Primary Biliary Cholangitis Cases Research Articles

Improving predictive accuracy in primary biliary cholangitis: Anew genetic risk score.

Genetic variants influence primary biliary cholangitis (PBC) risk. We established and tested an accurate polygenic risk score (PRS) using these variants. Data from two Italian cohorts (OldIT 444 cases, 901 controls; NewIT 255 cases, 579 controls) were analysed. The latest international genome-wide meta-analysis provided effect size estimates. The PRS, together with human leukocyte antigen (HLA) status and sex, was included in an integrated risk model. Starting from 46 non-HLA genes, 22 variants were selected. PBC patients in the OldIT cohort showed a higher risk score than controls: -.014 (interquartile range, IQR, -.023, .005) versus -.022 (IQR -.030, -.013) (p < 2.2 × 10-16). For genetic-based prediction, the area under the curve (AUC) was .72; adding sex increased the AUC to .82. Validation in the NewIT cohort confirmed the model's accuracy (.71 without sex, .81 with sex). Individuals in the top group, representing the highest 25%, had a PBC risk approximately 14 times higher than that of the reference group (lowest 25%; p < 10-6). The combination of sex and a novel PRS accurately discriminated between PBC cases and controls. The model identified a subset of individuals at increased risk of PBC who might benefit from tailored monitoring.

Comparative histologic features among liver biopsies with biliary-pattern injury and confirmed clinical diagnoses

Biliary-pattern injury in the liver (eg, duct injury, ductular reaction, cholestasis) can occur in several conditions, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), large duct obstruction (LDO), and drug-induced liver injury (DILI). While the histologic changes in these conditions have been individually well described, distinguishing among them remains often challenging, particularly when biopsy samples are limited in size, robust clinical information is unavailable, and/or the pathologist does not feel confident in evaluating liver disease. This study evaluated histologic features that could aid the diagnosis of biliary-pattern injury on biopsy. We reviewed 121 liver biopsies from clinically confirmed cases of PBC, PSC, chronic LDO, or DILI for multiple clinical and histologic parameters. The rates of these histologic findings were then compared among different entities. Onion-skin fibrosis was seen in 14% of PSC in comparison to 0%, 5%, and 0% of PBC, DILI, and chronic LDO (P = 0.031). Florid duct lesions were identified in 21% of PBC compared to 2% of PSC and 0% of DILI and LDO (P = 0.0065). Similarly, 42% of PBC showed lobular granulomas, compared to 7% of PSC, 11% of DILI, and 33% of chronic LDO (P = 0.0001). Cholestasis was more commonly seen in DILI (42%) and chronic LDO (83%) than in PBC (4%) and PSC (16%) (P < 0.0001). Lobular chronic inflammation was found in a significantly higher percentage of PBC and LDO than of PSC and DILI (P = 0.0009). There were significantly fewer cases of PBC showing neutrophils in ductular reaction than PSC, DILI, and LDO (P = 0.0063). Histologic findings that can help suggest a diagnosis in liver biopsies with biliary-pattern injury include florid duct lesions, lobular granulomas, lack of neutrophils in ductular reaction, and lobular chronic inflammation in PBC; onion-skin fibrosis in PSC; cholestasis and feathery degeneration in DILI; and lobular granulomas, lobular chronic inflammation, cholestasis, and feathery degeneration in chronic LDO. These findings are likely most helpful when complicating factors interfere with biopsy interpretation.

Primary Biliary Cholangitis and Rheumatoid Arthritis: An Emerging Association

Primary Biliary Cholangitis (PBC), formerly known as primary biliary cirrhosis, is an autoimmune-related cholestatic hepatopathy, representing a common cause of intrahepatic cholestasis due to progressive bile duct destruction. Often, PBC is linked with other autoimmune disorders such as Sjogren’s syndrome, thyroid dysfunction, scleroderma, and systemic lupus erythematosus. However, the association of PBC with rheumatoid arthritis (RA) is rare, estimated at 1.8 to 5.6%. We present a clinical case of PBC discovered in a patient with deforming rheumatoid arthritis.

Rare renal proximal tubular dysfunctions in primary biliary cholangitis

Introduction Renal involvement of primary biliary cholangitis (PBC) usually presents as distal renal tubular acidosis. Proximal tubular (PT) dysfunctions in PBC were rarely reported with unclear clinicopathological characteristics and renal prognosis. Methods We identified 11 cases of PBC with PT dysfunctions (PBC-PT). Their medical document, kidney pathology, and follow-up data were retrospectively reviewed and analyzed. Results The 11 PBC-PT patients were mainly middle-aged (57.8 ± 5.2 years) females (81.8%). Most of them were asymptomatic PBC (7, 63.6%) with a high prevalence of elevated serum immunoglobulin M (IgM, 81.8%) and G (IgG, 54.5%) levels. In the kidney, they had a mean estimated glomerular filtration rate (eGFR) level of 46.54 ± 23.03 ml/min/1.73m2, and 81.8% of them had eGFR below 60 ml/min/1.73m2. They showed different degrees of PT dysfunctions, including hyperuricosuria, hypouricemia, normoglycemic glycosuria, generalized aminoaciduria, hyperphosphaturia, and hypophosphatemia. Their kidney pathology showed tubulointerstitial nephritis with lymphoplasmacytic infiltrates, brush border defects, and proximal tubulitis. After glucocorticoids treatment, the PT dysfunctions manifesting as hypophosphatemia, hypouricemia, and renal glycosuria all recovered, and the eGFR levels were improved from 43.24 ± 19.60 ml/min/1.73m2 to 55.02 ± 21.14 ml/min/1.73m2 (p = 0.028), accompanied by significant improvements of serum IgM levels (from 5.97 ± 4.55 g/L to 2.09 ± 1.48 g/L, p = 0.019). Conclusions The PT dysfunctions were rare in PBC patients, and glucocorticoids treatment could benefit the improvements of eGFR and tubular functions.

P343 Pancreato-biliary disorders in patients with inflammatory bowel diseases – a single-centre report

Abstract Background Inflammatory bowel diseases (IBD) are regarded as multisystemic disorders due to the high prevalence of extraintestinal symptoms. Hepato-pancreato-biliary involvement can be present in up to 50% of patients, due to IBD extraintestinal manifestations and complications. Our aim was to evaluate the prevalence of the pancreato-biliary diseases in patients diagnosed with IBD. Methods We conducted a single-centre retrospective study which included patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC), admitted between 1 January 2018 and 1 August 2023 in the Gastroenterology and Surgery Departments of the Fundeni Clinical Institute (Romania). We analysed the medical history (including abdominal imaging - ultrasound, computed tomography or magnetic resonance imaging) of patients during hospital follow-up and we screened for pancreato-biliary disorders. Results We analysed 1736 patients, of which 303 patients (17%) associated pancreato-biliary involvement and 756 patients (44%) had no pancreato-biliary disorders, with both subgroups having at least one abdominal imaging scan during follow-up; 677 patients (39%) had neither history of pancreato-biliary disorders, nor abdominal imaging. 30 patients (1.72% of total; 56.6% CD, 77% male) had acute pancreatitis (93.3% mild), 66.67% being drug-induced (13 cases - azathioprine, six cases - 5-amynosalicilates, one case - metronidazole). Three patients were diagnosed with idiopathic chronic pancreatitis and one with type 2 autoimmune pancreatitis. In the subgroup that underwent abdominal imaging (1059 patients) we identified 124 patients (11.70%) with pancreatic steatosis, 11 patients (1.03%) with pancreatic cysts (one case of intraductal papillary mucinous neoplasm) and three patients (0.28%) with congenital pancreatic anomalies (two annular pancreases, one pancreas divisum). There were no patients diagnosed with pancreatic adenocarcinoma. We identified 14 patients (0.8% from total; 64.28% UC, 57.14% male) with primary sclerosing cholangitis, of which five underwent liver transplantation, one case of primary biliary cholangitis and three cases of cholangiocarcinoma. The subgroup with abdominal imaging included 46 patients (4.34%) with prior cholecystectomy and 147 patients (13.88%) with gallbladder lithiasis or sludge (59.86% CD; 53.06% male; 39.45% intestinal resection). Conclusion Up to one third of patients with IBD that underwent abdominal imaging associated pancreato-biliary involvement. The high risk of drug-induced acute pancreatitis in IBD has to be taken into consideration. Screening for possible extraintestinal manifestations and early diagnosis of extraintestinal complications might improve the IBD management.

Primary Biliary Cholangitis in Men: A Rare and Particular Presentation (About 2 Cases and Review of the Literature)

Primary biliary cholangitis (PBC) is a rare etiology of cholestatic jaundice in men. We report two rare cases of PBC in men revealed by chronic cholestasis (jaundice, pruritus, dark urine, discolored stools, ALP greater than 1.5 times the upper limit and GGT greater than 3 times the upper limit). The first case had positive anti-mitochondria type 2 antibodies, while in the second case they were negative with positive anti gp-210 antibodies. The histological study of liver biopsies in the first case confirmed PBC. The second case was diagnosed at the stage of cirrhosis.

Ultrasound imaging findings in primary biliary cholangitis

BackgroundOur study aimed to analyze the characteristics of ultrasound images corresponding to each histological stage of primary biliary cholangitis (PBC).MethodsWe prospectively analyzed 75 confirmed cases of PBC and used liver biopsy as the gold standard to determine the disease stage.ResultsThe typical ultrasound images of patients with PBC were characterized by a thickening of the portal vein wall (PVW) and periportal hypoechoic band (PHB) width with increasing histological stages, and significant increases in the left hepatic lobe diameter (LHLD) in stage II (by 64.0%) and stage III (by 69.2%). PHB width (r = 0.857, p < 0.001), PVW thickness (r = 0.488, p < 0.001), and spleen area (r = 0.8774, p < 0.001) were positively correlated with the histological stage. Significant changes were noted in the liver surface, echo texture, and edge between different stages. The areas under the receiver operating characteristic curve of composite indicators were 0.965 for predicting progressive PBC(≥ stage 2), and 0.926 for predicting advanced PBC(≥ stage 3).ConclusionsThe ultrasound imaging characteristics of patients with PBC varied according to the histological staging. LHLD, PVW thickness, and PHB width were significantly correlated with the histological stage. A combination of high- and low-frequency ultrasound imaging can provide relevant cues regarding the degree of PBC progression and important clinical reference values. The application of all the ultrasound image findings as the composite indicators can better predict progressive and advanced PBC, providing important clinical reference values.

Antimitochondrial antibody-negative primary biliary cirrhosis with secondary Sjogren syndrome: a case report

Introduction and importance: Primary biliary cholangitis (PBC) is a rare immune-mediated liver disease characterized by the destruction of intrahepatic bile ducts and a positive antimitochondrial antibody (AMA), which is considered a serological hallmark for the diagnosis. Rarely, AMA can be absent/nondetectable in a few cases and is referred to as ‘AMA-negative’. Case presentation: The authors present such an uncommon case of AMA-negative PBC in a 39-year-female with Sjogren’s syndrome who presented with fatigue, pruritus, and dry eyes. Clinical discussion: Previously published studies state that approximately only about 5% of patients with PBC are ‘AMA-negative’. For patients negative for AMA, the diagnosis has to be based on typical pathological features of this disease. Once a diagnosis of PBC is established, regardless of whether it is positive or negative for AMAs, ursodeoxycholic acid is a widely accepted treatment. Conclusion: The presence/absence of AMAs is associated with similar clinical, biochemical, and histopathological characteristics in PBC. The identification of AMAs alone should not impact the diagnosis or treatment of PBC.

A new method to estimate the histological stage of primary biliary cholangitis

ObjectiveTo analyze the diagnostic efficacy of the periportal hypoechoic band (PHB) in the histological stage of patients with primary biliary cholangitis (PBC).MethodsWe prospectively included 77 cases of PBC pathologically or clinically confirmed, and high-frequency ultrasound (HFUS) measurements of the PHB were performed in all included patients. Ludwig staging system of histopathology was used as the gold standard.ResultsThe width of the PHB was positively correlated with histological staging (r = 0.844, p < 0.001). By area under the receiving operating characteristic curve (AUROC), the best cutoff value for PHB for advanced stage (≥ stage 3) was 2.4 mm (AUROC: 0.934; 95%CI: 0.841–0.981) and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The correct rate for early-stage PBC was 87.9% and for the progressive stage was 93.1%. After multi-factor regression analysis, the PHB (OR = 1.331, CI = 1.105–1.603, p = 0.003) and total bilirubin (OR = 1.156, CI = 1.041–1.285, p = 0.007) were independent influencing factors for progressive PBC.ConclusionsMeasurement of the PHB to assess advanced PBC is a simple and effective method. This method may complement current methods for the histological staging assessment of patients with PBC.RegistrationClinical trial registration: ChiCTR 2000032053, 2020/04/19.Clinical relevance statementThe measurement of periportal hypoechoic band (PHB) provides a simple and easy assessment of the degree of disease progression in patients with PBC and provides an important clinical reference in predicting the histological staging of PBC from an ultrasound perspective.Key Points• The PHB is correlated with histological staging in the patient with PBC.• The area under the ROC curves of PHB for detecting advanced stage (≥ stage 3) were 0.934 and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The application of PHB can better assess the advanced PBC.• Measurement of the PHB to assess advanced PBC is a simple and effective method that can significantly reduce the need for liver biopsy.

Understanding immune mechanisms to create novel treatments for primary biliary cholangitis

Understanding immune mechanisms to create novel treatments for primary biliary cholangitis Professor Channakeshava S Umeshappa from Dalhousie University discusses the burden of primary biliary cholangitis and how understanding immune mechanisms may help to treat it. Primary biliary cholangitis (PBC) is characterised by chronic inflammation of the interlobular bile ducts, leading to fibrosis, cirrhosis, and liver failure if left untreated. Symptoms of PBC include fatigue, jaundice, itchy skin, abdominal pain, nausea or vomiting, dry eyes and mouth, and bone and joint aches. The incidence of PBC is increasing worldwide,(1) but is most common in Europe and North America.(2) PBC has a female predominance, affecting primarily middle-aged women (over 90% of the PBC cases). Clinically, it is often diagnosed by detecting anti-mitochondrial autoantibodies and elevated alkaline phosphatase enzymes in blood tests.

Evaluation of the Clinical Characteristics of Dry Eye Secondary to Different Types of Liver Diseases.

This study compares the clinical characteristics of dry eye secondary to primary biliary cholangitis (PBC), drug-induced liver injury (DILI), and viral hepatitis B(HBV) to evaluate the ocular surface damage caused by different types of liver diseases. Thirty healthy people were included as control group. Sixty patients with dry eye secondary to different types of liver disease were included, including 19 cases of PBC, 18 cases of DILI, and 23 cases of HBV. All patients were evaluated by the SPEED questionnaire, corneal fluorescein staining (CFS), noninvasive tear breakup time (NIBUT), Schirmer I test (SIt), tear meniscus height test (TMH), the area of meibomian glands dropout (MG dropout), partial blinking rate (PBR), lipid layer thickness (LLT), meibum expressibility, and meibum quality. There are statistical differences in ophthalmic examination results between different types of liver diseases and normal people (P < 0.05). Compared with DILI and HBV groups, the CFS score of PBC group score was higher (P < 0.05), the PBR was higher (P < 0.05), and the SIt was lower (P < 0.01). The TMH of PBC and DILI groups were significantly lower than the HBV group, and the difference was statistically significant (P < 0.05). Compared with the PBC group, the LLT of the DILI group decreased (P < 0.01). The area of meibomian glands dropout of the three groups had mild-to-moderate defects, but there was no significant statistical difference between groups (P > 0.05).The Meibum quality score in the DILI group was significantly higher than the HBV group (P < 0.05). The PBC group was more prone to aqueous-deficient dry eye. The DILI group was more prone to obstructive meibomian gland dysfunction (MGD).The HBV group was more prone to nonobstructive MGD. The symptoms of dry eye in the PBC group are mild-to-moderate discomfort, but the degree of corneal damage is higher, indicating that the corneal sensitivity is reduced, which may be related to the high rate of partial blinking.

A nationwide study of autoimmune liver diseases in the Faroe Islands: Incidence, prevalence, and causes of death 2004 - 2021

ABSTRACT Background and aims: Autoimmune liver diseases are rare diseases, and population-based studies on the epidemiology of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are sparse. We aimed to assess the incidence of AIH, PBC, and PSC in the Faroe Islands. Methods: All cases of AIH, PBC, and PSC diagnosed in the Faroe Islands between January 1st, 2004, and December 31st, 2021, were included in this nationwide registry-based cohort study. In addition, we searched all medical records to assess diagnostic criteria and cause of death. Results: The incidences of AIH, PBC, and PSC in the Faroe Islands were 5.2, 2.5 and 0.7 per 100,000 population per year, respectively. Point prevalence per 100,000 population on December 31st 2021, was 71.8 for AIH, 38.5 for PBC, and 11.0 for PSC. Nine AIH patients died after a median of 3 years, three died of hepatocellular carcinoma (HCC), and two died of liver failure. Five PBC patients died after a median of 7 years, one of HCC and one of liver failure. One PSC patient died of cholangiocarcinoma. Conclusion: The incidence and prevalence of AIH, PBC and PSC in the Faroe Islands are among the highest reported in population-based settings.

A case of primary biliary cholangitis – diagnostic and treatment approaches

Primary biliary cholangitis (PBC) is a chronic, autoimmune, slowly progressive liver disease, characterized by the presence of antimitochondrial antibodies (AMA), cholestatic syndrome, and histological lesions of the interlobular bile ducts, with the potential progression to liver fibrosis and cirrhosis. AMA or AMA-M2 are specific markers for diagnosis of PBC, detected in about 90 % of patients. Antinuclear antibodies (ANA) specific for primary biliary cholangitis, anti-sp100 or anti-gp210 subtypes, can be used as markers of PBC diagnosis in case of patients with negative AMA. In addition to being specific for diagnosis of PBC, the presence of anti-gp210 was associated with more severe forms, rapid progression and poor prognosis of the disease. The first therapeutic option for PBC is considered ursodeoxycholic acid (UDCA), and for patients with a suboptimal response, it is recommended second-line treatment with obeticholic acid. 8-10 % of patients with PBC may have overlap syndrome with autoimmune hepatitis (AIH), which occurs with biochemical, serological and/or histological features of AIH in patients with cholestatic manifestations of PBC. „Paris Criteria” help to identify patients with PBC/AIH overlap syndrome. The article also examines a clinical case of PBC, AMA negative, which required additional investigations for evaluation, diagnostic discussion and current management of overlap syndrome associating PBC and autoimmune hepatitis.

Immune signatures in variant syndromes of primary biliary cholangitis and autoimmune hepatitis.

Variant syndromes of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) share diagnostic features of both entities, but their immunological underpinnings remain largely unexplored. We performed blood profiling of 23 soluble immune markers and immunogenetics in a cohort of 88 patients with autoimmune liver diseases (29 typical AIH, 31 typical PBC and 28 with clinically PBC/AIH variant syndromes). The association with demographical, serological and clinical features was analyzed. While T and B cell receptor repertoires were highly skewed in variant syndromes compared to healthy controls, these biases were not sufficiently discriminated within the spectrum of autoimmune liver diseases. High circulating checkpoint molecules sCD25, sLAG-3, sCD86 and sTim-3 discriminated AIH from PBC on top of classical parameters such as transaminases and immunoglobulin levels. In addition, a second cluster of correlated soluble immune factors encompassing essentially TNF, IFNγ, IL12p70, sCTLA-4, sPD-1 and sPD-L1 appeared characteristic of AIH. Cases with complete biochemical responses to treatment generally showed a lower level of dysregulation. Unsupervised hierarchical clustering of classical and variant syndromes identified two pathological immunotypes consisting predominantly of either AIH or PBC cases. Variant syndromes did not form a separate group, but clustered together with either classical AIH or PBC. Clinically, patient with AIH-like variant syndromes were less likely to be able discontinue immunosuppressive treatment. Our analyses suggest that variants of immune mediated liver diseases may represent an immunological spectrum from PBC to AIH-like disease reflected by their pattern of soluble immune checkpoint molecules rather than separate entities.

Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells.

In patients with primary biliary cholangitis (PBC), the serum liver biochemistry measured during treatment with ursodeoxycholic acid-the UDCA response-accurately predicts long-term outcome. Molecular characterization of patients stratified by UDCA response can improve biological understanding of the high-risk disease, thereby helping to identify alternative approaches to disease-modifying therapy. In this study, we sought to characterize the immunobiology of the UDCA response using transcriptional profiling of peripheral blood mononuclear cell subsets. We performed bulk RNA-sequencing of monocytes and TH1, TH17, TREG, and B cells isolated from the peripheral blood of 15 PBC patients with adequate UDCA response ("responders"), 16 PBC patients with inadequate UDCA response ("nonresponders"), and 15 matched controls. We used the Weighted Gene Co-expression Network Analysis to identify networks of co-expressed genes ("modules") associated with response status and the most highly connected genes ("hub genes") within them. Finally, we performed a Multi-Omics Factor Analysis of the Weighted Gene Co-expression Network Analysis modules to identify the principal axes of biological variation ("latent factors") across all peripheral blood mononuclear cell subsets. Using the Weighted Gene Co-expression Network Analysis, we identified modules associated with response and/or disease status (q<0.05) in each peripheral blood mononuclear cell subset. Hub genes and functional annotations suggested that monocytes are proinflammatory in nonresponders, but antiinflammatory in responders; TH1 and TH17 cells are activated in all PBC cases but better regulated in responders; and TREG cells are activated-but also kept in check-in responders. Using the Multi-Omics Factor Analysis, we found that antiinflammatory activity in monocytes, regulation of TH1 cells, and activation of TREG cells are interrelated and more prominent in responders. We provide evidence that adaptive immune responses are better regulated in patients with PBC with adequate UDCA response.

Bioinformatic analysis identified novel candidate genes with the potentials for diagnostic blood testing of primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune disorder characterized by intrahepatic bile duct destruction and cholestatic liver injury. Diagnosis of PBC is generally based on the existence of anti-mitochondrial antibody (AMA) in blood samples; however, some PBC patients are negative for serum AMA tests, and invasive liver histological testing is required in rare PBC cases. The current study seeks novel candidate genes that are associated with PBC status and have potentials for blood diagnostic testing. Human transcriptomic profiling data of liver and blood samples were obtained from Gene Expression Omnibus (GEO). Three GEO data series (GSE79850, GSE159676, and GSE119600) were downloaded, and bioinformatic analyses were performed. Various differentially expressed genes were identified in three data series by comparing PBC patients and control individuals. Twelve candidate genes were identified, which were upregulated in both liver tissues and blood samples of PBC patients in all three data series. The enrichment analysis demonstrated that 8 out of 12 candidate genes were associated with biological functions, which were closely related to autoimmune diseases including PBC. Candidate genes, especially ITGAL showed good potentials to distinguish PBC with other diseases. These candidate genes could be useful for diagnostic blood testing of PBC, although further clinical studies are required to evaluate their potentials as diagnostic biomarkers.

S1252 Prevalence of Diagnosed Primary Biliary Cholangitis and Associated Conditions in the United States: Results From a National Electronic Patient Database

Introduction: Primary biliary Cholangitis (PBC) is an autoimmune disease that is associated with a number of autoimmune disorders. PBC is associated with liver and non-liver organ co-morbidities that contribute to clinical outcomes. Several studies have suggested an increase in the incidence and prevalence of PBC, although this has not been assessed in a large cohort and has not been consistent across all epidemiologic studies. We determined the nationwide prevalence of PBC and its association with other autoimmune and non-liver related conditions in the United States (US). Methods: A database (Explorys Inc, Cleveland, OH) of electronic health record data from 26 major integrated US healthcare systems was used. Based on Systematized Nomenclature of Medicine – Clinical Terms (SNOMED-CT), patients (age >18 years) with a diagnosis of PBC between 1999 to present were identified. Data were analyzed in patients with/without a diagnosis of PBC. The prevalence of associated diseases was compared in in the 2 groups, and statistical univariate binary logistic model was performed. Results: Of the 70,383,890 individuals in the database, we identified 11,070 cases of PBC, with a prevalence of 15.7/100,000 persons (0.02%). Prevalence was higher in females than males [odds ratio (OR) 32.84; 95% Confidence Interval (CI) 30.50-35.37, p < 0.0001], adults (≥ 65 years) versus adult (18-65 years) (OR) 2.18; 95% CI 2.07-2.30, p < 0.0001) and whites versus non-whites (OR 14.54; 95% CI 13.63-15.51, p < 0.0001) (Table). PBC patients were at higher odds (Table) of co-morbidities including ischemic heart disease, cerebrovascular accident, congestive heart failure and sarcopenia when compared to non-PBC patients (p < 0.0001). PBC patients were more likely than non-PBC patients to have primary sclerosing cholangitis ( OR 1061.43) autoimmune hepatitis (OR 537.93), Type 1 diabetes mellitus (OR 240.58), ulcerative colitis (OR 15.25), Crohn’s disease (OR 7.84), celiac disease (OR 8.99), autoimmune thyroiditis (OR 7.69), systemic lupus erythematosus (OR 14.66) and other autoimmune disorders (Figure). Conclusion: Our large nationwide analysis study demonstrates higher prevalence of PBC in the US than previously reported, which is likely a result of diagnosis at an early stage and prolonged survival that may be related to improved management. The high association between PBC and other autoimmune conditions suggest shared common pathogenesis of immune-mediated destruction of end organs in genetically susceptible individuals. Table 1. - Baseline Characteristic of Patients with Primary Biliary Cholangitis and Control Group PBC n=11,070 (%) No PBC n=70,372,820 (%) OR (95%CI) p-value Demographics Age 18-65 4,490(41%) 47,940,720(68%) 0.32(0.31-0.33) <0.0001 Age > 65 6,620(60%) 21,251,790(30%) 3.44(3.31-3.57) <0.0001 Male 1,610(15%) 31,420,380(45%) 0.21(0.20-0.22) <0.0001 Female 9,390(85%) 38,453,360(55%) 4.64(4.41-4.89) <0.0001 Caucasian 8,770(79%) 37,743,080(54%) 3.30(3.15-3.45) <0.0001 Comorbidities T2DM 2,810(25%) 5,650,420(8%) 3.90(3.73-4.07) <0.0001 HTN 1,950(18%) 3,493,560(5%) 4.09(3.89-4.29) <0.0001 HLD 5,940(54%) 11,779,380(17%) 5.76(5.55-5.98) <0.0001 Tobacco use 2,220(20%) 6,486,950(9%) 2.47(2.36-2.59) <0.0001 Hypothyroidism 3,300(30%) 4,049,030(6%) 6.96(6.68-7.25) <0.0001 Ischemic Heart Disease 1,240(11%) 2,496,690(4%) 3.43(3.23-3.64) <0.0001 CHF 1,070(10%) 1,834,510(3%) 4.00(3.75-4.26) <0.0001 Sarcopenia 4,910(44%) 5,480,850(8%) 9.44(9.09-9.80) <0.0001 Alcohol abuse 320(3%) 1,090,250(2%) 1.89(1.69-2.11) <0.0001 Univariate analysis used to calculate OR, OR; odds ratio, CI; confidence interval, T2DM;Type 2 Diabetes Miletus, HTN; Hypertension, HLD; Hyperlipidemia, CHF; Congestive Heart Failure. PBC; Primary Biliary Cholangitis. Figure 1.: Primary Biliary Cholangitis Associated Autoimmune Disorders. Univariate analysis used to calculate OR, OR; odds ratio, CI; confidence interval, PSC; Primary Sclerosing Cholangitis, AIH; Autoimmune Hepatitis, T1DM; Type 1 Diabetes Miletus, AIHA; Autoimmune Hemolytic Anemia, UC; Ulcerative Colitis, CD; Crohn's Disease, SLE; Systemic Lupus Erythematosus, ITP; Idiopathic Thrombocytopenia Purpura, AIT; Autoimmune Thyroiditis, RA; Rheumatoid Arthritis, MG; Myasthenia Gravis.

S3287 A Rare Case of Primary Biliary Cholangitis and Hepatic Sarcoidosis

S3287 A Rare Case of Primary Biliary Cholangitis and Hepatic Sarcoidosis

LLM-PBC: Logic Learning Machine-Based Explainable Rules Accurately Stratify the Genetic Risk of Primary Biliary Cholangitis.

Background: The application of Machine Learning (ML) to genetic individual-level data represents a foreseeable advancement for the field, which is still in its infancy. Here, we aimed to evaluate the feasibility and accuracy of an ML-based model for disease risk prediction applied to Primary Biliary Cholangitis (PBC). Methods: Genome-wide significant variants identified in subjects of European ancestry in the recently released second international meta-analysis of GWAS in PBC were used as input data. Quality-checked, individual genomic data from two Italian cohorts were used. The ML included the following steps: import of genotype and phenotype data, genetic variant selection, supervised classification of PBC by genotype, generation of “if-then” rules for disease prediction by logic learning machine (LLM), and model validation in a different cohort. Results: The training cohort included 1345 individuals: 444 were PBC cases and 901 were healthy controls. After pre-processing, 41,899 variants entered the analysis. Several configurations of parameters related to feature selection were simulated. The best LLM model reached an Accuracy of 71.7%, a Matthews correlation coefficient of 0.29, a Youden’s value of 0.21, a Sensitivity of 0.28, a Specificity of 0.93, a Positive Predictive Value of 0.66, and a Negative Predictive Value of 0.72. Thirty-eight rules were generated. The rule with the highest covering (19.14) included the following genes: RIN3, KANSL1, TIMMDC1, TNPO3. The validation cohort included 834 individuals: 255 cases and 579 controls. By applying the ruleset derived in the training cohort, the Area under the Curve of the model was 0.73. Conclusions: This study represents the first illustration of an ML model applied to common variants associated with PBC. Our approach is computationally feasible, leverages individual-level data to generate intelligible rules, and can be used for disease prediction in at-risk individuals.

The future risk of primary biliary cholangitis (PBC) is low among patients with incidental anti-mitochondrial antibodies but without baseline PBC.

Anti‐mitochondrial autoantibodies (AMAs) are highly specific for the diagnosis of primary biliary cholangitis (PBC) but are also occasionally found in other diseases. In the present study, we evaluated the incidence of and predictors for PBC development in AMA‐positive patients with other liver or non‐liver diseases at baseline. In this retrospective study, we screened patients who tested positive for AMA and/or anti‐mitochondrial M2 antibody (AMA‐M2) at Beijing Friendship Hospital, Capital Medical University, from October 2005 to January 2017. They were categorized by their diagnosis at the baseline as patients with PBC or non‐PBC cases. We followed up on the non‐PBC cases through telephone interviews and reviewing of medical records to obtain laboratory results and clinical outcomes. In total, 139 patients were AMA‐positive but did not fulfill the diagnostic criteria of PBC at baseline, including 51 patients with non‐PBC liver diseases and 88 cases with non‐liver diseases. The titers of AMA‐M2, alkaline phosphatase, gamma‐glutamyl transpeptidase, and immunoglobulin M were significantly higher in patients with PBC compared to those with non‐PBC liver diseases and non‐liver diseases. After a median follow‐up of 4.6 (interquartile range: 2.4–7.6) years, 4.3% (6 of 139) developed PBC, with an accumulative 5‐year incidence rate of 4.2%. None of the patients with non‐PBC liver diseases developed PBC, whereas the 5‐year incidence rate of PBC was 7.8% among 88 patients with non‐liver diseases. Lower alanine aminotransferase and higher immunoglobulin M were independent predictors for developing PBC. Conclusion: Our results suggest a low risk of developing PBC over time in AMA‐positive patients with other liver and non‐liver diseases.