Prognostic value of serum alpha-fetoprotein kinetics in liver failure on artificial liver support

Table 1 Baseline data of patients with liver failure, n (%)

	Parameter total cases (n = 194)	P value1
Age, range, mean ± SD (years)	15-65 (40.6 ± 13.2)	0.382
Sex		0.724
Male	115 (59.3)
Female	79 (40.7)
Hospital stays (days)	23.5 ± 12.1	0.563

¹The t-test or analysis of variance was used for comparison between groups.

The χ² test or Fisher’s exact probability method was used for comparison between groups. P > 0.05 indicates that there is no statistically significant difference among the groups.

Table 2 Comprehensive analysis of general data for patients with liver failure categorized by different alpha-fetoprotein levels

Group	Cases	Gender (n, male/female)	Age, mean ± SD (years)	P value1
Low AFP group (< 100 ng/mL)	60	36/24	41.6 ± 11.8	> 0.05
Medium AFP group (100-200 ng/mL)	70	40/30	40.9 ± 10.9	> 0.05
High AFP group (> 200 ng/mL)	64	39/25	40.5 ± 10.2	> 0.05

¹P > 0.05 indicates that there were no statistically significant differences in gender and age among the three groups (χ² test was used to compare gender, and one-way analysis of variance was used to compare age).

AFP: Alpha-fetoprotein.

Table 3 Laboratory parameters measured before treatment in different alpha-fetoprotein level groups, mean ± SD

Parameter	Low AFP group	Medium AFP group	High AFP group	P value1
Blood ammonia (μmol/L)	188.5 ± 50.1	185.2 ± 48.3	190.3 ± 52.7	0.8216
Albumin (g/L)	25.8 ± 3.9	26.1 ± 3.7	25.6 ± 4.0	0.9308
Total bilirubin (μmol/L)	145.3 ± 35.2	142.6 ± 33.8	148.1 ± 36.5	0.8627
ALT (U/L)	265.4 ± 70.8	260.2 ± 68.1	268.7 ± 72.3	0.8795
AST (U/L)	225.6 ± 60.3	220.3 ± 58.4	229.1 ± 61.9	0.8998
γ-GT (U/L)	485.2 ± 120.6	478.3 ± 118.1	492.7 ± 123.8	0.9339
PTA (%)	28.3 ± 5.1	29.1 ± 5.4	27.8 ± 4.9	0.9657

¹The t-test or analysis of variance was used for comparison between groups. P > 0.05 indicates that there were no statistically significant differences.

AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; γ-GT: γ-glutamyl transferase; PTA: Prothrombin activity.

Table 4 Relationship between alpha-fetoprotein levels and clinical classification of liver failure, n (%)

Type	Cases (n)	Low AFP group	Medium AFP group	High AFP group	P value1
ALF	24	5 (20.8)	15 (62.5)	4 (16.7)	0.004
SALF	38	5 (13.2)	15 (39.5)	18 (47.4)	0.008
ACLF	89	45 (50.6)	30 (33.7)	14 (15. 7)	< 0.001
CLF	43	28 (65.1)	10 (23.3)	5 (11.6)	< 0.001

¹The χ² test was conducted to assess the distributional differences across various liver failure classifications within each alpha-fetoprotein group. P < 0.05 suggests that the differences in distribution among alpha-fetoprotein groups regarding disease types are statistically significant.

AFP: Alpha-fetoprotein; ALF: Acute liver failure; SALF: Subacute liver failure; ACLF: Acute-on-chronic liver failure; CLF: Chronic liver failure.

Table 5 Statistical analysis of 3-month survival rate using a multiple logistic regression model

Variable	Three-month survival status
	OR1	95%CI	P value2	Significance
Age (per additional year)	1.03	1.01-1.05	0.005
Gender (male vs female)	0.81	0.57-1.15	0.241	NS
AFP grouping
Medium vs low	0.44	0.27-0.71	< 0.001
High vs low	0.325	0.148-0.714	< 0.001
Types of liver failure
ALF vs ACLF	0.36	0.20-0.66	0.001
SALF vs ACLF	0.46	0.26-0.81	0.007
CLF vs ACLF	0.64	0.33-1.23	0.178	NS
Liver function indicators
Blood ammonia (μmol/L)	1.01	1.00-1.01	0.002
Albumin (g/L)	0.91	0.88-0.95	< 0.001
Total bilirubin (μmol/L)	1.01	1.00-1.01	0.004
ALT (U/L)	1.01	0.98-1.03	0.467	NS
AST (U/L)	1.00	0.99-1.03	0.226	NS
γ-GT (U/L)	1.00	0.99-1.01	0.167	NS
PTA (%)	0.94	0.92-0.96	0.001

¹Odds ratio indicates the relative change in the likelihood of mortality associated with a one-unit increase (or category shift) in the independent variable.

²P < 0.05 indicates the presence of statistically significant differences, P > 0.05, not significant. Reference group: Liver failure type, acute-on-chronic liver failure; alpha-fetoprotein group, low alpha-fetoprotein group. Nagelkerke R² = 0.458; model χ² = 67.42 (P < 0.001).

OR: Odds ratio; CI: Confidence interval; AFP: Alpha-fetoprotein; ALF: Acute liver failure; ACLF: Acute-on-chronic liver failure; SALF: Subacute liver failure; CLF: Chronic liver failure; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; γ-GT: γ-glutamyl transferase; PTA: Prothrombin activity; NS: Not significant.

Table 6 Serial alpha-fetoprotein levels measured at different time points, mean ± SD

Group	Before treatment	Day 1 after treatment	Day 10 after treatment	Day 20 after treatment	Day 25 after treatment	P value
Low AFP group	65.2 ± 20.1	72.5 ± 18.3	85.4 ± 22.6	92.1 ± 25.4	98.3 ± 28.7	< 0.001
Medium AFP group	148.3 ± 35.6	160.8 ± 40.2	175.6 ± 45.3	190.2 ± 50.1	205.4 ± 55.8	< 0.001
High AFP group	320.5 ± 80.4	340.2 ± 85.6	365.7 ± 90.3	380.1 ± 95.2	395.6 ± 98.5	< 0.001
P value1	0.984	0.932	0.018	0.006	0.003

¹Inter-group P value, the inter-group comparison P value represents the overall differences among the three groups at each time point, and the trend P value represents the statistical significance of the time-dependent changes in each group. P < 0.05 indicates the presence of statistically significant differences.

AFP: Alpha-fetoprotein.

Table 7 Relationship between the number of plasma exchange treatments and alpha-fetoprotein levels, mean ± SD

Group	Treatment sessions	AFP increase	P value (within-group1vs baseline)	P value (between-group2vs other groups)
Low AFP group	4.2 ± 1.5	33.1 ± 10.2	< 0.001	Reference
Medium AFP group	3.5 ± 1.2	57.1 ± 15.6	< 0.001	vs low: 0.003; vs high: 0.012
High AFP group	2.8 ± 1.0	75.1 ± 20.3	< 0.001	vs low: < 0.001; vs medium: 0.009

¹Within-group, significant change from baseline alpha-fetoprotein values.

²Between-group, significant differences in treatment response magnitude between specified groups. P < 0.05 indicates the presence of statistically significant differences.

AFP: Alpha-fetoprotein.

Table 8 Comparison of laboratory indicators (last time) among different alpha-fetoprotein level categories after treatment, mean ± SD

Parameter	Low AFP group	Medium AFP group	High AFP group	Overall P value (ANOVA)1	Post-hoc test (Tukey HSD)2
Blood ammonia (μmol/L)	125.6 ± 45.3	98.4 ± 30.2	75.8 ± 25.1	0.003	Low vs med: 0.045
					Low vs high: 0.001
					Med vs high: 0.357
Albumin (g/L)	28.3 ± 4.1	32.5 ± 3.8	35.6 ± 4.2	0.001	Low vs med: 0.003
					Low vs high: < 0.001
					Med vs high: 0.032
Total bilirubin (μmol/L)	68.5 ± 22.1	45.2 ± 18.3	28.7 ± 12.6	< 0.001	Low vs med: 0.001
					Low vs high: < 0.001
					Med vs high: 0.017
ALT (U/L)	180.5 ± 60.2	150.3 ± 55.6	120.8 ± 48.3	0.012	Low vs med: 0.213
					Low vs high: 0.006
					Med vs high: 0.058
AST (U/L)	155.4 ± 50.7	120.6 ± 45.2	95.3 ± 38.4	0.005	Low vs med: 0.045
					Low vs high: < 0.001
					Med vs high: 0.038
γ-GT (U/L)	320.6 ± 105.4	240.8 ± 90.5	185.2 ± 75.3	0.008	Low vs med: 0.041
					Low vs high: 0.002
					Med vs high: 0.128
PTA (%)	55.4 ± 10.2	35.2 ± 8.6	72.8 ± 12.4	< 0.001	Low vs med: < 0.001
					Low vs high: 0.032
					Med vs high: < 0.001

¹ANOVA was conducted to compare parameters across alpha-fetoprotein groups, followed by Tukey’s honestly significant difference post-hoc tests for pairwise comparisons. Overall P value indicates significant inter-group differences for the parameter.

²Post-hoc P values highlights significant differences between specified alpha-fetoprotein subgroups.

AFP: Alpha-fetoprotein; HSD: Honestly significant difference; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; γ-GT: γ-glutamyl transferase; PTA: Prothrombin activity; med: Medium.

Table 9 Correlation between the incidence of complications and alpha-fetoprotein levels,%

Complication type	Low AFP group	Medium AFP group	High AFP group	P value1	Post-hoc test (Bonferroni correction)2
Allergic reaction	12.5	6.3	3.1	0.042	Low vs high: 0.038
					Low vs med: 0.215
					Med vs high: 0.417
Hypotension	18.8	12.5	6.3	0.023	Low vs high: 0.009
					Low vs med: 0.137
					Med vs high: 0.254
SBP	25.0	15.6	9.4	0.011	Low vs high: 0.003
					Low vs med: 0.062
					Med vs high: 0.168

¹The distribution differences of complications among alpha-fetoprotein groups were analyzed using χ² test or Fisher’s exact test. Overall P value: Significant differences exist in complication rates across Alpha-fetoprotein subgroups.

²Post-hoc pairwise comparisons with Bonferroni correction were performed when overall P < 0.05. Post-hoc P values: Significant differences between specific group pairs after multiple comparison adjustment.

AFP: Alpha-fetoprotein; SBP: Spontaneous bacterial peritonitis; med: Medium.

Table 10 Comparison of 3-month follow-up survival rates,%

Group	Survival rate at discharge	3-month survival rate	P value1
Low AFP group	70.0	56.7	< 0.001
Medium AFP group	81.4	72.9	< 0.001
High AFP group	96.9	90.6	< 0.001

¹P values compare differences in survival rates among groups using the log-rank test (P < 0.001).

AFP: Alpha-fetoprotein.