Primary Biliary Cirrhosis Overlap Research Articles

Overlap of Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis - A Rare Coincidence or a New Syndrome [Retraction

[This retracts the article DOI: 10.2147/IJGM.S11201.].

Primary Sclerosing Cholangitis and Primary Biliary Cirrhosis Overlap Syndrome: A Review.

Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are slow progressive diseases which have been increasing in prevalence. The pathogeneses of PBC and PSC are incompletely understood but the underlying mechanisms appear to be fundamentally autoimmune in origin. Although PBC and PSC appear to be separate entities, overlap has been described. Diagnosis depends on a combination of serological markers, imaging, and pathological criteria. The mainstay of treatment has been ursodeoxycholic acid and in some cases of extrahepatic biliary obstruction and overlap disorder, endoscopic retrograde cholangiopancreatography has been useful.

PWE-116 Gp210 and/or sp100 antibodies in primary biliary cirrhosis: predictors of cirrhosis/autoimmune (aih) overlap syndromes?

<h3>Introduction</h3> Primary Biliary Cirrhosis (PBC) is a progressive cholestatic liver disease, with Anti-mitochondrial antibodies (AMA) found in ∼ 95% of patients. Anti-GP210 and SP100 are suggested as additional markers in AASLD guidance, and may help in predicting disease prognosis. However, the role and benefit of anti-GP210 and SP100 testing in routine clinical practice is unclear. <h3>Method</h3> We conducted a retrospective study of all PBC patients (diagnosed according to AASLD criteria), across 3 hospitals in Surrey, England; serving a population 1.1million. Prospective ELISA testing for GP210 and SP100 antibodies were undertaken on all active PBC-patients in follow-up. Baseline characteristics (laboratory/clinical) and progression during follow-up were analysed and compared between both groups. <h3>Results</h3> 51 PBC patients were identified, with anti-GP210/SP100 demonstrated in 14 patients (27%); 9 with anti-SP100, 5 with anti-GP210. Demographic characteristics were similar between both groups: age 64 vs. 61 years, Females 80% vs. 70% in the PBC and GP210/SP100 groups. Consistent with the high sensitivity of AMA in PBC, only 1 (1/51) patient was AMA negative, and also negative for M2, GP210 and SP100. Baseline cirrhosis (imaging/biopsy) was present in 3/27 patients (11%) in the PBC group vs. 3/12 (25%) in the GP210/SP100 group. Quantitative mean M2 values were similar (100 vs. 96), as were baseline mean laboratory values (Bilirubin, ALT, ALP, GGT and IgM). Cirrhosis was present at follow-up (range 0.5–10 years) in 5/37 patients (13.5%) vs. 4/13 (31%) in the GP210/SP100 group. Treatment response to UDCA at one year (Barcelona criteria) was similar: 10/24 (42%) vs. 5/13 (38%) in the GP210/SP100 group. Post-treatment mean alkaline phosphatase levels were higher in the GP210/SP100 group 231 vs. 174 (p = 0.84). 8/51 PBC patients (16%) had diagnosed Autoimmune hepatitis (AIH)/PBC Overlap Syndrome (OS) (based on histological/serological features). OS cases were seen in 2/37 (5%) in the non-ANA group vs. 6/14 (43%) of those in the GP210/SP100 group, reaching statistical significance (p = 0.05); with no significant difference in ALT levels between the OS/non-OS groups. <h3>Conclusion</h3> Although a small sample, our findings support the role of anti-GP210/SP100 as possible markers of disease severity (cirrhosis), and suggest a role for these auto-antibodies in identifying patients with PBC/AIH overlap syndromes; even in the absence of a significant transaminitis. <h3>Disclosure of interest</h3> None Declared.

Primary biliary cirrhosis and hepatic sarcoidosis: A case report

Primary biliary cirrhosis (PBC) is an immune-mediated chronic progressive inflammatory liver disease leading to destruction of small interlobular bile ducts. Sarcoidosis is a chronic disorder of unknown etiology characterized by non-caseous granulomas. We reported a 69-year-old female patient with abdominal pain, malaise, vertigo, headaches, hands tremor and partial loss of hearing. Initial laboratory findings revealed elevated liver function tests and cholesterol with positive antimytochondrial and antinuclear antibodies. Liver biopsy revealed granuloma typical for PBC and granulomatous lesions typical for sarcoidosis. Elevated serum angiotensin-converting enzyme and granulomatous lesion on the brain magnetic resonance imaging (MRI) were detected and the patient was diagnosed with overlap of PBC and liver sarcoidosis and neurosarcoidosis. The patient was treated with ursodeoxicholic acid (UDCA) and prednisolone. Six months later the patient was symptom-free with laboratory findings within normal range. In PBC patients it is important to consider coexisting granulomatous liver diseases if elevated liver function tests persist despite UDCA therapy.

Myositis Portends Primary Biliary Cirrhosis: A Case Series

Purpose: Although the presence of anti-mitochondrial antibody (AMA) is 98% specific for primary biliary cirrhosis (PBC), AMA is associated with other autoimmune diseases, including inflammatory myopathies. A recent study in Brain found 23 case reports of concurrent PBC and polymyositis (PM), and only one of autoimmune hepatitis (AIH)-PBC overlap with PM. We present two patients from our institution with AIH-PBC overlap and PM, and discuss their management. Case 1: A 60-year-old woman with sicca syndrome was referred to us for persistently elevated aminotransferase values, immunoglobulin M (IgM) (666mg/dL), and immunoglobulin G (IgG) (1,950 mg/dL). A liver biopsy confirmed Scheuer stage I PBC with AIH, and she was started on prednisone and ursodiol. Concurrent to her PBC diagnosis and before prednisone therapy, she developed progressive proximal muscle weakness. Muscle biopsy, electromyography, and elevated muscle enzyme levels suggested PM. On prednisone, her liver enzyme levels normalized while muscle strength responded to several months of intermittent intravenous immunoglobulin. Three years later, she developed diastolic heart failure, which improved on diltiazem. Her disease was complicated by severe osteoporosis, treated with zoledronic acid, calcium, and vitamin D. Currently, she is doing well on ursodiol 500 mg daily, and prednisone 5 mg every other day. Case 2: A 58-year-old man presented to a neurologist after 1 year of truncal weakness. His muscle biopsy, elevated muscle enzymes, and symptoms suggested PM. He responded to prednisone, but was subsequently referred to hepatology for persistently elevated liver test results (AST 89, ALT 99, ALK PHOS 305). AMA (1:160), IgG (2350 mg/dL) and IgM (402 mg/dL) were elevated. Liver biopsy confirmed stage I PBC with confluent necrosis, suggesting AIH overlap. Prednisone 60 mg daily and ursodiol 500 mg twice-a-day were initiated. After 3 months of treatment, the patient's symptoms improved and liver enzyme activity normalized. Discussion: Although AIH-PBC with PM is an infrequently recognized syndrome, we encountered two such cases. The natural course of AIH-PBC and PM is unknown, but some studies show that PM with concurrent PBC may have a more indolent PM with frequent cardiac involvement, as seen in our first patient. Both patients responded to and are being maintained on prednisone and ursodiol. For PM with AIH, if prednisone treatment alone fails, the addition of immunosuppressive agents given singly or in combination with corticosteroids may be considered. Since corticosteroid use may worsen osteoporosis associated with advanced PBC, assessment of bone density with the potential use of bisphosphonates may be valuable.

A case of primary biliary cirrhosis and autoimmune hepatitis overlap showing acute presentation and transient seropositivity for immunoglobulin G and anti-nuclear antibody.

Autoimmune hepatitis (AIH) is generally regarded as a clinically and histologically "chronic" hepatitis. It often shows acute presentation like acute hepatitis without typical clinicopathological features of AIH, especially in a case of overlap with primary biliary cirrhosis (PBC). A 52-year-old man showed mild liver dysfunction for the first time at an annual medical check. Two months later, he showed jaundice, and laboratory tests revealed elevation of liver enzymes, hyperbilirubinemia and prolonged prothrombin time activity like acute liver failure. Anti-mitochondrial antibody was positive and other viral and autoimmune markers were negative. His liver function tests improved upon treatment with ursodeoxycholic acid and maximum intravenous glycyrrhizin (IVGL), but liver dysfunction was again exacerbated after the gradual reduction of IVGL. He showed transient elevation of immunoglobulin G (IgG) and anti-nuclear antibody (ANA) at only one point, and liver histology was compatible with PBC and AIH overlap syndrome. Corticosteroid was administered and his liver function tests returned to normal. It is important for the diagnosis of acute onset AIH to monitor IgG level and ANA titer, especially in patients without IgG and ANA elevations at first appearance.

Primary Biliary Cirrhosis Overlapping with Autoimmune Hepatitis in an HIV-Infected Patient on Antiretroviral Therapy.

Liver disease in HIV-infected patients is complex and multifactorial. Drug toxicity and infections are common causes of elevations in liver-associated enzymes. Immune reconstitution and unmasking of autoimmune disease may also play a role, particularly in the era of effective combination antiretroviral therapy. In this case report, we describe the first reported biopsy-confirmed case of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome presenting in an HIV-infected patient following initiation of antiretroviral therapy.

Primary biliary cirrhosis and auto immune hepatitis overlap syndrome mimicking cholangiocarcinoma.

Primary Biliary Cirrhosis (PBC) and Auto Immune Hepatitis (AIH) are autoimmune diseases of the liver which highlighted with slow destructive process of intra hepatic small bile ducts. As a result of these damages cholestasis and over the time tissue damage will happen, which leads to scarring, fibrosis and finally cirrhosis. Some patients may present with clinical and biochemical features of both conditions, which is called "Overlap syndrome". Here we are reporting a case of PBC-AIH overlap syndrome that primarily diagnosed as gallbladder carcinoma and went under operation and finally histological examination revealed to be PBC.

A case of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome treated with chinese herbs

Some patients present with overlapping features between disorders within the spectrum of autoimmune liver diseases, i1e1, autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC), and are commonly classified as having an "overlap syndrome"1 The pathophysiological mechanisms underlying AIH-PBC overlap remain unclear1 (1) Due to the lack of standardization and variations in the populations under study, the characteristics of these entities vary between studies and there have been few effective medical therapies for overlap syndrome up to now1 (2,3) Here, we report a case of woman diagnosed as AIH-PBC overlap syndrome who had suboptimal response to single ursodeoxycholic acid (UDCA) or combination with immunosuppressive drug but had optimal response to Chinese herbs1

Living‐donor liver transplantation for autoimmune hepatitis and autoimmune hepatitis–primary biliary cirrhosis overlap syndrome

Recurrent autoimmune hepatitis (AIH) following liver transplantation has been reported in 20-30% of cases, mainly of Western populations. The aim of this study was to review our experience of living-donor liver transplantation (LDLT) in Japanese patients with AIH. Among 375 adult (age ≥18 years) LDLT performed at our center between 1996 and 2010, 16 (4.2%) were for patients with AIH (n = 12) or AIH-primary biliary cirrhosis overlap syndrome (n = 4). The patient and donor characteristics and post-transplantation course were reviewed. All recipients were female with a median age of 48 years (range, 21-58). Low-dose methylprednisolone and calcineurin inhibitors were continued in all patients. Acute cellular rejection occurred in 10 (63%), which was more frequent than in our overall series of 28.5% (107/375 cases). Overall survival rate was 81.2% at 5 years. At the end of the follow up (median, 6.0 years [range, 0.1-9.6]), 13 patients were alive with normal liver function tests (aspartate transaminase, 18 ± 5 IU/mL; alanine transaminase, 16 ± 8 IU/mL). None of the survivors exhibited liver function test results suspicious for recurrent AIH, which might indicate liver biopsy. Survival after LDLT for AIH and overlap syndrome was excellent and there was no evidence of clinical recurrence. The recurrence rate of AIH after liver transplantation may differ among countries, and requires further investigation.

Patients With Autoimmune Hepatitis Who Have Antimitochondrial Antibodies Need Long-term Follow-up to Detect Late Development of Primary Biliary Cirrhosis

Patients with autoimmune hepatitis (AIH) who have antibodies against mitochondrial proteins (AMA positive) are believed to have an autoimmune syndrome that should be managed as AIH. Of patients with AMA-positive AIH, we report on 3 individuals to demonstrate how autoimmune liver disease can progress over time. Specific features of primary biliary cirrhosis (PBC) overlapped in time in these patients. Our observations indicate the importance of careful follow up of patients with AMA-positive AIH; health care professionals that treat such patients should therefore be aware of longitudinal clinical changes that might indicate development of PBC in this setting.

Low incidence of positive smooth muscle antibody and high incidence of isolated IgM elevation in Chinese patients with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a retrospective study

BackgroundUp to now, few data are available regarding the clinical characteristics of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome. The study was to investigate and analyze the prevalent and clinical features of Chinese patients with this disease.MethodsClinical data on patients diagnosed as autoimmune hepatitis and primary biliary cirrhosis overlap syndrome in our hospital from January 2001 to December 2006 were collected and analyzed.ResultsOverlap syndrome of autoimmune hepatitis and primary biliary cirrhosis accounted for 10.33% of patients with autoimmune liver diseases during the past six years. For these patients with overlap syndrome, xanthochromia, lethargy and anorexia were the predominant complaints; a low incidence (14/146) of smooth muscle antibody positivity and a high incidence (37/89) of isolated IgM elevation were the main serological characteristics.ConclusionsOverlap syndrome of autoimmune hepatitis and primary biliary cirrhosis was not rare in Chinese patients with clinical manifests of autoimmune liver diseases. Overlap of the diseases should not be disregarded when isolated IgM elevation was exhibited, and smooth muscle antibody might have little diagnostic significance in the overlap syndrome. If it was difficult to make a definite diagnosis, liver biopsy was necessary.

A Case of Reynolds Syndrome: Scleroderma and Primary Biliary Cirrhosis Overlap Syndrome

Primary biliary cirrhosis (PBC) is a chronic liver condition characterized by bile duct destruction, probably caused by a yet unknown immunological mechanism. Its association with several other autoimmune diseases has been described. The association of the limited cutaneous form of systemic scleroderma (lcSSc) and PBC is known as Reynolds syndrome. The authors describe a case of a 76 year old male patient with Raynaud’s phenomenon complaints in 1999. The physical examination revealed sclerodactyly, cutaneous calcifications, digital ulcers and facial telangiectasias. Chest radiography showed signs of lung fibrosis. Dilated capillary loop were found in nailfold capillaroscopy. The autoimmunity pattern was compatible with limited systemic sclerosis (antinuclear and anticentromere antibodies were positive). In 2005 the autoimmunity pattern changed, with positive antimitochondrial antibodies. The patient presented with fatigue, pruritus and dyspnea on exertion complaints. Liver function tests showed elevation of alkaline phosphatase and gamma-glutamyl transpeptidase. Although the patient refused liver biopsy, PBC diagnosis was established. In 2008 the patient was admitted to the hospital with anorexia, dyspepsia, ascites, abdominal pain and weight loss. Endoscopy showed esophageal varices and abdominal computed tomography revealed cirrhotic liver. The patient died in 2009 with acute myocardial infarction. doi:10.4021/jmc276w

Prevalence of Primary Biliary Cirrhosis–Autoimmune Hepatitis Overlap Syndrome

The prevalence of and the most appropriate way to diagnose the primary biliary cirrhosis (PBC)-chronic autoimmune hepatitis (AIH) overlap syndrome are uncertain. We investigated the prevalence of PBC and AIH and their level of overlap at a tertiary referral center, along with clinical, biochemical, and serologic characteristics. We reviewed data from all patients with PBC (n = 609) and/or AIH (n = 15) examined at the Tufts Medical Center (Boston, MA) from January 1, 2000, to June 20, 2006. PBC was diagnosed based on 2 of the following 3 results: 6 months of positive results in tests for cholestatic liver enzymes, a positive result in a test for antimitochondrial antibodies, or a liver biopsy that indicated PBC. AIH was defined as an alanine aminotransferase level of 200 U/L or greater (≥ 5-fold above normal), a liver biopsy that indicated severe interface hepatitis, and levels of immunoglobulin G 2-fold or greater than that of normal. Only 6 patients with PBC (1%) met the Paris criteria for the overlap syndrome. If we included 9 patients with PBC who did not meet the Paris criteria, but had results from liver enzyme tests and liver biopsy analyses that indicated improvement after treatment with prednisone, the prevalence was 15 (2.8%). This is at the low end of previously reported prevalence values for overlap of PBC and AIH (2%-20%). The prevalence of the PBC-AIH overlap syndrome varies among medical centers. We propose that if the definition of PBC-AIH overlap syndrome be modified to include patients with unequivocal responses to prednisone despite not meeting the Paris criteria, this would improve treatment of patients.

Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis triggered by fluvastatin

Although statins are generally well-tolerated drugs, recent cases of autoimmune hepatitis (AIH) associated with their use have been reported. A 59-year-old Japanese man reported with liver damage, which appeared one month after beginning treatment with fluvastatin and continued after discontinuation of the drug. Although drug-induced liver injury was possible, positive autoantibody tests (antinuclear antibodies >1/1280, anti-mitochondrial M2 antibodies 21 index value) also suggested autoimmune liver disease. Liver biopsy findings were consistent with an overlap of autoimmune hepatitis and primary biliary cirrhosis. Treatment with prednisone and ursodeoxycholic acid led to a good response. In this patient, manifestation of AIH and primary biliary cirrhosis overlap syndrome was possibly triggered by statin use. Autoimmune liver disease should be considered as a possible diagnosis in patients with evidence of prolonged liver damage after discontinuation of statins.

Paris Criteria Are Effective in Diagnosis of Primary Biliary Cirrhosis and Autoimmune Hepatitis Overlap Syndrome

Paris Criteria Are Effective in Diagnosis of Primary Biliary Cirrhosis and Autoimmune Hepatitis Overlap Syndrome

A Case of Reynolds Syndrome: Scleroderma and Primary Biliary Cirrhosis Overlap Syndrome

Primary biliary cirrhosis (PBC) is a chronic liver condition characterized by bile duct destruction, probably caused by a yet unknown immunological mechanism. Its association with several other autoimmune diseases has been described. The association of the limited cutaneous form of systemic scleroderma (lcSSc) and PBC is known as Reynolds syndrome. The authors describe a case of a 76 year old male patient with Raynaud’s phenomenon complaints in 1999. The physical examination revealed sclerodactyly, cutaneous calcifications, digital ulcers and facial telangiectasias. Chest radiography showed signs of lung fibrosis. Dilated capillary loop were found in nailfold capillaroscopy. The autoimmunity pattern was compatible with limited systemic sclerosis (antinuclear and anticentromere antibodies were positive). In 2005 the autoimmunity pattern changed, with positive antimitochondrial antibodies. The patient presented with fatigue, pruritus and dyspnea on exertion complaints. Liver function tests showed elevation of alkaline phosphatase and gamma-glutamyl transpeptidase. Although the patient refused liver biopsy, PBC diagnosis was established. In 2008 the patient was admitted to the hospital with anorexia, dyspepsia, ascites, abdominal pain and weight loss. Endoscopy showed esophageal varices and abdominal computed tomography revealed cirrhotic liver. The patient died in 2009 with acute myocardial infarction. J Med Cases. 2011;2(5):225-228 doi: https://doi.org/10.4021/jmc276w

Overlap Syndrome of Autoimmune Hepatitis and Primary Biliary Cirrhosis in a Patient with Limited Scleroderma: Case Report and Review of Literature

Purpose: Limited cutaneous scleroderma (lcSSc) associated with overlap of Autoimmune Hepatitis (AIH) and Primary Biliary Cirrhosis (PBC) has never been reported. There are few reported cases of systemic sclerosis (SSc) associated with PBC also called Reynold's Syndrome. Methods: We report the case of a 69-year-old female patient with past history of scleroderma, hypothyroidism and abnormal liver profile. The diagnosis of SSc was made at an outside hospital where she also had a liver biopsy. She then transferred her care to our hospital. Her presenting symptoms were weight loss, dysphagia, pruritus and color change of fingers to cold exposure. Physical exam was remarkable for sclerodactyly of distal extremities, cool to touch fingers and telangiectasia over both palms. Laboratory investigations revealed abnormal LFTs, with cholestatic index positive for alkaline phosphatase rising 4 fold and necrotic index positive for ALT rising 3 fold above the upper limit, with no hyperbilirubinemia. Immunological work up revealed positive ANA (1:1280), anticentromere Ab (1:640), antimitochondrial Ab (AMA) (1:40) and Anti smooth muscle Ab (1:20). Liver biospy slides were reviewed by our pathologist showing mild interface hepatitis with necroinflammatory activity and bile duct damage. Based on these overlap features it was reported as possible overlap syndrome of AIH and PBC. She was started on amlodipine for Raynaud's phenomenon and ursodeoxycholic acid with symptomatic improvement. Results: An overlap of PBC and SSc (PBC-SSc) characterized by jaundice, elevated alkaline phosphatase, calcinosis cutis, telangiectasias, and pruritus was first described by Telfer B. Reynolds. PBC-SSc is not uncommon with prevalence from 7.4 to 12.5 percent. Most of the patients with PBC-SSc have lcSSc and higher positivity for anticentromere and AMA. They also have slower progression of liver disease and significantly lower risk of liver transplantation or death from diagnosis. But association of SSc with AIH is very rare with only few reported cases. Among the overlap syndromes of autoimmune liver diseases 7 to 14 percent of patients with PBC may have immunological or clinical features suggestive of AIH while bile duct damage can be seen in upto 25 percent of patients with AIH. Studies have shown that patients with this overlap resemble more to PBC patients in terms of disease course and response to ursodeoxycholic acid. Conclusion: Our patient has lcSSc with serological, biochemical and pathological features of both AIH and PBC. In our patient four fold elevation of alkaline phosphatase with milder elevation of transaminases along with low titres of AMA favors a diagnosis of overlap syndrome of AIH and PBC.

Membranous glomerulonephritis associated with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a very rare condition

Membranous glomerulonephritis associated with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a very rare condition

P09 Hepatocellular carcinoma in primary biliary cirrhosis: defining risk in an era of ursodeoxycholic acid use

IntroductionHepatocellular carcinoma (HCC) is a rare complication in primary biliary cirrhosis (PBC). Current clinical guidance from the British Society of Gastroenterology advises that only male patients with histologically advanced PBC...