Graft-versus-host disease after liver transplantation: a comprehensive literature review

Aim: To determine the factors affecting mortality in patients who developed graft-versus-host disease (GvHD) after liver transplantation (LT).

Methods: We performed a review of studies of GvHD following LT published in the English literature and accessed the PubMed, Medline, EBSCO, EMBASE, and Google Scholar databases. Using relevant search phrases, 88 articles were identified. Of these, 61 articles containing most of the study parameters were considered eligible for the study. Risk factors were first examined using a univariate Kaplan-Meier model, and variables with a significant association (P < 0.05) were then subjected to multivariate analyses using a Cox proportional-hazards model.

Results: The 61 articles reported 87 patients, 58 male and 29 female, mean age, 40.4 ± 15.5 years (range: 8 mo to 74 years), who met the inclusion criteria for the present study. Deaths occurred in 59 (67.8%) patients, whereas 28 (32.2%) survived after a mean follow-up period of 280.8 ± 316.2 d (range: 27-2285 d). Among the most frequent symptoms were rash (94.2%), fever (66.6%), diarrhea (54%), and pancytopenia (54%). The average time period between LT and first symptom onset was 60.6 ± 190.1 d (range: 2-1865 d). The Kaplan-Meier analysis revealed that pancytopenia (42.8% vs. 59.3%, P = 0.03), diarrhea (39.2% vs. 61.0%, P = 0.04), age difference between the recipient and the donor (14.6 ± 3.1 years vs. 22.6 ± 2.7 years, P < 0.0001), and time from first symptom occurrence to diagnosis or treatment (13.3 ± 2.6 mo vs. 15.0 ± 2.3 mo, P < 0.0001) were significant factors affecting mortality, whereas age, sex, presence of rash and fever, use of immunosuppressive agents, acute rejection before GvHD, etiological causes, time of onset, and donor type were not associated with mortality risk. The Cox proportional-hazards model, determined that an age difference between the recipient and donor was an independent risk factor (P = 0.03; hazard ratio, 7.395, 95% confidence interval, 1.2-46.7).

Conclusion: This study showed that an age difference between the recipient and donor is an independent risk factor for mortality in patients who develop GvHD after LT.