Background/Aims: Advanced fibrosis (F≥3) indicates poor outcomes in nonalcoholic fatty liver disease (NAFLD). Here, we examined the diagnostic performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) for detecting (or excluding) advanced fibrosis in patients with biopsy-proven NAFLD. Methods: The diagnostic performance of each noninvasive test according to previously identified cutoff points indicating low and high risk for advanced fibrosis was determined in 463 patients with NAFLD. Patients who scored <1.3 and >2.67 on the FIB-4 were considered at low and high risk for advanced fibrosis, respectively. Patients who scored <-1.455 and >0.676 on the NFS were considered at low and high risk for advanced fibrosis, respectively. Results: Eightyone patients (17.5%) had biopsy-proven advanced fibrosis (F≥3). The published FIB-4 cutoff values for low and high risk were able to exclude advanced fibrosis with negative predictive values (NPVs) of 0.907 and 0.843 and specificities of 74% and 97%, respectively. The published NFS cutoff values for low and high risk were able to exclude advanced fibrosis with NPVs of 0.913 and 0.842 and specificities of 63% and 96%, respectively. If biopsies were performed in only patients with a FIB-4 above the low cutoff point (≥1.3), 67.1% could be avoided. Conversely, if biopsies were performed in only patients with an NFS above the low cutoff point (≥-1.455), 57.0% could be avoided. Conclusions: The main clinical utility of the FIB-4 and NFS in patients with NAFLD lies in the ability to exclude, not identify, advanced fibrosis.

Background: Patients with non-alcoholic fatty liver disease (NAFLD) and more advanced fibrosis tend to have more impairment in their health-related quality of life and other patient-reported outcomes (PROs). Aim: To assess the association of PROs with select non-invasive tests (NITs) for fibrosis including FAST, Agile 3+ and Agile 4 scores Methods: We enrolled patients with an established diagnosis of NAFLD who were seen in a tertiary care clinic into the NAFLD/NASH Registry. The FAST, Agile 3+ and Agile 4 scores were calculated using liver stiffness measurements by transient elastography and laboratory parameters. PROs were assessed using FACIT-F, CLDQ-NASH and WPAI instruments (total of 17 domain and summary scores).Results: There were 1509 patients with NAFLD (mean age: 49 ± 11 years, 50% men, 41% employed, 30% advanced fibrosis and 20% cirrhosis). The mean FAST, Agile 3+ and Agile 4 scores were 0.39 ± 0.26, 0.35 ± 0.31 and 0.12 ± 0.23, respectively. Subjects with lower FAST, Agile 3+ and Agile 4 scores had the highest scores in select domains of FACIT-F, CLDQ-NASH and WPAI (p < 0.05 in comparison to subjects with elevated or high-risk NIT scores). Correlations with continuous NITs were significantly negative for Emotional and Functional well-being (FACIT-F), Activity/energy, Systemic symptoms, Worry and total scores (CLDQ-NASH), and Activity of WPAI (p < 0.05); the strongest was for Worry (CLDQ-NASH) with FAST (R = −0.17, p < 0.0001). The PRO scores of patients with NAFLD were lower than those of matched patients with chronic hepatitis B (p < 0.05 for 9/17 domain and summary scores). Conclusion:Patients with NAFLD and high FAST, Agile 3+ or Agile 4 scores experience impairment of health-related quality of life.

Background Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased arterial stiffness. However, the question as to whether an association exists between the extent of vascular and liver stiffness in patients with biopsy-proven NAFLD remains open. In this study, we sought to investigate whether pulse wave velocity (PWV) and augmentation index (AIx) – two common indices of arterial stiffness – are associated with (a) liver stiffness measurement (LSM) on transient elastography (TE) and (b) histological liver fibrosis. Patients and methods We examined 125 patients with biopsy-proven NAFLD and 55 age-matched and sex-matched controls. Arterial stiffness of the brachial artery was measured using a Mobil-O-Graph arteriography system. LSM was assessed using TE, whereas the presence of advanced fibrosis (F ≥ 3) was determined on histology. Results Patients with NAFLD had higher PWV [median: 7.2 (6.3−8.2) and 6.2 (5.5−6.7) m/s, respectively, P < 0.001] and AIx (mean: 21.3 ± 13.5 and 17.2 ± 11.9%, respectively, P=0.01) compared with the controls. LSM showed positive correlations with both PWV (ρ = 0.300; P<0.01) and AIx (ρ = 0.223, P = 0.02). Both indices of arterial stiffness were higher in patients with advanced fibrosis than in those with nonadvanced fibrosis (F ≤ 2). Conclusion The severity of arterial and liver stiffness increases in parallel in patients with biopsy-proven NAFLD. Systematic risk assessment for reducing arterial stiffness is recommended in the presence of TE-determined advanced fibrosis.

Background and Aims: Programmed cell death-1 (PD-1) has a vital role in regulating T-cell function, and immune escape mechanism of cancer cells. It was shown that there could be a relationship between single nucleotide polymorphisms (SNPs) in the PD-1 gene and susceptibility to hepatocellular carcinoma (HCC) based on various studies. We aimed to investigate the role of three SNPs within the PD-1 gene in susceptibility to HCC in the Turkish population. Methods: Single nucleotide polymorphisms of PD-1.1, 1.5, and 1.6 were genotyped by using TaqMan Allelic Discrimination Assays in blood samples of 137 HCC and 136 control subjects, matched for age and gender. The genotype, allele and haplotype frequencies were compared in HCC and control groups using logistic regression analysis. Results: Genotype distributions of PD-1.1, PD-1.5 and PD-1.6 SNPs were in Hardy-Weinberg equilibrium. No significant difference was observed in the genotype distribution of PD-1.1, PD-1.5 and PD-1.6 polymorphisms among gender and age-matched HCC (M/F: 96/41; mean age: 61.4 ±11.7 years) and control group (M/F: 94/42; mean age: 61.4±10.1). In the haplotype analysis of PD-1.1/PD-1.5/PD-1.6, no significant difference was found among HCC and control group adjusted for sex and age (all p values>0.1). Conclusion: Our findings, firstly reporting the association of PD-1.5 polymorphism with HCC, and PD-1.1 and PD-1.6 with HCC in the Turkish population, suggest that PD-1 polymorphisms are not predisposing factors for HCC development. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.

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