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Letters to the Editor |
1 Bioscientia GmbH, Konrad Adenauer Strasse 17, D-55218 Ingelheim, Germany
2 Gerhard-Domagk-Institut für Pathologie, Universität Münster
Domagkstrasse 17 D-48149 Münster, Germany
3 Laborarztpraxis Dr. Linnemann, Grabbeallee 34, 13156 Berlin, Germany
4 Abteilung für Innere Medizin, St. Elisabeth Hospital, Elisabethstrasse 10, D-59269 Beckum, Germany
aAuthor for correspondence. Fax 49-6132-781-428, e-mail arndt{at}bioscientia.de.
To the Editor:
Carbohydrate-deficient transferrin (CDT) is currently the most specific laboratory marker of chronic alcohol abuse (1). We report a 15-year-old boy with autoimmune hepatitis type 1, increased serum CDT, and no history of alcohol abuse. The case is particularly important because patients in the early phase of autoimmune hepatitis may be asymptomatic. The diagnostic criteria for autoimmune hepatitis (2), which were used for our patient, are summarized together with the patient’s data in the Data Supplement that accompanies the online version of this letter at http://www.clinchem.org/content/vol49/issue6/.
The patient was admitted for evaluation of icterus 
1 week in duration, decreased performance, and fatigue for 6 months. He had mild splenomegaly, and biopsy revealed developing micronodular cirrhosis. The patient’s denial of alcohol intake was confirmed by his mother and by AUDIT (3) and MALT-F scores (4). One week before admission, the patient had herpes zoster treated successfully with Zovirax (orally) for 5 days. The patient had received no hepatotoxic medication and did not abuse drugs. Aspartate aminotransferase was increased 30-fold, alanine aminotransferase 14-fold, bilirubin 8-fold, and direct bilirubin 27-fold. Serum concentrations of IgA and IgM were within the appropriate reference intervals. IgG was increased approximately twofold. For more details and other test results, see the Data Supplement.
The patient fulfilled the scoring criteria for definite autoimmune hepatitis type 1 at both pretreatment (minimum scoring points, 15; patient scoring points, 18) and posttreatment (minimum scoring points, 17; patient scoring points, 20; see the Data Supplement).
The CDT:transferrin ratio, measured by two turbidimetric immunoassays based on microcolumn CDT and non-CDT fractionation, was 3.2% [cutoff, 2.5%; borderline, 2.5–2.7% (1)] for the ChronAlcoI.D. assay (Sangui) and 3.2% (cutoff, 2.6%; borderline, 2.6–3.0%; manufacturer’s test instructions) for the %CDT-TIA assay (Axis). Isoelectric focusing (IEF)-immunofixation-silver staining [slightly modified from the method of Hackler et al. (5)] showed an abnormal transferrin isoform band pattern with increased amounts of disialo-Fe2-transferrin, which led to a decreased trisialo-/disialo-Fe2-transferrin peak height (area) ratio of 1.20 (Fig. 1
, lane 3) compared with 2.2 for the healthy control (Fig. 1
, lane 2). Asialotransferrin, which is present with high prevalence in serum after chronic alcohol abuse (6) (Fig. 1
, lanes 1 and 4) and genetic transferrin variants were not detected in our patient’s serum (Fig. 1
, lane 3). In summary, the IEF transferrin isoform band pattern for our patient confirmed the immunologic CDT results qualitatively but was not typical for chronic alcohol abuse.
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We excluded the currently known clinical conditions for false-positive CDT results (1) as etiologies of our findings (see the Data Supplement). We know of no evidence that Zovirax alters transferrin glycosylation. Liver cirrhosis has been reported to increase CDT (7). In this study (7), this was most probably attributable to active viral hepatitis, which is known to increase serum CDT concentrations (1)(8). Our patient had tested negative for acute and chronic viral hepatitis as well as asialoglycoprotein receptor antibodies. Thus, his increased CDT:transferrin ratio cannot be explained by viral hepatitis and/or autoantibody-induced decreased clearance of the sialic acid-deficient transferrin isoforms (CDT) via the asialoglycoprotein receptor.
The underlying mechanism for the increased CDT in our patient might be different from that in viral liver cirrhosis. To explore the etiology of this finding, measurements of neuraminidase and sialyltransferase activity (9) and of the sialyltransferase mRNA concentration (10) may be useful. We consider autoimmune hepatitis as a new cause for pathologic CDT results despite typical alcohol intake.
References
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