Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked

We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sj?gren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Portal hemodynamics in primary biliary cirrhosis as evaluated by per-rectal portal scintigraphy with Tc-99m pertechnetate

BACKGROUND/AIMS: Portal circulation can be evaluated in a relatively noninvasive manner by per-rectal portal scintigraphy. We used this method to evaluate portal hemodynamics in patients with primary biliary cirrhosis and idiopathic portal hypertension. We did the procedures simultaneously in some patients to examine the relation between portal circulation and hepatic functional reserve in these diseases. METHODOLOGY: Per-rectal portal scintigraphy with Tc-99m pertechnetate was done in 17 healthy subjects, 154 patients with chronic hepatitis, 447 patients with cirrhosis, 40 patients with primary biliary cirrhosis, and 20 patients with idiopathic portal hypertension. Eighty-three patients (14 with hepatitis, 48 with cirrhosis, 16 with primary biliary cirrhosis, and 5 with idiopathic portal hypertension) also underwent scintigraphy with Tc-99m galactosyl human serum albumin with 2 weeks. A solution containing Tc-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. The per-rectal portal shunt index was calculated from the curves. A receptor index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest 15 min after the injection of Tc-99m galactosyl human serum albumin. The index of blood clearance was calculated by dividing the radioactivity of the heart region of interest at 15 min by that of the heart region of interest at 3 min. RESULTS: The shunt index was higher for more severe disorders, increasing in the order of chronic hepatitis, cirrhosis without varices, and cirrhosis with varices. The shunt indices in patients with primary biliary cirrhosis and idiopathic portal hypertension were higher than that in patients with chronic hepatitis. In terms of receptor index, the standard residuals were more than 0 in 10 of 16 patients with primary biliary cirrhosis and 4 of 5 patients with idiopathic portal hypertension. In terms of index of blood clearance, the standard residuals were more than 0 in 10 of 16 patients with primary biliary cirrhosis and 4 of 5 patients with idiopathic portal hypertension CONCLUSIONS: Abnormalities of portal hemodynamics in patients with primary biliary cirrhosis or idiopathic portal hypertension occur while hepatic functional reserve is still satisfactory as compared with patients who have chronic hepatitis or cirrhosis.     

Histological and Histometric Examination of the Intrahepatic Portal Vein Branches in Primary Biliary Cirrhosis without Regenerative Nodules

Histometric examination, based on the assumption that ratios of the sizes of portal vein branches to the sizes of the accompanying hepatic arterial branches in the portal tracts are relatively constant in normal livers, indicated that in primary biliary cirrhosis without regenerative nodules, lumens of the intrahepatic portal veins were narrowed and phlebosclerosis was frequent in patients with esophageal varices. Thus, each of these lesions of the intrahepatic portal veins might be related to the development of the presinusoidal portal hypertension that occurs in primary biliary cirrhosis without regenerative nodules. However, the exact causal relationship of this portal venopathy and the development of portal hypertension remains unknown. Damage to the intrahepatic bile ducts in primary biliary cirrhosis, associated with portal and periportal inflammation, may contribute to the development of the morphological lesions of the intrahepatic portal veins. Furthermore, spongiomatous vasculatures found around the larger portal veins, but not those around the smaller veins, appear to be related to the presence of esophageal varices.     

Portal hypertension in primary biliary cirrhosis: Relationship with histological features

The prevalence and type of portal hypertension (PH) in primary biliary cirrhosis (PBC) and their relationship with liver lesions have been investigated in 32 patients with the disease. Portal hypertension was considered when oesophageal or gastric varices were observed by endoscopy and/or when hepatic venous pressure gradient measured by hepatic vein catheterization was greater than 6 mmHg. Within 3 days of endoscopy, a liver biopsy was performed for histological staging and semiquantitative grading (0 to 3+) of portal and sinusoidal fibrosis, portal inflammation, piecemeal necrosis, lobular necrosis, cholestasis, as well as the presence of granulomas and Mallory's hyaline. Twenty patients (62.5%) had portal hypertension, five of them showing presinusoidal PH (15.5%) and the remaining 15 (47%) with sinusoidal component. The four patients in stage IV had sinusoidal PH and the only patient in stage I had no PH. The prevalence of portal hypertension was similar in patients in stage II (57%) and stage III (55%), but presinusoidal PH was only observed in patients in stage II. Patients with PH showed significantly higher portal inflammation and piecemeal necrosis than patients without PH. By contrast, there were no differences in portal and sinusoidal fibrosis, nor in the other histologic features. These results indicate that portal hypertension is common in PBC and it may be present in the early stages of the disease. The fact that presinusoidal PH was only observed in patients in stage II suggests that portal hypertension is initially of presinusoidal type, and then as the disease progresses is joined by a sinusoidal component.     

Nodular Hyperplasia of the Liver in Primary Biliary Cirrhosis of Early Histological Stages

Twenty-six patients with the clinical and histologic diagnosis of primary biliary cirrhosis were reviewed. Nodular hyperplasia of the liver without fibrous rims, not reported hitherto in patients with primary biliary cirrhosis, was found in several patients with early histological stages. These changes resembled "nodular regenerative hyperplasia of the liver" and were usually present as multicellular thickness in zones 1 and 2 of the hepatic lobules. Such lesions were preferentially found in patients with esophageal varices, suggesting that the nodular hyperplasia may occur in relation to a disturbance of portal venous blood flow within the liver in primary biliary cirrhosis in early histological stages.     

Primary biliary cirrhosis: current modes of presentation. Clinical, biochemical, immunologic and histologic study of 206 patients seen from 1978 to 1988

The aim of this study, based on a series of 206 patients (186 women and 20 men) with primary biliary cirrhosis seen from 1978 to 1988, was to assess the current modes of presentation of the disease. In approximately 30 percent of patients, primary biliary cirrhosis was recognized at an asymptomatic stage. Two thirds of these patients remained asymptomatic: they were older (mean age 57 years) and had less severe histological lesions than the patients who became symptomatic (mean age 45 years). The modes of presentation were not markedly different in the male and female patients of our series. The prevalence of cholelithiasis seemed to be particularly high (more than 20 percent in our patients). Complications of portal hypertension (bleeding esophageal varices or ascites) were the initial manifestations of primary biliary cirrhosis in 8 percent of our symptomatic patients. Alkaline phosphatase level was normal or only slightly increased in 15 percent of our patients: a normal level or a slight increase in alkaline phosphatases is not an argument against the diagnosis of primary biliary cirrhosis. Antinuclear antibodies with perinuclear fluorescence were demonstrated in 26 percent of our patients; in most of these patients, an antibody to a 200 kD protein of the nuclear envelope was present; in patients with this antibody, asthenia, arthralgias and associated extrahepatic diseases were less common and the titers of antibodies to mitochondria were lower than in the patients without this antibody.     

原发性胆汁性肝硬化患者食管静脉曲张程度与肝功能评价的相关性研究

目的 探讨原发性胆汁性肝硬化食管静脉曲张程度与门脾静脉内径、肝功能Child-Pugh分级,Meld评分间的关系.方法 对2008年9月至2011年5月间选择92例原发性胆汁性肝硬化患者行增强CT,测量门静脉主干及脾门部脾静脉直径,行胃镜了解食管静脉曲张的程度,并对其中44例出现过静脉曲张破裂出血患者采用Child-Pugh分级,Meld评分标准进行肝功能分级.结果 食管静脉曲张程度与门静脉内径（P =0.018）、脾静脉内径（P=O.O02）呈正相关,而Child-Pugh分级（P＞0.05）,Meld评分（P＞0.05）则与食管静脉曲张程度无相关性.结论 根据门、脾静脉内径可预测原发性胆汁性肝硬化的食管静脉曲张程度;而Child-Pugh分级,Meld评分对患者的食管静脉曲张程度及出血风险不能进行有效评估.     

Idiopathic Portal Hypertension Associated with Hashimoto''s Disease: Report of Three Cases

Three cases of idiopathic portal hypertension associated with Hashimoto's disease are described. All of the cases were middle-aged Japanese women showing splenomegaly, esophageal varices and pancytopenia in the absence of extrahepatic portal obstruction, and cirrhosis of the liver. Two patients were euthyroid with goiter, one of which revealed diffuse lymphocytic infiltration, obliteration of thyroid follicles, and fibrosis on histological examination of the thyroid; the third suffered from myxedema without goiter. Antithyroid microsomal antibody was positive in all patients and antithyroglobulin antibody was positive in none. These findings might imply an immunological role in the pathogenesis of idiopathic portal hypertension.     

Gastroduodenal and intestinal permeability in primary biliary cirrhosis

OBJECTIVES: To evaluate gastrointestinal permeability in primary biliary cirrhosis (PBC), using a sensitive method to detect epithelial damage, and to correlate it with the Mayo score, histological stage, ascites, spontaneous bacterial peritonitis, endoscopic signs of portal hypertension and Helicobacter pylori infection. METHODS: Fifty consecutive patients with PBC and 39 patients with cirrhosis of other aetiologies (non-PBC) were enrolled in the study. Coeliac disease was initially ruled out in all participants. Permeability was assessed using sucrose (gastro-duodenum) and lactulose-mannitol (intestine). RESULTS: Sucrose excretion was above the limit in both PBC and non-PBC patients. Twenty-two per cent of PBC patients had an increased result for the lactulose-mannitol test compared to 12.8% of non-PBC cirrhotic patients. PBC patients had high sucrose excretion levels irrespective of the presence of any oesophageal varices, which significantly increased the gastroduodenal permeability in non-PBC patients only when associated with hypertensive gastropathy. Sucrose excretion was significantly enhanced by hypertensive gastropathy in non-PBC patients (P < 0.001) but not in PBC patients. No significant correlation was found in either group between gastrointestinal permeability and the other parameters. CONCLUSIONS: Gastrointestinal permeability is increased in PBC. Portal hypertension contributes to altered gastric mucosal permeability in non-PBC cirrhosis, whereas different epithelial dysfunction can be hypothesized in PBC.     

A case of gastric adenocarcinoma presenting as portal hypertension

Portal vein thrombus has been detected in patients with liver cirrhosis, pancreatitis, ulcerative colitis, septicemia, myeloproliferative disorder, and neoplasm. The formation of portal tumor thrombus by hepatocellular carcinoma is well recognized, because of its high incidence, and subsequent development of portal hypertension such as rupture of varices, ascites and liver failure indicates the poor prognosis. In gastric cancer, portal hypertension as an initial presentation is extremely rare. Herein we report a case presenting as portal hypertension caused by tumor thrombus without invasion of liver parenchyma. It is presumed to be intraluminal tumor thrombus originating from primary foci of gastric adenocarcinoma. Tumor thrombus in the portal vein is demonstrated on the PET-CT.     

Role of liver atrophy, hepatic resection and hepatocyte hyperplasia in the development of portal hypertension in biliary disease.

Portal fibrosis is considered to be pivotal in the pathogenesis of portal hypertension associated with extrahepatic biliary obstruction. The histological features, however, include diffuse hepatocyte hyperplasia as well as portal fibrosis, but not cirrhosis, and it is possible that the contribution of hepatocyte hyperplasia in the initiation of portal hypertension is equally important. If so, we hypothesised that patients with biliary obstruction and a coincident condition such as liver atrophy, or hepatic resection, with the potential of accelerating the hepatocyte proliferation caused by biliary obstruction itself, might be expected to develop portal hypertension earlier than patients with biliary obstruction alone. To examine this concept we studied 10 patients with postcholecystectomy bile duct stricture, portal hypertension and liver atrophy, or hepatic resection (group I) and compared them with nine patients with postcholecystectomy stricture and portal hypertension, but no atrophy or resection (group II). Portal hypertension was diagnosed a mean 28 months (range 18-48 months) after cholecystectomy in group I compared with 62 months (range 36-100 months) for patients in group II (p less than 0.005 Mann-Whitney test). Thus hepatocyte hyperplasia may be an important part of the mechanism underlying the development of portal hypertension in chronic biliary disease.     

Observation of thoracic duct morphology in portal hypertension by endoscopic ultrasound

Background:Thoracic duct dilation has been demonstrated in portal hypertension and hepatic cirrhosis by lymphangiography and laparotomy and at autopsy. It is thought to be secondary to increased hepatic lymph flow and has been described in the absence of ascites or esophageal varices. The aim of the present study was to observe thoracic duct morphology by endoscopic ultrasound in various subsets of patients with portal hypertension and hepatic cirrhosis and also to validate existing radiologic/surgical data. Methods:The thoracic duct of 33 patients with cirrhosis and portal hypertension was studied by endoscopic ultrasound. Patients were divided into four groups: 1, patients with ascites and esophageal varices; 2, esophageal varices without ascites; 3, without esophageal varices or ascites; 4, extrahepatic portal hypertension due to pancreatic malignancy. The thoracic duct diameter was also measured in 14 control subjects (group 5). Results:When the thoracic duct diameter for the five groups was compared with analysis of variance, significance was p < 0.0001; by pairwise comparison, group 1 differed from the other four groups (p < 0.05). Thoracic duct dilation (5.61 mm) was seen in group 1 patients, whereas no dilation was present in groups 2 through 4. Additionally, thoracic duct diameter in 33 portal hypertensive and/or cirrhotic patients was significantly different from that in the 14 control subjects (p = 0.003). Conclusion:The thoracic duct can be reliably identified by EUS in patients with hepatic cirrhosis and portal hypertension. Dilation of the duct is seen only in patients with hepatic cirrhosis, ascites, and esophageal varices. No thoracic duct dilation is present in extrahepatic portal hypertension. Contrary to existing radiologic/surgical data, thoracic duct dilation is not seen in all patients with hepatic cirrhosis and portal hypertension signifying advanced disease. A dilated thoracic duct by endoscopic ultrasound should be considered yet another sign of portal hypertension. (Gastrointest Endosc 1998;48:588-92.)     

左侧门静脉高压的临床和内镜特征

目的 探讨左侧门静脉高压的临床特点和内镜特征。方法 对手术证实的8例左侧门静脉高压患者的临床资料进行回顾性分析。结果 左侧门静脉高压的临床表现主要为呕血、黑便和脾大、脾功能亢进，患者具有胰腺疾病的特点，而无肝脏疾病的表现和检查异常。内镜下以孤立性胃底静脉曲张为主，占62．5％；食管、胃底静脉同时曲张占37．5％。术前易误诊为血液系统疾病和肝硬化门静脉高压。结论 胰腺疾病可致门静脉高压，孤立性胃底静脉曲张是左侧门静脉高压的的特征性表现之一。     

Immunohistochemical differences in the portal tract and acinar infiltrates between primary biliary cirrhosis and autoimmune cholangitis

BACKGROUND: Antimitochondrial antibody-negative primary biliary cirrhosis, or autoimmune cholangitis, may be indistinguishable clinically and histologically from antimitochondrial antibody-positive primary biliary cirrhosis. AIMS: We aimed to compare the phenotypic markers of the portal and acinar infiltrates in autoimmune cholangitis and antimitochondrial antibody-positive primary biliary cirrhosis. PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded liver sections were identified from 32 patients with a clinical and histological diagnosis of primary biliary cirrhosis. Thirteen were antimitochondrial antibody-negative (autoimmune cholangitis group) and 19 were antimitochondrial antibody-positive. The groups were well matched for age, histological stage, liver biochemistry and drug treatment. Immunohistochemical staining was performed using monoclonal antibodies against CD3 (pan T cell), CD8 (cytotoxic), CD45RO (memory), CD45RA (naive), CD68 (macrophages) and against the secreted form of eosinophilic cationic protein (EG2). RESULTS: In autoimmune cholangitis, both portal and acinar CD3 cell counts were significantly higher than in antimitochondrial antibody-positive primary biliary cirrhosis (median portal count 421 vs 257 cells/graticule, P< 0.03; median acinar count 18 vs 9 cells/graticule, P< 0.02). There were no differences between the groups in portal or lobular CD8, CD45RO, CD45RA, CD68 or EG2. Of the total group (antimitochondrial antibody positives and negatives), there were significantly more CD45RA cells in early (stage 1) compared with cirrhotic (stage 4) disease (median 19.3 vs 14 cells/graticule, P< 0.03). EG2 staining was found in eight of the 32 sections overall, but not in the patients with stage 1 disease (P< 0.04). CONCLUSION: CD3 counts are higher in autoimmune cholangitis than in antimitochondrial antibody-positive primary biliary cirrhosis in both portal and acinar areas. However, there are no significant differences in memory/na?ve T-cell subsets between both conditions and, in both, loss of naive T lymphocytes and secretion of eosinophilic cationic protein occur with disease progression. This implies that the effector pathways of bile duct destruction are similar in autoimmune cholangitis and primary biliary cirrhosis.     

Primary biliary cirrhosis: lung involvement

Abstract: Sub-clinical lung impairment, mostly represented by a reduced diffusion of alveolar gases, is a recognised complication of advanced primary biliary cirrhosis. The aim of the study was to evaluate the prevalence and type of pulmonary involvement in primary biliary cirrhosis and the relationship between lung function abnormalities and selected epidemiological and clinical variables. Sixty-one patients with different stages of primary biliary cirrhosis consecutively seen in our outpatient clinic were evaluated. The advancement of primary biliary cirrhosis was characterised by the histological stage, the presence of signs of portal hypertension and the Mayo Risk Score: a Cox regression model using serum bilirubin and albumin levels, prothrombin time, age and degree of oedema as selected variables. We measured static and dynamic lung volumes, by means of a spirometer, and diffusing capacity for carbon monoxide. Rheumatological disorders were evaluated by an independent rheumatologist. No patient complained of respiratory symptoms. Airway obstruction was present in one patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did not find any significant relationship between diffusing capacity and smoking habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced diffusion capacity showed a significant correlation with the presence of complete or incomplete CREST syndrome (p<0.01) and with the presence of circulating anti-centromere antibodies (p<0.05). Alveolar diffusion capacity is frequently impaired in patients with primary biliary cirrhosis, usually in the absence of clinical manifestations. These alterations mostly affect patients with concomitant CREST syndrome. Prospective studies are needed to evaluate if these abnormalities will eventually lead to clinical symptoms and if their progression could be influenced by different therapeutic regimens for primary biliary cirrhosis.     

Portal hypertension and primary biliary cirrhosis.

Portal hypertension has been regarded as an uncommon and late complication of primary biliary cirrhosis (PBC). 24 patients with PBC were investigated for portal hypertension. Esophageal varices were present in 20, 50, and 90% of the patients 1, 3, and 9 years, respectively, after the onset of pruritus and/or jaundice. Portal hypertension was responsible for gastrointestinal bleedings in 11 patients; bleeding was the first clinical manifestation of PBC in two of them. Wedged hepatic venous pressure was increased in all the patients with portal hypertension whether regenerative nodules were present or absent. Portacaval shunt was performed in five patients and was well tolerated in three of them. It is concluded that (a) portal hypertension is common in PBC; (b) the intrahepatic block is of the so-called postsinusoidal type, even in patients without regenerative nodules; (c) gastro-intestinal bleeding due to portal hypertension occurs in about half of the patients and may be the first manifestation of PBC; (d) portacaval shunt seems to be indicated when gastro-intestinal bleeding occurs in earlier stage of the disease.     

Splenogastrorenal shunt in portal hypertension: a little known entity. Study of 6 cases and review of the literature

The authors report 6 cases of portal hypertension with gastrorenal shunt. This shunt did not arise from the left gastric vein, but from the splenic vein. Portal hypertension was related to alcoholic cirrhosis in 3 cases, to extensive portal thrombosis in 2 cases, and to nodular regenerative hyperplasia of the liver in one case. A gastrointestinal hemorrhage revealed portal hypertension and the liver disease in the 3 cases of alcoholic cirrhosis and complicated the course of the disease in the other cases. Hemorrhage was either massive and life-threatening or often recurred. It was related to a rupture of fundic varices in all cases. The fundic varices were not associated with esophageal varices in the 3 cases of cirrhosis. The degree of portal hypertension was above 20 mm Hg, as assessed by the portohepatic gradient (one case), or the pressure gradient between a tributary portal system vein and the inferior vena cava during laparotomy (5 cases). Definitive control of hemorrhage could not be achieved by endoscopic variceal sclerotherapy (2 cases) or percutaneous transhepatic embolization (one case). Portacaval shunt or splenectomy was performed in 5 cases. These findings suggest that spontaneous splenogastrorenal shunt is a clinical and hemodynamic entity which requires specific treatment when associated with gastric variceal bleeding.     

Endoscopic Evaluation of Rectal Mucosal Reddening in Patients with Liver Cirrhosis

Background: Colonic mucosal lesions observed in patients with portal hypertension have been reported as portal hypertensive colopathy. We studied the rectal mucosa in patients with liver cirrhosis to evaluate the prevalence of mucosal reddening which looks like gastric red spots in the portal hypertensive gastropathy and to determine whether there is a correlation between this lesion and portal hypertension or the severity of liver disease. Methods: Seventy‐two patients with liver cirrhosis and 50 control subjects were examined. Colonoscopy was performed to evaluate the presence of mucosal reddening in the rectum. We investigated the relations between rectal mucosal reddening and esophageal varices, portal hypertensive gastropathy and the severity of liver cirrhosis. Results: Rectal mucosal reddening was observed in eight of 72 patients with liver cirrhosis but in none of the 50 control subjects; its prevalence in cirrhosis patients was significantly higher than that in the control subjects (P < 0.05). Cirrhosis patients with esophageal varices were more likely to have rectal mucosal reddening than cirrhosis patients without esophageal varices (P < 0.05). In addition, the occurrence of rectal mucosal reddening correlated with the severity of cirrhosis, based on Child–Pugh's classification (P < 0.05). Conclusion: We have shown that rectal mucosal reddening develops in patients with liver cirrhosis and is associated with the existence of esophageal varices and the severity of liver cirrhosis. These results suggest the possibility that portal hypertension and impaired liver function may play an important role in the pathogenesis of rectal mucosal reddening in patients with cirrhosis.     

Clinical features of symptomatic primary biliary cirrhosis initially complicated with esophageal varices

Background Esophageal varices (EV), one feature of portal hypertension, have been regarded as a late complication of liver diseases. However, accumulating evidence indicates that EV sometimes develop early during the course of primary biliary cirrhosis (PBC). The prognosis is usually poorer for patients with symptomatic PBC than for those with asymptomatic PBC. Nevertheless, the clinical features and prognosis of patients with PBC whose initial symptoms are EV have not been clarified. Methods The clinical features and the prognosis of patients who initially developed EV without other symptoms (v-PBC) were retrospectively investigated in 54 patients with symptomatic PBC. Results The leukocyte and platelet counts were lower in patients with v-PBC than in those with PBC accompanied by other symptoms (s-PBC). Liver function tests, autoantibodies, and histological stage did not differ between patients with v-PBC and those with s-PBC. Although the prognosis did not differ, the incidence of hepatocellular carcinoma was significantly higher in v-PBC than in s-PBC (P = 0.0037). Conclusions These data indicate that v-PBC is a hypercarcinogenic state and constitutes a new subgroup of PBC.