Original article—liver, pancreas, and biliary tract
Value of Autoantibody Analysis in the Differential Diagnosis of Chronic Cholestatic Liver Disease

https://doi.org/10.1016/j.cgh.2009.07.012Get rights and content

Background & Aims

It is challenging to diagnose patients with chronic cholestatic liver diseases when all the classic criteria are not fulfilled. We evaluated the performance of the recently developed MIT3-based enzyme-linked immunosorbent assay (ELISA), which detects antimitochondrial autoantibodies (AMAs), together with ELISAs for other autoimmune liver disease–related antibodies in patients with chronic cholestatic liver disease.

Methods

Sera from 281 patients with chronic cholestatic conditions, including primary biliary cirrhosis (PBC), primary sclerosing cholangitis, AMA-positive autoimmune hepatitis, and “undetermined cholangiopathy” were tested for the following PBC-associated autoantibodies: anti-gp210, anti-sp100, conventional anti-M2, anti-M2 (MIT3) IgG, anti-M2 (MIT3) IgA, as well as anti-centromere, anti–soluble liver antigen, and anti-chromatin.

Results

Of 57 patients with PBC who were AMA-negative by conventional M2 ELISA, 14 were found to be AMA-positive by the MIT3-IgG assay. Furthermore, on the basis of the data from 3 tests (MIT3-IgG, gp210, and sp100), PBC was confirmed in 20 of 57 (35%) patients diagnosed with AMA-negative PBC. We confirmed that sp100 and gp210 antibodies were detected only in patients with PBC and AMA-positive autoimmune hepatitis, whereas gp210 was detected more frequently in patients known to have had a poor outcome. Of the 11 patients with an undetermined cholangiopathy, 3 (27%) tested positive for PBC with the MIT3-IgG assay. In contrast to previous findings, anti-centromere antibodies were not found to be associated with poor outcome in PBC.

Conclusions

ELISAs for AMAs and antinuclear antibodies are useful in diagnosis and prognosis of patients with features of PBC who lack conventional AMA and in patients with a cholangiopathy of undetermined etiology.

Section snippets

Materials and Methods

The study protocol was approved by the local ethics committee. Patient groups included AMA-positive autoimmune hepatitis (AIH) (IAH-G criteria fulfilled, no histologic features of PBC, and AMA-positive by routine ELISA; stable over many years); PSC (endoscopic retrograde cholangiopancreatography [ERCP]/magnetic resonance cholangiopancreatography [MRCP] diagnostic for PSC, except in 3 patients who fulfilled histologic criteria for small duct PSC); undetermined cholangiopathy (elevated alkaline

Results

The patient population comprised 281 individuals for whom clinical and demographic data are summarized in Table 1.

Discussion

In the present study, which included a large cohort of patients with various chronic, presumed autoimmune cholestatic liver conditions, we analyzed the prevalence of 5 PBC-specific (conventional anti-M2 IgG, anti-MIT3 IgG and IgA, anti-gp210, anti-sp100) and 3 autoimmune liver disease–associated autoantibodies (anti-SLA, anti-chromatin, and anti-centromere) and assessed their potential role in the differential diagnosis of patients with chronic cholestasis caused by presumed “autoimmune”

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    Conflicts of interest These authors disclose the following: Gary L. Norman and Zakera Shums are employees of INOVA Diagnostics, Inc. The remaining authors disclose no conflicts.

    Funding E. Jenny Heathcote has received an unrestricted grant from Axcan-Pharma.

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