Primary Biliary Cholangitis Flashcards
PBC
is an autoimmune liver disease that generally affects middle-aged women and is the most common chronic cholestatic liver disease in adults in the USA.
PBC
PBC is characterized by progressive intrahepatic bile duct destruction, which leads to cholestasis, complications, and symptoms related to cholestasis, cirrhosis, and portal hypertension.
highly characteristic of the PBC
The presence of an elevated alkaline phosphatase level and AMA in the serum
PBC treatment
UDCA is the only medication shown to improve LT-free survival.
Obeticholic acid (OBA) was approved for patients intolerant of UDCA or those who do not have an adequate biochemical response to UDCA.
epidemiology
PBC occurs worldwide and predominantly in women, with a female-to-male ratio of 9:1. The diagnosis of PBC usually is made between the ages of 40 and 60 years.
PATHOGENESIS
immune-mediated process that occurs as a result of complex interactions between the environment and genetically susceptible individuals.
PBC seems to be triggered by an immune-mediated response to one or more allo- or autoantigens, which leads to progressive destruction of bile ducts, chronic cholestasis, and eventual biliary cirrhosis.
regarded as the most sensitive and specific immunologic hallmark of the disease
AMA
AMA are directed to the E2 component of the pyruvate dehydrogenase complex (PDC-E2), the E2 unit of the branched-chain 2-oxo-acid dehydrogenase complex (BCOADC-E2), and the E2 subunit of the 2-oxoglutarate dehydrogenase complex (OGDC-E2).
AMA do not appear to be cytotoxic
(1) They persist after LT without evidence of disease recurrence;
(2) disease severity is unrelated to antibody titer;
(3) they are not always present in PBC; and (4) they develop in animal models after the injection of recombinant PDC-E2 protein, but without resulting bile duct destruction or inflammation
Symptomatic Disease
The typical patient with symptomatic disease is a middle-aged woman with a complaint of fatigue or pruritus.
Symptomatic pruritus
Pruritus may occur at any point, early or late, or intermittently in the course of the disease.
Pruritus generally is intermittent during the day and is most troublesome in the evening and at night.
Pruritus often resolves as the disease progresses, but in some patients, severe, intractable pruritus can develop in earlier stages of the disease and may require LT for effective management.
Pruritus in cholestatic liver disease may be partially mediated by lysophosphatidic acid and the enzyme autotaxin, which mediates the production of lysophosphatidic acid from lysophosphatidylcholine.
Serum levels of lysophosphatidic acid and activity of autotaxin correlate with the severity of pruritus.
DIAGNOSIS
The diagnosis of PBC is established when 2 out of 3 of the following criteria are met: chronic cholestatic liver test elevation (typically with alkaline phosphatase ≥1.5 times the upper limit of normal [ULN]), elevated serum AMA (titers ≥1:40), or a liver biopsy specimen consistent with PBC. A liver biopsy is typically not required (see later).
Biochemical features
all patients have increased serum levels of alkaline phosphatase and GGTP.
Serum aminotransferase (AST, ALT) levels are mildly elevated (usually less than 3 times the ULN); marked elevations (more than 5 times the ULN) are distinctly unusual and may suggest PBC-autoimmune hepatitis overlap syndrome
Histopathology
One of the earliest histologic changes associated with PBC may be a loss of the canals of Hering, which can be demonstrated by biliary cytokeratin 19 staining.
The most important and only diagnostic clue
The most important and only diagnostic clue in many cases is ductopenia, defined as the absence of interlobular bile ducts in greater than 50% of portal tracts.
The florid duct lesion
The florid duct lesion, in which the epithelium of the interlobular and segmental bile ducts degenerates segmentally, with formation of poorly defined, noncaseating epithelioid granulomas, is nearly diagnostic of PBC but is found in a relatively small number of cases, mainly in early stages.
