Relevance of Sarcopenia in Advanced Liver Disease

Official title

A Rapid, Non-invasive, Clinical Surveillance for CachExia, Sarcopenia, Portal Hypertension and Hepatocellular Carcinoma in End-Stage Liver Disease

Overview

Patients with established liver cirrhosis, or end-stage liver disease (ESLD), are at high risk of developing liver cancer (hepatic carcinoma; HCC), portal hypertension, and sarcopenia, all which lead to significant morbidity and mortality. In this patient group the annual incidence of HCC is c. 2-8% and these patients are therefore included in ultrasound HCC screening programs every 6 months. In this study, the investigators are aiming to assess sarcopenia, clinically significant portal hypertension (CSPH), and HCC with a single short magnetic resonance (MR) examination. A neck-to-knee MRI-examination will be acquired to derive body composition profile (BCP) measurements including visceral and abdominal subcutaneous adipose tissue (VAT and ASAT), thigh fat free muscle volume (FFMV) and muscle fat infiltration (MFI), as well as liver fat (PDFF), spleen volume, and liver stiffness. Images will be further processed by AMRA Medical AB. AMRA's solution includes FFMV in the context of virtual control groups (VCG; using AMRA's vast database) and MFI. Furthermore, the spleen volume will be used to monitor the development of portal hypertension and explored together with other BCP variables in relation to hepatic decompensation events. HCC screening will be performed using so-called abbreviated MRI (AMRI), which consists of time series of contrast-enhanced T1-weighted images. The AMRI images will be read by an experienced radiologist. In the literature the sensitivity of AMRI to detect HCC is above 80%, with a specificity of c. 95%, compared to ultrasound sensitivity of 60%. In treating ESLD there is a desire of physicians to be able to predict future decompensation events in order to initiate treatment to prolong survival. Moreover, the ability to assess processes of sarcopenia in the patient would be highly valuable for clinical practice due its severe clinical impact. Finally, ultrasound-based HCC screening has poor diagnostic performance and a MR-based screening approach would significantly improve treatment outcome as more treatable and earlier HCC may be identified.

Detailed description

150 patients with established or probable liver cirrhosis at the Department of Gastroenterology and Hepatology at Linköping University Hospital, as well as collaborating hospitals; District Hospital in Eksjö and County Hospital in Jönköping, will be included in the study. The study includes four visits every six months (in patients with LI-RADS 3 five visits will be performed); each patient participates actively in the study during a time period of approximately 24 months. All study visits are scheduled in conjunction with clinical routine visits.

During each study visit the following is performed:

* A detailed clinical work-up * Assessment of medical history or changes in health status since last visit * FibroScan * Magnetic resonance (MR) examination * Comprehensive blood panels and blood samples for research * Muscle function and mobility assessments (SPPB and hand grip strength). * Quality of life assessment (EQ-5D-5L, QLDQ-cirrhosis and SHS-liver). * Hepatic encephalopathy assessment (ANT test). * Assessment of the development of symptoms

Primary outcome measures

• Body composition (FFMVvcg) [Time frame: Baseline]
• Body composition (FFMVvcg) [Time frame: 6 months]
• Body composition (FFMVvcg) [Time frame: 1 year]
• Body composition (FFMVvcg) [Time frame: 18 months]
• Change from baseline Body composition (FFMVvcg) [Time frame: 6 months]
• Change from 6 months Body composition (FFMVvcg) [Time frame: 1 year]
• Change from 1 year Body composition (FFMVvcg) [Time frame: 18 months]
• Muscle fat infiltration (%) [MFI] [Time frame: Baseline]
• Muscle fat infiltration (%) [MFI] [Time frame: 6 months]
• Muscle fat infiltration (%) [MFI] [Time frame: 1 year]

Secondary outcome measures (12)

• Death [Time frame: 6 months]
• Death [Time frame: 1 year]
• Death [Time frame: 18 months]
• Death [Time frame: 2 years]
• Esophageal varices [Time frame: Baseline]
• Development of Esophageal varices [Time frame: 6 months]
• Development of Esophageal varices [Time frame: 1year]
• Development of Esophageal varices [Time frame: 18 months]
• Development of Esophageal varices [Time frame: 2 years]
• Liver stiffness by Fibroscan (kPa) [Time frame: Baseline]
• Liver stiffness by Fibroscan (kPa) [Time frame: 6 months]
• Liver stiffness by Fibroscan (kPa) [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• Established or probable liver cirrhosis according to clinical practice at the Department of Gastroenterology and Hepatology at Linköping University Hospital. This is not by necessity biopsy verified, it can be different criteria such as FibroScan, symptoms, biopsy, and radiology.
• Age ≥18 years
• Written informed consent from the participant

Exclusion criteria

• Contraindications for MRI
• Subjects suffering from primary sclerosing cholangitis (PSC)
• Subjects diagnosed with Hepatic carcinoma (HCC)
• Previous liver transplant

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Sweden · 3 centers

• Department of Gastroenterology), District Hospital in Eksjö — Eksjö
• Department of gastroenterology, County Hospital in Jönköping — Jönköping
• Department of gastroenterology and hepatology — Linköping

Publications

• Nasr P, Forsgren M, Balkhed W, Jonsson C, Dahlstrom N, Simonsson C, Cai S, Cederborg A, Henriksson M, Stjernman H, Rejler M, Sjogren D, Cedersund G, Bartholoma W, Ryden I, Lundberg P, Kechagias S, Leinhard OD, Ekstedt M. A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol PMID 38129794

Identifiers

NCT: NCT05502198 · 2020-07215

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗