with hepatitis B who were treated with tenofovir disoproxil fumarate (TDF; Viread) were less likely to develop
hepatocellular carcinoma (HCC) than those treated with entecavir (Baraclude) in a large observational
study, according to results presented at the 2019 International Liver Congress
last week in Vienna.
Although the analysis included nearly 30,000 people,
only a small proportion of them used TDF. While the researchers attempted to
control for other factors that might influence outcomes, it may be too early to
conclude that TDF is a superior option for hepatitis B treatment. If further data confirm these findings, it could have
public health implications because entecavir is off patent and less expensive
than TDF and the newer tenofovir alafenamide (Vemlidy).
years or decades, chronic hepatitis B virus (HBV) infection can lead to liver
cirrhosis, HCC and end-stage liver failure
necessitating a transplant. Nucleoside/nucleotide antivirals such as TDF and
entecavir can halt HBV replication during
long-term treatment. These medications usually do not lead to a cure,
but keeping the virus suppressed reduces the likelihood of developing of liver
- hepatocellular carcinoma (HCC)
Liver cancer. A long-term complication of chronic inflammation of the liver or cirrhosis.
Cheuk Fung Yip of the Chinese University of Hong Kong presented findings from
an observational study of people with hepatitis B who were treated with either TDF
or entecavir. Because this type of study does not randomly assign similar participants
to different treatments – but rather observes what happens in real-world practice – people
who receive different treatments could have other differences that affect
TDF and entecavir
are both potent and well-tolerated antivirals, and guidelines in many countries
recommend them equally for first-line chronic HBV treatment, Yip noted.
recent Korean study found that TDF was associated with a 39% lower risk of HCC compared with
Yip's analysis included adults with
chronic hepatitis B seen at all public hospitals and clinics in Hong Kong who
were treated with TDF or entecavir for at least six months between January 2008
and June 2018. People who already had HCC or other cancers at the start of the
study were excluded. This was also the case for people with hepatitis C,
hepatitis D or HIV co-infection and those previously treated with interferon or
Of the more than 55,000 Hong Kong people
treated with TDF or entecavir, 29,350 were included in this analysis. Most of
the excluded individuals had pre-existing cancer, had co-infection with hepatitis C, had previously tried other HBV therapies, started treatment
before 2008 or had less than six months of follow-up.
In the selected group, 1309 people – just
under 5% – started treatment with TDF while 28,041 started with entecavir. People
who used TDF were more likely to be female, were 10 years younger on average
(43 versus 53 years) and had fewer other health problems including diabetes and
hypertension. In addition, those taking TDF were less likely to have cirrhosis
(3% vs 13%), less likely to be hepatitis B 'e' antigen (HBeAg) negative, had
lower HBV DNA, lower ALT and more favourable biomarkers of liver function.
However, similar proportions achieved HBV suppression on treatment.
During follow-up, eight people treated
with TDF and 1386 treated with entecavir developed HCC. The cumulative
five-year incidence was 1.1% in the TDF group versus 7.0% in the entecavir
group. Looking at single factors in a univariate analysis, isolation, the
biggest risk factors for HCC were male sex (hazard ratio 2.17) and having
cirrhosis (hazard ratio 5.73).
In a multivariate analysis that accounted
for several risk factors, people treated with TDF had about a third of the risk
of developing HCC as those who used entecavir (adjusted hazard ratio 0.32).
The researchers attempted to control for
differences between the populations using statistical techniques including
imputation of missing data, propensity score weighting and competing risk
analysis. Doing so brought the hazard ratio to 0.36, or about a 60% lower risk.
A propensity score matching analysis, in which most TDF recipients were matched
with an entecavir recipient with similar characteristics, yielded a hazard
ratio of 0.42. Results were in the same range when considering only patients
Yip noted that another study presented at
the conference, this one from the United States, showed that Asian patients who
used TDF had about a 30% lower risk of HCC than those who used entecavir, while
non-Asian people who took TDF actually had a higher liver cancer risk.
"Tenofovir was associated with a
significantly lower risk of HCC than entecavir in this large population of
adults with chronic HBV infection," Yip said in a conference
press release. "Although we recognize the inherent limitations
of observational data, our findings are consistent with those of the Korean