EP-4740021-A2 - USE OF A BIOMARKER FOR DETERMINING THE CHILD-PUGH CLASS INTO WHICH AN INDIVIDUAL IS TO BE CLASSIFIED

Abstract

The present invention relates, amongst others, to the use of a marker chosen from the group consisting of high-density lipoprotein, apolipoprotein A1, valine, lactate, and pyruvate in an in vitro method for determining a Child-Pugh class into which an individual is to be classified.

Inventors

• SCHIFFER, Eric
• JAGDHUBER, Rudolf
• DE JEL, Sebastian
• STÄMMLER, Frank
• RÖTZER, Sebastian
• ROBERTSON, ANDREW
• EIGLSPERGER, Johannes

Assignees

• Numares AG

Dates

Publication Date

20260513

Application Date

20240704

Claims (15)

1. 1. Use of a marker chosen from the group consisting of high-density lipoprotein, apolipoprotein A1 , valine, lactate, and pyruvate in an in vitro method for determining a Child-Pugh class into which an individual is to be classified.
2. 2. Use according to claim 1 , characterized in that the determined Child-Pugh class is class A or class B/C.
3. 3. Use according to claim 1 , characterized in that the determined Child-Pugh class is class A, class B, or class C.
4. 4. Use according to any of the preceding claims, characterized in that at least one of high- density lipoprotein and apolipoprotein A1 is used together with pyruvate as marker.
5. 5. Use according to claim 4, characterized in that at least one of high-density lipoprotein and apolipoprotein A1 is used together with pyruvate and valine as marker.
6. 6. Use according to claim 4, characterized in that at least one of high-density lipoprotein and apolipoprotein A1 is used together with pyruvate and lactate as marker.
7. 7. Use according to any of claims 1 to 3, characterized in that at least one of high-density lipoprotein and apolipoprotein A1 is used together with valine as marker.
8. 8. Use according to any of claims 1 to 3, characterized in that at least one of high-density lipoprotein and apolipoprotein A1 is used together with lactate as marker.
9. 9. Use according to claim 8, characterized in that at least one of high-density lipoprotein and apolipoprotein A1 is used together with lactate and pyruvate as marker.
10. 10. Use according to any of claims 1 to 3, characterized in that lactate is used together with valine as marker.
11. 11 . Use according to any of claims 1 to 3, characterized in that valine is used together with pyruvate as marker.
12. 12. Use according to any of claims 1 to 3, characterized in that lactate is used together with pyruvate as marker.
13. 13. Marker chosen from the group consisting of high-density lipoprotein, apolipoprotein A1 , valine, lactate, and pyruvate for use in in-vivo diagnostics of the liver function of an individual by determining a Child-Pugh class into which the individual is to be classified.
14. 14. Method for analyzing an isolated body fluid sample in vitro, comprising the following steps: a) determining the concentration of at least one substance chosen from the group consisting of high-density lipoprotein, apolipoprotein A1 , valine, lactate, and pyruvate in an isolated body fluid sample from an individual by analyzing the body fluid sample with a suited measuring technique, b) calculating a score from the determined concentrations, the score being indicative for determining a Child-Pugh class into which the individual is to be classified.
15. 15. Method according to claim 14, characterized in that calculating the score involves calculating a ratio between at least two concentration values.

Description

Use of a biomarker for determining the Child-Pugh class into which an individual is to be classified Description The present invention relates to the in-vitro use of a marker for determining the Child-Pugh class into which an individual is to be classified according to the preamble of claim 1 , to the further medical use of such a marker according to the preamble of claim 13, and to an analysis method for determining the Child-Pugh class into which an individual is to be classified according to the preamble of claim 14. More generally, the present invention relates to biomarkers that are applicable for accurately estimating liver function. The term “liver function” is broad, given the vast array of physiological and biochemical functions the organ carries out, chiefly biliary synthesis for fatty acid digestion, metabolism of carbohydrate, protein and lipids, synthesis of protein and detoxification. Thus, hepatocyte function is paramount to physiological survival. Given the broad range of functions the liver carries out, it is challenging to accurately define liver function numerically, as opposed to the glomerular filtration rate of the kidney or the ejection fraction of the heart. A number of blood tests are available which reflect the general damage to hepatocytes - mostly products of hepatic metabolic pathways and enzymes - the most common in clinical practice being serum aminotransferases, bilirubin, alkaline phosphatase, albumin, and prothrombin time. These tests are commonly grouped together under the umbrella term ‘Liver Function Tests’ which is misleading, since most are unable to reflect how well the liver is functioning and abnormal values can be due to diseases unrelated to the liver. Moreover, these tests may be normal in patients with advanced liver disease yet abnormal in asymptomatic healthy individuals [1 -3]. The combination of detection of serial changes in this test panel interpreted together with patient symptomatology can assist in monitoring progression or remission of disease and can trigger subsequent and more advanced diagnostic testing. Current specific liver function tests are limited. The dye indocyanine green has been in practice for decades for liver function monitoring. The so-called indocyanine green tracer test (ICG) measures hepatic elimination of the dye and is hence a diagnostic tool of overall liver function and a prognostic predictor of mortality. For example, it has utility in peri-operative liver function monitoring during liver surgery, an assessment of liver failure acuity, and as a prognostic tool for critically ill patients. Adverse reactions are rare although it is contraindicated in known iodine allergy. Despite its utility, strong levels of evidence are lacking, and it is therefore not recommended for routine liver function assessment [4, 5]. Image-based modalities assessing liver function exist but are limited in scope and resource. Nuclear medicine scans metastable technetium-99 (99mTc) galactosyl and mebrofenin using plain scintigraphy and single-photon emission computed tomography (SPECT-CT) have been utilized, however these modalities deliver significant radiation exposure to the patient and user. Gadolinium enhanced MRI (Gd-EOB) can show high spatial and temporal metabolic resolution in the liver, yet is strictly limited by magnetic resonance imaging (MRI) availability and cost [6, 7]- A simpler measure of global liver function lies with the Child-Pugh score, particularly in patients having cirrhosis. Originally designed to assess the risk of non-shunt operations in patients with cirrhosis (namely transection of the esophagus for bleeding esophageal varices), it was further validated to stratify the risk of portacaval shunt surgery in patients with cirrhosis. It was also later demonstrated to correlate with survival in patients not undergoing surgery. Additionally, Child-Pugh class is also associated with the likelihood of developing complications of cirrhosis, such as variceal hemorrhage. Components of the modified Child-Pugh classification of the severity of liver disease are degree of ascites, the serum concentrations of bilirubin and albumin, the prothrombin time, and the degree of encephalopathy. A total Child-Pugh score (sometimes also referred to as Child-Turcotte-Pugh score) of 5 to 6 is considered Child-Pugh class A (well-compensated disease, 10 % postoperative mortality risk), a score of 7 to 9 is class B (significant functional compromise, 30 % postoperative mortality risk), and a score of 10 to 15 is class C (decompensated disease, 82 % postoperative mortality risk). These classes correlate with one- and two-year patient survival: class A: 100 and 85 %; class B: 80 and 60 %; and class C: 45 and 35 % [8-11 ]. As such, an accurate Child- Pugh score as an estimation of global liver function has significant utility in perioperative planning of patients with cirrhosis, resource management, prioritization of liver treatment, identification of thos