Long-term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients

Abstract

Summary:This retrospective study has aimed at determining the prevalence, aetiology and clinical evolution of chronic liver disease (CLD) after allogeneic bone marrow transplantation (BMT). A total of 106 patients who had been transplanted in a single institution and who had survived for at least 2 years after BMT were studied. The prevalence of CLD was 57.5% (61/106). In 47.3% of cases more than one aetiopathogenic agent coexisted. The causes of CLD were iron overload (52.4%), chronic hepatitis C (47.5%), chronic graft-versus-host disease (C-GVHD) (37.7%), hepatitis B (6.5%), non-alcoholic steatohepatitis (NASH) (4.9%), autoimmune hepatitis (AIH) (4.9%) and unknown two (3.3%). Twenty-three patients with iron overload underwent venesections which were well tolerated. An improvement in liver function tests (LFTs) was observed in 21 (91%) patients. All six patients with siderosis as the only cause of CLD normalized LFT as well as three patients with HCV infection. Clinical evolution was satisfactory for patients with GVHD, AIH, NASH and hepatitis B. At the last visit 23 patients continued with abnormal LFTs, and 19 of them were infected by the HCV. A sustained biochemical and virologic response was achieved in only one case out of six patients with CHC who received interferon . We have found that CLD is a common complication in long-term BMT survivors. The aetiology is often multifactorial, iron overload, CHC and C-GVHD being the main causes. The CLD followed a rather 'benign' and slow course in our patients as none of them developed symptoms or signs of liver failure and we did not observe an increase in morbidity or mortality in these patients, but a longer follow-up is necessary in HCV infected patients based on the natural history of this infection in other populations. Bone Marrow Transplantation (2000) Liver disease is a well-known cause of early morbidity and mortality following an allogeneic bone marrow transplantation (BMT) which affects 80% of patients and is responsible for up to 5-10% of toxic-related deaths.

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

“…16 Chronic liver disease after HSCT is common, with iron overload being one of the most frequent causes. [9][10][11] Besides iron chelation, phlebotomy is another safe, convenient and cost-effective option. 10,[14][15][16][17] Yet, data on phlebotomy are hitherto limited.…”

“…[2][3][4][5] Additionally, iron homeostasis is frequently complicated by factors known to modulate hepcidin expression such as ineffective erythropoiesis, inflammation, infections and hypoxia. 6 The negative impact of hyperferritinemia on survival after allogeneic HSCT is well recognized, 1,2,7,8 hepatic dysfunction may be exacerbated [9][10][11] and pre-HSCT iron chelation may be associated with improved survival and reduced non-relapse mortality. 13 Data suggest that post-HSCT SF is comparable to pre-HSCT values, 12 and hyperferritinemia up to day +720 post HSCT could significantly be associated with decreased survival.…”

Genomic screening and complications of hematopoietic stem cell transplantation: has the time come?

“…[104][105][106][107][108][109] The effects of iron in the HSCT setting deserve further investigation, since they contribute to long-term morbidity and are potentially modifiable by antioxidant therapy, phlebotomy, and chelation. [110][111][112][113][114] Autoimmune disease and heritable malignancy…”

Liver failure complicating non-alcoholic steatohepatitis following allogeneic bone marrow transplantation for Shwachman–Diamond syndrome

“…13 A number of these risk factors are present in the majority of patients undergoing BMT; a recent report identified NASH in 2.8% of 106 allogeneic BMT recipients. 14 While most individuals with hepatic steatosis within the general population do not develop serious liver disease, a proportion develop NASH, which may lead to fibrosis, cirrhosis and liver failure. 15 In our patient, pre-existing hepatic steatosis is likely to have predisposed to the development of progressive NASH following TPN, glucocorticoid and/or oestrogen exposure post transplant.…”