Cystic fibrosis, elevated gamma-glutamyltransferase, and lung transplant outcome

Abstract

Dear Sirs,In their study recently published in this journal [1], Wreeet al. have investigated the prognostic impact of liverfunction tests in patients with end-stage cystic fibrosis(CF) undergoing double lung transplant (DLTx). Theauthors’ focus was put on CF-associated liver injury asfactor possibly affecting the outcome of surgery even inabsence of overt signs of liver cirrhosis, such as portalhypertension. In a cohort of 31 cases with median follow-up of 1000 days, preoperatively elevated gamma-glutamyl-transferase (GGT) was identified to be associated withhigher mortality following DLTx. Postoperatively elevatedGGT was also associated with higher mortality, accompa-nied in this case by elevated bilirubin. Thus, the impor-tance of close monitoring of liver function in CFcandidates to DLTx is underscored [1].We would like to call the attention on a possiblealternative explanation for elevated serum GGT levels inCF patients. Despite the well-known and establishedrole of GGT as a marker of liver and biliary disease,the significance of this enzyme activity in fact hasrecently expanded to include several additional aspects,e.g., in tumor biology [2] and atherosclerosis [3]. Asfar as CF is concerned, GGT is known to increaseseveral fold in the lung lining fluid of CF patients [4].In CF sputum specimens, we have recently identifiedactivated neutrophilic granulocytes as the source ofGGT increase; neutrophils in fact contain GGT in theirspecific granules and can release it upon activation [5].Identification of the neutrophilic origin of increasedGGT was achieved by means of chromatographic tech-niques allowing to separate and compare distinctGGT-containing protein fractions deriving from differ-ent cellular sources [6].It has been suggested that CF neutrophils may havean increased propensity to release their granule proteins,because of increased secretion of cytokines and/or stillunknown priming mechanisms [7]. It would be ofinterest to verify whether the increased serum GGTobserved by Wree et al. might also derive from hyper-reactivity of peripheral blood neutrophils in selectedpatients. Rather than referring to underlying conditionsof liver dysfunction, the less favorable outcome of DLTxin these subjects could point then to a ‘‘hyperinflamma-tory’’ status [8], which could prompt the devisement ofmore specific pre- and/or postoperative therapeuticstrategies.Alessandro Corti,