Highlights
- •Study conducted in Caucasians with chronic hepatitis B, with or without cirrhosis, after 5 years of entecavir/tenofovir.
- •Age >50 years, baseline cirrhosis and liver stiffness ≥12 kPa at year 5 were independently associated with increased risk of HCC.
- •CAGE-B score based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 reliably predicted HCC risk >5 years.
- •SAGE-B score based only on age and LSM at year 5 was also a reliable predictor of HCC incidence >5 years.
Background & Aims
Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB)
even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors
of HCC development and the need for HCC surveillance in this setting.
Methods
Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had
completed >5 years of follow-up under therapy without developing HCC by year 5. Median
follow-up was 8.4 years from treatment onset. Points-based risk scores were developed
to predict HCC risk after year 5.
Results
In years 5–12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences
of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years,
baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently
associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics
than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it
was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age
at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was
based only on age and LSM at year 5 (c-index = 0.809–0.814, 0.805–0.806 after bootstrap
validation). Both scores offered 100% negative predictive values for HCC development
in their low risk groups.
Conclusions
In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy
depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly
SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance
beyond year 5 of therapy.
Lay summary
In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after
the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis
status and liver stiffness at year 5, which can provide simple and reliable risk scores
for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients
with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower
HCC risk, but surveillance may be still required.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: January 22, 2020
Accepted:
January 4,
2020
Received in revised form:
November 27,
2019
Received:
April 24,
2019
Footnotes
Author names in bold designate shared co-first authorship
Identification
Copyright
© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
