Anti-mitochondrial M2 antibody-positive autoimmune hepatitis

Abstract

Abstract. Anti-mitochondrial M2 antibody (AMA-M2) is specific to primary biliary cirrhosis (PBC), but can also be found in certain patients with autoimmune hepatitis (AIH). Effective methods of differentiating between PBC and AIH are required, as their clinical course and management are different. Titers of AMA-M2 were analyzed before and after follow-up in patients with PBC or AIH. Patients who underwent liver biopsy and were diagnosed with either AIH (10 patients) or PBC (3 patients) were enrolled in the study. The AMA-M2 antibody titers of these patients were analyzed upon hospital admission. AMA-M2 reacted with the pyruvate dehydrogenase complex-E2, branched-chain 2-oxo acid dehydrogenase complex and 2-oxoglutaric acid dehydrogenase complex in the assay utilized for this study. The cut-off value for AMA-M2 was 5. Six AIH patients were AMA-M2(-) and 4 were AMA-M2(+). The titer for the AIH patients who were AMA-M2(+) was 24.8±14.8, compared with 324±174 in the patients with PBC (P= 0.0138). Three AMA-M2(+) AIH patients were followed-up after liver biopsy. The AMA-M2 levels had decreased in all 3 patients, becoming undetectable in 2 of them. In conclusion, certain patients with AIH in this study were found to be AMA-M2(+), but the titers were significantly lower than those in the patients with PBC. At follow-up, the AIH patients exhibited decreased AMA-M2 titers. IntroductionAutoimmune hepatitis (AIH) is caused by an immune attack on the hepatocytes (1). Patients with AIH are positive for auto-antibodies, such as anti-nuclear, anti-smooth muscle and liver-kidney microsomal type 1 antibodies (2). Chronic inflammation in the liver can progress to liver cirrhosis (3). One major problem of AIH is that an acute presentation or exacerbation of the disease can progress to liver failure (4,5). Furthermore, patients with AIH can be susceptible to hepatocellular carcinoma (6); therefore, patients should be followed-up for exacerbation and hepatocellular carcinoma (7). Primary biliary cirrhosis (PBC) is characterized by nonsuppurative cholangitis and autoimmune-mediated destruction of the small or medium-sized bile ducts (8). Inflammation causes cholestasis and the liver develops cirrhosis (9). AIH is treated with immunosuppressive drugs, such as prednisolone or azathioprine (10,11), while PBC is treated with ursodeoxycholic acid (10). It is important to differentiate AIH from PBC due to the differences in the clinical course and management of the two diseases.Anti-mitochondrial antibody (AMA) can be tested via indirect immunofluorescence (12). In this technique, unfixed sections of the kidney and stomach of Wistar rats are used. AMA is used for the diagnosis of PBC (13), as 90-95% of patients with PBC are positive for AMA (14); however, the use of AMA as a differential test is problematic, as 5% of patients with AIH are positive for AMA (15), and the interpretation of a positive AMA result in AIH is difficult.The auto-antigens of AMA have been identified as pyruvate dehydrogenase complex-E2 (PDC-E2), branched-chain 2-oxo...

Auxiliary Liver Transplantation as a Transient Treatment for Acute Liver Failure: Two Cases

“…These findings are consistent with the known idea that centrilobular necrosis can be the only pathologic feature in up to 2-3% of patients presenting with AIH flares [11][12][13]. Moreover, the patient had positive antimitochondrial antibodies, which, while being more specific for primary biliary cholangitis, might be associated with AIH [14]. In these ALF cases, liver support systems were not used, since they were unavailable.…”

Recent advances in the diagnosis and treatment of primary biliary cholangitis

“…The non-classical clinical phenotypes of AIH, particularly AMA-positive AIH, should be distinguished from PBC. In general, AMAs-M2 antibody is specific to PBC patients, but may also be occasionally discovered in certain AIH patients[146]. Efficient means of discriminating between AIH and PBC are required, due to the fact that their clinical process and treatment are disparate[146].…”

“…In general, AMAs-M2 antibody is specific to PBC patients, but may also be occasionally discovered in certain AIH patients[146]. Efficient means of discriminating between AIH and PBC are required, due to the fact that their clinical process and treatment are disparate[146]. One recent study has shown that antibodies to filamentous-actin (anti-F-actin) protein can not only be considered the serological marker of type 1 AIH, but may also predict AIH recurrence[147].…”

“…Furthermore, the application of repetition hepatic biopsy is an efficient method for AIH diagnosing comorbid liver conditions[148]. Although certain AIH patients were detected to be AMAs-M2 (+), the titers were markedly reduced compared to PBC patients[146]. During the follow-up period, the serum titers of AMAs-M2 were reduced in AIH patients[146].…”

“…Although certain AIH patients were detected to be AMAs-M2 (+), the titers were markedly reduced compared to PBC patients[146]. During the follow-up period, the serum titers of AMAs-M2 were reduced in AIH patients[146]. …”