|Ahead of print publication
Evaluation of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus seroprevalence in patients with diffuse large B cell lymphoma and Hodgkin's lymphoma
Duygu Mert1, Alparslan Merdin2, Sabahat Ceken1, Mehmet Sinan Dal2, Mustafa Ertek1, Fevzi Altuntas2
1 Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkey
2 University of Health Sciences, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Hematology Clinic and Bone Marrow Transplantation Unit, Ankara, Turkey
|Date of Submission||30-Jun-2019|
|Date of Decision||20-Oct-2019|
|Date of Acceptance||01-Dec-2019|
|Date of Web Publication||22-Oct-2020|
University of Health Sciences Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Infectious Diseases and Clinic Microbiology Clinic, Mehmet Akif Ersoy Mah., Vatan Cad., No. 91, 06300, Yenimahalle/Ankara
Source of Support: None, Conflict of Interest: None
Backgrounds: Non-Hodgkin's lymphoma and Hodgkin's lymphomas (HL) are lymphoid neoplasms. Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are viruses that could proliferate in lymphoid tissues. These viruses may cause lymphoproliferative diseases. The aim of this study was to evaluate the seroprevalence of HBV, HCV, and HIV in patients with diffuse large B-cell lymphoma (DLBCL) and HL, to compare the relationship between these two disease groups and to determine the relationship between the three viruses and their characteristics. Materials and Methods: The study was a retrospective study. Patients who were followed up in hematology and hepatitis outpatient units between January 01, 2012, and May 01, 2019, were included in the study. Results: A statistically significant relationship was observed between the disease groups in terms of hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) IgG antibody, hepatitis B e antigen (HBeAg), and anti-HBe seropositivities (P = 0.004, P = 0.006, P = 0.041, and P = 0.014, respectively). There was also a statistically significant relationship between the disease groups in terms of anti-HCV seropositivity (P = 0.029). HBsAg, anti-HBc IgG, HBeAg, anti-Hbe, and HCV seropositivity rates were higher in patients with DLBCL than in patients with HL. Conclusion: These findings suggest that there may be a relationship between hepatitis viruses and DLBCL. Evaluation of HBV and HCV infections in these patients before starting treatment is thought to be beneficial in initiating antiviral prophylaxis to prevent reactivation in seropositive cases. In addition, care should be taken for the development of lymphoma in the follow-up of HCV and HBV infections.
Keywords: Diffuse large B-cell lymphoma, hepatitis B virus, hepatitis C virus, Hodgkin's lymphoma, human immunodeficiency virus
|How to cite this URL:|
Mert D, Merdin A, Ceken S, Dal MS, Ertek M, Altuntas F. Evaluation of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus seroprevalence in patients with diffuse large B cell lymphoma and Hodgkin's lymphoma. J Can Res Ther [Epub ahead of print] [cited 2021 Jun 22]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=298863
| > Introduction|| |
Non-Hodgkin's lymphoma (NHL), which is one of the most common cancers, constitutes 4%–5% of all cancers. Diffuse large B-cell lymphoma (DLBCL) is the most common type that covers 30%–60% of NHL. The cause of this disease is strongly correlated with the infection status and host immunity.
Hodgkin's lymphomas (HLs) are lymphoid neoplasms, in which malignant Hodgkin's/Reed–Sternberg cells are admixed with a heterogeneous population of nonneoplastic inflammatory cells. The incidence and distribution of HL histologic subtypes is influenced by geography, socioeconomic factors, human immunodeficiency virus (HIV) infection, and family history. Although Epstein–Barr virus (EBV) has been linked to the pathogenesis of HL, the virus is detected in only a subset of cases, and the absolute risk for HL after EBV infection is very small.
Hepatitis B virus infection (HBV) is a worldwide serious health problem. HBV, a hepatotropic virus, has the potential to proliferate in lymphoid cells. This suggests that HBV infection may have a potential role in the etiology of lymphomas. There are few clinical studies showing a higher prevalence of HBsAg in patients with DLBCL.
HCV is a hepatotropic and lymphotropic virus., Apart from HCV-attributable hepatocellular carcinoma, the strongest association between cancer and HCV is the epidemiologic link between the virus and subtypes of B-cell NHL, particularly DLBCL, marginal zone lymphoma, and lymphoplasmacytic lymphoma. Schöllkopf C et al reported that there was a positive association between HCV and risk of NHL and risk of NHL.
HIV infection results in impaired cellular immunity. NHL could develop in about 10% of HIV-infected people. In their study of Coté TR et al, compared with the people without AIDS, the relative risk was found as 261-fold for Burkitt lymphoma, among patients with HIV.
HBV, HCV, and HIV are viruses that could proliferate in lymphoid tissues, as mentioned above. The aim of this study was to evaluate the seroprevalence of HBV, HCV, and HIV in patients with DLBCL and HL; to compare the relationship between these two patient groups; and to determine the relationship between the three viruses and their characteristics. It is also to determine whether there is a difference between DLBCL and HL patients who have HBsAg positivity or innate immunity to HBV.
| > Subjects and Methods|| |
The study was a retrospective study. University of Health Sciences Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Ethics Committee's approval was obtained (approval date: February 20, 2019, and decision no. 2019-02/219).
Patients who were followed up in hematology and hepatitis outpatient units between January 01, 2012, and May 01, 2019, were included in the study.
Eighteen years olds and older than 18 years of age patients with DLBCL or HL were included in the study. Patients who were under 18 years old, pregnant patients, and those without DLBCL or HL were excluded from the study.
The current diagnoses and other results of the patients were recorded electronically as a retrospective file scan from the health records. The demographic data of the patients and their other information were recorded in a preprepared form.
The following information was recorded: age, sex, type of disease, HBsAg, anti-HBs, anti-hepatitis B core (HBc) IgM, anti-HBc IgG, hepatitis B e antigen (HBeAg), anti-HBe, anti-delta antibody, HBV DNA, anti-HCV, HCV RNA, HCV genotype, anti-HIV, and HIV RNA. A comparison of these data was made in patients with DLBCL and HL.
SPSS (IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp) program was used in the comparison of statistical data. The data were entered into statistical software program and analyzed by using the same computer software program. In order to interpret the findings, frequency tables and descriptive statistics were used.
The categorical descriptive data were presented as frequency distribution and percentages (%), and the measurable descriptive data were presented as mean ± standard deviation and median (the largest to the smallest values).
The “χ2-cross tables” were used to examine the relationship between two qualitative variables. “Mann–Whitney U”-test (Z-table value) statistics were used to compare the two nonnormally distributed independent groups. P < 0.05 was considered statistically significant.
| > Results|| |
Data of 366 patients with DLBCL and 378 patients with HL, who were followed up in hematology and hepatitis polyclinic between January 1, 2012, and January 5, 2019, were analyzed.
The tests related to seroprevalence of HBV, HCV, and HIV were recorded from all of these patients.
A total of 199 (54.4%) patients were male and 167 (45.6%) were female in the DLBCL group. A total of 215 (56.9%) patients were male and 163 (43.1%) were female in the HL group [Table 1].
|Table 1: Comparison of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus seroprevalence in patients with diffuse large B-cell lymphoma and Hodgkin's lymphoma|
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The mean age of the patients with DLBCL was 56.23 ± 16.56 years, and the mean age of the patients with HL was 42.48 ± 15.71 years. A statistically significant difference was found between the two disease groups in terms of age (P < 0.05). The ages of patients with DLBCL were significantly higher than the ages of patients with HL.
A statistically significant relationship was observed between both diseases in terms of HBs Ag seroprevalence (P < 0.05). HBsAg was negative in 340 (93.2%) patients with DLBCL and HBsAg was positive in 9 (2.4%) patients with HL. It was determined that HBsAg negativity was predominantly observed in HL patients and positivity was predominantly observed in DLBCL patients [Table 1].
There was a statistically significant relationship between diseases in terms of anti-HBc IgG positivity (P < 0.05). Anti-HBc IgG was negative in 167 (61.9%) patients with DLBCL and anti-HBc IgG was positive in 80 (28.2%) patients with HL. It was determined that frequency of anti-HBc IgG seropositivity was higher in patients with DLBCL than in patients with HL [Table 1].
A statistically significant relationship was found between the diseases and HBeAg (P < 0.05). HBeAg was positive in 4 (2.5%) patients with DLBCL and HBeAg was negative in 192 (100.0%) patients with HL. It was determined that frequency of HBeAg seropositivity was higher in patients with DLBCL than in patients with HL [Table 1].
There was a statistically significant relationship between diseases and anti-HBe (P < 0.05). Anti-HBe was negative in 132 (81.0%) patients with DLBCL and anti-HBe was positive in 19 (9.5%) patients with HL. It was determined that anti-HBe seropositivity was predominantly observed in DLBCL patients and negativity was predominantly observed in HL patients [Table 1].
Patients tested for HBV DNA were also analyzed. In patients with DLBCL, HBV DNA levels were negative in 72 patients, were below 10,000 copies/ml in nine patients, were above 10,000 copies/ml in four patients, and were over 100,000 copies/ml in six patients. In patients with HL, HBV DNA levels were negative in 41 patients, were below 10,000 copies/ml in seven patients, and were 1.3 × 107 copies/ml in only one patient.
There was a statistically significant relationship between diseases in terms of anti-HCV seropositivity (P < 0.05). Anti-HCV was positive in 5 (1.4%) patients with DLBCL and anti-HCV was negative in 376 (100.0%) patients with HL. It was determined that anti-HCV seronegativity was predominantly observed in HL patients and seropositivity was predominantly observed in DLBCL patients [Table 1].
| > Discussion|| |
Almost all HBV-related lymphomas are of B-cell origin, comprising a heterog'eneous group including an aggressive clinical course with a poor therapeutic effect of traditionally tolerated chemotherapy in DLBCL. In a study by Wang et al., it was reported that there was a correlation between HBV infection and DLBCL progression and that HBV may play a key role in the development of B-cell NHL. Serological studies have demonstrated an increased prevalence of B-cell NHL in patients infected with HBV infection in the last decade.
Dalia et al. demonstrated that there was an increased odds ratio of 2.24 for developing DLBCL in high HBV prevalence countries. Serological studies have shown that HBV-infected patients have a higher risk of developing B-cell NHL, typically DLBCLs, than noninfected patients, and the viral infection may play an etiopathologic role in oncogenesis in these subtypes of lymphomas.
There is an association between several of the risk factors for HL. As an example, compared with economically developed regions, there are higher rates of mixed cellularity classic HL and lymphocyte-depleted classic HL in geographic regions with lower socioeconomic development; these subtypes are more commonly associated with EBV-positive HL and higher rates of HIV infection.
In this study, HBsAg, anti-HBc IgG, HBeAg, and anti-HBe seroprevalence was significantly higher in patients with DLBCL compared to patients with HL [Table 1].
HBV can infect B lymphocytes and may be related to the development of DLBCL. The discovery of virogenic pathway inducing the development of DLBCL and HBV function remains a prospective study for treatment strategies.
High activity of viral replication is associated with a poor survival outcome of patients with both HBV infection and DLBCL. Chronic HBV infection leads to poorer outcomes and a poorer prognosis in DLBCL. In addition to antiviral therapy, more attention should be paid to the virological effects of HBV, especially HBsAg, during the progression of DLBCL.
Many epidemiological studies have found a strong relationship between HCV infection and DLBCL. In a study by Hosry et al., it was reported that HCV-infected patients appear to have more advanced stages at clinical presentation of DLBCL, with transformation occurring at a younger age than in uninfected patients. The inhibition of B cell apoptosis and sustained B-cell activation by HCV core proteins may explain the earlier transformation to DLBCL in infected patients.
Carloni et al. highlighted how mutually noncontrasting mechanisms cooperate with environmental factors toward the progression of HCV lymphoma by reviewing genetic alterations and disrupted signaling pathways.
In our study, a statistically significant difference was found between DLBCL and HL groups in terms of HCV seropositivity. Anti-HCV positivity was found to be higher in patients with DLBCL. In DLBCL patients tested for HBV DNA, one patient had 6.09 × 107 copies/ml of HCV RNA and genotype 1b and one patient had 7.38 × 106 copies/ml of HCV RNA.
In HIV-infected patients, HIV predisposes to the development of cancers. On the other hand, In our study, HIV infection was not detected in all patients with DLBCL and HL.
| > Conclusion|| |
HBsAg, anti-HBc IgG, HBeAg, anti-HBe, and HCV seropositivity rates were higher in patients with DLBCL than in patients with HL. These findings suggest that there may be a relationship between hepatitis viruses and DLBCL. HBV infection rate is higher in patients with DBBHL. Evaluation of HBV and HCV infections in these patients before starting treatment is thought to be beneficial in initiating antiviral prophylaxis to prevent reactivation in seropositive cases. In addition, care should be taken for the development of lymphoma in the follow-up of HCV and HBV infections.
We would like to thank Melih Uzunoglu.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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