En enkel blodanalys kan förutsäga risken att drabbas av en svår leversjukdom inom tio år.
Metoden kan användas inom primärvården för att tidigt upptäcka både skrumplever och levercancer.
Forskare vid Karolinska institutet har tagit fram en ny metod som med hög träffsäkerhet kan förutsäga risken att utveckla allvarlig leversjukdom.
www.core-model.com
Sådana sjukdomar blir allt vanligare – och prognosen är ofta dålig om de upptäcks sent.
– Vår metod kan förutsäga risken att insjukna inom tio år och bygger på tre enkla blodprover som redan tas rutinmässigt,
säger Rickard Strandberg, forskare vid institutionen för medicin i ett pressmeddelande från Karolinska institutet.
Modellen, som kallas CORE, har utvecklats med hjälp av avancerad statistik och
bygger på fem faktorer: ålder, kön samt nivåerna av levervärdena AST, ALT och GGT – som mäts vid många hälsokontroller.
Stor träffsäkerhet
Studien bygger på data från 480 000 personer i Stockholm som genomgick hälsokontroller mellan 1985 och 1996.
Deltagarna följdes i upp till 30 år.
Forskarna kunde se att cirka 1,5 procent utvecklade allvarliga leversjukdomar som skrumplever, levercancer eller behövde en levertransplantation.
CORE-modellen kunde identifiera riskpersoner med 88 procents träffsäkerhet.
Det är bättre än dagens vanligaste metod, FIB-4.
– Det har saknats bra verktyg i primärvården för att upptäcka risken för svår leversjukdom i tid.
FIB-4 är inte anpassad för den allmänna befolkningen och är mindre effektiv
när det gäller att förutsäga framtida risk för svår leversjukdom, säger Hannes Hagström, forskare vid Karolinska institutet.
Underlättar tidig screening
Målet har varit att ta fram ett verktyg som är enkelt att använda i primärvården,
där de flesta patienter först söker vård. En webbaserad kalkylator finns redan nu tillgänglig för vårdpersonal.
– Det här är ett viktigt steg mot att kunna erbjuda tidig screening för leversjukdomar i primärvården.
Läkemedelsbehandling finns nu tillgänglig, snart även i Sverige,
för att behandla personer med hög risk att utveckla leversjukdom, säger Hannes Hagström.
Modellen har även testats på två andra befolkningsgrupper i Finland och Storbritannien med goda resultat.
Forskarna understryker dock att CORE behöver testas ytterligare,
särskilt i riskgrupper som personer med typ 2-diabetes eller fetma.
De ser också ett behov av att integrera modellen i journalsystem för att underlätta användningen i vården.
Press release www.forskning,se
Vetenskaplig artikel:
Use of new CORE risk score to predict 10 year risk of liver cirrhosis in general population: population based cohort study, BMJ.
Use of new CORE risk score to predict 10 year risk of liver cirrhosis in general population: population based cohort study
BMJ 2025; 390 doi: https://doi.org/10.1136/bmj-2024-083182 (Published 29 September 2025) Cite this as: BMJ 2025;390:e083182
1. Rickard Strandberg , postdoctoral researcher1,
2. Fredrik Åberg, associate professor2,
3. Juho V Asteljoki, doctoral researcher3 4 5,
4. Panu K Luukkonen, associate professor3 4 5,
5. Veikko Salomaa, research professor emeritus6,
6. Antti Jula, research professor emeritus6,
7. Annamari Lundqvist, adjunct professor6,
8. Satu Männistö, research manager6,
9. Markus Perola, professor6,
10. Mats Talbäck, statistician7,
11. Niklas Hammar, professor emeritus7,
12. Hannes Hagström, adjunct professor1 8
Abstract
Objective
To develop and validate a novel risk prediction model for incident major adverse liver outcomes (MALO) in a primary care setting.
Design Population based cohort study.
Setting Sweden, with validation in Finland and the UK.
Participants
Model development in 480 651 individuals with no known history of liver disease and blood tests taken in primary care or at occupational healthcare screenings; validation in two cohorts with 24 191 and 449 806 individuals without known history of liver disease.
Main outcome
measures 10 year risk of a composite outcome of compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and liver related mortality, collectively referred to as MALO.
Results
A new risk model was created using flexible parametric survival models and several easily available laboratory based biomarkers. The model includes age, sex, aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase. The model’s performance was assessed in terms of discrimination (time dependent area under the curve), calibration (calibration curves), and clinical utility (decision curve analysis). External validation was done using data from the UK Biobank and the FINRISK and Health 2000 cohorts and compared with the FIB-4 score. The median follow-up time was 28 years, and 7168 MALO events were observed in that time. The incident risk of MALO at 10 years was 0.27%. The new risk score, termed CORE (Cirrhosis Outcome Risk Estimator), achieved a 10 year area under the curve of 88% (95% confidence interval 87% to 89%) compared with 79% (78% to 80%) for FIB-4. The calibration of CORE was good in all three cohorts, and according to the decision curve analysis CORE provides a higher net benefit than FIB-4 for all risk thresholds.
Conclusions
The CORE model, based on a flexible modelling approach and using biomarkers easily accessible in primary care, outperforms FIB-4 when predicting liver related outcomes in the general population and could be a novel means to stratify patients at risk for liver disease in the general population.
Läs hela artikeln pdf free
https://www.bmj.com/content/390/bmj-2024-083182
From the article
Introduction
The global burden of chronic liver disease is increasing.1 Liver cirrhosis is the 11th most common cause of death worldwide, and liver cancer—predominantly hepatocellular carcinoma—is the sixth most common type of cancer and fourth most common cause of death due to cancer.1 Such end stage liver diseases have poor prognosis, partly because liver disease is often asymptomatic until severe complications occur, such as the classical decompensation signs of oesophageal varices, ascites, or hepatic encephalopathy.2 Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common chronic liver disease, with an estimated global prevalence of 38%.3 The prevalence is particularly high among patients with type 2 diabetes or obesity.4 MASLD and other liver diseases have the potential to progress through different stages of metabolic dysfunction associated steatohepatitis and liver fibrosis to cirrhosis and hepatocellular carcinoma. This makes patients with confirmed or suspected MASLD particularly suitable to be screened for possible advanced fibrosis. MASLD is the most common cause of hepatocellular carcinoma in Sweden and elsewhere.5 By contrast, alcohol related liver disease is less common in the general population but is the leading cause of cirrhosis in many European countries.6 Together, alcohol related liver disease and MASLD are common liver diseases in the general population but are largely under-diagnosed. The primary risk factor for progression to cirrhosis or hepatocellular carcinoma remains the stage of liver fibrosis.7
In recent years, international societies have published recommendations for screening for advanced fibrosis in primary care among patients with or at risk for MASLD or alcohol related liver disease.89 Detecting pre-cirrhotic disease early can potentially improve prognosis through interventions including lifestyle changes (alcohol abstinence in alcohol related liver disease and weight loss in MASLD) or by novel treatments such as resmetirom for patients with fibrotic metabolic dysfunction associated steatohepatitis.10 Patients with screening detected compensated cirrhosis may benefit from surveillance for oesophageal varices and hepatocellular carcinoma, for example.8 As a first line test, guidelines recommend the non-invasive, blood based FIB-4 score. FIB-4 was originally developed to detect advanced fibrosis in patients with HIV and hepatitis C viral co-infection,11 but it has since been applied to other groups of patients with liver disease. Some concerns have been raised about its performance in the general population or in the primary care setting, where the prevalence of advanced fibrosis is relatively low.1213 Although FIB-4 and other novel diagnostic alternatives are relatively successful in detecting fibrosis at the time of testing, they are less effective for predicting future cirrhosis events.13
In this study, we developed and validated a new score—the Cirrhosis Outcome Risk Estimator (CORE)—intended for use in the primary care setting. CORE predicts the 10 year risk of cirrhosis, its related complications, or hepatocellular carcinoma. We directly compared CORE with FIB-4 and validated it in two external cohorts.
Discussion
In this study, we developed a new risk model—the CORE model—for predicting the 10 year risk of MALO in a primary care setting. It was trained on a very large dataset and validated in two external general population datasets. CORE handily outperformed FIB-4 in both the training data and the validation datasets, positioning it as a first line tool to predict incident MALO in the general population, complementing existing risk stratification strategies.
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