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Abstract Details
Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis
J Hepatol. 2022 Jun 28;S0168-8278(22)00411-1. doi: 10.1016/j.jhep.2022.06.017.Online ahead of print.
1Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris; Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France. Electronic address: christophe.corpechot@aphp.fr.
2Public Health Unit, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris; Pierre Louis Institute of Epidemiology and Public Health, Sorbonne University, Paris, France.
3Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris; Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France.
4Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Canada.
5Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Canada.
6Department of Medicine I and Martin Zeitz Center for Rare Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
7Liver Unit, Hospital Clínic, University of Barcelona, The August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Barcelona, Spain.
8Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, USA.
9Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), General University Hospital, Larissa, Greece.
10Division of Hepatology and Liver Transplantation, European Reference Network on Hepatological Diseases (ERN Rare-Liver), University Hospitals KU, Leuven, Belgium.
11Department of Surgery, Oncology and Gastroenterology, European Reference Network on Hepatological Diseases (ERN Rare-Liver), University of Padova, Padova, Italy.
12Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
13University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom.
14Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy.
15Department of Hepatology, University Hospitals of Bordeaux, Pessac, France.
16Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, USA.
17Department of Internal Medicine, Università del Piemonte Orientale, Novara, Italy.
18Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, European Reference Network on Hepatological Diseases (ERN Rare-Liver), University of Milano-Bicocca, Monza, Italy.
19Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
20The Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
21Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
22Department of Gastroenterology and Hepatology, Edouard Herriot Hospital, Hospices Civils de Lyon, Claude Bernard University, Lyon, France.
23Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
24Department of Hepatology and Liver Transplantation, University Hospital, Montpellier, France.
25Department of Hepatology and Liver Transplantation, Newcastle upon Tyne Hospitals, Newcastle University, United Kingdom.
Abstract
Background & aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) was shown to predict outcomes of primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study.
Methods: We performed an international, multicentre, retrospective follow-up study of 3985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least one reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n=2740) and validation (n=568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with confidence intervals (CIs) were determined using a time-dependent multivariable Cox regression analysis.
Results: LSM was independently associated with poor clinical outcomes in the derivation (5324 LSMs, mean follow-up 5.0 ± 3.1 yrs.) and validation (1470 LSMs, mean follow-up 5.0 ± 2.8 yrs.) cohorts: adjusted HRs (95%CI) per additional kPa were 1.040 (1.026-1.054) and 1.042 (1.029-1.056), respectively (p<0.0001 for both). Adjusted C-statistics (95%CI) at baseline were 0.83 (0.79-0.87) and 0.92 (0.89-0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8-kPa and 15-kPa cut-offs optimally separated low, medium, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM.
Conclusions: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered.
Lay summary: Serum levels of bilirubin and alkaline phosphatase are the only surrogate markers approved by regulatory authorities to assess patients with PBC in therapy trials. Liver histology has been shown to improve prediction of survival beyond these markers but liver biopsy is a potentially harmful, invasive procedure and a serious obstacle to clinical trial recruitment. In the present large, international retrospective cohort study, liver stiffness assessed by vibration-controlled transient elastography was validated as one of the strongest predictive factors of poor clinical outcome in PBC and was shown to improve the prognostic ability of established biochemical markers of treatment response. Studies to evaluate the prognostic impact of LSM changes over time are needed to determine whether LSM can be used as a new surrogate end point for PBC.