of chronic hepatitis B with nucleoside analogues including lamivudine (Epivir) and entecavir (Baraclude) can reduce the risk of
developing hepatocellular carcinoma, including cancer recurrence after
successful resection surgery, according to data presented at The Liver Meeting 2012, the 63rd
Annual Meeting of the American Association for the Study of Liver Diseases
(AASLD), and published in the Journal of the American Medical
Over years or decades, chronic
hepatitis B infection can lead to severe liver disease including advanced
fibrosis, cirrhosis and hepatocellular carcinoma (HCC), a form of primary liver
cancer. It is thought that the liver's ongoing attempt to repair itself after
injury triggers abnormal cell growth.
Wu from National Yang-Ming University in Taipei and colleagues looked at the
effect of hepatitis B treatment on HCC recurrence following curative resection,
or successful surgical removal of liver tumours. Although resection is amongst
the most effective HCC treatments for people with isolated tumours, liver
cancer recurs at least half the time.
As described at an oral
session on liver cancer at The Liver Meeting and in the 14 November 2012 Journal of the American Medical Association,
the researchers conducted a nationwide cohort study using data
from the Taiwan National Health Insurance Research Database collected between
October 2003 and September 2010.
Out of a total
100,938 newly diagnosed HCC patients, they identified 4569 with hepatitis B-related
liver cancer who underwent curative resection. More than 80% were men and the
mean age was about 55 years. Data on HBV viral load and liver function were not
available, but the researchers noted that Taiwan's national health programme only
reimburses nucleoside analogues for people considered to be at high risk for
liver disease progression.
Wu's team compared the risk of tumour recurrence between people taking
nucleoside analogues and those not taking antiviral drugs. In the treated cohort 487 patients received just one
nucleoside analogue, including 159 who took lamivudine, 292 who took entecavir
and 36 who took telbivudine (Sebivo
or Tyzeka); the rest received more
than one nucleoside drug. Treated participants
used antiviral therapy for a mean duration of 1.5 years.
People treated with nucleoside analogues were found to have a
significantly lower risk compared with untreated people for HCC recurrence (21
vs 44%, respectively) and death (11 vs 28%), despite having a higher
prevalence of liver cirrhosis (49 vs 39%).
After adjusting for competing causes of death, nucleoside analogue-treated
patients had a significantly lower six-year HCC recurrence rate compared with
untreated individuals (46 vs 55%, respectively). Six-year overall mortality
rates were 29% for treated patients compared with 42% for untreated people.
The primary identifiable causes of death for both
nucleoside-treated and untreated people were HCC or HCC treatment-related
mortality, liver cirrhosis, sepsis and pneumonia.
In a multivariate analysis, factors independently
associated with reduced risk of HCC recurrence were use of nucleoside analogues
(hazard ratio [HR] 0.67, or 33% risk reduction), use of statin drugs (HR 0.68)
and use of non-steroidal anti-inflammatory drugs or aspirin (HR 0.80). These associations were seen in all patient sub-groups,
including those without liver cirrhosis.
Based on these findings the researchers
concluded, "Nucleoside analogue use was associated with a lower
risk of HCC recurrence among patients with HBV-related HCC after liver
In their discussion, they noted that, while prior studies had linked
statin use and lower liver cancer risk, this study was the first to see such an
association for non-steroidal anti-inflammatory drugs or aspirin.
In an editorial accompanying the JAMA report, Anna Lok from the University of Michigan at
Ann Arbor noted that surgical resection is the treatment of choice for HCC
patients with solitary tumours and no evidence of cirrhosis. HCC recurrence
after resection is common, however, occurring in 50 to 70% of patients within five
years. Early recurrence is usually due to metastasis from the original primary
tumour, whilst late recurrence is often due to newly developed primary tumours
in people with ongoing active HBV infection or cirrhosis.
"Given the long interval between cell damage,
malignant transformation and tumour development, it is unrealistic to expect
that administration of antiviral therapy for one to two years can prevent HCC
recurrence, particularly because early recurrence is likely due to previously
undiscovered metastasis from the primary tumour," Lok wrote.
"However, nucleoside/nucleotide analogues may
decrease short-term mortality after liver resection, particularly among
patients with underlying cirrhosis, high levels of HBV replication or active
hepatic inflammation", she continued. "For patients who do not
experience early HCC recurrence, continued therapy with nucleoside/nucleotide
analogues may prevent de novo primary tumours and further progression of liver
disease, thereby decreasing late HCC recurrence and long-term mortality."