Clinical trial NCT05502198: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Liver Cirrhosis
Hepatocellular Carcinoma
Sarcopenia
Portal Hypertension
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
Collaborators: name: Amra Medical AB
First posted: 2022-08-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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

Eligibility criteria: 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

Primary outcomes:
measure: Body composition (FFMVvcg)
timeFrame: Baseline
measure: Body composition (FFMVvcg)
timeFrame: 6 months
measure: Body composition (FFMVvcg)
timeFrame: 1 year
measure: Body composition (FFMVvcg)
timeFrame: 18 months
measure: Change from baseline Body composition (FFMVvcg)
timeFrame: 6 months
measure: Change from 6 months Body composition (FFMVvcg)
timeFrame: 1 year
measure: Change from 1 year Body composition (FFMVvcg)
timeFrame: 18 months
measure: Muscle fat infiltration (%) [MFI]
timeFrame: Baseline
measure: Muscle fat infiltration (%) [MFI]
timeFrame: 6 months
measure: Muscle fat infiltration (%) [MFI]
timeFrame: 1 year
measure: Muscle fat infiltration (%) [MFI]
timeFrame: 18 months
measure: Change from baseline Muscle fat infiltration (%) [MFI]
timeFrame: 6 months
measure: Change from 6 months Muscle fat infiltration (%) [MFI]
timeFrame: 1 year
measure: Change from 1 year Muscle fat infiltration (%) [MFI]
timeFrame: 18 months
measure: Presence of previous decompensation
timeFrame: Baseline
measure: New episode of decompensation since baseline
timeFrame: 6 months
measure: New episode of decompensation since 6 months
timeFrame: 1 year
measure: New episode of decompensation since 1 year
timeFrame: 18 months
measure: New episode of decompensation since 18 months
timeFrame: 2 years
measure: Hepatocellular carcinoma
timeFrame: Baseline
measure: Significant liver lesion
timeFrame: Baseline
measure: Significant liver lesion
timeFrame: 6 months
measure: Significant liver lesion
timeFrame: 1 year
measure: Significant liver lesion
timeFrame: 18 months
measure: Hepatocellular carcinoma
timeFrame: 6 months
measure: Hepatocellular carcinoma
timeFrame: 1 year
measure: Hepatocellular carcinoma
timeFrame: 18 months
measure: Hepatocellular carcinoma
timeFrame: 2 years
measure: Hand grip strength (kg)
timeFrame: Baseline
measure: Hand grip strength (kg)
timeFrame: 6 months
measure: Hand grip strength (kg)
timeFrame: 1 year
measure: Hand grip strength (kg)
timeFrame: 18 months
measure: Muscle function
timeFrame: Baseline
measure: Muscle function
timeFrame: 6 months
measure: Muscle function
timeFrame: 1 year
measure: Muscle function
timeFrame: 18 months
measure: Child-Pugh score
timeFrame: Baseline
measure: Child-Pugh score
timeFrame: 6 months
measure: Child-Pugh score
timeFrame: 1 year
measure: Child-Pugh score
timeFrame: 18 months
measure: Child-Pugh score
timeFrame: 2 year
measure: MELD-score
timeFrame: Baseline
measure: MELD-score
timeFrame: 6 months
measure: MELD-score
timeFrame: 1 year
measure: MELD-score
timeFrame: 18 months
measure: MELD-score
timeFrame: 2 years
Secondary outcomes:
measure: Death
timeFrame: 6 months
measure: Death
timeFrame: 1 year
measure: Death
timeFrame: 18 months
measure: Death
timeFrame: 2 years
measure: Esophageal varices
timeFrame: Baseline
measure: Development of Esophageal varices
timeFrame: 6 months
measure: Development of Esophageal varices
timeFrame: 1year
measure: Development of Esophageal varices
timeFrame: 18 months
measure: Development of Esophageal varices
timeFrame: 2 years
measure: Liver stiffness by Fibroscan (kPa)
timeFrame: Baseline
measure: Liver stiffness by Fibroscan (kPa)
timeFrame: 6 months
measure: Liver stiffness by Fibroscan (kPa)
timeFrame: 1 year
measure: Liver stiffness by Fibroscan (kPa)
timeFrame: 18 months
measure: Liver stiffness by MRE (kPa)
timeFrame: Baseline
measure: Liver stiffness by MRE (kPa)
timeFrame: 6 months
measure: Liver stiffness by MRE (kPa)
timeFrame: 1 year
measure: Liver stiffness by MRE (kPa)
timeFrame: 18 months
measure: Spleen volume (ml)
timeFrame: Baseline
measure: Spleen volume (ml)
timeFrame: 6 months
measure: Spleen volume (ml)
timeFrame: 1 year
measure: Spleen volume (ml)
timeFrame: 18 months
measure: Quality of life (Questionnaire)
timeFrame: Baseline
measure: Quality of life (Questionnaire)
timeFrame: 6 months
measure: Quality of life (Questionnaire)
timeFrame: 1 year
measure: Quality of life (Questionnaire)
timeFrame: 18 months
measure: Quality of life (Questionnaire)
timeFrame: Baseline
measure: Quality of life (Questionnaire)
timeFrame: 6 months
measure: Quality of life (Questionnaire)
timeFrame: 1 year
measure: Quality of life (Questionnaire)
timeFrame: 18 months
Other outcomes:
Locations:
city: Eksjö
country: Sweden
facility: Department of Gastroenterology), District Hospital in Eksjö
city: Jönköping
country: Sweden
facility: Department of gastroenterology, County Hospital in Jönköping
city: Linköping
country: Sweden
facility: Department of gastroenterology and hepatology
Study officials:
affiliation: Linkoeping University
name: Mattias Ekstedt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: