatic biliary trees, determining the typical "beading" appearance. Associated inflammatory bowel diseases are often observed. To date, no medical therapy is able to modify the course of this disease. Autoimmune cholangitis is an anti-mitochondrial antibody-negative cholestatic disease with most of the features of primary biliary cirrhosis. "Overlap" syndromes where autoimmune hepatitic and cholestatic features coexist in the same patient, have also been reported. Autoimmune phenomena secondary to hepatitis C virus-related liver disease such as the occurrence of antinuclear, anti-smooth muscle antibodies and liver-kidney microsomal antibody type 1 are often observed.     

Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases

Background/AimPlasma cells infiltrate in the liver is a prototype lesion of autoimmune liver diseases. The possible role of plasma cells isotyping (IgM and IgG) in the liver in the diagnostic definition of autoimmune liver disease, and particularly in variant syndromes such as autoimmune cholangitis and the primary biliary cirrhosis/autoimmune hepatitis overlap syndrome, is less defined.MethodsWe analysed the clinical, serological and histological features of 83 patients with autoimmune liver disease (40 primary biliary cirrhosis, 20 autoimmune hepatitis, 13 primary sclerosing cholangitis, 4 autoimmune cholangitis and 6 overlap syndrome) compared to 34 patients with chronic hepatitis C and evaluated the expression of IgM and IgG plasma cells in their liver by immunostaining.ResultsBy Spearman's correlation, the mean-counts of IgM plasma cells in portal tracts were significantly correlated with female gender, serum alkaline phosphatase, gamma-glutamyl transferase and IgM values, positivity for anti-mitochondrial antibody-M2 and, on liver biopsy, with bile duct changes, orcein-positive granules and granulomas. Whereas IgG plasma cells resulted more correlated with alanine aminotransferase levels. IgG/IgM ratio lower than 1 was found no only in primary biliary cirrhosis but also in all patients with autoimmune cholangitis. Conversely, all patients with overlap syndrome showed IgG/IgM ratio higher than 1.ConclusionImmunostaining for IgM and IgG plasma cells on liver tissue can be a valuable parameter for better diagnosis of autoimmune liver disease and also for variant or mixed syndromes.     

Primary biliary cirrhosis associated with type A gastritis and chronic thyroiditis

We report a patient with primary biliary cirrhosis (PBC) associated with type A gastritis, chronic thyroiditis, and iron deficiency anemia. The patient was a 45-year-old Japanese woman who was admitted to our hospital with severe microcytic and hypochromic anemia, abnormal results for liver function tests, and a diffuse goiter. The diagnosis of PBC (Scheuer's stage II) was confirmed by the presence of specific anti-mitochondrial antibody in high titers and histological examination showing chronic non-suppurative destructive cholangitis with bridging fibrosis. Additionally, marked atrophic mucosa throughout the body and fundus of the stomach was observed endoscopically, and there was positivity for intrinsic factor antibody, an extremely low ratio of serum pepsinogen A to C, and hypergastrinemia, indicating coexisting type A gastritis. The severe anemia was thought to be caused by failure of dietary iron absorption related to achlorhydria with this gastritis. However, the serum level of vitamin B₁₂ was normal. She also had autoimmune thyroiditis. PBC is frequently associated with extrahepatic autoimmune diseases, including ductular lesions. However, the association of PBC with type A gastritis is quite rare, although the stomach is also an exocrine glandular structure. This particular case, in addition to previous reports, leads to a discussion of whether type A gastritis should be regarded as a possible, although uncommon, component disorder of so-called dry gland syndrome. Received: July 8, 1998/Accepted: November 27, 1998     

Celiac disease-associated autoimmune cholangitis

There is an association between celiac disease (CD) and primary biliary cirrhosis, but there is little information regarding the association between CD and autoimmune cholangitis (antimitochondrial antibody-negative primary biliary cirrhosis). We describe a case of a 60-yr-old woman with chronic serum liver biochemistry elevations, recent onset of pruritus, and unexplained iron deficiency anemia. Liver biopsy was suggestive of stage 1 primary biliary cirrhosis, but serum antimitochondrial antibody testing was negative. Subsequent evaluation revealed CD based on markedly elevated antiendomysial antibody titers and characteristic histological features on mucosal biopsies. Initiation of a gluten-free diet led to resolution of iron deficiency anemia, pruritus, and elevated serum liver biochemistries. This suggests that CD may play a direct role in the development of autoimmune cholangitis. Additionally, normalization of hepatic biochemistries may be achieved without the use of immunosuppressive agents in some patients. CD should be considered in all patients diagnosed with autoimmune cholangitis as a gluten-free diet may avoid the need for immunosuppressive therapy in affected patients.     

Association cirrhose biliaire primitive et maladie de Biermer. �� propos d��une nouvelle observation

Primary biliary cirrhosis is often associated with autoimmune diseases. However, its association with pernicious anemia has rarely been reported. We report a case of a 68-year-old woman who presented jaundice and pruritus. Mildly elevated serum levels of alkaline phosphatase and g-glutamyl transpeptidase were detected. The titer of anti-mitochondrial M2 antibody was elevated. Histology of liver biopsy showed features of primary biliary cirrhosis. She presented also a macrocytic anemia. The diagnosis of pernicious anemia was confirmed by the low level of serum vitamin B12 and the presence of anti-parietal cell antibody and anti-intrinsic factor antibody. The association of primary biliary cirrhosis and pernicious anemia may be explained by an autoimmune mechanism commonly shared by the two diseases.     

Elevation of serum eosinophil cationic protein in primary biliary cirrhosis

It has recently been reported that in patients with primary biliary cirrhosis (PBC), eosinophils are not only increased in the peripheral blood, but also infiltrted in the liver portal tracts. There is general agreement that eosinophils and eosinophil cationic protein (ECP) released from eosinophils contribute to cellular damage, particularly in allergic inflammation. In the present study, ECP was measured by the radioimmunoassay in sera of patients with a variety of liver diseases including PBC. Serum ECP levels were significantly higher in patients with PBC than in those with chronic viral hepatitis, in those with liver cirrhosis, and in healthy subjects. There were no significant differences in serum ECP levels between symptomatic and asymptomatic PBC. The present study suggests that high levels of serum ECP may reflect high grades of eosinophil infiltration around the septal and interlobular bile ducts characterized by chronic non-suppurative destructive cholangitis, particularly in the early stages of PBC.     

Manifestations of nonsuppurative cholangitis in chronic hepatobiliary diseases: morphologic spectrum, clinical correlations and terminology

The features of nonsuppurative cholangitis were studied in liver biopsy specimens from 185 patients with chronic active hepatitis (CAH), 280 patients with primary biliary cirrhosis (PBC), and 55 patients with primary sclerosing cholangitis (PSC). Specimens from patients with other liver diseases in which the presence of nonsuppurative cholangitis had been recorded were also studied. We identified four types of nonsuppurative cholangitis: granulomatous cholangitis, lymphoid cholangitis, fibrous cholangitis, and pleomorphic cholangitis. Granulomatous cholangitis almost always seemed to be destructive; the other types were either destructive or nondestructive. Granulomatous cholangitis was, for all practical purposes, diagnostic of PBC and the obliterative form of fibrous cholangitis was similarly diagnostic for the hepatic manifestations of PSC in adults and paucity of intrahepatic bile ducts in infants. All other types of cholangitis were found in CAH, PBC, PSC, and other liver diseases. Thus, the term "nonsuppurative cholangitis" describes a spectrum of morphologic lesions that differ in incidence, morphogenesis, usefulness for liver biopsy diagnosis, and, probably, pathogenesis.     

Primary biliary cirrhosis

Primary biliary cirrhosis is a chronic cholestatic liver disease of adults. This disorder is characterised histologically by chronic non-suppurative destruction of interlobular bile ducts leading to advanced fibrosis, cirrhosis, and liver failure. The precise aetiopathogenesis of primary biliary cirrhosis remains unknown, although dysregulation of the immune system and genetic susceptibility both seem to be important. Affected patients are typically middle-aged women with abnormal serum concentrations of alkaline phosphatase. Presence of antimitochondrial antibody in serum is almost diagnostic of the disorder. Identification of primary biliary cirrhosis is important, because effective treatment with ursodeoxycholic acid has been shown to halt disease progression and improve survival without need for liver transplantation. However, therapeutic options for disease-related complications-including fatigue and metabolic bone disease-remain unavailable. Mathematical models have been developed that accurately predict the natural history of primary biliary cirrhosis in individuals. Despite advances in understanding of the disease, it remains one of the major indications for liver transplantation worldwide.     

Multiple myeloma of IgG-lambda type associated with asymptomatic primary biliary cirrhosis

Multiple myeloma associated primary biliary cirrhosis (PBC) is very rare and only two cases have been reported. In this paper, we reported the first case of male patient with asymptomatic PBC and multiple myeloma. A 66 year-old Japanese male was referred to our hospital for the further examination of a monoclonal gammopathy. He was diagnosed of multiple myeloma (IgG-lambda type) because of 2.3 g/day of Bence Jones proteinuria (lambda type), 3,401 mg/dl of monoclonal IgG (lambda type), 12.8% of bone marrow plasmocytosis and generalized osteoporosis. The alkaline phosphatase was 314 mU/ml and serum IgM level (polyclonal) 937 mg/dl. The patient was started on intermittent courses of melphalan and prednisolone, achieving transient improvement. After two years, hepatosplenomegaly developed gradually and the levels of serum ALP elevated increasingly. At that time, relevant investigation results were: serum ALP 663 mU/ml, serum IgG 4,144 mg/dl, serum IgM 823 mg/dl, positive anti-mitochondrial antibody test x 320. The liver biopsy showed chronic nonsuppurative destructive cholangitis. PBC (stage 1-2 according to Sheuer's criteria) associated with multiple myeloma was diagnosed. A pathogenetic relationship such as loss of immunoregulatory function could be speculated although the simultaneous occurrence of PBC and multiple myeloma could be coincidental.     

Hepatocellular carcinoma arising in an elderly male with primary biliary cirrhosis

We report the case of an elderly male with asymptomatic primary biliary cirrhosis (PBC) who developed a hepatocellular carcinoma (HCC). The 89-year-old man, who was otherwise healthy, was admitted for investigation of mild hepatic dysfunction, which had been detected during a routine physical check-up. Serum chemistry, positive anti-mitochondrial antibody (M2) and liver biopsy results led to a diagnosis of PBC. Three years later, at age 92, computed tomography (CT) and ultrasound scans of his abdomen revealed a large hepatic tumour, which was confirmed on liver biopsy to be HCC. The tumour ruptured 3 months after diagnosis and the patient was successfully stabilized by coil embolization of his right hepatic artery. We believe that, to date, this is the oldest reported patient to have had interventional radiology for the management of HCC.     

Production of histological changes mimicking primary biliary cirrhosis in rabbits by immunization with bile duct antigen

Histopathological liver changes resembling primary biliary cirrhosis were induced in an experimental animal model. A special strain of rabbit received an antigen prepared from scrapings of bovine gallbladder mucosa. Eventually, 47 out of 84 antigen-treated rabbits displayed histopathological liver features resembling those of chronic non-suppurative destructive cholangitis as seen in humans. In addition, granuloma formation, ductular proliferation and fibrosis were seen in some cases. However, advanced lesions consistent with micronodular cirrhosis have not been found. Lymphocytes seemed to play an important role triggering early pathogenetic mechanisms, judging from the presence of lymphocytes invading the basement membrane of the affected bile ducts. Furthermore, we observed by electron microscopy that the epithelial cells of the involved bile ducts revealed both mitochondrial swelling and dilatation of endoplasmic reticulum cisternae. In summary, our experimental animal model offers interesting possibilities regarding the study of pathogenesis and development of primary biliary cirrhosis.