PBC-AIH Overlap Research Articles

The contribution of antinuclear antibodies in Primary Biliary Cholangitis (PBC): An experience from the immunology laboratory at University Hospital Center Hassan II, Fes, Morocco.

Patients older than 18 with chronic hepatitis or cirrhosis were recruited from September 2021 to January 2023. Clinical data were collected, including age, sex, symptoms, and biochemical parameters (ALT), (AST), (ALP), (GGT), (TB), (PT) and (PN), autoantibodies associated with hepatic autoimmune disorders: (AMA), anti-gp 210, anti-Sp100 and anti-F-actin antibodies were identified using HEp-2 cells as substrate (Fig. 1); and/or multiple Immunodot liver tests. HBsAg, anti-HCV, and HIV test results of the patients were found to be negative. 19 out of 71 had a confirmed diagnosis of PBC; 5 patients with AIH-PBC overlap (26.3%), and 14 patients with PBC (73.7%). Patients mainly were females with a 0.12-sex ratio. ANA patterns were dominated by cytoplasmic filamentous staining (AC-21) with punctuate nuclear envelope staining (AC-12). Multiple Immunodot tests were performed on all patients: AMA was present in 89.4%, anti-gp 210, and anti-Sp100 antibodies in 57.8% and 21.1%, respectively (Table 1).Patients were divided into groups depending on the positivity of AMA, anti-gp 210, and anti-Sp100 antibodies. 10.5% of PBC patients (2) had negatives AMA and positive anti-gp210. Almost half of PBC patients (11) had associated positive AMA and positive anti-gp210 and/or anti-Sp100, while 26.3% of them (5) had only positive AMA (Table 2). The findings in this work support the role of anti-gp 210 and anti-Sp100 in identifying patients with PBC and overlap syndromes. Moreover, Anti-gp 210 antibodies are found to be helpful for the diagnosis of PBC patients who are negative for AMAs.

The differences in post-liver transplant outcomes of patients with autoimmune hepatitis who present with overlapping autoimmune liver diseases.

Patients with autoimmune hepatitis (AIH) may co-present with features of primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). Using a national transplant registry, the outcomes of patients with these autoimmune liver conditions were compared. The UNOS-STAR registry was used to select a study population of AIH, PSC, and PBC liver transplant (LT) patients. Living and multi-organ transplant cases were excluded. Using the UNOS-registered diagnoses, the study population was subdivided into those with nonoverlapping autoimmune liver diseases and those with overlapping forms (e.g., AIH-PBC). Outcomes were compared, using endpoints such as all-cause mortality, graft failure, and organ-system specific causes of death. The main analysis featured 2048 entries, with 1927 entries having nonoverlapping AIH, 52 entries having PSC overlap, and 69 entries having PBC overlap. Patients with PBC overlap were more likely to have graft failure (adjusted hazard ratio [aHR] 3.46 95% CI 1.70-7.05), mortality secondary to respiratory causes (aHR 3.57 95% CI 1.23-10.43), and mortality secondary to recurrent disease (aHR 9.53 95% CI 1.85-49.09). Case incidence rates reflected these findings, expressed in events per 1000 person-years. For patients with PBC overlap and nonoverlapping AIH cases, respectively. Graft failure: 28.87 events vs. 9.42 events, mortality secondary to respiratory causes: 12.83 deaths vs. 3.77 deaths, mortality secondary to recurrent disease: 6.42 deaths vs. 1.26 deaths. Those with AIH-PSC overlap experienced a higher risk of death from graft infection (aHR 10.43 95% CI 1.08-100.37; case-incidence rate: 3.89 vs. 0.31 mortalities per 1000 person-years). Supplementary analysis showed similar findings, in which overlapping autoimmune conditions were associated with higher adverse outcome rates. Patients with AIH-PBC overlap have higher risk of mortality due to recurrent liver disease and respiratory causes, and patients with AIH-PSC overlap have higher risk of mortality due to graft infection. While further prospective studies are needed to clarify the underlying mechanisms related to these findings, our study characterizes the prognostic implications of AIH overlap on post-LT mortality and graft failure risks.

S1070 Is Smoking a Novel Risk Factor for the Development of Autoimmune Hepatitis-Primary Biliary Cholangitis (AIH-PBC) Overlap Syndrome?

Introduction: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are both immune-mediated liver diseases, targeting biliary epithelial cells and hepatocytes, respectively. Due to their immune-mediated nature, some patients can develop overlap syndrome of AIH-PBC and have characteristics from both disease states. The aim of this study is to determine the risk factors that can predict the development of AIH-PBC overlap syndrome as compared to a related disorder, PBC-only disorder. Methods: This case-control study was performed at the Liver Associates of Texas Hepatology clinics in Houston, Texas. All patients diagnosed with AIH-PBC and PBC from January 2018 to May 2021 were included. Demographics and clinical parameters including patient characteristics and lab values were collected and compared. Patients were diagnosed with AIH-PBC overlap syndrome using liver biopsy and serological evidence. A binary logistic regression was used to determine the effects of demographic and clinical factors in the development AIH-PBC overlap syndrome compared to PBC-only controls. Results: A total of 136 PBC patients were included. Median age was 62 years, with 91.2% female. 36.8% were White, 14.7% Hispanic, 12.5% African American, 3.7% Asian, 2.2% Native American, and 30.1% unspecified. Of those 136 patients, 40 were identified to have PBC-AIH overlap syndrome (29.4%). No statistical differences were found in gender or ethnicity between the PBC-only and AIH-PBC overlap syndrome patients. Smoking was found to be significantly correlated with the presence of AIH-PBC overlap syndrome (p = 0.004). Accounting for BMI and alcohol use, patients with a smoking history were found to be 4.9 times (CI: 1.685-14.226) more likely to have AIH-PBC overlap syndrome than non-smokers. Alcohol use and BMI did not have a statistically significant effect on the presence of the AIH-PBC overlap syndrome. Conclusion: Smoking was found to be significantly correlated to the presence of the PBC-AIH overlap syndrome. This insight might provide support for counseling on smoking cessation in AIH or PBC patients who smoke. Further studies will be needed to determine other predictors and risk factors that might influence the development of AIH-PBC.Table 1.: Model Estimates of Possible Predictors for Overlap Syndrome in Primary Biliary Cholangitis Patients. Estimates represent log odds of patients with AIH-PBC overlap syndrome vs. PBC patients.

Two decades of research on autoimmune liver disease in Turkey.

Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are the 3 main autoimmune liver diseases (AILDs). The epidemiology of AILD in Turkey is not known. To determine the scientific status, we performed a scientometric analysis of AILD-related original articles that originated from Turkey. We searched the Web of Science database, the Science Citation Index Expanded (SCI-E), and the Social Sciences Citation Index (SSCI) by using the keywords "autoimmune hepatitis," "primary biliary cholangitis/primary biliary cirrhosis," and "primary sclerosing cholangitis" in conjunction with "Turkey." A scientometric analysis was done on the search results. We identified 117 AILD-related papers that were published in Turkey from 1997 to 2019. Among these, 70 case reports, letters, and reviews and 2 original articles that were not cited in SCI-E/SSCI were excluded. The remaining 45 original articles were further analyzed. These studies were related to AIH (n=22), PBC (n=7), PSC (n=9), PBC-AIH overlap (n=5), and others (n=2). Four of the publications originated in pediatric settings; 9 of 45 papers were published from 1997 to 2008 and 36 papers were published from 2009 to 2019. Most papers (75%) were reported from 5 centers; 9 papers (20%) were published in journals with an impact factor of 3 or higher. The overall number and quality of AILD-related papers in Turkey are unexpectedly low, although a number of papers have received considerable international recognition. More epidemiologic, prospective, and multicenter research projects are warranted to advance AILD knowledge and to produce high-quality research from Turkey.

The treatment response and corticosteroid therapy was predicted by GGT, chol, and fibrosis in patients of PBC-AIH overlap syndrome: a real-world study

The treatment response and corticosteroid therapy was predicted by GGT, chol, and fibrosis in patients of PBC-AIH overlap syndrome: a real-world study

Clinical characteristics of patients with autoimmune liver disease complicated with gallbladder stone

Objective To explore the clinical characteristics of liver function of patients with autoimmune liver disease (AILD) complicated with gallbladder stone (GS), so as to guide clinical practice. Methods From November 2009 to October 2018, at General Hospital of Tianjin Medical University, the clinical data of 386 patients with AILD were retrospectively analyzed. According to the relevant diagnostic criteria, 208 cases of autoimmune hepatitis (AIH), 129 cases of primary biliary cholangitis (PBC) and 49 cases of PBC-AIH overlap syndrome were screened out. The incidence, clinical characteristics and the changes of laboratory indicators including albumin, alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) of AILD patients complicated with GS were analyzed. Chi-square test, t test and rank sum test were performed for statistical analysis. Results There was no significant difference in the incidence between AILD, AIH, PBC and PBC-AIH overlap syndrome patients complicated with GS (32.9%, 127/386; 28.8%, 60/208; 36.4%, 47/129 and 40.8%, 20/49; respectively; P>0.05). Gallstones of AILD patients complicated with GS mostly were multiple and small stones with maximum diameter <1 cm (45.7%, 58/127 and 57.7%, 60/104, respectively). The age of initial diagnosis, the proportion of liver cirrhosis at inital diagnosis and the levels of ALP and GGT were higher in AILD patients complicated with GS than those of AILD patients without GS ((60.5±11.5) years vs. (57.6±11.5) years; 53.5%, 68/127 vs. 42.1%, 109/259; 154.00 U/L (89.00 U/L, 257.00 U/L) vs. 125.00 U/L (86.00 U/L, 212.00 U/L); 169.00 U/L (79.00 U/L, 343.00 U/L) vs. 128.60 U/L (48.00 U/L, 284.00 U/L); respectively); however the albumin level was lower than that of AILD patients without GS ((36.46±7.30) g/L vs. (38.34±7.58) g/L), and the differences were statistically significant (t=-2.361, χ2=4.506, Z=-2.192, -2.443, t=2.322; all P<0.05). The incidence of GS in AILD patients≥60 years old was higher than that AILD patients<60 years old (37.6%, 73/194 vs. 28.1%, 54/192), and the difference was statistically significant (χ2=3.948, P=0.047). The incidence of GS in AILD patients and AIH patients complicated with liver cirrhosis was higher than that in patients without liver cirrhosis (38.4%, 68/177 vs. 28.2%, 59/209; 35.7%, 35/98 vs. 22.7%, 25/110; respectively), and the differences were statistically significant (χ2=4.506 and 4.259, P=0.034 and 0.039). Conclusions AILD patients complicated with GS are common, most are multiple and small stones. When complicated with GS, the initial diagnosis may be delayed and the rate of liver cirrhosis at initial diagnosis may increase. The incidence of GS is high in AILD patients with older age and liver cirrhosis. Key words: Liver cirrhosis; Autoimmune liver disease; Gallbladder stone; Liver function; Age

2487 Primary Biliary Cholangitis With Autoimmune Hepatitis Overlap in Twin Males: A Unique Case of Related Autoimmune Diseases

INTRODUCTION: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are immune-mediated liver diseases with female predominance. Combined features of both, termed AIH-PBC overlap syndrome, occurs in rare instances. We present a unique case of AIH-PBC overlap syndrome in twin males. CASE DESCRIPTION/METHODS: Twin #1 was a 36-year-old man when he presented in 2012 with asymptomatic liver enzyme elevation. No new medications, herbals, alcohol or illicit drug use. No known family history of liver disease. Labs showed total bilirubin (TB) 0.5, alkaline phosphatase (ALP) 478, aspartate aminotransferase (AST) 81, alanine aminotransferase (ALT) 111, gamma-glutamyl transferase (GGT) 625, positive anti-mitochondrial antibody (AMA) &gt;1:640, and hypergammaglobulinemia (2128 mg/dL). Liver biopsy showed moderate plasma rich cell infiltrate with bile duct damage and mild fibrosis, consistent with AIH-PBC overlap. Patient was treated with steroids, azathioprine (AZA), and ursodeoxycholic acid (UDCA), later switched to obeticholic acid due to refractory PBC. He subsequently experienced marked biochemical improvement without disease progression. Twin #2 presented in 2017 with elevated liver enzymes and pruritus. Labs showed TB 1.1, ALP 755, AST 81, ALT 116, GGT 838, positive ANA &gt;1:2560, positive AMA &gt;100, and positive ASMA &gt;100. Liver biopsy showed moderate bile duct epithelial injury with lymphoplasmacytic infiltrate, consistent with AIH-PBC overlap, and stage II/IV hepatic fibrosis. He was treated with steroids, AZA, and UDCA. He also experienced marked biochemical improvement without disease progression. DISCUSSION: PBC, a rare autoimmune disorder with female preponderance, can lead to cirrhosis and liver failure. PBC-AIH overlap syndrome, described in 4.8-9.2% patients with PBC, is more likely to have rapid disease progression and hepatic decompensation. Combination of steroids, AZA and UDCA has been variably effective and can delay disease progression. To the best of our knowledge, this is the first case of AIH-PBC overlap syndrome reported in twin males and highlights the importance of inherited factors in immune mediated liver disorders. Although it is known that PBC and AIH are associated with human leukocyte antigen genes on chromosome 6, further study of the association between these disorders is limited by the paucity of patients. Early diagnosis of this condition is essential to prevent liver related complications with medical management.

FRI-018-High risk of no response and poor prognosis of immunosuppressive therapy in patients of pbc-aih overlap syndrome

FRI-018-High risk of no response and poor prognosis of immunosuppressive therapy in patients of pbc-aih overlap syndrome

The Efficacy and Safety of Obeticholic Acid (OCA) in Primary Biliary Cholangitis (PBC)

Introduction: Primary biliary cholangitis (PBC) is an inflammatory disease affecting intra-lobular bile ducts. Ursodeoxycholic acid (UDCA) was the sole standard treatment for PBC for many years and is currently first line.Obeticholic acid (OCA), a farnesoid X receptor agonist, is approved as additional therapy for PBC in UDCA non-responders or as monotherapy for UDCA intolerant patients.This study reports the real world experience for the efficacy and safety of OCA from 2 large academic centers. Methods: Retrospective screening for PBC by chart review and OCA treated patients identified.Demographic information, baseline laboratory tests, clinical data were collected and patients followed for a minimum of 1 year on OCA. Statistical analysis performed using stat software SPSS IBM. Results: We identified 230 PBC and PBC-AIH overlap patients and within this group 38 patients were on treatment with OCA either because of poor response (n=37) or intolerance to UDCA (n=1).Diagnosis was based on liver biopsy [95%] and AMA serologies [86%]. Overall 30 patients had PBC alone (78%) and PBC predominant with AIH features was seen in 8 patients (22%).Majority of patients were women [n=36/38, 95%] with an age ranging between 40-74 (mean 61).Cirrhosis was noted in fifteen patients [n=15/38, 40%]. OCA was initiated with low dose 5 mg daily and titrated up to 10mg daily at 3 months if lack of response as determined by alkaline phosphatase >1.67 ULN. All patients were on Ursodiol as primary PBC treatment with (12-15 mg/kg calculated dose per weight).Results: Nineteen patients [50%] needed dose upregulation to 10 mg OCA due to lack of response in alkaline phosphatase at 6 months.Overall eighteen patients have achieved biochemical response [47%] which occurred mainly in non-cirrhosis PBC patients versus cirrhosis PBC [16/23 vs 4/15 - OR 0.159 CI 0.03-0.67]. Reasons for treatment failure were side effects in 11 patients and lack of biochemical response in 8 patients.In the biochemical treatment failure six patients were cirrhotic and mean alkaline phosphatase was 360 mg/dl in treatment failure versus 150 mg/dl in responders (p=0.0001).The commonest side effects resulting in discontinuation was pruritus Conclusion: OCA efficacy is 47% in real world PBC patients with tolerability the major issue for treatment failure and with decreased efficacy in cirrhotic patients. Careful patient selection and optimizing side effect management will be necessary to ensure improved outcomes.

Evaluation of classical and novel autoantibodies for the diagnosis of Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome (PBC-AIH OS).

Background and aimsUp to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS. In our well defined PBC patient cohorts, a comprehensive assessment of various classical and novel autoantibodies was evaluated for their utility in identifying PBC-AIH OS patients.MethodsPBC-AIH OS was classified according to the Paris criteria and PBC as per the European Association for the Study of the Liver guidelines. Biobanked serum samples from 197 patients at the University of Calgary Liver Unit and the University of Alberta were analyzed for classical and novel autoantibodies. Anti-dsDNA was measured by the Crithidia luciliae immunofluorescence (CLIFT) assay (1:20 dilution) and chemiluminescence (CIA: QUANTA Flash®, Inova Diagnostics, San Diego). Anti-p53, anti-Ro52/TRIM21, anti-YB 1, anti-GW182, anti-Ge-1, and anti-Ago 2 were measured by either an addressable laser bead immunoassay (ALBIA) or line immunoassay (LIA). Autoantibodies against MIT3, gp210, sp100, LKM1, SLA, and the novel autoantibodies Hexokinase-1 (HK-1), and Kelch like protein 12 (KLHL-12) were measured using QUANTA Lite® ELISA assays. We applied non-parametric methods to compare the biomarkers frequencies between study groups. We used multivariate adjusted models and AUROC to compare the diagnostic accuracy of the different autoantibodies alone or in combination with serum biochemistry.Results16 out of 197 PBC patients (8.1%) were classified as PBC-AIH OS. Compared to PBC patients, PBC-AIH OS patients were similar in age (median: 59 vs. 63, P = 0.21) and female predominance (94% vs. 89%, P = 1.00). Anti-dsDNA-by CLIFT (37.5% in PBC-AIH OS vs 9.9% in PBC alone, P <0.01) was the only autoantibody associated with PBC-AIH OS; a finding consistent with previous reports. Significant elevation in serum ALT (62 IU/L in PBC-AIH OS vs 37 IU/L in PBC alone, P < 0.01), and serum IgG (17.6 g/L in OS vs 12.1 g/L in PBC alone, P <0.01) were observed in patients with PBC-AIH OS receiving medical/immunosuppressive therapy. In a multivariate model, positive anti-dsDNA by CLIFT, ALT and IgG were significant predictors of PBC-AIH OS with an area under the receiver operator curve (AUROC) value of 0.84.ConclusionsConsistent with previous findings, the presence of anti-dsDNA by CLIFT is associated with PBC-AIH OS. Contrary to previous reports, anti-p53 was not associated with PBC-AIH OS. Our comprehensive evaluation of various classical and novel autoantibody biomarkers including Ro52/TRIM21, anti-p53, anti-KLHL-12 and anti-HK-1 were not significantly associated with PBC-AIH OS. Our findings highlight the ongoing need for the research and development of new autoantibody biomarkers to aid in the diagnosis of PBC-AIH OS.

Diagnosis of Liver Involvement in Primary Sjögren Syndrome.

Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sjögren syndrome (SS). In the 1990s, a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of liver disease, liver function and a complete panel of autoantibodies. Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS. The most recent studies have shown that, after eliminating hepatotoxic drugs and fatty liver disease, the two main causes of liver disease in primary SS are chronic viral infections and autoimmune liver diseases. The differential diagnosis of liver disease in primary SS (viral vs autoimmune) is clinically important, since the two processes require different therapeutic approaches and have different prognoses. With respect to viral infections, chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area, while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries. After eliminating viral hepatitis, primary biliary cirrhosis (PBC) should be considered the main cause of liver disease in primary SS. PBC-related SS patients may have a broad spectrum of abnormalities of the liver, including having no clinical or analytical data suggestive of liver disease. Autoimmune hepatitis (AIH) is the second most frequently found autoimmune liver disease to be associated with SS (all reported cases are type I), and nearly 10% of these patients have an AIH-PBC overlap. Finally, IgG4-related disease must be investigated in patients with SS presenting with sclerosing cholangitis, especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present.

全身性強皮症に自己免疫性肝炎と原発性胆汁性胆管炎のオーバーラップ症候群を合併し，瘢痕肝の所見を呈した一例

全身性強皮症に自己免疫性肝炎と原発性胆汁性胆管炎のオーバーラップ症候群を合併し，瘢痕肝の所見を呈した一例

Analysis of prognosis and coexistence with other autoimmune diseases in 232 patients with autoimmune liver disease

Objective To study the probability of other autoimmune diseases in primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) and explore its effects on the prognosis. Methods From January 1994 to March 2014, the data of 232 patients with autoimmune liver diseases (AILD) were collected. The type and case number of coexisting with other autoimmune diseases of patients with PBC, AIH and PSC were analyzed and compared. Cox regression model was performed to analyze the effects of coexisting with autoimmune diseases on the prognosis of AILD. Results Among 135 PBC patients, there were 64 cases that coexisted with Sjogren's syndrome (SS), seven cases with systemic lupus erythematosus (SLE), seven cases with rheumatoid arthritis (RA), nine cases with systemic sclerosis (SSc), three cases with polymyositis and/or dermatomyositis (PM/DM) and one case with Crohn's disease. Among 55 AIH patients, threre were 19 cases that coexisted with SS, 10 cases with SLE, one case with RA, two cases with SSc and two cases with PM/DM. Among 24 PSC patients, there were seven cases combined with ulceric colitis, one case with Crohn's disease and one case with RA. Among 18 patients with PBC-AIH overlap syndrome, there were five cases with SS and one case with RA. Compared with PBC patients, the risk of pulmonary interstitial fibrosis increased in PBC patiento coexisting with SS (OR=34.0, 95%CI 8.9 to 130.1). After gender, age, disease course and medicine intervention were adjusted, the prognosis of AILD which included death, liver transplantation and liver cirrhosis complications was not affected by the coexistence with other autoimmune diseases. Conclusions AILD patients coexisting with other autoimmune diseases is common, most of which are SS, SLE, SSc and RA. PBC patients coexisting with SS is the risk factor of pulmonary interstitial fibrosis, and coexisting with other autoimmune disease does not independently affect the prognosis of AILD. Key words: Hepatitis, autoimmune; Comorbidity; Autoimmune diseases; Prognosis

Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy.

Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren's syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, cholinergic agents, and scrupulous oral and dental care. Complications of cirrhosis from advanced PBC include esophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatoma formation.

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: simplified criteria may be effective in the diagnosis in Chinese patients.

To evaluate the Paris criteria, the revised diagnostic criteria and the simplified diagnostic scoring system in the diagnosis of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome in Chinese patients. Medical records of the patients who were diagnosed with PBC at the Union Hospital and Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology (Wuhan, Hubei Province, China) from 2003 to 2012 were retrospectively reviewed. The overlap syndrome was diagnosed based on the Paris criteria, the revised criteria and the simplified criteria, respectively. Patients' clinical characteristics, laboratory examination results and histological findings were collected. The sensitivity and specificity of the three criteria for diagnosing PBC-AIH overlap syndrome were calculated. PBC-AIH overlap syndrome was diagnosed in 2, 13 and 10 patients with PBC based on the Paris, the revised and the simplified criteria, respectively. The sensitivity and specificity of the simplified criteria in diagnosing the overlap syndrome was 90.0% and 98.2%, which were the highest among the three criteria, followed by the revised criteria. The Paris criteria showed a high specificity (100%) but a relatively low sensitivity (20.0%). In addition, some patients who did not fulfil the Paris criteria still benefited from the immunosuppressive agents. For Chinese patients with the PBC-AIH overlap syndrome, the simplified criteria appear to be the most efficacious compared with the Paris criteria and the revised criteria. Further studies should be performed to confirm these observations with respect to long-term outcomes and therapeutic implications.

Sequential presentation of primary biliary cirrhosis and autoimmune hepatitis

Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is used to describe the coexistence of both diseases, with either a sequential or a simultaneous presentation in the same patient. Available studies have focused on the simultaneous form, whereas there is limited information on sequential PBC-AIH. We carried out a retrospective study of patients who sequentially developed PBC-AIH overlap syndrome. The medical data of 1065 patients diagnosed with PBC (n=483) and AIH (n=582) were retrospectively analyzed. A sequential development of PBC-AIH was observed in 19 (1.8%) patients after a mean of 6.5 (1-14) years of follow-up. AIH developed in 12 (2.5%) PBC patients, whereas PBC occurred in seven (1.2%) patients with AIH. The baseline serologic and histological findings of patients who developed PBC-AIH were similar to those of patients with typical PBC or AIH. Eighteen patients were treated with a combination of ursodeoxycholic acid (UDCA) and immunosuppression after the diagnosis of PBC-AIH was established. One patient showed a spontaneous resolution of hepatitic flare under UDCA therapy. Biochemical remission was achieved in 16 patients, whereas three progressed to decompensated cirrhosis and required liver transplantation. The sequential overlap of PBC-AIH can occur during the follow-up of patients with pure PBC or AIH. In our cohort, we could not identify any factors that predicted the development of this rare condition. The combination of UDCA and immunosuppression seems to be an appropriate therapy in the setting of PBC-AIH.

Overlap Syndrome of Primary Biliary Cirrhosis and Autoimmune Hepatitis with Unusual Initial Presentation as an Acute Hepatic Failure

Primary Biliary Cirrhosis (PBC) and Autoimmune Hepatitis (AIH) may simultaneously coexist in some patients, designated as PBC-AIH overlap syndrome. Acute hepatic failure is an unusual initial form of presentation of PBCAIH overlap syndrome. We report the case of a 31 year-old woman with autoimmune PBC-AIH overlap syndrome who presented with an acute hepatic failure. She revealed a good response to corticosteroid and ursodeoxycholic acid 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.

Expression of micro‐RNAs in peripheral blood mononuclear cells from primary biliary cirrhosis patients

The aim of this study was to clarify the relationship between the expression of micro-RNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) and clinical presentation in patients with primary biliary cirrhosis (PBC). This study involved 58 patients with PBC, patients with control diseases including 25 patients with autoimmune hepatitis (AIH), six patients with PBC-AIH overlap syndrome, 23 patients with systemic lupus erythematosus (SLE), and 30 healthy controls. After miRNA was extracted from PBMCs, the expressions of miR-26a, miR-328, miR-299-5p, miR-146a, miR-155, miR-16, miR-132 and let7a were quantified by real-time PCR. The relationships between all miRNA expressions and clinical test parameters were also examined. In PBC, the expressions of miR-155 and miR-146a were significantly increased compared to those in healthy controls. For miR-26a, miR-299-5p, miR-328 and let-7a, although no significant difference was observed in expression between patients and healthy controls, expressions were significantly increased in PBC compared to those in AIH. Expressions of miR-299-5p were significantly increased in PBC patients resistant to treatment with ursodeoxycholic acid (n = 18) compared to those in healthy controls. In the evaluation of the relationship between miRNA expression and clinical test parameters, significant and positive correlations were found for miR-299-5p with alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin and immunoglobulin M levels. The preset results suggest the existence of miRNAs that exhibit disease-specific increases in expression and miRNAs closely correlated with clinical test values in PBC. Further analyses of these miRNAs may contribute to the elucidation of the pathology of PBC.

Overlap Syndromes of Autoimmune Liver Disease

Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic liver diseases of presumed autoimmune origin. Conditions exhibiting features of two different autoimmune liver diseases are commonly designated overlap syndromes, although there is no current agreement on what constitutes an overlap syndrome or specific diagnostic criteria. Identification of patients with features of overlap syndrome is relevant for management as outcomes may differ from outcomes of patients with diagnosis of classic autoimmune liver diseases and treatment may need to be adjusted. Due to their rarity, no large therapeutic trials are available and treatment of overlap conditions is empirical and based upon extrapolation of data from the primary autoimmune liver diseases. AIH-PBC overlap is the most frequently described overlap syndrome and may be associated with a poor prognosis. This may represent an important and unrecognized cause of resistance to ursodeoxycholic acid (UDCA) in patients with PBC. AIH-PSC overlap is less commonly reported. Prognosis may be better than in patients with PSC alone, however worse than in patients with AIH alone. Further studies are needed for determining diagnosis, natural history and optimal therapeutic strategies of overlap syndromes of autoimmune liver diseases.