Chronic Hepatitis B Virus Infection and Risk of Pancreatic Cancer: A Meta-analysis

  • Li, Lei (Department of Gastroenterology, Shandong Provincial Hospital, Shandong University) ;
  • Wu, Bo (Department of General Surgery, Taian Eighty Eight Hospital) ;
  • Yang, Li-Bo (Taian Central Hospital) ;
  • Yin, Guan-Cheng (Taian Central Hospital) ;
  • Liu, Ji-Yong (Department of Gastroenterology, Shandong Provincial Hospital, Shandong University)
  • Published : 2013.01.31


Objectives: A number of studies have shown that chronic hepatitis B virus infection is implicated in susceptibility to pancreatic cancer. However, the results are still controversial. This meta-analysis aimed to quantitatively assess the relationship between chronic hepatitis B virus infection and incidence of pancreatic cancer of cohort and case-control studies. Methods: A literature search was performed for entries from 1990 to 2012 using PUBMED and EMBASE. Studies were included if they reported odds ratios (ORs) and corresponding 95% CIs of pancreatic cancer with respect to the infection of hepatitis B virus. Results: Eight studies met the inclusion criteria, which included five case-control studies and three cohort studies. Compared with individuals who have not infection of hepatitis B virus, the pooled OR of pancreatic cancer was 1.403 (95%CI: 1.139-1.729, P=0.001) for patients with hepatitis B virus infection. Sub-group analysis by study design showed that the summary OR was 1.43 (95%CI: 1.06-1.94, P=0.021) when pooling case-control studies and 1.31 (95%CI: 1.00-1.72, P=0.05) when pooling cohort studies. Conclusion: Findings from this meta-analysis suggest that chronic hepatitis B virus infection may increase the risk of pancreatic cancer. This relationship needs to be confirmed by further follow-up studies.


  1. Li J, de Gonzalez A.B, Patrica H, et al (2010). Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts. Cancer Causes Control, 21, 1305-14.
  2. Lucenteforte E, La Vecchia C, Silverman D, et al (2012). Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol, 23, 374-82.
  3. Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  4. Mason A, Wick M, White H, et al (1993). Hepatitis B virus replication in diverse cell types during chronic hepatitis B virus infection. Hepatology, 18, 781-9.
  5. Ni YH, Chang MH, Wang KJ, et al (2004). Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma. Gastroenterology, 127, 1733-8.
  6. Shimoda T, Shikata T, Karasawa T, et al (1981). Light microscopic localization of hepatitis B virus in the human pancreas. Possibility of multiplication of hepatitis B virus in the human pancreas. Gastroenterology, 81, 998-1005.
  7. Wang DS, Chen DL, Ren C, et al (2012). ABO blood group, hepatitis B viral infection and risk of pancreatic cancer. Int J Cancer, 131, 461-8.
  8. Wells GA, Shea B, O'Connell D, et al (2000). The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, Ontario: Ottawa Health Research Institute, University of Ottawa, Available at: oxford.html, Presented 2000.
  9. Bao Y, Michaud DS, Spiegelman D, et al (2011). Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies. J Natl Cancer Inst, 103, 1840-50.
  10. Yoo KS, Lee KH, Huh KR, et al (2009). Acute pancreatitis complicating spontaneous acute exacerbation of chronic hepatitis B virus infection: case report and review of literature. Gut Liver, 3, 64-6.
  11. Yoshimura M, Sakurai I, Shimoda T, et al (1981). Detection of HBsAg in the human pancreas. Acta Pathol Jpn, 31, 711-7.
  12. Zhu F, Li HR, Du GN, et al (2011). Chronic hepatitis B virus infection and pancreatic cancer: A case-control study in Southern China. Asian Pac J Cancer Prev, 12, 1405-8.
  13. Iloeje UH, Yang HI, Jen CL, et al (2009). Risk of pancreatic cancer in chronic hepatitis B virus infection: data from the REVEAL-HBV cohort study. Liver Int, 30, 423-9.
  14. Iodice S, Gandini S, Maisonneuve P, et al (2008). Tobacco and the risk of pancreatic cancer: a review and meta-analysis. Langenbecks Arch Surg, 393, 535-48.
  15. Jemal A, Siegel R, Ward E, et al (2008). Cancer statistics. CA Cancer J Clin, 58, 71-96.
  16. Kao JH, Chen PJ, Lai MY, et al (2003). Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology, 124, 327-34.
  17. Katakura Y, Yotsuyanagi H, Hashizume K, et al (2005). Pancreatic involoement in chronic viral hepatitis. World J Gastroenterol, 11, 3508-13.
  18. Larsson SC, Wolk A (2012). Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies. Br J Cancer, 106, 603-7.
  19. Le Scodan R, Mornex F, Girard N, et al (2009). Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review. Ann Oncol, 20, 1387-96.
  20. Ben QW, Li ZS, Liu CX, et al (2012). Hepatitis B virus and Risk of pancreatic ductal adenocarcinoma: A case-control study from China. Pancreas, 41, 435-40.
  21. Chang MH (2011). Hepatitis B virus and cancer prevention. Recent Results. Cancer Res, 188, 75-84.
  22. Cochran WG (1954). The combination of estimates from different experiments. Biometrics, 10, 101-29.
  23. de Gonzalez AB, Yun JE, Lee SY, et al (2008). Pancreatic cancer and factors associated with the insulin resistance syndrome in the Korean cancer prevention study. Cancer Epidemiol Biomarkers Prev, 17, 359-64.
  24. Dejean A, Lugassy C, Zafrani S, et al (1984). Detection of hepatitis B virus DNA in pancreas, kidney and skin of two human carriers of the virus. J Gen Virol, 65, 651-5.
  25. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  26. Dong J, Zou J, Yu XF (2011). Coffee drinking and pancreatic cancer risk: A meta-analysis of cohort studies. World J Gastroenterol, 17, 1204-10.
  27. Donna F.S, Jesse A.B, Thacker SC, et al, for the Meta-analysis Of Observational Studies in Epidemiology Group, (2000). Meta-analysis of observational studies in epidemiology: A proposal for reporting. JAMA, 283, 2008-12.
  28. Egger M, Davey SG, Schneider M, et al (1997). Bias in metaanalysis detected by a simple, graphical test. Br Med J, 315, 629-34.
  29. El-Serag HB, Engels EA, Landgren O, et al (2009). Risk of hepatobiliary and pancreatic cancer after hepatitis C virus infection: a population-based study of US veterants. Hepatology, 49, 116-23.
  30. EI-Serag HB (2012). Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma. Gastroenterology, 142, 1264-73.
  31. Epstein AS, O'Reilly EM (2012). Exocrine pancreas cancer and thromboembolic events: a systematic literature review. J Natl Compr Canc Ne, 10, 835-46.
  32. Fattovich G, Stroffolini T, Zagni I, et al (2004). Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology, 127, 35-50.
  33. Gordon SC, Gish RG (2009). Hepatitis B not a player in Pancreatic Cancer. American Association for the Study of Liver Diseases(AASLD) 60th Annual Meeting Poster 1486, Presented November, 2, 2009.
  34. Hassan M.M, Li DH, El-Deeb AS, et al (2008). Association between hepatitis B virus and pancreatic cancer. J Clin Oncol, 26, 4557-62.
  35. Hoefs JC, Renner IG, Askhcavai M, et al (1980). Hepatitis B surface antigen in pancreatic and biliary secretions. Gastroenterology, 79, 191-4.
  36. Hong SG, K JH, Lee YS et al (2010). The relationship between hepatitis B virus infection and the incidence of pancreatic cancer: a retrospective case-control study. Korean J Hepatol, 16, 49-56.
  37. Aune D, Chan DS, Vieira AR, et al (2012). Dietary fructose, carbohydrates, glycemic indices and pancreatic cancer risk: a systematic review and meta-analysis of cohort studies. Ann Oncol, 20, 1387-96.

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