Chronic liver disease after allogeneic hematopoietic cell transplantation

Abstract

Background aims

There are few descriptions of the epidemiology of chronic liver disease (CLD) after allogeneic hematopoietic stem cell transplantation (allo-HCT). Among those transplanted before 2000, viral hepatitis was the dominant cause of CLD. Recently, the prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD, previously known as nonalcoholic fatty liver disease) is increasing in the general population. In addition, survivors of allo-HCT are known to be at increased risk of metabolic syndrome. We set out to describe the epidemiology of CLD in a modern cohort of allo-HCT recipients. We hypothesized that MASLD would be the most common cause of CLD in the cohort.

Methods

We undertook a retrospective cohort and nested case-control study of 2-year survivors of allo-HCT in Alberta transplanted between 2008 and 2018.

Results

Among 392 2-year survivors of allo-HCT between 2008 and 2018, the prevalence of CLD was 41.8% and MASLD was identified in 56% of those with CLD, followed by iron overload in 47% of those with CLD. The prevalence of MASLD among the entire cohort was 46%. Although most patients developed CLD before 2 years post-transplant, there was a 13% cumulative incidence of new CLD after 2 years posttransplant. Grade 2-4 acute graft-versus-host disease and/or moderate-to-severe chronic graft-versus-host disease and pretransplant CLD were strongly associated with CLD. In the case-control study examining the association between cardiovascular risk factors and CLD, type 2 diabetes was associated with CLD. Cirrhosis developed in 1.5% of survivors, and MASLD was an underlying etiology in one half of these cases. There was no difference in overall survival and non-relapse mortality between those who did and did not develop CLD.

Conclusions

MASLD is the main cause of CLD in recent long-term survivors of allo-HCT and may be associated with post-transplant corticosteroid exposure and type 2 diabetes. We note a shift in the underlying etiology of CLD post-HCT: previous studies describe viral hepatitis as the most common cause of CLD. The high prevalence of MASLD in allo-HCT recipients has important implications for survivorship care.