title: Graft Versus Host Disease After Liver Transplantation in Adults: A Case series, Review of Literature, and an Approach to Management.
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.
authors: 1 Department of Internal Medicine, Division of Gastroenterology & Hepatology, University of Iowa Hospitals and Clinics, Iowa City, IA.2 Department of Surgery, Division of Transplantation & Hepatobiliary Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA.3 Department of Pediatrics, Division of Blood and Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN.4 Department of Internal Medicine, Division of Hematology and Oncology, Bone Marrow Transplant, University of Iowa Hospitals and Clinics, Iowa City, IA.
authors: Arvind R
authors: AR
authors: Murali
authors: Subhash
authors: S
authors: Chandra
authors: Zoe
authors: Z
authors: Stewart
authors: Bruce R
authors: BR
authors: Blazar
authors: Umar
authors: U
authors: Farooq
authors: M Nedim
authors: MN
authors: Ince
authors: Jeffrey
authors: J
authors: Dunkelberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D006528:Carcinoma, Hepatocellular / Q000601:surgery*; D016208:Databases, Factual; D048909:Diabetes Complications / Q000601:surgery; D005260:Female; D006086:Graft vs Host Disease / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D007484:Iowa; D008113:Liver Neoplasms / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014481:United States; D014495:Universities; D055815:Young Adult