Chronic liver disease Digestive System Other diseases of liver
Conditions
Interventions
Patients will be randomised to either:
1. ELF arm: patients in the ELF arm will undergo follow-up screening for cirrhosis with the ELF test
2. Standard care arm: patien
Sponsors
University of Leeds (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Registration: 1. Patients with chronic liver disease and pre-cirrhotic moderate to severe fibrosis as classified by clinical, laboratory, or histological evidence, due to viral hepatitis B or C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), haemochromatosis, or combinations of these diseases 2. Clinical evidence of chronic liver disease as evidenced by documented abnormalities of liver function for more than six months including: 2.1. Elevated liver enzymes (alanine aminotransferase [ALT], asparate aminotransferase [AST], gamma glutamyl-transferase [GGT]) 2.2. Elevated bilirubin with raised liver enzymes 2.3. Symptoms or signs of chronic liver disease (including jaundice, clubbing, palmar erythema, spider naevae) 3. Chronic liver disease due to: 3.1. Virus-serological and nucleic acid evidence of chronic Hepatitis C, chronic Hepatitis B 3.2. Fat: ultrasound evidence of fatty liver disease 3.3. Alcohol: history of excessive alcohol consumption 3.4. Autoimmune hepatitis (smooth muscle antibodies [SMA], anti-nucleur antibodies [ANA], liver-kidney-microsome antibodies [LKMA] and raised immunoglobins) 3.5. Primary biliary cirrhosis (anti-mitochondrial antibodies [AMA], M2 antibodies) 3.6. Primary sclerosing cholangitis (endoscopic retrograde cholangiopancreatography [ERCP] or magnetic resonance cholangiopancreatography [MRCP] evidence of beading of biliary tree) 3.7. Haemochromatosis-HFE genotype HDCY or HHYY with liver biopsy evidence of iron overload 4. Aged greater than or equal to 18 years old and less than 75 years of age, either sex 5. Give their written, informed consent to participate 6. Likelihood of ability to comply with the follow-up schedule 7. Life expectancy greater than 6 months Randomisation: 8. An ELF score of greater than or equal to 10.5
Exclusion criteria
Exclusion criteria: Registration: 1. Unable to provide consent 2. Clinical, histological or laboratory diagnosis of cirrhosis (other than ELF) such as hepatic impairment as evidenced by any one of the following: 2.1. Platelets less than the lower limit of normal (LLN) 2.2. Albumin less than LLN 2.3. Ultrasound of other imaging evidence of cirrhosis (coarse echo texture, irregular outline to liver, splenomegally) OR 3. Any episode of hepatic decompensation compatible with cirrhosis including: 3.1. Encephalopathy, variceal bleeding, ascites 3.2. Established diagnosis of hepatocellular cancer 3.3. Elevated alpha feto-protein without investigation to exclude HCC 4. Previously screened and found ineligible for the ELUCIDATE Trial Note that human immunodeficiency virus (HIV) co-infection is NOT an exclusion criterion. Randomisation: 5. An ELF score of less than 10.5
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time from clinical diagnosis of cirrhosis to incidence of any of the following severe complications: 1. Variceal haemorrhage 2. Mortality due to variceal haemorrhage 3. Spontaneous bacterial peritonitis 4. Mortality due to hepatocellular cancer (HCC) Patients will undergo follow-up visits at 6-monthly intervals, increasing to 3-monthly intervals after diagnosis of cirrhosis, for 30 months post-randomisation. Outcome data will be collected at each visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time from randomisation to clinical diagnosis of cirrhosis (to allow instigation of prophylaxis and screening) 2. Detection and timing of complications following cirrhosis, including: 2.1. Detection of small varices 2.2. Detection of large varices 2.3. Incidence of treatable hepatocellular cancer (HCC) 2.4. Incidence of inoperable HCC 3. All causes of mortality 4. Economic evaluation of the ELF test in the early detection of cirrhosis and as such in the initiation of measures to reduce the incidence of severe complications following cirrhosis Patients will undergo follow-up visits at 6-monthly intervals, increasing to 3-monthly intervals after diagnosis of cirrhosis, for 30 months post-randomisation. Outcome data will be collected at each visit. | — |
Countries
United Kingdom
Outcome results
None listed