Hannes Hagström

Bakgrund: Fettleversjukdom har en hög prevalens, cirka 38% globalt, och personer med fettlever utvecklar ofta hjärt-kärlsjukdom. En minoritet drabbas även av svårare leverskador som cirrhos eller levercancer. Det är i nuläget oklart hur man hos de personer med riskfaktorer för både hjärt-kärlsjukdom och leversjukdom bäst kan identifiera personer med en ökad risk för respektive utfall. Det är också oklart hur förändringar i fettlever påverkar risk för hjärt-kärlsjukdom, om det finns ärftliga faktorer som modifierar risken, samt om det går att minska risken för leversjukdom med vanligt förekommande läkemedel. Målsättning: Vi arbetar under paradigmet att en riskfaktor för utveckling av hjärtsjukdom är fettinlagring i levern, och kommer närmare studera flera aspekter inom denna relation. Våra hypoteser inkluderar: a. Leverstelhet och fettinnehåll i levern, mätt med VCTE, är associerat med klinisk och subklinisk hjärtsjukdom, framför allt högersidig hjärtsvikt. Dessa parametrar kan också bidra till prediktering av framtida hjärtsjukdom. b. Datortomografi-uppmätt leverfett och tecken till leverfibros kan prediktera både framtida hjärtsjukdom men även allvarliga leverkomplikationer. c. En minskning av leverfett är associerat med en förbättrad riskprofil för utveckling av hjärt-kärlsjukdom och i förlängningen minskad incidens av detta. d. Vi kan utveckla modeller för att riskstratifiera patienter med kardiometabola riskfaktorer med eller utan fettlever för dessas risk att drabbas av leversjukdom, hjärtkärlsjukdom, eller både och. e. Genetiska data kan användas för att dela in personer med MASLD i en grupp med högre risk för leversjukdom, och en grupp med hög risk för hjärt-kärlsjukdom. f. Vanligt förekommande kardioprotektiva läkemedel (aspirin och SGLT-2-hämmare som exempel) har även en sekundär skyddande effekt på levern. Arbetsplan: Vi kommer använda SCAPIS-data samt egna insamlade omfattande kohorter för att undersöka om det går att riskstratifiera patienter i risken att drabbas av hjärtkärlsjukdom, leversjukdom, eller både och. Slutligen kommer vi använda nya unika kohorter med granulära data för att undersöka relationen mellan lever och hjärta med avancerade statistiska metoder. Betydelse: Projekten kan ge ny kunskap i om fettlever kan anses vara en riskfaktor för hjärt-kärlsjukdom, bättre prediktion av svåra utfall hos patienter med känd eller sannolik fettleversjukdom samt om man kan minska risken för svåra leverutfall med tillgängliga läkemedel.

Liver disease is the second most common cause of working life-years lost in the European working-age population, with steatotic liver disease affecting nearly one-third of the global population. As liver disease progresses silently toward cirrhosis or liver cancer, early detection of pre-cirrhotic stages is critical to prevent severe complications with poor prognosis. However, current non-invasive diagnostic tools lack precision since they have been developed using liver biopsy as the gold standard, which is prone to sampling errors and misclassification bias.This project aims to develop and validate improved prediction tools for cirrhosis and liver cancer across diverse populations. Instead of relying on liver biopsy as the reference, we use hard clinical outcomes from registers as the gold standard. We have established large, well-characterized cohorts spanning primary care and specialized hepatology settings. By combining clinical expertise with advanced biostatistical methods, we will develop and externally validate risk prediction models tailored to their target populations. Preliminary data suggest our new model for primary care outperforms existing tools, with potential to enhance early identification of high-risk patients. Additional projects include novel biomarker discovery for liver fibrosis and emulated target trials for drug repositioning. With unique data and expertise, our team is well-positioned to advance the field and improve liver disease outcomes.

I work daily with patients with chronic liver disease, who often develop liver cancer. Unfortunately, liver cancer is often detected late, and few patients can receive curative treatment. In those who can be treated, the tumor often returns, and in the case of widespread disease, the tumor-slowing treatments are often associated with troublesome side effects. The project was started to improve several aspects of the care of patients with liver cancer. By using advanced statistical methods on detailed databases with unique material, we want to contribute to simplifying the early detection of liver cancer and improve the care of those who develop liver cancer. The project has an epidemiological basis, and uses data from several unique data sources to meet our goals. We specifically study the most common form of liver cancer. This is today an increasingly common form of cancer, and one of the deadliest. Part of the project concerns the identification of those with the highest risk of developing cancer. With these, we are studying whether commonly used drugs are associated with a reduced risk. Finally, we investigate whether it is possible to improve the detection of tumor recurrence in patients who have developed cancer, as well as which palliative treatment may be preferable in specific patient groups with disseminated cancer. Liver cancer is a complicated form of tumor that is often detected too late. Here we hope to improve the care of patients with liver cancer on several levels. Our results can hopefully contribute to patients with a high risk of developing cancer being identified and included in specific surveillance programs. In the patients who develop cancer, we want to improve the identification of those with the highest risk of recurrence of the tumor so that specific treatment can be given, and in those with spread cancer, we want to investigate which palliative treatment is best for which patient groups.

Obesity and adult-onset diabetes are becoming more common in the world. In Sweden today, more than half of the population is overweight, and about four percent have adult-onset diabetes. In obesity and diabetes, fat is often stored in the liver, this is called fatty liver. Fatty liver is found today in over 25% of the world's population. In a small proportion of these, liver cancer can occur. Fatty liver globally today causes more cases of liver cancer than alcohol and hepatitis C. There are no good methods to be able to identify those individuals with obesity, diabetes and fatty liver who are at increased risk of developing liver cancer. In this project, we study in a number of unique cohorts people with obesity, diabetes or diagnosed fatty liver in different stages of the disease. Through advanced statistical methods, we try to identify the groups of people who are most at risk of developing liver cancer. The advantage of the project is access to a number of unique cohorts that are large enough to be able to meet the goals of the studies. We have a broad competence in the research group, with access to experts in liver diseases and liver cancer, epidemiology and statistics. This ensures that the studies can be carried out with the highest possible quality. Fatty liver is a potentially major societal problem. As the liver is very resistant to disease, it often takes over 20 years of exposure to fatty liver before liver cancer occurs. The obesity epidemic risks leading to a larger number of individuals in the future will develop liver cancer. However, the individual risk for this is low. We hope to be able to identify relevant risk groups with obesity, adult-onset diabetes and fatty liver where the risk of developing liver cancer is particularly high. We also hope to propose methods to reduce the risk of liver cancer in people in these risk groups.

Obesity and adult-onset diabetes are becoming more common in the world. In Sweden today, more than half of the population is overweight, and about four percent have adult-onset diabetes. In obesity and diabetes, fat is often stored in the liver, this is called fatty liver. Fatty liver is found today in over 25% of the world's population. In a small proportion of these, liver cancer can occur. Fatty liver globally today causes more cases of liver cancer than alcohol and hepatitis C. There are no good methods to be able to identify those individuals with obesity, diabetes and fatty liver who are at increased risk of developing liver cancer. In this project, we study in a number of unique cohorts people with obesity, diabetes or diagnosed fatty liver in different stages of the disease. Through advanced statistical methods, we try to identify the groups of people who are most at risk of developing liver cancer. The advantage of the project is access to a number of unique cohorts that are large enough to be able to meet the goals of the studies. We have a broad competence in the research group, with access to experts in liver diseases and liver cancer, epidemiology and statistics. This ensures that the studies can be carried out with the highest possible quality. Fatty liver is a potentially major societal problem. As the liver is very resistant to disease, it often takes over 20 years of exposure to fatty liver before liver cancer occurs. The obesity epidemic risks leading to a larger number of individuals in the future will develop liver cancer. However, the individual risk for this is low. We hope to be able to identify relevant risk groups with obesity, adult-onset diabetes and fatty liver where the risk of developing liver cancer is particularly high. We also hope to propose methods to reduce the risk of liver cancer in people in these risk groups.