Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy: risk factors and survival

Abstract

IntroductionHepatitis B virus (HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBcAb]-positive). This study aimed to assess HBV reactivation and hepatitis occurrence in diffuse large B-cell lymphoma (DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reactivation and hepatitis occurrence and to analyze whether HBV reactivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.MethodsWe reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center, China. Predictive factors for HBV reactivation, hepatitis development, and survival were examined by univariate analysis using the chi-square or Fisher’s exact test and by multivariate analysis using the Cox regression model.ResultsAmong the 278 patients, 165 were HBsAg-negative. Among these 165 patients, 6 (10.9%) of 55 HBcAb-positive (resolved HBV infection) patients experienced HBV reactivation compared with none (0%) of 110 HBcAb-negative patients (P = 0.001). Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients (21.8% vs. 8.2%, P = 0.013). HBcAb positivity and elevated baseline alanine aminotransferase (ALT) levels were independent risk factors for hepatitis. Among the 55 patients with resolved hepatitis B, patients with elevated baseline serum ALT or aspartate aminotransferase (AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels (P = 0.037, P = 0.005, respectively). An elevated baseline AST level was an independent risk factor for hepatitis in these patients. Six patients with HBV reactivation recovered after immediate antiviral therapy, and chemotherapy was continued. HBcAb positivity, HBV reactivation, or hepatitis did not negatively affect the survival of DLBCL patients.ConclusionsDLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reactivation and hepatitis than HBsAg-negative/HBcAb-negative patients. Close monitoring and prompt antiviral therapy are required in these patients.

Hepatitis B virus screening and reactivation and management of patients with nasopharyngeal carcinoma: A large‐scale, big‐data intelligence platform–based analysis from an endemic area

“…However, the American Society of Clinical Oncology recommended screening for patients who were at high risk for HBV infection and for those receiving highly suppressive chemotherapy regimens such as hematopoietic stem cell transplantation and rituximab‐based therapy before any forms of chemotherapy . According to previously published studies, the reactivation risk ranged from 6% to 10% for patients with HBV infections when they were receiving rituximab‐based chemotherapy . Our study demonstrated a higher reactivation rate with some types of high‐risk regimens for the treatment of NPC.…”

“…11 According to previously published studies, the reactivation risk ranged from 6% to 10% for patients with HBV infections when they were receiving rituximab-based chemotherapy. [19][20][21] Our study demonstrated a higher reactivation rate with some types of high-risk regimens for the treatment of NPC. In addition, the American Gastroenterological Association recently published guidelines on the management of HBV reactivation, 22 and they defined high-risk patients as those with a reactivation risk exceeding 10% or those positive for HBsAg and receiving anthracycline-based chemotherapy.…”

Role of surface antibody in hepatitis B reactivation in patients with resolved infection and hematologic malignancy: A meta‐analysis

“…A positive anti‐HBs versus only anti‐HBc reduced reactivation with a pooled OR of 0.21 (95% CI 0.14‐0.32) (Fig. ) . The regression test for funnel plot asymmetry was not significant ( P = 0.84).…”

“…). Of the 19 observational studies, 11 were prospective and eight were retrospective . One RCT compared entecavir HBV prophylaxis (before chemotherapy) versus entecavir treatment for HBV reactivation …”

Optimizing antiviral agents for hepatitis B management in malignant lymphomas

“…One factor is lymphomagenesis which provides a milieu of immunosuppression which favors HBV replication. In addition (50,51), when immunosuppressive agents are initiated in lymphoma, induced immunosuppression triggers viral replication that manifests as HBV reactivation (38,(52)(53)(54). It is important to note that spontaneous reactivation can occur in individuals without lymphoma, especially individuals with positive HBeAg, likewise coinfection with HIV, bacterial infections or stressors (emotional and physical) (55).…”