Preoperative aspartate aminotransferase-to-platelet-ratio index as a predictor of posthepatectomy liver failure for resectable hepatocellular carcinoma

Figures & data

Table 1 Baseline characteristics of the included 1,044 patients with HCC and comparison of factors between patients with or without PHLF

Characteristics	All patients (n=1,044)	PHLF		P-value
		No (n=831)	Yes (n=213)
Age, ≥60/<60 years	211 (20.2%)/833 (79.8%)	161 (19.4%)/670 (80.6%)	50 (23.5%)/163 (76.5%)	0.184
Sex, male/female	899 (86.1%)/145 (13.9%)	704 (84.7%)/127 (15.3%)	195 (91.5%)/18 (8.5%)	0.010
HBsAg, positive/negative	919 (88.0%)/125 (12.0%)	725 (87.2%)/106 (12.8%)	194 (91.1%)/19 (8.9%)	0.124
HBV DNA >2,000/≤2,000 IU/mL	598 (57.3%)/446 (42.7%)	450 (54.2%)/381 (45.8%)	148 (69.5%)/65 (30.5%)	<0.001
Plt count (10^9/L)	208.0 (162.8–269.0)	214.0 (172.9–277.0)	174.0 (230.3–247.0)	<0.001
TBil (μmol/L)	11.8 (8.8–16.1)	11.1 (8.3–15.0)	15.6 (11.7–19.7)	<0.001
PA (mg/L)	184.0 (137.0–231.0)	192.5 (144.0–239.3)	148.0 (114.0–197.0)	<0.001
Alb (g/L)	40.5±4.6	40.6±4.5	39.0±4.5	<0.001
ALT (U/L)	34.0 (23.0–48.0)	32.0 (22.0–45.0)	43.0 (29.0–63.0)	<0.001
AST (U/L)	38.0 (29.0–56.0)	35.0 (28.0–51.0)	54.0 (36.0–74.0)	<0.001
BUN (mmol/L)	4.9 (4.1–5.9)	4.9 (4.1–5.8)	4.8 (3.9–5.9)	0.824
Cre (μmol/l)	78.0 (68.0–89.0)	78.0 (68.0–89.0)	77.0 (68.0–87.0)	0.047
PT (seconds)	12.8 (12.1–13.7)	12.7 (12.0–13.5)	13.4 (12.6–14.4)	<0.001
INR	1.0 (1.0–1.1)	1.0 (1.0–1.1)	1.1 (1.0–1.2)	<0.001
AFP ≥400/<400 (ng/mL)	466 (44.6%)/578 (55.4%)	361 (43.4%)/470 (56.6%)	105 (49.3%)/108 (50.7%)	0.140
Ascites	95 (9.1%)	66 (7.9%)	29 (13.6%)	0.010
CSPH	88 (8.4%)	59 (7.1%)	29 (13.6%)	0.002
Child–Pugh score	5 (5–5)	5 (5–5)	5 (5–5)	<0.001
MELD score	4 (2–6)	4 (2–6)	6 (4–8)	<0.001
ALBI score	−2.74 (−2.97 to −2.44)	−2.79 (−2.99 to −2.51)	−2.53 (−2.85 to −2.22)	<0.001
APRI score	0.48 (0.32–0.76)	0.42 (0.30–0.65)	0.79 (0.51–1.22)	<0.001
Cirrhosis	424 (40.6%)	310 (37.3%)	114 (53.5%)	<0.001
Tumor size (cm)	6.0 (4.0–10.0)	6.0 (4.0–10.0)	7.2 (5.0–11.0)	<0.001
Tumors, n, multiple/single	98 (9.4%)/946 (90.6%)	63 (7.6%)/768 (92.4%)	35 (16.4%)/178 (83.6%)	<0.001
Operation time (minutes)	195 (160–240)	191 (160–240)	210 (170–250)	0.033
Blood loss ≥400/<400 (mL)	411 (39.4%)/633 (60.6%)	297 (35.7%)/534 (64.3%)	114 (53.5%)/99 (46.5%)	<0.001
Extent of resection, major/minor	388 (37.2%)/656 (62.8%)	276 (33.2%)/555 (66.8%)	112 (52.6%)/101 (47.4%)	<0.001

Note: Data are mean ± SD or median (IQR 25–75) unless otherwise indicated.

Abbreviations: Alb, albumin; ALBI, albumin–bilirubin; APRI, aspartate aminotransferase-to-platelet-ratio index; BUN, blood urea nitrogen; Cre, creatinine; CSPH, clinically significant portal hypertension; HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; INR, international normalized ratio; IQR, interquartile range; MELD, model for end-stage liver disease; PA, prealbumin; PHLF, posthepatectomy liver failure; Plt, platelet; PT, prothrombin time; TBil, total bilirubin.

Table 2 Univariate logistic analyses to identify predictors of PHLF in patients with HCC

Characteristics	OR (95% CI)	P-value
Male sex	0.512 (0.305–0.859)	0.011
Positive HBsAg	1.493 (0.893–2.494)	0.126
HBV DNA >2,000 IU/mL	1.928 (1.297–2.660)	<0.001
Plt count (10^9/L)	0.994 (0.992–0.996)	<0.001
TBil (μmol/L)	1.086 (1.061–1.110)	<0.001
PA (mg/L)	0.993 (0.990–0.995)	<0.001
Alb (g/L)	0.926 (0.895–0.958)	<0.001
ALT (U/L)	1.009 (1.005–1.012)	<0.001
AST (U/L)	1.012 (1.008–1.015)	<0.001
Cre (μmol/L)	0.992 (0.985–1.000)	0.037
PT (seconds)	1.513 (1.340–1.709)	<0.001
INR	62.65 (18.08–217.1)	<0.001
Ascites	1.827 (1.147–2.909)	0.011
CSPH	2.062 (1.285–3.308)	0.003
Child–Pugh score	1.720 (1.315–2.251)	<0.001
MELD score	1.088 (1.042–1.136)	<0.001
ALBI score	4.179 (2.818–6.197)	<0.001
APRI score	3.012 (2.303–3.939)	<0.001
Cirrhosis	1.935 (1.428–2.622)	<0.001
Tumor size (cm)	1.062 (1.028–1.097)	<0.001
Multiple tumor, n	2.397 (1.537–3.738)	<0.001
Operation time (minutes)	1.002 (0.999–1.004)	0.138
Blood loss ≥400 mL	2.070 (1.527–2.807)	<0.001
Major resection	2.230 (1.643–3.026)	<0.001

Abbreviations: Alb, albumin; ALBI, albumin–bilirubin; APRI, aspartate aminotransferase-to-platelet-ratio index; BUN, blood urea nitrogen; Cre, creatinine; CSPH, clinically significant portal hypertension; HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; INR, international normalized ratio; MELD, model for end-stage liver disease; PA, prealbumin; Plt, platelet; PT, prothrombin time; TBil, total bilirubin.

Table 3 Multivariate logistic analyses to identify predictors of PHLF in patients with HCC

Characteristics	Child–Pugh score*		MELD score**		ALBI score‡		APRI score‡‡
	OR (95% CI)	P-value	OR (95% CI)	P-value	OR (95% CI)	P-value	OR (95% CI)	P-value
Male sex	0.352 (0.193–0.642)	0.001	0.409 (0.219–0.762)	0.005	0.369 (0.199–0.684)	0.002	0.388 (0.205–0.732)	0.003
HBV DNA	1.445 (1.025–2.038)	0.036	1.468 (1.040–2.071)	0.029	1.502 (1.068–2.112)	0.019	1.462 (1.021–2.093)	0.038
>2,000 IU/mL
Plt count (10^9/L)	0.991 (0.989–0.994)	<0.001	0.992 (0.990–0.995)	<0.001	0.992 (0.990–0.995)	<0.001
TBil (μmol/L)							1.068 (1.042–1.096)	<0.001
PA (mg/L)	0.994 (0.992–0.998)	<0.001	0.995 (0.992–0.998)	<0.001	0.997(0.994–0.999)	0.016	0.996 (0.993–0.999)	0.004
ALB (g/L)			1.008 (1.004–1.012)	0.532			0.959 (0.923–0.997)	0.035
ALT (U/L)	1.002 (0.997–1.007)	0.427	1.001 (0.996–1.007)	0.592	1.002 (0.997–1.007)	0.451	0.999 (0.994–1.004)	0.730
AST (U/L)	1.009 (1.005–1.014)	<0.001	1.009 (1.005–1.013)	<0.001	1.009 (1.005–1.013)	<0.001
Cre (μmol/L)	0.998 (0.991–1.006)	0.635			1.001 (0.993–1.007)	0.929	0.999 (0.992–1.006)	0.768
PT (seconds)			1.256 (1.083–1.457)	0.003	1.266 (1.094–1.464)	0.002	1.272 (1.101–1.471)	0.001
INR					9.174 (2.311–36.42)	0.002	18.95 (4.842–74.15)	<0.001
Ascites			1.114 (0.648–1.916)	0.695	1.104 (0.641–1.901)	0.721	1.024 (0.590–1.775)	0.934
CSPH	1.055 (0.590–1.886)	0.856	0.994 (0.566–1.746)	0.984	0.893 (0.491–1.624)	0.711	0.852 (0.450–1.614)	0.624
Child–Pugh score	1.524 (1.150–2.019)	0.003
MELD score			1.060 (1.012–1.111)	0.015
ALBI score					2.000 (1.204–3.321)	0.007
APRI score							2.046 (1.542–2.714)	<0.001
Cirrhosis	1.600 (1.119–2.289)	0.010	1.453 (1.009–2.092)	0.044	1.461 (1.014–2.104)	0.042	1.519 (1.066–2.166)	0.021
Tumor size (cm)	1.050 (1.001–1.101)	0.045	1.054 (1.004–1.106)	0.032	1.055 (1.005–1.107)	0.030	1.074 (1.034–1.114)	<0.001
Multiple tumors, n	1.816 (1.097–3.006)	0.012	1.878 (1.127–3.128)	0.015	1.853 (1.111–3.090)	0.018	1.743 (1.048–2.898)	0.032
Blood loss ≥400 mL	1.436 (1.003–2.057)	0.048	1.462 (1.017–2.104)	0.041	1.443 (1.001–2.081)	0.049	1.498 (1.050–2.138)	0.026
Major resection	1.900 (1.287–2.806)	0.001	2.002 (1.345–2.978)	0.001	2.006 (1.436–2.990)	0.001	1.976 (1.365–2.858)	<0.001

Notes:

* Without TBil, Alb, PT, INR, ascites, MELD, ALBI, and APRI scores.

** Without TBil, INR, CRE, Child–Pugh, ALBI, and APRI scores.

‡ Without TBil, Alb, Child–Pugh, MELD, and APRI scores.

‡‡ Without AST, Plt count, Child–Pugh, MELD, and ALBI scores.

Abbreviations: Alb, albumin; ALBI, albumin–bilirubin; APRI, aspartate aminotransferase-to-platelet-ratio index; Cre, creatinine; CSPH, clinically significant portal hypertension; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; INR, international normalized ratio; MELD, model for end-stage liver disease; PA, prealbumin; Plt, platelet; PT, prothrombin time; TBil, total bilirubin.

Figure 1 ROC curves of APRI, Child–Pugh, MELD, and ALBI scores for predicting PHLF.

Notes: (A) Entire cohort of patients. (B) Patients positive for HBsAg and HBV DNA >2,000 IU/mL. (C) Patients positive for HBsAg and HBV DNA ≤2,000 (IU/mL). (D) Patients with cirrhosis. (E) Patients without cirrhosis. (F) Patients with major liver resection. (G) Patients with minor liver resection. (H) Patients with intraoperative blood loss ≥400 (mL). (I) Patients with intraoperative blood loss <400 mL. Area under the curve: (A) 0.743 for APRI vs 0.562 for Child–Pugh, 0.647 for MELD, and 0.662 for ALBI; (B) 0.746 vs 0.572, 0.659, and 0.681; (C) 0.699 vs 0.554, 0.614, and 0.661; (D) 0.732 vs 0.585, 0.641, and 0.677; (E) 0.729 vs 0.533, 0.638, and 0.640; (F) 0.718 vs 0.558, 0.634, and 0.648; (G) 0.758 vs 0.563, 0.684, and 0.669; (H) 0.743 vs 0.538, 0.638, and 0.641; (I) 0.729 vs 0.574, 0.656, and 0.667, respectively.

Abbreviation: HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus MELD, model for end-stage liver disease; ALBI, albumin–bilirubin; APRI, aspartate aminotransferase-to-platelet-ratio index; PHLF, posthepatectomy liver failure.

Figure 2 Correlations between risk cohorts of APRI score and incidence and grade of PHLF.

Notes: (A) Entire cohort of patients. (B) Patients positive for HBsAg and HBV DNA >2,000 IU/mL. (C) Patients positive for HBsAg and HBV DNA ≤2,000 IU/mL. (D) Patients with cirrhosis. (E) Patients without cirrhosis. (F) Patients with major liver resection. (G) Patients with minor liver resection. (H) Patients with intraoperative blood loss ≥400 mL. (I) Patients with intraoperative blood loss <400 mL (incidence, P<0.001 for all [χ²-test]; grade, P<0.001 for all [Kruskal-Wallis H-test]).

Abbreviations: HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; APRI, aspartate aminotransferase-to-platelet-ratio index; PHLF, posthepatectomy liver failure.

Figure S1 Correlations between patients with Child–Pugh grade A or grade B and incidence and grade of PHLF.

Notes: (A) Entire cohort of patients. (B) Patients positive for HBsAg and HBV DNA >2,000 IU/mL. (C) Patients positive for HBsAg and HBV DNA ≤2,000 IU/mL. (D) Patients with cirrhosis. (E) Patients without cirrhosis. (F) Patients with major liver resection. (G) Patients with minor liver resection. (H) Patients with intraoperative blood loss ≥400 mL. (I) Patients with intraoperative blood loss <400 mL (incidence [C, E, H], P>0.05; others, P<0.05 [χ² test]; grade [C, E, H], P>0.05; others, P<0.05 [Kruskal–Wallis H-test]).

Abbreviations: HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; PHLF, posthepatectomy liver failure.

Figure S2 Correlation between the patients with MELD score >11 or <9 and the incidence and grade of PHLF.

Notes: (A) Entire cohort of patients. (B) Patients positive for HBsAg and HBV DNA >2,000(IU/mL). (C) Patients positive for HBsAg and HBV DNA ≤2,000 (IU/mL). (D) Patients with cirrhosis. (E) Patients without cirrhosis. (F) Patients with major liver resection. (G) Patients with minor liver resection. (H) Patients with intraoperative blood loss ≥400 (mL). (I) Patients with intraoperative blood loss <400 mL (incidence: [F] P<0.05, others P>0.05 [χ²-test]; grade: P<0.001 for all [Kruskal–Wallis H-test].

Abbreviations: HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; MELD, model for end-stage liver disease; PHLF, posthepatectomy liver failure.

Figure S3 Correlation between the patients with ALBI grade 1 or grade 2–3 and the incidence and grade of PHLF.

Notes: (A) Entire cohort of patients. (B) Patients positive for HBsAg and HBV DNA >2,000 IU/mL. (C) Patients positive for HBsAg and HBV DNA ≤2,000 IU/mL. (D) Patients with cirrhosis. (E) Patients without cirrhosis. (F) Patients with major liver resection. (G) Patients with minor liver resection. (H) Patients with intraoperative blood loss ≥400 mL. (I) Patients with intraoperative blood loss <400 mL (incidence, P<0.001 for all [χ²-test]; grade, P<0.001 for all [Kruskal–Wallis H-test]).

Abbreviation: HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; ALBI, albumin–bilirubin; PHLF, posthepatectomy liver failure.