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.
type of tumour affecting the lymph nodes.
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.