Exploring algorithms to select candidates for non-selective beta-blockers in cirrhosis: a post-hoc analysis of the PREDESCI trial.

Background & aims: Whether non-invasive tests (NITs) can accurately select patients with cirrhosis requiring non-selective beta-blockers (NSBB) for clinically significant portal hypertension (CSPH) and prevention of decompensation is unclear. Our aim was to test the performance of NIT-based algorithms for CSPH diagnosis using the prospective PREDESCI cohort. We investigated a new algorithm combining NITs with endoscopy to improve performance.

Methods: We included patients with compensated cirrhosis and available liver elastography who were screened during the trial. The performance of models based on liver stiffness measurement (LSM) and platelet count was evaluated. An algorithm considering endoscopy for patients with inconclusive results (the "grey zone") was then developed and validated in an independent cohort of 195 patients in whom also spleen stiffness was available.

Results: We included 170 patients from the PREDESCI cohort. An LSM≥25 kPa alone (Baveno VII criteria) or an LSM>20 kPa plus thrombocytopenia (AASLD criteria) ruled-in CSPH with positive predictive value of 88 and 89%, respectively. However, 37%-47% patients fell into the grey zone while at high-risk of decompensation or death. Performing endoscopy in inconclusive cases identified patients with varices that, when re-classified as high-risk for CSPH, significantly reduced the grey zone to 22%. In this algorithm, 86% of CSPH patients were correctly classified as high-risk. The diagnostic performance was confirmed in the external validation cohort, where combining Baveno VII criteria with spleen stiffness showed similar accuracy to the model using endoscopy.

Conclusions: Algorithms based only on LSM and platelet count are suboptimal to identify NSBB treatment candidates. Performing endoscopy in patients with indeterminate findings from NITs improved diagnostic performance and risk stratification. Endoscopy may be substituted by spleen stiffness for stratifying the risk in the grey zone.

Impact and implications: The PREDESCI trial demonstrated that non-selective beta-blockers prevent decompensation in CSPH patients. Still it is unclear whether we can select treatment candidates using non-invasive tests to assess the presence of CSPH without measuring HVPG. In the prospective cohort of patients screened during the trial, we showed that algorithms based on liver stiffness and platelet count had suboptimal performance, mainly due to a high rate of indeterminate results. Performing endoscopy in the grey zone patients allowed to significantly increase the number of patients with CSPH and improved the risk stratification for decompensation or death on long-term follow-up. These findings were validated in an independent cohort. In addition, a model using spleen stiffness instead of endoscopy showed similar diagnostic performance in the external validation cohort, suggesting that adequate risk stratification to select treatment candidates can be achieved with a fully non-invasive algorithm.