Treatment of Acute Graft-versus-Host Disease in Liver Transplant Recipients

Abstract

Acute graft-versus-host disease (aGvHD) is a rare complication of liver transplantation associated with high morbidity and mortality. Death typically occurs due to complications related to severe infection, shock, and multiorgan failure. The clinical presentation involves dysfunction of multiple organ systems with overlapping symptoms that often results in a diagnostic delay. As there are a limited number of cases reported in the literature, there are no clear guidelines for treatment. Many different therapeutic measures have been utilized that target various immune system pathways, but steroids remain the first line of therapy. We report on two patients who developed aGvHD after liver transplantation who were treated with ruxolitinib, a novel Janus kinase 1/2 (JAK) inhibitor that has been shown to improve outcomes in steroid refractory cases of aGvHD after allogenic hematopoietic stem cell transplantation. We reviewed the literature to discuss various therapeutic options currently available for aGvHD after liver transplantation.

JAK Inhibitors in Solid Organ Transplantation

“…Therefore, dose adjustment is of considerable significance in treating patients with these drugs. Another issue is the duration of drug administration, because long‐term use did not appear to be reasonable, and better outcomes were achieved with temporary administration 27,37,41–43,73 …”

“…Finally, despite some encouraging results, there is not sufficient evidence for the efficacy of JAK inhibitors in managing acute GvHD after solid organ transplantation. In fact, the low number of case reports, the critical situation of steroid‐refractory patients, the overlap between symptoms of GvHD and adverse effects of JAK inhibitors, and the old age of most cases render our present knowledge inconclusive 69–71,73 …”

“…Another issue is the duration of drug administration, because long-term use did not appear to be reasonable, and better outcomes were achieved with temporary administration. 27,37,[41][42][43]73 Among the FDA-approved JAK inhibitors, tofacitinib has been one of the first drugs accepted to be used in the clinic, and the most studied JAK inhibitor in transplantation. However, novel agents, in particular baricitinib, seem to hold promise because of the wide range of immune dysregulations that they have been shown to control efficiently.…”

“…Ruxolitinib was added to his treatment regimen, but he expired as a result of septic shock associated with vancomycinresistant enterococcus faecium bacteremia. 73 Finally, the administration of ruxolitinib to a 2-year-old male ameliorated the symptoms of chronic GvHD following a composite intestine transplant. The patient did not respond to the high-dose steroids and anti-thymocyte globulin, but his skin rashes and colon lesions resolved after 7 days of treatment with ruxolitinib.…”

“…Later, the patient developed acute renal failure. Ruxolitinib was added to his treatment regimen, but he expired as a result of septic shock associated with vancomycin‐resistant enterococcus faecium bacteremia 73 . Finally, the administration of ruxolitinib to a 2‐year‐old male ameliorated the symptoms of chronic GvHD following a composite intestine transplant.…”