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Predictive Factors Associated with
Hepatocellular Carcinoma Incidence and
Mortality after Hepatitis B Surface Antigen
Seroclearance in Patients with Chronic
Hepatitis B
Tetsuya Hosaka1, Fumitaka Suzuki1, Masahiro Kobayashi1,
Shunichiro Fujiyama1, Yusuke Kawamura1, Hitomi Sezaki1,
Norio Akuta1, Yoshiyuki Suzuki1, Satoshi Saitoh1, Yasuji
Arase1, Kenji Ikeda1, Mariko Kobayashi2 and Hiromitsu
Kumada1, (1)Hepatology, Toranomon Hospital, (2)Research
Institute for Hepatology, Toranomon Hospital
Background: Hepatitis B surface antigen (HBsAg)
seroclearance is the realistic goal of anti-viral treatment, and
means a functional cure of hepatitis B virus (HBV) infection.
A few reports showed that patients who achieve HBsAg
seroclearance often have a favorable outcome. However, even
low risk of hepatocellular carcinoma (HCC) is still remaining
in patients achieving HBsAg seroclearance, and factors
associated with HCC incidence after HBsAg seroclearance
are unclear. Methods: We conducted a retrospective cohort
study of 564 adult patients who had chronical HBV monoinfection
and subsequently achieved HBsAg seroclearance
with or without anti-viral treatment. HBsAg seroclearance
was confirmed by the measurements of ARCHITECT HBsAg
QT assay (Abbott laboratories) in all patients. Patients were
excluded if they had HCC before HBsAg seroclearance,
or had hepatitis C or D virus co-infection. Patients were
followed from HBsAg seroclearance until any confirmed HCC
diagnosis (primary outcome) or death (secondary outcome).
We examined the predictive factors associated with HCC
incidence and mortality after HBsAg seroclearance in patients
with chronic hepatitis B. Results: Mean age at HBsAg
seroclearance (baseline) was 53.8 years old. 407 patients
(72%) were male and 157 patients (28%) female. During
follow-ups of median 5.2 years after HBsAg seroclearance, 13
patients (2.3%) had developed HCC (3.6/1,000 person-years),
and 19 patients (3.4%) died (5.1/1,000 person-years). The
cumulative HCC incidence rates after HBsAg seroclearance
were 1.6% at 5-year and 4.2% at 10-year, respectively.
Multivariate Cox regression analysis, adjusted for a number
of known HCC risk factors, showed that older age and low
platelet counts were associated with HCC incidence. However,
alcohol, cigarette, diabetes mellitus and anti-viral treatment
before HBsAg seroclearance were not associated with HCC
incidence. Next, we calculated PAGE-B score which was a
risk estimation scale of HCC derived by Papatheodoridis G, et
al. and consisted of age, gender and platelet, and categorized
into three groups as following; <6 points into low, 6-10 into
intermediate, and >10 into high risk group. The cumulative
HCC incidence rates were significantly higher in high risk
group than in the other two groups (P = 0.004). Regarding
mortality, univariate analysis showed that only older age was
associated with all-cause death after HBsAg seroclearance.
Standardized mortality ratio (observed/expected) matched
age and gender was 1.26, compared to general population.
Most of the causes of death were liver-unrelated. Conclusion:
Older age and low platelet counts were associated with HCC
incidence after HBsAg seroclearance. PAGE-B score may
have a potential to predict HCC incidence and be useful to
HCC surveillance after HBsAg seroclearance. Mortality after
HBsAg seroclearance was similar to general population.作者: StephenW 时间: 2018-10-7 18:55
