
==== Front
BMC Gastroenterol
BMC Gastroenterol
BMC Gastroenterology
1471-230X
BioMed Central London

3387
10.1186/s12876-024-03387-5
Research
Prognostic performance of Hong Kong Liver Cancer with Barcelona Clinic Liver Cancer staging systems in hepatocellular carcinoma
Kohla Mohamed 1
Ashour Reham 1
Taha Hossam 1
El-Abd Osama 2
Osman Maher 3
Abozeid Mai 1
ELKhadry Sally Waheed drsallywaheed@liver.menofia.edu.eg

4
1 https://ror.org/05sjrb944 grid.411775.1 0000 0004 0621 4712 Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511 Egypt
2 https://ror.org/05sjrb944 grid.411775.1 0000 0004 0621 4712 Department of Diagnostic Medical Imaging and Interventional Radiology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511 Egypt
3 https://ror.org/05sjrb944 grid.411775.1 0000 0004 0621 4712 Department of Hepatopancreatobiliary surgery, National Liver Institute, Menoufia University, Shebin El-Kom, 32511 Egypt
4 https://ror.org/05sjrb944 grid.411775.1 0000 0004 0621 4712 Department of Epidemiology and Preventive Medicine, National Liver Institute, Menoufia University, Shebin El-Kom, 32511 Egypt
18 9 2024
18 9 2024
2024
24 3185 1 2024
27 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Background

Accurate staging is necessary for predicting hepatocellular carcinoma (HCC) prognosis and guiding patient management. The Barcelona Clinic Liver Cancer (BCLC) staging system has limitations due to heterogeneity observed among patients in BCLC stages B and C. In contrast, the Hong Kong Liver Cancer (HKLC) staging system offers more aggressive treatment strategies.

Aim

To compare the prognostic performance of HKLC and BCLC staging systems in Egyptian patients with HCC.

Methods

We conducted a retrospective study at the National Liver Institute, Menoufia University, Egypt, on 1015 HCC patients. Data was collected from patients’ medical records over 10 years (from 2008 to 2018). The BCLC and HKLC stages were identified, and Kaplan-Meier survival analysis was used to compare patients’ overall survival rates within each staging system. Additionally, we evaluated the comparative prognostic performance of the two staging systems.

Results

Hepatitis C was identified as the underlying etiology in 799 patients (78.7%), hepatitis B in 12 patients (1.2%), and non-viral causes in 204 patients (20.1%). The survival analysis demonstrated significant differences across the various stages within both the BCLC and HKLC systems. The receiver operating characteristic (ROC) curves indicated a marginally superior performance of the HKLC system in predicting survival at 1, 2, and 3 years compared to the BCLC system. Furthermore, the HKLC staging provided a slightly enhanced prognostic capability, particularly for patients classified under BCLC stages B and C, suggesting a potential survival benefit.

Conclusion

HKLC classification had a slightly better prognostic performance than BCLC staging system and may offer a survival advantage for certain patients with HCC in BCLC stage B and C HCC cases.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12876-024-03387-5.

Keywords

Hepatocellular carcinoma
Staging systems
Hong Kong Liver Cancer
Barcelona Clinic Liver Cancer
Prognostic performance
Egypt
Minufiya UniversityOpen access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcIntroduction

Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide in 2020. Hepatocellular carcinoma (HCC) is the dominant type comprising 75-85% of cases [1]. The incidence rates have increased in recent decades with the highest rates observed in Asia and Africa [2]. In Egypt, HCC is one of the most challenging health problems as it represents the fourth common cancer and the leading cause of cancer-related mortality and morbidity [3]. Up to 90% of HCC cases have a cirrhotic liver, but it may also arise without cirrhosis, most commonly in patients with chronic hepatitis B or Non-alcoholic fatty liver disease (NAFLD) [4–7].

Prognostic assessment in HCC patients remains extremely difficult due to the complex interaction of tumor characteristics with the degree of liver dysfunction, patient health status and available treatment options. Several staging systems have been proposed to estimate the prognosis of HCC patients [8].

The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely applied HCC staging system that has been extensively validated. It is used to guide stage-appropriate treatment and prognostic prediction. Major leading international liver study groups such as the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of Liver (EASL) have recommended the BCLC staging system for HCC management [5, 9]– [11]. Despite its popularity, the BCLC staging system has some limitations mainly related to the heterogeneity of BCLC stages B and C patients in respect to tumor burden and liver function [12]. The BCLC approach tends to compromise the application rate of surgical and locoregional therapies in selected patients with BCLC B and C stages especially with recent advances in the surgical and radiological techniques [13].

A group of liver experts developed the Hong Kong Liver Cancer (HKLC) staging system in order to provide more aggressive treatment guidance for Asian HCC patients. According to the HKLC classification, tumor multicentricity or intrahepatic vascular invasion doesn’t contraindicate surgical resection or trans arterial chemoembolization. In addition, advanced liver disease (Child C) and early tumor without extrahepatic vascular invasion or metastases leave patients eligible for liver transplantation [14, 15].

The HKLC staging system can be used both as a prognostic score and as a staging system for treatment assignment. Compared to BCLC classification, HKLC system better stratifies patients assigned to BCLC intermediate and advanced stages resulting in better survival outcomes. The pitfall of HKLC staging system is the lack of solid external validation in non-Asian populations with clinical, biological and etiological heterogeneity since it was developed at a single Asian center that principally treats patients with hepatitis B virus (HBV) infection [8, 16]. So, it’s important to study the prognostic performance of HKLC staging system in different countries where there are more heterogeneous causes of HCC.

Materials and methods

Study design

This retrospective cohort included 1015 HCC patients who attended the multidisciplinary HCC clinic over a 10-year period (from 2008 to 2018) at the National Liver Institute, Menoufia University, Egypt.

Inclusion and exclusion criteria

Patients with a confirmed diagnosis of HCC according to the AASLD Practice Guidelines [17] were included, while those with incomplete records or other primary malignancies were excluded.

Data collection

Data were collected from patient records, including demographic details, clinical characteristics, laboratory findings, imaging results, Child-Turcotte-Pugh (CTP) class, performance status, tumor characteristics, and treatment modalities for HCC.

Data analysis

The BCLC and HKLC stages were determined using the collected data. Overall survival (OS) was defined as the period from the initial diagnosis of HCC to the date of death or last follow-up. The BCLC and HKLC staging systems were compared by calculating the median OS for all patients treated under each classification. The outcomes of patients with BCLC stage B and C HCC treated according to BCLC recommendations were compared with those treated according to HKLC guidelines [5, 14].

Statistical analysis

Statistical analysis was conducted using SPSS version 22 (Armonk, NY: IBM Corp.). Quantitative data were presented as mean, standard deviation (SD), and range, while qualitative data were reported as frequency and percentage. Kaplan-Meier survival analysis was employed to assess survival rates. The Cox regression model was utilized to compute the adjusted hazard ratio and 95% confidence intervals for the effects of various risk factors on survival. The risk ratio (RR) quantified the likelihood of an event occurring in an exposed group relative to a non-exposed comparison group. Confidence intervals (CI) provided estimates of the population parameters, with the proportion of intervals containing the true parameter value reflecting the specified confidence level. Two-sided confidence limits form a confidence interval, while one-sided limits are referred to as lower or upper confidence bounds. The receiver operating characteristic (ROC) curve was used to evaluate the overall effectiveness of tests, with larger areas under the ROC curve indicating better test performance. The Delong test was applied to compare ROC curves and assess the discriminatory ability of different staging systems in predicting survival (18). Statistical significance was defined as a p-value less than 0.05.

Results

A total of 1015 cirrhotic patients with HCC were included in the study. The baseline descriptive data of these patients were presented in Table 1. Their mean age was 58.65 ± 7.95 and 83.5% of them were males. All patients had liver cirrhosis, and the underlying etiology was mainly hepatitis C virus infection (78.7%) with 71.3% having CTP A and 75.6% with an Eastern Cooperative Oncology Group score of 0. The results of various baseline laboratory parameters were also summarized in Table 1.

Table 1 Baseline demographic, clinical criteria, lab, and tumor characteristics of all patients

Baseline demographic, clinical criteria, performance status and Child Pugh class of all patients.	
Studied variable	Frequency	Percent (%)	
Gender	Male	848	83.5	
Female	167	16.5	
Age	Mean ± SD

Median (Min - Max)

	58.65 ± 7.95

58 (20–89)

	
Smoking	No	489	48.2	
Yes	454	44.7	
EX	72	7.1	
Alcohol consumption	No	1015	100	
Diabetes mellitus	No	719	70.8	
Yes	296	29.2	
Hypertension	No	803	79.1	
Yes	212	20.9	
Ascites	No	837	82.5	
Yes	178	17.5	
Splenomegaly	No	251	24.7	
Yes	737	72.6	
Splenectomy	27	2.7	
Underlying aetiology	Hepatitis C virus (HCV)	799	78.7	
Hepatitis B virus (HBV)	12	1.2	
Non-viral	204	20.1	
Performance Status	0	767	75.6	
1	215	21.1	
2	22	2.2	
3	11	1.1	
Child Pugh Class	A	724	71.3	
B	253	25	
C	38	3.7	
Baseline laboratory findings of all patients.	
Studied variable	Mean ± SD	Median (Min-Max)	
Total Bilirubin (mg/dl)	1.42 ± 1.09	1.2 (0.1–14)	
Direct Bilirubin (mg/dl)	0.72 ± 0.89	0.5 (0.01-10)	
Alanine Aminotransferase (U/L)	47.39 ± 32.63	38 (4-250)	
Aspartate Aminotransferase (U/L)	59.49 ± 41.42	50 (4-300)	
Alkaline Phosphatase (U/L)	166.20 ± 123.95	134 (10–741)	
Gamma-glutamyl transferase (U/L)	95.74 ± 114.68	72 (20–765)	
Albumin (g/dl)	3.51 ± 1.56	3.5 (1.6–5.7)	
Prothrombin concentration (%)	75.05 ± 15.56	76 (33–101)	
International normalized ratio (INR)	1.22 ± 0.21	1.2 (0.8–2.9)	
Hemoglobin level (g/dl)	12.29 ± 1.92	12.40 (7-17.80)	
Total leucocytic count (X 103/cmm)	5.64 ± 2.44	5.20 (1.40–18.8)	
Platelet count(X 103/cmm)	125.02 ± 68.97	110 (10–622)	
Urea (mg/dl)	34.35 ± 15.41	31 (8-132)	
Creatinine (mg/dl)	0.91 ± 0.25	0.9 (0.3–3.1)	
Alpha-fetoprotein (ng/ml)	2305.24 ± 18570.72	50 (0.2-514180)	
Baseline tumor characteristics of all patients.	
		Frequency	Percent (%)	
Lesion Number:	Single	555	54.7	
Multiple	420	41.4	
Diffuse	40	3.9	
Site of nodule (s):	Unilobar	782	77	
Left lobe	217	21.3	
Right lobe	565	55.7	
Bilobar	233	23	
Size of nodule (s):	≤ 2	58	5.7	
3–5	439	43.3	
> 5	518	51	
Vascular invasion	No	857	84.4	
Yes	158	15.6	
Different sites of vascular invasion	Main PVT	63	6.2	
RT segmental PVT	39	3.8	
RT PVT	22	2.2	
LT PVT	15	1.5	
LT segmental PVT	14	1.4	
PVT & SV	1	0.1	
PVT & SV & SMV	1	0.1	
PVT & SMV & IVC	1	0.1	
PVT & HV & IVC	1	0.1	
Rt HVT	1	0.1	
Extrahepatic Metastasis	N	972	95.7	
Y	43	4.3	
Site of extra hepatic metastasis	Lymph node	18	1.8	
Bone metastasis	12	1.2	
Near organs	5	0.5	
Lung metastasis	5	0.5	
Near organ + lung	1	0.1	
Near organ + bone	1	0.1	
Lymph node + lung	1	0.1	
PVTPortal vein thrombosis SVSplenic vein, SMVSuperior mesenteric vein, IVCInferior vena cava, HVTHepatic vein thrombosis

Nearly half of the patients (54.7%) had a solitary tumor, 158 patients (15.6%) had either intrahepatic or extrahepatic vascular invasion and extrahepatic metastasis was observed in 43 patients (4.3%), mainly in the lymph nodes, lungs, and skeleton. According to BCLC classification, 54 patients (5.3%) were included in BCLC stage 0, 367 (36.2%) in stage A, 375 (37%) in stage B, 178 (17.5%) in stage C and 41 (4%) in stage D. When patients were classified using the HKLC staging system, 299 patients (29.4%) were categorized into HKLC stage I, 145 (14.3%) into stage IIa, 205 (20.2%) into stage IIb, 84 (8.3%) into stage IIIa, 153 (15.1%) into stage IIIb, 60 (5.9%) into stage IVa, 16 (1.6%) into stage IVb, 17 (1.7%) into stage Va and 36 patients (3.5%) into stage Vb. The comparison between BCLC and HKLC staging systems were presented in Table 2 with agreement between both systems regarding early and late stages while in intermediate stage that represent BCLC B, we found that 8.8% of patients were HKLC stage I, 7.7% were stage IIa, and 37.9% were stage IIb, so these patients could be treated with curative therapies rather than TACE and also in advanced BCLC stage C we found that 15.2% of patients were HKLC stage IIb, 0.6% were stage IIIa, and 34.8% were stage IIIb and also they could be treated with curative therapies or TACE rather than systemic therapies.

Table 2 BCLC versus HKLC staging of all patients

	HKLC Stage	Total	
I	IIa	IIb	IIIa	IIIb	IVa	IVb	Va	Vb	
BCLC Stage	0	42

77.8%

	12

22.2%

	0	0	0	0	0	0	0	54	
A	224

61%

	104

28.4%

	36

9.8%

	3

0.8%

	0	0	0	0	0	367	
B	33

8.8%

	29

7.7%

	142

37.9%

	80

21.3%

	91

24.3%

	0	0	0	0	375	
C	0	0	27

15.2%

	1

0.6%

	62

34.8%

	60

33.7%

	16

8.9%

	3

1.7%

	9

5.1%

	178	
D	0	0	0	0	0	0	0	14

34.1%

	27

65.9%

	41	
Total	299	145	205	84	153	60	16	17	36	1015	

According to the different therapeutic options suggested by both staging systems, in our study, agreement between the HKLC and BCLC staging systems regarding treatments offered was found in 556 (54.8%) of patients while 336 (33.1%) patients received treatment according to BCLC treatment options and 123 patients (12.1%) were already treated according to the HKLC recommendations Table 3. Those 123 patients were included in BCLC stages B (23.6%) and C (76.4%). Certain patients were treated with curative therapies rather than TACE in BCLC stage B and also in advanced BCLC stage C, some of them were treated with curative therapies or TACE rather than systemic therapies Supplementary Table 1.

Table 3 Concordance between BCLC and HKLC staging systems regarding treatment modalities received in all patients

Treatment	Within BCLC and HKLC	Within BCLC only	Beyond BCLC (within HKLC only)	Total	
Surgical resection	N	78	0	49	127	
%	14%	0%	39.8%	12.5%	
Ethanol injection	N	30	0	0	30	
%	5.4%	0%	0%	3%	
Microwave ablation	N	8	0	1	9	
%	1.4%	0%	0.8%	0.3%	
Radiofrequency ablation	N	67	0	2	69	
%	12.1%	0%	1.6%	6.8%	
Transarterial Chemoembolization	N	203	291	48	542	
%	36.5%	86.6%	39%	53.4%	
Sorafenib	N	43	10	0	53	
%	7.7	3%	0%	5.2%	
Multiple modalities	N	60	29	23	112	
%	10.8%	8.6%	18.7%	11%	
Best supportive care	N	67	6	0	73	
%	12.1%	1.8%	0%	7.1%	
Total	556 (54.8%)	336 (33.1%)	123 (12.1%)	1015	

At the end of the study, 159 patients (15.7%) were alive while 775 patients (76.4%) were dead. The overall mean survival of all patients was 23.168 months while the median was 14.467 months from the date of diagnosis (Fig. 1a). There was a statistically significant difference in survival regarding different stages of both BCLC and HKLC staging systems (p-value 0.0001) (Fig. 1b) (Fig. 1c). Patients’ survival according to HKLC classification (median survival time of 15.2 months) was slightly higher than patients’ survival according to BCLC classification with median survival time of 13.7 months (p-value 0.07) (Fig. 1d). Of 459 BCLC stages B and C patients, 123 patients were treated beyond BCLC treatment options according to HKLC recommendations. Their median survival time was 14.6 months which was higher than the 336 patients treated according to BCLC options but not matching HKLC recommendations with median survival time of 12.3 months (p-value 0.01) (Fig. 1e).

Fig. 1 a Kaplan-Meier curve for overall survival for all patients. b Kaplan-Meier curve for overall survival analysis for all patients regarding treatment according to BCLC versus according to HKLC staging systems. c Kaplan-Meier survival curve for BCLC stages B and C patients regarding treatment within BCLC VS. Within HKLC. d Kaplan-Meier survival curve for all patients regarding BCLC Stage. e Kaplan-Meier survival curve regarding HKLC Stage

Regarding comparison between the two staging systems, HKLC and BCLC according to ROC curves as shown in Fig. 2, There were statistically significant differences between them at 1, 2 and 3 years. The areas under the receiver operating characteristic curves (AUC) estimated at 1 year were 0.680, 0.635 (p-value < 0.0001), at 2 years were 0.661, 0.619 (p-value 0.001) and at 3 years were 0.667, 0.619 (p-value 0.0048) for the HKLC stage and BCLC Stage, respectively. Higher values (lager AUC) indicate larger separation of classification, indicating better discriminatory ability of the HKLC staging system to predict survival than BCLC staging system and that the HKLC system might be more suitable for predicting prognosis than the BCLC.

Fig. 2 Receiver operating characteristic (ROC) curves for HKLC and BCLC staging systems at one, two & three years

In univariate Cox regression analysis, there was increase in the hazard risk of death with the following factors, increase age, male gender, ascites, splenomegaly, hepatitis C, alkaline phosphatase, total and direct bilirubin, AST, creatinine, and AFP levels while there was decrease in hazard risk of death with elevated albumin, prothrombin concentration and INR levels (P-value < 0.05). Regarding tumor characteristics, there was increase in the hazard risk of death with all the following factors, multiplicity of focal lesions, increase size, patients who had PVT and patients who had extrahepatic metastasis (P-value < 0.05). Also in different patients’ classification, there was increase in the hazard risk of death with upgrading all the following, Child Score, performance status, BCLC stages and HKLC stages (P-value < 0.05) Supplementary Table 2. On Multivariate Cox regression analysis, performance status, tumor size, portal vein thrombosis, total bilirubin and INR were the independent prognostic factors affecting OS for studied cases (Table 4).

Table 4 Multivariate analysis for detection of the independent factors affecting patients overall survival

	Sig.	Hazard ratio
Exp(B)	95.0% CI for Exp(B)	
Lower	Upper	
Age	0.097	1.015	0.997	1.034	
Gender	0.170	0.770	0.529	1.119	
Smoker	0.620	1.068	0.824	1.383	
Diabetes mellitus	0.156	1.210	0.929	1.576	
Hypertension	0.198	0.814	0.595	1.114	
Ascites	0.580	0.894	0.601	1.329	
Splenomegaly	0.569	1.089	0.812	1.462	
HBs-Ag	0.856	0.844	0.135	5.277	
HCV-Ab	0.559	0.679	0.186	2.484	
Platelets	0.487	1.001	0.999	1.003	
Total Bilirubin	0.004a	1.351	1.102	1.656	
Albumin	0.576	1.069	0.846	1.351	
INR	0.025a	2.709	1.133	6.476	
Creatinine	0.370	1.224	0.787	1.903	
AFP	0.993	1.000	1.000	1.000	
Performance Status	0.001a	1.556	1.189	2.036	
Lesion Size	0.001a	1.532	1.202	1.953	
Portal vein thrombosis	0.003a	1.593	1.170	2.167	
Extrahepatic METS	0.380	1.268	0.746	2.157	
aSignificant variables in the cox regression

Discussion

Over the years, numerous staging systems have been developed to address the complex relationship between prognostic factors in HCC patients and to recommend appropriate therapies based on disease stage. However, due to the clinical, biological, and etiological variability among different populations, no single staging system has gained universal acceptance for reliably predicting prognosis or recommending therapeutic approaches [18, 19]. Despite the BCLC staging system being the most widely used and endorsed by organizations such as EASL, EORTC, and AASLD [10, 20, 21], it has its limitations. Even with the 2022 update [22], controversial issues remain, such as the maximum tumor diameter in BCLC-A, and the lack of consideration for transitioning from palliative to curative therapy in TACE responders. Traditionally, the BCLC system recommended TACE for all patients with intermediate-stage tumors (BCLC-B) and did not advance to systemic therapy for TACE non-responders or those with multifocal tumors without metastases until the recent update [18].

In contrast, the HKLC staging system, introduced in 2014, identifies subgroups within intermediate and advanced HCC stages and advocates for more aggressive treatments to improve survival outcomes. This study aimed to compare the prognostic performance of the HKLC and BCLC staging systems in a cohort of 1,015 Egyptian HCC patients and to assess their accuracy in predicting survival. Generally, in most populations, the incidence of HCC increases with age until approximately 75 years, though the median age at diagnosis tends to be younger. In Africa, the median age at diagnosis differs significantly between Egypt (58 years) and other African countries (46 years) [2, 23]. In this study, the majority of patients (52.8%) were smokers or ex-smokers, a known co-factor for hepatocarcinogenesis [24–27].

Globally, around 80% of HCC cases are caused by HBV or HCV, with liver cirrhosis more likely to develop in HCV patients [28]. In many HBV-related HCC cases, particularly in African and Asian populations, cirrhosis is less common, resulting in better-preserved liver function [29, 30]. Therefore, patients, especially Asians, may benefit more from the aggressive treatments proposed by the HKLC system. In our cohort, chronic hepatitis C was the leading cause, reflecting the high prevalence of HCV infection in Egypt and the reduced rate of HBV infection following national infant immunization efforts [31].

Previous studies involving predominantly Western patients with chronic HCV and liver cirrhosis have suggested that the HKLC system may offer superior survival outcomes compared to the BCLC algorithm [18, 32, 33]. However, a multicenter study in France found that the HKLC system did not outperform the BCLC system in prognostic or therapeutic efficacy [34]. Notably, BCLC-B patients classified as HKLC-I/II, for whom the BCLC system recommends only TACE, could benefit from radical therapies as previously reported [35, 36]. Similarly, while surgical resection is contraindicated for BCLC stage C HCC with major vascular invasion according to the BCLC algorithm, it has led to long-term survival in a subset of such patients [37, 38]. BCLC stage C patients with intrahepatic venous invasion, classified as HKLC-II, could also benefit from radical therapies. Recent studies have confirmed that liver resection provided acceptable outcomes among selected patients with BCLC stage B and C HCC [39, 40]. BCLC stage C patients, classified as HKLC-III, could also achieve survival benefits from TACE, as previously observed [41–43].

This study also evaluated the ability of the HKLC and BCLC staging systems to discriminate survival across different stages. Both systems were effective in stratifying patients, consistent with findings from other studies [19, 44–46]. For further analysis, established statistical methods such as the DeLong test and AUC were used to assess the prognostic capabilities of the staging systems. The DeLong test, which measures discrimination between staging systems, yielded significant results [47]. AUC at 1, 2, and 3 years also differentiated patients with varying prognoses for overall survival. Our results, in line with other studies, assigned the HKLC system a higher score compared to the BCLC system [19, 44–46].

Several factors may contribute to the superior prognostic accuracy of the HKLC system. For instance, patients with mild tumor-related symptoms have a better prognosis and may benefit from aggressive therapies, yet the BCLC system categorizes these patients as having at least advanced HCC. Additionally, the HKLC system accounts for differences in prognosis between patients with main portal trunk invasion and those with smaller vascular branch involvement, a distinction not made by the BCLC system [45, 48]. Studies from Taiwan and Italy also suggest that more aggressive treatments than those recommended by the BCLC system could improve outcomes for each BCLC stage [49, 50]. Our results indicate that hepatic resection in a carefully selected subgroup of advanced HCC patients could yield substantial survival benefits. TACE may also provide survival advantages in some BCLC-C/HKLC-III patients in agreement with other studies [16, 19, 45].

Moreover, studies have shown that patients with preserved liver function, even those with multiple tumors, may achieve better survival with hepatic resection compared to nonsurgical treatments [51, 52]. The HKLC system’s ability to identify patients suitable for more aggressive treatments is one of its most significant features. Although the BCLC system has reasonably good discriminatory power, the HKLC system is significantly better at stratifying HCC patients into different prognostic groups [17]. Studies by Liu et al. and others have demonstrated that patients treated according to the HKLC staging system have better overall survival than those treated according to the BCLC scheme [45]. However, Li et al. found the BCLC system to be a better prognostic model than the HKLC system, even among a predominantly HBV-related HCC population in Asia [53, 54]. This discrepancy may be due to the heterogeneity of HCC in terms of clinical characteristics, biological nature, etiology, and pathophysiology across different populations. Additionally, the Child-Turcotte-Pugh (CTP) classification, integral to both BCLC and HKLC systems, may not be sensitive enough, particularly when liver function is well-preserved [55].

These findings suggest that while the BCLC system, which is simpler and more intuitive, should be applied in all HCC cases, the HKLC system can provide valuable information for managing patients, especially in the intermediate stages (BCLC B & C). Identifying independent predictors of survival for HCC patients is also essential. In this study, pretreatment variables were analyzed using univariate and multivariate methods. Several commonly available clinical, laboratory, and tumor parameters were statistically significant in univariate analysis. Multivariate analysis confirmed that ECOG performance status, tumor size, portal vein thrombosis, total bilirubin, and INR are independent predictors of survival. Treatment strategies for HCC are primarily determined by tumor size, number, liver function, and performance status, parameters that have been consistently supported by other studies as significant predictors [56–59].

This study has some limitations, including its single-center, retrospective design, which may introduce bias and limit the ability to draw definitive conclusions. Prospective, multicenter validations are needed to address these issues.

Conclusion

In conclusion, while both the BCLC and HKLC staging systems are effective in predicting and distinguishing the prognosis of HCC, the HKLC classification demonstrated slightly better prognostic performance compared to the BCLC system. This suggests that the HKLC system may offer a survival advantage by expanding treatment options for patients with intermediate-stage HCC, specifically those classified under BCLC B and C.

Supplementary Information

Supplementary Material 1.

Acknowledgements

Not applicable.

Authors’ contributions

Kohla M, Taha H designed the study; Ashour R, El-Abd O, Osman M participated in the acquisition of data; ELKhadry SW performed the data analysis; Ashour R, ELKhadry SW, Abozeid M, Kohla M participated in the interpretation of the data; Ashour R wrote the first draft of the manuscript; Ashour R, ELKhadry SW, Abozeid M wrote the manuscript; Kohla M, Ashour R, ELKhadry SW, Taha H, El-Abd O, Osman M revised the article critically.

Funding

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Availability of data and materials

Available upon request from the corresponding author.

Declarations

Ethics approval and consent to participate

The study was reviewed and approved (IRB approval number 00238/2021) by the institutional review board of National Liver institute (NLI IRB 00003413), Menoufia University, Egypt. Informed consent statement was waived by the institutional review board of National Liver institute due to the retrospective nature of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Sung H Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin 2021 71 3 209 249 10.3322/caac.21660 33538338
Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. 10.3322/caac.21660.33538338
2. McGlynn KA Petrick JL El-Serag HB Epidemiology of hepatocellular carcinoma Hepatology 2021 73 S1 4 13 10.1002/hep.31288 32319693
McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of hepatocellular carcinoma. Hepatology. 2021;73(S1):4–13. 10.1002/hep.31288.32319693
3. Rashed WM Kandeil MAM Mahmoud MO Ezzat S Hepatocellular Carcinoma (HCC) in Egypt: a comprehensive overview J Egypt Natl Canc Inst 2020 32 1 5 10.1186/s43046-020-0016-x 32372179
Rashed WM, Kandeil MAM, Mahmoud MO, Ezzat S. Hepatocellular Carcinoma (HCC) in Egypt: a comprehensive overview. J Egypt Natl Canc Inst. 2020;32(1):5. 10.1186/s43046-020-0016-x.32372179
4. Loomba R Lim JK Patton H El-Serag HB AGA clinical practice update on screening and surveillance for hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: expert review Gastroenterology 2020 158 6 1822 30 10.1053/j.gastro.2019.12.053 32006545
Loomba R, Lim JK, Patton H, El-Serag HB. AGA clinical practice update on screening and surveillance for hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: expert review. Gastroenterology. 2020;158(6):1822–30. 10.1053/j.gastro.2019.12.053.32006545
5. Raees A Kamran M Özkan H Jafri W Updates on the diagnosis and management of hepatocellular carcinoma Euroasian J. hepato-gastroenterology 2021 11 1 32 40 10.5005/jp-journals-10018-1335
Raees A, Kamran M, Özkan H, Jafri W. Updates on the diagnosis and management of hepatocellular carcinoma. Euroasian J hepato-gastroenterology. 2021;11(1):32–40. 10.5005/jp-journals-10018-1335.
6. Yen YH Cheng YF Wang JH Lin CC Wang CC Characteristics and etiologies of hepatocellular carcinoma in patients without cirrhosis: when East meets West PLoS One 2021 16. 1 e0244939 10.1371/journal.pone.0244939 33439893
Yen YH, Cheng YF, Wang JH, Lin CC, Wang CC. Characteristics and etiologies of hepatocellular carcinoma in patients without cirrhosis: when East meets West. PLoS One. 2021;16.(1):e0244939. 10.1371/journal.pone.0244939.33439893
7. Mehta N Parikh ND Kelley RK Hameed B Singal AG Surveillance and monitoring of hepatocellular carcinoma during the COVID-19 pandemic Clin Gastroenterol Hepatol 2021 19 8 1520 1530 10.1016/j.cgh.2020.06.072 32652308
Mehta N, Parikh ND, Kelley RK, Hameed B, Singal AG. Surveillance and monitoring of hepatocellular carcinoma during the COVID-19 pandemic. Clin Gastroenterol Hepatol. 2021;19(8):1520–30. 10.1016/j.cgh.2020.06.072.32652308
8. Vitale A Overview of prognostic systems for hepatocellular carcinoma and ITALICA external validation of MESH and CNLC classifications Cancers (Basel). 2021 13 7 1673 10.3390/cancers13071673 33918125
Vitale A, et al. Overview of prognostic systems for hepatocellular carcinoma and ITALICA external validation of MESH and CNLC classifications. Cancers (Basel). 2021;13(7):1673. 10.3390/cancers13071673.33918125
9. Marrero JA Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases Hepatology 2018 68 2 723 750 10.1002/hep.29913 29624699
Marrero JA, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases. Hepatology. 2018;68(2):723–50. 10.1002/hep.29913.29624699
10. European Association for the Study of the Liver . Electronic address: easloffice@easloffice.eu , European Association for the Study of the Liver EASL clinical practice guidelines: management of hepatocellular carcinoma J Hepatol 2018 69 1 182 236 10.1016/j.jhep.2018.03.019 29628281
European Association for the Study of the Liver . Electronic address: easloffice@easloffice.eu , European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236. 10.1016/j.jhep.2018.03.019.29628281
11. Llovet JM Hepatocellular carcinoma Nat Rev Dis Prim 2021 7 1 6 10.1038/s41572-020-00240-3 33479224
Llovet JM, et al. Hepatocellular carcinoma. Nat Rev Dis Prim. 2021;7(1):6. 10.1038/s41572-020-00240-3.33479224
12. Moris D A farewell to Barcelona Clinic Liver Cancer (BCLC) classification for hepatocellular carcinoma J BUON 2021 26 2 298 302 34076971
Moris D. A farewell to Barcelona Clinic Liver Cancer (BCLC) classification for hepatocellular carcinoma. J BUON. 2021;26(2):298–302. Available: https://www.ncbi.nlm.nih.gov/pubmed/34076971.34076971
13. Vitale A Trevisani F Farinati F Cillo U Treatment of hepatocellular carcinoma in the precision medicine era: from treatment stage migration to therapeutic hierarchy Hepatology 2020 72 6 2206 2218 10.1002/hep.31187 32064645
Vitale A, Trevisani F, Farinati F, Cillo U. Treatment of hepatocellular carcinoma in the precision medicine era: from treatment stage migration to therapeutic hierarchy. Hepatology. 2020;72(6):2206–18. 10.1002/hep.31187.32064645
14. Cheung TT-T Hong Kong consensus statements for the management of unresectable hepatocellular carcinoma Liver Cancer 2018 7 1 40 54 10.1159/000485984 29662832
Cheung TT-T, et al. Hong Kong consensus statements for the management of unresectable hepatocellular carcinoma. Liver Cancer. 2018;7(1):40–54. 10.1159/000485984.29662832
15. Chui AMN Yau TCC Cheung TT An overview in management of hepatocellular carcinoma in Hong Kong using the Hong Kong Liver Cancer (HKLC) staging system Glob Heal Med. 2020 2 5 312 318 10.35772/ghm.2020.01062
Chui AMN, Yau TCC, Cheung TT. An overview in management of hepatocellular carcinoma in Hong Kong using the Hong Kong Liver Cancer (HKLC) staging system. Glob Heal Med. 2020;2(5):312–8. 10.35772/ghm.2020.01062.
16. Yau T Tang VYF Yao T-J Fan S-T Lo C-M Poon RTP Development of Hong Kong liver cancer staging system with treatment stratification for patients with hepatocellular carcinoma Gastroenterology 2014 146 7 1691 700.e3 10.1053/j.gastro.2014.02.032 24583061
Yau T, Tang VYF, Yao T-J, Fan S-T, Lo C-M, Poon RTP. Development of Hong Kong liver cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology. 2014;146(7):1691–700.e3. 10.1053/j.gastro.2014.02.032.24583061
17. Bruix J Sherman M American Association for the study of liver diseases, management of hepatocellular carcinoma: an update Hepatology 2011 53 3 1020 2 10.1002/hep.24199 21374666
Bruix J, Sherman M. American Association for the study of liver diseases, management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2. 10.1002/hep.24199.21374666
18. de Freitas LBR Longo L Santos D Grivicich I Álvares-da-Silva MR Hepatocellular carcinoma staging systems: Hong Kong liver cancer vs Barcelona clinic liver cancer in a Western population World J Hepatol 2019 11 9 678 688 10.4254/wjh.v11.i9.678 31602288
de Freitas LBR, Longo L, Santos D, Grivicich I, Álvares-da-Silva MR. Hepatocellular carcinoma staging systems: Hong Kong liver cancer vs Barcelona clinic liver cancer in a Western population. World J Hepatol. 2019;11(9):678–88. 10.4254/wjh.v11.i9.678.31602288
19. Jan Lee Y-S. Can more aggressive treatment improve prognosis in patients with hepatocellular carcinoma? A direct comparison of the Hong Kong liver cancer and Barcelona clinic liver cancer algorithms Gut Liver 2018 12 1 94 101 10.5009/gnl17040 28873509
Jan Lee Y-S., et al. Can more aggressive treatment improve prognosis in patients with hepatocellular carcinoma? A direct comparison of the Hong Kong liver cancer and Barcelona clinic liver cancer algorithms. Gut Liver. 2018;12(1):94–101. 10.5009/gnl17040.28873509
20. Heimbach JK AASLD guidelines for the treatment of hepatocellular carcinoma Hepatology 2018 67 1 358 380 10.1002/hep.29086 28130846
Heimbach JK, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358–80. 10.1002/hep.29086.28130846
21. Bruix J Reig M Sherman M Evidence-based diagnosis, staging, and treatment of patients with Hepatocellular Carcinoma Gastroenterology 2016 150 4 835 53 10.1053/j.gastro.2015.12.041 26795574
Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with Hepatocellular Carcinoma. Gastroenterology. 2016;150(4):835–53. 10.1053/j.gastro.2015.12.041.26795574
22. Reig M BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update J Hepatol 2022 76 3 681 693 10.1016/j.jhep.2021.11.018 34801630
Reig M, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76(3):681–93. 10.1016/j.jhep.2021.11.018.34801630
23. Feb Yang JD. Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa liver cancer consortium Lancet Gastroenterol Hepatol 2017 2 2 103 11 10.1016/S2468-1253(16)30161-3 28403980
Feb Yang JD., et al. Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa liver cancer consortium. Lancet Gastroenterol Hepatol. 2017;2(2):103–11. 10.1016/S2468-1253(16)30161-3.28403980
24. Barsouk A Thandra KC Saginala K Rawla P Barsouk A Chemical risk factors of primary liver cancer: an update Hepat. Med. 2020 12 179 188 10.2147/HMER.S278070 33447099
Barsouk A, Thandra KC, Saginala K, Rawla P, Barsouk A. Chemical risk factors of primary liver cancer: an update. Hepat Med. 2020;12:179–88. 10.2147/HMER.S278070.33447099
25. Petrick JL Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: the liver cancer pooling project Br J Cancer 2018 118 7 1005 1012 10.1038/s41416-018-0007-z 29520041
Petrick JL, et al. Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: the liver cancer pooling project. Br J Cancer. 2018;118(7):1005–12. 10.1038/s41416-018-0007-z.29520041
26. Tanaka K Cigarette smoking and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among Japanese Jpn J Clin Oncol 2006 36 7 445 56 10.1093/jjco/hyl040 16782973
Tanaka K, et al. Cigarette smoking and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among Japanese. Jpn J Clin Oncol. 2006;36(7):445–56. 10.1093/jjco/hyl040.16782973
27. El-Zayadi AR Heavy smoking and liver World J Gastroenterol 2006 12 38 6098 101 10.3748/wjg.v12.i38.6098 17036378
El-Zayadi AR. Heavy smoking and liver. World J Gastroenterol. 2006;12(38):6098–101. 10.3748/wjg.v12.i38.6098.17036378
28. Zhang X Risk factors and prevention of viral hepatitis-related hepatocellular carcinoma Front Oncol 2021 11 686962 10.3389/fonc.2021.686962 34568017
Zhang X, et al. Risk factors and prevention of viral hepatitis-related hepatocellular carcinoma. Front Oncol. 2021;11:686962. 10.3389/fonc.2021.686962.34568017
29. Perisetti A Goyal H Yendala R Thandassery RB Giorgakis E Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: current insights and advancements World J Gastroenterol 2021 27 24 3466 3482 10.3748/wjg.v27.i24.3466 34239263
Perisetti A, Goyal H, Yendala R, Thandassery RB, Giorgakis E. Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: current insights and advancements. World J Gastroenterol. 2021;27(24):3466–82. 10.3748/wjg.v27.i24.3466.34239263
30. Jiang Y Han Q Zhao H Zhang J The mechanisms of HBV-induced hepatocellular carcinoma J. Hepatocell. carcinoma 2021 8 435 450 10.2147/JHC.S307962 34046368
Jiang Y, Han Q, Zhao H, Zhang J. The mechanisms of HBV-induced hepatocellular carcinoma. J Hepatocell carcinoma. 2021;8:435–50. 10.2147/JHC.S307962.34046368
31. Elbahrawy A Ibrahim MK Eliwa A Alboraie M Madian A Aly HH Current situation of viral hepatitis in Egypt Microbiol Immunol 2021 65 9 352 372 10.1111/1348-0421.12916 33990999
Elbahrawy A, Ibrahim MK, Eliwa A, Alboraie M, Madian A, Aly HH. Current situation of viral hepatitis in Egypt. Microbiol Immunol. 2021;65(9):352–72. 10.1111/1348-0421.12916.33990999
32. Parikh ND A comparison of Staging systems for hepatocellular carcinoma in a multicenter US cohort Clin Gastroenterol Hepatol 2018 16 5 781 2 10.1016/j.cgh.2017.10.001 28987503
Parikh ND, et al. A comparison of Staging systems for hepatocellular carcinoma in a multicenter US cohort. Clin Gastroenterol Hepatol. 2018;16(5):781–2. 10.1016/j.cgh.2017.10.001.28987503
33. Wallace MC HKLC triages more hepatocellular carcinoma patients to curative therapies compared to BCLC and is associated with better survival Dig Dis Sci 2017 62 8 2182 2192 10.1007/s10620-017-4622-y 28547649
Wallace MC, et al. HKLC triages more hepatocellular carcinoma patients to curative therapies compared to BCLC and is associated with better survival. Dig Dis Sci. 2017;62(8):2182–92. 10.1007/s10620-017-4622-y.28547649
34. Adhoute X Penaranda G Bronowicki J-P Raoul JL Usefulness of the HKLC vs. the BCLC staging system in a European HCC cohort J Hepatol 2015 62 2 492 3 10.1016/j.jhep.2014.08.035 25194894
Adhoute X, Penaranda G, Bronowicki J-P, Raoul JL. Usefulness of the HKLC vs. the BCLC staging system in a European HCC cohort. J Hepatol. 2015;62(2):492–3. 10.1016/j.jhep.2014.08.035.25194894
35. Kim JY Transarterial chemoembolization versus resection for intermediate-stage (BCLC B) hepatocellular carcinoma Clin Mol Hepatol 2016 22 2 250 8 10.3350/cmh.2016.0015 27377909
Kim JY, et al. Transarterial chemoembolization versus resection for intermediate-stage (BCLC B) hepatocellular carcinoma. Clin Mol Hepatol. 2016;22(2):250–8. 10.3350/cmh.2016.0015.27377909
36. Galle PR Tovoli F Foerster F Wörns MA Cucchetti A Jul Bolondi L The treatment of intermediate stage tumours beyond TACE: from surgery to systemic therapy J Hepatol 2017 67 1 173 83 10.1016/j.jhep.2017.03.007 28323121
Galle PR, Tovoli F, Foerster F, Wörns MA, Cucchetti A, Jul Bolondi L. The treatment of intermediate stage tumours beyond TACE: from surgery to systemic therapy. J Hepatol. 2017;67(1):173–83. 10.1016/j.jhep.2017.03.007.28323121
37. Apr Pawlik TM. Hepatectomy for hepatocellular carcinoma with major portal or hepatic vein invasion: results of a multicenter study Surgery 2005 137 4 403 10 10.1016/j.surg.2004.12.012 15800485
Apr Pawlik TM., et al. Hepatectomy for hepatocellular carcinoma with major portal or hepatic vein invasion: results of a multicenter study. Surgery. 2005;137(4):403–10. 10.1016/j.surg.2004.12.012.15800485
38. Ikai I Results of hepatic resection for hepatocellular carcinoma invading major portal and/or hepatic veins Surg Oncol Clin N Am 2003 12 1 65 75 10.1016/s1055-3207(02)00082-0 12735130
Ikai I, et al. Results of hepatic resection for hepatocellular carcinoma invading major portal and/or hepatic veins. Surg Oncol Clin N Am. ix,Jan. 2003,;12(1):65–75. 10.1016/s1055-3207(02)00082-0.12735130
39. Liu YW Liver resection of hepatocellular carcinoma within and beyond the barcelona clinic liver cancer guideline recommendations: results from a high-volume liver surgery center in East Asia J Surg Oncol 2020 122 8 1587 1594 10.1002/jso.26183 32815189
Liu YW, et al. Liver resection of hepatocellular carcinoma within and beyond the barcelona clinic liver cancer guideline recommendations: results from a high-volume liver surgery center in East Asia. J Surg Oncol. 2020;122(8):1587–94. 10.1002/jso.26183.32815189
40. Chen YS Surgical resection significantly promotes the overall survival of patients with hepatocellular carcinoma: a propensity score matching analysis BMC Gastroenterol 2021 21 1 220 10.1186/s12876-021-01807-4 33990184
Chen YS, et al. Surgical resection significantly promotes the overall survival of patients with hepatocellular carcinoma: a propensity score matching analysis. BMC Gastroenterol. 2021;21(1):220. 10.1186/s12876-021-01807-4.33990184
41. Kalva SP Safety and effectiveness of chemoembolization with drug-eluting beads for advanced-stage hepatocellular carcinoma Cardiovasc Intervent Radiol 2014 37 2 381 7 10.1007/s00270-013-0654-7 23754191
Kalva SP, et al. Safety and effectiveness of chemoembolization with drug-eluting beads for advanced-stage hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2014;37(2):381–7. 10.1007/s00270-013-0654-7.23754191
42. Kong JY Li SM Fan HY Zhang L Zhao HJ Li SM Transarterial chemoembolization extends long-term survival in patients with unresectable hepatocellular carcinoma Medicine (Baltimore) 2018 97 33 e11872 10.1097/MD.0000000000011872 30113483
Kong JY, Li SM, Fan HY, Zhang L, Zhao HJ, Li SM. Transarterial chemoembolization extends long-term survival in patients with unresectable hepatocellular carcinoma. Medicine (Baltimore). 2018;97(33):e11872. 10.1097/MD.0000000000011872.30113483
43. Dec Chang K-H. Predictive imaging for tumor response to drug-eluting microsphere transarterial chemoembolization in patients with BCLC-C advanced hepatocellular carcinoma Sci Rep 2019 9 1 20032 10.1038/s41598-019-56545-1 31882969
Dec Chang K-H., et al. Predictive imaging for tumor response to drug-eluting microsphere transarterial chemoembolization in patients with BCLC-C advanced hepatocellular carcinoma. Sci Rep. 2019;9(1):20032. 10.1038/s41598-019-56545-1.31882969
44. Chuncharunee A Siramolpiwat S Validation of the Hong Kong liver cancer staging system in patients with hepatocellular carcinoma after curative intent treatment Asian Pac J Cancer Prev 2017 18 6 1697 1701 10.22034/APJCP.2017.18.6.1697 28670891
Chuncharunee A, Siramolpiwat S. Validation of the Hong Kong liver cancer staging system in patients with hepatocellular carcinoma after curative intent treatment. Asian Pac J Cancer Prev. 2017;18(6):1697–701. 10.22034/APJCP.2017.18.6.1697.28670891
45. Liu P-H Hong Kong liver cancer staging system is associated with better performance for hepatocellular carcinoma: special emphasis on viral etiology Medicine (Baltimore) 2015 94 41 e1772 10.1097/MD.0000000000001772 26469917
Liu P-H, et al. Hong Kong liver cancer staging system is associated with better performance for hepatocellular carcinoma: special emphasis on viral etiology. Medicine (Baltimore). 2015;94(41):e1772. 10.1097/MD.0000000000001772.26469917
46. Yan X Fu X Cai C Zi X Yao H Qiu Y Validation of models in patients with hepatocellular carcinoma: comparison of Hong Kong Liver Cancer with Barcelona Clinic Liver Cancer staging system in a Chinese cohort Eur. J. Gastroenterol. Hepatol. 2015 27 10 1180 1186 10.1097/MEG.0000000000000418 26067223
Yan X, Fu X, Cai C, Zi X, Yao H, Qiu Y. Validation of models in patients with hepatocellular carcinoma: comparison of Hong Kong Liver Cancer with Barcelona Clinic Liver Cancer staging system in a Chinese cohort. Eur J Gastroenterol Hepatol. 2015;27(10):1180–6. 10.1097/MEG.0000000000000418.26067223
47. DeLong ER DeLong DM Clarke-Pearson DL Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach Biometrics 1988 44 3 837 45 10.2307/2531595 3203132
DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837–45. Available: https://www.ncbi.nlm.nih.gov/pubmed/3203132.3203132
48. Shi J Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus Ann Surg Oncol 2010 17 8 2073 80 10.1245/s10434-010-0940-4 20131013
Shi J, et al. Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus. Ann Surg Oncol. 2010;17(8):2073–80. 10.1245/s10434-010-0940-4.20131013
49. Vitale A Validation of the BCLC prognostic system in surgical hepatocellular cancer patients Transplant Proc 2009 41 4 1260 3 10.1016/j.transproceed.2009.03.054 19460533
Vitale A, et al. Validation of the BCLC prognostic system in surgical hepatocellular cancer patients. Transplant Proc. 2009;41(4):1260–3. 10.1016/j.transproceed.2009.03.054.19460533
50. May Wang J-H. The efficacy of treatment schedules according to Barcelona clinic liver cancer staging for hepatocellular carcinoma - survival analysis of 3892 patients Eur J Cancer 2008 44 7 1000 6 10.1016/j.ejca.2008.02.018 18337087
May Wang J-H., et al. The efficacy of treatment schedules according to Barcelona clinic liver cancer staging for hepatocellular carcinoma - survival analysis of 3892 patients. Eur J Cancer. 2008;44(7):1000–6. 10.1016/j.ejca.2008.02.018.18337087
51. Ishizawa T Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma Gastroenterology 2008 134 7 1908 16 10.1053/j.gastro.2008.02.091 18549877
Ishizawa T, et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology. 2008;134(7):1908–16. 10.1053/j.gastro.2008.02.091.18549877
52. Ho MC Liver resection improves the survival of patients with multiple hepatocellular carcinomas Ann Surg Oncol 2009 16 4 848 55 10.1245/s10434-008-0282-7 19159983
Ho MC, et al. Liver resection improves the survival of patients with multiple hepatocellular carcinomas. Ann Surg Oncol. 2009;16(4):848–55. 10.1245/s10434-008-0282-7.19159983
53. Sherman M Staging for hepatocellular carcinoma: complex and confusing Gastroenterology 2014 146 7 1599 602 10.1053/j.gastro.2014.04.026 24780213
Sherman M. Staging for hepatocellular carcinoma: complex and confusing. Gastroenterology. 2014;146(7):1599–602. 10.1053/j.gastro.2014.04.026.24780213
54. Li JW Goh BBG Chang PE Tan CK Barcelona clinic liver cancer outperforms hong kong liver cancer staging of hepatocellular carcinoma in multiethnic asians: real-world perspective World J Gastroenterol 2017 23 22 4054 4063 10.3748/wjg.v23.i22.4054 28652658
Li JW, Goh BBG, Chang PE, Tan CK. Barcelona clinic liver cancer outperforms hong kong liver cancer staging of hepatocellular carcinoma in multiethnic asians: real-world perspective. World J Gastroenterol. 2017;23(22):4054–63. 10.3748/wjg.v23.i22.4054.28652658
55. Lee YH A new child-turcotte-pugh class 0 for patients with hepatocellular carcinoma: determinants, prognostic impact and ability to improve the current staging systems PLoS One 2014 9 6 e99115 10.1371/journal.pone.0099115 24906132
Lee YH, et al. A new child-turcotte-pugh class 0 for patients with hepatocellular carcinoma: determinants, prognostic impact and ability to improve the current staging systems. PLoS One. 2014;9(6):e99115. 10.1371/journal.pone.0099115.24906132
56. Chapiro J Geschwind JF Hepatocellular carcinoma: have we finally found the ultimate staging system for HCC? Nat Rev Gastroenterol Hepatol 2014 11 6 334 6 10.1038/nrgastro.2014.67 24798199
Chapiro J, Geschwind JF. Hepatocellular carcinoma: have we finally found the ultimate staging system for HCC? Nat Rev Gastroenterol Hepatol. 2014;11(6):334–6. 10.1038/nrgastro.2014.67.24798199
57. Liu C Prognosis evaluation in patients with hepatocellular carcinoma after hepatectomy: comparison of BCLC, TNM and Hangzhou criteria staging systems PLoS One 2014 9 8 e103228 10.1371/journal.pone.0103228 25133493
Liu C, et al. Prognosis evaluation in patients with hepatocellular carcinoma after hepatectomy: comparison of BCLC, TNM and Hangzhou criteria staging systems. PLoS One. 2014;9(8):e103228. 10.1371/journal.pone.0103228.25133493
58. Kim BK Prospective comparison of prognostic values of modified response evaluation criteria in solid tumours with European Association for the Study of the Liver criteria in hepatocellular carcinoma following chemoembolisation Eur J Cancer 2013 49 4 826 34 10.1016/j.ejca.2012.08.022 22995582
Kim BK. Prospective comparison of prognostic values of modified response evaluation criteria in solid tumours with European Association for the Study of the Liver criteria in hepatocellular carcinoma following chemoembolisation. Eur J Cancer. 2013;49(4):826–34. 10.1016/j.ejca.2012.08.022.22995582
59. Tateishi R Proposal of a new prognostic model for hepatocellular carcinoma: an analysis of 403 patients Gut 2005 54 3 419 25 10.1136/gut.2003.035055 15710994
Tateishi R, et al. Proposal of a new prognostic model for hepatocellular carcinoma: an analysis of 403 patients. Gut. 2005;54(3):419–25. 10.1136/gut.2003.035055.15710994
