Relevance of Sarcopenia in Advanced Liver Disease (ACCESS-ESLD)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis; Hepatocellular Carcinoma; Sarcopenia; Portal Hypertension

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

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Mattias Ekstedt, MD, PhD; Phone Number: +46709296267; Email: mattias.ekstedt@liu.se
• Study Contact Backup: Name: Mikael Forsgren, PhD; Email: mikael.forsgren@amramedical.com

Study Locations

• Sweden
  • Eksjö, Sweden, 57581
    • Recruiting
    • Department of Gastroenterology), District Hospital in Eksjö
    • Contact: Martin Rejler, PhD, MD; Email: martin.rejler@rjl.se
    • Contact: Daniel Sjögren, MD; Email: daniel.sjogren@rjl.se
    • Principal Investigator: Martin Rejler, PhD, MD
    • Sub-Investigator: Daniel Sjögren, MD
  • Jönköping, Sweden, 55185
    • Recruiting
    • Department of gastroenterology, County Hospital in Jönköping
    • Contact: Henrik Stjernman, PhD, MD; Email: henrik.stjernman@rjl.se
    • Principal Investigator: Henrik Stjernman, PhD, MD
  • Linköping, Sweden
    • Recruiting
    • Department of gastroenterology and hepatology
    • Contact: Camilla Holmgren; Phone Number: +46101030000; Email: camilla.holmgren@regionostergotland.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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. All etiologies of cirrhosis will be included except patients with primary sclerosing cholangitis.

Description

Inclusion Criteria:

1. 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.
2. Age ≥18 years
3. Written informed consent from the participant

Exclusion Criteria:

1. Contraindications for MRI
2. Subjects suffering from primary sclerosing cholangitis (PSC)
3. Subjects diagnosed with Hepatic carcinoma (HCC)
4. Previous liver transplant

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body composition (FFMVvcg)	FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.	Baseline
Body composition (FFMVvcg)	FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.	6 months
Body composition (FFMVvcg)	FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.	1 year
Body composition (FFMVvcg)	FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.	18 months
Change from baseline Body composition (FFMVvcg)	FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.	6 months
Change from 6 months Body composition (FFMVvcg)	FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.	1 year
Change from 1 year Body composition (FFMVvcg)	FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.	18 months
Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	Baseline
Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	6 months
Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	1 year
Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	18 months
Change from baseline Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	6 months
Change from 6 months Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	1 year
Change from 1 year Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	18 months
Presence of previous decompensation	If the patient previously has had ascites, bleeding esophageal varices, or encephalopathy.	Baseline
New episode of decompensation since baseline	If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.	6 months
New episode of decompensation since 6 months	If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.	1 year
New episode of decompensation since 1 year	If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.	18 months
New episode of decompensation since 18 months	If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.	2 years
Hepatocellular carcinoma	Detection of HCC by AMRI	Baseline
Hepatocellular carcinoma	Detection of HCC by AMRI	6 months
Hepatocellular carcinoma	Detection of HCC by AMRI	1 year
Hepatocellular carcinoma	Detection of HCC by AMRI	18 months
Hepatocellular carcinoma	Chart review	2 years
Hand grip strength (kg)	Measured at each visit with a hand-grip dynamometer	Baseline
Hand grip strength (kg)	Measured at each visit with a hand-grip dynamometer	6 months
Hand grip strength (kg)	Measured at each visit with a hand-grip dynamometer	1 year
Hand grip strength (kg)	Measured at each visit with a hand-grip dynamometer	18 months
Muscle function	Measured using the validated Short Physical Performance Battery.	Baseline
Muscle function	Measured using the validated Short Physical Performance Battery.	6 months
Muscle function	Measured using the validated Short Physical Performance Battery.	1 year
Muscle function	Measured using the validated Short Physical Performance Battery.	18 months
Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	Baseline
Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	6 months
Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	1 year
Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	18 months
Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	2 year
MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	Baseline
MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	6 months
MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	1 year
MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	18 months
MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	2 years
Significant liver lesion	LI-RADS 3-5	Baseline
Significant liver lesion	LI-RADS 3-5	6 months
Significant liver lesion	LI-RADS 3-5	1 year
Significant liver lesion	LI-RADS 3-5	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	Chart review	6 months
Death	Chart review	1 year
Death	Chart review	18 months
Death	Chart review	2 years
Esophageal varices	Assessed by gastroscopy and captured through chart review.	Baseline
Development of Esophageal varices	Assessed by gastroscopy and captured through chart review.	6 months
Development of Esophageal varices	Assessed by gastroscopy and captured through chart review.	1year
Development of Esophageal varices	Assessed by gastroscopy and captured through chart review.	18 months
Development of Esophageal varices	Assessed by gastroscopy and captured through chart review.	2 years
Liver stiffness by Fibroscan (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	Baseline
Liver stiffness by Fibroscan (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	6 months
Liver stiffness by Fibroscan (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	1 year
Liver stiffness by Fibroscan (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	18 months
Liver stiffness by MRE (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	Baseline
Liver stiffness by MRE (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	6 months
Liver stiffness by MRE (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	1 year
Liver stiffness by MRE (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	18 months
Spleen volume (ml)	A surrogate marker for portal hypertension and measured by MR.	Baseline
Spleen volume (ml)	A surrogate marker for portal hypertension and measured by MR.	6 months
Spleen volume (ml)	A surrogate marker for portal hypertension and measured by MR.	1 year
Spleen volume (ml)	A surrogate marker for portal hypertension and measured by MR.	18 months
Quality of life (Questionnaire)	EQ-5D-5L	Baseline
Quality of life (Questionnaire)	EQ-5D-5L	6 months
Quality of life (Questionnaire)	EQ-5D-5L	1 year
Quality of life (Questionnaire)	EQ-5D-5L	18 months
Quality of life (Questionnaire)	Short Health Scale-liver	Baseline
Quality of life (Questionnaire)	Short Health Scale-liver	6 months
Quality of life (Questionnaire)	Short Health Scale-liver	1 year
Quality of life (Questionnaire)	Short Health Scale-liver	18 months

Collaborators and Investigators

• Sponsor: Linkoeping University
• Collaborators: Amra Medical AB
• Investigators: Principal Investigator: Mattias Ekstedt, MD, PhD, Linkoeping University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neurologic Manifestations; Digestive System Neoplasms; Liver Neoplasms; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Fibrosis; Muscular Atrophy; Atrophy; Liver Diseases; Hypertension; Carcinoma; Carcinoma, Hepatocellular; Liver Cirrhosis; Sarcopenia; Hypertension, Portal
• Other Study ID Numbers: 2020-07215

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No