Abnormal liver enzymes 2 years after haematopoietic stem cell transplantation in children: prevalence and risk factors

Abstract

To establish the prevalence of elevated liver enzymes in children transplanted in a Dutch haematopoietic stem cell transplantation (HSCT) centre, we retrospectively assessed AST and ALT values at 2 years after HSCT. Age, sex, diagnosis, type of transplant, conditioning regimen and early post-transplant complications involving the liver (veno-occlusive disease, acute GVHD, viral reactivation) were analysed as risk factors. AST and ALT values were available at 2 years after HSCT in 216 of 290 patients (75%) alive at that time and were above normal in 53 (25%) and at least twice normal in 17 (8%) patients. Older age at HSCT and a diagnosis of benign haematological disease are risk factors for abnormal liver enzymes late after HSCT. In half of the patients with benign haematological disease, iron overload is the most likely aetiological factor. Chronic hepatitis B or C is uncommon in our centre. In conclusion, the prevalence of abnormal liver enzymes late after HSCT in our centre is lower than reported in previous studies. Abnormal liver enzymes occur more often in children who are older at HSCT and transplanted for benign haematological disease. Longterm follow-up is crucial to establish if elevated liver enzymes precede clinical liver disease.

HLA, GVHD, and parenteral nutrition are risk factors for hepatic complications in pediatric HSCT

“…The AST elevation was more prominent than ALT elevation. A similar trend of persisting aminotransferase elevation in patients that displayed values at least twice normal has been noted in other studies .…”

“…A number of patient characteristics and HSCT‐related factors such as older age, TBI‐conditioning, HLA mismatch, delayed engraftment, and methotrexate as GVHD prophylaxis have been associated with a higher risk of liver dysfunction in other studies . We found no such correlations.…”

“…However, as corticosteroids are also used to treat GVHD, it is difficult to determine whether the dysfunction was attributed to the GVHD, the steroid treatment, or both. A number of patient characteristics and HSCT-related factors such as older age, TBI-conditioning, HLA mismatch, delayed engraftment, and methotrexate as GVHD prophylaxis have been associated with a higher risk of liver dysfunction in other studies (4,5,17). We found no such correlations.…”

“…In our study, no such deaths could be found. Others reported that 9% of children who died within two yr of HSCT died, at least in part, due to liver disease . We too could identity liver dysfunction contributing to death, but mainly in the cases of severe aGVHD.…”

National Cancer Institute, National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplantation Consortium First International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: The Need for Pediatric-Specific Long-Term Follow-up Guidelines

“…Although several studies have defined increased risks of mortality and a high incidence of late effects after HCT in cohorts comprised largely of adults, 7–9 only a handful of relatively small studies have focused on children. 10–14 Many of the recommendations we will review are either based upon studies comprised mainly of adults or upon survivor studies in children that were not designed to specifically address unique issues associated with HCT (allogenicity, prolonged altered immunity, graft vs. host-disease, specific effects of megadose therapy, etc. ).…”