Incidence, etiology, and risk factors for liver dysfunction in children following hematopoietic stem cell transplantation.
OBJECTIVE
To identify risk factors which predispose children to develop liver dysfunction (LD) during the initial 100 days following hematopoietic stem cell transplantation (HSCT).


METHODS
Retrospective analysis of all patients (<21 yr) who had undergone HSCT from July 1998 to June 2003. LD was defined by the presence of clinical jaundice and/or elevated alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) (1.5 times normal).


RESULTS
One hundred and six patients underwent HSCT during the study period. LD was seen in 91 (85.5%) patients and the majority (58.2%) had moderate to severe LD. The primary cause of LD could be ascertained in 2/3 of patients and was multifactorial in the rest. The odds ratio and 95% CI for risk factors associated with LD following HSCT on univariate analysis were as follows: allogeneic source of stem cells 4.2 (1.2-14.2), engraftment >12 days 4.3 (1.3-14.2), total parenteral nutrition >35 days 8.2 (1.1-66.2), pretransplant ALT >40 U/L 7.4 (0.9-58.6), use of cyclosporine and methotrexate 9.5 (1.2-77.9), and use of amphotericin-B 3.1 (0.9-10.6). On multivariate analysis only elevated pre transplantation ALT and delayed engraftment were associated with post-HSCT LD. LD was seen in all 13 patients who died within 100 days following HSCT, and it was felt to be the primary cause of death in six (46%) patients. The factors associated with increased risk of mortality were: allogeneic source of stem cells, delayed engraftment (>18 days), higher mean peak GGT (>250 U/L), and total bilirubin (>6 mg/dL).


CONCLUSIONS
LD was common and severe in the majority of children following HSCT. Risk of LD was higher in children who had elevated pretransplantation ALT or had delayed engraftment. LD contributes significantly to morbidity and mortality following HSCT.
Subbarao
Girish
G
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, IN 46202-5225, USA. gsrao@iupui.edu
Haut
Paul R
PR
Johnson
Cynthia S
CS
Gowan
Darla
D
Molleston
Jean P
JP
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007223:Infant; D007565:Jaundice / Q000201:enzymology / Q000209:etiology; D008107:Liver Diseases / Q000201:enzymology / Q000209:etiology*; D008111:Liver Function Tests; D016015:Logistic Models; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D018709:Statistics, Nonparametric; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D005723:gamma-Glutamyltransferase / Q000097:blood
D007166:Immunosuppressive Agents; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase