Nomogram for Estimation of Acute Liver Failure Risk in Spontaneous Ruptured Hepatocellular Carcinoma

Figures & data

Figure 1 Flowchart of the study. (A) Selection process for participants in the study, (B) The development and evaluation of the nomogram.

Abbreviations: SRHCC, spontaneous ruptured hepatocellular carcinoma; ALF, acute liver failure; MELD, Model for End-Stage Liver Disease; ALBI, Albumin-Bilirubin.

Table 1 Baseline Characteristics of the Enrolled Patients

Index	Patients (n=284)	%
Sex
Female	56	19.7%
Male	228	80.3%
Age, y	59.0[51.0;67.0]	–
BMI, kg/m²	23.3[21.0;25.4]	–
Hypertensive
No	215	75.7%
Yes	69	24.3%
Diabetes
No	255	89.8%
Yes	29	10.2%
Smoking
No	197	69.4%
Yes	87	30.6%
Drinking
No	207	72.9%
Yes	77	27.1%
Vital hepatitis
None	64	22.5%
HBV	187	65.8%
HCV	33	11.6%
Cirrhosis
No	120	42.3%
Yes	164	57.7%
Portal hypertension
No	166	58.5%
Yes	118	41.5%
LTS, cm	7.15[4.80;9.93]	–
Tumor counts
Solitary	155	54.6%
Multiple	129	45.4%
Tumor location
Caudate lobe	9	3.17%
Left lobe	84	29.6%
Right lobe	149	52.5%
Multiple lobes	42	14.8%
Distant metastasis
No	258	90.8%
Yes	26	9.15%
AFP, ng/mL
≤20	122	43.0%
20–400	56	19.7%
>400	106	37.3%
Therapy
Conservative treatment	57	20.1%
TACE	173	60.8%
Hepatectomy	27	9.54%
TACE + Hepatectomy	27	9.54%
ALF
No	219	77.1%
Yes	65	22.9%
Child.Pugh Score	7.00[6.00;8.00]	–
R.MELD	18.3[14.7;22.2]	–
ALBI	−2.01[−2.35;-1.62]	-
OS
1-year	-	50.2%
2-year	-	31.5%
3-year	-	19.8%

Abbreviations: BMI, body mass index; HBV, hepatitis B virus; HCV, hepatitis C virus; LTS, Largest tumor size; AFP, α-Fetoprotein; TACE, transcatheter arterial chemoembolization; ALF, acute liver failure; MELD, Model for End-Stage Liver Disease; ALBI, Albumin-Bilirubin; OS, overall survival.

Table 2 Univariate Logistic Regression Analysis of ALF Presence Based on Variables Possible

Variables	OR (95% CI)	p
Sex, male vs female	0.77 (0.39–1.5)	0.44
Age, y	1.01 (0.98–1.04)	0.5
Vital hepatitis
HBV vs none	0.88 (0.46–1.68)	0.69
HCV vs none	0.28 (0.07–1.02)	0.05
Imaging results
Cirrhosis, positive vs negative	2.28 (1.24–4.17)	0.01*
Portal hypertension, positive vs negative	2.66 (1.51–4.69)	<0.001*
LTS, cm	1.19 (1.1–1.28)	<0.001*
Tumor counts	1.68 (0.96–2.94)	0.07
Blood test results
WBC, x10^9/L	1 (0.95–1.05)	0.99
NLR	1 (0.95–1.05)	0.96
Hemoglobin, g/L	0.99 (0.98–0.99)	<0.001*
Platelet, x10^9/L	0.99 (0.98–0.99)	<0.001*
AST, U/L	1 (1–1.01)	<0.001*
ALT, U/L	1 (1–1.01)	0.02*
Albumin, g/L	0.88 (0.84–0.93)	<0.001*
Bilirubin, μmoI/L	1.04 (1.02–1.06)	<0.001*
Creatinine, μmoI/L	1.01 (1–1.01)	0.01*
Na, mmol/L	0.99 (0.96–1.02)	0.57
Pronged PT, s	2.21 (1.78–2.75)	<0.001*
AFP, ng/mL
20–400 vs ≤20	4.72 (2.65–8.42)	<0.001*
>400 vs 20–400	0.59 (0.33–1.06)	0.08
Main treatments
TACE vs Conservative treatment	0.41 (0.21–0.77)	0.01*
Hepatectomy vs Conservative treatment	0.06 (0.01–0.45)	0.01*
TACE + Hepatectomy vs Conservative treatment	0.26 (0.08–0.84)	0.02*

Note: *Statistically significant p value.

Abbreviations: OR, Odds Ratio; CI, Confidence Interval; HBV, hepatitis B virus; HCV, hepatitis C virus; LTS, Largest tumor size; WBC, white blood cells; NLR neutrophil to lymphocyte ratio; AST, aspartate aminotransferase; ALT, alanine aminotransferase; Na, serum sodium; PT, prothrombin time; AFP, α-Fetoprotein; TACE, transcatheter arterial chemoembolization.

Table 3 Multivariate Logistic Regression Analysis of ALF Presence Based on Variables Possible

Variables	β^α	OR (95% CI)	p
Imaging results
Cirrhosis, positive vs negative	−0.867	0.42 (0.12–1.44)	0.2
Portal hypertension, positive vs negative	0.636	1.89 (0.66–5.59)	0.2
LTS, cm	0.243	1.28 (1.12–1.47)	<0.001*
Blood test results
Hemoglobin, g/L	0.007	1.01 (0.99–1.03)	0.5
Platelet, x10^9/L	−0.012	0.99 (0.98–1.00)	0.004*
AST, U/L	0.003	1 (1.00–1.01)	0.14
ALT, U/L	−0.001	1 (0.99–1.01)	0.8
Albumin, g/L	0.012	1.01 (0.93–1.11)	0.8
Bilirubin, μmoI/L	0.016	1.02 (1.00–1.04)	0.082
Creatinine, μmoI/L	0.007	1.01 (1.00–1.02)	0.15
Pronged PT, s	0.799	2.22 (1.57–3.32)	<0.001*
AFP, ng/mL
20–400 vs ≤20	1.558	4.75 (2.03–13.2)	<0.001*
>400 vs 20–400	−0.595	0.55 (0.23–1.31)	0.2
Main treatments
TACE vs Conservative treatment	−0.298	0.74 (0.27–2.10)	0.6
Hepatectomy vs Conservative treatment	−2.197	0.11 (0.00–1.49)	0.13
TACE + Hepatectomy vs Conservative treatment	0.469	1.6 (0.26–8.82)	0.6

Note: *Statistically significant p value; β^α Regression coefficient.

Abbreviations: OR, Odds Ratio; CI, Confidence Interval; LTS, Largest tumor size; AST, aspartate aminotransferase; ALT, alanine aminotransferase; PT, prothrombin time; AFP, α-Fetoprotein; TACE, transcatheter arterial chemoembolization.

Figure 2 Linear correlation analysis of the four indicators (LTS, platelet, pronged PT, and AFP). The number in the right of the plot was the correlation coefficient.

Abbreviations: LTS, largest tumor size; AFP, α-Fetoprotein PT, prothrombin time.

Figure 3 Nomogram for preoperative estimation of acute liver failure risk.

Abbreviations: LTS, largest tumor size; PT, prothrombin time; AFP, α-Fetoprotein; ALF, acute liver failure.

Figure 4 Comparison of receiver operating characteristic curve (A), calibration curve (B) and decision curve analysis (C) between diagnostic nomogram and each independent predictor.

Abbreviations: LTS, largest tumor size; AFP, α-Fetoprotein; PT, prothrombin time; AUC area under the receiver operating characteristic curve.

Table 4 Accuracy of the Prediction Score of the Nomogram for Estimating the Risk of ALF Presence Compared with Other Models

Variable	Value
	Nomogram	Child.Pugh	R.MELD	ALBI
C-index, AUC	0.91	0.81	0.77	0.78
Delong test	–	p<0.001*	p<0.001*	p<0.001*
Accuracy, %	82.90	78.20	80.30	80.60
Precision, %	58.60	51.90	57.60	56.30
Sensitivity,%	83.10	63.10	52.30	69.20
Specificity, %	87.20	82.60	88.60	84.00
Positive predictive value, %	65.90	51.90	57.60	56.30
Negative predictive value, %	94.60	88.30	86.20	90.20

Note: *Statistically significant p value.

Abbreviations: MELD, Model for End-Stage Liver Disease; ALBI, Albumin-Bilirubin; AUC, area under the receiver operating characteristic curve.

Figure 5 The receiver operating characteristic curve of each model. (A) Nomogram. (B) Child.Pugh. (C) R.MELD. (D) ALBI.

Abbreviations: AUC, area under the receiver operating characteristic curve; MELD, Model for End-Stage Liver Disease; ALBI, Albumin-Bilirubin.

Figure 6 The calibration curve of each model. (A) Nomogram. (B) Child.Pugh. (C) R.MELD. (D) ALBI.

Abbreviations: MELD, Model for End-Stage Liver Disease; ALBI, Albumin-Bilirubin.

Figure 7 The comparison of decision curve analysis for each model.

Abbreviations: MELD, Model for End-Stage Liver Disease; ALBI, Albumin-Bilirubin.