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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 10  |  Page : 774-778

Hepatitis B and C rates are significantly increased in certain solid tumors: A large retrospective study


1 Department of Internal Medicine, Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Istanbul, Turkey
2 Department of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey
3 Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Istanbul, Turkey
4 Department of Hematology, Akdeniz University Faculty of Medicine, Antalya, Turkey
5 Department of Hematology, Ankara Numune Education and Research Hospital, Ankara, Turkey

Date of Web Publication24-Sep-2018

Correspondence Address:
Hakan Kocoglu
Department of Internal Medicine, Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Zuhuratbaba District, Tevfik Saglam Street, No. 11, 34147 Bakirkoy, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.174544

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 > Abstract 


Objective: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with significant morbidity and mortality among cancer patients who received cytotoxic chemotherapy. The aim of current study was to elucidate the prevalence of HBV and HCV among large population of solid cancers and lymphoma and to compare them with large number of control group.
Patients and Methods: Between 2000 and 2014, 8322 cancer patients who were admitted to Oncology Departments were evaluated retrospectively and 3890 patients in whom hepatitis serology were available were included in this study. Their results were compared with control group that consisted of 96,000 subjects.
Results: In control groups, hepatitis B surface antigen (HBsAg) positivity rate was 3.3% and anti-HCV positivity rate was 0.84%. In cancer patients, HBsAg positivity rate was 3.65% and anti-HCV positivity rate was 1.2%. Neither HBsAg positivity rate nor anti-HCV positivity rate was statistically significant between groups (P = 0.12 and P = 0.09, respectively). HBsAg positivity rates of head and neck cancer (5.88%; P = 0.02), rectum (5.6%; P = 0.025), and gastric and esophagus cancer (5.88%; P = 0.025) were significantly higher than control groups. Anti-HCV positivity rate (2.5%; P = 0.0016) was significantly higher in lung cancer when compared with control group.
Conclusion: The current study elucidated the prevalence of HBV and HCV among large population of solid cancers and lymphoma and we showed that hepatitis B and C positivity rates are significantly increased in certain solid tumors. Our findings should also be clarified with large prospective studies.

Keywords: Cancer, hepatitis B, hepatitis C, prevalence


How to cite this article:
Kocoglu H, Karaca M, Tural D, Hocaoglu E, Okuturlar Y, Fetullahoglu Z, Gunaldi M, Ciftci R, Tuna S, Yuce OK, Ozet G, Ozet A, Benekli M. Hepatitis B and C rates are significantly increased in certain solid tumors: A large retrospective study. J Can Res Ther 2018;14, Suppl S3:774-8

How to cite this URL:
Kocoglu H, Karaca M, Tural D, Hocaoglu E, Okuturlar Y, Fetullahoglu Z, Gunaldi M, Ciftci R, Tuna S, Yuce OK, Ozet G, Ozet A, Benekli M. Hepatitis B and C rates are significantly increased in certain solid tumors: A large retrospective study. J Can Res Ther [serial online] 2018 [cited 2020 Oct 28];14:774-8. Available from: https://www.cancerjournal.net/text.asp?2018/14/10/774/174544




 > Introduction Top


Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with significant morbidity and mortality among patients with cancer who received cytotoxic chemotherapy.[1] HBV reactivation rates in HBV carriers who received chemotherapy were 14–72% and mortality rates were 5–52%.[1] HCV reactivation are also significant problem, however it seems to be less common than HBV reactivation and usually associated with lower morbidity and mortality when compared HBV.[1] Hepatitis B and C reactivation can lead to liver failure, hepatic encephalopathy, and death. In addition, it may lead disruption of chemotherapy as a result of hepatitis reactivation which may cause a decrease in survival of patients with cancer.[2],[3] Problems related to hepatitis, such as HBV reactivation and their management, is well defined in patients with hematological malignancies, but limited data are available in patients with solid cancer. The risk factors and mechanisms of HBV reactivation are not well understood. In limited studies performed in East Asian region, risk factors for HBV reactivation were demonstrated as high HBV DNA levels, use of systemic corticosteroid, and certain cancer types, such as lymphoma or breast cancer.[4] The American Society of Clinical Oncology suggests screening patients who have risk factors for HBV infection or for whom is planned an immunosuppressive therapy that may cause HBV reactivation.[5] However, more than 65% of patients with HBV infection are unaware of their infection.[6] However, there are many unanswered questions about HBV screening prior to chemotherapy for solid tumors and there is no sufficient evidence about which appropriate population to screen.

To our knowledge, there are no available detailed data in literature in regard to HBV and HCV rates in solid cancer types. The aim of current study is to elucidate the prevalence of HBV and HCV among large population of solid cancers and lymphoma and to compare them with those of large number of control group.


 > Patients and Methods Top


Between 2000 and 2014, 8322 cancer patients who were admitted to our Oncology Departments were evaluated retrospectively. Patients' data were retrospectively evaluated and a total number of 3890 patients for whom hepatitis serology was available were included in this study. Control group was consisted of 96,000 healthy volunteer blood donors who admitted to blood bank for blood donation. Cancer type of each patient was coded according to the International Classification of Diseases for Oncology.[7] The data were primarily obtained from hospital files and electronic data, as well as directly from patients and patient's relatives. Laboratory results of patients were obtained from hospital files and electronic data (hospital information system). Enzyme linked immunosorbent assays have being using in order to assay hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. Patients who had not any code for pathological cancer diagnosis were excluded. In addition, patients who have liver cancer were excluded.

Statistical analysis

Association of HBsAg and anti-HCV serologic markers with cancer types were determined by using the χ2 or Fisher's exact test as appropriate for categorical variables. In addition, Mann–Whitney U-test was used for numerical variable. Two-tailed P < 0.05 were considered significant.


 > Results Top


Between 2000 and 2014, 8322 patients with cancer were retrospectively evaluated and 3890 patients (47%) for whom hepatitis serology was available were included in this study. Study group was consisted of 2042 female (52.48%) and 1848 male (47.52%) patients (P = 0.1) with mean age of 59.55 ± 13.71 years (range: 19–93).

Mean age was 51.75 ± 16.14 years (range: 25–81) for HBsAg positive patients and 59.84 ± 13.54 years (range: 19–93) years for HBsAg negative patients, and this difference was statistically significant (P = 0.001). Forty-five percent of all HBsAg positive patients was female (n = 64) and 55% of all HBsAg positive patients was male (n = 78), and the difference was not significant (P = 0.1).

Mean age was 48.58 ± 15.81 years (range: 27–86) for anti-HCV positive patients and 59.72 ± 13.62 years (range: 19–93) for anti-HCV negative patients, and this difference was also statistically significant (P = 0.0001). Forty-eight percent of all anti-HCV positive patients was female (n = 23) and 52% of all anti-HCV positive patients was male (n = 25) and the difference was not significant (P = 0.1) [Table 1].
Table 1: Age and gender distribution of patients with hepatitis B surface antigen positive or with anti-hepatitis C virus positive

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In control groups, HBsAg positivity rate was 3.3% and anti-HCV positivity rate was 0.84%. In cancer patients, HBsAg positivity rate was 3.65% and anti-HCV positive rate was 1.2%. When we compared cancer patients and control group neither HBsAg positivity rate nor anti-HCV positivity rate was not statistically significant (P = 0.12 and P = 0.09, respectively).

Subgroup analyses of cancer patients for HBsAg positivity rate and their comparisons with control group were as follows: Breast cancer 2.98% (P = 0.11), lung cancer 3.35% (P = 0.15), gastric and esophageal cancers 5.67% (P = 0.027), colon cancer 3.8% (P = 0.1), rectum cancer 5.6% (P = 0.025), head and neck cancers 5.88% (P = 0.02), lymphoma 3% (P = 0.2), central nervous system cancers 2.88% (P = 0.3), pancreas and biliary tract cancers 4.3% (P = 0.09), urogenital cancers 2.3% (P = 0.12), gynecologic cancers 4% (P = 0.08), skin cancer 2% (P = 0.11), and other cancers 3.26% (P = 0.1).

Subgroup analyses of cancer patients for anti-HCV positivity rate and their comparisons with control group were as follows: Breast cancer 0.09% (P = 0.1), lung cancer 2.5% (P = 0.0016), gastric and esophageal cancers 1.57% (P = 0.12), colon cancer 1.3% (P = 0.14), rectum cancer 1.25% (P = 0.26), head and neck cancers 0.49% (P = 0.09), lymphoma 0.75% (P = 0.1), central nervous system cancers 0.96% (P = 0.11), pancreas and biliary tract cancers 0.86% (P = 0.99), urogenital cancers 1.16% (P = 0.12), and gynecologic cancers 0.5% (P = 0.07), skin cancer 1.39% (P = 0.17), and other cancers 1.39% (P = 0.18) [Table 2].
Table 2: Distribution of hepatitis B surface antigen and anti-hepatitis C virus positivity in each type of cancer and their comparison with control group

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 > Discussion Top


The United States Centers for Disease Control and Prevention recommends HBV screening in patients with cancer before any form of immunosuppressive therapy including cytotoxics.[8] However, there are many unanswered questions about HBV screening prior to chemotherapy for solid tumors. In addition, there is no sufficient evidence about which appropriate population to screen, and the benefits and potential harms of antiviral therapy in solid cancer patients with HBV positive.[9] Importantly, HBV screening in all patients with solid tumors may not be cost effective where prevalence of HBV is low,[10] and when chemotherapy regimens associated with low hepatitis B reactivation risk. In 2010, the American Society of Clinical Oncology issued a clinical opinion stating insufficient evidence to support routine HBV screening for all cancer patients undergoing cytotoxic chemotherapy.[11]

Hepatitis serology of patients who will receive immunosuppressive therapy including cytotoxics is a very important knowledge. Rates of HBV reactivation in HBV carriers who undergo chemotherapy vary, with reported values ranging from 14% to 72%.[2],[3],[12] Differences in patient populations, types of tumors, chemotherapy regimens, definitions of reactivation, and study designs are some possible explanations for this large variation.[1] Our study results which we showed HBsAg positivity rates are different among cancer types may also contribute to explain for this wide variation. HCV reactivation following immunosuppressive therapy is rare.[13],[14] Although HCV reactivation seems to be more common in patients with hematologic malignancies,[13],[15] it also has been reported in patients with solid tumors.[16],[17],[18]

To our knowledge, there are no satisfying available data in regard to HBsAg positivity ratios in solid cancer patients. Previous studies have focused on hepatic complications during cytotoxic chemotherapy in hematologic cancer patients with HBsAg-seropositive. A few study elucidated HBsAg seropositivity in patients with solid cancer. Alexopoulos et al.[12] elucidated that HBsAg was determined in 54 (5.3%) of the 1008 cancer patients who received chemotherapy and 14% had hepatitis was attributed to HBV reactivation. In addition, in a study of 448 cancer patients, HBsAg and anti-HCV positivity rates have been determined as 4.2% and 0.7%, respectively.[19] According to our study, in cancer patients, HBsAg positivity rate was 3.65% and anti-HCV positive rate was 1.2%.

In this study, we retrospectively evaluated 8322 cancer patients who underwent chemotherapy in our Oncology Departments during 14 years. Information regarding the hepatitis serology for 53% of all patients was unavailable and a total of 3890 patients (47%) for whom hepatitis serology was available were included in this study. Therefore, overall screening rates of HBV and HCV in solid cancer patients were determined as 47% in this study. A large retrospective cohort study that was performed in an experienced single center has shown that the prevalence of HBV screening was <4% in patients with solid tumors.[20] The reason for such a high result may be because most of patients who underwent surgical intervention have been screening for HBV and HCV.

In current study, HBsAg positivity rate of control group, which was consisted of 96,000 healthy volunteer blood donors, was determined as 3.3% and anti-HCV positivity rate was determined as 0.84%. Moreover, to the best of our knowledge, this is one of the largest scale studies determining HBV and HCV prevalence in Turkey. Rates of HBsAg positivity vary within Turkey.[21] In a meta-analysis evaluating studies published between 1999 and 2009, Toy et al. estimated that the prevalence rates of HBsAg positivity in the West, Middle, and Eastern regions were 3.5%, 4.9%, and 6.8%, respectively.[22] In another study conducted 225,483 people between 2005 and 2012 in Turkey, prevalence of HBsAg seropositivity and anti-HCV antibody positivity were found 10% and 1.2%, respectively.[23]

We compared HBV and HCV positivity rates between subtype of cancers and control group. In head and neck cancers (5.88%), rectum cancer (5.6%), and gastric and esophageal cancers (5.88%), HBsAg positivity rates were statistically significantly higher than control groups. In addition, anti-HCV positivity rate (2.5%) was significantly higher (approximately × 3 times) in lung cancer patients when compared to control group (0.84%). There are some evidences that cancer rates (other than liver) among patients with HCV are increased when compared to those not infected.[24],[25] Moreover, a study conducted 236 elderly cancer patients showed a significant difference in anti-HCV seroprevalence between patients with kidney cancer, bladder cancer, or prostate cancer and the control group.[26] In a previous study, it has been shown that HBV infection was positively related with gastric cancer, especially for patients without family history of gastric cancer.[27] However, to the best of our knowledge, there is no published study that shows association between HBV and head and neck cancers, rectum cancer, and esophageal cancer. In addition, in our study, we could not have determined a relationship between HBV and pancreatic cancer as it has been stated in a study by Hassan et al.[28] However, our results should be clarified by large prospective studies.

We also evaluated 1004 breast cancer patients that underwent chemotherapy and 2.98% (n = 30) of patients were determined as HBsAg positive and 0.9% (n = 9) of patients were determined as anti-HCV positive. The positivity rates of HBV and HCV were not statistically significant when we compared with healthy controls. However, Yeo et al. demonstrated that 41% breast cancer patients who underwent chemotherapy developed HBV reactivation.[29] Therefore, routine screening should be done in patients with certain types of cancer that has higher prevalence of hepatitis and also in those who will receive chemotherapy that can reactivate hepatitis.


 > Conclusion Top


In current study, HBsAg positivity ratio was determined statistically significantly higher in patients with head and neck cancer, rectum cancer, and gastric and esophageal cancer when compared control group. In addition, HCV positivity rate was higher in patients with lung cancer when compared control group. The current study elucidated the prevalence of HBV and HCV among large population of solid cancer and lymphoma and demonstrated that hepatitis rates are significantly increased in certain solid tumors. However, this information should be clarified with large prospective study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Yeo W, Zee B, Zhong S, Chan PK, Wong WL, Ho WM, et al. Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Br J Cancer 2004;90:1306-11.  Back to cited text no. 4
    
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Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin L, Parkin D, et al. International Classification of Diseases for Oncology, (ICD-O-3). 3rd ed. Geneva, Switzerland: World Health Organization; 2000.  Back to cited text no. 7
    
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Day FL, Karnon J, Rischin D. Cost-effectiveness of universal hepatitis B virus screening in patients beginning chemotherapy for solid tumors. J Clin Oncol 2011;29:3270-7.  Back to cited text no. 10
    
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Alexopoulos CG, Vaslamatzis M, Hatzidimitriou G. Prevalence of hepatitis B virus marker positivity and evolution of hepatitis B virus profile, during chemotherapy, in patients with solid tumours. Br J Cancer 1999;81:69-74.  Back to cited text no. 12
    
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Kawatani T, Suou T, Tajima F, Ishiga K, Omura H, Endo A, et al. Incidence of hepatitis virus infection and severe liver dysfunction in patients receiving chemotherapy for hematologic malignancies. Eur J Haematol 2001;67:45-50.  Back to cited text no. 13
    
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Markovic S, Drozina G, Vovk M, Fidler-Jenko M. Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosuppressive therapy. A prospective study in 305 patients. Hepatogastroenterology 1999;46:2925-30.  Back to cited text no. 14
    
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Takai S, Tsurumi H, Ando K, Kasahara S, Sawada M, Yamada T, et al. Prevalence of hepatitis B and C virus infection in haematological malignancies and liver injury following chemotherapy. Eur J Haematol 2005;74:158-65.  Back to cited text no. 15
    
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Turhanoglu M, Onur A, Bilman FB, Ayaydin Z, Aktar GS. Eight-year seroprevalence of HBV, HCV and HIV in Diyarbakir training and research hospital. Int J Med Sci 2013;10:1595-601.  Back to cited text no. 23
    
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Wei XL, Qiu MZ, Jin Y, Huang YX, Wang RY, Chen WW, et al. Hepatitis B virus infection is associated with gastric cancer in China: An endemic area of both diseases. Br J Cancer 2015;112:1283-90.  Back to cited text no. 27
    
28.
Hassan MM, Li D, El-Deeb AS, Wolff RA, Bondy ML, Davila M, et al. Association between hepatitis B virus and pancreatic cancer. J Clin Oncol 2008;26:4557-62.  Back to cited text no. 28
    
29.
Yeo W, Chan PK, Hui P, Ho WM, Lam KC, Kwan WH, et al. Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: A prospective study. J Med Virol 2003;70:553-61.  Back to cited text no. 29
    



 
 
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