Non-alcoholic steatohepatitis in liver transplant recipients diagnosed by serum cytokeratin 18 and transient elastography: A prospective study

Table 1 Characteristics of patients at study entry

	Whole cohort	Patients who developed NAFLD	Patients who developed NASH
	n = 40	n = 22	n = 17
Age (yr)	57.3 ± 8.5	55.5 ± 9.2	56.3 ± 7.9
Male (%)	28 (70)	18 (82)	14 (82)
Ethnicity (%)
Caucasian	32 (80)	19 (86)	15 (88)
Other (Asian, Black, Arab)	8 (20)	3 (14)	2 (11)
Etiology of liver disease (%)
NASH	21 (52.5)	13 (52)	12 (70)
HCC	9 (22.5)	2 (9)	2 (12)
HCV (excluding genotype 3)	8 (20)	6 (27)	3 (18)
Alcoholic liver disease	1 (2.5)	1 (4.5)	0
Other	1 (2.5)	0	0
BMI (kg/m2)	24.8 ± 4.6	26.2 ± 5.1	26.6 ± 4.5
BMI >25 (%)	18 (40)	14 (64)	12 (70)
Comorbidities (%)
Diabetes	14 (35)	9 (41)	8 (47)
Hypertension	15 (37.5)	7 (32)	8 (47)
Dyslipidemia	6 (15)	6 (27)	5 (29)
MELD-Na Score	< 9	< 9	< 9
Laboratory
AST (U/L)	27.6 ± 33	31.8 ± 41.2	34.5 ± 45.1
ALT (U/L)	32.8 ± 42.8	37.6 ± 52.6	40.6 ± 57.7
GGT (U/L)	177.5 ± 256.6	177.7 ± 271.4	188.1 ± 297.6
Bilirubin (µmol/L)	17 ± 15.9	18.2 ± 17.3	18 ± 18.2
INR	1.25 ± 1.39	1.05 ± 0.12	1.04 ± 1.3
Albumin (g/L)	39.6 ± 3.69	38.7 ± 4.3	39.4 ± 3.9
Platelets (109/L)	172.3 ± 86.9	185 ± 92.5	170.5 ± 93.6

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; GGT: Gamma-glutamyl transpeptidase; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; INR: International normalized ratio; MELD-Na: Model for end stage liver disease-sodium; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis.

Table 2 Diagnostic accuracy of non-invasive tests compared to liver histology (N = 35 from 24 patients)

	NAFLD		NASH	Liver fibrosis
	CAP	HSI	CAP + CK-18	LSM	FIB-4	APRI
Sensitivity (%)	58	64.3	75	61.9	7.1	14.3
Specificity (%)	86	33	83	54.2	73.9	78.3
PPV (%)	70	39	37	54.2	14.3	28.6
NPV (%)	79	58	96	61.9	56.7	60
LR+	4.28	0.96	4.5	1.35	0.27	0.66
LR-	0.48	1.07	0.3	0.7	1.26	1.1
Accuracy (%)	76	45.7	82	57.8	48.7	54.1

APRI: Aspartate aminotransferase-to-Platelets Ratio Index; CAP: Controlled attenuation parameter; CK-18: Cytokeratin 18; FIB-4: Fibrosis 4 index; HSI: Hepatic steatosis index; LSM: Liver stiffness measurement; LR: Likelihood ratio; MELD-Na: Model for end stage liver disease-sodium; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; NPV: Negative predictive value; PPV: Positive predictive value.

Table 3 Risk factors for post-Liver Transplant development of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis using univariate and multivariate Cox regression analysis

	NAFLD				NASH
	Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	aHR (95%CI)	P value	HR (95%CI)	P value	aHR (95%CI)	P value
Female sex (yes vs no)	0.6 (0.4-1.2)	0.1	0.9 (0.3-1.7)	0.5	0.6 (0.3-1.1)	0.1	0.9 (0.4-2.1)	0.8
Age (per year)	1.0 (0.9-1.0)	0.6			1.0 (0.9-1.0)	0.9
BMI (per kg/m2)	1.1 (1.0-1.2)	< 0.01	1.1 (1.0-1.2)	< 0.01	1.1 (1.0-1.2)	0.01	1.1 (1.0-1.3)	< 0.01
Diabetes (yes vs no)	1.7 (1.0-2.7)	0.02			1.3 (0.7-2.1)	0.3
Dyslipidemia (yes vs no)	4.6 (1.7-12.8)	< 0.01			4.4 (1.5-13)	0.007
ALT (per U/L)	1.0 (0.9-1.0)	0.09	1 (0.9-1.0)	0.3	1.0 (1.0-1.0)	0.03	1 (0.9-1.0)	0.1

aHR: Adjusted hazard ratio; ALT: Alanine aminotransferase; BMI: Body mass index; CI: Confidence interval; HR: Hazard ratio; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis.