Hepatitis B raises the risk of some cancers

Chinese people with chronic hepatitis B infection had an increased risk of several digestive system cancers, especially stomach cancer, researchers report in JAMA Network Open.

Approximately 250 million people are living with hepatitis B virus infection and the prevalence of hepatitis B infection is high in Asia and sub-Saharan Africa. Hepatitis B virus is estimated to cause around 80% of all liver cancers (hepatocellular carcinoma) as a result of persistent infection of liver tissue by hepatitis B virus. Some cohort studies have found an increased risk of several other cancers in people with chronic hepatitis B infection, notably lymphoma and pancreatic cancer.

Conflicting findings regarding cancer risks in people with hepatitis B led Chinese researchers to investigate the risk of non-liver cancers in large population cohorts, and to look for the presence of hepatitis B in tumour tissue from people with hepatitis B who had been diagnosed with non-liver cancers in two prospective cohort studies.

The study looked at three cohorts: a population of 512,891 people recruited from ten regions in China (the China Kadoorie Biobank (CKB) cohort) between 2004 and 2008, the Qidong cohort of 37,927 adults in Jiangsu province recruited between 2007 and 2011, and the Changzhou case control study of 17,723 adults recruited in 2004 and 2005.

In each cohort, participants were screened at baseline for hepatitis B surface antigen (HBsAg), which indicates chronic hepatitis B infection. The incidence of cancer in each cohort was calculated using provincial cancer registries.

The prevalence of hepatitis B infection was lower in the CKB cohort (3.1%) than the Qidong (9.5%) cohort. The Changzhou cohort was used as a case control study in which incident cases of stomach cancer were matched with healthy controls to examine risk factors for cancer.

In the CKB cohort, 20,891 new cases of cancer were reported during 4.4 million person-years of follow-up. People with hepatitis B infections were twice as likely to develop any form of cancer (hazard ratio 2.18, 95% CI 2.05-2.32) and at especially heightened risk of developing hepatocellular carcinoma (HR 15.77, 95% CI 14.15-17.57).

People with hepatitis B in the CKB cohort were also at heightened risk of several digestive system cancers, including stomach cancer (HR 1.41, 95% CI 1.11-1.80), colorectal cancer (HR 1.42, 95% CI 1.12-1.81), oral cavity cancer (HR 1.58, 95% CI 1.01-2.49) and pancreatic cancer (HR 1.65, 95% CI 1.03-2.65).

People with hepatitis B also had an increased risk of developing lymphoma (HR 1.65, 95% CI 1.03-2.65).

In the Qidong cohort, 1386 cases of cancer were diagnosed during 255,752 person-years of follow-up. In this cohort, hepatitis B infection was associated with increased risks of hepatocellular carcinoma (HR 17.51, 95% CI 13.86-22.11) and stomach cancer (HR 2.02, 95% CI 1.24-3.29). The incidence of other digestive system cancers was very low, and they were not associated with hepatitis B infection.

A study of biopsies from all tumour samples available in people diagnosed with cancer in the Jiangsu cohort and Changzhou case control study found that all stomach cancer samples showed hepatitis B protein expression in people who had tested positive for hepatitis B surface antigen, and 55% contained hepatitis B DNA. However, samples did not contain HBV cccDNA, which is produced during hepatitis B replication, so it was not possible to confirm that these tissues were a site of active hepatitis B replication.

Hepatitis B protein and DNA were also detectable in pancreatic tumour samples, but not in lung cancer tumour samples.

The researchers note that hepatitis B viral proteins were only detectable in the tumour samples and not in non-cancerous tissues also included in the samples.

Based on the evidence from tumour samples, they speculate that hepatitis B infects and actively replicates in tissues outside the liver. Chronic inflammation caused by viral infection of these tissues may encourage the development of cancer. However, the limited evidence for viral replication in the tissues sampled in this study means that more research is needed to explain why hepatitis B infection is linked to a higher risk of some cancers and why hepatitis B proteins are present in tumours when active infection with hepatitis B is associated with a higher risk of that cancer.

The researchers say that people infected with hepatitis B ought to receive screening for digestive system cancers. Screening for some digestive system cancers is already standard practice in most countries. For example, screening for colorectal cancer in people aged 50 and over is now recommended in many higher income countries. However, cancer screening practices vary in lower income and middle-income countries, and routine screening for stomach cancer is not recommended except in some Asian countries.