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Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans
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Hepatology Jan 2009
Hashem B. El-Serag 1 2 *, Eric A. Engels 3, Ola Landgren 3, Elizabeth Chiao 1 2, Louise Henderson 1 2, Harshinie C. Amaratunge 1 2, Thomas P. Giordano 1 2
1Department of Medicine, Baylor College of Medicine, Houston, TX
2Houston Center for Quality of Care and Utilization Studies, Health Services Research and Development Service, Department of Veterans Affairs Medical Center, Houston, TX
3Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD_
"A new study shows that infection with hepatitis C virus (HCV) increases a person's risk for a highly fatal cancer of the biliary tree, the bile carrying pathway between the liver and pancreas.....The researchers followed the subjects for an average of 2.3 years to determine the incidence these cancers. They found that "risk for biliary tree cancer in the HCV-infected cohort, although low (4 per 100,000 person-years), was more than double that in the HCV-uninfected cohort.". The study is the first to formally examine the association between HCV and pancreatic cancer. It is also the first time a significant association has been detected between HCV and this type of cancer in a large cohort study. The findings may lead to greater examination of rare malignancies."
"Hepatitis C virus (HCV) causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The prevalence of HCV infection in the United States general population is estimated to be 1.6%, and an estimated 4.1 million infected persons live in the United States.[1] HCV infection is more common in U.S. military veterans who use the Veterans Affairs (VA) medical system, where approximately 5% are infected with HCV.[2]"
"Uncertainty persists over whether HCV causes cancers other than HCC, including intrahepatic cholangiocarcinoma (ICC), which is increasingly common, or extrahepatic cholangiocarcinoma (ECC). Apart from sclerosing cholangitis, risk factors for ICC are poorly understood"
"In this cohort study of 718,687 U.S. military veterans - the largest study ever conducted on the risk conferred by HCV infection for cholangiocarcinoma - we found in 146,394 veterans with HCV infection a significant 2.55-fold increase in the risk of ICC and a 15-fold increase in the risk of HCC but no evidence that HCV infection increases the risk of ECC. A small increase (HR = 1.23) detected in the risk of pancreatic cancer could have been attributable to confounding by alcohol use or other factors....
.....Cholangiocarcinoma is a highly fatal cancer of the biliary tree. In the United States, approximately 5000 new cases of cholangiocarcinoma are diagnosed annually, and these cases are equally distributed between ICC and ECC.[17] Data from the SEER program indicate that the incidence of ICC tripled between 1975 and 1999 before declining slightly afterward, whereas the rates of ECC have been steady.[18]. To our knowledge this is the first time a significant association has been detected between HCV and ICC in a large cohort study.....
....In conclusion, among 146,394 HCV-infected U.S. military veterans, we found a 2.55-fold elevated risk of ICC. Our study is the largest epidemiological study ever conducted to evaluate the relationship between HCV and ICC, ECC, and pancreas cancer. We adjusted our analyses for multiple confounding variables and found that the relationship between HCV and ICC remained significantly positive and that the association between HCV and ECC remained negative. Results also suggested a possible relationship to pancreatic cancer that requires further study.....
....From a clinical perspective, early intervention strategies, including screening HCV-positive individuals earlier or more rigorously, may improve the outcomes for both HCC and ICC. Additional epidemiological studies of ICC are needed, and new evaluations of the effects of early interventions, including HCV treatment, on the molecular carcinogenesis of ICC are warranted."
Abstract
Hepatitis C virus (HCV) may increase the risk of hepatopancreaticobiliary tumors other than hepatocellular carcinoma (HCC). Previous case control studies indicated a possible association between HCV and intrahepatic cholangiocarcinoma (ICC). Little is known about the association between HCV and extrahepatic cholangiocarcinoma (ECC) or pancreatic cancer. We conducted a cohort study including 146,394 HCV-infected and 572,293 HCV-uninfected patients who received care at Veterans Affairs health care facilities. Patients with two visits between 1996 and 2004 with HCV infection were included, as were up to four matched HCV-uninfected subjects for each HCV-infected subject. Risks of ICC, ECC, pancreatic cancer, and HCC were assessed using proportional hazards regression. In the 1.37 million person-years of follow-up, which began 6 months after the baseline visit, there were 75 cases of ECC, 37 cases of ICC, 617 cases of pancreatic cancer, and 1679 cases of HCC. As expected, the risk of HCC associated with HCV was very high (hazard ratio [HR], 15.09; 95% confidence interval [95% CI], 13.44, 16.94). 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). Adjustments for cirrhosis, diabetes, inflammatory bowel disease, hepatitis B, alcoholism, and alcoholic liver disease did not reduce the risk for ICC below twofold. The risk of pancreatic cancer was slightly elevated (1.23; 1.02, 1.49), but was attenuated after adjusting for alcohol use, pancreatitis, and other variables. Conclusions: Findings indicated that HCV infection conferred a more than twofold elevated risk of ICC. Absence of an association with ECC was consistent in adjusted and unadjusted models. A significant association with pancreatic cancer was erased by alcohol use and other variables.
"A new study shows that infection with hepatitis C virus (HCV) increases a person's risk for a highly fatal cancer of the biliary tree, the bile carrying pathway between the liver and pancreas.....The researchers followed the subjects for an average of 2.3 years to determine the incidence these cancers. They found that "risk for biliary tree cancer in the HCV-infected cohort, although low (4 per 100,000 person-years), was more than double that in the HCV-uninfected cohort.". The study is the first to formally examine the association between HCV and pancreatic cancer. It is also the first time a significant association has been detected between HCV and this type of cancer in a large cohort study. The findings may lead to greater examination of rare malignancies."
Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans
Hepatology Jan 2009
Hashem B. El-Serag 1 2 *, Eric A. Engels 3, Ola Landgren 3, Elizabeth Chiao 1 2, Louise Henderson 1 2, Harshinie C. Amaratunge 1 2, Thomas P. Giordano 1 2
1Department of Medicine, Baylor College of Medicine, Houston, TX
2Houston Center for Quality of Care and Utilization Studies, Health Services Research and Development Service, Department of Veterans Affairs Medical Center, Houston, TX
3Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD_
"Hepatitis C virus (HCV) causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The prevalence of HCV infection in the United States general population is estimated to be 1.6%, and an estimated 4.1 million infected persons live in the United States.[1] HCV infection is more common in U.S. military veterans who use the Veterans Affairs (VA) medical system, where approximately 5% are infected with HCV.[2]"
"Uncertainty persists over whether HCV causes cancers other than HCC, including intrahepatic cholangiocarcinoma (ICC), which is increasingly common, or extrahepatic cholangiocarcinoma (ECC). Apart from sclerosing cholangitis, risk factors for ICC are poorly understood"
"In this cohort study of 718,687 U.S. military veterans - the largest study ever conducted on the risk conferred by HCV infection for cholangiocarcinoma - we found in 146,394 veterans with HCV infection a significant 2.55-fold increase in the risk of ICC and a 15-fold increase in the risk of HCC but no evidence that HCV infection increases the risk of ECC. A small increase (HR = 1.23) detected in the risk of pancreatic cancer could have been attributable to confounding by alcohol use or other factors....
.....Cholangiocarcinoma is a highly fatal cancer of the biliary tree. In the United States, approximately 5000 new cases of cholangiocarcinoma are diagnosed annually, and these cases are equally distributed between ICC and ECC.[17] Data from the SEER program indicate that the incidence of ICC tripled between 1975 and 1999 before declining slightly afterward, whereas the rates of ECC have been steady.[18]. To our knowledge this is the first time a significant association has been detected between HCV and ICC in a large cohort study.....
....In conclusion, among 146,394 HCV-infected U.S. military veterans, we found a 2.55-fold elevated risk of ICC. Our study is the largest epidemiological study ever conducted to evaluate the relationship between HCV and ICC, ECC, and pancreas cancer. We adjusted our analyses for multiple confounding variables and found that the relationship between HCV and ICC remained significantly positive and that the association between HCV and ECC remained negative. Results also suggested a possible relationship to pancreatic cancer that requires further study.....
....From a clinical perspective, early intervention strategies, including screening HCV-positive individuals earlier or more rigorously, may improve the outcomes for both HCC and ICC. Additional epidemiological studies of ICC are needed, and new evaluations of the effects of early interventions, including HCV treatment, on the molecular carcinogenesis of ICC are warranted."
Abstract
Hepatitis C virus (HCV) may increase the risk of hepatopancreaticobiliary tumors other than hepatocellular carcinoma (HCC). Previous case control studies indicated a possible association between HCV and intrahepatic cholangiocarcinoma (ICC). Little is known about the association between HCV and extrahepatic cholangiocarcinoma (ECC) or pancreatic cancer. We conducted a cohort study including 146,394 HCV-infected and 572,293 HCV-uninfected patients who received care at Veterans Affairs health care facilities. Patients with two visits between 1996 and 2004 with HCV infection were included, as were up to four matched HCV-uninfected subjects for each HCV-infected subject. Risks of ICC, ECC, pancreatic cancer, and HCC were assessed using proportional hazards regression. In the 1.37 million person-years of follow-up, which began 6 months after the baseline visit, there were 75 cases of ECC, 37 cases of ICC, 617 cases of pancreatic cancer, and 1679 cases of HCC. As expected, the risk of HCC associated with HCV was very high (hazard ratio [HR], 15.09; 95% confidence interval [95% CI], 13.44, 16.94). 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). Adjustments for cirrhosis, diabetes, inflammatory bowel disease, hepatitis B, alcoholism, and alcoholic liver disease did not reduce the risk for ICC below twofold. The risk of pancreatic cancer was slightly elevated (1.23; 1.02, 1.49), but was attenuated after adjusting for alcohol use, pancreatitis, and other variables. Conclusions: Findings indicated that HCV infection conferred a more than twofold elevated risk of ICC. Absence of an association with ECC was consistent in adjusted and unadjusted models. A significant association with pancreatic cancer was erased by alcohol use and other variables.
Table 2. Associations of Intrahepatic cholangiocarcinoma, Extrahepatic Cholangiocarcinoma, Pancreatic Carcinoma, and Hepatocellular Carcinoma with Hepatitis C Virus Infection Among Veterans
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