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Review
. 2016 Dec;100(12):2661-2670.
doi: 10.1097/TP.0000000000001406.

Graft Versus Host Disease After Liver Transplantation in Adults: A Case series, Review of Literature, and an Approach to Management

Arvind R Murali  1 , Subhash Chandra, Zoe Stewart, Bruce R Blazar, Umar Farooq, M Nedim Ince, Jeffrey Dunkelberg
Affiliations
Review

Graft Versus Host Disease After Liver Transplantation in Adults: A Case series, Review of Literature, and an Approach to Management

Arvind R Murali et al. Transplantation. 2016 Dec.

Abstract

Background: Graft-versus-host-disease (GVHD) after liver transplantation (LT) is a deadly complication with very limited data on risk factors, diagnosis and management. We report a case series and a comprehensive review of the literature.

Methods: Data were systematically extracted from reports of GVHD after LT, and from the United Network for Organ Sharing database. Group comparisons were performed.

Results: One hundred fifty-six adult patients with GVHD after LT have been reported. Median time to GVHD onset was 28 days. Clinical features were skin rash (92%), pancytopenia (78%), and diarrhea (65%). Six-month mortality with GVHD after LT was 73%. Sepsis was the most common cause of death (60%). Enterobacter bacteremia, invasive aspergillosis, and disseminated Candida infections were frequently reported. Recipient age over 50 years is a risk factor for GVHD after LT. Hepatocellular carcinoma was overrepresented, whereas chronic hepatitis C was underrepresented, in reported United States GVHD cases relative to all United Network for Organ Sharing database LT cases. Mortality rate with treatment of GVHD after LT was 84% with high-dose steroids alone, 75% to 100% with regimens using dose increases of calcineurin inhibitors, and 55% with IL-2 antagonists. Mortality was 25% in small case series using the CD2-blocker alefacept or TNF-α antagonists.

Conclusions: Age older than 50 years and hepatocellular carcinoma appear to be risk factors for GVHD. Hepatitis C may be protective. High-dose steroids and calcineurin inhibitors are ineffective in the treatment of GVHD after LT. CD2-blockers and TNF-α antagonists appear promising. We propose a diagnostic algorithm to assist clinicians in managing adults with GVHD after LT.

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Conflict of interest statement

No conflicts of interest.

Figures

Figure 1
Figure 1
Maculopapular skin rash in a patient with graft versus host disease after liver transplantation.
Figure 2
Figure 2
Skin biopsy demonstrating perivascular mononuclear infiltrate (arrow) in the superficial dermis as well as vacuolar interface change, including scattered apoptotic keratinocytes (Grade 2 Graft Versus Host Disease).
Figure 3
Figure 3
Ileal biopsy demonstrates apoptotic crypt epithelial cells (arrow) and degenerating crypts suggestive of graft versus host disease.
Figure 4
Figure 4
Proposed diagnostic algorithm for GVHD in liver transplantation recipients.
See this image and copyright information in PMC

References

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