Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis

Table 1 Pre-operative demographics and baseline characteristics of the study population

	mean ± SD/ n (%)
Age in years (mean ± SD)	59.23 ± 6.52
HCV-related liver disease, n (%)	105 (87.5)
Hypertensive, n (%)	34 (28.3)
Diabetic, n (%)	36 (30)
Previous abdominal operations, n (%)	34 (28.3)
Child-Pugh class, n (%)
A5	90 (75)
A6	30 (25)
MELD score (mean ± SD)	8.54 ± 1.78
MELD score, n (%)
< 10	90 (75)
10-20	30 (25)
BCLC stage, n (%)
0	12 (10)
A	72 (60)
B	36 (30)
Pre-operative upper endoscopy
Oesophageal Varices, n (%)
No	78 (65)
Yes	42 (35)
Pre-operative imaging
Diameter of largest tumor in cm (mean ± SD)	4.57 ± 2.03
Tumor diameter > 5 cm, n (%)
No	86 (71.7)
Yes	34 (28.3)
Serum Bilirubin (mg/dL)	0.87 ± 0.34
Aspartate Aminotransferase (U/L)	53.2 ± 29.6
Alanine Aminotransferase (U/L)	44.32 ± 25.65
Serum Albumin (g/dL)	3.78 ± 0.48
International normalized ratio	1.16 ± 0.1
Serum creatinine (mg/dL)	0.86 ± 0.22
Platelets count ( 103/mm3)	141 ± 64.32
Serum AFP (ng/mL)	193.37 ± 343.37
Serum AFP (ng/mL), n (%)
< 20	52 (43.3)
20-400	30 (25)
> 400	20 (16.7)
Undocumented	18 (15)
Platelets < 150.000/mm3, n (%)	64 (53.3)
Anatomical resection, n (%)	22 (18.3)
Use of Harmonic scalpel, n (%)	40 (33.3)
Use of Habib sealer, n (%)	40 (33.3)
Use of CUSA, n (%)	2 (1.7)
Intraoperative bleeding, n (%)	4 (3.3)
Blood transfusion, n (%)	12 (10)
Plasma transfusion, n (%)	6 (5)
Grade of differentiation, n (%)
1 or 2	58 (48.3)
3 or 4	38 (31.7)
Undocumented	24 (20)
Lymph/vascular invasion, n (%)	44 (36.7)

HCV: Hepatitis C virus; MELD: Model for end-stage liver disease; BCLC: Barcelona clinic liver cancer; AFP: Alpha-fetoprotein; CUSA: Cavitron Ultrasonic Surgical Aspirator.

Table 2 Post-operative data and complications after resection in the study population

	mean ± SD/ n (%)
Serum bilirubin (mg/dL)	1.5 ± 0.64
AST (U/L)	29.95 ± 11.31
ALT (U/L)	20.51 ± 10.03
Serum albumin (g/dL)	3.21 ± 0.41
INR	1.25 ± 0.14
Serum Creatinin (mg/dL)	0.87 ± 0.23
Serum AFP (ng/mL)	2109.7 ± 10795.17
CRP (mg/L)	45.99 ± 31.19
Length of the hospital stay (d)	8.9 ± 5.05
ICU stay (d)	4.28 ± 4.19
Child-Pugh score
On discharge	6.62 ± 1.54
3-mo post-operative	6.51 ± 1.1
MELD score	10.63 ± 2.27
ICU stay, n (%)	58 (48.3)
MELD score, n (%)
≤ 10	68 (56.7)
> 10	52 (43.3)
50-50 criteria, n (%)
Absent	116 (96.7)
Present	4 (3.3)
PHLF, n (%)
Absent	76 (63.3)
Grade A	16 (13.3)
Grade B	22 (18.3)
Grade C	6 (5)
Post-operative complications, n (%)
Hemorrhage	4 (3.3)
Bile leak	2 (1.7)
Wound infection	4 (3.3)
Chest infection	14 (11.7)
Recurrence of HCC, n (%)	34 (28.3)
Post-operative decompensation, n (%)	50 (41.7)
Peri-operative mortality, n (%)	4 (3.3)
Overall survival, n (%)
Alive	70 (58.3)
Died	50 (41.7)

HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; PHLF: Post-hepatectomy liver failure; ICU: Intensive care units; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; INR: International normalized ratio; CRP: C-reactive protein.

Table 3 Univariate analysis of pre-operative, operative and post-operative factors predictive of hepatic decompensation after liver resection for hepatocellular carcinoma (calculated at 3 mo post-operative)

	No decompensation (70 patients)	Decompensation (50 patients)		P value
Age, n (%)
< 60 yr	36 (58.1)	26 (41.9)	0.004	0.951
≥ 60 yr	34 (58.6)	24 (41.0)
Antiviral therapy for HCV, n (%)
No treatment	34 (46.6)	39 (53.4)	29.143	< 0.001c
DAAs	34 (82.9)	7 (17.1)
Interferon	2 (33.3)	4 (66.7)
Clinically significant portal hypertension, n (%)
No	52 (66.7)	26 (33.3)	7.7	0.006b
Yes	17 (40.5)	25 (59.5)
BCLC stage, n (%)
0	12 (100)	0 (0)	40.0	< 0.001c
A	52 (72.2)	20 (27.8)
B	6 (16.7)	30 (83.3)
MELD score, n (%)
< 10	60 (68.2)	28 (31.8)	22.721	< 0.001c
10-20	4 (15.4)	22 (84.6)
Pre-operative Child-Pugh score, n (%)
A5	54 (60)	36 (40)	0.411	0.521
A6	16 (53.3)	14 (46.7)
AFP (ng/mL), n (%)
< 20	30 (57.7)	22 (42.3)	3.509	0.173
20-400	20 (66.7)	10 (33.3)
> 400	8 (40)	12 (60)
Pre-operative serum bilirubin (mg/dL), n (%)
≤ 1	46 (57.5)	34 (42.5)	0.201	0.654
> 1	18 (52.9)	16 (47.1)
Tumor diameter > 5 cm, n (%)
No	64 (74.4)	22 (25.6)	32.311	< 0.001c
Yes	6 (17.6)	28 (82.4)
Number of tumors, n (%)
Single	68 (60.7)	44 (39.3)	5.869	0.027a
More than one	0 (0)	4 (100)
Site of tumor(s), n (%)
Right lobe	36 (62.1)	22 (37.9)	1.626	0.443
Left lobe	32 (57.1)	24 (42.9)
Bilobar	2 (100)	0 (0)
Milan criteria, n (%)
Within	36 (69.2)	16 (30.8)	15.537	< 0.001c
Beyond	8 (25)	24 (75)
Tumor differentiation, n (%)
Grade 1 or 2	38 (63.3)	22 (36.7)	1.646	0.2
Grade 3 or 4	18 (50)	18 (50)
Lymph/vascular invasion, n (%)
No	38 (70.4)	16 (29.6)	8.593	0.003b
Yes	18 (40.9)	26 (59.1)
Type of resection, n (%)
Open	28 (42.4)	38 (57.6)	13.473	< 0.001c
Laparoscopic	12 (100)	0 (0)
Anatomical resection, n (%)
No	38 (57.6)	28 (42.4)	0.978	0.323
Yes	10 (45.5)	12 (54.5)
Extension of hepatectomy, n (%)
One segment	30 (51.7)	28 (48.3)	2.241	0.326
Two segments	8 (44.4)	10 (55.6)
Three segments	2 (100)	0 (0)
ICU admission, n (%)
No	44 (71)	18 (29)	8.425	0.004b
Yes	26 (44.8)	32 (55.2)
Postoperative complications, n (%)
Hemorrhage	4 (100)	0 (0)	2.956	0.14
Bile leak	0 (0)	2 (100)	2.847	0.172
Wound infection	0 (0)	4 (100)	5.793	0.028a
Chest infection	2 (14.3)	12 (85.7)	12.652	< 0.001c
PHLF, n (%)
Absent	54 (71.1)	22 (28.9)	22.305	< 0.001c
Grade A	10 (62.5)	6 (37.5)
Grade B	6 (27.3)	16 (72.7)
Grade C	0 (0)	6 (100)
50-50 criteria, n (%)
Absent	70 (60.3)	46 (39.7)	5.793	0.028a
Present	0 (0)	4 (100)
HCC recurrence, n (%)	16 (47.1)	18 (52.9)	2.481	0.115
	No decompensation	Decompensation	t-test	P value
	mean ± SD
Post-operative bilirubin (mg/dL)	1.21 ± 0.49	1.98 ± 0.57	-7.353	< 0.001c
Post-operative AFP (ng/mL)	3020.12 ± 13277.79	371.63 ± 761.79	0.931	0.355
Post-operative Child-Pugh score	5.78 ± 0.65	7.62 ± 0.58	-14.768	< 0.001c
Age	58.77 ± 6.68	59.88 ± 6.29	-0.918	0.36
Pre-operative Bilirubin (mg/dL)	0.87 ± 0.31	0.87 ± 0.38	0.007	0.994
Pre-operative MELD score	8.03 ±1.44	9.2 ± 1.96	-3.541	0.001b
Pre-operative Child score	5.23 ± 0.42	5.28 ± 0.45	-0.637	0.525
Pre-operative AFP (ng/mL)	149.58 ± 239.28	251.09 ± 441.64	-1.379	0.173
Tumor diameter (cm)	3.77 ± 1.32	5.68 ± 2.33	-5.238	< 0.001c
ICU stay (d)	2.92 ± 1.35	5.38 ± 5.29	-2.522	0.016a
Hospital stay (d)	6.86 ± 2.08	11.26 ± 6.34	-4.092	< 0.001c
Post-operative bilirubin (mg/dL)	1.21 ± 0.49	1.98 ± 0.57	-7.353	< 0.001c
Post-operative AFP (ng/mL)	3020.12 ± 13277.79	371.63 ± 761.79	0.931	0.355
Post-operative Child-Pugh score	5.78 ± 0.65	7.62 ± 0.58	-14.768	< 0.001c

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

AFP: Alpha-fetoprotein; BCLC: Barcelona clinic liver cancer; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; PHLF: Post-hepatectomy liver failure; ICU: Intensive care units; HCV: Hepatitis C virus; DAAs: Direct-acting antiviral agents.

Table 4 Multivariate analysis of factors predictive of hepatic decompensation after resection

	OR	95%CI	P value
Age	1.09	0.96-1.25	0.184
Preoperative MELD score	2.65	1.23-5.72	0.013a
Preoperative serum bilirubin	0.15	0.01-3.63	0.242
Clinically significant portal hypertension
No	Reference	Reference	0.191
Yes	4.39	0.48-40.25
Tumor diameter (cm)	5.42	1.99-14.77	0.001b
Hospital stay (d)	2.49	1.46-4.22	0.001b
ICU admission
No	Reference	Reference	0.448
Yes	0.42	0.05-3.92

^aP < 0.05.

^bP < 0.01.

CI: Confidence interval; MELD: Model for end-stage liver disease; OR: Odds ratio; ICU: Intensive care units.

Table 5 Univariate survival analysis of the predictors of survival in study population

	Mean survival time (mo)	95%CI	Log-rank test	P value
Clinically significant portal hypertension
No	40.6	35.3-46	0.551	0.458
Yes	39.5	30.9-48.1
Preoperative AFP > 400 ng/mL
No	43.9	38.3-49.5	8.787	0.003b
Yes	24.6	14.1-35.2
Preoperative MELD score
< 10	46.38	41.13-51.63	19.209	< 0.001c
10-20	22.55	13.44-31.65
BCLC stage
0	51.9	40.5-63.2	22.328	< 0.001c
A	47.9	42.1-53.6
B	26.1	18.3-33.8
PHLF
No	47.1	41.4-52.8	8.489	0.004b
Yes	32.1	24.8-39.4
PHLF grade
Absent	47.1	41.4-52.8	114.117	< 0.001c
A	42.2	30.4-53.9
B	31.7	23-40.4
C	2.1	0.5-3.6
50-50 criteria
Absent	43.6	38.8-48.3	156.853	< 0.001c
Present	0.8	0.7-0.8
Post-operative MELD score
≤ 10	49.3	43.4-55.3	12.29	< 0.001c
> 10	32.7	25.8-39.7
Post-operative decompensation
No	52.2	47.1-57.4	27.716	< 0.001c
Yes	28.3	21.1-35.5
HCC recurrence
No	53.3	48.7-57.9	69.639	< 0.001c
Yes	13.2	9.6-16.8

^bP < 0.01.

^cP < 0.001.

AFP: Alpha-fetoprotein; BCLC: Barcelona clinic liver cancer; CI: Confidence interval; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; PHLF: Post-hepatectomy liver failure.

Table 6 Multivariate analysis of independent prognostic factors for the survival of patients after the liver resection surgery for hepatocellular carcinoma

	HR	95%CI	P value
Age (yr)	1.02	0.96-1.08	0.493
Preoperative MELD score	1.37	1.16-1.62	< 0.001c
Preoperative AFP (ng/mL)	1.001	1-1.002	0.08
BCLC stage
0	Reference	Reference	0.757
A	0.59	0.12-2.91
B	0.45	0.06-3.65
PHLF grade
Absent	Reference	Reference	< 0.001c
A	2.33	0.59-9.24
B	3.15	1.11-8.95
C	373.41	66.23-2105.43
Postoperative MELD score > 10	1.03	0.39-2.67	0.958
Postoperative decompensation	2.03	0.64-6.46	0.23
HCC recurrence	11.67	4.19-32.52	< 0.001c

^cP < 0.001.

AFP: alpha-fetoprotein; BCLC: Barcelona clinic liver cancer; CI: Confidence interval; HCC: Hepatocellular carcinoma; HR: Hazard ratio; MELD: Model for end-stage liver disease; PHLF: Post-hepatectomy liver failure.