In the JournalsPerspective

HBV increases risk for digestive system cancers

Chronic hepatitis B virus infection is associated with the risk for nonliver cancers, especially digestive system cancers, according to findings from a population-based cohort study published in JAMA Network Open.

“In a large prospective Chinese cohort of 496,732 adults, we found that participants who were (hepatitis B surface antigen (HBsAg)] seropositive were at an increased risk of developing [hepatocellular carcinoma (HCC)] and several nonliver cancers, including stomach cancer, oral cancer, colorectal cancer, pancreatic cancer, and lymphoma,” Ci Song, MD, from Nanjing Medical University in China, and colleagues wrote.

Song and colleagues analyzed the China Kadoorie Biobank (CKB) — a study from 2004 to 2008 that investigated the primary environmental and genetic causes of common chronic diseases in the Chinese population. In the study, researchers used a dipstick assay to detect serum HBsAg among the nearly 500,000 participants to determine the association between HBV infection and risk for all cancer types, according to the study.

The mean age of the cohort was 51.5 years, and 59% of participants were women. Participants who were HBsAg seropositive (n = 15,355) had a higher risk for HCC (HR = 15.77; 95% CI, 14.15-17.57), stomach cancer (HR = 1.41.; 95% CI, 1.11-1.8), colorectal cancer (HR = 1.42; 95% CI, 1.12-1.81), oral cancer (HR = 1.58; 95% CI, 1.01-2.49), pancreatic cancer (HR = 1.65; 95% CI, 1.03-2.65) and lymphoma (HR = 2.1; 95% CI, 1.34-3.31) compared with participants who were HBsAg seronegative (n = 481,377), according to the study.

Photo of HBV 
Hepatitis B virus infection affects more than 2 billion people worldwide.
Source: CDC/ Dr. Erskine Palmer

The researchers analyzed two smaller cohort studies to validate the associations they found in the CKB study. A cohort from Qidong County in Jiangsu Province (n = 37,336) validated associations between HBV and HCC (HR = 17.51; 95% CI, 13.86-22.11) and stomach cancer (HR = 2.02; 95% CI, 1.24-3.29). The second small cohort (n = 17,723), a nested case-control study from Changzhou City, also in Jiangsu Province, validated only an association between HBV infection and stomach cancer (OR = 1.76; 95% CI, 1.04-2.98).

“This study provides compelling evidence for the association between HBV infection and all types of cancer,” Song and colleagues wrote. “Strengths of the CKB study included its prospective design, the inclusion of a geographically widespread Chinese population living in urban and rural areas, and careful adjustment for potential confounders.”

However, they also noted some study limitations, including the rate of HBsAg positivity among the CKB cohort, which was 3.1% lower than a rate found in a national serosurvey.

“The low detection rate may lead to a neglectable false-negativity,” the researchers wrote.

They also said further tests involving more nonliver tissues are warranted to confirm the HBV DNA-positive rate and the strength of the association they found between HBV and extrahepatic cancer. – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.

Chronic hepatitis B virus infection is associated with the risk for nonliver cancers, especially digestive system cancers, according to findings from a population-based cohort study published in JAMA Network Open.

“In a large prospective Chinese cohort of 496,732 adults, we found that participants who were (hepatitis B surface antigen (HBsAg)] seropositive were at an increased risk of developing [hepatocellular carcinoma (HCC)] and several nonliver cancers, including stomach cancer, oral cancer, colorectal cancer, pancreatic cancer, and lymphoma,” Ci Song, MD, from Nanjing Medical University in China, and colleagues wrote.

Song and colleagues analyzed the China Kadoorie Biobank (CKB) — a study from 2004 to 2008 that investigated the primary environmental and genetic causes of common chronic diseases in the Chinese population. In the study, researchers used a dipstick assay to detect serum HBsAg among the nearly 500,000 participants to determine the association between HBV infection and risk for all cancer types, according to the study.

The mean age of the cohort was 51.5 years, and 59% of participants were women. Participants who were HBsAg seropositive (n = 15,355) had a higher risk for HCC (HR = 15.77; 95% CI, 14.15-17.57), stomach cancer (HR = 1.41.; 95% CI, 1.11-1.8), colorectal cancer (HR = 1.42; 95% CI, 1.12-1.81), oral cancer (HR = 1.58; 95% CI, 1.01-2.49), pancreatic cancer (HR = 1.65; 95% CI, 1.03-2.65) and lymphoma (HR = 2.1; 95% CI, 1.34-3.31) compared with participants who were HBsAg seronegative (n = 481,377), according to the study.

Photo of HBV 
Hepatitis B virus infection affects more than 2 billion people worldwide.
Source: CDC/ Dr. Erskine Palmer

The researchers analyzed two smaller cohort studies to validate the associations they found in the CKB study. A cohort from Qidong County in Jiangsu Province (n = 37,336) validated associations between HBV and HCC (HR = 17.51; 95% CI, 13.86-22.11) and stomach cancer (HR = 2.02; 95% CI, 1.24-3.29). The second small cohort (n = 17,723), a nested case-control study from Changzhou City, also in Jiangsu Province, validated only an association between HBV infection and stomach cancer (OR = 1.76; 95% CI, 1.04-2.98).

“This study provides compelling evidence for the association between HBV infection and all types of cancer,” Song and colleagues wrote. “Strengths of the CKB study included its prospective design, the inclusion of a geographically widespread Chinese population living in urban and rural areas, and careful adjustment for potential confounders.”

However, they also noted some study limitations, including the rate of HBsAg positivity among the CKB cohort, which was 3.1% lower than a rate found in a national serosurvey.

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“The low detection rate may lead to a neglectable false-negativity,” the researchers wrote.

They also said further tests involving more nonliver tissues are warranted to confirm the HBV DNA-positive rate and the strength of the association they found between HBV and extrahepatic cancer. – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Chari Cohen

    Chari Cohen

    About 292 million people are living with chronic HBV infection a major cause of morbidity and mortality globally. The link between HBV and liver cancer is well known, and screening for liver cancer is recommended as part of routine medical management for people living with HBV. Previous studies have indicated a potential link between HBV infection and additional types of cancer, including pancreatic cancer and lymphoma. Study results, however, have been mixed.

    This study provides compelling new evidence for the increased risk of nonliver cancers in people with chronic HBV. The study uses a strong methodology, triangulating results of a large biosample analysis with both prospective cohort and nested case control studies. The results are provocative, suggesting that HBV might replicate and express proteins in nonliver cells and possibly play a role in the development of nonliver cancers. Even with study limitations, these results highlight the need for more exploration, and perhaps for additional (nonliver) cancer screenings for those who have chronic HBV. To me, these results highlight the overall need for better prevention and testing for HBV around the world. We have a safe and effective vaccine that can prevent and help to eliminate HBV from the planet yet the vaccine remains underutilized, with only 46% of newborns receiving the birth dose. Globally, only 10% of people living with HBV have been diagnosed, and far fewer treated. We have the tools to save millions of lives. These new data provide more evidence about the negative health impact of HBV. In addition to spurring new research, perhaps these findings will help create a much-needed sense of urgency among stakeholders around the world to prioritize HBV prevention, testing, treatment and the need for a cure.

    • Chari Cohen, DrPH, MPH
    • Senior vice president, Hepatitis B Foundation
      Associate professor, Baruch S. Blumberg Institute

    Disclosures: Cohen reports no relevant financial disclosures.