Author information

• ¹Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
• ²European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.
• ³Bicocca Bioinformatics Biostatistics and Bioimaging Centre - B4, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
• ⁴Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy.
• ⁵Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
• ⁶Division of Hepatology, Ospedale San Giuseppe, University of Milan, Milan, Italy.
• ⁷Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy.
• ⁸CRC "A. M. e A. Migliavacca" Center for Liver Diseases, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
• ⁹Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino "Sapienza" University of Rome, Latina, Italy.
• ¹⁰Department of Internal Medicine, University of Genova, Genova, Italy.
• ¹¹San Gerardo Hospital, Pathology department, Monza, Italy.
• ¹²Histopathology Unit, AOU Maggiore della Carità, Novara, Italy.
• ¹³Department of Precision and Translational Medicine, Sapienza University of Rome, Rome, Italy.
• ¹⁴Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
• ¹⁵Università Politecnica delle Marche", Department of Gastroenterology, Ancona, Italy.
• ¹⁶Studiosa Senior, University of Padova, Italy, Padova.
• ¹⁷Scientific Consultant, IRCCS Negrar, Verona, Italy.
• ¹⁸Department of Movement, Human and Health Science, University of Rome "Foro Italico", Rome, Italy.
• ¹⁹Department of Mathematics, University of Rome Tor Vergata, Rome, Italy.

Abstract

Background & aims: Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Non-invasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis at disease presentation in PBC.

Approach & results: We collected data from 167 consecutive treatment-naïve PBC patients who underwent liver biopsy(LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves(AUROCs) for advanced fibrosis (Ludwig stage≥III). The effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. Derivation cohort consisted of 126 patients with valid LSM and LB, VCTE identified patients with advanced fibrosis with AUROC of 0.89. LSM cut-offs ≤6.5kPa and >11.0kPa enabled to exclude and confirm, respectively, advanced fibrosis (negative predictive value[NPV]=0.94, positive predictive value[PPV]=0.89, error rate=5.6%). These values were externally validated in an independent cohort of 91 PBC patients(NPV=0.93, PPV=0.89, error rate=8.6%). Multivariable analysis found the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry.

Conclusions: In a multicenter study of treatment-naïve PBC patients, we identified two cut-offs (LSM≤6.5kPa and>11.0kPa) able to discriminate at diagnosis the presence or the absence, respectively, of advanced fibrosis in PBC patients, with external validation. In patients with LSM between these two cut-offs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.