PBC is thought to be an autoimmune disorder, but as with other autoimmune diseases the triggers that initiate PBC are unknown. Anti-mitochondrial antibodies are the most http://ebooksmedicine.net
Table 16.5 Main Features of Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
ClinicalProgressiveUnpredictable,butcourse
AMA, Anti-mitochondrialantibody;ANA, anti-nuclearanti-body;ANCA, anti-neutrophilcytoplasmicantibody.
characteristic finding in PBC. T cells specific for certain mitochondrial enzymes are another feature of the disease, supporting the notion of an immune-mediated process. Other findings suggestive of altered immunity include aberrant expression of MHC class II molecules on bile duct epithelial cells, accumulation of autoreactive T cells around bile ducts, and the frequent presence of other autoantibodies against nuclear pore proteins centromeric proteins, and other cellular components.
MORPHOLOGYInterlobular bile ducts are actively destroyed by lymphoplasmacytic inflammation with or without granulomas (the florid duct lesion) (
Fig.16.27 ).Somebiopsyspecimens,however,donothaveactivelesionsandonlyshowtheabsenceofbileductsinportaltracts.Thediseaseisquitepatchyindistribution;itiscommontoseeasinglebileductunderimmuneattackinonelevelofabiopsyspecimen,whileothernearbyducts,areunaffected.Ductular reactions followonthisductinjury,andtheseinturnparticipateinthedevelopmentof portal-portal septal fibrosis.
Intheabsenceoftreatment,thediseasefollowsoneoftwopathstoend-stagedisease.Inthefirst,mostclassicpathway,thereisincreasinglywidespreadductloss,slowlyleadingtoestablishedcirrhosisandeventuallytoprofoundcholestasis.Alternatively,somepatientseventuallydevelopedprominentportalhypertensionratherthanseverecholestasis.Fortunately,bothoftheseoutcomesarenowrarelyseen.
Fig. 16.27 Primarybiliarycirrhosis.Aportaltractismarkedlyexpandedbyaninfiltrateoflymphocytesandplasmacells.Notethegranulomatousreac-tiontothebileductundergoingdestruction(the“floridductlesion”).
Most patients are diagnosed while asymptomatic following a workup triggered by the identification of an elevated serum alkaline phosphatase level or severe itching.
Hypercholesterolemia is common. Anti-mitochondrial antibodies are present in 90% to 95% of patients. They are highly characteristic of PBC, although other autoantibodies may be seen in a small number of cases. The disease is confirmed by liver biopsy, which is considered diagnostic if a florid duct lesion is present. When symptoms appear, their onset is insidious, with patients typically complaining of slowly increasing fatigue and pruritus.
In recent years, early treatment with oral ursodeoxycholic acid has dramatically improved outcomes by slowing disease progression. Its mechanism of action remains unclear, but is presumably related to the ability of ursodeoxycholate to enter the bile acid pool and alter the biochemical composition of bile.
With time, even with treatment, secondary features may emerge, including skin hyperpigmentation, xanthelasmas, steatorrhea, and vitamin D malabsorption–related osteomalacia and/or osteoporosis. Individuals with PBC may also have extrahepatic manifestations of autoimmunity, including the sicca complex of dry eyes and mouth (Sjögren syndrome), systemic sclerosis, thyroiditis, rheumatoid arthritis, Raynaud phenomenon, and celiac disease. Liver transplantation is the best treatment for individuals with advanced liver disease.