Multicenter Validation Study of a Diagnostic Algorithm to Detect NASH and Fibrosis in NAFLD Patients With Low NAFLD Fibrosis Score or Liver Stiffness

Abstract

OBJECTIVES:Nonalcoholic steatohepatitis (NASH) and fibrosis play critical roles for the prognosis of patients with nonalcoholic fatty liver disease (NAFLD). Identification of patients at risk of NASH and fibrosis is therefore critical for disease management. NAFLD Fibrosis Score (NFS) and transient elastography (TE) have been suggested to exclude advanced fibrosis. However, there is increasing evidence that also patients with NASH and early fibrosis are at risk of disease progression and complications, emphasizing the need for improved noninvasive risk stratification in NAFLD.METHODS:Because hepatocyte apoptosis plays an early role in NASH pathogenesis, we evaluated whether the apoptosis biomarker M30 might identify NAFLD patients who are at risk of NASH and fibrosis despite low NFS or TE values. Serum M30 levels were assessed by enzyme-linked immunosorbent assay in combination with NFS and/or TE in an exploration (n = 103) and validation (n = 100) cohort of patients with biopsy-proven NAFLD.RESULTS:Most patients with low NFS (cutoff value < −1.455) revealed increased M30 levels (>200 U/L) in the exploration (62%) and validation (67%) cohort, and more than 70% of them had NASH, mostly with histological fibrosis. Vice versa, most patients with NFS < −1.455 but nonelevated M30 levels showed no NASH. NASH was also detected in most patients with indeterminate NFS (−1.455 to 0.676) but elevated M30 levels, from which ∼90% showed fibrosis. Similar results were obtained when using TE instead of NFS.DISCUSSION:The combination of the M30 biomarker with NFS or TE enables a more reliable identification of patients with an increased risk of progressed NAFLD and improves patient stratification.

Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial

“…A total of 285 adults with NAFLD that met the initial eligibility criteria were invited for a screening visit. NAFLD diagnosis was confirmed by abdominal ultrasound with liver stiffness > 9.6 kpa [18, 19]. Inclusion criteria were as follows: BMI > 24 kg/m 2 ; age between 18 and 65 years; stable body weight for 3 months prior to the beginning of the study (< 5 kg weight loss or weight gain).…”

Accuracy of cytokeratin 18 (M30 and M65) in detecting non-alcoholic steatohepatitis and fibrosis: A systematic review and meta-analysis

“…CK-18 can potentially improve risk stratification in combination with other synergistic markers, such as TE or NFS, by testing for elevated M30 levels among patients under the low threshold or in patients with intermediate TE/NFS values (between the high and low threshold) [64]. In the study by Liebig et al, risk stratification was considerably improved with this approach, showing more than 70% of patients with low TE/NFS but elevated M30 revealing presence of NASH (mostly with fibrosis).…”

Adipokines and Endotoxemia Correlate with Hepatic Steatosis in Non-Alcoholic Fatty Liver Disease (NAFLD)

“…However, NASH was defined by liver histology in a subset of patients. In patients without liver histology, we required the presence of hepatic steatosis and elevated cytokeratin 18 fragments (M30 > 200 µg/mL) as an indicator of disease activity [17] and as such the study population is enriched with patients suffering from NASH. The degree of hepatic steatosis was stratified into mild (grade 1; n = 20), moderate (grade 2; n = 31) or severe (grade 3, n = 12) steatosis according to published semiquantitative scoring systems in a standardized manner by a trained study physician [18].…”