Treatment of Liver Transplant Graft-Versus-Host Disease With Antibodies Against Tumor Necrosis Factor-α

Abstract

Acute graft-versus-host disease is uncommon after liver transplant. We recently treated a 60-year-old man with liver transplant for hepatocellular carcinoma. After the primary liver transplant graft did not function, revision liver transplant resulted in excellent function. Subsequently, the patient developed watery diarrhea, systemic inflammatory response syndrome, a skin rash on his limbs and trunk, and palmar erythema. Skin biopsy suggested viral exanthems consistent with cytomegalovirus. Despite treatment for cytomegalovirus, intestinal symptoms worsened. Analysis of peripheral blood with fluorescence-activated cell sorting showed a high proportion of T lymphocytes, with 5% to 10% T cells specific to the second donor, suggestive of graft-versus-host disease. Within 48 hours after beginning therapy with antibodies against tumor necrosis factor-α (infliximab), the skin rash disappeared and endoscopy showed slight improvement of the mucosal regeneration. However, despite antifungal prophylaxis with caspofungin, the patient developed angioinvasive pulmonary aspergillosis and multiple organ failure, and he died. In conclusion, typical clinical symptoms of graftversus-host disease after liver transplant may include skin rash and gastrointestinal symptoms, and diagnosis may be confirmed by histologic examination and testing for blood chimerism. A consensus for the treatment of graft-versus-host disease still is lacking, but tumor necrosis factor-α is an encouraging target for therapy to decrease the symptoms of graft-versus-host disease and enable mucosal regeneration.

Graft Versus Host Disease After Liver Transplantation in Adults

“…In 61 cases (60.4%), sepsis was documented as cause of death. The causative organism was reported in 25 cases (41%); invasive aspergillosis was noted in 9 cases 1, 9, 12–17 (36%), disseminated candidiasis in 7 (28%) (3 albicans , 1 kruseii , 1 glabrata and 2 unspecified species) 1, 9, 18, 19 , enterococci in 7 (28%) 1, 20–23 and Enterobacter in 2 (8%) 1, 24 .…”

Skin-Limited Graft-versus-Host Disease after Pancreatic Transplantation

“…Concern for cutaneous GVHD should prompt further evaluation of other organs for GVHD. Though there is no consensus treatment for GVHD following SOT, tumor necrosis factor- α inhibitors and T-cell depleting antibodies are encouraging therapeutic options [ 4 , 5 ].…”

Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review

“…One patient was given TNF inhibitors and anti‐IL2R inhibitors and is alive 2 years after transplant. Similarly, for the 4 patients reported in the literature to have had TNF‐α–inhibition treatment, the reported survival rate was high (75%) . The 2 other patients from our series who received mAb treatment died from GVHD.…”

“…Duplicates excluded were the reports by Kuball et al (Schuchmann et al reported their patient ), by Sudhindran et al and Taylor et al (Key et al had described their patients ), and by Neumann et al (Kohler et al had previously published their patient ). A total of 78 studies were withheld, in which a total of 150 patients with LTx‐associated GVHD were identified …”

“…P ‐values <.05 were considered significant. The comparison with the no‐mAb group was done for the overall group of patients receiving mAb treatment (daclizumab, basiliximab, infliximab, etanercept, rituximab, or alemtuzumab), as well as for patients receiving TNFAb treatment (infliximab or etanercept ) and patients receiving IL2RAb treatment (daclizumab or basiliximab ). The treatment regimens in the no‐mAb group consisted of corticosteroids, cyclosporine, mycophenolate mofetil, tacrolimus, Muromonab‐CD3 (OKT3), and ATG.…”