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Patients with m2 antibodies: what diagnosis and follow-up are they given?
  1. E A L Byrne1,
  2. R Katbamna1,
  3. C Scott1,
  4. C Blanshard2,
  5. R Marley1,
  6. S W Coppack1,
  7. G R Foster1
  1. 1The Royal London Hospital, Whitechapel, London, UK
  2. 2Hommerton Hospital, London, UK
  1. Correspondence to Dr E A L Byrne, ICMS The Royal London Hospital, Whitechapel Road, London,E1 1BB, UK; elizabethbyrne{at}

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In a recent issue of Gut Feuchinger et al report a novel marker antibody for primary biliary cirrhosis (PBC) which may become useful in the diagnosis of PBC in the future.1 At present diagnosis is based on the presence of the M2 substrate of anti-mitochondrial antibody (AMA) in the sera and liver function tests. The American Association for the Study of Liver Disease (AASLD) recommend that a diagnosis of PBC can be made with a positive M2 antibody and cholestatic liver biochemistry (biopsy can be used to confirm) and that patients who are M2 positive only should be followed up with annual liver biochemistry.2 Interventions are available which may modify disease progression.3

We have recently reviewed the records of a group of patients testing positive for M2 autoantibodies to evaluate whether the AASLD guidelines were followed. We identified all patients testing positive for M2 antibody between January 2004 and July 2008 at two East London hospitals.

The results are summarised in figure 1. In total, 121 patients had a positive M2 antibody present in the time period investigated. Eight patients died leaving 113 patients testing positive alive. Of these only 46 had been formally assessed and diagnosed with early PBC/probable PBC. Two patients were re-tested and found to be M2 antibody negative and one patient was lost to follow-up. Sixty-four patients were not referred or investigated further. Of the 64 patients who were not investigated further 17 had a raised alkaline phosphatase at the time of M2 testing, 39 had normal ALP and eight had no liver biochemistry at that time. Of the 64 patients who were M2 positive but without a diagnosis of PBC, 28 have not had liver biochemistry measured within the last year and eight of the 64 patients have had no liver investigations at all.

Figure 1

An illustration of the diagnosis received by patients testing M2 positive, and their liver biochemistry at the time of the test.

We concluded that early PBC is being under-diagnosed and under-investigated as only 40% (49/121) of patients testing positive for M2 antibodies were followed up appropriately. Of the patients with positive M2 antibody who were not diagnosed with early PBC 44% (28/64) were not receiving the advised annual follow-up; this figure could be higher as we are yet to see whether patients testing positive in 2008 are appropriately followed up (n=5). At least 17 of the 64 patients (27%) with anti-M2 antibodies and no further evaluation had other evidence of PBC (a raised alkaline phosphatase at the time of the test). The majority of patients with a positive M2 antibody test are being seen in a tertiary care setting but patients are not receiving the recommended diagnosis and follow-up, suggesting a need for better education of medical practitioners in the role of M2 antibodies in the diagnosis of PBC.

Our findings raise concerns that current poor understanding of the diagnostic importance of the M2 autoantibody undermine the value of future developments as reported by Feuchtinger et al.1


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  • Competing interests None.

  • Provenance and peer review Not commissioned; not externally peer reviewed.

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