The Impact of HCV Sero-Positivity of Recipients on Clinical Outcomes Following Allogeneic HSCT in Japan

It is estimated that over 2,000,000 people suffer from hepatitis C virus (HCV) infection in Japan. Therefore, HCV infection is one of major liver diseases. In hematopoietic stem cell transplantation (HSCT), HCV infections of recipients might induce a transient liver dysfunction, and an increasing risk of veno-occlusive disease (VOD), although these are controversial. In addition, the genotypes of HCV in Japan are considered different from those in Western countries. Therefore, we have assessed the impact of HCV sero-positivity of recipients on clinical outcomes in Japan. The population was based on TRUMP data confirmed in 2010. The eligible population included the all recipients who received an initial allogeneic HSCT since 2006 and whose data about age, gender, HCV sero-positivity of recipients and status of survival at last observation were available. We identified 136 and 7720 recipients with and without HCV, respectively. Although more recipients with HCV tended to be male (p = 0.054) and to receive female to male HSCT (p = 0.081), there were no differences in other background. The recovery of more than 5x10^10/L platelet was significantly later in recipients with HCV (38 vs 47 days, p = 0.013), while there was no significant difference in neutrophil engraftment. There were no differences between groups without and with HCV in the incidences of grade2-4 aGVHD (35.9% vs 31.6%, p = 0.18) and cGVHD (29.3% vs 30.5%, p = 0.67). However, the liver involvement of aGVHD was higher in recipients with HCV (13.9% vs 23.9%, p = 0.031), while there was no differences in liver involvement of cGVHD (37.3% vs 45%, p = 0.33) and VOD (10.7% vs 17.3%, p = 0.17). Furthermore, the recipients with HCV had significantly higher non-relapse mortality (NRM; 25.9% vs 38.0% at 2 year, p<0.01) and poor overall survival (OS; 51.4% vs 41.1% at 2 year, p<0.01). Multivariate analysis revealed that HCV sero-positivity remained significant as a risk factor for NRM (HR 1.60, p<0.01) and OS (HR 1.34, p = 0.016) after adjusting with gender, age, disease, and donor source. Proportions of patients who died due to hepatic failure (4.9% vs 14.3%) and bacterial infection (9.4% vs 18.2%) were significantly higher in recipients with HCV than in those without HCV. HCV sero-positivity was identified as a risk factor for poor survival in HSCT. In addition, we should carefully manage not only liver dysfunction but also bacterial infection in HCV positive patients.