Helicobacter is Implicated in Pancreatic Cancer

Association between Helicobacter pylori infection and pancreatic cancer. M Raderer, F Wrba, G Kornek, T Maca, DY Koller, G Weinlaender, M Hejna, W Scheithauer. Oncology 1998 Jan-Feb;55(1):16-19. 65% of 92 patients with pancreatic adenocarcinoma, and 69% of 30 with gastric cancer, were seropositive for HP, versus 45% of other controls (35 with colorectal cancer and 27 healthy volunteers). OR= 2.1 (1.1-4.1), p=0.035.

Raderer - Oncology 1998 abstract / PubMed
Raderer - Oncology 1998 full article / UCSF

Detection of Helicobacter DNA in bile from bile duct diseases. IH Roe, JT Kim, HS Lee, JH Lee. J Korean Med Sci 1999;14:182-186. HP DNA was detected in 7/15 bile duct cancers, 2/6 pancreatic head cancers, and 3/11 cases of intrahepatic duct stones.

Roe - J Korean Med Sci 1999 abstract / PubMed
Roe / J Korean Med Sci 1999 full article (pdf, 5pp)

Helicobacter pylori seropositivity as a risk factor for pancreatic cancer. RZ Stolzenberg-Solomon, MJ Blaser, PJ Limburg, G Perez-Perez, PR Taylor, J Virtamo, D Albanes. J Natl Cancer Inst 2001 Jun 20;93(12):937-941. 82% of 121 cases versus 73% of 226 controls were positive for HP, OR 2.01 (1.09-3.70) with CagA+ strains.

Stolzenberg-Solomon - JNCI 2001 abstract / PubMed
Stolzenberg-Solomon - JNCI 2001 Full Article

Helicobacter species ribosomal DNA in the pancreas, stomach and duodenum of pancreatic cancer patients. HO Nilsson, U Stenram, I Ihse, T Wadstrom. World J Gastroenterol 2006 May 21;12(19):3038-3043. "Patients with exocrine pancreatic cancer (n = 40), neuroendocrine cancer (n = 14), multiple endocrine neoplasia type 1 (n = 8), and chronic pancreatitis (n = 5) were studied. Other benign pancreatic diseases (n = 10) and specimens of normal pancreas (n = 7) were included as controls... Helicobacter DNA was detected in pancreas (tumor and/or surrounding tissue) of 75% of patients with exocrine cancer, 57% of patients with neuroendocrine cancer, 38% of patients with multiple endocrine neoplasia, and 60% of patients with chronic pancreatitis. All samples from other benign pancreatic diseases and normal pancreas were negative. Thirty-three percent of the patients were helicobacter-positive in gastroduodenal specimens. Surprisingly, H. bilis was identified in 60% of the positive gastroduodenal samples. All gallbladder and ductus choledochus specimens were negative for helicobacter." "DNA of different Helicobacter species in the pancreas compared with gastroduodenal tissue was identified in patients who were Helicobacter-positive both in the stomach and pancreas. Moreover, many pancreas-positive PC patients were negative in stomach samples and vice versa, not supporting migration of helicobacter microorganisms colonizing the stomach to the pancreas in the studied PC patients."

Nilsson / World J Gastroenterol 2006 full article

The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. J Luo, C Nordenvall, O Nyrén, HO Adami, J Permert, W Ye. Int J Cancer 2007 Jan 15;120(2):368-372. "During years 3-38 of follow-up, we observed a 20% excess risk (95% confidence interval [CI] 10-40%) for pancreatic cancer among unoperated gastric ulcer patients. The excess increased to 50% (95% CI 10-110%) 15 years after first hospitalization (p for trend = 0.03). SIR was 2.1 (95% CI 1.4-3.1) 20 years after gastric resection. Unoperated duodenal ulcer was not associated with pancreatic cancer risk, nor was vagotomy."

Luo - Int J Cancer 2007 abstract / PubMed

Helicobacter pylori infection and development of pancreatic cancer. C de Martel, AE Llosa, GD Friedman, JH Vogelman, N Orentreich, RZ Stolzenberg-Solomon, J Parsonnet. Cancer Epidemiol Biomarkers Prev 2008 May;17(5):1188-1194. 104 randomly selected subjects among 507 who developed pancreatic cancer, and 262 pancreatic cancer–free subjects from a pool of 730 controls in the Kaiser Permanente Medical Care Program, by serology. "Neither H. pylori [odds ratio (OR), 0.85; 95% confidence interval (95% CI), 0.49-1.48] nor its CagA protein (OR, 0.96; 95% CI, 0.48-1.92) was associated with subsequent development of pancreatic cancer." Among a number of peculiar findings, the most peculiar was a supposedly higher risk from a college education, than from smoking!

de Martel / Cancer Epidemiol Biomarkers Prev 2008 full article

A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer. B Lindkvist, D Johansen, A Borgström, J Manjer. BMC Cancer 2008 Nov 5;8:321. 87 cases and 263 controls, by serology from stored samples. "H. pylori seropositivity was not associated with pancreatic cancer in the total cohort (adjusted OR 1.25 (0.75–2.09)). However, a statistically significant association was found in never smokers (OR 3.81 (1.06–13.63) adjusted for alcohol consumption) and a borderline statistically significant association was found in subjects with low alcohol consumption (OR 2.13 (0.97–4.69) adjusted for smoking)." "There was a slightly higher proportion of current smokers among H. pylori positive subjects." "In the small subgroup of subjects who reported a low risk alcohol consumption and were never smokers (8 cases and 55 controls), the crude OR for pancreatic cancer related to a positive H. pylori serology was 13.20 (2.31–75.31) (not shown in table)."

Lindkvist / BMC Cancer 2008 full article
Lindkvist - BMC Cancer 2008 full article / PubMed Central

ABO Blood Group, Helicobacter pylori Seropositivity, and Risk of Pancreatic Cancer: A Case-Control Study. HA Risch, H Yu, L Lu, MS Kidd. J Natl Cancer Inst 2010 Apr 7;102(7):502-505. 373 cases and 690 controls. "Increased risk of pancreatic cancer was associated with non-O blood group (adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.02 to 1.83, P = .034) and CagA-negative H pylori seropositivity (OR = 1.68, 95% CI = 1.07 to 2.66, P = .025), but no association was observed for CagA seropositivity (OR = 0.77, 95% CI = 0.52 to 1.16). An association between pancreatic cancer risk and CagA-negative H pylori seropositivity was found among individuals with non-O blood type but not among those with O blood type (OR = 2.78, 95% CI = 1.49 to 5.20, P = .0014; OR = 1.28, 95% CI = 0.62 to 2.64, P = .51, respectively). This study demonstrates an association between pancreatic cancer and H pylori colonization, particularly for individuals with non-O blood types."

Risch - J Natl Cancer Inst 2010 abstract / PubMed

Helicobacter pylori in autoimmune pancreatitis and pancreatic carcinoma. R Jesnowski, B Isaksson, C Möhrcke, C Bertsch, M Bulajic, W Schneider-Brachert, G Klöppel, AB Lowenfels, P Maisonneuve, JM Löhr. Pancreatology 2010;10(4):462-466. 35 pancreatic juice samples and 30 pancreatic tissues. "In the pancreas of 11 patients with autoimmune pancreatitis, no H. pylori DNA could be detected. Further, in none of the other tissue samples of chronic pancreatitis or PDAC [pancreatic ductal adenocarcinoma] could we detect any Helicobacter sequences. Out of the pancreatic juice samples, none demonstrated either of the 2 Helicobacter gene sequences investigated."

Jesnowski - Pancreatology 2010 abstract / PubMed

Association between Helicobacter pylori infection and pancreatic cancer. A cumulative meta-analysis. G Trikudanathan, A Philip, CA Dasanu, WL Baker. JOP 2011 Jan 5;12(1):26-31. Six studies involving 2,335 patients. "A significant association between H. pylori seropositivity and development of pancreatic cancer (AOR 1.38, 95% CI: 1.08-1.75; P=0.009) was seen. No significant association was seen on pooled analysis of the three studies assessing the relationship between cytotoxin-associated gene A (CagA) positivity and pancreatic cancer. A cumulative meta-analysis suggested a reducing, albeit statistically significant association as the evidence was accumulated."

Trikudanathan / JOP 2011 full article

[Helicobacter pylori infection in pancreatic cancer]. A Gawin, T Wex, M Ławniczak, P Malfertheiner, T Starzyńska. Pol Merkur Lekarski 2012 Feb;32(188):103-107. 139 patients with pancreatic cancer and 177 controls. "The frequency of H. pylori in pancreatic cancer patients and controls were compared adjusted for age, sex, cigarette smoking and a family history of cancer in the logistic regresion model. No significant differences between pancreatic cancer patients and controls were seen according to H. pylori seropositivity (87.1 vs 82.5%; OR = 1.27; CI95%: 0.64-2.61; p = 0.514) and CagA seropositivity (83.5 vs 84.9%; OR = 0.90; CI95%: 0.46-1.73; p = 0.744)." [Inappropriate adjustment for smoking may have artificially reduced risks - cast.]

Gawin - Pol Merkur Lekarski 2012 abstract / PubMed

Helicobacter pylori Seropositivities and Risk of Pancreatic Carcinoma. HA Risch, L Lu, MS Kidd, J Wang, W Zhang, Q Ni, YT Gao, H Yu. Cancer Epidemiol Biomarkers Prev 2014 Jan;23(1):172-178. 761 cases, 794 controls. "Compared to individuals seronegative for both H. pylori and CagA, decreased pancreas-cancer risk was seen for CagA seropositivity (adjusted odds ratio [OR], 0.68; 95% confidence interval (CI), 0.54-0.84), while some increased risk was suggested for CagA-negative H. pylori seropositivity (OR, 1.28; 95% CI, 0.76-2.13). No risk interactions were observed between CagA seropositivity and gender, cigarette smoking, or age-21 body mass index."

Risch - Cancer Epidemiol Biomarkers Prev 2014 abstract / PubMed

The relationship between Helicobacter pylori and cancer risk. WY Hsu, CH Lin, CC Lin, FC Sung, CP Hsu, CH Kao. Eur J Intern Med 2014 Mar;25(3):235-240. 6022 cancer patients infected with HP versus 24,088 cancer patients not infected. "Our results showed that the proportion of peptic ulcers in the HP cohort was nearly 4 times higher than that in the comparison cohort. The HP cohort was significantly associated with increased colorectal (HR=1.73, 95% CI=1.08-2.77), stomach (HR=5.21, 95% CI=2.46-11.05) and pancreatic (HR=2.77, 95% CI=1.04-7.39) cancer risks compared to the comparison cohort."

Hsu - Eur J Intern Med 2014 abstract / PubMed

Preliminary Study of Pancreatic Cancer Associated with Helicobacter pylori Infection. F Ai, X Hua, Y Liu, J Lin, Z Feng. Cell Biochem Biophys 2015 Jan;71(1):397-400. 56 patients, 60 controls. "The H. pylori infection rate was 64.29 % in the observation group, and that in the control group was 46.67 %. Our results showed that the H. pylori infection rate in the observation group was significantly higher than that in the control group, which was statistically different (P < 0.01). The positive rate of CagA-Hp in the observation group was 38.88, and 21.53 % in the control group, for which the observation group was significantly higher than the control group (P < 0.05)."

Ai - Cell Biochem Biophys 2015 abstract / PubMed

Association between Helicobacter pylori and pancreatic cancer risk: a meta-analysis. A Schulte, N Pandeya, J Fawcett, L Fritschi, HA Risch, PM Webb, DC Whiteman, RE Neale. Cancer Causes Control 2015 Jul;26(7):1027-1035. 580 patients and 626 controls. "No overall association was observed between H. pylori seropositivity and risk of pancreatic cancer (OR 1.00; 95 % CI 0.74-1.35). Nonsignificantly decreased pancreatic cancer risk was observed with CagA seropositivity (OR 0.74; 95 % CI 0.48-1.15) and increased risk with CagA-negative H. pylori seropositivity (OR 1.23; 95 % CI 0.83-1.82). Ten studies were included in the meta-analysis. There was no significant overall association between H. pylori seropositivity and pancreatic cancer risk (OR 1.13; 95 % CI 0.86-1.50), but evidence of CagA strain-specific associations (OR 0.78; 95 % CI 0.67-0.91 and OR 1.30; 95 % CI 1.02-1.65 for CagA-positive and CagA-negative strains, respectively)."

Schulte - Cancer Causes Control 2015 abstract / PubMed

Association of helicobacter pylori infection and chronic atrophic gastritis with risk of colonic, pancreatic and gastric cancer: A ten-year follow-up of the ESTHER cohort study. XZ Chen, B Schöttker, FA Castro, H Chen, Y Zhang, B Holleczek, H Brenner. Oncotarget 2016 Mar 29;7(13):17182-17193. 46 incident pancreatic cancers. "There was no association between H. pylori infection and ... pancreatic cancer (HR = 1.32; 0.73-2.39), regardless of either CagA seropositivity or AG status."

Chen / Oncotarget 2016 abstract / PubMed
Chen / Oncotarget 2016 full article

Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: a nested case-control study. J Huang, U Zagai, G Hallmans, O Nyrén, L Engstrand, R Stolzenberg-Solomon, EJ Duell, K Overvad, VA Katzke, R Kaaks, M Jenab, JY Park, R Murillo, A Trichopoulou, P Lagiou, C Bamia, KE Bradbury, E Riboli, D Aune, KK Tsilidis, G Capellá, A Agudo, V Krogh, D Palli, S Panico, E Weiderpass, A Tjřnneland, A Olsen, B Martínez, D Redondo-Sanchez, MD Chirlaque, PH Peeters, S Regnér, B Lindkvist, A Naccarati, E Ardanaz, N Larrańaga, MC Boutron-Ruault, V Rebours, A Barré, HB Bueno-de-Mesquita, W Ye. Int J Cancer 2017 Apr 15;140(8):1727-1735. 448 cases. "pancreatic cancer risk was neither associated with H. pylori seropositivity (OR=0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR=1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR=0.94; 95% CI: 0.63, 1.38)."

Huang - Int J Cancer 2017 abstract / PubMed

Helicobacter pylori infection, atrophic gastritis, and risk of pancreatic cancer: A population-based cohort study in a large Japanese population: the JPHC Study. M Hirabayashi, M Inoue, N Sawada, E Saito, SK Abe, A Hidaka, M Iwasaki, T Yamaji, T Shimazu, S Tsugane. Sci Rep 2019 Apr 15;9(1):6099. 119 cases. "Our findings suggest H. pylori seropositivity and AG, individually or in combination, are not associated with the risk of pancreatic cancer in a general Japanese population."

Hirabayashi - Sci Rep 2019 full article / PubMed Central
Hirabayashi / Sci Rep 2019 full article

Hepatitis B Virus Is Implicated in Pancreatic Cancer

Association between hepatitis B virus and pancreatic cancer. MM Hassan, D Li, AS El-Deeb, RA Wolff, ML Bondy, M Davila, JL Abbruzzese. J Clin Oncol 2008 Oct 1;26(28):4557-4562. 476 patients with pathologically confirmed adenocarcinoma of the pancreas and 879 controls. "Anti-HCV was positive in seven cases (1.5%) and nine controls (1%). Anti-HBc was positive in 36 cases (7.6%) and 28 controls (3.2%). The estimated AORs and 95% CIs were as follows: anti-HCV-positive, 0.9 (95% CI, 0.3 to 2.8), anti-HBc-positive, 2.5 (95% CI, 1.5 to 4.2), anti-HBc-positive/anti-HBs-positive, 2.3 (95% CI, 1.2 to 4.2), and anti-HBc-positive/anti-HBs-negative, 4 (95% CI, 1.4 to 11.1). Risk modification by past exposure to HBV was observed among diabetics (AOR, 7.1; 95% CI, 1.7 to 28.7)."

Hassan - J Clin Oncol 2008 full article / PubMed Central
Hassan / J Clin Oncol 2008 full article

The results in Hassan 2008 were challenged by Berrington de Gonzalez (who happens to be a crony of arch-anti-smoker Jonathan M. Samet, co-author of a meta-analysis of studies which nearly all ignored either HBV or HCV!), et al. Their challenge was answered thusly: "However, we did not comment on the authors' report of a nonsignificant association between hepatitis B virus (HBV) surface antigen (HBsAg) and pancreatic cancer, because we believed that the analysis of this association was a post-hoc analysis, and the study was not designed to address the association between HBV infection and pancreatic cancer. Our reasons for this belief were, first, pancreatic cancer was diagnosed according to the International Statistical Classification of Diseases and Related Health Problems (C25, 10th revision; WHO); thus, the study included patients with all types of pancreatic neoplasms, including neuroendocrine and unspecified pancreatic tumors, rather than just patients with pancreatic adenocarcinoma. Second, patients with underlying liver diseases were excluded; thus, there was no information about the viral status of these patients, nor about the incidence of pancreatic cancer among these patients. Three, data on HBsAg were missing for 68% of the study population. Fourth, no information was provided regarding the laboratory methodology used for HBsAg testing, or whether the HBsAg-positive results were confirmed. False-positive HBsAg test results may have increased the denominator of the exposed cohort, and resulted in underestimation of the association between HBV exposure and pancreatic cancer. Fifth, no information was provided about antibodies to HBV core antigen (anti-HBc) and HBsAg. Because vertical transmission is the most common mode of HBV infection among Asians, some patients with long-term chronic HBV infection may experience spontaneous HBsAg seroclearance, and only be positive for anti-HBc.2 Given these reasons, and in light of guidelines for reporting observational studies in epidemiology,3 we believed that the study of Berrington de Gonzalez et al was not aimed at investigating the association between HBV and adenocarcinoma of the pancreas." (In Reply. J Clin Oncol 2009 Feb 1;27(4):648-649.)

Hassan / J Clin Oncol 2009 full article

Risk of pancreatic cancer in chronic hepatitis B virus infection: data from the REVEAL-HBV cohort study. UH Iloeje, HI Yang, CL Jen, J Su, LY Wang, SL You, SN Lu, CJ Chen. Liver Int 2010 Mar;30(3):423-429. 48 cases. "Chronic carriers of HBsAg had a significantly increased risk of pancreatic cancer showing an HR(adj) (95% CI) of 1.95 (1.01-3.78). This association was most striking in females, individuals < or =50 years, non-smokers and non-drinkers. The HR(adj) (95% CI) of developing pancreatic cancer was 5.73 (1.73-19.05) for HBeAg-seropositive carriers and 1.64 (0.79-3.42) for HBeAg-seronegative carriers compared with HBsAg-seronegative non-carriers."

Iloeje - Liver Int 2010 abstract / PubMed

Chronic hepatitis B virus infection and pancreatic cancer: a case-control study in southern China. F Zhu, HR Li, GN Du, JH Chen, SR Cai. Asian Pac J Cancer Prev 2011;12(6):1405-1408. 533 cases, 533 controls. "Compared to 77 patients (14.4%) in the control group, 80 pancreatic cancer patients (15.0%) were seropositive for HBV surface antigen (not statistically significant, P=0.8). The prevalence of HBV e antigen was higher in study group than that of control group (P=0.03). Further analysis indicated that HBeAg was a risk factor for pancreatic cancer (OR=2.935, 95% CI: 1.048-8.220)."

Zhu - Asian Pac J Cancer Prev 2011 abstract / PubMed

Hepatitis B virus status and risk of pancreatic ductal adenocarcinoma: a case-control study from China. Q Ben, Z Li, C Liu, Q Cai, Y Yuan, K Wang, L Xiao, J Gao, H Zhang. Pancreas 2012 Apr;41(3):435-440. 943 patients with pancreatic ductal adenocarcinoma and 1128 matched controls. "Chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer, with an adjusted odds ratio of 1.60 (95% confidence interval [CI], 1.15-2.24). Furthermore, significant interactions were detected between a history of DM and chronic hepatitis B and inactive HBsAg positive, but not with antibodies to hepatitis B core antigen (anti-HBc) positive/antibodies to HBsAg (anti-HBs) negative, with an adjusted odds ratio of 5.42 (95% CI, 2.76-10.64), compared with those who were HBsAg negative/anti-HBc negative without a history of DM."

Ben - Pancreas 2012 abstract / PubMed

ABO blood group, hepatitis B viral infection and risk of pancreatic cancer. DS Wang, DL Chen, C Ren, ZQ Wang, MZ Qiu, HY Luo, DS Zhang, FH Wang, YH Li, RH Xu. Int J Cancer 2012 Jul 15;131(2):461-468. 645 patients with pancreatic adenocarcinoma, 711 controls. "The estimated AORs (95% CI) were as follows: A blood type, 1.425 (1.071-1.894), HBsAg-positive/anti-HBc-positive, 1.610 (1.125-2.304), anti-HBs-positive/anti-HBc-positive, 1.526 (1.159-2.011). The effect of A blood type significantly modified the risk of pancreatic cancer among subjects with anti-HBc-positive (AORs = 1.882, 95% CI, 1.284-2.760)."

Wang - Int J Cancer 2012 abstract / PubMed

Chronic hepatitis B virus infection and risk of pancreatic cancer: a meta-analysis. L Li, B Wu, LB Yang, GC Yin, JY Liu. Asian Pac J Cancer Prev 2013;14(1):275-279. 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."

Li / Asian Pac J Cancer Prev 2013 full article

Hepatitis B or C viral infection and risk of pancreatic cancer: A meta-analysis of observational studies. JH Xu, JJ Fu, XL Wang, JY Zhu, XH Ye, SD Chen. World J Gastroenterol 2013 Jul 14;19(26):4234-4241. 8 studies. "Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50)."

Xu - World J Gastroenterol 2013 full article / PubMed Central

Identification and impact of hepatitis B virus DNA and antigens in pancreatic cancer tissues and adjacent non-cancerous tissues. Y Jin, H Gao, H Chen, J Wang, M Chen, G Li, L Wang, J Gu, H Tu. Cancer Lett 2013 Jul 28;335(2):447-454. "In this study, HBsAg and HBcAg were expressed in 21.0% (34/162) of PC and 29.0% (47/162) of non-tumor pancreatic tissues, and they were significantly associated with chronic pancreatitis (P=0.000). The HBV S, C and X genes were identified in 20% (6/30) of PC and 26.9% (7/26) of non-tumor tissues by PCR. A serological survey revealed that the prevalence of HBV DNA and anti-HBc was significantly increased in PC patients compared with healthy controls."

Jin - Cancer Lett 2013 abstract / PubMed

Risk of pancreatic cancer among individuals with hepatitis C or hepatitis B virus infection: a nationwide study in Sweden. J Huang, M Magnusson, A Törner, W Ye, AS Duberg. Br J Cancer 2013 Nov 26;109(11):2917-2923. 34 pancreatic cancers in HCV- and 5 in HBV-infected subjects. "The SIRHCV was 2.1 (95% confidence interval, CI: 1.4, 2.9) and the SIRHBV was 1.4 (0.5, 3.3). In the Cox model analysis, the HR for HCV infection was 1.9 (95% CI: 1.3, 2.7), diminishing to 1.6 (1.04, 2.4) after adjustment for potential confounders. Conclusion: Our results indicated that HCV infection might be associated with an increased risk of pancreatic cancer but further studies are needed to verify such association. The results in the HBV cohort indicated an excess risk, however, without statistical significance due to lack of power."

Huang - Br J Cancer 2013 abstract / PubMed

Chronic hepatitis virus infection increases the risk of pancreatic cancer: a meta-analysis. S Xing, ZW Li, YF Tian, LM Zhang, MQ Li, P Zhou. Hepatobiliary Pancreat Dis Int 2013 Dec;12(6):575-583. Meta-analysis of eight case-control and two cohort studies. "We found that HBsAg and anti-HCV seropositivity significantly increased risk of PC (OR=1.28, 95% CI: 1.11-1.48 and OR=1.21, 95% CI: 1.02-1.44). The presence of HBsAb was associated with a statistically significant decrease in the risk of PC (OR=0.40, 95% CI: 0.20-0.79) and HBeAb (OR=0.62, 95% CI: 0.39-0.99)."

Xing - Hepatobiliary Pancreat Dis Int 2013 abstract / PubMed

Hepatitis B and C viruses are not risks for pancreatic adenocarcinoma. MC Chang, CH Chen, JD Liang, YW Tien, C Hsu, JM Wong, YT Chang. World J Gastroenterol 2014 May 7;20(17):5060-5065. 585 cases, 1716 controls. Meaningless results, because many controls were infected by HBV: "In our study, the positive frequency of HBsAg, anti-HBs and anti-HBc was 12.4% (213/1716), 61.1% (1048/1716) and 66.4% (1140/1716) in our controls."

Chang - World J Gastroenterol 2014 full article / PubMed Central
Chang / World J Gastroenterol 2014 full article

Association Between HBsAg Positivity and Pancreatic Cancer: a Meta-Analysis. S Majumder, B Bockorny, WL Baker, CA Dasanu. J Gastrointest Cancer 2014 Sep;45(3):347-352. Two case-control studies and one cohort study, involving 1,636 patients. "The OR of developing pancreatic cancer was 1.50 (95 % CI 1.21 to 1.87) for individuals who were HBsAg-positive. The type of study, case-control versus cohort, did not appear to influence the results. Only two of the three studies reported the association between anti-HBc positivity and pancreatic cancer. Our analysis revealed a nonsignificant increased risk of cancer in patients with positive anti-HBc status (OR 1.23, 95 % CI 0.95-1.59). No statistically significant heterogeneity or publication bias was noted."

Majumder - J Gastrointest Cancer 2014 abstract / PubMed

The hepatitis B virus X protein promotes pancreatic cancer through modulation of the PI3K/AKT signaling pathway. Y Chen, X Bai, Q Zhang, L Wen, W Su, Q Fu, X Sun, Y Lou, J Yang, J Zhang, Q Chen, J Wang, T Liang. Cancer Lett 2016 Jun 21;380(1):98-105. 64 patients. "HBV DNA was detected in clinical specimens, even in PDAC patients considered "HBV-free", potentially due to occult infection. HBx expression significantly enhanced cellular proliferation and migration and induced an epithelial-mesenchymal transition phenotype. Expression of ErbB4 and TGF-α was increased in parallel with HBx expression, and several downstream pathways including PI3K/AKT, MAPK, and ERK were upregulated. Inhibition of the PI3K/AKT pathway reversed the effects of HBx in PDAC cell lines."

Chen - Cancer Lett 2016 abstract / PubMed

Chronic hepatitis infection is associated with extrahepatic cancer development: a nationwide population-based study in Taiwan. AB Kamiza, FH Su, WC Wang, FC Sung, SN Chang, CC Yeh. BMC Cancer 2016 Nov 8;16(1):861. 15,888 patients with HBV infection, identified 2000-2005 followed to 2011. "The patients with HBV infection exhibited an increased risk of colorectal cancer (HR: 1.36, 95 % CI: 1.09-1.70), liver cancer (HR: 21.47, 95 % CI: 18.0-25.6), gallbladder and extrahepatic bile duct cancer (HR: 2.05, 95 % CI: 1.07-3.91), pancreatic cancer (HR: 2.61, 95 % CI: 1.47-4.61), kidney cancer (HR: 1.72, 95 % CI: 1.10-2.68), ovarian cancer (HR: 2.31, 95 % CI: 1.21-4.39), and non-Hodgkin's lymphoma (HR: 2.10, 95 % CI: 1.25-3.52). The patients with HCV infection exhibited an increased risk of liver cancer (HR: 25.10, 95 % CI: 20.9-30.2), gallbladder and extrahepatic bile duct cancer (HR: 2.60, 95 % CI: 1.42-4.73), ovarian cancer (HR: 5.15, 95 % CI: 1.98-13.4), and non-Hodgkin's lymphoma (HR: 2.30, 95 % CI: 1.34-3.96)."

Kamiza - BMC Cancer 2016 full article / PubMed Central
Kamiza / BMC Cancer 2016 full article

See Also:

Hepatitis Viruses are the Real Cause of "Smoking Related" Liver Cancer

Helicobacter is implicated in biliary tract disease

Bacteria closely resembling Helicobacter pylori detected immunohistologically and genetically in resected gallbladder mucosa. M Kawaguchi, T Saito, H Ohno, S Midorikawa, T Sanji, Y Handa, S Morita, H Yoshida, M Tsurui, R Misaka, T Hirota, M Saito, K Minami. J Gastroenterol 1996 Apr;31(2):294-298. "A microorganism with close immunohistological and genetic resemblance to Helicobacter pylori was found in the resected gallbladder mucosa of a 41-year-old woman." It was detected incidentally on pathological examination.

Kawaguchi - J Gastroenterol 1996 abstract / PubMed

Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis. JG Fox, FE Dewhirst, Z Shen, Y Feng, NS Taylor, BJ Paster, RL Ericson, CN Lau, P Correa, JC Araya, I Roa. Gastroenterology 1998 Apr;114(4):755-763. 9 of 23 gallbladder tissues were positive for Helicobacter by PCR. By phylogenetic analysis, five represented strains of H. bilis, two of "Flexispira rappini" (ATCC 49317), and one of H. pullorum.

Fox - Gastroenterology 1998 abstract / PubMed

Are infectious agents involved in primary biliary cirrhosis? A PCR approach. A Tanaka, TP Prindiville, R Gish, JV Solnick, RL Coppel, EB Keeffe, A Ansari, ME Gershwin. J Hepatol 1999 Oct;31(4):664-671. 29 patients with primary biliary cirrhosis, versus "patients with primary sclerosing cholangitis, chronic hepatitis, alcoholic liver disease and otherwise normal donors." "Neither Archaeabacteria nor Mycobacteria products were detected in liver specimens of patients with primary biliary cirrhosis, and Helicobacter pylori DNA was detected in only one primary biliary cirrhosis patient."

Tanaka - J Hepatol 1999 abstract / PubMed

Identification of Helicobacter pylori and other Helicobacter species by PCR, hybridization, and partial DNA sequencing in human liver samples from patients with primary sclerosing cholangitis or primary biliary cirrhosis. HO Nilsson, J Taneera, M Castedal, E Glatz, R Olsson, T Wadstrom. J Clin Microbiol 2000 Mar;38(3):1072-1076. 9/12 patients with primary sclerosing cholangitis and 11/12 with primary biliary cirrhosis were positive by PCR with Helicobacter genus-specific primers, versus 1/13 with noncholestatic liver cirrhosis and 0/10 normal livers (P = <0.00001).

Nilsson / J Clin Microbiol 2000 full article
Nilsson - J Clin Microbiol 2000 full article / PubMed Central

Lack of association between Helicobacter sp colonization and gallstone disease. N Méndez-Sánchez, R Pichardo, J González, H Sánchez, M Moreno, F Barquera, HO Estevez, M Uribe. J Clin Gastroenterol 2001 Feb;32(2):138-141. "Only 1 of the 95 specimens was positive for Helicobacter by immunohistochemistry analysis; 1 of 32 cases, by PCR."

Méndez-Sánchez - J Clin Gastroenterol 2001 abstract / PubMed

Identification of Helicobacter pylori DNA in human cholesterol gallstones. HJ Monstein, Y Jonsson, J Zdolsek, J Svanvik. Scand J Gastroenterol 2002 Jan;37(1):112-119. "Cholesterol gallstones from 20 patients were subjected to polymerase chain reaction, bacterial profiling by temporal temperature gradient gel electrophoresis, automated DNA sequencing, and Southern blot analysis using a Helicobacter sp. specific primer. A nested ureI-PCR assay was used to discriminate between gastric and non-gastric H. pylori. RESULTS: TTGE, partial 16S rDNA sequencing, and hybridization analysis revealed the presence of DNA presumably representing a mixed bacterial flora in cholesterol gallstones, including H. pylori in the gallstone centres in 11 out of 20 patients. In three cases, the urel-PCR assay revealed non-gastric H. pylori."

Monstein - Scand J Gastroenterol 2002 abstract / PubMed

Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract. N Matsukura, S Yokomuro, S Yamada, T Tajiri, T Sundo, T Hadama, S Kamiya, Z Naito, JG Fox. Jpn J Cancer Res 2002 Jul;93(7):842-847. "Thirteen out of 15 (87%) Japanese and 11 out of 14 (79%) Thai patients with bile duct or gallbladder cancer tested positive for the presence of H. bilis in their bile. Eight out of 16 (50%) Japanese and 10 out of 26 (38%) Thai patients with gallstone and / or cholecystitis tested positive for H. bilis. Only 4 out of 14 (29%) subjects without biliary disease tested positive for H. bilis among the Japanese. Bile duct and gallbladder cancer showed significantly higher positive rates for H. bilis than did the non-biliary diseases among the Japanese (P < 0.01) and the odds ratios for bile duct or gallbladder cancer with H. bilis in comparison with gallstone and / or cholecystitis were 6.50 (95%CI 1.09 - 38.63) in the Japanese and 5.86 (1.31 - 26.33) in the Thai patients."

Matsukura - Jpn J Cancer Res 2002 abstract / PubMed

Helicobacter pylori and the risk of benign and malignant biliary tract disease. M Bulajic, P Maisonneuve, W Schneider-Brachert, P Muller, U Reischl, B Stimec, N Lehn, AB Lowenfels, M Lohr. Cancer 2002 Nov 1;95(9):1946-1953. 89 patients: 63 with biliary calculi, 15 with carcinoma of the biliary tract, and 11 with neither gallstones nor carcinoma. "Patients with gallstones were 3.5 times as likely to have H. pylori in the bile compared with patients in a control group (95% confidence interval [95%CI], 0.8-15.8; P = 0.100), and H. pylori was 9.9 times more frequent in patients with biliary tract carcinoma compared with patients in the control group (95%CI, 1.4-70.5; P = 0.022)."

Bulajic - Cancer 2002 abstract / PubMed

Helicobacter DNA in bile: correlation with hepato-biliary diseases. CA Fallone, S Tran, M Semret, F Discepola, M Behr, AN Barkun. Aliment Pharmacol Ther 2003 Feb;17(3):453-458. Bile collected from 75 patients with biliary stones, 15 with pancreatico-biliary malignancies and four with primary sclerosing cholangitis. "Helicobacter was detected in all positive controls. Only three samples had polymerase chain reaction inhibitors. All remaining bile samples (122 patients with hepato-biliary diseases) were negative for Helicobacter DNA."

Fallone - Aliment Pharmacol Ther 2003 abstract / PubMed

Common presence of Helicobacter DNA in the gallbladder of patients with gallstone diseases and controls. W Chen, D Li, RJ Cannan, RS Stubbs. Dig Liver Dis 2003 Apr;35(4):237-243. By PCR in gallbladder samples and by enzyme linked immunosorbent assay in serum and bile, "Helicobacter DNA was detected in 61 (50.0%) gallbladder samples: 29 of 60 (48.3%) patients with symptomatic gallstone, six of 10 (60.0%) patients with asymptomatic gallstones, 11 of 15 (73.3%) patients with other biliary diseases, and 15 of 37 (40.5%) control patients, respectively. Among them, 39 samples were positive for Helicobacter pylori but none were positive for Helicobacter bilis. Sequence analysis of Helicobacter genus-positive samples showed that 56 samples were Helicobacter pylori and five were Helicobacter species 'Liver 3' strain. Overall, there was no significant difference in the detection rate of Helicobacter DNA or the levels of serum and bile Helicobacter pylori-specific immunoglobulin G in the various biliary disease groups compared with control patients."

Chen - Dig Liver Dis 2003 abstract / PubMed

Association of the presence of Helicobacter in gallbladder tissue with cholelithiasis and cholecystitis. CP Silva, JC Pereira-Lima, AG Oliveira, JB Guerra, DL Marques, L Sarmanho, MM Cabral, DM Queiroz. J Clin Microbiol 2003 Dec;41(12):5615-5618. Nested PCR of 16S rRNA genes in gallbladder tissue and bile from 46 Brazilian subjects with and 18 without cholelithiasis. "When the logistic regression model was applied in the multivariate analysis, cholelithiasis remained independently associated with increasing age (P = 0.002; odds ratio [OR] = 1.07; 95% confidence interval [CI] = 1.03 to 1.12), female gender (P = 0.02; OR = 5.68; 95% CI = 1.38 to 23.49), and the presence of H. pylori DNA in the gallbladder tissue (P = 0.009; OR = 14.72; 95% CI = 1.97 to 108.90)."

Silva / J Clin Microbiol 2003 full article
Silva - J Clin Microbiol 2003 full article / PubMed Central

Helicobacter bilis infection in biliary tract cancer. H Murata, S Tsuji, M Tsujii, HY Fu, H Tanimura, M Tsujimoto, N Matsuura, S Kawano, M Hori. Aliment Pharmacol Ther 2004 Jul;20 Suppl 1:90-94. Archival gallbladder specimens from 34 patients (14 males and 20 females), "consisting of 11 cases of gallbladder cancer, three of bile duct cancer, 16 of cholecystolithiasis and four of pancreatic cancer. DNA was extracted and nested PCR using primers specific for 16S rRNA of H. bilis was performed. RESULTS: Amplification was observed in 3 of 11 gallbladder cancer cases (27.2%) and one of three cases with biliary duct cancer (33.3%). In total, four of 14 cases with biliary tract cancer were positive for H. bilis (28.6%). In addition, the presence of H. bilis was shown in two of 16 cases (12.5%) with cholecystolithiasis. Notably, although the number of cases examined was small, none of the four cases with pancreatic cancer showed the presence of H. bilis infection in the gallbladder without apparent abnormalities."

Murata - Aliment Pharmacol Ther 2004 abstract / PubMed

Relation between gallbladder neoplasm and Helicobacter hepaticus infection. SB Pradhan, S Dali. Kathmandu Univ Med J (KUMJ) 2004 Oct-Dec;2(4):331-335. Of 100 cases that were willing to provide gallbladder for study; "82% cases were found to have Helicobacter hepaticus infection. Only one out of 7 malignant cases (14.29%) was found to be negative for Helicobacter Hepaticus infection."

Pradhan - Kathmandu Univ Med J (KUMJ) 2004 abstract / PubMed

Identification of Helicobacter pylori DNA in Iranian patients with gallstones. Sh Farshad, A Alborzi, SA Malek Hosseini, B Oboodi, M Rasouli, A Japoni, J Nasiri. Epidemiol Infect 2004 Dec;132(6):1185-1189. Gallstone and bile samples from 33 patients and 40 normal autopsied gallbladders. H. pylori DNA was detected by PCR in 18.1% of stone and 12.1% of bile samples. The PCR was negative in the control group.

Farshad - Epidemiol Infect 2004 abstract / PubMed

Helicobacter pylori and other Helicobacter species in gallbladder and liver of patients with chronic cholecystitis detected by immunological and molecular methods. E Apostolov, WA Al-Soud, I Nilsson, I Kornilovska, V Usenko, V Lyzogubov, Y Gaydar, T Wadström, A Ljungh. Scand J Gastroenterol 2005 Jan;40(1):96-102. In gallbladder and liver biopsy specimens from 22 adult Ukrainian patients with chronic cholecystitis, "Helicobacter DNA was found in 16/22 (73%) of the gallbladder samples and in 11/22 (50%) of the liver samples. IHC showed the presence of the H. pylori specific cytotoxins CagA and VacA inside the gallbladder epithelial cells without co-localization of H. pylori at the epithelial lining."

Apostolov - Scand J Gastroenterol 2005 abstract / PubMed

Helicobacter pylori in the etiology of cholesterol gallstones. B Abayli, S Colakoglu, M Serin, S Erdogan, YF Isiksal, I Tuncer, F Koksal, H Demiryurek. J Clin Gastroenterol 2005 Feb;39(2):134-137. "Different bacterium were isolated from 22 gallbladder samples (12 Escherichia coli, 8 Pseudomonas, and 2 clostridium) and H. pylori was isolated in 6 gallbladder samples. Helicobacter spp was found in 7 gallstones by PCR amplification. Helicobacter-like organisms were demonstrated in 18 samples by three different histopathologic methods. Helicobacter-like organisms were also found in five samples by the same histopathologic methods (Warthin-Starry, hematoxylin-eosin, and gram staining). Only four samples were found positive for Helicobacter spp/H. pylori by all methods."

Abayli - J Clin Gastroenterol 2005 abstract / PubMed

The role of Helicobacter spp. in the pathogenesis of primary biliary cirrhosis and primary sclerosing cholangitis. SY Boomkens, S de Rave, RG Pot, HF Egberink, LC Penning, J Rothuizen, PE Zondervan, JG Kusters. FEMS Immunol Med Microbiol 2005 May 1;44(2):221-225. 18 patients with PBC, 13 with PSC, versus 29 patient controls (9 with hepatitis B, 14 with alcoholic cirrhosis, 6 with non-cirrhotic metabolic liver disease. "There was no significant difference between the incidence of Helicobacter spp.-specific DNA in PBC/PSC (9/31; 29%) and the control group (10/29; 34%)." [Patient controls may have had high rates of infection -cast].

Boomkens - FEMS Immunol Med Microbiol 2005 abstract / PubMed

Gallbladder cancer worldwide: geographical distribution and risk factors. G Randi, S Franceschi, C La Vecchia. Int J Cancer 2006 Apr 1;118(7):1591-602. Review. "History of gallstones was the strongest risk factor for gallbladder cancer, with a pooled relative risk (RR) of 4.9 [95% confidence interval (CI): 3.3-7.4]. Consistent associations were also present with obesity, multiparity and chronic infections like Salmonella typhi and S. paratyphi [pooled RR 4.8 (95% CI: 1.4-17.3)] and Helicobacter bilis and H. pylori [pooled RR 4.3 (95% CI: 2.1-8.8)]. Differences in incidence ratios point to variations in gallbladder cancer aetiology in different populations."

Randi - Int J Cancer 2006 abstract / PubMed

Helicobacter pylori and other Helicobacter species DNA in human bile samples from patients with various hepato-biliary diseases. SK Tiwari, AA Khan, M Ibrahim, MA Habeeb, CM Habibullah. World J Gastroenterol 2006 Apr 14;12(14):2181-2186. Sixty bile samples were obtained from patients diagnosed with various hepato-biliary diseases and control subjects with various gastric disorders. "No Helicobacters were grown in culture from the bile samples. Helicobacter DNA was detected in bile of 96.7% and 6.6% of groups I and II respectively."

Tiwari - World J Gastroenterol 2006 abstract / PubMed
Tiwari / World J Gastroenterol 2006 full article

H pylori exist in the gallbladder mucosa of patients with chronic cholecystitis. DF Chen, L Hu, P Yi, WW Liu, DC Fang, H Cao. World J Gastroenterol 2007 Mar 14;13(10):1608-1611. Paraffin specimens of 524 cases of cholecystitis screened by Warthy-Starry (W-S) silver stain and immunohistochemistry stain with anti-H pylori antibodies; and fresh tissue specimens from 81 cases of cholecystitis analyzed by PCR. "H pylori-like bacteria were found in 13.55% of the gallbladders of the cholecystitis patients using W-S stain. Meanwhile, bacteria positive for H pylori antibodies were also found in 7.1% of the gallbladders of patients with cholecystitis by immunohistochemistry. Of 81 gallbladders, 11 were positive for both HPUA and HPUB, 4 were positive for HPUA only and 7 were positive for HPUB only."

Chen - World J Gastroenterol 2007 abstract / PubMed
Chen / World J Gastroenterol 2007 full article

Low prevalence of Helicobacteraceae in gall-stone disease and gall-bladder carcinoma in the German population. UR Bohr, d Kuester, f Meyer, T Wex, M Stillert, A Csepregi, H Lippert, A Roessner, P Malfertheiner. Clin Microbiol Infect 2007 May;13(5):525-531. 57 cases of gall-stone disease, 20 cases of GBC, and 22 control patients. "Of the 99 cases investigated, only one patient with GSD was PCR-positive for Helicobacteraceae."

Bohr - Clin Microbiol Infect 2007 abstract / PubMed

Helicobacter pylori in areas of gastric metaplasia in the gallbladder and isolation of H. pylori DNA from gallstones. V Misra, SP Misra, M Dwivedi, Y Shouche, M Dharne, PA Singh. Pathology 2007 Aug;39(4):419-24. 111 gallbladders with evidence of gastric metaplasia; "Helicobacter pylori was present in 50 of 111 (45%) sections with gastric metaplasia. Areas adjacent to gastric metaplasia in gallbladder showed acute inflammation (6%) and lymphoid follicle formation in 58% of cases with H. pylori that were significantly higher than those seen in sections without H. pylori. In molecular study, 8 of 11 gallstones showed 16S rDNA."

Misra - Pathology 2007 abstract / PubMed

Helicobacter species are associated with possible increase in risk of biliary lithiasis and benign biliary diseases. M Pandey. World J Surg Oncol 2007 Aug 20;5:94. Review. "A total of 12 articles were identified. One study used IgG for diagnosis while others used the PCR for Ure A gene, 16 S RNA or Cag A genes. A couple of studies used culture or histopathology besides the PCR. The cumulative results show a higher association of Helicobacter with chronic liver diseases (30.48%), and stone diseases (42.96%)(OR 1.77 95% CI 1.2-2.58; Z = 2.94, p = 0.003), the effect of each could not be identified as it was difficult to isolate the effect of helicobacter due to mixing of cases in each study."

Pandey / World J Surg Oncol 2007 full article
Pandey - World J Surg Oncol 2007 full article / PubMed Central

Helicobacter pylori may play a contributory role in the pathogenesis of primary sclerosing cholangitis. AM Krasinskas, Y Yao, P Randhawa, MP Dore, AR Sepulveda. Dig Dis Sci 2007 Sep;52(9):2265-2270. 25 patients with end-stage PSC and 31 controls. "Seven of the 25 (28%) patients with PSC and 3 of the 31 (9.7%) controls were positive for Helicobacter (P=.087). H pylori DNA was detected in microdissected hilar biliary epithelium in more PSC patients than controls..."

Krasinskas - Dig Dis Sci 2007 abstract / PubMed

Helicobacter species in cancers of the gallbladder and extrahepatic biliary tract. C de Martel, M Plummer, J Parsonnet, LJ van Doorn, S Franceschi. Br J Cancer 2009 Jan 13;100(1):194-199. Review. "Nine studies of BT cancers were identified, all with 30 or fewer BT cancers; eight included cancer-free control subjects and used polymerase chain reaction (PCR) as a means of Helicobacter species detection. In four of these studies, Helicobacter species were detected in patients with BT cancer significantly more frequently than in controls, at least when controls without BT diseases were used. In two studies, no Helicobacter species were detected in either cases or controls. Helicobacter species were also often detected in benign BT diseases such as gallstone disease or chronic cholecystitis."

de Martel - Br J Cancer 2008 abstract / PubMed
de Martel / Br J Cancer 2008 full article

Helicobacter species are associated with possible increase in risk of hepatobiliary tract cancers. M Pandey, M Shukla. Surg Oncol 2009 Mar;18(1):51-56. Review. "The cumulative sample size of cases was 205, of which 115 were positive (56%) for Helicobacter, while among 263 controls 53 (20%) were found to be positive for Helicobacter infection. The positivity rate in case control studies was higher than that observed in single group studies. The cumulative odds ratio for the study sample was 8.72 (95% CI 4.78-15.91) (Z=7.07; p<0.00001). CONCLUSIONS: There is enough evidence to suggest a possible role of Helicobacter species in hepatobiliary tract cancers. However, the results from different regions of the world differ. Studies also differ on method of Helicobacter detection, subsite of cancer with in the hepatobiliary tract and choice of controls thus introducing heterogeneity. Further case control studies with larger sample size are required to settle the question."

Pandey - Surg Oncol 2009 abstract / PubMed

Helicobacter species DNA in liver and gastric tissues in children and adolescents with chronic liver disease. TH Casswall, A Németh, I Nilsson, T Wadström, HO Nilsson. Scand J Gastroenterol 2010;45(2):160-167. "The Helicobacter PCR was positive in 3/23 (13%) livers from patients with primary sclerosing cholangitis and UC, and in 1/2 livers from patients with autoimmune hepatitis (AIH) and UC. Sequenced PCR products matched the 16S rDNA of H. hepaticus, H. muridarum, H. canis, and H. pylori, respectively. H. ganmani and H. bilis were detected in gastric tissues from two AIH patients. H. hepaticus and H. pullorum were found in livers from two patients with acute liver failure and intrahepatic cholestasis."

Casswall - Scand J Gastroenterol 2010 abstract / PubMed

Serological analysis of Helicobacter hepaticus infection in patients with biliary and pancreatic diseases. T Shimoyama, R Takahashi, D Abe, I Mizuki, T Endo, S Fukuda. J Gastroenterol Hepatol 2010 May;25 Suppl 1:S86-89. Serum from 55 patients with cholelithiasis, 18 with bile duct or gallbladder cancer and 19 with pancreatic cancer, and 34 controls. "Prevalence of antibody to H. hepaticus-specific antigen in patients with bile tract cancer was 38.8% and was significantly higher than in control subjects (13.1%, P < 0.05). Prevalence of antibody to H. hepaticus-specific antigen was 18.2% and 10.5% in patients with cholelithiasis and pancreatic cancer, respectively. Seropositivity for H. pylori was similar in all groups."

Shimoyama - J Gastroenterol Hepatol 2010 abstract / PubMed

Gallstones and Concomitant Gastric Helicobacter pylori Infection. W Attaallah, N Yener, MU Ugurlu, M Manukyan, E Asmaz, AO Aktan. Gastroenterol Res Pract 2013;2013:643109. Gallbladder mucosa of 35 (37%) of 94 patients with symptomatic gallstones were positive for H. pylori.

Attaallah - Gastroenterol Res Pract 2013 full article / PubMed Central
Attaallah / Gastroenterol Res Pract 2013 full article

Helicobacter pylori cag Pathogenicity Island (cagPAI) Involved in Bacterial Internalization and IL-8 Induced Responses via NOD1- and MyD88-Dependent Mechanisms in Human Biliary Epithelial Cells. W Boonyanugomol, C Chomvarin, C Hahnvajanawong, B Sripa, M Kaparakis-Liaskos, RL Ferrero. PLoS One 2013 Oct 15;8(10):e77358. "We showed that the cagPAI encodes factors involved in H. pylori internalization in CCA cells, but not for adhesion to these cells. Consistent with previous studies in hepatocytes, actin polymerization and α5β1 integrin may be involved in H. pylori internalization in CCA cells. As for AGS cells, we observed significantly reduced levels of NF-κB activation and IL-8 production in CCA cells stimulated with either cagA, cagL or cagPAI bacteria, when compared with wild-type bacteria. Importantly, these IL-8 responses could be inhibited via either pre-treatment of cells with antibodies to α5β1 integrins, or via siRNA-mediated knockdown of the innate immune signaling molecules, nucleotide oligomerization domain 1 (NOD1) and myeloid differentiation response gene 88 (MyD88). Taken together, the data demonstrate that the cagPAI is critical for H. pylori pathogenesis in bile duct cells, thus providing a potential causal link for H. pylori in biliary tract disease."

Boonyanugomol - PLoS One 2013 full article / PubMed Central
Boonyanugomol / PLoS One 2013 full article

Detection of Helicobacter pylori infection in Egyptian patients with chronic calcular cholecystitis. GF Helaly, EF El-Ghazzawi, AH Kazem, N Dowidar, MM Anwar, NM Attia. Br J Biomed Sci 2014;71(1):13-18. "Immunohistochemistry testing showed 73.3% and 66.7% positivity among GB neck and body biopsies, respectively, demonstrating high sensitivity and specificity. A significant association was found between gastric and GB H. pylori positivity (P < 0.01). H. pylori antigen was detected in bile from three CCC cases. The greatest number of stones were of the calcium bilirubinate type."

Helaly - Br J Biomed Sci 2014 abstract / PubMed

Helicobacter pylori infection is positively associated with gallstones: a large-scale cross-sectional study in Japan. Y Takahashi, N Yamamichi, T Shimamoto, S Mochizuki, M Fujishiro, C Takeuchi, Y Sakaguchi, K Niimi, S Ono, S Kodashima, T Mitsushima, K Koike. J Gastroenterol 2014 May;49(5):882-889. "Gallstones were detected in 409 of 8,625 men (4.74 %) and 285 of 6,926 women (4.11 %) by ultrasonography... HP infection (OR/β = 1.51/0.206)... The gallstone prevalence among HP-negative, HP-eradicated, and HP-positive subjects was 3.81, 4.73 and 6.08 %, respectively."

Takahashi - J Gastroenterol 2014 abstract / PubMed

Association of seropositivity to Helicobacter species and biliary tract cancer in the ATBC study. G Murphy, A Michel, PR Taylor, D Albanes, SJ Weinstein, J Virtamo, D Parisi, K Snyder, J Butt, KA McGlynn, J Koshiol, M Pawlita, GY Lai, CC Abnet, SM Dawsey, ND Freedman. Hepatology 2014 Dec;60(6):1963-1971. 64 biliary cancers, 122 liver cancers, 224 controls. "Among the controls, 88% were seropositive to H. pylori at baseline. Among those who subsequently developed hepatobiliary cancer, the prevalence of seropositivity was higher: 100% for gallbladder cancer, 97% of extrahepatic bile duct cancer, 91% of Ampula of vater cancer, 96% of intrahepatic bile duct cancer, and 94% of hepatocellular carcinoma. Although the OR for gallbladder cancer could not be calculated, the OR for the other sites were 7.01 (0.79-62.33), 2.21 (0.19-25.52), 10.67 (0.76- 150.08), and 1.20 (0.42-3.45), respectively, with an OR of 5.47 (95%CI: 1.17-25.65) observed for the biliary tract cancers combined."

Murphy - Hepatology 2014 abstract / PubMed

Helicobacter pylori infection is associated with gallstones: Epidemiological survey in China. FM Zhang, CH Yu, HT Chen, Z Shen, FL Hu, XP Yuan, GQ Xu. World J Gastroenterol 2015 Aug 7;21(29):8912-8919. 10,016 subjects with 1122 with H pylori eradicated. "The prevalence of gallstones among H. pylori-positive, H. pylori-eradicated, and H. pylori-negative subjects was 9.47%, 9.02%, and 8.46%, respectively. The matched analysis showed that gallstones among H. pylori eradicated subjects was significantly lower compared with H. pylori-positive subjects (P < 0.05)."

Zhang - World J Gastroenterol 2015 full article / PubMed Central
Zhang / World J Gastroenterol 2015 full article

Association of Helicobacter pylori with hepatobiliary stone disease, a prospective case control study. MY Dar, S Ali, AH Raina, MA Raina, OJ Shah, MA Shah, S Mudassar. Indian J Gastroenterol 2016 Sep;35(5):343-346. H. pylori was detected in 20/50 cases and 0/25 controls.

Dar - Indian J Gastroenterol 2016 abstract / PubMed

Prevalence and Risk Factors of Gallbladder Polypoid Lesions in a Healthy Population. YS Choi, JH Do, SW Seo, SE Lee, HC Oh, YJ Min, H Kang. Yonsei Med J 2016 Nov;57(6):1370-1375. 23827 screening subjects. "On multivariate analysis, chronic hepatitis B infection (CHB) and the presence of metabolic syndrome (MS) were risk factors for GB polypoid lesions. CHB and MS were also significant independent risk factors for multiple GB polypoid lesions when compared with solitary GB polypoid lesions. In addition, gastric Helicobacter pylori infection and MS were significant risk factors for GB polypoid lesions with stones when compared with GB polypoid lesions without stones."

Choi / Yonsei Med J 2016 full article

Association between helicobacter pylori infection and gallbladder diseases: a retrospective study. MY Xu, JH Ma, BS Yuan, J Yin, L Liu, QB Lu. J Gastroenterol Hepatol 2018 Jun;33(6):1207-1212. "There were 7803 (43.4%) subjects with H. pylori infection, 995 (5.5%) with gallstones, 219 (1.2%) with cholecystitis and 1003 (5.6%) with cholecystic polypus amongst 17,971 subjects, respectively. In subjects aged 45 years or less, the prevalence of gallstones in the H. pylori (+) group was lower than that in the H. pylori (-) group (OR=0.653; 95%CI: 0.468-0.911; P=0.012). The prevalence of cholecystic polypus in the H. pylori (+) group was significantly higher than that in the H. pylori (-) group (OR=1.160; 95%CI 1.012-1.328; P=0.033)."

Xu - J Gastroenterol Hepatol 2018 abstract / PubMed

Linking Helicobacter pylori with gallbladder and biliary tract cancer in Moroccan population using clinical and pathological profiles. S Cherif, H Rais, A Hakmaoui, S Sellami, S Elantri, A Amine. Bioinformation 2019 Oct 31;15(10):735-743. 89 cases. "Helicobacter pylori was detected in 54% of cases linking with the presence of bile duct stones characterized by the histological subtype, the macroscopic classification and lymph node's presence (p<0.001)."

Cherif - Bioinformation 2019 full article / PubMed Central

Other bacteria

Role of bile bacteria in gallbladder carcinoma. V Sharma, VS Chauhan, G Nath, A Kumar, VK Shukla. Hepatogastroenterology 2007 Sep;54(78):1622-1625. Bile culture in 65 gallbladder carcinoma patients, 125 cholelithiasis patients, and 200 controls. "Significantly higher number of patients with gallbladder carcinoma 40 (65%) had culture positive bile as compared to cholelithiasis 52 (42%) and control 24 (12%). Vi Antibodies suggestive of chronic typhoid carrier state were found to be significantly higher in the gallbladder carcinoma group 20 (31%) as compared to controls 22 (11%) (OR 3.596, p < 0.05) however, the difference was statistically insignificant in the cholelithiasis group 12 (11%) (OR 0.859, p > 0.05). There was a 6.84 times higher risk of developing gallbladder carcinoma in culture positive cholelithiasis patients and 5.14 times if both Vi antibody and cultures were positive." Levels of primary bile acids were lower and secondary bile acids were higher in the gallbladder carcinoma group.

Sharma - Hepatogastroenterology 2007 abstract / PubMed

Non-typhoidal Salmonella DNA traces in gallbladder cancer. P Iyer, SG Barreto, B Sahoo, P Chandrani, MR Ramadwar, SV Shrikhande, A Dutt. Infect Agent Cancer 2016 Mar 3;11:12. 26 primary gall bladder tumour and paired normal samples. "association of typhoidal Salmonella species were found in 11 of 26 gallbladder cancer samples, and non-typhoidal Salmonella species in 12 of 26 gallbladder cancer, with 6 samples were found co-infected with both."

Iyer - Infect Agent Cancer 2016 full article / PubMed Central
Iyer / Infect Agent Cancer 2016 full article

Association of diverse bacterial communities in human bile samples with biliary tract disorders: a survey using culture and polymerase chain reaction-denaturing gradient gel electrophoresis methods. E Tajeddin, SJ Sherafat, MR Majidi, M Alebouyeh, AH Alizadeh, MR Zali. Eur J Clin Microbiol Infect Dis 2016 Aug;35(8):1331-1339. "In total, 41.2 % (42/102) of the patients showed bacterial infection in their bile samples. This infection was detected in 21 % (4/19), 45.4 % (5/11), 53.5 % (15/28), and 54.5 % (24/44) of patients with common bile duct stone, microlithiasis, malignancy, and gallbladder stone, respectively. Escherichia coli showed a significant association with gallstones."

Tajeddin - Eur J Clin Microbiol Infect Dis 2016 abstract / PubMed

See Also:

Helicobacter pylori causes ulcers and stomach cancer
H. pylori is Implicated in Colorectal Adenomas


cast 12-30-19