Hepatitis Viruses Cause Cholangiocarcinomas

Both HBV and HCV are implicated as causes of intrahepatic cholangiocarcinomas. Hepaitis B surface antigen (HBsAg) alone fails to identify many cases of HBV infection. Core antigen (HBcAg) and HBV DNA in tissue samples should also be tested. And HCV DNA by reverse transcriptase PCR as well as antibodies to HCV.

[Expression of five different antigens of HBV in human intrahepatic cholangiocarcinoma and cholangiohepatocarcinoma]. WL Wang. Zhonghua Zhong Liu Za Zhi 1993 Jul;15(4):252-255. 12 intrahepatic cholangiocarcinomas, 8 cholangiohepatocarcinomas, and neighboring liver tissues with chronic hepatitis or cirrhosis surrounding the tumor. By IHC, "15 were positive for HBxAg (75%), 8 positive for pre-S1 and pre-S2 (40%), respectively and 2 for HBsAg (10%). Sixteen of 19 liver tissues surrounding the tumor were also positive for HBxAg (84.2%), 9 for pre-S1 and pre-S2 each (47.4%), 6 for HBsAg and HBcAg each (31.6%)."

Wang - Zhonghua Zhong Liu Za Zhi 1993 abstract / PubMed

[Expression and significance of hepatitis B virus genes in human primary intrahepatic cholangiocarcinoma and its surrounding tissue]. W Wang, G Gu, M Hu. Zhonghua Zhong Liu Za Zhi 1996 Mar;18(2):127-130. By ISH, "33 cases (82.5%) were positive for HBV DNA, while 31 (77.5%), 26 (65.0%), 24 (60.0%) and 27 (67.5%) cases were positive for X gene, pre-S gene, S gene and C gene, respectively. The results of this study suggest that there exists a close relationship between human primary intrahepatic cholangiocarcinoma and HBV chronic persistent infection. The expression of X gene might play an important role in the pathogenesis of the primary intrahepatic cholangiocarcinoma."

Wang - Zhonghua Zhong Liu Za Zhi 1996 abstract / PubMed

Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy. F Donato, U Gelatti, A Tagger, M Favret, ML Ribero, F Callea, C Martelli, A Savio, P Trevisi, G Nardi. Cancer Causes Control 2001 Dec;12(10):959-964. 26 ICC cases from a liver cancer group, 824 controls. "Seropositivity for anti-HCV, HBsAg, alcohol intake >80 g/day and history of hepatolithiasis were found in 25%, 13%, 23.1%, and 26.9% of ICC cases and in 5.8%, 6.7%, 32.9%, and 10.6% of controls, respectively. The odds ratios adjusted for demographic factors by logistic regression (95% confidence interval; 95% CI) were 9.7 (1.6-58.9) for anti-HCV, 2.7 (0.4-18.4) for HBsAg, and 6.7 (1.3-33.4) for hepatolithiasis, whereas no association was found with alcohol drinking."

Donato - Cancer Causes Control 2001 abstract / PubMed

Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma. S Yamamoto, S Kubo, S Hai, T Uenishi, T Yamamoto, T Shuto, S Takemura, H Tanaka, O Yamazaki, K Hirohashi, T Tanaka. Cancer Sci 2004 Jul;95(7):592-595. A "hospital-based case-control study including 50 ICC patients and 205 other surgical patients without primary liver cancer. HCV seropositivity was detected in 36% of ICC patients and 3% of controls. By univariate analysis, the odds ratio (OR) for association of anti-HCV antibodies with development was 16.87 (95% confidence interval (CI), 5.69 to 50.00)." Tests for HCV not specified in the abstract.

Yamamoto - Cancer Sci 2004 abstract / PubMed

Clinicopathologic characteristics of hepatitis C virus-associated intrahepatic cholangiocarcinoma. S Hai, S Kubo, S Yamamoto, T Uenishi, H Tanaka, T Shuto, S Takemura, O Yamazaki, K Hirohashi. Dig Surg 2005;22(6):432-439. In Osaka, Japan, 19 of 50 patients who underwent surgical treatment were positive for HCV. "In 15 patients in the HCV-positive group, ICC was detected during follow-up for chronic hepatitis C." Tests for HCV not specified in the abstract.

Hai - Dig Surg 2005 abstract / PubMed

Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study. YH Shaib, HB El-Serag, JA Davila, R Morgan, KA McGlynn. Gastroenterology 2005 Mar;128(3):620-626. 625 cases and 90,834 controls, from the SEER-Medicare database [which was reported elsewhere to have a viral hepatitis prevalence of only 30% in liver cancer -cast]. "Several risk factors were significantly more prevalent among cases. These included nonspecific cirrhosis (adjusted odds ratio, 27.2; P <.0001), alcoholic liver disease (adjusted odds ratio, 7.4; P <.0001), hepatitis C virus infection (adjusted odds ratio, 6.1; P <.0001), human immunodeficiency virus infection (adjusted odds ratio, 5.9; P=.003), diabetes (adjusted odds ratio, 2.0; P <.0001), and inflammatory bowel diseases (adjusted odds ratio, 2.3; P=.002)." Viral tests not specified in the abstract.

Shaib - Gastroenterology 2005 abstract / PubMed

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a hospital-based case-control study. YH Shaib, HB El-Serag, AK Nooka, M Thomas, TD Brown, YZ Patt, MM Hassan. Am J Gastroenterol 2007 May;102(5):1016-1021. 246 cases (83 ICC and 163 ECC) and 236 controls, at M.D. Anderson Cancer Center. "ICC patients had a higher prevalence of anti-HCV antibodies (6.0%vs 0.8%, P=0.01), anti-HBc (9.6%vs 0%, P<0.0001), and heavy alcohol consumption (21.7%vs 3.8%, P<0.0001). The adjusted odds ratio and 95% confidence interval (CI) were 7.9 (95% CI 1.3-84.5), 28.6 (95% CI 3.9-1,268.1), and 5.9 (95% CI 2.1-17.4), respectively. Only heavy alcohol consumption was higher in patients with ECC than in controls (17.8%vs 3.8%, P=0.003). The prevalence of diabetes and smoking were not significantly different between cases (ICC or ECC) and controls."

Shaib - Am J Gastroenterol 2007 abstract / PubMed

Clinicopathologic characteristics of intrahepatic cholangiocarcinoma in patients with positive serum a-fetoprotein. YM Zhou, JM Yang, B Li, ZF Yin, F Xu, B Wang, P Liu, ZM Li. World J Gastroenterol 2008 Apr 14;14(14):2251-2254. "Positive serum hepatitis B surface antigen (HBsAg) and hepatitis C antibody were biomarkers of chronic viral hepatitis." "The positive rate of HBsAg (78.1%) and transaminase of the positive AFP group was higher than that of the negative AFP group (P = 0.000 and P = 0.036 respectively)..."

Zhou - World J Gastroenterol 2008 full article / PubMed Central
Zhou / World J Gastroenterol 2008 full article

Hepatitis B virus infection and intrahepatic cholangiocarcinoma in Korea: a case-control study. TY Lee, SS Lee, SW Jung, SH Jeon, SC Yun, HC Oh, S Kwon, SK Lee, DW Seo, MH Kim, DJ Suh. Am J Gastroenterol 2008 Jul;103(7):1716-1720. 622 patients and 2,488 healthy controls. "HBV infection (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.6-3.3), but not HCV infection, was significantly related to ICC." Tests for viruses not specified in abstract.

Lee - Am J Gastroenterol 2008 abstract / PubMed

Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans. HB El-Serag, EA Engels, O Landgren, E Chiao, L Henderson, HC Amaratunge, TP Giordano. Hepatology 2009 Jan;49(1):116-123. 75 cases of ECC, 37 cases of ICC, 617 cases of pancreatic cancer, and 1679 cases of HCC, among a cohort of 146,394 HCV-infected U.S. veterans. "Risk for ICC was elevated with HCV infection 2.55; 1.31, 4.95), but risk for ECC was not significantly increased (1.50; 0.60, 1.85)."

El-Serag - Hepatology 2009 author manuscript / PubMed Central

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a case-control study in China. LY Tao, XD He, Q Qu, L Cai, W Liu, L Zhou, SM Zhang. Liver Int 2010 Feb;30(2):215-221. 190 patients (61 ICC; 129 ECC) and 380 age- and sex-matched controls. "HBsAg (P<0.001) and anti-HBc without HBsAg (P=0.001) were significantly related to ICC. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were 18.1 (95% CI: 7.5-44.0) and 3.6 (95% CI: 1.7-7.6) respectively. Diabetes mellitus (P=0.007), cholecystolithiasis (P=0.004) and previous cholecystectomy (P<0.001) were significantly associated with ECC. The prevalence of cirrhosis was higher in ICC than that in ECC (P<0.001). Furthermore, on excluding the ICC patients with cirrhosis, ICC patients showed significant independent associations with HBsAg (OR: 7.3; 95% CI: 3.1-17.2) and anti-HBc without HBsAg (OR: 2.4; 95% CI: 1.1-5.2)."

Tao - Liver Int 2010 abstract / PubMed

Etiological and clinicopathologic characteristics of intrahepatic cholangiocarcinoma in young patients. HB Zhou, H Wang, DX Zhou, H Wang, Q Wang, SS Zou, HP Hu. World J Gastroenterol 2010 Feb 21;16(7):881-885. 317 consecutive ICC patients in Shanghai, China. 34 (85.0%) of patients less than or at 40 years of age were seropositive for HBsAg. Only one case of ICC had HCV.

Zhou / World J Gastroenterol 2010 full article
Zhou - World J Gastroenterol 2010 full article / PubMed Central

Impact of hepatitis B virus infection on outcome following resection for intrahepatic cholangiocarcinoma. L Zhang, JQ Cai, JJ Zhao, XY Bi, XG Tan, T Yan, C Li, P Zhao. J Surg Oncol 2010 Mar 1;101(3):233-238. 29 of 40 (74.4%) consecutive ICC patients were positive for HBsAg or anti-HBc.

Zhang - J Surg Oncol 2010 abstract / PubMed

Hepatitis B virus-associated intrahepatic cholangiocarcinoma and hepatocellular carcinoma may hold common disease process for carcinogenesis. H Zhou, H Wang, D Zhou, H Wang, Q Wang, S Zou, Q Tu, M Wu, H Hu. Eur J Cancer 2010 Apr;46(6):1056-1061. 317 ICC patients and 634 healthy controls in China. 154 patients (48.6%) were seropositive for HBsAg. "The age and sex distribution profiles were nearly identical between seropositive-HBsAg ICC patients and HBV-associated HCC patients."

Zhou - Eur J Cancer 2010 abstract / PubMed

Risk factors for intrahepatic cholangiocarcinoma: a possible role of hepatitis B virus. M Tanaka, H Tanaka, H Tsukuma, A Ioka, A Oshima, T Nakahara. J Viral Hepat 2010 Oct;17(10):742-748. 11 cases of ICC among 154,814 blood donors in Japan during an average of 7.6 years. "Compared with those who tested negative for both HBsAg and anti-HCV, those who tested HBsAg-positive had a significantly higher risk for ICC (HR: 8.56; 95%CI: 1.33-55.20)." "The hazard ratio for anti-HCV positivity was 2.63, although it was not significant." "The mechanism of carcinogenesis by HBV in intrahepatic bile ducts has not yet been elucidated, but HBV infection is an established risk factor for hepatocellular carcinoma. Because both hepatocytes and cholangiocytes differentiate from the same progenitor cells, HBV might induce carcinogenesis in both cell types through the same mechanism. The HBV gene has been detected in cholangiocarcinoma tissue in some studies, and its presence has been associated with the potential of carcinogenesis in human cholangiocytes. Alternatively, hepatitis-associated ICC may arise from hepatic progenitor cells, as suggested by Lee et al."

Tanaka - J Viral Hepat 2010 full article / PubMed Central

Intrahepatic cholangiocarcinoma: new insights in pathology. C Sempoux, G Jibara, SC Ward, C Fan, L Qin, S Roayaie, MI Fiel, M Schwartz, SN Thung. Semin Liver Dis 2011 Feb;31(1):49-60. 73 ICCs from The Mount Sinai Medical Center in New York City. "Cholangiocarcinomas are malignant tumors that derive from cholangiocytes of small intrahepatic bile ducts or bile ductules (intrahepatic cholangiocarcinoma; ICC), or of large hilar or extrahepatic bile ducts (extrahepatic cholangiocarcinoma; ECC). ICC and ECC differ in morphology, pathogenesis, risk factors, treatment, and prognosis... Classical ICCs (54.8%) were characterized by a tubular, glandular, or nested pattern of growth, were significantly associated with tumor size of more than 5 cm and the absence of underlying liver disease and/or advanced fibrosis. Nonclassical ICCs (45.2%) consisted of tumors with trabecular architecture, tumors that exhibited features of extrahepatic carcinomas, and carcinomas considered to be derived from hepatic progenitor cells, i.e., combined hepatocellular/cholangiocarcinomas and cholangiolocellular carcinomas (ductular type of ICC). They were smaller and often arose in chronic liver disease, mostly HCV infection, and/or with significant fibrosis."

Sempoux - Semin Liver Dis 2011 abstract / PubMed

Hepatitis B virus infection: a favorable prognostic factor for intrahepatic cholangiocarcinoma after resection. HB Zhou, H Wang, YQ Li, SX Li, H Wang, DX Zhou, QQ Tu, Q Wang SS Zou, MC Wu, HP Hu. World J Gastroenterol 2011 Mar 14;17(10):1292-1303. 87 of 155 ICC patients in China were positive for HBsAg in serum or liver tissue.

Zhou - World J Gastroenterol 2011 full article / PubMed Central
Zhou / World J Gastroenterol 2011 full article

Hepatitis B virus infection and risk of intrahepatic cholangiocarcinoma and non-Hodgkin lymphoma: a cohort study of parous women in Taiwan. CW Fwu, YC Chien, SL You, KE Nelson, GD Kirk, HS Kuo, M Feinleib, CJ Chen. Hepatology 2011 Apr;53(4):1217-1225. Cohort study from Taiwan, with "18 cases of ICC and 192 cases of NHL, including 99 cases of diffuse large B-cell lymphoma (DLBCL). Incidence rates of ICC were 0.09 and 0.43 per 100,000 person-years, respectively, among women who were hepatitis B surface antigen (HBsAg)-seronegative and HBsAg-seropositive, showing an age-adjusted hazard ratio (HR(adj) ) (95% confidence interval [CI]) of 4.80 (1.88-12.20)... Among NHL subtypes, HBsAg-seropositive women had an increased risk of DLBCL compared with those who were HBsAg-seronegative (incidence rates: 1.81 and 0.60 per 100,000 person-years, respectively; HR(adj) [95% CI]: 3.09 [2.06-4.64])."

Fwu - Hepatology 2011 abstract / PubMed

Evaluation of risk factors and clinicopathologic features for intrahepatic cholangiocarcinoma in Southern China: a possible role of hepatitis B virus. NF Peng, LQ Li, X Qin, Y Guo, T Peng, KY Xiao, XG Chen, YF Yang, ZX Su, B Chen, M Su, LN Qi. Ann Surg Oncol 2011 May;18(5):1258-1266. 98 patients with pathologically confirmed ICC and 196 healthy control subjects. Viral tests not specified. "There was an association between ICC and each of HBV infection, liver cirrhosis, hepatolithiasis, and liver fluke infestation with the odds ratios (95% confidence intervals) of 2.75 (1.27-5.95), 8.42 (2.50-28.37), 22.81 (7.16-72.68), and 3.55 (1.60-7.89), respectively, with a marked synergism of cirrhosis and HBV infection (20.67; 5.40-79.06)."

Peng - Ann Surg Oncol 2011 abstract / PubMed

Viral hepatitis is associated with intrahepatic cholangiocarcinoma with cholangiolar differentiation and N-cadherin expression. TH Yu, RH Yuan, YL Chen, WC Yang, HC Hsu, YM Jeng. Mod Pathol 2011 Jun;24(6):810-819. 69 of 170 patients (41%) were positive for hepatitis B and/or C virus, tests not specified in abstract. N-cadherin was strongly associated with hepatitis virus infection.

Yu - Mod Pathol 2011 abstract / PubMed

Detection of hepatitis B virus DNA in paraffin-embedded intrahepatic and extrahepatic cholangiocarcinoma tissue in the northern Chinese population. Y Wu, T Wang, S Ye, R Zhao, X Bai, Y Wu, K Abe, X Jin. Hum Pathol 2012 Jan;43(1):56-61. 23 patients with intrahepatic cholangiocarcinoma and 43 with extrahepatic cholangiocarcinoma. "Hepatitis B surface antigen seropositivity was found in 52.2% (12/23) of intrahepatic cholangiocarcinoma cases and 13.9% (6/43) of extrahepatic cholangiocarcinoma cases. Hepatitis B virus DNA (X region) was detectable in 34.8% (8/23) of intrahepatic cholangiocarcinoma cases. Hepatitis B surface antigen and/or hepatitis B core antigen was detectable in 30.4% (7/23) of intrahepatic cholangiocarcinoma cases. All cases with detected viral protein were also positive for hepatitis B virus DNA. In contrast, no hepatitis B virus antigens or hepatitis B virus gene was detected in any of the 43 extrahepatic cholangiocarcinoma cases."

Wu - Hum Pathol 2012 abstract / PubMed

Epidemiological survey of biomarkers of hepatitis virus in patients with extrahepatic cholangiocarcinomas. Z Qu, N Cui, M Qin, X Wu. Asia Pac J Clin Oncol 2012 Mar;8(1):83-87. 305 patients with extrahepatic cholangiocarcinoma and 480 with benign biliary disease. "Compared with BBD patients, ECC patients had a higher prevalence of prior infection with HBV (6.2 vs 2.3%) and chronic HBV infection (9 vs 1.9%). The overall seropositive rate for HBV markers in the two groups was 22.6 versus 6% (P < 0.01) and for HBxAg detection it was 75 versus 26% (P < 0.001). The seroprevalence of anti-HCV was 4.3% in the EEC patients and 5.6% in BBD patients with no significant difference between them."

Qu - Asia Pac J Clin Oncol 2012 abstract / PubMed

Evaluation of risk factors for extrahepatic cholangiocarcinoma: ABO blood group, hepatitis B virus and their synergism. Y Zhou, Q Zhou, Q Lin, R Chen, Y Gong, Y Liu, M Yu, B Zeng, K Li, R Chen, Z Li.. Int J Cancer 2013 Oct 15;133(8):1867-1875. 239 patients, 478 controls. "The estimated AORs were as follows: A blood group, 1.784; HBsAg+/HbcAb+, 1.848 and HBsAg-/HbcAb+, 1.501. The A blood type had a significant effect on modifying the risk of ECC among subjects with HBsAg+/HbcAb+ (AOR 3.795, 95% CI 1.427-10.090)."

Zhou - Int J Cancer 2013 abstract / PubMed

Hepatitis B and C Virus Infection is a Risk Factor for the Development of Cholangiocarcinoma. K Matsumoto, T Onoyama, S Kawata, Y Takeda, K Harada, Y Ikebuchi, M Ueki, N Miura, K Yashima, M Koda, T Sakamoto, M Endo, Y Horie, Y Murawaki. Intern Med 2014;53(7):651-654. 145 consecutive patients (50 patients with intrahepatic cholangiocarcinoma, 95 patients with extrahepatic cholangiocarcinoma). "The seroprevalence of HBsAg was 10% in the ICC patients and 4.2% in the ECC patients. The prevalence of HCV-Ab was 20% in the ICC patients and 7.4% in the ECC patients," while "The prevalence of HBsAg and HCV-Ab is 0.8-2.2% and 1-2%, respectively, in the Japanese population living in the Tottori area."

Matsumoto / Intern Med 2014 full article landing page

Risk factors for combined hepatocellular-cholangiocarcinoma: A hospital-based case-control study. YM Zhou, XF Zhang, LP Wu, CJ Sui, JM Yang. World J Gastroenterol 2014 Sep 21;20(35):12615-12620. 126 patients, tested for HBV surface antigen (HBsAg) and anti-HCV antibody; and 504 controls. "Multivariate stepwise logistic regression analysis showed that HBV infection (OR = 19.245, 95%CI: 13.260-27.931) and heavy alcohol consumption (OR = 2.186, 95%CI: 1.070-4.466) were independent factors contributing to the development of CHC."

Zhou / World J Gastroenterol 2014 full article

Occult Hepatitis B Virus Infection in Chinese Cryptogenic Intrahepatic Cholangiocarcinoma Patient Population. Y Li, H Wang, D Li, J Hu, H Wang, D Zhou, Q Li, X Jiang, H Zhou, H Hu. J Clin Gastroenterol 2014 Nov-Dec;48(10):878-882. 183 cryptogenic ICC patients (group I), and the controls were 549 healthy individuals (group II). "Compared with group II, group I had a lower prevalence of anti-HBs (antibody against HBsAg) and a higher prevalence of anti-HBe (antibody against hepatitis B e antigen) and anti-HBc (antibody against hepatitis B c antigen). Multivariate analysis confirmed that anti-HBe and anti-HBc positivity were associated with ICC. The odds ratios and 95% confidence intervals for anti-HBe and anti-HBc were 2.482 and 1.482-4.158, 4.556 and 2.938-7.066, respectively. Compared with group III, cryptogenic ICC cases showed more frequent detection of intrahepatic total HBV DNA (63.64% vs. 18.75%, P=0.002)."

Li - J Clin Gastroenterol 2014 abstract / PubMed

Hepatitis B virus infection, diabetes mellitus, and their synergism for cholangiocarcinoma development: a case-control study in Korea. BS Lee, EC Park, SW Park, CM Nam, J Roh. World J Gastroenterol 2015 Jan 14;21(2):502-510. 276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma (ECC) and 83 intrahepatic cholangiocarcinoma (ICC)], and 552 healthy controls. "There was an association between cholangiocarcinoma and hepatitis B virus (HBV) infection, diabetes mellitus (DM), cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted odds ratios (AORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic interaction on the additive model was investigated between HBV infection and DM (AOR = 12.2; 95%CI: 1.9-80.1). In the subgroup analyses, cholecystolithiasis, choledocholithiasis, hepatolithiasis, and DM were significant risk factors for ECC (AOR = 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis, hepatolithiasis, HBV infection, and DM were risk factors for ICC (AOR = 8.6, 157.4, 5.3 and 4.9, respectively). Synergistic interaction was also observed between HBV infection and DM (OR = 22.7; 95%CI: 2.4-214.1)." "HBV infection was defined as a positive hepatitis B surface antigen, and HCV infection was defined as a positive HCV RNA."

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

Hepatitis C virus infection and the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma: evidence from a systematic review and meta-analysis of 16 case-control studies. H Li, B Hu, ZQ Zhou, J Guan, ZY Zhang, GW Zhou. World J Surg Oncol 2015 Apr 23;13(1):161. "A total of 16 case-control studies were included in the final analysis. Pooled risk estimates showed a statistically significant increasing risk of CCA (odds ratio (OR) = 5.44, 95% CI, 2.72 to 10.89). The pooled risk estimate of ICC (OR = 3.38, 95% CI, 2.72 to 4.21) was higher than that of ECC (OR = 1.75, 95% CI, 1.00 to 3.05). In a subgroup analysis, the pooled risk estimate of ICC in studies from North America was obviously higher than in Asia (6.48 versus 2.01). The Begg funnel plot and Egger test showed no evidence of publication bias." They noted that occult HCV infection may have led to underestimation of the effect.

Li / World J Surg Oncol 2015 full article

Programmed death-ligand 1 is upregulated in intrahepatic lymphoepithelioma-like cholangiocarcinoma. L Wang, H Dong, S Ni, D Huang, C Tan, B Chang, W Sheng. Oncotarget 2016 Oct 25;7(43):69749-69759. 13 cases. "We found that eight patients with LELCC were infected with Epstein-Barr Virus (EBV), and EBV infection correlated with poor prognosis in LELCC. Four patients among the five (80.0%) without EBV had a history of chronic viral hepatitis B. None of the 15 cases of conventional cholangiocarcinoma were positive for EBV."

Wang - Oncotarget 2016 abstract / PubMed
Wang / Oncotarget 2016 full article

Effect of Nucleos(t)ide Analogue Therapy on Risk of Intra-hepatic Cholangioarcinoma in Patients With Chronic Hepatitis B. TY Lee, YC Hsu, SH Yu, JT Lin, MS Wu, CY Wu. Clin Gastroenterol Hepatol 2018 Jun;16(6):947-954.e4. 185,843 HBV patients. " In multivariable regression analysis, nucleos(t)ide analogue therapy was independently associated with a reduced risk of ICC (HR, 0.44; 95% CI, 0.25-0.78; P= 0.005)."

Lee - Clin Gastroenterol Hepatol 2018 abstract / PubMed

Free episomal and integrated HBV DNA in HBsAg-negative patients with intrahepatic cholangiocarcinoma. T Pollicino, C Musolino, C Saitta, G Tripodi, M Lanza, G Raffa, FCD Tocco, C Raggi, MC Bragazzi, A Barbera, G Navarra, P Invernizzi, D Alvaro, G Raimondo. Oncotarget 2019 Jun 11;10(39):3931-3938. "HBV DNA was detected in tumor and/or non-tumor specimens from 29/47 (61.7%) ICC patients."

Pollicino - Oncotarget 2019 full article / PubMed Central
Pollicino / Oncotarget 2019 full article

Effect of Statins on the Risk of Extrahepatic Cholangiocarcinoma. S Lavu, TM Therneau, WS Harmsen, KC Mara, N Wongjarupong, M Hassan, HA Ali, S Antwi, NH Giama, K Miyabe, LR Roberts. Hepatology 2020 Mar 2 [Epub ahead of print]. 394 patients, 788 controls. "Hepatitis C virus infection (OR=15.84, 95% CI 4.06-61.87; p<0.001) was the most significant risk factor for [perihilar cholangiocarcinoma]."

Lavu - Hepatology 2020 abstract / PubMed

See Also:

Hepatitis Viruses are the Real Cause of "Smoking Related" Liver Cancer
Hepatitis B Virus Is Implicated in Pancreatic Cancer


cast 03-03-20