Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut‐Off Approach

Abstract

on the behalf of the Italian PBC RegistryBaCKgRoUND aND aIMS: Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive 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 (AF) at disease presentation in PBC. appRoaCH aND 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 the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and >11.0 kPa enabled to exclude and confirm, respectively, AF (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 that 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 cutoffs (LSM ≤6.5 and >11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs. (Hepatology 2021;74:1496-1508. P rimary biliary cholangitis (PBC) is an autoimmune liver disease characterized by destructive cholangitis affecting the small intrahepatic

Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis

“…Among the different techniques available, VCTE (FibroScan  ) was the first to be marketed, has been the most extensively evaluated, and is today one of the most popular and commonly used, especially in hepatology units [14,35]. Prior studies in patients with PBC have shown an association of LSM with histological fibrosis stage, degree of portal hypertension, and risk of death or need for LT [16,17,19,20,[36][37][38]. However, these results are still supported by limited data and a few small-size single-centre studies.…”

“…Today, of the various alternative techniques of liver elastography, VCTE remains one of the most popular and widely used worldwide [15]. Liver stiffness measurement (LSM) by VCTE has indeed been shown as a very simple and reliable means for diagnosing cirrhosis or advanced fibrosis in many chronic liver diseases, including PBC [16,17]. It has further been linked to the risk of portal hypertension, cirrhotic decompensation, hepatocellular carcinoma, and liver-related mortality in different liver conditions, including PBC [16,[18][19][20].…”

Role of ductular reaction and ductular–canalicular junctions in identifying severe primary biliary cholangitis

“…J o u r n a l P r e -p r o o f 9 Histological staging was performed on all slides according to multiple histological scoring systems and criteria (Ludwig, Nakanuma, Ishak, Scheuer, Metavir). 6,9,10,15 For the purposes of this study, patients were categorized as early (Ludwig I-II) and advanced stage (Ludwig III-IV).…”

“…The leading cause(s) of the diverse disease progression have been poorly studied, and few biomarkers are available to follow people with PBC along their clinical course, whereas risk stratification at diagnosis relies only on age, histological stage, signs of hepatic dysfunction and/or portal hypertension, and liver stiffness. 6 , 7 Alkaline phosphatase (ALP) is a marker of cholestasis and bile duct injury and represents the pillar of the ‘UDCA response’ 7 ; the magnitude of its reduction after UDCA therapy relates to long-term outcomes as confirmed by large-scale, observational studies. 8 However, the mechanisms underlying UDCA effects in cholestasis and the heterogeneous response in people with PBC remain to be evaluated.…”

Clinical characterization of patients with primary biliary cholangitis: A report from multiple Canadian centres

“…Over the past few decades, there have been many changes in the diagnosis and management of PBC, with more patients being recognized with earlier-stage disease and with the use of the recommended first-line pharmacotherapy, ursodeoxycholic acid (UDCA) (6,7). The use of liver stiffness measurement (LSM), using vibration-controlled transient elastography (VCTE), is now routinely performed in PBC (8,9).…”