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      Concurrent Infection of Hepatitis B Virus Negatively Affects the Clinical Outcome and Prognosis of Patients with Non-Hodgkin’s Lymphoma after Chemotherapy

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          Abstract

          Hepatitis B virus (HBV) is hepatotropic and lymphotropic. HBV-infected individuals have an increased risk of developing malignant lymphoma, and the HBV infection rate in lymphoma patients is significantly higher than that in the general population. However, the exact mechanism and correlation between HBV infection and lymphoma onset and progression currently remain unclear. We retrospectively analyzed clinical data from non-Hodgkin’s lymphoma (NHL) patients with different HBV infection statuses. The results showed that the HBV infection rate was significantly higher in patients with B-cell type and late stage of NHL. The chemotherapy efficacy for NHL patients with chronic active HBV infection was significantly lower than that for the patients with chronic inactive HBV infection, the patients with HBV carriers and the patients without HBV infection. In addition, the NHL chemotherapy activated HBV replication and caused significant liver dysfunction, which could further reduce the chemotherapy efficacy. Through Kaplan-Meier survival curve and log-rank analysis, we found that the HBV infection status in NHL patients was significantly correlated with the patients’ progression-free survival (PFS) and overall survival (OS). Compared with the patients without HBV infection (PFS: 95% CI 47.915 to 55.640; OS: 95% CI 81.324 to 86.858), the PFS and OS of the patients with chronic active HBV infection were significantly shorter (PFS: 95% CI 9.424 to 42.589, P < 0.001; OS: 95% CI 42.840 to 82.259, P = 0.006). The study demonstrated that the sustained HBV replication in patients with chronic active HBV infection could be a key factor that influences the prognosis of NHL patients after chemotherapy, and thus may provide information for designing rational clinical treatments for NHL patients with different HBV infection statuses and improve the treatment efficacy and prognosis.

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          Hepatitis B and C Virus Infection and Hepatocellular Carcinoma in China: A Review of Epidemiology and Control Measures

          Masahiro Tanaka, Francisco Katayama, Hideaki Kato … (2011)
          China has one of the highest carrier prevalences of hepatitis B virus (HBV) in the world: nearly 10% of the general population. The disease burden of HBV infection and hepatocellular carcinoma (HCC) is also believed to be among the world’s largest, and that of hepatitis C virus (HCV) infection is likely to be substantial as well. However, the epidemiology and measures to control HBV and HCV infection in China remain relatively unknown outside the country. We review the epidemiology of HBV and HCV infection, the disease burden of and risk factors for HCC, and current control measures against HBV and HCV infection in China. We also discuss the relevant literature and implications for future studies of hepatitis and HCC in China.
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            Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors.

            James H P Hui, S. Zhong, Luis Steinberg … (2000)
            Hepatitis B virus (HBV) reactivation is a well-described complication in cancer patients who receive cytotoxic chemotherapy and may result in varying degrees of liver damage. As chemotherapy is used increasingly in cancer patients, HBV reactivation during cytotoxic treatment may become a more common problem. In lymphoma patients, the incidence of chronic HBV infection has been reported to be 26%, of whom 47% developed HBV reactivation during chemotherapy. However, corresponding data for patients with other malignancies undergoing cytotoxic chemotherapy are not known. In this prospective study, hepatitis B surface antigen (HBsAg) was determined in 626 consecutive cancer patients who received cytotoxic chemotherapy over a 12-month period. Seventy-eight patients (12%) were found to be HBsAg positive. Thirty-four (44%) developed raised alanine transaminase during their course of chemotherapy. In these 34 patients, hepatitis was attributed to HBV reactivation in 15 patients (44%), chronic active HBV infection in 1 patient (3%), hepatitis C infection in 1 patient (3%), malignant hepatic infiltration in 2 patients (6%), and the use of hepatotoxic chemotherapeutic agents in 11 patients (32%). The causes of hepatitis were unknown in 4 patients (12%). HBV reactivation was more likely to develop in patients who were male, younger age, HBeAg seropositive, and those with lymphoma. Presence of malignant hepatic infiltration, baseline pre-treatment alanine transaminase, total bilirubin, and HBV DNA levels did not correlate with the development of HBV reactivation. Of the 15 patients who developed HBV reactivation, antiviral therapy with lamivudine was available and used in 9. There was no HBV-related mortality during chemotherapy. It is concluded that in patients with chronic HBV infection under chemotherapy, HBV reactivation occurs in nearly 20% of them and accounts for 44% of hepatitis cases. The risk factors identified include male sex, younger age, HBeAg seropositive, and the diagnosis of lymphoma. In HBV endemic areas, patients with risk factors for HBV reactivation should be identified prior to receiving cytotoxic treatment and monitored closely. The potential benefit of lamivudine requires further confirmation.
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              Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study.

              Sun Jee, E. Cho, Josephine Engels (2010)
              Hepatitis B virus (HBV) infection is common throughout Asia and Africa. Whether chronic HBV infection increases risk of non-Hodgkin lymphoma (NHL) is unclear. We aimed to assess the association between chronic HBV infection and subsequent development of NHL in a South Korean cohort. The Korean Cancer Prevention Study is a cohort study of South Korean workers and their dependants enrolled during 1992-95. From this cohort, we excluded individuals who died before Jan 1, 1993, who had cancer at or before the initial visit, who had missing information about weight, height, alanine aminotransferase or aspartate aminotransferase concentrations, or alcohol use, or who had evidence of HIV or HCV infection. Of 1,284,586 eligible participants, 603,585 had baseline data for serum hepatitis B surface antigen (HBsAg) status and were included in our study. We regarded HBsAg positivity at baseline as evidence of chronic HBV infection. Participants were followed up from baseline until Dec 31, 2006. We used national databases of inpatient and outpatient diagnoses and mortality records to ascertain occurrence of haematological malignancies. We assessed incidence of NHL overall and of NHL subtypes, malignant immunoproliferation, Hodgkin's lymphoma, multiple myeloma, and various leukaemias. We used Cox regression to evaluate associations with HBsAg status, adjusting for sex, age, and enrolment year. 53,045 (9%) of 603,585 participants tested positive for HBsAg at baseline. Subsequently, 133 HBsAg-positive and 905 HBsAg-negative individuals developed NHL. HBsAg-positive participants had an increased risk of NHL overall compared with those who were HBsAg-negative (incidence 19.4 vs 12.3 per 100,000 person-years; hazard ratio [HR] 1.74, 95% CI 1.45-2.09, adjusted for sex, age at baseline, and enrolment year). Among NHL subtypes, HBsAg positivity was associated with increased risk of diffuse large B-cell lymphoma (n=325, incidence 6.86 vs 3.79 per 100,000 person-years; adjusted HR 2.01, 1.48-2.75) and other or unknown subtypes (n=591, incidence 10.5 vs 7.07 per 100,000 person-years; adjusted HR 1.65, 1.29-2.11), compared with HBsAg negativity. Increased risk was also recorded for malignant immunoproliferation (n=14, incidence 0.44 vs 0.15 per 100,000 person-years; adjusted HR 3.79, 1.05-13.7). Risk of these malignancies was consistently raised in HBsAg-positive participants throughout 14 years of follow-up. HBsAg positivity was not associated with follicular or T-cell NHL, Hodgkin's lymphoma, multiple myeloma, or various leukaemias. During extended follow-up, HBsAg-positive individuals had an increased risk of NHL, suggesting that chronic HBV infection promotes lymphomagenesis. Korean Seoul City Research and the National Research and Development Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea; US National Cancer Institute. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Man-Fung Yuen: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2013
                Publication date (Electronic): 8 July 2013
                Volume: 8
                Issue: 7
                Electronic Location Identifier: e69400
                Affiliations
                [1]Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China
                The University of Hong Kong, Hong Kong
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JC JW. Performed the experiments: JC JW JY WZ. Analyzed the data: JC JY WZ XS. Contributed reagents/materials/analysis tools: JC JW LC. Wrote the manuscript: JC JW.

                Article
                Publisher ID: PONE-D-13-15592
                DOI: 10.1371/journal.pone.0069400
                PMC ID: 3704665
                PubMed ID: 23861969
                SO-VID: 5c9bd81e-1d4e-4b24-899c-c7543e469b2f
                Copyright statement: Copyright @ 2013
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 15 April 2013
                Date accepted : 10 June 2013
                Funding
                This work was funded by a grant from the National Natural Science Foundation of China (No. 81170499). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article

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