Sinakos, Emmanouil

Abstract Background and Aim Following the approval of the first agent for the management of metabolic dysfunction‐associated steatohepatitis (MASH), identification of patients with fibrotic MASH (MASH with NAS ≥ 4 and fibrosis stage ≥ 2) is crucial. We assessed the performance of FibroScan‐aspartate aminotransferase (AST) score (FAST) for ruling in/out fibrotic MASH. Methods We searched Medline, Cochrane Library, Web of Science, Scopus, and gray literature sources up to January 11, 2024. Studies were eligible if they assessed the accuracy of FAST score for the detection of fibrotic MASH using biopsy as the reference standard at previously reported thresholds (FAST ≥ 0.67 for ruling‐in and ≤ 0.35 for ruling‐out fibrotic MASH). We calculated pooled sensitivity and specificity estimates for FAST thresholds alongside 95% confidence intervals following bivariate random‐ effects models. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Results We included 16 studies with 8838 participants. A FAST score ≥ 0.67 yielded a pooled specificity of 0.87 (0.82–0.90) while a FAST score ≤ 0.35 yielded a summary sensitivity of 0.88 (0.83–0.91). At a prevalence of 30%, the positive predictive value for ruling‐in fibrotic MASH was 60% while the negative predictive value for ruling‐out the target condition was 91%. AST levels, cirrhosis prevalence, and number of pathologists reviewing biopsies were sources of heterogeneity among studies. The certainty of evidence was low to very low. Conclusions FAST score can be used as a triage test for ruling out fibrotic MASH. Nevertheless, its low positive predictive value necessitates sequential testing for ruling‐in fibrotic MASH.

AbstractBackgroundBiochemical tests have been recommended as endpoints for clinical trials in primary biliary cirrhosis (PBC) because the use of liver transplantation and death as endpoints in ursodeoxycholic acid (UDCA) therapeutic trials is unfeasible. The best inclusion criteria cut‐off values and cut‐off for demonstrating treatment success have not been defined.AimOur aim was to determine the optimal biochemical values for patient inclusion and to define values for treatment success in therapeutic trials.MethodsWe performed a retrospective review of 73 patients with PBC treated with UDCA followed over 36 months. Following one year of UDCA therapy, the likelihood of developing clinical endpoints of varices, ascites, encephalopathy, death or transplantation over the ensuing two years, based on degrees of elevation of biochemical markers, was analyzed using chi‐square or Fisher's exact test.ResultsPatients with ALP≥2 X upper limit of normal (ULN) had a 2‐fold greater likelihood of developing endpoints compared to patients with lower values (23% versus 11%), (p < 0.05). Patients with bilirubin > 1 mg/dL were 4 times more likely to develop endpoints compared to those with lower values (33% versus 8%), (p = 0.02). These values help identify the patient population for adjunctive therapy trials. Patients with ALP ≤1.67 X ULN and bilirubin ≤1mg/dL demonstrated the least likelihood of reaching adverse clinical endpoints and can be used to define treatment success.ConclusionOptimal ALP and Bilirubin levels can be used as appropriate biochemical criteria for patient selection and defining treatment success in future clinical trials in patients with PBC.