Effect Of Human Pegivirus Infection On Prognosis Of Patients With Hematopoietic Stem Cell Transplantation

Background and objective: Hepatitis G virus is a member of Flaviviridae with single-stranded,positive-sense RNA genome,which has been renamed Human Pegivirus(HPgV) virus in recent years.The virus does not generally cause liver damage,but can play a positive role in the treatment of HIV-infected and Ebola virus-infected individuals.Meanwhile,HPgV is also a risk factor for non-Hodgkin lymphoma and hepatitis-related aplastic anemia.Our previous study found that the prevalence of HPgV infection in hematopoietic stem cell transplantation patients can be as high as 18.6%,which is significantly higher than that in healthy blood donors(2.3%),and that blood transfusion is one important risk factor for HPgV infection.Considering the high prevalence of HPgV infection and the extremely low immunity in hematopoietic stem cell transplantation(HSCT)patients,it is of great significance to investigate the prognosis of HPgV infection on HSCT patients.Based on previous work and clinical data,we attempt to analyze the correlation between HPgV infection and prognosis of HSCT patients,so as to provide a theoretical basis for optimizing the treatment regimen and evaluating the prognosis of HSCT.Methods: 1.188 HSCT patients in department of HSCT(June 2011-December 2017) and 228 patients with gastrointestinal disease in Department of gastroenterology(January 2012-December 2017)were enrolled in this study.The prevalence of hepatitis viruses(especially HPgV)were recorded and analyzed.2.188 HSCT patients were enrolled to analyze the risk factors of HPgV infection,including age,sex,marital status,ethnicity,leukemia type,blood transfusion,HBV and HCV infection.A total of 694 healthy blood donors were included as controls.3.The HSCT patients were divided into 3 groups according to the leukemia type.The correlation between prognosis and various parameters was analyzed,including immune reconstruction,graft-versus-host response,overall survival,relapse rate,treatment-related mortality,and leukemia-free survival.Results: 1.The prevalence of HBs Ag,Anti-HCV,HEV RNA and HPgV RNA was 4.8%,0.5%,0.5%,and 18.6% in HSCT patients,as well as 12.7%,2.6%,0.9%,and 0.4% in patients with digestive system diseases,respectively.No HAV and HDV infections were detected in these patients.Gender,age,blood group,marital status,ethnicity,and blood transfusion had no significant effects on HBV infection.2.The prevalence of HPgV in HSCT patients(18.6%)was significantly higher than that in healthy donors(2.3%).Ethnicity and blood transfusion were risk factors for HPgV infection.There were no significant differences in the prevalence of HPgV infection among age,sex,sex,blood type,HBV infection,HCV infection,marital status,and leukemia type.3.The median times of neutrophil reconstruction in HPgV-positive and HPgV-negative patients in AML,ALL,and MDS were 13.5(IQR,11-15)days vs 13(IQR,11-14)days,12(IQR,11-14)days vs 13(IQR,11.5-14)days,and 12(IQR,11-15) days vs 14(IQR,11-16)days,respectively.The median platelet reconstitution times in HPg V-positive and HPgV-negative patients in AML,ALL,and MDS were 14(IQR,12-16) days vs 14(IQR,12-17) days,15(IQR,10-17)) days vs 13.5(IQR,12-15) days,and 19(IQR,16-28) days vs 15(IQR,12-30) days,respectively.There was no significant difference in hematopoietic reconstitution among the three groups(AML,ALL,and MDS).The incidences of skin a GVHD(grade ?-?),skin cGVHD,and gastrointestinal cGVHD in HPg V-positive patients in AML were significantly higher than those in HPg V-negative patients,which were characterized with 25% vs 6.9%,60.6% vs 24.7%,12% vs 1.4%,respectively.OS in HPgV-negative ALL patients was significantly higher than that of HPg V-positive ALL patients(93.7% vs 69.3%).In MDS patients,OS and LFS in HPg V-negative patients was significantly higher than that of HPgV-positive patients(92.9% vs 50%,85.7% vs 50%),while TRM and the incidence of liver grade ?-? a GVHD in HPgV-negative patients were significantly lower than those of HPg Vpositive patients(0%vs 33.3%,0% vs 25%).All the differences were statistically significant.Conclusions: 1.The dominant hepatitis viruses in Department of Gastroenterology in our hospital were HBV,followed by HCV.HEV and HPgV infections were rarely detected.No HAV and HDV infections were detected.Gender,age,blood type,marital status,ethnicity,and transfusion had no significant effects on HBV infection.There was no significant differences in prevalence of HAV,HBV,HCV,HDV,and HEV infections between HSCT patients and healthy blood donors.The prevalence of HPgV infection in HSCT patients was significantly higher than patients with digestive system diseases.2.HSCT patients are at high risk for HPgV infection.The HPgV infection has no significant association with gender,age,blood type,HBV infection,HCV infection,marital status,and leukemia type.Ethnicity may be the risk factors for HPgV infection.Blood transfusion can significantly increase the risk of HPgV infection.3.HPgV infection can increase the incidence of grade ?-? a GVHD(skin),skin cGVHD,and gastrointestinal cGVHD in AML patients.It can also increase the incidence of grade ?-? a GVHD(liver) in MDS patients,while reducing OS in ALL and MDS patients,reducing LFS in MDS patients.In order to reduce the risk of HPgV infection after blood transfusion in HSCT patients and avoid potential impact of HPgV infection on patient prognosis,HPgV screening is recommended in blood donors and stem cell donors of HSCT patients.Surveillance of HPgV infection after HSCT is also recommended so as that patients can acquire the corresponding therapeutics.