Surgical Resection is An Effective Therapy for Single Large Hepatocellular Carcinom

doi:10.21203/rs.3.rs-909527/v1

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Surgical Resection is An Effective Therapy for Single Large Hepatocellular Carcinom

https://doi.org/10.21203/rs.3.rs-909527/v1

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Background

Identifying prognostic factors and therapeutic strategies for single large hepatocellular carcinoma (HCC) is crucial. This retrospective study investigated prognostic factors in patients with single large HCC (≥5 cm) and Child–Pugh (CP) class A liver disease and recommended therapeutic strategies.

Methods

In total, 305 patients with single large HCC and CP class A liver disease but without distant metastasis or macrovascular invasion were included. Their clinicopathological data, overall survival (OS), and progression-free survival (PFS) were recorded. OS and PFS rates were analyzed using the Kaplan–Meier method and Cox regression analysis.

Results

In this study, 77.8% of the patients were men; the median age was 63 years. Approximately 34.1% of the patients had cirrhosis and 89.6% had CP class A5 disease. The most common initial treatment was resection (49.5%), followed by transarterial chemoembolization (TACE; 48.2%). OS and PFS rates 1, 5, and 10 years after initial treatment were 88.6%, 58.0%, and 46.8% and 73.6%, 48.2%, and 31.3%, respectively. OS and PRS rates were significantly higher in patients receiving surgical resection than in those receiving TACE. The 1-, 5-, and 10-year OS rates were 94.6%, 76.7%, and 66.7% after resection and 83.1%, 39.0%, and 26.6% after TACE. The 1-, 5-, and 10-year PRS rates were 82.5%, 55.7%, and 51.0% after resection and 64.3%, 40.5%, and 22.7% after TACE. In multivariate analysis, CP class A5/6 (A5 vs. A6; hazard ratio [HR]: 0.23; 95% confidence interval [CI]: 0.15–0.38, P < 0.001) and initial treatment (resection vs. TACE; HR: 0.22; 95% CI: 0.15–0.36, P < 0.001; resection vs. other treatments; HR: 0.37; 95% CI: 0.17–0.65, P = 0.016) were significantly associated with OS. In addition, CP class A5/6 (A5 vs. A6; HR: 0.32; 95% CI: 0.18–0.56, P < 0.001) and initial treatment (resection vs. TACE; HR: 0.30; 95% CI: 0.16–0.51, P < 0.001; resection vs. other treatments; HR: 0.51; 95% CI: 0.26–0.81, P = 0.042) were significantly associated with PFS.

Conclusion

Surgical resection achieved significantly higher OS and PRS rates than TACE. Surgical resection is an effective and safe therapy for single large HCC.

Gastroenterology & Hepatology

Surgical resection

large hepatocellular carcinoma

overall survival

progression-free survival

prognosis

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of cancer-related death worldwide [1–5]. Although HCC surveillance with alpha-fetoprotein (AFP) and ultrasound is recommended in patients at risk of HCC [3–5], the proportion of HCC that is large at diagnosis is still high [6]. Liver resection has been reported to promote overall survival (OS) in patients with HCC across various Barcelona Clinic Liver Cancer (BCLC) stages [7, 8]. In 2012, the BCLC system designated a single large HCC (>5 cm) as BCLC stage A rather than stage B [9]. The revised BCLC classification schema has been endorsed by the American Association for the Study of Liver Diseases (AASLD) [3] and the European Association for the Study of the Liver [4]. Furthermore, the most recent version of the 2017 combined American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis staging system states that patients with multiple tumors, any of which are >5 cm, can be classified as T3 [10]. Recent studies have reported that approximately two-thirds of patients with tumor size >10 cm present microvascular invasion; more favorable outcomes have been reported after resection in these patients; thus, surgical resection should be considered for single large HCC [6, 11]. Several studies have also demonstrated that liver resection is a safe and effective treatment for single large HCC [12–17]. However, these studies had limitations, such as limited data availability, lack of comparison with different treatments, and/or selection bias. The treatment for single large HCC (≥5 cm) still remains largely unknown and needs to be studied further. This study investigated prognostic factors and effective therapies for single large HCC.

Patients and follow-up

We retrospectively enrolled 4092 HCC patients from 2007 to 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. In total, we excluded 3787 patients due to multiple tumors, tumor size <5 cm, presence of macrovascular invasion and/or distal metastasis, or Child–Pugh (CP) classes B and C. Ultimately, 305 patients with HCC and CP class A liver disease, a single tumor ≥5 cm, and no macrovascular invasion and/or distal metastasis were included in this retrospective study (Fig. 1). This study was approved by the Institutional Review Board at E-Da Hospital.

HCC was diagnosed based on histology or typical imaging methods on the basis of the guideline of the AASLD [18]. Demographic characteristics, etiology, blood tests, CP class, cirrhotic of liver, tumor size, AFP, mortality, disease progression, and follow-up time, were recorded. Tumor size and number were determined according to pathological confirmation and radiologic findings. Patients were treated with surgical resection, transarterial chemoembolization (TACE), hepatic artery infusion chemotherapy (HAIC), or liver transplantation. Our multidisciplinary team chose suitable therapies for each patient. Patients were followed up every 3 to 6 months by abdominal ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI), and AFP. OS and PFS was defined as the time from the date of diagnosis to the date of death and disease progression or the last visit; the last follow-up date was December 2020.

Data analysis and statistics

Numerical data are shown using medians and ranges. Categorical data are shown as numbers and percentages. OS and PFS rates were used by the Kaplan–Meier method. OS and PFS rates was analyzed by Cox proportional hazards regression. A P value of <0.05 was considered statistically significant. All statistical analyses were performed using SPSS 23.0 (SPSS, Chicago, IL, USA).

Baseline characteristics

The demographic and clinical features of 305 patients with HCC and CP class A disease (77.8% male, median age 63 years) with single large tumors (≥5 cm) but without distant metastasis and/or macrovascular invasion are listed in Table 1. Regarding the etiology of HCC, 44.1% of the patients had hepatitis B virus (HBV) infection, 23.0% had hepatitis C virus (HCV) infection, and 30.9% had neither HBV nor HCV. Approximately 34.1% of patients had liver cirrhosis, and 89.6% had CP class A5 disease. The most common initial treatment modality was resection (49.5%), followed by TACE (48.2%), HAIC (1.3%), and liver transplantation (1%). The median follow-up time was 33 months.

OS and PFS rates in all patients

Kaplan–Meier analysis demonstrated that the 1-, 3-, 5-, and 10-year OS rates after initial treatment were 88.6%, 66.7%, 58.0%, and 46.8%, respectively (Fig. 2A), and the 1-, 3-, 5-, and 10-year PFS rates were 73.6%, 56.9%, 48.2%, and 31.3%, respectively (Fig. 2B). OS and PRS rates were significantly higher in patients receiving surgical resection than those receiving TACE, HAIC, or liver transplantation. The 1-, 3-, 5-, and 10-year OS rates were 94.6%, 82.4%, 76.7%, and 66.7% after resection and 83.1%, 50.1%, 39.0%, and 26.6% after TACE, respectively (P < 0.001, Fig. 3A). The 1-, 3-, 5-, and 10-year PRS rates were 82.5%, 66.8%, 55.7%, and 51.0% after resection and 64.3%, 47.2%, 40.5%, and 22.7% after TACE, respectively (P < 0.001, Fig. 3B).

Factors affecting OS and PFS

Sex, hypertension, CP class A5/6, ALT, AFP, tumor size ≥10 cm, and initial treatment were significantly associated with OS in univariate analysis (Table 2). Furthermore, in multivariate analysis, CP class A5/6 (A5 vs. A6; hazard ratio [HR]: 0.23; 95% confidence interval [CI]: 0.15–0.38, P < 0.001) and initial treatment (resection vs. TACE; HR: 0.22; 95% CI: 0.15–0.36, P < 0.001; resection vs. other treatments; HR: 0.37; 95% CI: 0.17–0.65, P = 0.016) remained significantly associated with OS (Table 2). Furthermore, CP class A5/6, total bilirubin, INR, AFP, and initial treatment were significantly associated with PFS in univariate analysis (Table 2). Moreover, in multivariate analysis, CP class A5/6 (A5 vs. A6; HR: 0.32; 95% CI: 0.18–0.56, P < 0.001) and initial treatment (resection vs. TACE; HR: 0.30; 95% CI: 0.16–0.51, P < 0.001; resection vs. other treatments; HR: 0.51; 95% CI: 0.26–0.81, P = 0.042) remained significantly associated with PFS (Table 2).

OS in subgroup analysis

OS and PRS rates were significantly higher in patients with CP class A5 than in those with CP class A6 (P < 0.001, Figs. 4A-B). Of the 147 patients who underwent TACE as the initial treatment, 13 underwent resection as the secondary treatment. Their OS rates was similar to that of patients who underwent resection as the initial treatment (P = 0.241; Fig. 4C). In subgroup analysis in patients with CP class A5/6, no significant difference was observed in OS rates between resection and TACE as the initial treatment in patients with CP class A5 or A6 (all P > 0.05; Fig. 4D).

Our study demonstrated that OS and PRS rates were significantly higher in patients receiving surgical resection than in those receiving TACE. The 10-year OS rates after surgical resection and TACE were 66.7% and 26.6%, respectively. The 10-year PFS rates after surgical resection and TACE were 51.0% and 22.7%, respectively. CP class A5/6 and initial treatment were significantly associated with OS and PFS in multivariate analysis. Surgical resection is a safe and effective treatment for single large HCC.

Surgical resection is widely used as the first-line therapy in patients with HCC with favorable liver function and tumor factors [19, 20]. Previous studies have reported that hepatic resection in patients with CP class A resulted in favorable outcomes, with a 5-year OS rate of over 60% and a 5-year PFS rate of over 40% [12, 21, 22]. Our study demonstrated that 151 patients (49.5%) underwent surgical resection and showed higher 5-year OS rates (76.7%) and PFS (55.7%) rates. This is consistent with previous findings of a comparable prognosis in patients with large HCC, and hepatectomy can be considered regardless of tumor size [6, 11]. Previous studies have reported that patients receiving surgical resection had higher OS rates than those receiving TACE among patients with BCLC stage B HCC [8, 23]. Recently, several studies have reported a survival benefit for liver resection in patients with BCLC stage B HCC [16, 17, 24–27]. Our study finding is also consistent with that of a previous study demonstrating that surgical resection is significantly associated with higher OS and PFS than TACE [12].

Thirteen patients received resection as secondary treatment after TACE. Their OS rates were similar to that of patients who underwent resection as the initial treatment, suggesting that hepatectomy after TACE may be another choice for patients with single large HCC. This finding is similar to that of studies reporting that resection after TACE may be considered an effective treatment in patients with BCLC stage B HCC [28, 29].

CP class was significantly associated with OS in patients with different BCLC stages of HCC [3–5]. Our study demonstrated that CP class A5 was significantly associated with higher OS and PFS rates in patients with single large HCC in multivariate analysis. Our results differed from those of previous studies reporting no significant difference in OS or PFS between CP class A5 and A6 patients with single large HCC in multivariate analysis [12]. To the best of our knowledge, our study is the first to reveal that CP class A5 is significantly associated with OS and PFS in patients with single large HCC.

Limitations of the study include the following: First, the retrospective nature of the study might have resulted in unintended bias. Second, PFS may be biased, especially in patients receiving noncurative therapies.

Surgical resection was associated with significantly higher OS and PRS rates than TACE. CP class A5/6 and initial treatment were significantly associated with OS and PFS. Surgical resection is an effective and safe therapy for single large HCC.

HCC

Hepatocellular carcinoma

BCLC

Barcelona Clinic Liver Cancer

AASLD

American Association for the Study of Liver Disease

TACE

Transarterial chemoembolization

HAIC

Hepatic artery infusion chemotherapy

Overall survival

PFS

Progression-free survival

C-P class

Child–Pugh class

Hazard ratio

Confidence interval

Ethics approval and consent to participate

The study was conducted in accordance with the guidelines of the International Conference on Harmonization for Good Clinical Practice and was approved by the Ethics Committee of E-Da Hospital, I-Shou University (EMRP-107-130). The consent for study participation is informed and signed.

Consent for Publication

Not applicable.

Availability of data and material

Data is available from the corresponding author upon reasonable request.

Competing interests

None declared.

Funding

This study was supported by grants from MOST (110-2314-B-214-004-MY1), NHRI-109BCCO-MF202016-03, National Cheng Kung University-E-Da Hospital Joint Research Program (NCKUEDA10803 and NCKUEDA10916), and E-Da Hospital (EDAHP108036, EDAHP108037, EDAHP108038, EDPJ109025, EDPJ109072, EDDHM109001, EDAHP110035, EDAHP110036, EDAHP110037, and EDAHP110040) to Chih-Wen Lin. The funders had a role in study design, decision to publish and preparation of the manuscript. No additional external funding was received for this study.

Authors’ contributions

PH, JHY and CMH: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; HYL, TQT, PNC, KCH, PMH, and YSC: study concept and design; critical revision of the manuscript for important intellectual content; administrative, technical, or material support; CWL: study concept and design; analysis and interpretation of data; critical revision of the manuscript for important intellectual content administrative, technical, or material support; study supervision. All authors approved the final version of the manuscript.

Acknowledgements

We thank Yu-Chan Li and Huang Ya Ling to collected the data.

This manuscript was edited by Wallace Academic Editing.

Author information

Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan.

Pojen Hsiao, Jen-Hao Yeh, TaoQian Tan & Chih-Wen Lin

Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung 807, Taiwan.

Pojen Hsiao, Jen-Hao Yeh, TaoQian Tan & Chih-Wen Lin

Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan.

Chih-Wen Lin

School of Medicine, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan.

Pojen Hsiao, Jen-Hao Yeh, Chao-Ming Hung, Hung-Yu Lin, Pei-Min Hsieh, Yaw-Sen Chen, & Chih-Wen Lin

Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan.

Chao-Ming Hung, Hung-Yu Lin, Kun-Chou Hsieh, Pei-Min Hsieh & Yaw-Sen Chen

School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan.

Chih-Wen Lin

Research Center for Traditional Chinese Medicine, China Medical University Hospital, Taichung 404, Taiwan.

Chih-Wen Lin

Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 704, Taiwan;

Pin-Nan Cheng

Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021; 7(1):6.
McGlynn KA, Petrick JL, El-Serag HB Epidemiology of Hepatocellular Carcinoma. Hepatology. 2021; 73 Suppl 1:4–13.
Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM 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.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018; 69(1):182–236.
Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017; 11(4):317–70.
Hwang S, Lee YJ, Kim KH, Ahn CS, Moon DB, Ha TY et al. Long-Term Outcome After Resection of Huge Hepatocellular Carcinoma >/= 10 cm: Single-Institution Experience with 471 Patients. World J Surg. 2015; 39(10):2519–28.
Vitale A, Burra P, Frigo AC, Trevisani F, Farinati F, Spolverato G et al. Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona Clinic Liver Cancer stages: a multicentre study. J Hepatol. 2015; 62(3):617–24.
Lin CW, Chen YS, Lo GH, Hsu YC, Hsu CC, Wu TC et al. Comparison of overall survival on surgical resection versus transarterial chemoembolization with or without radiofrequency ablation in intermediate stage hepatocellular carcinoma: a propensity score matching analysis. BMC Gastroenterol. 2020; 20(1):99.
European Association For The Study Of The L, European Organisation For R, Treatment Of C EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012; 56(4):908–43.
Eighth Edition Updates and Corrections. Ajcc Cancer Staging Manual. 2017.
Zhou YM, Li B, Xu DH, Yang JM Safety and efficacy of partial hepatectomy for huge (>/=10 cm) hepatocellular carcinoma: a systematic review. Med Sci Monit. 2011; 17(3):RA76-83.
Hong SK, Lee KW, Hong SY, Suh S, Hong K, Han ES et al. Efficacy of Liver Resection for Single Large Hepatocellular Carcinoma in Child-Pugh A Cirrhosis: Analysis of a Nationwide Cancer Registry Database. Front Oncol. 2021; 11:674603.
Fang KC, Kao WY, Su CW, Chen PC, Lee PC, Huang YH et al. The Prognosis of Single Large Hepatocellular Carcinoma Was Distinct from Barcelona Clinic Liver Cancer Stage A or B: The Role of Albumin-Bilirubin Grade. Liver Cancer. 2018; 7(4):335–58.
Zhong JH, Rodriguez AC, Ke Y, Wang YY, Wang L, Li LQ Hepatic resection as a safe and effective treatment for hepatocellular carcinoma involving a single large tumor, multiple tumors, or macrovascular invasion. Medicine (Baltimore). 2015; 94(3):e396.
Noh JH, Kim TS, Ahn KS, Kim YH, Kang KJ Prognostic factors after hepatic resection for the single hepatocellular carcinoma larger than 5 cm. Ann Surg Treat Res. 2016; 91(3):104–11.
Yang XD, Pan LH, Wang L, Ke Y, Cao J, Yang C et al. Systematic Review of Single Large and/or Multinodular Hepatocellular Carcinoma: Surgical Resection Improves Survival. Asian Pac J Cancer Prev. 2015; 16(13):5541–7.
Liu YW, Lin CC, Yong CC, Wang CC, Chen CL, Wang JH et al. Prognosis after resection of single large hepatocellular carcinoma: Results from an Asian high-volume liver surgery center. PLoS One. 2020; 15(3):e0230897.
Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018; 67(1):358–80.
Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM et al. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg. 2001; 234(1):63–70.
Lang H, Sotiropoulos GC, Domland M, Fruhauf NR, Paul A, Husing J et al. Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis. Br J Surg. 2005; 92(2):198–202.
Chen HY, Juan CC, Ker CG Laparoscopic liver surgery for patients with hepatocellular carcinoma. Ann Surg Oncol. 2008; 15(3):800–6.
Yin Z, Fan X, Ye H, Yin D, Wang J Short- and long-term outcomes after laparoscopic and open hepatectomy for hepatocellular carcinoma: a global systematic review and meta-analysis. Ann Surg Oncol. 2013; 20(4):1203–15.
Lin CT, Hsu KF, Chen TW, Yu JC, Chan DC, Yu CY et al. Comparing hepatic resection and transarterial chemoembolization for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma: change for treatment of choice? World J Surg. 2010; 34(9):2155–61.
Zhong JH, Ke Y, Wang YY, Li LQ Liver resection for patients with hepatocellular carcinoma and macrovascular invasion, multiple tumours, or portal hypertension. Gut. 2015; 64(3):520–1.
Zhong JH, Ke Y, Gong WF, Xiang BD, Ma L, Ye XP et al. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma. Ann Surg. 2014; 260(2):329–40.
Kim H, Ahn SW, Hong SK, Yoon KC, Kim HS, Choi YR et al. Survival benefit of liver resection for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma. Br J Surg. 2017; 104(8):1045–52.
Chen YS, Hsieh PM, Lin HY, Hung CM, Lo GH, Hsu YC 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.
Lee HS, Kim KM, Yoon JH, Lee TR, Suh KS, Lee KU et al. Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study. J Clin Oncol. 2002; 20(22):4459–65.
Chen J, Lai L, Lin Q, Huang W, Cai M, Zhu K et al. Hepatic resection after transarterial chemoembolization increases overall survival in large/multifocal hepatocellular carcinoma: a retrospective cohort study. Oncotarget. 2017; 8(1):408–17.

Table 1

Basic demographic and clinical characteristics of the included patients.
Variables	Total patients
Demographic variables
Age (years)	63 (23-92)
Sex: Male	240 (78.70
BMI (kg/m²)	25.1 (15.9-38.9)
Diabetes	60 (19.7)
Hypertension	51 (16.7)
Smoking	84 (27.5)
Alcohol use	56 (18.4)
Etiology
Non-B Non-C	94 (30.9)
HBV positive	134 (44.1)
HCV positive	70 (23.0)
HBV+HCV	6 (2.0)
Cirrhosis	104 (34.1)
Child-Pugh class A5/A6	272/33 (89.2/10.8)
Antiviral therapy	98 (32.1)
Laboratory variable
Platelet count (10⁹/L)	173 (62-401)
Total Bilirubin (mg/dL)	0.9 (0.1-2.9)
Serum albumin (g/dL)	4.1 (3.1-4.8)
AST (IU/L)	53 (16-259)
ALT (IU/L)	54 (13-403)
INR	1.1 (0.9-2.8)
Creatinine (mg/dL)	1.2 (0.5-8.2)
Alpha-fetoprotein (ng/mL)	1138 (2-101685)
Tumor variable	126 (42.0)
Maximum tumor size (cm)	7.6 (5.0-18.4)
Treatment variable	279 (93.0)
Initial treatment	21 (7.0)
Resection	151 (49.5)
TACE	147 (48.2)
HAIC	4 (1.3)
Liver transplantation	3 (1.0)
Data are shown as number (%) or median (range). BMI: Body mass index; HBV: Hepatitis B virus; HCV: Hepatitis C virus; AST: Aspartate Transaminase; ALT: Alanine aminotransferase; INR: International Normalized Ratio; TACE: Transarterial chemoembolization; HAIC: Hepatic artery infusion chemotherapy;

Table 2

Univariate and multivariate analyses of factors associated with overall survival and progression-free survival.
Demographic variables	N=305	Overall survival			Progression-free survival
		Univariate	Multivariate		Univariate	Multivariate
		P-value	HR (95% CI)	P-value	P-value	HR (95% CI)	P-value
Age (years)
< 60	99	1			1
≥ 60	206	0.977			0.381
Gender
Female	65	1	1		1
Male	240	0.030	0.91 (0.57-1.45)	0.672	0.682
BMI (kg/m²)
< 25	172	1			1
≥ 25	133	0.400			0.522
Diabetes
Absent	254	1			1
Present	51	0.091			0.690
Hypertension
Absent	245	1	1		1
Present	60	0.032	1.38 (0.78-2.38)	0.256	0.437
Smoking
Absent	221	1			1
Present	84	0.996			0.299
Alcohol use
Absent	249	1			1
Present	56	0.375			0.574
Etiology
Non-B Non-C	94	1			1
HBV positive	134	0.133			0.243
HCV positive	70	0.952			0.786
HBV+HCV	6	0.787			0.167
Cirrhosis
Absent	201	1			1
Present	104	0.192			0.668
Child-Pugh class
A5	272	1	1		1	1
A6	33	<0.001	0.23 (0.15-0.38)	<0.001	<0.001	0.32 (0.18-0.56)	<0.001
Antiviral therapy
Absent	207	1			1
Present	98	0.656			0.360
Laboratory variable
Platelet count (10⁹/L)
< 150	131	1			1
≥ 150	174	0.837			0.655
Total Bilirubin (mg/dL)
< 1.2	238	1			1	1
≥ 1.2	67	0.276			0.005	0.62 (0.31-1.25)	0.095
Serum albumin (g/dL)
< 3.5	14	1			1
≥ 3.5	291	0.329			0.971
AST (IU/L)
< 50	179	1	1		1
≥ 50	172	0.041	0.72 (0.48-1.07)	0.105	0.347
ALT (IU/L)
< 50	198	1			1
≥ 50	107	0.102			0.846
INR
< 1.2	282	1			1	1
≥ 1.2	23	0.057			<0.001	1.78 (0.33-1.22)	0.177
Creatine (mg/dL)
< 1.1	105	1			1
≥ 1.1	200	0.971			0.617
Alpha-fetoprotein (ng/mL)
< 200	256	1	1		1	1
≥ 200	49	0.015	0.55 (0.52-1.11)	0.068	0.004	0.72 (0.43-1.16)	0.181
Tumor variable
Maximum tumor size (cm)
< 10	256	1	1		1
≥ 10	49	0.038	1.28 (0.68-2.32)	0.440	0.645
Treatment variable
Initial treatment
Resection	151	1	1		1	1
TACE	147	<0.001	0.22 (0.15-0.36)	<0.001	<0.001	0.30 (0.16-0.51)	<0.001
Others	7	0.011	0.37 (0.17-0.65)	0.016	0.033	0.51 (0.26-0.81)	0.042
HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; HBV: Hepatitis B virus; HCV: Hepatitis C virus; AST: Aspartate Transaminase; ALT: Alanine aminotransferase; INR: International Normalized Ratio; TACE: Transarterial chemoembolization; HAIC: Hepatic artery infusion chemotherapy;

No competing interests reported.

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Surgical Resection is An Effective Therapy for Single Large Hepatocellular Carcinom

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