Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis

Table 1 Demographic, clinical, and laboratory features of patients included in the study with cryptogenic cirrhosis and hepatitis C virus-related cirrhosis

	Cryptogenic cirrhosis	Hepatitis C virus cirrhosis	P value
No. of patients	102	110
Age at diagnosis (yr), median	66 (38-84)	65 (48-86)	NS
Male sex (M:F ratio)	36 (1:1.8)	58 (3:1)	< 0.01
BMI (mean ± SD)	30 ± 5.7	27.1 ± 3.9	< 0.05
Low alcohol intake	11.8%	12.8%	NS
Past and current smokers	29.4%	27.2%	NS
AST (U/L), mean ± SD	47 ± 43	122 ± 88	< 0.01
ALT (U/L), mean ± SD	35 ± 25	102 ± 63	< 0.01
Υ-GT (U/L), mean ± SD	126 ± 124	82 ± 61	< 0.05
Alph (U/L), mean ± SD	172 ± 181	198 ± 180	NS
Total bilirubin (mg/dL), mean ± SD	2.8 ± 5.2	2.6 ± 4.2	NS
Albumin (g/dL), mean ± SD	3.4 ± 0.8	3.4 ± 0.9	NS
INR, mean ± SD	1.3 ± 0.6	1.4 ± 0.8	NS
Platelets (103/mm3), mean ± SD	120 ± 80	115 ± 60	NS
Creatininemia (mg/dL), mean ± SD	1.1 ± 0.7	1.1 ± 0.6	NS
Ferritin (ng/mL), mean ± SD	163 ± 153	186 ± 162	NS
α-fetoprotein (ng/mL), median	3.4 (0.6-3300)	36 (2-600)	NS
Child-Pugh class A/B/C (%)	47/31/22	48/29/23	NS
HBsAb/HBcAb positive	27.5%	42.7%	< 0.03
Extrahepatic tumors	12.6%	4.4%	NS

NS: Not significant.

Table 2 Characteristics and complications of the 102 patients with cryptogenic cirrhosis according to metabolic syndrome components

	With full metabolic syndrome, n = 54 (52.9%)	Without full metabolic syndrome, n = 36 (35.8%)	Without components of metabolic syndrome, n = 12 (11.8%)
Age (yr), median	66 (48-84)	66 (42-84)	70 (38-81)
Female sex	70.4%	58.3%	50%a
Obesity	69%	39%	0%a
Overweight	27%	55.5%	0%a
IFG/T2D	81.8%	61%	33%a
Ascites	50%	61.3%	55%
HCC	20%	14%	18%
Cardiovascular diseases	48%	41.6%	25%a

^aP < 0.05. HCC: Hepatocellular carcinoma; IFG: Impaired fasting glucose.

Table 3 Outcome observed during follow up of the 102 patients with cryptogenic cirrhosis and 110 patients with hepatitis C virus-related cirrhosis

	Cryptogenic cirrhosis	Hepatitis C virus cirrhosis
Follow up, median, mo (range)	42 (10-96)	40.8 (10-95)
Liver decompensation	60.8%	55.4%
Ascites	54.9%	51.8%
Encephalopathy	25.5%	21.8%
Esophageal variceal bleeding	6.9%	6.3%
Hepatocellular carcinoma	16.7%	17.2%
Orthotopic liver transplantation	1.0%	3.6%
Death	39.2%	30.0%
Liver-related	77.5%	78.8%
Cardiovascular events	10.0%	9.1%
Non-liver-related cancer	7.5%	3.0%
Other causes	5.0%	9.1%
Time to death, median, mo (range)	26 (1-96)	28 (4-86)

Table 4 Characteristics, prevalence and incidence of hepatocellular carcinoma in 102 patients with cryptogenic cirrhosis and in 110 patients with hepatitis C virus-related cirrhosis

	Cryptogenic cirrhosis	HCV cirrhosis
HCC at first diagnosis	6 (5.8%)	4 (3.6%)
HCC during follow-up	12 (12.5%)	15 (14.1%)
HCC overall	17.6%	17.2%
Annual rate of incidence	3.5%	4.5%
Age, median, yr (range)	73 (63-82)	72 (60-80)
Male sex (M:F ratio)	52% (1.5:1)	58% (3:1)
Child-Pugh A/B/C (%)	39/39/22	21/42/37
Ratio Child-Pugh A:(B-C)	0.5	0.27
α-fetoprotein (ng/mL), median (range)	48 (6-800)	66 (6-680)

HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus.

Table 5 Predictors of outcomes of the 102 patients with cryptogenic cirrhosis

Outcome	Univariate analysis, OR (95%CI)	P value	Multivariate analysis, OR (95%CI)	P value
Liver decompensation
Age at diagnosis	1.06 (1.01-1.11)	< 0.01	0.97 (0.90-1.05)	NS
Male sex	1.00 (0.41-2.40)	NS	0.85 (0.18-4.12)	NS
Child B vs A	40.0 (8.03-199)	< 0.001	111 (11-1101)	< 0.001
Child C vs A	60.8 (7.2-513)	< 0.001	102 (7-1480)	< 0.001
Renal impairment1	3.75 (1.14-12.3)	< 0.023	2.90 (0.40-21.1)	NS
Hyponatremia2	4.45 (1.50-13.2)	< 0.005	2.89 (0.48-17.4)	NS
Hepatocellular carcinoma
Age at diagnosis	1.04 (0.99-1.10)	NS	1.03 (0.95-1.12)	NS
Male sex	2.30 (0.79-6.70)	NS	2.38 (0.67-8.44)	NS
Child B vs A	1.09 (0.31-3.84)	NS	0.62 (0.13-2.86)	NS
Child C vs A	1.67 (0.46-6.10)	NS	0.76 (0.14-4.04)	NS
Renal impairment1	3.62 (1.18-11.0)	< 0.019	2.37 (0.52-10.9)	NS
Hyponatremia2	4.37 (1.18-13.15)	< 0.006	4.11 (1.14-14.9)	< 0.031

¹Renal impairment: serum creatinine > 1.20 mg/dL;

²Hyponatremia: serum Na < 135 mE/L. In addition to the variables reported in the table, analysis included also: ALT/AST, α-fetoprotein, metabolic syndrome, obesity, serum cholesterol, type 2 diabetes mellitus, cardiovascular events. NS: Not significant.

Table 6 Predictors of mortality of the 102 patients with cryptogenic cirrhosis

Outcome	Univariate analysis, HR (95%CI)	P value	Multivariate analysis, HR (95%CI)	P value
Overall mortality
Age at diagnosis	1.07 (1.03-1.10)	< 0.001	1.11 (1.04-1.18)	0.001
Male sex	1.10 (0.55-2.20)	NS	1.07 (0.46-2.48)	NS
Child B vs A	9.75 (2.85-33.32)	< 0.001	8.35 (2.16-32.29)	< 0.002
Child C vs A	23.62 (6.64-84.05)	< 0.005	34.64 (7.5-160.7)	< 0.001
Renal impairment1	2.63 (1.31-5.30)	< 0.007	0.65 (0.28-1.54)	NS
Hyponatremia2	2.66 (1.34-27)	< 0.005	0.84 (0.36-1.95)	NS

¹Renal impairment: serum creatinine > 1.20 mg/dL;

²Hyponatremia: serum Na < 135 mE/L. In addition to the variables reported in the table, analysis included also: ALT/AST, α-fetoprotein, metabolic syndrome, obesity, serum cholesterol, type 2 diabetes mellitus, cardiovascular events. NS: Not significant.