A validated clinical tool for the prediction of varices in PBC: The Newcastle Varices in PBC Score

Background & Aims

Gastro-oesophageal varices (GOV) can occur in early stage primary biliary cirrhosis (PBC), making it difficult to identify the appropriate time to begin screening with oesophageo-gastro-duodenoscopy (OGD). Our aim was to develop and validate a clinical tool to predict the probability of finding GOV in PBC patients.

Methods

A cross-sectional retrospective study analysing clinical data of 330 PBC patients who underwent an OGD at the Freeman Hospital, Newcastle was used to create a predictive tool, the Newcastle Varices in PBC (NVP) Score, that was externally validated in PBC patients from Cambridge (UK) and Toronto (Canada).

Results

48% of the Newcastle, 31% of the Cambridge, and 22% of the Toronto cohorts of PBC patients had GOV. Twenty-five percent (95% CI 18–32%) of the Newcastle cohort had GOV diagnosed at an index variceal bleed. Of the others, 37% (95% CI 28–46%) bled after a median of 1.5 years (IQR 3.75). Transplant-free survival was significantly better in those without GOV than in those with GOV (p <0.001), but similar in patients with GOV that bled and those that did not (p = 0.1). The NVP score (%Probability) = 1/[1 + exp^−(9.186 + 0.001 * alkaline phosphatase in IU − 0.178 * albumin in g/L − 0.015 * platelet × 10⁹) was validated in 2 external cohorts and was highly discriminant (AUROC 0.86). Cost consequences analyses revealed the NVP score to be as accurate as, but more economical than using either OGD directly or other risk scores for screening PBC patients.

Conclusions

The NVP score is an inexpensive, non-invasive, externally validated tool that accurately predicts GOV in PBC.

Introduction

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterised by progressive damage to small intrahepatic bile ducts resulting in cholestasis, fibrosis, and ultimately cirrhosis. Portal hypertension in PBC, and gastro-oesophageal varices (GOV) in particular, denote poor prognosis [1], [2], [3]. In a comprehensive report, almost half of those with PBC who developed GOV experienced variceal haemorrhage with survival of 63% and 43% after 1 and 3 years [4]. Earlier reports suggested portal hypertension in PBC was rare [5] and characteristic of advanced symptomatic disease. In reality, variceal haemorrhage in PBC has a reported prevalence of around 30% [4]. Notably, GOV may develop in asymptomatic patients with PBC [2], may be the presenting feature preceding jaundice [6], [7], [8], and may precede cirrhosis [9].

Current EASL and AASLD guidelines recommend screening with oesophageo-gastro-duodenoscopy (OGD) in advanced (Stage IV) disease [10], [11], although it is recognised that histology may underestimate disease severity [12] and that the evidence regarding the selection of patients and timing of screening is contradictory [10], [11], especially in patients with early stage disease. The default of indiscriminate screening is associated with increased cost and risk to patients, supporting development of validated, more rational ways to stratify the risk of varices. Alternative triggers are therefore needed to decide when to screen for varices, independent of histology. Several non-invasive tools based on laboratory parameters alone, or in combination with imaging, help identify patients with PBC and GOV appropriate for OGD screening [9], [10], [13], [14], [15]. It is not clear if such approaches are cost effective. We sought to develop and validate a non-invasive, cost-evaluated composite scoring tool, utilising parameters measured routinely during follow-up in office-based practice, to identify the percentage probability of finding GOV in patients with PBC which accommodated important aspects of the natural history of variceal haemorrhage in PBC.