A Rapid, Non-invasive, Clinical Surveillance for CachExia, Sarcopenia, Portal Hypertension and Hepatocellular Carcinoma in End-Stage Liver Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 3
- 主要终点
- Body composition (FFMVvcg)
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Contraindications for MRI
- •Subjects suffering from primary sclerosing cholangitis (PSC)
- •Subjects diagnosed with Hepatic carcinoma (HCC)
- •Previous liver transplant
结局指标
主要结局
Body composition (FFMVvcg)
时间窗: 18 months
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.
Change from 1 year Muscle fat infiltration (%) [MFI]
时间窗: 18 months
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Change from baseline Body composition (FFMVvcg)
时间窗: 6 months
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.
Change from 6 months Muscle fat infiltration (%) [MFI]
时间窗: 1 year
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Presence of previous decompensation
时间窗: Baseline
If the patient previously has had ascites, bleeding esophageal varices, or encephalopathy.
Change from 6 months Body composition (FFMVvcg)
时间窗: 1 year
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.
Change from 1 year Body composition (FFMVvcg)
时间窗: 18 months
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.
Muscle fat infiltration (%) [MFI]
时间窗: 18 months
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Change from baseline Muscle fat infiltration (%) [MFI]
时间窗: 6 months
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
New episode of decompensation since baseline
时间窗: 6 months
If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
New episode of decompensation since 6 months
时间窗: 1 year
If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
New episode of decompensation since 18 months
时间窗: 2 years
If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
Hand grip strength (kg)
时间窗: 18 months
Measured at each visit with a hand-grip dynamometer
New episode of decompensation since 1 year
时间窗: 18 months
If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
MELD-score
时间窗: 2 years
A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium
Hepatocellular carcinoma
时间窗: 2 years
Chart review
Muscle function
时间窗: 18 months
Measured using the validated Short Physical Performance Battery.
Child-Pugh score
时间窗: 2 year
A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
Significant liver lesion
时间窗: 18 months
LI-RADS 3-5
次要结局
- Death(2 years)
- Esophageal varices(Baseline)
- Development of Esophageal varices(2 years)
- Liver stiffness by Fibroscan (kPa)(18 months)
- Liver stiffness by MRE (kPa)(18 months)
- Spleen volume (ml)(18 months)
- Quality of life (Questionnaire)(18 months)
研究者
Mattias Ekstedt
Associate Professor
Linkoeping University