ORIGINAL ARTICLE
Bali Medical Journal (Bali MedJ) 2025.
Volume 14.
Number 3: 677-683 P-ISSN.
E-ISSN: 2528-6641
Post-resection survival analysis in non-cirrhotic hepatocellular carcinoma based on preoperative PLR.
NLR, and MxC values Denny Krystian Tandi Ose1*.
Agi Satria Putranto1
ABSTRACT
Department of Surgery.
Faculty of Medicine Universitas Indonesia.
Cipto Mangunkusumo Hospital.
Jakarta.
Indonesia.
*Corresponding author:
Denny Krystian Tandi Ose.
Department of Surgery.
Faculty of Medicine.
Universitas Indonesia.
Cipto Mangunkusumo Hospital.
Jakarta.
Indonesia.
dennytandiose@yahoo.
Received: 2025-07-19 Accepted: 2025-09-23 Published: 2025-10-23 Background: To predict the prognosis of hepatocellular carcinoma (HCC), various staging systems have been developed, one of which is the Barcelona Clinic Liver Cancer (BCLC) staging system.
However, this system has limitations in integrating systemic inflammatory markers that are relevant to tumor progression.
Recent studies have shown that hematological parameters such as Platelet-to-Lymphocyte Ratio (PLR).
Neutrophil-to-Lymphocyte Ratio (NLR), and Monocyte y C-reactive Protein (MxC) can serve as independent predictors of survival in non-cirrhotic HCC patients following resection.
Methods: A retrospective cohort study was conducted using secondary data.
Preoperative laboratory parameters collected included PLR.
NLR, and MxC values.
Risk factors compared included age, gender, tumor size, tumor margin, and BCLC stage.
Multivariate analysis was performed to identify survival predictors.
Data were analyzed using SPSS version 25.
Results: A total of 59 subjects were included in the study.
Eleven patients .
5%) died, while 48 .
4%) survived.
Cut-off values to differentiate between high and low groups were 186.
5 for PLR, 2.
05 for NLR, and 1.
11 for MxC.
Bivariate analysis showed that high MxC .
= 0.
and age >50 years .
= 0.
were significantly associated with higher mortality risk.
Subsequent multivariate analysis revealed that MxC was the strongest mortality predictor .
= 0.
HR = 12.
4, 95% CI:
56Ae99.
, indicating that patients with MxC Ou1.
11 were 12.
4 times more likely to experience earlier mortality after Conclusion: Post-resection survival in non-cirrhotic hepatocellular carcinoma patients can be assessed using preoperative laboratory parameters and age.
Elevated MxC values and age over 50 years may assist clinicians in predicting a higher risk of early mortality following surgical resection.
Keywords: Non-cirrhotic Hepatocellular Carcinoma.
PLR.
NLR.
MxC.
Survival.
Cite This Article: Ose.
Putranto.
Post-resection survival analysis in non-cirrhotic hepatocellular carcinoma based on preoperative PLR.
NLR, and MxC values.
Bali Medical Journal 14.
: 677-683.
DOI: 10.
15562/bmj.
INTRODUCTION
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for 75Ae85% of all liver cancer cases worldwide.
1-3 Various systems have been developed to predict HCC prognosis, one of which is the Barcelona Clinic Liver Cancer (BCLC) staging system.
However, this system has limitations in integrating systemic inflammatory factors that are relevant to tumor progression.
Recent parameters such as the Platelet-toLymphocyte Ratio (PLR).
Neutrophil-toLymphocyte Ratio (NLR), and Monocyte y C-reactive Protein (MxC) suggest their role as independent predictors for patient survival after resection of HCC.
A study by Zhang et al.
that PLR.
NLR, and MxC values significantly predicted overall survival (OS) in HCC patients.
5 Patients with elevated ratios had worse prognosis, reflecting higher systemic inflammation and more likely advanced tumor stage.
Validation using a nomogram showed better accuracy in predicting OS compared to conventional staging systems.
Therefore.
PLR.
NLR, and MxC values may serve as simple, affordable, and reliable tools to guide the clinical management of HCC patients and support more personalized therapy strategies.
To date, there is no evidence that preoperative PLR.
NLR, and MxC values influence postoperative survival in patients with non-cirrhotic HCC.
This study aims to evaluate preoperative PLR.
NLR.
MxC, along with age, sex, tumor number, tumor margin, and BCLC stage as predictors of Bali Medical 14.
: 677-683 | doi: 10.
15562/bmj.
Open access:Journal postoperative survival in non-cirrhotic HCC patients.
METHODS
This retrospective cohort study was conducted at Cipto Mangunkusumo Hospital.
Jakarta, from January 2020 to December 2024.
The study used secondary .
ematological contrast-enhanced scan.
obtained from medical records.
The subjects included all patients with non-cirrhotic HCC who underwent hepatic resection and had complete data on hematologic parameters, multiphase abdominal contrast CT scans, and postoperative follow-up.
Total sampling was used to determine the sample size.
Inclusion criteria included Radiological and clinical diagnosis of HCC.
Treatment677
ORIGINAL ARTICLE
nayve patients.
ECOG performance status 0Ae1, underwent curative resection, and non-cirrhotic liver based on laboratory and imaging screening for risk factors.
Exclusion criteria included Patients with a histopathological diagnosis of intrahepatic cholangiocarcinoma (ICC) or combined HCC-ICC.
Concurrent malignancies.
Distant metastases.
Postoperative survival less than one month.
Blood sampling taken during active infection.
Liver function Child-Pugh B or C, who received targeted therapy, immunotherapy.
TACE, or HAIC prior to surgery.
Outcome measured: Survival status .
live Preoperative hematologic values (PLR.
NLR.
MxC) measured within 7 days before surgery.
Risk variables including age, sex, tumor margin, tumor size, and BCLC stage.
Statistical analysis: Univariable analysis was conducted to describe each variable .
requency and percentag.
ROC analysis was used to determine cut-off values for PLR.
NLR, and MxC based on the Youden Index.
The Kaplan-Meier method and log-rank test were used to calculate and compare survival outcomes.
The Proportional Hazard (PH) assumption was tested using goodness-of-fit (GOF).
Variables meeting the PH assumption .
> 0.
were analyzed with Cox proportional hazard regression.
Cox time-dependent regression was used.
Multivariate analysis used backward stepwise Cox regression to determine significant predictors of postoperative A p-value < 0.
05 was considered statistically significant.
Ethical approval was obtained from the Research Ethics Committee of Cipto Mangunkusumo Hospital.
Universitas Indonesia.
Statistical analysis was performed using SPSS version 25 for Windows.
Table 1.
Postoperative Characteristics of Hepatocellular Carcinoma Patients at Cipto Mangunkusumo Hospital (N=.
Variable Age (Year.
O50
>50
Gender Male Female Number of Tumors Single Multiple Size of Tumor .
BCLC Stage
PLR
Low (<186.
High (Ou186.
NLR
Low (<2.
High (Ou2.
MxC Low (<1.
High (Ou1.
Frequency .
Percentages (%) RESULTS The sample in this study consisted of 59 patients with hepatocellular carcinoma (HCC) who underwent liver resection at Cipto Mangunkusumo Hospital and had complete data on hematologic parameters and postoperative followup during the period from January 2020 to December 2024 (Table .
Figure 1.
ROC Curves of PLR.
NLR, and MxC for Predicting Postoperative Mortality in Patients with Hepatocellular Carcinoma.
From Table 1, it was found that the majority of patients were in the >50 years age group .
5%), male .
5%), had a single tumor .
2%), tumor size >5 cm .
3%).
BCLC stage B .
5%).
PLR
<186.
%).
NLR Ou2.
8%), and MxC Ou1.
5%).
The determination of cut-off points for the PLR.
NLR, and Bali Medical Journal 2025.
: 677-683 | doi: 10.
15562/bmj.
ORIGINAL ARTICLE
Table 2.
Determination of Cut-Off Points for Parameters (PLR.
NLR.
MxC) Parameter PLR
NLR
MxC Table 3.
AUC .
252 Ae 0.
361 Ae 0.
540 Ae 0.
Cut-off Postoperative Survival Status of Hepatocellular Carcinoma Patients at Cipto Mangunkusumo Hospital (N=.
Overall Survival (OS) Deceased (Even.
Alive (Senso.
Figure 2.
Youden Index Frequency .
Percentage (%) Kaplan-Meier Curve of Cumulative Overall Survival After Resection in Hepatocellular Carcinoma Patients.
MxC parameters was conducted using Receiver Operating Characteristic (ROC) analysis by evaluating the area under the curve (AUC) (Figure .
The optimal cutoff point for each parameter was selected based on the highest Youden Index value.
In Table 2, the AUC value for PLR 455, indicating that the ability of PLR to predict postoperative mortality in hepatocellular carcinoma patients falls into the poor classification category.
Nevertheless, a cut-off point was still determined for PLR to allow for patient stratification, with the optimal cut-off value being 186.
5 (Table .
For NLR, the AUC was 0.
530, suggesting a fair classification in predicting mortality, with the best cut-off point determined at 2.
Meanwhile, the AUC for MxC was 0.
which also falls into the fair classification category, with an optimal cut-off point of 11 (Table .
Patient survival was assessed based on two variables: survival status .
live or decease.
and length of survival .
n month.
The survival period was evaluated over a 3-year .
-mont.
follow-up duration (Table .
Table 3 shows that among hepatocellular carcinoma patients who underwent liver resection, 11 patients .
5%) died, while 48 patients .
4%) were still alive.
The cumulative survival probability (Figure .
represents the likelihood of a patient surviving over a specific period .
months of observatio.
, taking into account the entire time span.
Survival probability ranges from 0 to 1, with 1 indicating a 100% chance of survival.
The results showed that the cumulative overall survival (OS) probability in non-cirrhotic hepatocellular carcinoma patients gradually declined over time.
the end of the 36-month follow-up period.
Bali Medical Journal 2025.
: 677-683 | doi: 10.
15562/bmj.
the cumulative OS probability was 0.
7%).
This means that by the end of the observation period, 74.
7% of non-cirrhotic HCC patients who underwent resection were still alive.
The median survival could not be calculated because fewer than 50% of the patients had died by the end of the observation period (Table 3 and Figure .
The survival profile of hepatocellular influencing risk factors is presented in Table 4.
In Table 4, the cumulative survival probability was lower in the PLR Ou186.
group compared to the PLR <186.
5 group .
2% vs 77.
1%).
Similarly, patients with NLR Ou2.
05 had a lower cumulative survival probability than those with NLR <2.
9% vs 81.
1%).
For the MxC parameter, the cumulative survival probability was significantly lower in the MxC Ou1.
11 group compared to the MxC <1.
11 group .
3% vs 96.
3%) (Table .
The cumulative survival probability was also lower in patients aged >50 years compared to those aged O50 years .
vs 91%).
Female patients had a slightly lower survival probability than male patients .
% vs 76.
9%).
Patients with single tumors had slightly lower survival than those with multiple tumors .
1%).
In terms of tumor size, patients with tumors >5 cm had lower survival than those with tumors O5 cm .
9% vs 5%).
Finally, patients with BCLC stage A had a slightly lower survival probability compared to those with stage B .
0% vs 5%) (Table .
Before conducting the bivariate analysis, the proportional hazard (PH) assumption was assessed to determine whether any variables interacted with timeAii.
, whether any variable had a hazard ratio that varied over time.
The PH assumption was tested using the Goodness-of-Fit (GOF) test.
A global test p-value greater than 0.
05 indicates that the PH assumption is met (Table .
Based on Table 5, one variableAi genderAidid not meet the proportional hazard (PH) assumption .
-value > Therefore, both the bivariate and multivariate analyses for gender were conducted using the Cox Extended/Cox Time-Dependent model.
Based on the monthly survival and hazard curves, a ORIGINAL ARTICLE Table 4.
Postoperative Survival in Hepatocellular Carcinoma Patients Based on Risk Factors at Cipto Mangunkusumo Hospital Variable PLR Low (<186,.
High (Ou186,.
NLR
Low (<2,.
High (Ou2,.
MxC Low (<1,.
High (Ou1,.
Age (Year.
O50
>50
Gender Male Female Number of Tumors Single Multiple Size Tumor .
O5 BCLC stage Table 5.
Mean Survival (Month.
Cumulative probability OS 771 .
579 Ae 0.
334 Ae 0.
561 Ae 0.
399 Ae 0.
764 Ae 0.
289 Ae 0.
677 Ae 0.
291 Ae 0.
475 Ae 0.
507 Ae 0.
526 Ae 0.
463 Ae 0.
468 Ae 0.
531 Ae 0.
479 Ae 0.
518 Ae 0.
Results of the Proportional Hazard (PH) Assumption Test
Variable PLR
NLR
MxC Age Gender Number of Tumors Size of Tumor BCLC stage Global Test .
-valu.
split time was set for the gender variable at t O 12 months, allowing the analysis to estimate separate hazard ratios before and after this time point (Table .
The purpose of the bivariate analysis was to examine the relationship between hematological parameters (PLR.
NLR.
MxC) and patient characteristics .
ge, gender, tumor number, tumor size.
BCLC stag.
with the dependent variableAi postoperative survival or mortality in hepatocellular carcinoma patients.
The results of the bivariate analysis are presented in Table 6.
Table 6 shows that for the PLR variable, the proportion of patients who experienced Explanation Meets the PH assumption Meets the PH assumption Meets the PH assumption Meets the PH assumption Does not meet the PH assumption Meets the PH assumption Meets the PH assumption Meets the PH assumption the event .
was higher in the PLR Ou186.
5 group .
1%) compared to the PLR <186.
5 group .
4%).
However.
Cox regression analysis showed no significant association between PLR and overall survival (OS) in hepatocellular carcinoma patients post-resection .
-value = 0.
HR = 1.
05, 95% CI: 0.
28Ae3.
For the NLR variable, the mortality rate was also higher in the NLR Ou2.
05 group .
compared to the NLR <2.
05 group .
8%).
Cox regression results again showed no significant association between NLR and OS .
-value = 0.
HR = 1.
71, 95%
CI: 0.
50Ae5.
In contrast, for the MxC variable, the percentage of deaths was markedly higher in the MxC Ou1.
11 group .
3%) compared to the MxC <1.
11 group .
6%).
Cox regression analysis showed a significant association between MxC and OS .
-value = 0.
HR = 9.
82, 95% CI:
25Ae77.
This indicates that patients with MxC Ou1.
11 had a 9.
82 times higher risk of earlier death than those with MxC <1.
11 (Table .
Regarding age, mortality was higher in the >50 years group .
%) compared to those aged O50 years .
1%).
Cox regression revealed a significant association between age and OS .
-value = 0.
HR = 5.
95% CI: 1.
21Ae26.
, meaning patients older than 50 had a 5.
69 times higher risk of dying earlier than younger patients.
For the gender variable, more deaths occurred in female patients .
%) than male patients .
9%).
However.
Cox regression showed no significant association between gender and OS .
-value = 0.
HR = 6.
72, 95%
CI: 0.
81Ae55.
Regarding tumor number, patients with multiple tumors had a higher mortality rate .
5%) than those with single tumors .
7%).
However, this was not statistically significant .
-value = 548.
HR = 1.
46, 95% CI: 0.
43Ae4.
For tumor size, mortality was slightly higher in the >5 cm group .
%) compared to O5 cm .
7%), with Cox regression showing no significant relationship .
-value = 908.
HR = 0.
93, 95% CI: 0.
27Ae3.
Finally, for the BCLC stage, the mortality rate was slightly higher in stage B .
compared to stage A .
9%), but Cox regression found no significant association with OS .
-value = 0.
HR = 0.
96, 95%
CI: 0.
29Ae3.
(Table .
Multivariate analysis was performed using a determinant modeling approach with a backward stepwise method, aiming to identify factors that significantly influenced postoperative overall survival (OS) in patients with hepatocellular The analysis used multiple Cox regressions.
In the first step, all independent variables were included simultaneously with the dependent variable to construct the whole model, as shown in Table 7.
The next step involved the gradual elimination of variables, starting with those that had the highest p-values (>0.
, namely PLR.
NLR.
BCLC stage.
Bali Medical Journal 2025.
: 677-683 | doi: 10.
15562/bmj.
ORIGINAL ARTICLE
Table 6.
Association Between Independent Variables and Postoperative Survival in Hepatocellular Carcinoma Patients at Cipto Mangunkusumo Hospital (N=.
Total
95% CI
OS HCC patients Deceased Ref.
28 Ae 3.
Ref.
50 Ae 5.
Ref.
25 Ae 77.
Ref.
21 Ae 26.
Ref.
81 Ae 55.
04 Ae 3.
Alive Variable PLR Low (<186,.
High (Ou186,.
NLR Low (<2,.
High (Ou2,.
MxC Low (<1,.
High (Ou1,.
Age O50 years >50 years Gender Male Female .
Female .
Number of Tumors Single Multiple Size of Tumor O5 cm >5 cm BCLC stage Ref.
43 Ae 4.
Ref.
27 Ae 3.
Ref.
29 Ae 3.
tumor number, age, and tumor size.
The elimination process was completed once no variables with p-values >0.
05 remained, resulting in the final multivariate model presented in Table 8.
In Table 8, the final multivariate model identified MxC and age as significant predictors of postoperative survival in hepatocellular carcinoma patients .
-value < 0.
Among these.
MxC was the strongest factor influencing mortality.
Patients with MxC Ou1.
11 had a 12.
44 times higher risk of earlier death compared to those with MxC <1.
11, after adjusting for the gender variable (HR = 12.
44, 95%
CI: 1.
56Ae99.
(Table .
DISCUSSION