Noninvasive markers of liver steatosis and fibrosis after liver transplantation – Where do we stand?

Table 1 Studies investigating the role of nonalcoholic fatty liver disease in post-liver transplant setting

Ref.	Type of the study	Study population	Follow up	Diagnostic method	Incidence of NAFLD	Major outcomes
Bhagat et al[11]	Retrospective	71 NAFLD, 81 alcoholic liver disease	Median 1517-1686 d	43.4% biopsy, 56.6% US	30% NAFLD, 0% alcoholic liver disease	NAFLD recurrence more common than de novo; acute cellular rejections more common in NAFLD group; no influence on CVD and overall mortality
Bhati et al[12]	Retrospective	103 NAFLD	Median 47-78 mo	90% biopsy or TE	87.5% steatosis (TE), reccurent NAFLD 88.2% (biopsy)	20.6% had bridging fibrosis (TE); advanced fibrosis (> F3) was seen in 26.8% (biopsy)
Seo et al[4]	Retrospective	68 non-NAFLD	Median 28 mo		18% de novo NAFLD, 9% NASH	Increase in BMI > 10% risk factor for de novo NAFLD; ACE-I protective role
Dumortier et al[14]	Retrospective	421 non-NAFLD	48 mo	Biopsy	53% had steatosis grade 1, 31% grade 2 and 16% grade 3 steatosis; 29% perisinusidal fibrosis; 3.8% NASH. 2.25% cirrhosis	MetS and its individual components, tacrolimus-based immunosuppressive therapy, alcoholic liver disease as the primary indication for LT and liver graft steatosis were associated with post-LT steatosis
Vallin et al[15]	Retrospective	80 de novo NAFLD, 11 recurrent NAFLD	5 yr		NASH and severe fibrosis (stages 3 and 4) were more common in recipients with recurrent than in those with de novo NAFLD (71.4% vs 12.5% and 71.4% vs 17.2%, respectively)	Recurrent NAFLD is a more severe disease with an earlier onset; prevalence of diabetes mellitus was higher in patients with recurrent NAFLD
Narayanan et al[19]	Retrospective	588 LT recipients; 9.7% NAFLD; 90.3% non-NAFLD	10 yr	41.5% biopsy, other US, CT, MR	Recurrent steatosis developed 77.6% and de novo 44.7%	Allograft steatosis did not influence post-LT survival or adverse CVD events, while underlying; NAFLD diagnosis was associated with a 2.04 increased risk of adverse cardiovascular events

LT: Liver transplantation; NAFLD: Nonalcoholic liver fatty disease; NASH: Nonalcoholic stetohepatitis, MeS: Metabolic syndrome; TE: Transient elastography; US: Ultrasound; CT: Computed tomography; BMI: Body mass index; ACE-I: Angiotensin converting enzyme inhibitors; MR: Magnetic resonance; CVD: Cardiovascular disease.

Table 2 Asparthate-aminotraspherase-to-platelet ratio index and fibrosis score 4 for fibrosis detection in liver transplant recipients

Ref.	Study population and etiology of ESLD	Prevalence F2-F4 (%)	Months after LT	Biochemical marker	Cut-off	Se	Sp	AUC	PPV	NPV
Toniutto et al[27], 2007	51 patients; HCV	32.4	24	APRI	1.4	76	77	0.80	46	93
Pissaia et al[28], 2009	50 patients; various etiologies	28	30.7	APRI	0.5	81	80	0.87	62	91
Kamphues et al[29], 2010	135 recipients; 94 HCV, 41 alcoholic cirrhosis	68.1	80.6	APRI	0.48	70	63	0.68	80	80
Pinto et al[30], 2014	30; biliary atresia, metabolic disease, other	20	60	APRI	0.4	83	58	0.74	31	94
Crespo et al[31], 2016	72; HCV	33	12	APRI	1.36	69	87	0.83	75	83
Pissaia et al[28], 2009	50 patients; various etiologies	28	30.7	FIB-4	3.25	31	94	0.78	67	77
Kamphues et al[29], 2010	135 recipients; 94 HCV, 41 alcoholic cirrhosis	68.1	80.6	FIB-4	2.8	44	87	0.66	88	42
Crespo et al[31], 2016	72; HCV	33	12	FIB-4	3.23	77	80	0.81	69	86

ESLD: End-stage liver disease; F: Fibrosis; Se: Sensitivity; Sp: Specificity; AUC: The area under the curve; PPV: Positive predictive value; NPV: Negative predictive value; HCV: Hepatitis C; APRI: AST-to-platelet ratio index; FIB-4: Fibrosis score 4.

Table 3 Factors that influence liver stiffness measurement measurements

Factors	Influence
Food intake	Increase LSM
Active alcohol consumption	Increase LSM
Liver inflammation	Increase LSM
Cholestasis	Increase LSM
Right heart failure	Increase LSM
Ascites	Unreliable measurements
Operator inexperience	High rate of unsuccessful measurements and examinations

LSM: Liver stiffness measurement.