Researchers have hoped that treating hepatitis B
patients with antivirals would reduce both their viral loads and their
liver cancer risk. However, a new study that followed 1,378 treated and
1,014 untreated patients over five years found antivirals did not
reduce liver cancer rates as hoped.
The study tracked new liver
cancer cases among patients infected with the hepatitis B virus (HBV)
(average age 47, 65% male) who had been treated primarily with
entecavir (Baraclude) for their high viral loads and liver damage. They
compared that group's liver cancer occurrence to those of patients
whose "inactive" HBV infection did not require treatment.
Among the treated group, 70
patients (6.2%) developed liver cancer during the study period compared
to only 11 (1.1%) in the untreated group. Notwithstanding the ability
of antivirals to reduce viral load, a life-long history of HBV
infection and liver damage appeared to increase cancer risk, despite
the reduction in viral load later in life.
What is especially
disappointing is that liver cancer developed even in treated patients
who had no history of cirrhosis (severe liver scarring) which increases
cancer risk. Among the antiviral-treated patients:
- 20 of 223 HBeAg-negative patients who had cirrhosis at the start of treatment developed liver cancer.
- 15 of 316 HBeAg-negative patients who had no cirrhosis also developed liver cancer.
- Among the treated patients who developed liver
cancer, 30 were positive for the hepatitis B "e" antigen (HBeAg) and 30
were HBeAg-negative.
How well the antiviral worked
in patients also determined who remained cancer-free. Of the 246
patients who failed to achieve low or undetectable viral loads as a
result of treatment, 36 (18.8%) patients developed liver cancer over
the five-year study.
The risk of cancer was
increased overall by male gender, underlying cirrhosis and older age in
the treated group. Curiously, having high viral loads (HBV DNA) at the
start of treatment did not appear to increase liver cancer risk.
The key message for doctors is
that liver cancer risk remains despite a dramatic reduction in viral
load, researchers noted. "...Patients on (antiviral) treatment that
effectively suppressed viral replication are still at higher risk of
liver cancer compared with patients with inactive stage chronic
hepatitis B," they concluded in the study published in the March issue
of the journal Gut.
Persistent liver damage before the start of
antiviral treatment, evidenced by elevated alanine aminotransferase
(ALT) levels, may predispose patients to liver cancer, they also noted.
"The inactive group may have
more intact immune response to HBV and therefore may also have entered
the inactive stage early in life, with a shorter period of high viral
replication and active hepatitis," they wrote.
