https://www.ncbi.nlm.nih.gov/pubmed/30026108 Drug induced liver injury

Biol Blood Marrow Transplant. 2018 Jul 16. pii: S1083-8791(18)30396-3. doi: 10.1016/j.bbmt.2018.07.009. [Epub ahead of print].Vanishing bile ducts in the long-term following paediatric haematopoietic stem cell transplantation.Maximova N1, Sonzogni A2, Matarazzo L3, Ghirardi A4, D'Antiga L5.

Abstract

There are no structured studies on liver histology following haematopoietic stem cell transplantation (HSCT). We aimed to prospectively describe the clinico-pathological features of liver disease in the long-term following HSCT in an observational, longitudinal study of liverhistology in a consecutive cohort of children undergoing allogeneic HSCT. First liver biopsy was performed in presence of abnormal liverfunction tests and repeated per protocol thereafter. A previously reported semi-quantitative score evaluating inflammation, cholestasis and ductopenia (bile ducts to portal tracts ratio ≤0.5) was adopted. Graft-versus-host disease (GVHD) was diagnosed according to standard criteria. 131 biopsies taken in 50 HSCTs performed in 47 children (mean age 9.7±5.2 years) were evaluated. Pre-HSCT chemotherapy was administered to 36/50 (72%). GVHD was diagnosed in 17/50 (34%). Over time the overall score decreased from a mean of 6±2.7 to 3.25±0.96 (p<0.01), inflammation from 1.22±1.19 to 1±0 (p=ns), cholestasis from 3.9±2.08 to 1.5±0.58 (p<0.01). Ductopenia, diagnosed in 113/131 (93%), worsened from 0.63±0.35 to 0.16±0.14 (p<0.01). On multivariate analysis severe ductopenia (ratio ≤0.2) was associated with previous chemotherapy (p=0.04), and in particular with thiotepa, but not with history of GVHD. Vanishing bile duct syndrome after HSCT may be due to drug-induced liver disease. Longer follow up will reveal whether these patients are prone to late liver-related morbidity and mortality.