Application of a biochemical and clinical model to predict individual survival in patients with end-stage liver disease

Table 1 Baseline characteristics of the patient population

Variables	Derivation set n = 172	Validation set n = 85
Follow-up period	56 (4-104)	58 (8-104)
Age (yr)	56 (20-79)	59 (23-78)
Sex, n (%)
Male	106 (62)	58 (68)
Female	66 (38)	27 (32)
Cause of cirrhosis, n (%)
Alcohol	30 (17)	16 (19)
Alcohol plus viral infection	15 (9)	4 (5)
HBV	20 (12)	12 (14)
HCV	92 (53)	50 (59)
Viral co-infection (HBV/HCV)	1 (1)	1 (1)
Unknown	13 (7)	1 (1)
NAFL	1 (1)	1 (1)
Complications on admission, n (%)
Ascites
Absent or controlled	147 (85)	72 (85)
Uncontrolled	25 (15)	13 (15)
BEV
Absent or present without relapses	167 (97)	79 (94)
Present with relapses	5 (3)	5 (6)
Encephalopathy
Absent or controlled	160 (93)	79 (93)
Uncontrolled	12 (7)	6 (7)
SBP
Absent or present without relapses	168 (98)	82 (96)
Present with relapses	4 (2)	3 (4)
Hepatorenal syndrome, n (%)	3 (2)	1 (1)
Prothrombin time (s)	19 (13-55)	17 (13-53)
Partial thromboplastin time (s)	38 (26-165)	39 (26-167)
INR for prothrombin time	1.7 (1-7.5)	1.5 (1-6.9)
Albumin (g/L)	37 (20-48)	36 (21-47)
Creatinine (mmol/L)1	100 (42-516)	98 (39-489)
Bilirubin (mmol/L)2	20 (8-130)	23 (12-137)
Cholesterol (mmol/L)	3.8 (1.9-10.2)	3.9 (2-9.6)
Child-Pugh score3	7 (5-14)	7 (5-14)
Child-Pugh A, n (%)	67 (39)	30 (35)
Child-Pugh B, n (%)	75 (44)	34 (40)
Child-Pugh C, n (%)	30 (17)	21 (25)
MELD score	17 (9-42)	18 (10-43)
BioCliM score	7.7 (6.1-13.6)	7.9 (6-13.8)

HBV: Hepatitis B virus; HCV: Hepatitis C virus; NAFL: Non-alcoholic fatty liver; BEV: Bleeding esophageal varices; SBP: Spontaneous bacterial peritonitis; INR: International normalized ratio; MELD: Model for End-stage Liver Disease; BioCliM: Biochemical and Clinical Model. All quantitative variables are expressed as median (ranges).

¹To convert mmol/L into mg/dL, multiply by 0.01131.

²To convert mmol/L into mg/dL, multiply by 0.0585.

³The Child-Pugh, MELD and BioCliM scores are measures of the severity of liver disease.

Table 2 Association of baseline characteristics with mortality in 170 cirrhotic patients, results from univariate Cox proportional hazards models

Variables	P	Hazard ratio	95% CI for Hazard ratio
Age (yr)	0.68	0.56	0.36-1.06
Sex (male)	0.54	0.44	0.89-1.26
Etiology (viral)	0.66	0.58	0.40-1.11
ALT (IU/L) (logn value)	0.85	0.84	0.34-1.12
AST (IU/L) (logn value)	0.43	0.90	0.56-1.34
ALT/AST ratio	0.64	0.87	0.50-1.21
Platelet count (× 109/L) (logn value)	0.54	0.89	0.52-1.30
Prothrombin time (s)1 (logn value)	0.01	2.23	1.24-4.89
INR for prothrombin time (logn value)	0.03	1.99	1.13-3.96
Partial thromboplastin time (s)2 (logn value)	0.04	1.78	1.10-3.23
Albumin (mg/dL) (logn value)	0.001	3.12	1.89-5.23
Bilirubin (mmol/L) (logn value)	< 0.001	3.89	2.12-6.14
Creatinine (mmol/L) (logn value)	< 0.001	3.95	2.18-6.56
Cholesterol (mmol/L) (loge value)	0.03	1.83	1.34-3,42
Ascites	< 0.001	4.05	2.27-6.33
Spontaneous bacterial peritonitis	0.001	3.05	2.10-5.07
Encephalopathy	< 0.001	4.50	2.90-6.50
Bleeding esophageal varices	< 0.001	4.78	3.11-7.11

CI: Confidence interval; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase. Hazard ratios (95% CI) for quantitative variables are expressed for 1 relevant unit increase of log. INR: International normalized ratio.

¹Prothrombin time (s): Value in seconds.

²Partial thromboplastin time (s): Value in seconds.

Table 3 Contributions of different variables to survival prediction at 104 wk, results from multivariate Cox regression models¹

Variable	Variable χ2	Regression coefficient	Hazard ratio	95% CI for Hazard ratio		P value	c-statistic	BIC
Ascites	53.90	2.310	10.2	3.78	28.1	< 0.0001	0.76	2014.15
+ Ln (creatinine)	63.43	1.370	3.99	1.57	10.9	0.006	0.83	1988.15
+ BEV	65.71	1.195	3.25	1.01	9.77	0.048	0.85	1970.65
+ HE	68.91	0.909	2.50	0.915	6.88	0.070	0.89	1961.89
+ Ln (bilirubin)2	70.11	0.349	1.46	0.66	3.33	0.427	0.90	1951.77

¹Estimated from Cox proportional hazards models.

²Biochemical (bilirubin and creatinine) and Clinical (ascites, encephalopathy and bleeding esophageal varices) Model; BEV: Bleeding esophageal varices; HE: Hepatic encephalopathy; BIC: Bayesian Information Criterion. Ln was used to normalize distributions and improve the fit for individual predictors. Hazard ratio for quantitative variables are expressed for 1 relevant unit increase of log. + indicates the addition of each variable separately to the model with ascites only. χ² is the likelihood ratio statistic for each group of variables when added to the model. The risk prediction was based on data from the model derivation cohort (n = 170) at 104 wk follow-up.