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

Abstract

Background 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.

FIG. 1

Flow chart of the study. Notes: ⁽¹⁾We considered interpretable LB specimens those with at least 10 evaluable portal spaces. ⁽²⁾We considered valid LSM when 10 valid measurements were collected and classified as “very reliable” and “reliable” according to Boursier’s criteria.^{( 19 )} Abbreviation: MRCP, magnetic resonance cholangiopancreatography.

FIG. 2

Distribution of LSM according to histological stage by Ludwig in the derivation cohort. LSM increased significantly in fibrotic stages III and IV by the Ludwig system (Kruskal‐Wallis test, P < 0.00001).

FIG. 3

Logistic curve of the relationship between predicted probabilities of AF and LSM. The grey area highlights the portion of the curve in which VCTE may not be reliable in predicting AF.

FIG. 4

Density plot of LSM (A), FIB‐4 (B), and APRI score (C) in the derivation cohort. Patients with Ludwig stage I and II at liver biopsy are represented in purple lines, those with Ludwig stage III and IV in red lines. In the LSM density plot (A), the grey area highlights the interval of LSM in which TE is not reliable. In the APRI and FIB‐4 density plots (B,C), the peak of density of patients in early and advanced stage are almost overlapped, which underlies the limits of these tools in PBC. Note: The grey area in the FIB‐4 density plot (B) expresses the range of LSM in which FIB‐4 as proposed by Sterling et al.^{( 16 )} The black straight line in the APRI score density plot (C) expresses the cutoff of 0.54 validated in PBC.^{( 20 )} Extreme observations were excluded (4 cases).

FIG. 5

Proposed algorithm for risk stratification at diagnosis in PBC patients.