Jasirwan 2019

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JID: YMCN [mUS1Ga;May 23, 2019;14:15]

Current Problems in Cancer xxx (xxxx) xxx
Contents lists available at ScienceDirect
Current Problems in Cancer
journal homepage: www.elsevier.com/locate/cpcancer
Risk factors of mortality in the patients with

hepatocellular carcinoma: A multicenter study
in Indonesia
Chyntia Olivia Maurine Jasirwan∗, Irsan Hasan,
Andri Sanityoso Sulaiman, Cosmas Rinaldi A. Lesmana,
Juferdy Kurniawan, Kemal Fariz Kalista, Saut Horas Nababan,
Rino Alvani Gani
Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto
Mangunkusumo National General Hospital, Jakarta, Indonesia
a b s t r a c t
Background and Aims: Hepatocellular carcinoma (HCC) is considered a significant burden, and its associ-
ated rate of mortality is increasing. Therefore, a population-based cancer registry is considered an essential
element in the baseline and comprehensive analysis of the risk factors associated with HCC. We present a
multicenter analysis of HCC registry from 2 hospitals in Indonesia.
Methods: We performed a follow-up on patients with HCC who were admitted between January 2015
and November 2017 in Cipto Mangunkusumo National General Hospital and Dharmais Hospital, Jakarta,
Indonesia. Patient’s death was considered the primary outcome of the study. A multivariate analysis was
conducted using logistic regression, and odds ratio (OR) with 95% confidence intervals (CIs) were calculated.
Results: A total of 282 patients with HCC included. At the last follow-up, 136 (48.2%) patients had died.
Mortality rate was not significantly affected by sex, age, etiology, the presence of cirrhosis, nor surveil-
lance of HCC. Based on the Child-Pugh (CP) classification, the OR increased progressively in CP C patients
(OR 1.95; 95% CI 1.08-3.53; P = 0.026). The progressive increase was also found in patients with a higher
Barcelona Clinic Liver Cancer stage, and the OR for CP C and D patients were 3.50 (95% CI 1.18-10.38;
P = 0.024) and 3.41 (95% CI 1.02-11.41; P = 0.047), respectively. Supportive treatment was the most com-
mon treatment modality with an OR of 2.17 (95% CI 1.14-4.16; P = 0.019), and it was associated with the
mortality rate of HCC.
∗
Correspondence to: Chyntia, Jasirwan, Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine,
Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia.
E-mail addresses: chynmadu@gmail.com, hepatologibilierfkuirscm@gmail.com (C.O.M. Jasirwan).
https://doi.org/10.1016/j.currproblcancer.2019.05.003
0147-0272/© 2019 Elsevier Inc. All rights reserved.
Please cite this article as: C.O.M. Jasirwan, I. Hasan and A.S. Sulaiman et al., Risk factors of mortality in the patients
with hepatocellular carcinoma: A multicenter study in Indonesia, Current Problems in Cancer, https://doi.org/10.1016/j.
currproblcancer.2019.05.003
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2 C.O.M. Jasirwan, I. Hasan and A.S. Sulaiman et al. / Current Problems in Cancer xxx (xxxx) xxx
Conclusions: The CP classification, Barcelona Clinic Liver Cancer staging system, and treatment modality
might predict mortality in patients with HCC. Moreover, other parameters must be further evaluated.
© 2019 Elsevier Inc. All rights reserved.
a r t i c l e i n f o
Keywords: Hepatocellular carcinoma; Cirrhosis; Mortality; Risk factors
Introduction
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths world-
wide. It is the most common primary liver cancer with inferior prognosis and outcome. Its in-
cidence is significantly higher in men, and it is the third most common cancer among men and
seventh in women. The highest incidence rates with an age-standardized ratio of 31.9 and 22.2
per 10 0,0 0 0 person-years were observed in eastern and southeastern Asia, respectively.1 A study
in Indonesia by Mulyana (2001) has shown that the survival rate of patients with HCC in Cipto
Mangunkusumo National General Hospital was extremely low, with a median survival of only
4.8 months. Further, the 1-year survival rate was 24.1%. After 15 years, a recent study in Indone-
sia has shown no improvement in the survival of patients with HCC, with a 1-year survival rate
of 29.4%.2 Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the primary cause
of HCC, and HBV infection is more common in Asia and developing countries.3 Moreover, the
endemicity of HBV infection in Indonesia is intermediate to high, and it varies between regions
ranging from 4.7% to 11.2%.4
Lack of physician awareness and screening program for risk factors in the Indonesian popu-
lation might have contributed to the low level of HCC surveillance. This leads to an increasing
number of HCC-related mortality despite having considerable preventive measures, screening
tools, and treatment modalities. Therefore, we presented a population-based cancer registry to
provide physicians and health practitioners a baseline data for the management of patients with
HCC.
Materials and methods
Study design and population
We conducted a cohort retrospective data study at 2 tertiary hospitals (Cipto Mangunkusumo

National General Hospital and Dharmais Hospital) between January 2015 and November 2017.
A total of 282 patients with HCC were recruited in this study (158 patients from Cipto Man-
gunkusumo National General Hospital and 124 patients from Dharmais Hospital). The inclusion
criterion included a confirmed diagnosis of HCC. Patients with other malignancies and incom-
plete laboratory or clinical data were excluded.
Data collection
Baseline clinical data were collected at the time of diagnosis. A diagnosis of HCC was con-
firmed on biopsy and radiology. The specific finding on computed tomography scan or magnetic
resonance imaging is hypervascular in the arterial phase and washout in the venous and delayed
phases. Based on biopsy results, liver cell differentiation accompanied by tumor tissue stroma
consisting of sinusoid-like blood space lined by a layer of endothelial cells was noted. The in-
cidence of nonliver metastasis was not observed. Patients were grouped according to whether
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C.O.M. Jasirwan, I. Hasan and A.S. Sulaiman et al. / Current Problems in Cancer xxx (xxxx) xxx 3
they were diagnosed during routine surveillance or based on their symptoms. Information on
patients’ gender, age, hepatitis marker level, laboratory data of liver function (albumin, bilirubin,
aspartate aminotransferase, and alanine aminotransferase levels), and clinical conditions (ascites,
encephalopathy, cirrhosis, and portal vein thrombus) were collected. The Child-Pugh score was
calculated using albumin levels, bilirubin levels, international normalized ratio, ascites, and en-
cephalopathy, and it was then classified into 3 classes: a score of 5-6, 7-9, and 10-15 for CP A,
CP B, and CP C, respectively. The staging was conducted using the Barcelona Clinical Liver Cancer
(BCLC) staging system.5
Patients were also classified into 3 groups based on their treatment modality: curative, pal-
liative, and supportive. The curative protocol consisted of surgical resection and radiofrequency
ablation. The palliative protocol consisted of radiation therapy, transarterial chemoembolization,
and transarterial chemo-infusion (sorafenib). Meanwhile, the supportive protocol provided pa-
tients with the best supportive care therapy.
Patients’ death was investigated by reviewing medical records or contacting their families via
phone. If the phone number could not be reached, the medical team conducted follow-up by
visiting their home address, providing an assignment letter from the hepatobiliary division.
Statistical analysis
The IBM Statistical Package for the Social Sciences software version 23.0 was used for analy-
sis. Continuous data were presented as mean (±SD) or median (range), depending on the result
of the normality test. Categorical data were expressed as frequency (percentage). The Kaplan-
Meier method was used to calculate mortality and the significant parameter for the risk of HCC-
related mortality was identified using the log-rank test. Multivariate analyses were performed
using the Cox Proportional Hazard Regression. Variables with a P value <0.25 were included in
the regression model. A P value <0.05 was considered statistically significant. The magnitude of
the association between the risk factors and mortality was explained by odds ratio (OR) with
95% confidence intervals (CIs).
Ethics approval
This study was approved by the ethics committee of The Faculty of Medicine, University of
Indonesia.
Results
The characteristics of the study population are presented in Table 1. A total of 282 pa-
tients with HCC were included in this study. Among them, 158 patients were from Cipto Man-
gunkusumo National General Hospital and 124 from Dharmais Hospital. HCC was more com-
monly observed in male patients. The mean age at the time of diagnosis was 55 ± 12.75 years.
The number of patients with HBV accounted for more than half of the study population, and
HBV infection was the most common etiology. The other etiologies were HCV infection, non-B,
non-C infection, and coinfection of HBV and HCV. The mean albumin level of the patients was
3.5 (±0.83) g/dL, and the median total bilirubin level was 1.20 (0.23−34.58) mg/dL. A slight in-
crease was noted in the median values of liver function tests: aspartate aminotransferase, 87
(1−1613) U/L and alanine aminotransferase, 46 (3−1331) U/L.
In all the groups, most patients were classified as CP A, followed by CP B and CP C. However,
half of the patients in Cipto Mangunkusumo National General Hospital were classified as CP A,
whereas patients classified as CP B were more commonly found in Dharmais Hospital. Approxi-
mately 58.2% of patients presented with cirrhosis and only 6% of patients were diagnosed with
HCC during routine surveillance. Around 94% of the patients were diagnosed with HCC based on
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Table 1
Characteristics of patients with HCC from each center from 2015 to 2017.
Total number of Patients with HCC Patients with HCC

patients with HCC from Cipto M from Dharmais
(N = 282) Hospital (N = 158) Hospital (N = 124)
Sex, n (%)
Female 71 (25.2%) 45 (28.5%) 26 (21%)
Male 211 (74.8%) 113 (71.5%) 98 (79%)
Age, mean (SD) 55 (12.75) 56 (12.78) 55 (12.75)
Etiology, n (%)
HBV∗ 178 (63.1%) 101 (63.9%) 77 (62.1%)
HCV† 48 (17%) 33 (20.9%) 15 (15.1%)
HBV and HCV 10 (3.5%) 10 (6.3%) 0 (0%)
NBNC‡ 46 (16.3%) 14 (8.9%) 32 (25.8%)
Albumin, mean (SD) 3.50 (0.83) 3.53 (0.66) 3.45 (1.07)
Bilirubin, median (range) 1.20 (0.23-34.58) 1.09 (0.23-22.90) 1.41 (0.29-34.58)
SGOT, median (range)§ 87 (1-1613) 78 (11-983) 57 (9-566)
SGPT, median (range)║ 46 (3-1331) 42 (3-1331) 114 (1-1613)
Child–Pugh Classification, n (%)
A 137 (48.6%) 84 (53.2%) 53 (42.7%)
B 107 (37.9%) 47 (29.7%) 60 (48.4%)
C 38 (13.5%) 27 (17.1%) 11 (8.9%)
Presence of Cirrhosis, n (%)
No 118 (41.8%) 61 (38.6%) 57 (46%)
Yes 164 (58.2%) 97 (61.4%) 67 (54%)
Vein portal thrombus, n (%)
No 190 (67.4%) 112 (70.9%) 78 (62.9%)
Yes 92 (32.6%) 46 (29.1%) 46 (37.1%)
HCC detected during surveillance, n (%)
No 265 (94%) 141 (89.2%) 124 (100%)
Yes 17 (6%) 17 (10.8%) 0 (0%)
BCLC staging, n (%)
A 24 (8.5%) 17 (10.8%) 7 (5.6%)
B 101 (35.8%) 66 (41.8%) 35 (28.2%)
C 117 (41.5%) 56 (35.4%) 61 (49.2%)
D 40 (14.2%) 19 (12%) 21 (16.9%)
Modality therapy, n (%)
Curative 44 (15.6%) 36 (22.8%) 8 (6.5%)
Palliative 110 (39%) 62 (39.2%) 48 (38.7%)
Supportive 129 (45.4%) 60 (38%) 68 (54.8%)
Notes:
###
BCLC: Barcelona Clinic Liver Cancer.
∗
HBV: Hepatitis B Virus.
†
HCV: Hepatitis C Virus.
‡
NBNC: Non-B Non-C.
§
SGOT: Serum Glutamic Oxaloacetic Transaminase.
║
SGPT: Serum Glutamic Piruvic Transaminase.
their clinical symptoms. In Cipto Mangunkusumo National General Hospital, BCLC stage B was
the most common stage of HCC, whereas BCLC stage C was more commonly observed in patients
in Dharmais Hospital. In both hospitals, most patients could only receive supportive therapy.
Mortality rate and risk factor analysis
Among the 282 patients analyzed in this study, 136 (48.2%) patients had died. The mortality
rate of the study population is depicted in Table 2. Of 282 patients, 56 (23.4%) patients died
within 6 months of diagnosis with HCC. Within 1 year of diagnosis with HCC, 90 (45.2%) patients
died, and within 3 years after the diagnosis of HCC, 134 (94.4%) patients died. Results of the
bivariate analysis of OR for each risk factor are depicted in Table 3. The mortality rates were
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Table 2
The mortality rate of patients with HCC.
Time of follow-up after diagnosis
All the time 6 months 1 year 2 years 3 years
Number of study participants (n) 282 239 199 156 142

Mortality (n) 136 56 90 128 134
Mortality rate (%) 48.2% 23.4% 45.2% 82.1% 94.4%
Table 3
Parameters that contribute to all-time mortality.
Survivors Nonsurvivors P value
Sex, n (%)
Female 35 (24%) 36 (26.5%) 0.730
Male 111 (76%) 100 (73.5%)
Age, n (%)
<60 years 87 (59.6%) 84 (61.8%) 0.801
≥60 years 59 (40.4%) 52 (38.2%)
Etiology, n (%)
HBV∗ 93 (63.7%) 85 (62.5%) 0.939
HCV† 24 (16.4% 24 (17.6%)
HBV and HCV 6 (4.1%) 4 (2.9%)
NBNC‡ 23 (15.8%) 23 (16.9%)
Child-Pugh classification, n (%)
A 84 (57.5%) 53 (40%) 0.001
B 54 (37%) 53 (40%)
C 8 (5.5%) 30 (20%)
Presence of cirrhosis, n (%)
No 61 (41.8%) 57 (41.9%) 1.0 0 0
Yes 85 (58.2%) 79 (58.1%)
HCC detected during surveillance, n (%)
No 135 (92.5%) 130 (95.6%) 0.323
Yes 11(7.5%) 6 (4.4%)
Portal vein thrombus, n (%)
No 108 (74%) 82 (60.3%) 0.001
Yes 38 (26%) 54 (39.7%)
BCLC staging, n (%)§
A 20 (13.7%) 4 (2.9%) 0.001
B 63 (43.2%) 38 (27.9%)
C 52 (35.6%) 65 (47.8%)
D 11 (7.5%) 29 (21.3%)
Modality therapy, n (%)
Curative 30 (20.5%) 15 (10.3%) 0.001
Palliative 62 (42.5% 48 (35.3%)
Supportive 54 (37%) 73 (54.4%)
Notes:
∗
HBV: Hepatitis B Virus.
†
HCV: Hepatitis C Virus.
‡
NBNC: Non-B Non-C.
§
BCLC: Barcelona Clinic Liver Cancer.
higher in patients with CP C score (20% vs 5.5%, P = 0.001), those with portal vein thrombus
(39.7% vs 26%, P = 0.016), those with BCLC stage D (21.3% vs 7.5%, P = 0.001), and those who
received supportive treatment (54.4% vs 37%, P = 0.006). Results of the multivariate analysis are
depicted in Table 4.
Based on the multivariate analysis of mortality from HCC and the CP score, the OR increased
progressively in CP C patients (OR: 1.95; 95% CI: 1.08-3.53; P = 0.026). The progressive increase
was also found in patients with a higher BCLC stage of HCC with ORs for CP C and D patients of
3.50 (95% CI: 1.18-10.38, P = 0.024) and 3.41 (95% CI: 1.02-11.41, P = 0.047), respectively. Support-
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Table 4
Multivariate analysis.
Bivariate P value Multivariate P value
Child–Pugh classification, n (%)

A 1 - 1 -
B 1.75 (1.19-2.57) 0.004 1.25 (0.83-1.92) 0.283
C 2.99 (1.90-4.74) 0.001 1.95 (1.08-3.53) 0.026
Portal vein thrombus, n (%)
No 1 - 1 -
Yes 1.80 (1.27-2.56) 0.001
BCLC staging, n (%)
A 1 - 1 -
B 2.80 (0.99-7.85) 0.051 2.14 (0.73-6.28) 0.166
C 5.80 (2.10-15.97) 0.001 3.50 (1.18-10.38) 0.024
D 8.33 (2.92-23.77) 0.001 3.41 (1.02-11.41) 0.047
Treatment modality, n (%)
Curative 1 - 1 -
Palliative 1.97 (1.07-3.66) 0.030 1.49 (0.77-2.85) 0.235
Supportive 3.41 (1.88-6.19) 0.001 2.17 (1.14-4.16) 0.019
ive treatment for patients with an OR of 2.17 (95% CI: 1.14-4.16, P = 0.019) was associated with
the mortality rate of HCC.
Survival rate
Based on our study, the overall median survival rate was 17 months from the date of diag-
nosis. If compared according to CP score, CP A patients had a median survival of 21 months,
CP B patients had 17 months, and CP C patients had 9 months (Fig 1). Based on our data, pa-
tients with a higher CP score had a lower survival rate. Moreover, the survival rate of each BCLC
stage decreased proportionally to the increase in the BCLC stage. The median survival rates for
patients with BCLC stages B, C, and D were 21, 14, and 9 months, respectively (Fig 2). Based
on treatment modality, the median survival rate of patients receiving palliative therapy was 19
months, and those receiving supportive therapy was 12 months (Fig 3).
Discussion
Based on data the data from the World Health Organization in 2018, the age-standardized
mortality rate of HCC in Indonesia is 7.5 per 10 0,0 0 0 population.1 The 3-year HCC mortality rate
in our study centers was 94.4%. Three years after the diagnosis of HCC, the majority of patients
died.
Similar to the study by Loho et al (2016), the occurrence of HCC was observed in men, which
is in accordance to the incidence of HCC.2 In Southeast Asia, the incidence rate in men is >20
per 10 0,0 0 0 population.6 This phenomenon might be caused by the presence of the androgen
receptor in men, which has been associated with the progression of HCC. AR inhibits the role of
P-53, DNA repair, and production of oxidative stress. Besides, men usually smoke and consume
alcohol more than women, and this is considered one of the reasons why HCC is more often
observed in men than in women.6,7
In our study, the median age of patients with HCC was 55 years. This result is similar to that
of the study by Loho et al (2016), which reported that the median age of patients with HCC was
54 years.2 In Asian countries, such as Indonesia, which have a high prevalence of HBV infection,
patients who are aged under 60 years are diagnosed with HCC.8
Interestingly, based on our bivariate analysis, age was not associated with HCC-related mor-
tality. Meanwhile, a study by Golabi et al (2017) stated that age is a risk factor and reported a
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Fig. 1. Survival of patients with HCC based on the child-pugh score.
2-year mortality after the diagnosis of HCC (hazard ratio: 1.01 [95% CI: 1.01-1.01]).9 Fujiwara et
al (2014) have also assessed the significant association between age and mortality.10 This result
might be explained by the fact that age is only correlated to death that is not associated with
liver diseases. Thus, the result of our study differed because we analyzed the overall HCC mor-
tality whether or not it was associated with liver disease. Moreover, several age-related factors
also contributed to mortality, which includes the fact that younger patients have good tolerance
and overall prognosis.11
The median age of the participants in our study was 55 years, and it was associated with
etiologies, such as HBV infection, which was observed in younger individuals.12 We found that
the most common cause of HCC was HBV, followed by HCV infection, non-B, non-C infection,
and coinfection of HBV and HCV. The incidence rate of HBV infection in Asia was as high as
75%, and the high prevalence of HBV infection was observed in countries, including Indonesia.6,13
Some meta-analysis studies have shown that the relative risk of HBV developing to HCC was
as high as 15-20 times higher. A study by Loho et al (2016) in one of our study centers has
reported that 14% of patients with HCC acquired HCV infection. In our study, the incidence rate
of HCV infection had increased to 20.9%.2 It may be caused by the increase of HCV genotype 6
that progressed significantly to HCC in Southeast Asia and also to the increase in the number
of users of injectable drugs.14 The incidence of HBV infection slightly decreased in the present
study compared with that during the 2013-2014 period,2 which is probably attributed to HBV
vaccination. Based on our multivariate analysis, the etiology was not associated with HCC-related
mortality. This finding was different from that of a study by Wei et al (2017), which showed
that HBV was correlated to mortality. In that study, HBV was associated with the age of patients
with HCC.12 It claimed that a rapid progression to death was observed in younger HBV-infected
patients with HCC. This result was different from that of our study because we did not analyze
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Fig. 2. Survival of patients with HCC based on the Barcelona Clinic Liver Cancer score.
the association between age at diagnosis and mortality rate. We only analyzed the overall age
of patients with HCC and mortality rate.
To determine the HCC stage, the BCLC has been widely used in clinical practice.5 Based on
our multivariate analysis, BCLC stages C and D were significantly associated with mortality (P
values of BCLC stages C and D: 0.024 and 0.047, respectively). The score used to determine liver
function or CP score, notably CP C, was also correlated with mortality. According to the previ-
ously mentioned data, we concluded that the higher the BCLC stage and CP C score were, the
higher was the significance of the correlation to mortality (P = 0.001). The correlation between
the BCLC stage and CP score as well as mortality has been observed in several studies. Kikuchi
et al (2017) have reported that patients with BCLC stage D had a survival rate lower than others
(hazard ratio = 4.0, 95% CI: 1.67-9.8; P < 0.001).15 Besides, Khalaf et al (2017) have validated
that BCLC stage is correlated to mortality (P < 0.0 0 01).16
The American Association for the Study of Liver Diseases guideline stated that surveillance
is essential and cost effective for HCC. Surveillance can detect HCC in early stages, and cura-
tive treatment can then be initiated. In our study, only 17 (6%) patients were diagnosed dur-
ing HCC surveillance. From the 17 patients, 6 presented with HCC with BCLC stage A and 11
with BCLC stage B. This result was similar to that of the study conducted in the United States
showing that only less than 20% of patients were diagnosed during HCC surveillance.17 In our
study, this small percentage of HCC diagnosis during surveillance was noted only in Cipto Man-
gunkusumo General National Hospital. Dharmais Hospital is a cancer-referral hospital, and it did
not have a surveillance program. Therefore, all patients who were referred to Dharmais Hospital
had already been diagnosed with HCC. Most patients (52.9%) receiving curative treatment were
from the HCC surveillance group. Compared to a study in Cipto Mangunkusumo National Gen-
eral Hospital from 2013 to 2014, the surveillance rate during the 2015-2017 period has increased
considerably.2 From 2015 to 2017, 24 individuals participated in the routine surveillance, and 17
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Fig. 3. Survival of patients with HCC based on treatment modality.
patients were diagnosed with HCC. On the contrary, during the 2013-2014 period, only 5 indi-
viduals participated in the routine surveillance, and 2 patients were diagnosed with HCC. This
increase was possibly due to more frequent visits of patients to hepatologists and their previous
diagnosis of decompensated cirrhosis with ascites and encephalopathy. In contrast, patients with
fewer symptoms did not visit hepatologists for surveillance. Besides, the lack of a physician’s
awareness and screening program for risk factors in our population might have contributed to
the low level of HCC surveillance. This leads to an increasing number of HCC-related mortal-
ity despite having considerable preventive measures, screening tools, and treatment modalities
available.18,19
Interestingly, in our multivariate analysis, surveillance did not correlate with mortality. It was
different from a meta-analysis conducted by Singal et al (2014),20 which reported that HCC
surveillance could improve survival rate (pooled OR: 1.90; 95% CI: 1.67-2.17). However, some
studies have found that HCC surveillance did not correlate with mortality and shown that the
treatment should start since the initial diagnosis of HCC.21 Surveillance did not correlate with
mortality in our study. This is attributed to the fact that data came from only one institution,
and this resulted in bias and disproportional data.
In our study, supportive treatment was the most common treatment, followed by palliative
and curative. This result was attributed to the fact that several patients had been diagnosed
with advanced stage HCC when referred to our study centers. In our multivariate analysis, the
risk of mortality also correlated to treatment. Supportive treatment had a significant association
with mortality because patients who received supportive care had a high BCLC stage and CP
score, both of which were also associated with HCC-related mortality. Based on these data, we
can conclude that curative therapy was critical in reducing HCC mortality. A study conducted by
Golabi et al (2017) has shown that HCC therapy with liver transplant as curative treatment can
reduce 2-year mortality.9
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Three factors were associated with mortality. The survival rate between each factor showed
that an increase in each Child Pugh score (CP) and BCLC stage was followed by a decrease in the
survival rate. This can be observed in the Kaplan-Meier chart. Besides, patients who underwent
supportive treatment had lower survival rates other treatment modalities.
In our study, the HCC-related mortality rate in 3 years from our study centers was 94.4%. It
can be concluded that 3 years after the diagnosis of HCC, the majority of patients died.
The strength of our study included a discussion on the relationship between risk factors and
HCC mortality, which has never been discussed before, particularly in Indonesia. However, the
present study also had a limitation. That is, there is a lack of follow-up data because several
patients were not reached. Therefore, we cannot examine several variables associated with HCC-
related mortality, which include AFP or tumor size.
In conclusion, the risk factors significantly associated with mortality in patients with HCC
were BCLC stage, CP score, and treatment modality. A higher BCLC stage or CP score is correlated
to a higher HCC mortality. Supportive treatment was associated with high mortality from HCC.
More HCC surveillance must be conducted to detect patients with earlier stages of HCC who
can receive curative treatment as these patients can have a better prognosis and lower mortality
rate. In future studies, other parameters must also be examined.
Author’s contribution
Chyntia Olivia Maurine Jasirwan proposed and conducted the study, and Irsan Hasan per-
formed the research and wrote the first draft of the manuscript. Andri Sanityoso Sulaiman, Rino
Alvani Gani, and Cosmas Rinaldi A. Lesmana collected and analyzed the data. All authors con-
tributed in designing the study, interpreting results, and writing the final manuscript. Chyntia
Olivia Maurine Jasirwan is the guarantor.
Acknowledgments
This study did not receive any grant supports. The authors would like to thank Enago (www.
enago.com) for the English language review.
Supplementary materials
Supplementary material associated with this article can be found, in the online version, at
doi:10.1016/j.currproblcancer.2019.05.003.
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ARTICLE IN PRESS

JID: YMCN [mUS1Ga;May 23, 2019;14:15]

Contents lists available at ScienceDirect

Current Problems in Cancer

journal homepage: www.elsevier.com/locate/cpcancer

Risk factors of mortality in the patients with

Keywords: Hepatocellular carcinoma; Cirrhosis; Mortality; Risk factors

Materials and methods

Study design and population

We conducted a cohort retrospective data study at 2 tertiary hospitals (Cipto Mangunkusumo

Total number of Patients with HCC Patients with HCC

Mortality rate and risk factor analysis

Time of follow-up after diagnosis

All the time 6 months 1 year 2 years 3 years

Number of study participants (n) 282 239 199 156 142

Survivors Nonsurvivors P value

Bivariate P value Multivariate P value

Child–Pugh classiﬁcation, n (%)

Fig. 1. Survival of patients with HCC based on the child-pugh score.

Fig. 3. Survival of patients with HCC based on treatment modality.

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