Chronic Liver Disease after Allogeneic Hematopoietic Cell Transplantation

Background There are few descriptions of the epidemiology of chronic liver disease (CLD) after allo-HCT. Amongst those transplanted prior to 2000, viral hepatitis was the dominant cause of CLD. Recently, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD, previously known as non-alcoholic fatty liver disease) is rising in the general population. In addition, survivors of allo-HCT are known to be at increased risk of metabolic syndrome. Objective 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. Study Design We undertook a retrospective cohort and nested case-control study of two-year survivors of allo-HCT in Alberta transplanted between 2008 and 2018. Results Amongst 392 two-year survivors of allo-HCT between 2008-2018, 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 amongst the entire cohort is 46%. While most patients developed CLD before two years post-transplant, there was a 13% cumulative incidence of new CLD after two years post-transplant. Grade 2-4 aGVHD and/or moderate-severe cGVHD and pre-transplant 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 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: prior 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.