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The funding for the development of this Practice Guidance was provided by the American Association for the Study of Liver Diseases.This practice guidance was approved by the American Association for the Study of Liver Diseases on April 26, 2018. Preamble This American Association for the Study of Liver Diseases (AASLD) 2018 Practice Guidance on Primary Biliary Cholangitis (PBC) is an update of the PBC guidelines published in 2009. The 2018 updated guidance on PBC includes updates on etiology and diagnosis, role of imaging, clinical manifestations, and treatment of PBC since 2009. The AASLD 2018 PBC Guidance provides a data‐supported approach to screening, diagnosis, and clinical management of patients with PBC. It differs from more recent AASLD practice guidelines, which are supported by systematic reviews and a multidisciplinary panel of experts that rates the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations Assessment, Development, and Evaluation system. In contrast, this guidance was developed by consensus of an expert panel and provides guidance statements based on formal review and analysis of published literature on the topics. The quality (level) of the evidence and the strength of each guidance statement are not rated. Intended for use by health care providers, this guidance identifies preferred approaches to the diagnostic and therapeutic aspects of care for patients with PBC. As with clinical practice guidelines, it provides general guidance to optimize the care of the majority of patients and should not replace clinical judgment for a unique patient. The major changes from the last guideline to this guidance include information about obeticholic acid (OCA) and the adaptation of the guidance format. Etiology of Primary Biliary Cholangitis Primary Biliary Cholangitis (PBC) is considered an autoimmune disease because of its hallmark serologic signature, antimitochondrial antibody (AMA), and specific bile duct pathology.1The etiology of PBC is thought to be due to a combination of genetic risk factors and environmental triggers.5 AMA is a highly disease‐specific autoantibody8 that targets the lipoic acid present on the 2‐oxo‐acid dehydrogenase complexes located on the inner mitochondrial membrane.9 In addition to a loss in humoral tolerance, there is an increase of autoreactive cluster of differentiation (CD)4+CD8+ pyruvate dehydrogenase complex (PDC‐E2)‐specific T cells in the liver.10 In addition to the high concordance among monozygotic twins compared with dizygotic twins with PBC5, the strong association with human leukocyte antigen alleles, which vary by ethnicity, supports a genetic cause of inherited risk.12 Despite progress, only an estimated 15% of the variability of the disease has been accounted for by genetic studies.21 Environmental risks have been suggested by several large case‐control cohort studies that have found associations with urinary tract infections, reproductive hormone replacement, nail polish, and past cigarette smoking.22 Studies of geographic clustering have suggested environmental exposure and socioeconomic factors as well.25 The interaction between genetic and environmental effects has only begun to be assessed in PBC, with several possible gene‐modifying mechanisms being supported.15 Specific environmental agents that may lead to the loss of tolerance of PDC‐E2 are xenobiotics that may either mimic or modify lipoic acid, such as 2‐octynoic acid, which is common in cosmetics, and 6,8‐bis (acetylthio) octanoic acid, a metabolite of acetaminophen. AMA‐positive serum from PBC patients strongly cross‐reacts with these xenobiotics.30 Further experimental support for the role of xenobiotics in PBC pathogenesis comes from the ability of xenobiotics to induce a PBC‐like pathology, including AMA, in animal models.32 The enigma of PBC pathogenesis has been the specific targeting of the biliary epithelial cells in the setting of a ubiquitous autoantigen. The majority of AMA produced by plasmablasts is immunoglobulin A (IgA), which may undergo transcytosis through the biliary epithelium and disrupt mitochondrial function. Alternatively, the specificity of the immune attack may be due to the incomplete proteolysis of pyruvate dehydrogenase complex PDC‐E2 and other mitochondrial enzymes of biliary epithelial a unique of this the evidence strongly supports the antimitochondrial as a of the pathology, other mechanisms may a role as PBC is a disease with a that may The of among the past there have been changes in the and management of PBC. patients are being with and of these patients to In and the of for PBC is the of the disease is of and in the The of AMA in is not It is estimated that of the general in are AMA In a from of AMA AMA may be in serum patients are and are of AMA‐positive for to found that the of PBC was In a the from the AMA to was with a between and of these patients developed the The of clinical disease in has been to because of the of the vary between and of PBC recent has an of with a of in and in as to other studies a of to PBC may and with from the The of AMA in of PBC patients is 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patients with a AMA and PBC are these patients to there are Liver is for in PBC is by that and bile changes and bile the duct is The is in with the of and of and cells In are more in the of are In contrast, are and by the are in with of and in duct or is as of bile The of the is The of and bile duct with the of because of the of the to should be and should be to or and include with or and bile is not disease has are is by with or bile duct In this to the is by the increase of the to as and the is by or of by and are of The is which is the association of or with This is to the found in autoimmune is biliary which is by a to as is by and the with Studies of PBC patients have that of is highly of development of is by a of the with with the of a that bile duct and to a is a of PBC and should be from it may to in PBC with and a PBC with and bile PBC with PBC with of on for was the high disease specificity of a AMA the role of in PBC is is the and are the Liver may be in patients and to 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