THIS YEAR, the vibrant city of Amsterdam, the Netherlands played host to the European Association for the Study of the Liver (EASL) Congress 2025, welcoming 7,742 participants from 119 countries. The event served as a powerful hub of scientific exchange, advocacy, and professional development for clinicians, researchers, policymakers, and allied health professionals committed to tackling liverdisease worldwide.
Over four dynamic days, attendees were invited to explore 190 scientific sessions spanning a broad spectrum of hepatology, from basic science to translational research, and clinical best practices to public health initiatives. The congress featured a rich mix of symposia, abstract presentations, hands-on training, and the popular ‘Do’s and Don’ts’ sessions, offering something of value for everyone in the hepatology community.
The Opening Ceremony set a powerful tone, with a panel discussion addressing the urgent health crisis of alcohol-related liver disease. This discussion featured Aleksander Krag, EASL Secretary General; Riina Sikkut, Member of the Estonian Parliament and former Minister of Health of Estonia; and Carina Ferreira-Borges, Regional Advisor for Alcohol and Illicit Drugs, WHO, Geneva, Switzerland. The panel, ‘From Evidence to Action’, was moderated by David Barrett, WHO, Geneva, Switzerland, and explored the challenge of translating science into policy. Krag highlighted the scale of the issue, citing over 800,000 alcohol-related deaths annually in Europe, and called for action on three evidence-based policy levers: pricing, availability restrictions, and marketing regulation. “The challenge is not evidence, it’s political will,” he stated.
Ferreira-Borges emphasised the need for cross-sector collaboration and support for policymakers facing pressure from powerful industry lobbies. “There is no safe level of alcohol consumption. That’s not opinion, it’s evidence,” she said, while detailing WHO’s effort to combat misinformation and raise awareness of under-recognised risks such as the link between alcohol and breast cancer. The panel’s message was clear: while science provides the solutions, meaningful progress depends on coordinated advocacy and political courage. “We must be louder than the lobbyists,” Krag concluded.
This year’s Congress also highlighted EASL’s commitment to its four strategic pillars: Education, Advocacy, Science, and Leadership, the letters that form the organisation’s acronym. With its clear vision of ‘Beating liver disease’ and its mission to be ‘The Home of Hepatology for everyone engaged in beating liver disease’, the Opening Ceremony reaffirmed EASL’s central role in shaping the future of liver health.
The awards provided a fitting conclusion to the session, celebrating excellence and emerging leadership within the field. Silvia Affo, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain, and Mattias Mandorfer, Medical University of Vienna, Austria, were recognised as recipients of the EASL Emerging Leader Award. Meanwhile, the EASL Rising Star Award was presented to Sally Tilden, University Hospitals Bristol NHS Foundation Trust, UK, and Thomas Maurel, Pitié Salpêtrière University Hospital, Paris, France. Meanwhile the EASL Daniel Alagille Award, honouring outstanding contributions to paediatric hepatology, was awarded to Barbora Smolkova, Oslo University Hospital, Norway.
From educational initiatives, such as the updated clinical guideline app and postgraduate courses, to advocacy efforts like the ‘Love Your Liver’ project and the newly launched European Health Alliance on Alcohol, the EASL Congress 2025 showcased a united global effort to confront the burden of liver disease head-on.
As EASL continues to foster inclusive leadership, scientific innovation, and public health advocacy, the Congress in Amsterdam will be remembered not just for its depth of knowledge, but for its heart, driven by a shared mission to improve lives.
Stay tuned for EASL 2026, and in the meantime, explore our full coverage and reflections on an unforgettable week in hepatology.
Evaluating Non-Invasive Tools for MASLD Diagnosis
A RECENT, large, prospective, multi-centre study, presented at the EASL Congress 2025, has marked a step forward in the search for non-invasive tools to diagnose metabolic dysfunction-associated steatotic liver disease (MASLD).1
The study aimed to assess the diagnostic accuracy of a wide range of imaging and blood-based biomarkers against liver biopsy, the current gold standard, in patients with MASLD. Participants underwent clinical evaluation, blood sampling, liver stiffness measurement, and MRI imaging within 6 months of biopsy, with all data centrally processed and histology scored by expert pathologists using standardised methods.
Of the 357 participants included, 50% had Type 2 diabetes, with a mean BMI of 33.8 kg/m². Fibrosis staging revealed a significant burden of liver disease, with over 70% of participants showing Stage F2 or greater. When assessing biomarkers for diagnosing ‘at-risk metabolic dysfunction-associated steatohepatitis (MASH)’, defined as active steatohepatitis with moderate fibrosis, NIS2+® (Genfit, France) showed the highest accuracy (area under the curve [AUC]: 0.82) but did not surpass the statistical threshold required to be considered a valid replacement for biopsy. Other biomarkers, such as controlled attenuation parameter (CAP), magnetic resonance imaging derived proton density fat fraction (MRI-PDFF), and iron-corrected T1 mapping (cT1), yielded lower diagnostic accuracies.
For identifying advanced fibrosis (≥F3), magnetic resonance elastography and the composite scoring system AGILE3+™ (Echosens, Paris, France) performed exceptionally, both exceeding the minimum acceptable criterion, with AUCs of 0.91 and 0.84, respectively. Magnetic resonance elastography also proved the most reliable marker for cirrhosis (F4), followed by vibration-controlled transient elastography, AGILE3+, and AGILE4™ (Echosens), all meeting or surpassing the minimum acceptable criterion. In contrast, several blood biomarkers, such as PROC3 andCK18 variants, fell short of theperformance threshold.
The study reinforces the utility of elastography-based imaging for fibrosis assessment in MASLD, while simultaneously exposing the ongoing limitations in reliably diagnosing active steatohepatitis non-invasively. Although promising, the current biomarkers, including NIS2+, require further validation before they can replace biopsy. Ongoing studies aim to assess the prognostic value of these biomarkers, with the ultimate goal of improving patient stratification and guiding treatment decisions without the need for invasive procedures.
Primary Prevention of Variceal Bleeding: Carvedilol or Band Ligation?
THE MAIN findings from the CALIBRE trial, recently presented at the EASL Congress 2025, indicate no significant difference between carvedilol and variceal band ligation (VBL) in preventing first variceal bleeding in patients with cirrhosis and medium to large oesophageal varices, with both treatments demonstrating similar safety profiles.2
The CALIBRE trial was designed to address the ongoing uncertainty regarding the optimal primary prevention strategy for variceal bleeding in liver cirrhosis, specifically comparing the efficacy and safety of carvedilol, a non-selective β-blocker, with VBL.
This multicentre, randomised controlled, open-label study was conducted across 60 UK hospitals, enrolling adult patients with cirrhosis and medium to large oesophageal varices who had not previously bled or received either intervention. The trial’s primary aim was to determine if carvedilol 12.5 mg daily was superior or equivalent to VBL in reducing the risk of first variceal bleed within one year of randomisation.
A total of 265 participants were randomised between January 2019–August 2022, with 133 assigned to carvedilol and 132 to VBL. The incidence of variceal bleeding within 1 year was 3.8% in the carvedilol group and 7.6% in the VBL group, with a risk ratio of 0.50 (95% CI: 0.17–1.41; p=0.189) and a risk difference of –0.038 (95% CI: –0.094–0.017; p=0.178). No statistically significant differences were observed in secondary outcomes, including mortality, transplant-free survival, or other complications of cirrhosis. Both interventions were well tolerated, with only one serious treatment-related adverse event in each arm, and no treatment-related deaths. Economic analysis favoured carvedilol, which was less costly and associated with a slight increase in quality-adjusted life years. Qualitative findings suggested no strong patient preference for either intervention, though clinicians tended to favour carvedilol as a first-line therapy.
In conclusion, the CALIBRE trial, despite being underpowered due to early recruitment closure, found no evidence of a difference in efficacy or safety between carvedilol and VBL for primary prevention of variceal bleeding in cirrhosis. Future research should focus on larger, adequately powered studies to confirm these findings and further explore patient-centred outcomes and cost-effectiveness.
New Therapy Significantly Slows Liver Disease in Patients With Cystic Fibrosis
A LANDMARK French study presented at the EASL Congress 2025 has revealed that the introduction of Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy has dramatically reduced the progression of liver disease and mortality in people living with cystic fibrosis.3
The 10-year national study analysed data from nearly 10,000 patients aged 12 years and older, comparing cystic fibrosis liver disease outcomes before and after ETI became available in France in December 2019. Researchers used data from the French National Discharge Database to examine liver disease progression, transplant rates, and mortality.
The incidence of liver disease progression dropped sharply in the ETI era, from 20.7 to just 1.14 cases per 1,000 person-years. Five-year risk of cystic fibrosis liver disease progression fell from 11.4% to 0.27%, while transplant-free mortality decreased from 18.5% to 0.57%. All major liver-related complications, including gastro-oesophageal varices and hepatocellular carcinoma, declined significantly during the same period.
The study also showed that these improvements were not simply due to reduced life expectancy. Even after accounting for mortality as a competing risk, the adjusted hazard ratio for liver disease progression was 0.083, with transplant-free mortality at just 0.011.
The findings strongly support incorporating ETI into clinical care for patients with cystic fibrosis who have liver involvement, shifting the outlook from high-risk to manageable with modern therapy.
Liver Stiffness Identified as Key Predictor in Primary Biliary Cholangitis
AT THE EASL Congress 2025, new data from the GLOBAL-PBC study revealed that liver stiffness measurement (LSM) is a more robust predictor of liver-related complications in primary biliary cholangitis (PBC) than biochemical response alone.4
In the multinational cohort of 1,793 patients, selected from 4,096 with available LSMs, participants had at least two reliable LSMs performed via vibration-controlled transient elastography at least 6 months apart. Patients with prior hepatic decompensation (HD), liver transplantation, or hepatocellular carcinoma were excluded.
Over a median follow-up of 22 months, 3.3% of patients developed HD. Biochemical response, defined using the Paris-2 criteria, was achieved in 51% of patients, while 52% had stable or reduced LSMs. ALP normalisation and deep biochemical response were seen in 39% and 25% of patients, respectively, all associated with a significantly reduced risk of HD (p<0.05 for all).
However, LSM response alone did not predict HD unless the reduction exceeded certain thresholds. Reductions in LSM of 10%, 20%, and 30% were each independently associated with lower HD risk (p<0.05), but the clearest predictor was the most recent LSM value (LSMc). An LSMc ≥10 kPa was strongly predictive of HD (hazard ratio [HR]: 14.5; 95% CI: 6.9–30.6), with LSMc alone having a predictive accuracy (C-statistic) of 0.87.
Among patients with discordant biochemical and LSM responses (seen in 52%), LSMc >10 kPa remained predictive of HD (HR: 37.4; 95% CI: 4.8–289.7) and of the composite outcome of liver transplantation or liver-related death (HR: 2.6; 95% CI: 1.3–5.4).
Researchers concluded that in routine clinical practice, LSMc alone offers a simple yet highly effective means of prognostication, particularly when biochemical markers are inconclusive.
‘3-in-1’ Metabolomic Test Could Transform Cholangiocarcinoma Detection
A NEW metabolomic blood test could transform the way clinicians diagnose and monitor primary sclerosing cholangitis (PSC) and detect associated cholangiocarcinoma (CCA) at an early stage.5
In a large international study, presented at the EASL Congress 2025, researchers evaluated serum samples from 434 individuals across 13 centres in eight countries. Participants included patients with PSC, those who developed CCA during follow-up (PSC-to-CCA), individuals with concurrent PSC-CCA, patients with ulcerative colitis, and healthy controls. The team employed ultra-high-performance liquid chromatography–mass spectrometry to assess metabolite profiles, followed by machine learning to identify the most predictive biomarkers. The study aimed to uncover serum-based markers capable of diagnosing PSC, detecting CCA in patients with PSC, and predicting CCA development prior to clinical manifestation.
Results identified 50 metabolites strongly associated with PSC, unaffected by age, sex, cirrhosis, or ulcerative colitis status. A 13-metabolite model differentiated patients with PSC from healthy controls with 98% accuracy in both discovery and validation cohorts. Among those with PSC-CCA, 57 metabolites showed significant alterations. Another 13-metabolite model accurately distinguished PSC-CCA from PSC cases with area under the curve (AUC) values of 0.91 and 0.90, excelling in early-stage cancer detection (AUC=0.930) and outperforming CA19-9 (AUC=0.646). Impressively, this model retained diagnostic power (AUC=0.92) in patients with low CA19-9 levels. Furthermore, a separate seven-metabolite model predicted future CCA development in patients with PSC, with positive predictive values of 83% and 73% in discovery and validation cohorts, respectively.
This ‘3-in-1’ blood test offers a promising, non-invasive solution for diagnosing PSC, detecting early PSC-CCA, and forecasting cancer risk before clinical signs emerge. Its clinical adoption could enable earlier intervention, tailored surveillance, and more precise management strategies in high-risk PSC populations.
New Treatment Offers Relief for PBC-Related Itch
A NEW Phase III clinical study, presented at the EASL Congress 2025, has shown promising results for patients experiencing cholestatic pruritus associated with primary biliary cholangitis.6
This debilitating and often undertreated condition significantly impacts quality of life, particularly due to persistent itching and sleep disturbance. The trial evaluated the efficacy and safety of linerixibat, an ileal bile acid transporter inhibitor, in individuals with moderate-to-severe pruritus.
In the double-blind, randomised, placebo-controlled study, 238 patients received either linerixibat 40 mg or a placebo twice daily over 24 weeks. The majority of participants were female, with a mean itch severity score of 7.34 at baseline. The primary endpoint measured the change in the worst itch score, while secondary outcomes assessed sleep interference, early response at Week 2, and overall patient impressions of symptom changes.
In this trial, linerixibat demonstrated a significant and rapid reduction in pruritus compared to the placebo. By Week 24, patients treated with linerixibat reported a greater mean reduction in itch severity, with an adjusted mean difference of –0.72 (p=0.001). Improvements were noticeable as early as Week 2, with a significant difference of –0.71 (p<0.001). Sleep quality also improved more markedly in the linerixibat group, with a statistically significant reduction in pruritus-related sleep interference (p=0.024).
Moreover, a higher proportion of patients on linerixibat achieved clinically meaningful improvements in itch relief, with 41% experiencing a ≥4-point reduction, and 21% reporting an absence of pruritus altogether. While gastrointestinal side effects such as diarrhoea and abdominal pain were more common with linerixibat, they were generally manageable, with only 4% of patients discontinuing treatment due to these issues.
These results support the potential use of linerixibat for pruritus in patients with primary biliary cholangitis, offering meaningful symptom relief and improved sleep.
Phase II Study Reveals New Treatments for Hepatitis B Virus
THE PHASE II MARCH study, presented at the EASL Congress 2025, investigated the efficacy and safety of tobevibart (VIR-3434) and elebsiran (VIR-2218), administered alone or combined with pegylated interferon (IFN) alfa-2a, in people living with chronic hepatitis B virus (HBV) infection.7
Tobevibart is an engineered human monoclonal antibody targeting the hepatitis B surface antigen (HBsAg), while elebsiran is a small interfering RNA designed to silence the HBx region of the HBV genome.
Participants receiving nucleos(t)ide-reverse transcriptase inhibitors were treated for 44–48 weeks with either tobevibart alone, tobevibart plus elebsiran, or the combination of tobevibart, elebsiran, and pegylated IFN alfa-2a. All medications were administered via subcutaneous injection at specified intervals. The study primarily evaluated treatment-emergent adverse events and rates of HBsAg seroclearance (defined as HBsAg levels below 0.05 IU/mL) at the end of treatment (EOT). The authors noted that functional cure rate at 24 weeks post-EOT, measured in participants who discontinued nucleos(t)ide-reverse transcriptase inhibitors after achieving seroclearance, will be reported later.
At EOT, no participants treated with tobevibart alone achieved HBsAg seroclearance, whereas 15.7% of those receiving tobevibart plus elebsiran and 22.2% of those receiving the triple combination, which included pegylated IFN alfa-2a, did. Notably, participants with lower baseline HBsAg levels (<1,000 IU/mL) experienced higher seroclearance rates: 38.9% in the two-drug group, and 45.5% in the three-drug group.
Treatment-emergent adverse events were mostly mild or moderate (Grade 1–2). Severe adverse events (Grade ≥3) were rare, but more common in the triple therapy group, including one case of leukopenia and one hepatitis event linked to the study drugs. Both of these were resolved without lasting issues.
These encouraging findings highlight the potential of tobevibart combined with elebsiran, with or without pegylated IFN alfa-2a, to achieve HBsAg loss in chronic HBV infection, especially in patients with lower antigen levels, and support further clinical development.
Portal Hypertension Found in Half of Patients After Vein Thrombosis
RESEARCH presented at the EASL Congress 2025 has found that nearly half of patients with non-cirrhotic, non-tumoural recent portal vein thrombosis (RPVT) develop signs of portal hypertension within 5 years.8
The study, conducted across multiple centres and published after two decades of patient data collection, followed 485 individuals with RPVT for a median of 67 months. Portal hypertension was defined by the presence of portosystemic collaterals, gastro-oesophageal varices, ascites, gastrointestinal bleeding, or hepatic encephalopathy. The cumulative incidence of portal hypertension reached 48% by the 5th year.
The results showed that patients who did not achieve full recanalisation of the portal vein system were at a significantly higher risk, with a 67% incidence at 5 years. In contrast, those who achieved complete recanalisation had a much lower risk of 17%.
Several clinical factors were independently associated with the development of portal hypertension. These included the presence of ascites at diagnosis, a diagnosis of myeloproliferative neoplasm, thrombosis affecting multiple veins, and incomplete or absent recanalisation during follow-up.
Interestingly, a small group of patients did not develop portal hypertension, although there was no evidence of recanalisation. A majority of these individuals had clots confined to intrahepatic portal vein branches, suggesting that the location and extent of the thrombosis are critical to long-term outcomes.
This research highlights the importance of long-term monitoring and early intervention in patients with RPVT, even in the absence of cirrhosis or cancer. The authors emphasise that early identification of high-risk patients may allow for more targeted follow-up, recanalisation strategies, and preventive care to avoid the development of complications linked to portal hypertension.
Dual Immunotherapy Extends Survival in Unresectable Liver Cancer
AT THE EASL Congress 2025, an interim analysis of the Phase III CheckMate 9DW trial revealed that first-line immunotherapy with nivolumab plus ipilimumab significantly improves survival in patients with unresectable hepatocellular carcinoma, regardless of liver function status.9
In the study of 668 previously untreated patients, nivolumab plus ipilimumab demonstrated superior overall survival (OS) compared with lenvatinib or sorafenib, with a median OS of 23.7 months versus 20.6 months (hazard ratio [HR]: 0.79; p=0.018). Objective response rate was markedly higher with nivolumab plus ipilimumab (36% versus 13%; p<0.0001), with responses lasting over twice as long (median duration of response: 30.4 versus 12.9 months).
Outcomes were stratified by liver function using albumin-bilirubin (ALBI) scores. Among the 396 patients with ALBI Grade 1 (better liver function), median OS was 35.4 months with nivolumab plus ipilimumab versus 23.2 months with lenvatinib or sorafenib (HR: 0.75). In those with ALBI Grades 2 or 3 (272 patients), OS was 16.9 versus 14.0 months, respectively (HR: 0.75).
In both subgroups, nivolumab plus ipilimumab showed higher objective response rates (37% versus 14% in Grade 1; 35% versus 11% in Grades 2 or 3) and greater complete response rates. Safety profiles were consistent across ALBI grades.
These findings support nivolumab plus ipilimumab as a promising first-line treatment for unresectable hepatocellular carcinoma, offering durable responses and survival benefits irrespective of underlying liver function.
Novel Therapy Reduces Flare Risk in IgG4-Related Disease
A NOVEL treatment targeting B cells significantly reduces disease flares in patients with IgG4-related disease affecting the pancreas, bile ducts, or liver, according to new results from the MITIGATE Phase III trial, presented at the EASL Congress 2025.10
IgG4-related disease is a chronic, immune-mediated fibroinflammatory condition that commonly affects the pancreas and hepatobiliary system, leading to progressive organ damage. The MITIGATE study, a global, randomised, placebo-controlled trial, evaluated the safety and efficacy of inebilizumab, a CD19-targeting monoclonal antibody that depletes B cells. A post hoc subgroup analysis focused on patients with active pancreatic, biliary, or liver involvement at baseline. Participants with a history of multi-organ disease and recent glucocorticoid-treated flare were randomised to receive inebilizumab or placebo at set intervals during a 1-year treatment period. Glucocorticoids were tapered off by Week 8, and no other immunosuppressants were allowed.
Of 135 trial participants, 52% had prior pancreatic disease, 32% had biliary involvement, and 7% had liver disease. At baseline, active disease was present in 38% (pancreas), 21% (bile ducts), and 4% (liver). Inebilizumab dramatically reduced flare risk in all groups. In the pancreas group, the hazard ratio for flare compared to placebo was 0.03 (nominal p=0.005). Notably, none of the inebilizumab-treated patients with biliary or liver involvement experienced a flare, while 12/15 and 3/3 placebo-treated patients did, respectively.
Annualised flare rates were significantly lower with inebilizumab in all subgroups, with a rate ratio of 0.04 for pancreatic disease (nominal p=0.0015). Complete remission without treatment was achieved more frequently with inebilizumab, with an odds ratios of 10.8 and 35.8 in the pancreas and bile duct groups, respectively. Steroid use was also significantly lower in these groups (nominal p<0.001). Adverse events were consistent with the overall trial population, with no new safety concerns identified.
These findings highlight the therapeutic potential of CD19-targeted B cell depletion in managing IgG4-related disease with pancreatic and hepatobiliary involvement. Inebilizumab may offer a more effective, steroid-sparing option for long-term disease control.
