Characteristic differences according to the cirrhotic pattern of advanced primary biliary cirrhosis: Macronodular cirrhosis indicates slow progression.

It is important to evaluate advanced primary biliary cirrhosis (PBC) clinicopathologically to clarify its progressive mechanism. According to the cirrhotic pattern, 26 cases of explanted PBC were classified into non-cirrhotic (n=4), macronodular (n=4), mixed nodular (n=6), and micronodular cirrhosis (n=12), to compare their clinical and morphological features. In addition, the degree of preserved intrahepatic bile ducts and other histologic features were analyzed. Patients at living donor liver transplantation (LDLT) in the macronodular cirrhosis were significantly older than those in the micronodular cirrhosis. The mean duration between clinical presentation and LDLT in the macronodular cirrhosis was significantly longer than in the micronodular cirrhosis. The non-cirrhotic group showed a short duration between clinical presentation and LDLT. The ratio of explanted liver volume to standard liver volume (ELV/SLV) indicates that macronodular cirrhosis revealed more atrophic change than that in the other three types. The density of remnant intrahepatic bile ducts of less than 50mum per group in cases of macronodular cirrhosis was significantly higher than that in cases of micronodular cirrhosis. Therefore, different cirrhotic patterns of advanced PBC were correlated with the disease progression and the degree of bile duct disappearance. The macronodular cirrhotic patients were older, had a longer disease course, yet had less bile duct loss. We suggest that macronodular cirrhosis and micronodular cirrhosis of PBC are different type of PBC.     

The role of the pathologist in diagnosing and grading biliary diseases

Pathological features of primary biliary cirrhosis (PBC) are reviewed. Immune-mediated, non-suppurative cholangitis is the initial lesion and is followed by the gradual and extensive destruction of bile ducts and development of chronic cholestasis. Simultaneously, necro-inflammatory activities of the hepatic parenchyma and limiting plates of milder form develop not infrequently. Eventually, liver fibrosis and cirrhosis develop. A new system applicable to needle liver biopsies in which staging is evaluated using a combination of three factors (fibrosis, cholestasis, and bile duct loss) and necro-inflammatory activities of the bile duct and hepatic parenchyma are graded, is proposed. The clinical and therapeutic evaluation of PBC using this system is warranted.     

Primary biliary cirrhosis: from induction to destruction

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that predominantly affects middle-aged women; fatigue and pruritus are the most common symptoms at presentation. Liver function tests are consistent with cholestasis and reveal an elevation of serum alkaline phosphatase and gamma-glutamyl transpeptidase with or without elevation of aminotransferase levels. Histologically, PBC is characterized by the destruction of the intrahepatic small bile ducts and subsequently fibrosis. The serological hallmark of the disease is the presence of antimitochondrial antibodies, which are found in 95% of patients with PBC. The antimitochondrial antibodies are directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of the mitochondria. PBC generally slowly progresses, even over decades, and may lead to liver failure. In symptomatic patients, advanced age, elevated serum bilirubin levels, decreased serum albumin levels, and cirrhosis each correlate with shortened survival. Immunosuppressive and anti-inflammatory drugs have been used in the treatment of PBC based on the presumed autoimmune pathogenesis, but satisfactory agents leading to complete reversal or cure of the disease are not available. At present ursodeoxycholic acid appears to be the only effective therapy in preventing or delaying the need for liver transplantation and improving survival. However, a number of patients receiving ursodeoxycholic acid still develop progressive disease and require transplantation; transplantation is the only effective therapy at the end stage of the disease.     

An electron microscopic and morphometric study of ursodeoxycholic effect in primary biliary cirrhosis

BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a chronic liver disease that results in cholestasis and bile duct loss. Ursodeoxycholic acid (UDCA) has been shown to reduce hepatocellular damage in PBC. The study attempted to quantify perisinusoidal collagenization and the number of apoptotic bodies in PBC liver biopsies from patients in a randomized control trial treated with UDCA compared to those who received placebo. METHODS: Twenty-eight patients with PBC (10 cirrhotic, 18 non-cirrhotic; 13 treated with UDCA, 15 treated with placebo) were compared with 32 controls with normal hepatic histology on light microscopy. Liver biopsies were examined for degree of perisinusoidal fibrosis and apoptotic activity using electron microscopy. RESULTS: The degree of perisinusoidal fibrosis and apoptotic activity was similar in pretreatment biopsies of UDCA and placebo-treated patients. After two years of placebo, patients showed a significant increase in fibrosis (P < 0.001). In contrast, there were no changes in non-cirrhotic and a decrease in fibrosis in cirrhotic patients given UDCA. At baseline, PBC patients had higher numbers (apoptotic cells/100 hepatocytes +/- SE) of apoptotic cells (7 +/- 3), than controls (2 +/- 0.5) (P < 0.05), with no difference between cirrhotic and non-cirrhotic patients in the two groups of patients. After two years, the numbers of apoptotic cells in UDCA-treated patients decreased significantly compared to baseline (3 +/- 2) (P < 0.05); with placebo patients the number of apoptotic cells increased (12 +/- 5) (P < 0.05). CONCLUSION: Treatment with UDCA prevents the deposition of perisinusoidal collagen and reduces the apoptotic activity in PBC patients after 2 years of therapy.     

原发性胆汁性胆管炎的免疫遗传研究现状

原发性胆汁性胆管炎(PBC)的病理特征是免疫介导的小胆管上皮细胞凋亡性坏死所导致的进行性肝内胆汁淤积,具有进展为胆管纤维化、肝硬化和肝细胞癌的风险。PBC具有免疫遗传特性,PBC患者免疫应答的遗传调控异常包括人类白细胞抗原(HLA)和非HLA基因参与的、以肝内小胆管上皮细胞线粒体内的丙酮酸脱氢酶复合体E2亚基为抗原的T、B淋巴细胞免疫应答异常。超过30%的PBC患者对熊去氧胆酸治疗反应差,因此明确PBC免疫调控异常的机制对PBC免疫治疗具有广泛临床指导意义。     

Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines

Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver, which predominantly affects women once over the age of 20 years. Most cases are diagnosed when asymptomatic (60%). The antimitochondrial antibody is present in serum in most, but not in all, patients with PBC. The disease generally progresses slowly but survival is less than an age- and gender-matched general population. The symptomatic patient may have fatigue, generalized pruritus, portal hypertension, osteoporosis, skin xanthomata, fat soluble vitamin deficiencies, and/or recurrent asymptomatic urinary tract infections. Many nonhepatic autoimmune diseases are found in association with PBC and may prompt initial presentation. To date, immunosuppressive therapy has not been shown to prolong survival in PBC. The hydrophilic bile acid, ursodeoxycholic acid (UDCA), has been shown when given in a dose of 13 to 15 mg/kg daily for up to 4 years to delay the time to liver transplantation or death. This therapy also causes a significant improvement of all the biochemical markers of cholestasis but has no beneficial effects on any of the symptoms or associated disorders. Treatment with UDCA does not obviate the need for liver transplantation. Therapies to prevent complications arising from malabsorption, portal hypertension, and/or osteoporosis are required as well. Good control of pruritus can be achieved in most patients. PBC is diagnosed with increasing frequency, but the agent(s) responsible for this slowly progressive destruction of the interlobular bile ducts remains elusive and hence a specific therapy remains unavailable.     

Ursodeoxycholic acid treatment of vanishing bile duct syndromes

Vanishing bile duct syndromes (VBDS) are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from liver failure. The majority of adult patients with VBDS suffer from primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA), a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and anticholestatic effects have been reported for several other cholestatic syndromes. Several potential mechanisms of action of UDCA have been proposed including stimulation of hepatobiliary secretion, inhibition of apoptosis and protection of cholangiocytes against toxic effects of hydrophobic bile acids.     

Review: Treatment of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a slowly progressive chronic cholestatic disease of the liver thought to be caused by immune destruction of the interlobular bile ducts. One-third of patients are asymptomatic and one-third of these develop symptoms within 5 years. Therapeutic regimens should be directed at the control of symptoms, prevention of complications and specific therapy aimed at controlling progression of the disease. Symptoms may be secondary to cholestasis or due to other associated diseases. The cause of pruritus secondary to cholestasis remains unknown; the anion exchange resin cholestyramine generally brings relief. In patients resistant or intolerant to this therapy, rifampin may be helpful, as well as ultraviolet light without sunblock. Liver transplantation may rarely be the only option for uncontrollable pruritus. Clinical manifestations of keratoconjunctivitis sicca and xerostomia need constant attention to prevent corneal ulcers and dental caries. Preventative therapy includes regular screening for thyroid dysfunction and replacement therapy when necessary and the administration of the fat soluble vitamins A, D and K once hyperbilirubinaemia is present. Osteoporosis is a complication of all cholestatic liver disease. There is no satisfactory preventative therapy. It may be appropriate to give hormone replacement therapy to all post-menopausal women with PBC to reduce osteoporosis. Liver transplantation is the best option for those with fractures. Oesophageal varices may develop early in the course of PBC, non-selective beta-blocker therapy should be used as prophylaxis against variceal haemorrhage. The only specific therapy shown to cause both a biochemical and survival benefit in patients with PBC is ursodeoxycholic acid (UDCA). Treatment with UDCA delays progression, but does not result in a cure of this disease. Currently, liver transplantation is the only definitive treatment available for end-stage disease.     

Treatment of primary biliary cirrhosis

Primary biliary cirrhosis is a chronic liver disease of unknown etiology, characterized by inflammation and destruction of the intrahepatic biliary ducts, resulting in chronic cholestasis and eventually cirrhosis. The main clinical manifestations consists of pruritus, jaundice, xanthomas, and the consequences of intestinal malabsorption, including vitamin deficiencies and osteodystrophy. Treatment of PBC is addressed at preventing or relieving the symptoms and clinical consequences of chronic cholestasis, and also at correcting the bile duct abnormalities by specific treatments. Pruritus is treated with cholestyramine, but in some cases other drugs, such as rifampicin or opioid antagonists are needed. Bisphosphanates are effective for increasing bone mass in osteopenic patients. Vitamin D and cAlcium supplements are also recommended, particularly in patients with severe cholestasis. Ursodeoxycholic acid (UDCA) has become the standard treatment (13-15 mg/kg/day), resulting in marked relieving of cholestasis. UDCA also prevents the histological progression of the disease, although the effects on survival are less apparent. Small trials of combination therapy using UDCA with methotrexate, colchicine, or prednisone, have been reported but have not shown any increased efficacy over UDCA therapy. Liver transplantation is the only treatment available when cholestasis progresses, with very good survival rates.     

Recurrence of primary biliary cirrhosis and development of autoimmune hepatitis after liver transplant: A blind histologic study

Aim:  This long-term study aimed to evaluate recurrence and evolution of primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT).
Methods:  We reviewed "blindly" allograft biopsy specimens of women who underwent transplantation for PBC ( n  = 84), and women who received a transplant for chronic hepatitis C virus infection (CHCV ) ( n  = 108). All needle liver biopsy specimens obtained more than 6 months post-OLT were examined, including 83 specimens from 44 PBC patients and 152 specimens from 58 CHCV patients.
Results:  Granulomatous destructive cholangitis was found in five biopsies from four PBC patients ( P  = 0.0048). Non-necrotizing epithelioid cell granulomas were present in four biopsies from four PBC patients, and in two biopsies from one CHCV patient. Piecemeal necrosis ( P  = 0.0002), lobular necroinflammatory activity ( P  < 0.0001), steatosis ( P  < 0.0001) and fibrosis ( P  < 0.0001) were more prevalent in CHCV patients than PBC patients. Four PBC patients developed histologic evidence of autoimmune hepatitis (AIH), at a mean time of 3.66 years post-OLT. One of these patients had histologic features of AIH/PBC overlap syndrome. All four patients developed bridging fibrosis ( n  = 2) or cirrhosis ( n  = 2). No other PBC patient had evidence of cirrhosis after OLT.
Conclusions:  Histologic findings indicative of recurrent PBC were present in 15.9% of the PBC patients undergoing biopsy in this series. However, this group of patients did not suffer significant bile duct loss or fibrosis, as compared to the control group, suggesting that recurrent PBC is a mild or slowly progressive disease. Histologic evidence of AIH was observed in allograft biopsies of some PBC patients.     

Idiopathic adulthood ductopenia: case report and review of the literature

The clinical and pathological findings of idiopathic ductopenia were studied in a 30-year-old woman who initially manifested jaundice and pruritus. Serum biochemical tests of liver function indicated severe and progressive cholestasis. Viral hepatitis markers and circulating autoantibodies were absent. The patient had a normal cholangiogram and lacked evidence of inflammatory bowel disease. Histological examination of a liver specimen showed severe cholestasis and absence of interlobular bile ducts. Severe jaundice and intractable pruritus developed in the patient and served as the indications for liver transplantation 4 months after initial examination. Transplantation resulted in prompt and complete resolution of the jaundice and pruritus. Two types of idiopathic adulthood ductopenia associated with different prognoses are recognized. Patients with type 1 idiopathic adulthood ductopenia are asymptomatic or manifest symptoms of cholestatic liver disease. They tend to have less destruction of the intrahepatic bile ducts on liver biopsy specimens. Their clinical course ranges from spontaneous improvement to progression to biliary cirrhosis. In contrast, patients with type 2 idiopathic adulthood ductopenia generally manifest initial symptoms of decompensated biliary cirrhosis, have extensive destruction of the intrahepatic bile ducts on liver biopsy, and frequently require orthotopic liver transplantation.     

Autoimmune overlapping syndromes

The overlap syndrome raises several questions. First could these patients have two coincident autoimmune diseases? Such possibility cannot be discarded in particular in the setting of consecutive occurrence of the two conditions (eg, PBC followed by AIH) and this is consistent with the fact that autoimmune diseases are associated with one another in about 5% to 10% of cases. Furthermore, it is presumed that they share similar genetic susceptibility. A second possibility could be that overlap syndrome represents the middle of a continuous spectrum of two autoimmune liver diseases. The systematic study of the relationships between elementary histologic lesions and biochemistries in "pure" PBC patients pleads strongly for such a hypothesis. Pure PBC is characterized by 2 different groups of elementary lesions that are not interrelated: first, florid bile duct lesions and bile duct paucity and second, lymphocytic piecemeal necrosis and lobular necro-inflammatory changes. Furthermore, the first set of lesions is selectively associated with biochemical cholestasis and IgM levels, whereas the second set of lesions is selectively associated with serum transaminase activities and IgG levels. These observations are consistent with the assumption that two main mechanisms are involved in the progression of liver injury in PBC. The first is bile duct destruction leading to chronic cholestasis and fibrosis of biliary pattern. The second is lymphocytic piecemeal necrosis of hepatocytes, which tends to lead to cirrhosis, the pattern of which resembles cirrhosis following various forms of chronic active hepatitis. The author has therefore speculated that the picture of pure PBC results always forms the clinical and biochemical expression of the two main histologic lesions, and combination of these processes might explain why the spectrum of PBC varies from typical PBC to AIH or PBC overlap. A third hypothesis is that an exaggerated hepatitic response in PBC is associated with the HLA haplotype commonly seen in AIH, eg, B8, DR3, DR4. Further studies are obviously needed to confirm such an attractive hypothesis. Other possible explanation for the concurrent occurrence of features of both conditions in the same individual includes the selective modulation of HLA class 1, class 2 expression and Rantes by cholestasis itself and in particular bile acids. It is conceivable that the degree of interface and lobular inflammation in PBC and PSC may be modulated by chemokines, their receptors, and the parenchymal concentrations of individual bile acids that are all, at least in part, genetically determined.     

Treatment of primary biliary cirrhosis: therapy with choleretic and immunosuppressive agents

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of presumed autoimmune etiology affecting predominantly middle-aged women; it is a slowly progressive disease causing loss of intrahepatic bile ducts, resulting in advanced fibrosis, cirrhosis, and liver failure. Many drugs have been studied for treatment, including agents with choleretic and immunosuppressive properties. Ursodeoxycholic acid (UDCA) has been evaluated most widely. After liver failure, the only effective treatment is liver transplantation. Effective therapy reduces the need for transplantation and improves life expectancy. For advanced liver disease or incomplete response to UDCA, new therapies to cure or retard the progression of disease in PBC are needed.     

Primary biliary cirrhosis--presentation and diagnosis

Primary biliary cirrhosis is predominantly seen in middle-aged women. Typical symptoms are fatigue, pruritus, and abdominal pain. Jaundice develops in the endstage disease. At presentation, about 40% of the patients are asymptomatic, but 30% to 50% already have hepatomegaly, and 15% present with splenomegaly. Even patients with fully developed liver cirrhosis may be free of symptoms. Abnormal physical signs and advanced histological stage are more frequent in symptomatic than in asymptomatic patients. Fatigue, pruritus, and Sj?gren's syndrome are more common in women than men, but other signs and symptoms do not differ in the two sexes. PBC is associated with a large variety of other diseases, like arthropathy, CREST syndrome, autoimmune thyroiditis, and so on, which in addition will or will not produce symptoms. Hepatocellular carcinoma is a rare complication in women, but more frequent in men. Diagnosis can be established by the triad antimitochondrial antibodies (AMA), cholestatic indices, and liver histology, diagnostic or compatible with PBC. When AMA are not detected, then antinuclear antibodies (autoantibodies against gp.210 and others) can be detected in 50% of AMA-negative patients. AMA titers do not correlate with the course of the disease nor histological progression. After liver transplantation, AMA recur in nearly 100%. The liver enzyme pattern in PBC patients is cholestatic: alkaline phosphatase and gammaglutamyltransferase increase to 10 or more times the upper limit of normal. The amount of enzymes does not correlate with disease progression or stage of the disease. The only prognostic factor in PBC is serum bilirubin. AMA-negative patients account for about 10% to 15%. Routine biochemical tests are not different from AMA-positive patients, but usually higher ANA, SMA, and IgG concentrations are detected. Histologically, it is PBC. The overlap-syndrome, autoimmune hepatitis-PBC presents with the histological features of autoimmune hepatitis and PBC, with AMA, ANA, or SMA. Imaging procedures are not helpful for the diagnosis of PBC, except for liver histology. Histologically, four different stages can be assessed, ranging from florid bile duct lesions, ductular proliferation, and fibrosis to liver cirrhosis. Liver histology is of interest for the assessment of the diagnosis and for staging of the disease.     

Natural course of primary biliary cirrhosis. I. A morphological, clinical and serological analysis of 103 cases

Clinical, biochemical and serological data obtained in 103 patients with primary biliary cirrhosis (PBC) were analysed with respect to the four defined morphological stages. Evaluation of the initial biopsies (99 needle biopsies/4 wedge biopsies) revealed that most patients were in stage I (focal bile duct destruction). Unequivocal distinction between stages I and II was possible in most cases, while considerable overlapping of criteria was observed in stages II to IV. Morphological cholestasis, a characteristic sign of stage IV was already found in 7% of PBC I cases. Four out of 12 autopsy specimens showed micronodular biliary cirrhosis (Hanot's type) and eight specimens had a macronodular type of biliary cirrhosis. No predominant clinical symptoms were found in patients with PBC I or II, but pruritus was observed in about 30%. Increased serum alkaline phosphatase (AP) and IgM levels as well as a positive antimitochondrial antibody (AMA) test were typical features of all stages in up to 80-90%, but patients with normal AP or IgM or negative AMA have been observed, especially in stages I and II. Five of 57 patients at stage I had increased bilirubin levels and in three patients IgM and IgG were simultaneously elevated in stage I. The natural course of PBC, as it is reflected in histological staging, was studied in 30 patients in whom biopsies were regularly taken over a period of 2-18 years. About 80% of PBC I-cases lasted between 1 and 7 years before reaching stage II, while another 5-10 years were necessary for the development of stage III-IV. Thus it appears that in the vast majority of patients PBC lasts about 10-15 years and in some instances even more than 20 years. The finding in stage I and II of normal AP indicates a benign course, while morphological and biochemical cholestasis seems to be associated with a rather progressive course.     

The pathogenesis of biliary atresia: evidence for a virus-induced autoimmune disease

Biliary atresia is a mystifying cause of neonatal cholestasis, manifested by progressive inflammation and fibrosis of both the extrahepatic and intrahepatic bile ducts. It is a devastating disease that leads to cirrhosis and the need for liver transplantation in the majority of children. The etiology is unknown, and one theory is that it may involve a primary perinatal hepatobiliary viral infection and a secondary generation of an autoimmune-mediated bile duct injury. This review will outline the evidence from both human and murine studies supporting a potential cholangiotropic viral infection as the initiator of bile duct injury in biliary atresia and the role of the adaptive immune response and autoimmunity in progression of disease. Delineating the pathways of immune and autoimmune-mediated bile duct injury within biliary atresia could stimulate development of new medical interventions aimed at suppressing the specific immune response, decreasing the inflammatory damage to bile ducts, and delaying or negating the need for liver transplantation.     

Primary biliary cirrhosis in adults

Primary biliary cirrhosis (PBC) is a chronic, autoimmune, cholestatic liver disease. It is characterized by slow destruction of small intrahepatic bile ducts, impaired biliary secretion and stasis of toxic endogenous bile acids within the liver with progression to liver fibrosis and cirrhosis. It has an increasing prevalence worldwide. It occurs more commonly in women than men at a ratio of 10:1. In most cases, diagnosis relies on a positive antimitochondrial antibody in the context of chronic cholestasis, without the need for a liver biopsy. Ursodeoxycholic acid improves survival even in patients with advanced liver disease. Certain findings such as fatigue, anti-nuclear antibodies, anti-centromere antibodies and the GP210 antinuclear antibody predict a poor outcome. Up to 40% of patients do not respond satisfactorily to ursodeoxycholic acid therapy and should be considered for adjunctive therapies. Several adjunctive and newer therapies are being tested and some appear promising. We provide a review of PBC with a focus on advances in therapies that may impact the management of PBC in the near future.     

Idiopathic biliary ductopenia in adults: a report of five cases

The clinical and pathological findings of five adult cases of idiopathic nonsyndromatic paucity of interlobular bile ducts are reported. Patients were 18-32 years old at the onset of the disease; four presented with pruritus and/or jaundice and one with bleeding of the esophageal varices. Two patients were siblings. Serum alkaline phosphatase counts ranged from 1 to 16 times the upper normal value, and total bilirubin counts ranged from 0.6 to 8.8 mg/dL (10 to 150 mumol/L). Initial liver biopsy showed portal and periportal fibrosis with cholangiolar proliferation and reduction in the number of interlobular bile ducts. Antimitochondrial antibodies were absent, and bile ducts were normal after opacification. The patients were observed for 3-11 years. Repeated liver biopsies in the five patients showed progression of the lesions, with development of biliary type cirrhosis in four. Two of the four patients with cirrhosis died of hepatic failure 3 and 11 years after onset of the disease. In the two other cases, liver transplantation was performed successfully. These cases suggest that chronic cholestasis with marked ductopenia resembling the nonsyndromatic paucity described in infancy and childhood may reveal itself at an adult age. This disorder, possibly familial, may rapidly progress to severe and even fatal liver disease and could be a new indication for liver transplantation.     

Prim?r bili?re Zirrhose

Primary biliary cirrhosis (PBC) is characterized by immune-mediated destruction of small intrahepatic bile ducts and subsequent development of liver fibrosis and cirrhosis, occuring mainly in middle-aged women. PBC is diagnosed on the basis of a cholestatic serum enzyme pattern, elevated serum IgM, the presence of antimitochondrial antibodies (AMA) in serum directed against the E₂ subunit of the pyruvate dehydrogenase complex, and a ?florid bile duct lesion” of mid size intrahepatic bile ducts and bile duct paucity. The cholestatic serum enzyme pattern and serum AMA are mandatory for the diagnosis. PBC is frequently associated with other autoimmune disorders such as Sjögren’s syndrome, Hashimoto’s thyroiditis, and celiac disease. Early diagnosis and medical therapy with ursodeoxycholic acid aim to hinder progression of the disease toward cirrhosis. Additional medical treatments are under evaluation. Liver transplantation is an effective treatment of end-stage PBC.     

Pediatric-onset primary biliary cirrhosis

Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has not been reported in childhood. We report 2 cases of PBC diagnosed at 16 and 15 years of age, respectively. The first girl was noted to have increased liver enzyme levels at 16 years of age. Antimitochondrial antibody (AMA) was strongly positive, and serum quantitative immunoglobulin M level was 8.26 g/L (normal, 0.6-3 g/L). A liver biopsy specimen showed stage II PBC. Despite treatment with ursodeoxycholic acid, she developed progressive cholestasis, intractable pruritus, and a significant sensory neuropathy and weight loss eventually requiring liver transplantation. Her mother had PBC/autoimmune overlap syndrome and underwent successful liver transplantation at 34 years of age. The second girl had persistently elevated liver enzyme levels following cholecystectomy at 15 years of age for symptomatic cholelithiasis. Endoscopic retrograde cholangiopancreatography showed no abnormalities. AMA was positive at 1:160, and serum quantitative immunoglobulin was 6.96 g/L. A liver biopsy specimen showed stage II PBC, and her liver enzyme levels almost normalized after starting treatment with ursodeoxycholic acid. In conclusion, we present 2 liver biopsy-confirmed cases of pediatric-onset AMA-positive PBC. With increased awareness of early-onset PBC, further pediatric cases may be discovered.