Golgi protein-73: A biomarker for assessing cirrhosis and prognosis of liver disease patients

Table 1 Baseline demographic, biochemical, histological and clinical characteristics of patients

	Total cohort (n = 632)
Greek/Hungarian, n (%)	366/266 (57.9/42.1)
Age, median (IQR), yr	56.5 (17)
Sex, male/female, n (%)	376/256 (59.5/40.5)
CHB/CHC/Alcoholic/PBC+PSC/AIH/other, n	203/183/198/28/15/5
GP73, median (IQR), units, (ULN: 20 units)	17.3 (20.4)
GP73, pos/neg, n (%)	277/355 (43.8/56.2)
INR, median (IQR), (normal: 0.85-1.15)	1.15 (0.33)
Platelets, median (IQR), x103/μL	153 (114)
AST, median (IQR), (ULN: 40 U/L)	50 (54)
ALT, median (IQR), (ULN: 40 U/L)	40 (44)
γ-GT, median (IQR), (ULN: 37 U/L)	62 (113)
ALP, median (IQR), (ULN: 104 U/L)	95 (77)
Bilirubin, median (IQR), (ULN: 1.1 mg/dL)	1.2 (1.7)
Albumin, median (IQR), (normal: 3.5-5.2 g/dL)	3.9 (1.3)
AFP, median (IQR), (ULN: 10 ng/ml)	4 (6.1)
Fibrosis METAVIR stage, (F0, F1/≥ F2, n (%)	96/100 (49/51)
Cirrhosis, yes/no, n (%)	450/182 (71.2/28.8)
Decompensation of cirrhosis, yes/no, n (%)	226/224 (50.2/49.8)
HCC, yes/no, n (%)	79/553 (12.5/87.5)
HCC BCLC stage, 0/A/B/C/D1, n (%)	2/23/22/21/10 (2.6/29.5/28.2/26.9/12.8)
HCC BCLC stage, 0-A-B/C-D1, n (%)	47/31 (60.3/39.7)
HCC dimensions (very early/intermediate/advanced)	2/32/44 (2.6/41/56.4)
Follow-up ≥ 6 mo, yes/no, n (%)	479/153 (75.8/24.2)
Duration of follow-up, median (IQR), mo	50 (57)

¹One missing case because diagnosis set on autopsy. IQR: Interquartile range; GP73: Golgi protein 73; ULN: Upper limit of normal; CHB: Chronic hepatitis B; CHC: Chronic hepatitis C; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; AIH: Autoimmune hepatitis; INR: International normalized ratio; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γ-GT: γ-glutamyl transpeptidase; ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma; BCLC: Barcelona clinic liver cancer.

Table 2 Baseline demographic, clinical and laboratory characteristics of patients according to golgi protein 73positivity

	GP73-positive (n = 277)	GP73-negative (n = 355)	P value
Age, median (IQR), yr	59 (15)	55 (22)	< 0.001
Sex, male/female, n (%)	169/108 (61/39)	207/148 (58.3/41.7)	0.545
INR, median (IQR)	1.28 (0.36)	1.09 (0.23)	< 0.001
Platelets, median (IQR), x103/μL	125 (99.3)	180 (113.7)	< 0.001
AST, median (IQR), U/L	59 (67)	40 (44)	< 0.001
ALT, median (IQR), U/L	43 (45)	39 (43)	0.127
γ-GT, median (IQR), U/L	105 (171)	45 (79)	< 0.001
ALP, median (IQR), U/L	111 (80)	85 (66)	< 0.001
Bilirubin, median (IQR), mg/dL	1.9 (3.1)	0.9 (0.9)	< 0.001
Albumin, median (IQR), g/dL	3.4 (1.1)	4.3 (0.9)	< 0.001
AFP, median (IQR), ng/mL	5 (14.4)	3.5 (5)	< 0.001
APRI score, median (IQR)	1.4 (2.1)	0.6 (1)	< 0.001
Fibrosis stage (METAVIR) F0, F1 / ≥ F2, n (%)	4/28 (12.5/87.5)	92/72 (56.1/43.9)	< 0.001
Cirrhosis, yes/no, n (%)	267/10 (96.4/3.6)	183/172 (51.5/48.5)	< 0.001
Decompensation of cirrhosis, yes/no, n (%)	161/106 (60.3/39.7)	65/118 (35.5/64.5)	< 0.001
HCC, yes/no, n (%)	51/226 (18.4/81.6)	28/327 (7.9/92.1)	< 0.001
HCC BCLC stage, 0/A/B/C/D, n (%)	1/12/11/18/9 (2/23.5/21.6 /35.3/17.6)	1/11/11/3/11 (3.7/40.7/40.7 /11.1/3.7)	0.029
HCC BCLC stage, 0-A-B/ C-D, n (%)	24/27 (47.1/52.9)	23/41 (85.2/14.8)	0.002
HCC dimensions (very early/intermediate/advanced), n (%)	1/19/31 (2/37.3/60.8)	1/13/131 (3.7/48.1/48.1)	0.543

¹One missing case because diagnosis set on autopsy. GP73: Golgi protein 73; IQR: Interquartile range; INR: International normalized ratio; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γ-GT: γ-glutamyl transpeptidase; ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; APRI: AST to platelet ratio index; HCC: Hepatocellular carcinoma; BCLC: Barcelona clinic liver cancer.

Table 3 Binary logistic regression analysis of baseline factors associated with golgi protein 73 positivity at initial evaluation of patients

Variables	Adjusted OR	95%CI	Adjusted P value
Age	0.990	0.971-1.010	0.336
INR	2.122	0.824-5.467	0.119
Platelets	1.000	1.000-1.000	0.160
AST	1.002	0.998-1.006	0.322
γ-GT	1.001	0.999-1.002	0.229
ALP	1.000	0.997-1.003	0.960
Bilirubin	0.999	0.926-1.078	0.978
Albumin	0.540	0.375-0.778	0.001
AFP	1.000	1.000-1.000	0.187
Presence of cirrhosis	7.608	3.310-17.488	< 0.001
Presence of HCC	1.329	0.704-2.510	0.381

GP73: Golgi protein 73; INR: International normalized ratio; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γ-GT: γ-glutamyl transpeptidase; ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma. No multi-collinearity was found between the independent variables in regression analysis and the variance inflation factors ranged from 1.147 to 1.600.

Table 4 Binary logistic regression analysis of baseline factors associated with golgi protein 73 positivity at initial evaluation of the cirrhotic patients

Variables	Adjusted OR	95%CI	Adjusted P value
Age	0.996	0.975-1.018	0.733
INR	2.242	0.820-6.128	0.116
Platelets	1.000	1.000-1.000	0.719
AST	1.002	0.997-1.006	0.405
γ-GT	1.001	0.999-1.002	0.278
ALP	1.000	0.997-1.003	0.959
Bilirubin	1.002	0.929-1.081	1.002
Albumin	0.713	0.478-1.064	0.098
AFP	1.000	1.000-1.000	0.282
Presence of decompensation	1.812	1.059-3.101	0.030
Presence of HCC	1.302	0.687-2.467	0.419

No multi-collinearity was found between the independent variables in regression analysis and the variance inflation factors ranged from 1.067 to 1.583. GP73: Golgi protein 73; INR: International normalized ratio; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γ-GT: γ-glutamyl transpeptidase; ALP: Alkaline phosphatase; AFP: Alpha fetoprotein; HCC: Hepatocellular carcinoma.