Clinical Research Of HBV Reactivation After Chemotherapy In Patients With Malignant Heamatologic Disease

Aims:Hepatitis B virus (HBV) infection is one of the important reasons for liver damage in patients with hematologic malignancies undergoing chemotherapy and immunosuppressive therapy.HBV reactivation play a primary role in this condiction. The risk factors for HBV reactivation in patients with malignant disease are still not well known, and preemptive nucleoside analogues therapy can probablely prevent HBV reactivation. We performed a retrospective assessment on 152 HBV carrying patients with hematologic malignancie and 152 non- HBV carrying patients with hematologic malignancie, evaluat the incidence and severity of liver damage between these two groups. In this paper, we also studied the following questions:1.Frequency fo liver damage and severity of HBV infection in patients HBV carrying patients with hematologic malignancie and compare it with non- HBV carrying patients.2.Whether the liver function on baseline and chemotherapeutics would effect liver damage after chemotherapy or not.3.Whether preemptive nucleoside analogues therapy can reduce the frequency of liver damage and HBV reactivation.4.Is there any relationships among the following factors:HBV reactivation,chemotherapeutics,number of chemotherapy courses, serum HBV markers and liver damage.Methods:We performed a retrospective research and 152 HBV carrying patients with hematologic malignancies were involves from January 1,1999 to March 1,2010, who were in our hospital(Department of Hematology,Nanfang Hospital, Guangzhou,China). Of these 152 patients,87 were men and 65 were women; their mean age was 38 yr, with a range from 13 to 81 yr. The mean number of chemotherapy courses was 6.5, with a range from 1 to 26. By chemotherapy they were divided into 4 groups:1, conventional chemotherapy group (38 cases).2, steroids treatment group (52 cases),3, immunosuppressive treatment group (11 cases), 4, steroids combine immune inhibitor treatment group (51 cases). Hematopoietic stem cell transplantation was performed on 23 cases,4 cases of autologous haematopoietic stem cell transplantation,19 allogeneic haematopoietic stem cell transplant patients. 152 patients without HBV infection were selected as a control group. Liver function and serum markers of HBV were measured in all patients before and after chemotherapy. In HBV infection group, HBV DNA quantitative detection was conducted in 47 patients before and after chemotherapy. AST,ALT and TBIL were used to evaluate liver function. When hepatitis B virus DNA increased by 10 times or more, or it's absolute value increased to 109copies/ml we defined it as hepatitis B virus breakout. Delayed for more than 8 days of chemotherapy was defined as chemotherapy delay. Statistical software SPSS 17.0 was used for data analysis.χ2 test, Fisher exact test and independent samples nonparametric test, was used.All tests were bilateral,when P<0.05 it was considered to be statistically significant.Results:Liver damage occurred in 102 cases in HBV infection group and 93 cases in non-HBV infection group.There was no significant difference between these two groups (67.1% vs 61.2%, P>0.05).The mean number of chemotherapy course when the patients suffered from liver damage for the first time was 3.06 in HBV infection group and 3.77 in non-HBV infection group,where was no significant difference either(P=0.053).It indicated that the HBV infection patients did not suffer from liver fuction injury earlier that other patients. The severity of liver damage in HBV infection group was larger than non-HBV infection group(with a mean rank 104.65 and 89.58, respectively. P=0.047).We studied the HBV infection group by parameters of gender, and there was no statistically significant difference between man and woman on incidence of liver damage(72.4% vs 60.0%, P=0.107) and peak levels of liver damage(with a mean rank 53.12 and 48.88, respectively. P=0.463). HbsAg-positive or not on baseline did not effect the incidence of liver damage (67.1% vs 33.3%, P= 0.970),incidence of HBV reactivation(40.9 vs 40.0%, P= 1.000),hepatitis reduced by HBV reactivation(25 vs 40.0%, P= 0.598) and peak levels of liver damage(P=0.934). HbeAg-positive or not in HbsAg-positive patients did not effect the incidence of HBV reactivation (45.0% vs 34.2%, P= 0.421) and hepatitis reduced by HBV reactivation(30.0% vs 23.7%, P=0.602)either. In both groups,liver function disorder on baseline did not effect the incidence of liver damage after chemotherapy (HBV infection group, P=0.957, non-HBV infection P= 0.306).In HBV infection group, the patients were divided into 4 groups by chemotherapy:1, conventional chemotherapy group (37 cases).2, steroids treatment group (53 cases),3, immunosuppressive treatment group (11 cases),4, steroids combine immune inhibitor treatment group (51 cases).The incidence of liver damage of these 4 groups was 59.5%,67.9%,63.6% and 72.5%, respectively,P=684, which indicated that there was no significant difference among them. The incidence of HBV reactivation of these 4 groups was 16.7%,28.6%,50.0% and 53.6%,respectively. The incidence of hepatitis reduced by HBV reactivation of these 4 groups was 8.3%,23.8%,0% and 39.3%,respectively.There is significant difference between groupland group4 on incidence of HBV reactivation(P=0.041), no significant difference among the other groups. Preemptive nucleoside analogues therapy can reduce the incidence of HBV reactivation (29.3% vs 54.5%, P=0.049) and hepatitis reduced by HBV reactivation (14.7% vs 50.0%, P=0.003).The incidence of liver damage in patients received preemptive nucleoside analogues therapy was not lower than patients who didn't receive preemptive nucleoside analogues therapy (59.7% vs74.7%, P=0.0556).44.0% of the patients with a high viral load on baseline (greater than or equal to 104copies/ml) suffered from HBV reactivation,compared with 37.5% of the patients with low viral load on baseline (less than 104copies/ml),there was no significant difference between them.At the same time,these patients undergoing the hepatitis reduced by HBV reactivation with a incidence of 24.0% compare with 29.2% in the patients with low viral load (P=0.607).Conclusion:Hepatitis B virus (HBV) infection is one of the important reasons of liver damage in patients with malignant disease undergoing chemotherapy and immunosuppressive therapy. Patients with HBV infection suffered from more serious liver damage undergoing chemotherapy and immunosuppressive therapy than non-HBV infection patients. Gender, HbsAg-positive, chemotherapy composition did not effect the incidence of liver damage. HbeAg-positive, HbsAg-positive, chemotherapy composition, high viral load on baseline(≥104 copies/ml) did not effect the incidence of HBV reactivation. Preemptive nucleoside analogues therapy can reduce the incidence of HBV reactivation and hepatitis reduced by HBV reactivation.The incidence of liver damage in patients received preemptive nucleoside analogues therapy was not lower than patients who didn't receive preemptive nucleoside analogues therapy.