Antimitochondrial Antibody–Negative Primary Biliary Cirrhosis
Section snippets
Clinical and Biochemical Features
AMA-negative PBC, like AMA-positive PBC, occurs predominantly in middle-aged women and is commonly asymptomatic. When symptoms are present, fatigue, pruritus, and symptoms of sicca syndrome are common initial features, whereas jaundice is usually a late finding. Elevation of the alkaline phosphatase is the typical biochemical feature, with transaminases being only mildly elevated. Several studies comparing the clinical and laboratorial findings between patients who have AMA-negative PBC and
Serologic Features
Some serologic characteristics aside from the absence of the antimitochondrial antibody may be different between AMA-negative and -positive PBC.
Several studies have reported a significantly higher rate of positivity for antinuclear antibodies (ANA) and smooth muscle antibodies (SMA) in patients who have AMA-negative PBC than that seen in AMA-positive PBC. In the different studies the prevalence of ANA ranged between 71% to 100%, and of SMA between 14% to 41% in patients who had AMA-negative
Histopathologic Features
According to the current thinking classic PBC and AMA-negative PBC share the same histologic features, but minor differences might emerge as more experience is gained in the latter group. Some authors have identified differences in the inflammatory infiltrates of patients who have AMA-negative and AMA-positive PBC [10], [11].
Ludwig [12] proposes applying the same criteria for diagnosis and staging used for PBC to AIC or AMA-negative PBC. Stage 1 (portal stage) is characterized by infiltration
Response to Treatment
The treatment of PBC involves two treatment modalities: ursodeoxycholic acid (UDCA) and orthotopic liver transplantation (OLT). UDCA has been shown to improve liver biochemistry and to slow disease progression, delaying time to death or liver transplantation in patients who have PBC, especially in those who have earlier-stage disease [13], [14]. In patients who have end-stage liver disease from PBC, OLT has been shown to prolong survival and to improve quality of life [15], [16]. Given the
Prognosis
Several models to predict survival in patients who have PBC have been developed [18], [19], [20]; the Mayo risk score is the most widely validated. It takes into account age, total bilirubin, serum albumin, prothrombin time, and presence or absence of edema [19]. Although these models have not been validated specifically in the AMA-negative population, it is reasonable to use them in this setting, given that most of the evidence available supports that the prognosis and natural history of
Summary
AMA-negative PBC, also known as AIC, shares similar clinical, biochemical, histologic, and prognostic features with classic PBC. Management of AMA-negative PBC should not differ from treatment of AMA-positive disease. The development of more sensitive and specific assays and increased understanding of the immunopathogenetic mechanisms of these diseases may, in the near future, prove them to be the same disease entity.
References (20)
Primary biliary cirrhosis and autoimmune cholangiopathy
Clin Liver Dis
(2004)- et al.
Does antimitochondrial antibody status affect response to treatment in patients with primary biliary cirrhosis? Outcomes of ursodeoxycholic acid therapy and liver transplantation
Hepatology
(1997) - et al.
Histopathologic comparison of anti-mitochondrial antibody-positive primary biliary cirrhosis and autoimmune cholangiopathy
Hepatol Res
(2001) The pathology of primary biliary cirrhosis and autoimmune cholangitis
Baillieres Best Pract Res Clin Gastroenterol
(2000)- et al.
Ursodeoxycholic acid in the treatment of primary biliary cirrhosis
Gastroenterology
(1994) - et al.
Updating prognosis in primary biliary cirrhosis using a time-dependent Cox regression model. PBC1 and PBC2 trial groups
Gastroenterology
(1993) - et al.
Primary biliary cirrhosis
N Engl J Med
(2005) - et al.
Autoimmune cholangitis within the spectrum of autoimmune liver disease
Hepatology
(2000) - et al.
Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis
Hepatology
(1997) - et al.
Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis
Gut
(1994)
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2023, Molecular ImmunologyBile Duct Diseases
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2018, MacSween's Pathology of the LiverAn Update on the Treatment and Follow-up of Patients with Primary Biliary Cholangitis
2017, Clinics in Liver DiseaseCitation Excerpt :Novel immunologic treatments such as anti–interleukin-12, anti-CD80, anti-CD20 (rituximab), mesenchymal stem cells, and cytotoxic T-lymphocyte antigen 4 (abatacept) are currently under investigation for the treatment of PBC.60–62 The 5% to 10% of patients with PBC with AMA-negative disease have a similar clinical presentation, natural history, response to UDCA, and appearance on liver biopsy as AMA-positive patients.63,64 The pathogenesis is similar, and nearly all of these patients have positive antinuclear (in particular anti-gp210 and anti-Sp100) and/or anti–smooth muscle antibodies.
The diagnosis of antimitochondrial antibody-negative primary biliary cholangitis
2016, Clinics and Research in Hepatology and GastroenterologyCitation Excerpt :Fatigue can be so severe that impairs the quality of life and pruritis is a more specific symptom of PBC that often precedes the development of jaundice. Historical clues are also very important to support the PBC diagnosis, such as concomitant autoimmune diseases especially rheumatic and thyroid disorders, familial PBC history, recurrent urinary tract infections, and others [8,39–41]. The other practical issue is that PBC is characterized by “chronic incomplete cholestasis” for years because of the focal-segmentary nature of the biliary injury [2,8,9].
A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis
2015, Hepatobiliary and Pancreatic Diseases International