People with hepatitis B who were treated with nucleoside/nucleotide
antivirals did not have a higher rate of malignancies overall, but did show an
increased incidence of colorectal and cervical cancer, underlining the need for
regular screening, according to a study presented at the recent 2016
International Liver Congress in Barcelona.
Antiviral therapy using nucleoside/nucleotide analogues such as
entecavir (Baraclude) or tenofovir (Viread) is the mainstay of treatment for
chronic hepatitis B. While these drugs can
effectively suppress hepatitis B virus replication during therapy, they
usually do not lead to a cure, and thus often must be taken for a long period.
Grace Wong of the Chinese University of Hong Kong and
colleagues analysed the incidence rates of various malignancies among
antiviral-treated hepatitis B patients compared to untreated patients.
type of tumour affecting the lymph nodes.
Prior studies have produced conflicting evidence about
whether long-term nucleoside/nucleotide analogue therapy increases risk of
various cancers, they noted as background. Entecavir, in particular, has
been linked to cancer in some animal studies.
The researchers did a retrospective cohort study using the database of
the Hospital Authority, which manages Hong Kong's public hospitals. Using
diagnostic codes they identified 68,492 chronic hepatitis B patients diagnosed between 2000 and 2012. People with pre-existing
malignancies at baseline and those co-infected with hepatitis C, hepatitis
delta, hepatitis E or HIV were excluded.
The outcome of interest was incident or new
malignancies other than hepatocellular carcinoma, a type of liver cancer known
to be caused by hepatitis B virus. Participants were analysed after a
cancer-free 'landmark period' of 2, 3 or 4 years after baseline and followed
until death, 7 years or the end of the study in 2012.
Within this group, 44,949 participants were included
in the 3-year landmark analysis. Of these, 4782 patients (about 11%) had been
treated with nucleoside/nucleotide antivirals while 39,712 remained untreated.
Demographics and laboratory biomarkers differed between the treated and
untreated groups, so the groups were weighted to make them more similar. About
75% of the treated patients were men and the mean age was 46 years.
As expected, hepatocellular carcinoma was much more
common among chronic hepatitis B patients compared to the Hong Kong general
population: 300.0 vs 25.0 cases per 100,000 persons.
Incidence rates for other types of cancer were much
lower. All gastrointestinal malignancies occurred at a rate of 21.2 cases per
100,000 hepatitis B patients. Incidence rates were 28.8, 11.8, and 6.2 per
100,000, respectively, for colorectal, gastric (stomach) and oesophageal
All other types of cancer occurred at a rate of 38.0
per 100,000 persons. Incidence rates were 74.4 per 100,000 for lung cancer,
24.1 for breast cancer, 20.0 for retroperitoneal malignancies, 1.0 for urinary
or kidney malignancies, 18.5 for lymphoma, 18.0 for cervical cancer (females
only) and 14.9 for brain cancer.
In an unweighted analysis, rates of lymphoma and
cervical cancer were found to be higher among chronic hepatitis B patients
compared to the general population.
Looking at the effect of nucleoside/nucleotide
treatment, incidence of all malignancies, lung cancer, urinary/kidney cancer,
breast cancer and lymphoma were statistically similar between treated and
untreated hepatitis B patients.
However, treated hepatitis B patients had a
significantly higher incidence of colorectal cancer and cervical cancer, with
weighted hazard ratios of 2.17 (about twice the risk) and 7.33 (more than seven
times the risk), respectively.
Similar findings were observed when results were
analysed according to patient sex, age above or below 50 years, use of
entecavir versus other nucleoside/nucleotides and consistency of antiviral
treatment. Results were also similar in the 2-year and 4-year landmark
analyses. The exception was that women with hepatitis B had a higher risk of
colorectal cancer than men, but the number of cases was small.
"This large-scaled population-based study does
not suggest an increased risk of all malignancies in [nucleoside/nucleotide
analogue]-treated chronic hepatitis B patients," the researchers
However, they recommended, "colorectal and
cervical cancer screening should be offered to those with risk factors,"
and added that "the risks of colorectal and cervical cancers in
[nucleoside/nucleotide analogue]-treated female patients require independent
"In light of these findings we strongly urge regular screening of
these cancers to help prevent them from developing in patients taking
[nucleoside/nucleotide analogue] treatment," Dr Grace stated in an European
Association for the Study of the Liver (EASL) press release.
"This large-scale study determines an important link between [nucleoside/nucleotide
analogue] treatment and cervical and colorectal cancer," added EASL vice
secretary Tom Hemming Karlsen. "The results are important and could change
cancer surveillance and management of patients treated for hepatitis B."