Metabolic Liver Disease Reshapes Europe’s Rising Liver Cancer Burden

Hepatocellular carcinoma, the most common form of primary liver cancer, is undergoing a profound epidemiological transformation across Europe, and a new comprehensive analysis warns that health systems are not yet prepared for the shift. A series paper published in The Lancet Regional Health – Europe, led by Bernhard Scheiner of the Medical University of Vienna and colleagues including Matthias Pinter, Jeroen Dekervel, Fabio Piscaglia and Jeffrey V. Lazarus, synthesizes data from Global Burden of Disease estimates, population-based registries and tertiary cohorts across the continent. Its central message is stark: while viral hepatitis-related liver cancer is declining thanks to vaccination and antiviral therapy, cases driven by fatty metabolic liver disease are climbing rapidly, and alcohol-related disease remains stubbornly high. The result is a rising overall burden that no single clinical specialty or ministry of health can address alone.

The scale of the problem is considerable. Primary liver cancer caused nearly 900,000 deaths worldwide in 2022, and hepatocellular carcinoma accounts for 75 to 85 percent of cases. Europe recorded around 62,000 new cases and approximately 54,000 deaths that year. Unlike most cancers, liver cancer incidence is still increasing, and in Europe the age-standardized incidence rose by an average annual percentage change of 1.05 percent between 1990 and 2021, far above the global figure of 0.12 percent. Incidence rates vary widely within the continent, with the highest rates in Southern Europe at 9.7 per 100,000 among men, and the lowest in parts of Northern and Eastern Europe. The authors emphasize that more than half of liver cancers are potentially preventable by targeting modifiable risk factors, yet preventive measures remain critically under-implemented at the population level.

The etiological composition of the disease is changing in ways that carry direct consequences for clinical practice. Global Burden of Disease estimates suggest chronic hepatitis C infection accounted for roughly 41 percent of European hepatocellular carcinoma cases in 2019, but that proportion is expected to fall as highly effective direct-acting antivirals and elimination programs take hold. Hepatitis B-related cases are also declining modestly, supported by childhood vaccination programs now established in 27 of 30 EU and European Economic Area countries. In contrast, alcohol consumption remains responsible for around 35 to 50 percent of cases, the highest proportion worldwide, and in countries such as France, Austria, Germany, Slovakia and Madeira, up to every second case is linked to harmful alcohol use.

The most worrisome trend, however, is the rapid rise of hepatocellular carcinoma driven by metabolic dysfunction-associated steatotic liver disease and its inflammatory form, formerly known as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. In Sweden, metabolic liver disease has already become the leading cause of the cancer, surpassing viral hepatitis. A Spanish multicenter registry documented a striking increase, with the proportion of cases attributed to metabolic syndrome-related liver disease rising from 4.9 percent in 2008 and 2009 to 24 percent in 2022 and 2023, while the absolute case number in participating centers grew from 21 to 118. Similar shifts are reported across Western, Southern and Eastern Europe, and the pattern is mirrored globally, from South America where metabolic disease now drives more than a third of cases to the United States where antiviral therapy has halved the viral contribution to transplantations.

One consequence of this shift is particularly challenging for clinicians: hepatocellular carcinoma arising in non-cirrhotic livers. Because surveillance has historically been recommended only for patients with established cirrhosis, tumors developing in the absence of cirrhosis are frequently diagnosed at later stages. Up to 40 percent of metabolic-disease-related hepatocellular carcinomas occur without cirrhosis. The authors argue that surveillance decisions must now be individualized, with possible consideration of screening for non-cirrhotic patients who have severe fibrosis, typically indicated by liver stiffness above 10 kilopascals, together with additional risk factors such as diabetes, older age, male sex and low platelet counts. Even so, annual incidence in many such patients often fails to exceed the 0.5 to 0.7 percent threshold generally considered necessary to justify cost-effective surveillance, highlighting an unresolved dilemma for guideline developers.

The changing disease profile also reshapes treatment. Patients with metabolic-related tumors frequently carry the complications of metabolic syndrome, including diabetes and cardiovascular disease, which raise perioperative risk after liver resection and predict major complications. The authors call for structured multidisciplinary prehabilitation integrating hepatology, surgery, cardiology, diabetology and nutrition, and note that minimally invasive liver surgery has been shown to reduce major complications and post-hepatectomy liver failure in patients with metabolic syndrome. For advanced disease, cardiovascular comorbidity may influence the choice between VEGF-targeted therapies, which carry risks of hypertension and thromboembolic events, and dual immune checkpoint blockade. Encouragingly, metabolic-related tumors appear to have a less aggressive biological phenotype, with better long-term survival after resection than hepatitis C-related disease, though the authors caution that emerging perioperative immunotherapy data, such as the CARES-009 trial, come from populations that were almost entirely Chinese and hepatitis B-positive and cannot yet be generalized to European patients.

Treating the underlying liver disease itself emerges as a powerful lever. Viral suppression and cure can reverse fibrosis and even cirrhosis: in a five-year follow-up of chronic hepatitis B patients receiving tenofovir, fibrosis regressed in 51 percent of patients with paired biopsies and cirrhosis resolved in 74 percent of those with cirrhosis at baseline. According to a recent meta-analysis, etiological cure or control led to recompensation in roughly one-third of patients with decompensated cirrhosis, the highest rates being seen in viral etiologies. Because nearly all hepatocellular carcinoma treatments other than transplantation require preserved liver function, such improvement can transform eligibility, reopening the door to systemic or even curative therapies for patients previously deemed untreatable. Etiological treatment may also reduce late recurrence after curative therapy, which reflects ongoing liver disease rather than metastatic spread.

The paper also highlights the role of population mobility and health inequities. As of January 2025, 46.7 million people born outside the EU lived in the Union, and migrants account for an estimated 25 percent of chronic hepatitis B and 14 percent of chronic hepatitis C infections in the EU and EEA. Hepatocellular carcinoma mortality has been reported to be four to five times higher in some foreign-born groups than in native-born populations, and among sub-Saharan African and Afro-Surinamese individuals with chronic hepatitis B living in Europe, ten-year cumulative incidence reached 12.1 percent in those with advanced fibrosis. Structural barriers, including legal precarity, language obstacles and stigma, delay diagnosis and restrict access to care, particularly for refugees, asylum seekers and undocumented people. The authors call for equitable testing, universal access to antiviral treatment irrespective of legal status, and culturally adapted metabolic prevention as core components of universal health coverage.

On the policy front, the authors lay out a detailed agenda. Minimum unit pricing for alcohol, volumetric taxation, cancer warning labels and advertising restrictions are backed by modeling from the HEPAHEALTH II study, which found that a minimum unit price of one euro would be the most effective single policy to reduce liver cancer burden. The WHO’s SAFER initiative and its European alcohol policy playbook offer ready-made frameworks, yet industry lobbying and lack of political will continue to block implementation. For metabolic disease, the authors recommend taxing sugar-sweetened beverages, front-of-pack labeling, food reformulation, restricting the marketing of ultra-processed foods, which supply between 14 and 44 percent of dietary energy across 22 European countries, and expanding access to healthy diets through programs such as Food is Medicine and social prescribing. Tobacco control measures, including taxation and graphic warnings, complete the picture, since quitting smoking for more than three decades reduces liver cancer risk to near that of never smokers.

The authors conclude that halting the rising tide of liver cancer will require an annual reduction of at least 2 percent in age-standardized incidence, a target achievable only through coordinated public health action at European Union and WHO European region levels. Their key recommendations include integrating liver health pathways into primary care with fibrosis screening and viral hepatitis testing, prioritizing evidence-based surveillance programs with individualized approaches for high-risk non-cirrhotic patients, embedding liver health explicitly into European health policy with sustainable funding, and strengthening the European evidence base for emerging strategies such as prehabilitation and perioperative immunotherapy. As viral hepatitis recedes, the battle against Europe’s liver cancer burden is shifting from the virology ward to the supermarket aisle, the tax code and the primary care clinic, and the success of that shift will determine whether the coming decades bring fewer deaths or a growing epidemic of a preventable cancer.

Subject of Research: Changing epidemiology and etiology of hepatocellular carcinoma in Europe and its implications for clinical practice and health policy

Article Title: Changing epidemiology and etiology of hepatocellular carcinoma in Europe: implications for clinical practice and health policy

Article References: Changing epidemiology and etiology of hepatocellular carcinoma in Europe: implications for clinical practice and health policy. (n.d.). https://doi.org/10.1016/j.lanepe.2026.101837

Image Credits: AI Generated

DOI: 10.1016/j.lanepe.2026.101837

Keywords: hepatocellular carcinoma, MASLD, alcohol-related liver disease, viral hepatitis, liver cancer surveillance, HCC prevention, cirrhosis, public health policy, Europe, metabolic syndrome, immunotherapy, recompensation