Journal Reading

Association of Postoperative Biomarker Response with

Recurrence and Survival in Patients with
Hepatocellular Carcinoma and High Alpha-
Fetoprotein Expressions (>400 ng/ml)
Journal of Hepatocellular Carcinoma 2021:8

SHOFIA WIDYA MURTI

FAJAR WASILAH
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INTRODUCTION

Alpha-Fetoprotein
Hepatocellular (AFP) 
carcinoma (HCC) The main detection,
ranks as the sixth treatment of HCC screening,
most prevalent is surgical surveillance,
malignancies and resection, but therapeutic
the third leading recurrency of the efficacy
cause of cancer- tumor is high measurement, and
related deaths prognostic
evaluation
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INTRODUCTION

The cut-off value of AFP 20 The cut-off value increases to

ng/mL  sensitivity 60~70% 400 ng/mL  the diagnostic
and specificity 80~90% for specificity for HCC almost
HCC diagnosis 100%

No studies have been published

A high AFP expression (>400
on liver resection with HCC
ng/mL)  bad prognosis after
and high AFP expressions
various treatment modalities
(>400 ng/mL)
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AIM

To study the clinical characteristics, long-term

oncologic prognosis and prognostic factors after
curative liver resection for HCC patients with high-
AFP levels (>400 ng/mL)
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METHODS

Accordance with the

The subject of this
Declaration of
study  Patients who Written informed
Helsinki and the
underwent liver consent was obtained
Ethical Guidelines for
resection for HCC at to use their medical
Clinical Studies.
11 hospitals in China records for scientific
Approved by the
between January research from all
Institutional Review
2008 and December patients when they
Board of the Eastern
2015. The end follow- were admitted to
Hepatobiliary
up was December 31, hospital.
Surgery Hospital of
2019.
Shanghai, China.
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METHODS

Clinical Characteristic
Postoperative Follow-Up
• 4-6 weeks after surgery

Postoperative Biomarker Response of serum AFP

• Complete Biomarker Respons (CBR)
• Incomplete Biomarker Respons (IBR)

Study endpoints
• Overall survival (OS)
• Recurrence-free survival (RFS)
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METHODS
The SPSS software version 25.0

• Proportions (%) or
Cate- The OS • Kaplan–Meier method
numbers (n) and compared
gorical and RFS generated by the Log rank
using the χ2 test or Fisher’s
variables rates test.
exact test.

Outcomes • Compared between • Identify independent

Cox
after patients with postoperative predictors with poor OS
regression
resection IBR and CBR. and RFS, with hazard
analyses
ratios (HRs) and 95% CI
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RESULTS

 The postoperative mortality and overall recurrence rates for patients in the
IBR group were significantly higher than those in the CBR group (97.8% vs
56.4%, and 80.6% vs 47.1%, respectively, both P < 0.001). The rate of early
HCC recurrence in the IBR group was also significantly higher than those in
the CBR group (92.5% vs 33.3%, P < 0.001), despite the two groups having
comparable rates of late HCC recurrence (62.5% vs 35.3% , P = 0.142).
Multivariate Cox-regression analysis demonstrated that postoperative IBR
was also independently associated with increased early recurrence rate
following curative liver resection for high-AFP HCC (HR, 5.43; 95% CI,
4.08–7.25; P < 0.001).
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RESULTS

469 (85.4%) males

Sex
80 (14.6%) females

N=549
456 (83.1%) CBR
Postoperative
serum AFP level
93 (16.9%) IBR
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RESULTS
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RESULTS

 <

Cumulative incidence of early recurrence (< 2 years after surgery)

curves comparisons between patients with postoperative incomplete
biomarker response (IBR) and complete biomarker response (CBR)
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Similar results of early HCC recurrence with significant difference (both P<0.001) were
showed in the subgroup cohorts of patients with preoperative intermediately high (Figure
3A) and extremely high (Figure 4A) AFP level
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DISCUSSION

Published studies on AFP use to predict recurrence and survival after curative liver
resection are very limited.

Shen et al and by Rungsakulkij et

Li et al measured Zhou et al used a
Allard et al used al around used
serum AFP before post-operative
90 days after 180 days after
surgery (AFP0) and daily decrease in
surgery as surgery as
1 week after surgery AFP of 9% as the
postoperative postoperative
(AFP7) using cut-off value to
measurement measurement
log10AFP7/log10AF evaluate AFP
points of serum points of serum
P0 formula response
AFP levels AFP levels

DISCUSSION
 In the past two decades, accurate
prediction and early detection of
tumor recurrence can be predicted by
detecting circulating tumor cells, cell-
free DNA, or microRNAs.
 These techniques suffer from the need
for high technology and high costs
which limit their generalizability.
14
 In this study, the rate of early
recurrence within 2 years after surgery
among patients with postoperative IBR
was as high as 92.5%, suggesting that
these patients with high risks of early
recurrence should be given close
surveillance to detect early HCC
recurrence and to consider offering
early treatments against recurrence.
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DISCUSSION

 This study had several limitations.

a Retrospective cohort study with its inherent defects.
 Most patients enrolled in this study had a history of chronic HBV infection.
Therefore, the conclusions from this study may not be applicable to patients
with HCC due to other etiologies, such as HCV and alcoholic liver disease.
 Antiviral therapy against HBV has been shown to reduce the baseline AFP
level, thus affecting the diagnostic accuracy of AFP in patients who had
chronic HBV infection
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CONCLUTION

Postoperative biomarker response of serum AFP can be used

in predicting recurrence and survival for high-AFP HCC
patients.
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THANK
YOU
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Alpha-Fetoprotein

 Alpha-fetoprotein (AFP) is a plasma protein produced by the

embryonic yolk sac and the fetal liver. AFP levels in serum, amniotic
fluid, and urine functions as a screening test for congenital
disabilities, chromosomal abnormalities, as well as some other adult
occurring tumors and pathologies
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Elevated AFP Level

 The mechanism of increasing AFP serum level is not quite clear, but the AFP
levels may be elevated because of production by the tumor or by regenerating
hepatocytes
 AFP levels can also be elevated because of other conditions, such as following
liver resection (transient until regeneration complete), recovery following toxic
injury, or seroconversion following hepatitis B infection (typically inducing
transient exacerbation of inflammation
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Strategies for recurrence

 History taking
 Physical examination
 Detection of serum AFP level
 If the AFP serum is not rise  Ultrasonography or contrast-enhanced computed tomography
(CT) or magnetic resonance imaging (MRI) of the upper abdomen
 Bone scan or positron emission tomography were performed as clinically indicated
 The first follow-up evaluation, either during hospitalization or at an outpatient setting, was
performed at 4-6 weeks after surgery. These patients were subsequently followed-up at 2- or 3-
monthly intervals for the first half-year after surgery, 3- to 4-monthly for the next 1.5 years, and
then 3- to 6-monthly thereafter.
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HBV and HCV Infection

 Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are
the most important causes of hepatocellular carcinoma (HCC)
 HBV and HCV infection can cause chronic injury to the liver, with
subsequent progression to severe fibrosis and cirrhosis. The presence of
cirrhosis is a major risk factor for the development of HCC.
 HBV and HCV may be directly and indirectly involved in
hepatocarcinogenesis.
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 HBV incites chronic injury to the hepatocytes, with continuous necro-

inflammation and regeneration activity and a resultant increase in
hepatocyte turnover. The net effect of this is the accumulation of
potential critical mutations in the hepatocyte genome, with subsequent
malignant transformation and clonal expansion, leading to HCC.
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 Similar to nonviral liver diseases, HBV and HCV infection can cause
chronic injury to the liver, with subsequent progression to severe
fibrosis and cirrhosis. The presence of cirrhosis is a major risk factor
for the development of HCC.
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Post-treatment biomarker response

 Post-treatment biomarker response is an important variable that

reflects the degree of tumor removal which is associated with long-
term recurrence and overall survival outcomes after curative HCC
resection.
 To allow clinical generalizability and improve feasibility, two
postoperative biomarker responses of serum AFP after surgery were
compared, ie, postoperative complete biomarker response (CBR) and
incomplete biomarker conversion (IBR).
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 Postoperative CBR was defined as normalization of postoperative

AFP levels to <20 ng/mL in HCC patients with preoperative
intermediately-high-AFP levels (401-1200 ng/mL), or to <1/60 (-26) for
patients with preoperative extremely-high-AFPlevels (>1200 ng/mL).
 The patients that failed to decrease AFP levels <20 ng/mL at first
follow-up were defined to have postoperative IBR.
HCC 28
Tumor
Marker
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Limitation of This Study

 A retrospective cohort study with its inherent defects.

 Most patients enrolled in this study had a history of chronic HBV
infection. Therefore, the conclusions from this study may not be applicable
to patients with HCC due to other etiologies, such as HCV and alcoholic
liver disease.
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Interfering factor of AFP

 The following have been implicated in false-positive results:

 Two weeks after radiodiagnosis involving the use of radioactive tracers
 Multiple gestations
 Gestational diabetes
 Cigarette smoking
 Race (slightly higher levels in black women, and lower in women of Asian
descent as compared to whites)