Risk factors for hepatocellular carcinoma in cirrhosis: A comprehensive analysis from a decade-long study

Table 1 Demographic and clinical characteristics

Parameter	HCC cases (n = 1352)	Non-HCC controls (n = 4065)	P value
Sex (Male), n (%)	969 (71.7)	2598 (63.9)	< 0.001
Age	56 (50, 62)	54 (46, 62)	< 0.001
Hypertension, n (%)	255 (18.9)	727 (17.9)	0.419
Diabetes, n (%)	321 (23.7)	860 (21.2)	0.046
Coronary disease, n (%)	35 (2.6)	154 (3.8)	0.037
Gastrointestinal bleeding, n (%)	243 (18.0)	978 (24.1)	< 0.001
Hepatic encephalopathy, n (%)	219 (16.2)	633 (15.6)	0.584
Decompensated cirrhosis, n (%)	999 (73.9)	3150 (77.5)	0.007
Child-Pugh grade A, n (%)	430 (32.6)	1162 (29.5)	0.003
Child-Pugh grade B, n (%)	648 (49.1)	1893 (48.0)
Child-Push grade C, n (%)	241 (18.3)	890 (22.6)
HBV, n (%)	372 (27.5)	889 (21.9)	< 0.001
HCV, n (%)	93 (6.9)	261 (6.4)
AC, n (%)	261 (19.3)	1013 (24.9)
MASLD, n (%)	9 (0.7)	42 (1.0)
PBC, n (%)	72 (5.3)	398 (9.8)
Drug-induced cirrhosis, n (%)	12 (0.9)	54 (1.3)
Cryptogenic cirrhosis, n (%)	387 (28.6)	1072 (26.4)
Mixed cirrhosis, n (%)	146 (10.8)	336 (8.3)
ALT (U/L)	31.1 (21.2, 53.1)	27.0 (18.2, 47.5)	< 0.001
AST (U/L)	47.7 (31.7, 77.4)	44 (29.1, 79.9)	< 0.001
Albumin (g/L)	31.2 (27.4, 34.6)	30.7 (26.8, 34.8)	0.106
Globin (g/L)	31.6 (26.5, 37.1)	31.3 (25.7, 38.0)	0.268
INR	1.27 (1.12, 1.45)	1.32 (1.16, 1.54)	0.002
Prothrombin time (S)	14.2 (12.6, 16.3)	14.8 (13.0, 17.4)	0.017
Direct bilirubin (μmol/L)	11.0 (6.3, 19.2)	12.7 (6.6, 33.6)	0.001
Triglycerides (mmol/L)	0.81 (0.62, 1.11)	0.89 (0.67, 1.26)	< 0.001
Platelets (× 109/L)	78 (54, 109)	80 (54, 118)	0.096
γ-GT (U/L)	50.1 (26.0, 119.8)	53.7 (25.4, 143.8)	0.157
AFP (ng/mL)	4.64 (2.60, 10.35)	3.36 (2.02, 6.26)	< 0.001
CA19-9 (U/mL)	26.72 (13.76, 48.40)	25.00 (11.93, 52.82)	0.070
Neutrophils (× 109/L)	2.30 (1.59, 3.44)	2.43 (1.59, 3.76)	0.024
Serum ammonia (μg/dL)	73 (51, 95)	67 (46, 95)	< 0.001
MELD	8 (4, 12)	10 (5, 15)	< 0.001

HBV: Hepatitis B virus; HCV: Hepatitis C virus; AC: Alcohol-associated cirrhosis; MASLD: Metabolic dysfunction-associated liver disease; PBC: Primary biliary cirrhosis; Mixed cirrhosis: Cirrhosis caused by two or more etiologies; MELD: Model for end-stage liver disease; ALT: Alanine aminotransferase; AST: Aspartate transaminase; INR: International normalized ratio; γ-GT: Gamma-glutamyltransferase; AFP: Alpha fetoprotein; CA: Carbohydrate antigen; HCC: Hepatocellular carcinoma.

Table 2 Hepatocarcinogenesis hazard ratio in Cox and competing risk regression analysis

Parameter	Univariate Cox regression analysis		Multivariable Cox regression analysis		Multivariable competitive risk regression analysis
	aHR (95%CI)	P value	aHR (95%CI)	P value	aHR (95%CI)	P value
Age	1.023 (1.018-1.027)	< 0.001	1.029 (1.024-1.034)	< 0.001	1.025 (1.020-1.030)	< 0.001
Sex (male)	1.321 (1.174-1.487)	< 0.001	1.537 (1.359-1.738)	< 0.001	1.482 (1.313-1.673)	< 0.001
Diabetes	1.155 (1.019-1.309)	0.025
Hypertension	1.128 (0.984-1.292)	0.084
Coronary disease	0.951 (0.680-1.330)	0.769
HBV	1.801 (1.602-2.025)	< 0.001	1.963 (1.742-2.211)	< 0.001	1.950 (1.734-2.193)	< 0.001
HCV	1.837 (1.352-1.981)	< 0.001	1.567 (1.293-1.900)	< 0.001	1.533 (1.274-1.846)	< 0.001
HBV and HCV	2.062 (1.068-3.980)	0.031	2.456 (1.270-4.747)	0.008	2.074 (1.038-4.143)	0.039
Decompensation	1.146 (1.015-1.295)	0.028
ALT	1.000 (1.000-1.000)	0.974
AST	1.000 (1.000-1.000)	0.815
Albumin	0.976 (0.967-0.985)	< 0.001	0.986 (0.977-0.995)	0.002	0.995 (0.987-1.005)	0.381
Globulin	1.017 (1.010-1.023)	< 0.001	1.016 (1.009-1.023)	< 0.001	1.012 (1.005-1.019)	< 0.001
INR	1.271 (1.084-1.490)	0.003
Prothrombin time	1.016 (1.002-1.031)	0.024
Direct bilirubin	1.000 (0.999-1.001)	0.943
Triglycerides	0.854 (0.776-0.939)	0.001
Hemoglobin	1.004 (1.002-1.006)	< 0.001
γ-GT	1.000 (0.999-1.000)	0.075
AFP	1.000 (1.000-1.001)	0.543
CA19-9	1.000 (0.999-1.001)	0.713
Platelets	0.999 (0.998-1.000)	0.017	0.999 (0.998-1.000)	0.015	0.998 (0.998-1.000)	0.011
Neutrophils	0.998 (0.976-1.020)	0.829
Serum ammonia	1.002 (1.001-1.003)	0.004	1.002 (1.001-1.003)	0.003	1.002 (1.001-1.003)	< 0.001
MELD	0.999 (0.990-1.008)	0.843

HBV: Hepatitis B virus; HCV: Hepatitis C virus; MELD: Model for end-stage liver disease; ALT: Alanine aminotransferase; AST: Aspartate transaminase; INR: International normalized ratio; γ-GT: Gamma-glutamyltransferase; AFP: Alpha fetoprotein; CA: Carbohydrate antigen; aHR: Adjusted hazard ratio; CI: Confidence interval.