Rare liver diseases are associated with diagnostic delay, fragmented care, inconsistent management, and limited patient support. Patient pathways may help address these challenges by translating clinical guidance and patient priorities into practical, coordinated care processes. This manuscript presents a European template for developing patient-centred pathways for rare liver diseases within ERN RARE-LIVER. The template was developed through multidisciplinary collaboration involving hepatologists, specialist nurses, patient representatives, patient organisations, and EURORDIS, and was informed by clinical guidance, patient-journey principles, and iterative expert and patient review. The proposed framework follows four phases of the patient journey: pre-diagnosis, diagnosis, management, and long-term follow-up. It includes disease-specific sections, educational resources, frequently asked questions, and “10 key questions” to support shared decision-making. Pathways for non-cirrhotic portal vein thrombosis, polycystic liver disease, and portosinusoidal vascular disorder illustrate the practical application of the template. This European template provides a practical, adaptable framework aimed at supporting harmonised, multidisciplinary, and patient-centred care for rare liver diseases across European healthcare settings. Future work should evaluate implementation, usability, and impact on care coordination and patient experience.

Autoimmune hepatitis (AIH) is a rare, complex and chronic immune-mediated disease in which loss of tolerance to hepatocyte antigens leads to T-cell-driven liver inflammation, typically associated with autoantibodies and elevated IgG. The understanding of disease mechanisms is limited, patient presentations are heterogeneous, and clinical care varies. Predniso(lo)ne and azathioprine or mycophenolate mofetil are the first-line treatments. These medications are life-saving, but lack specificity, and are marred by side-effect profiles that negatively affect adherence and quality of life. Less than 70% of patients achieve a complete biochemical response (normalization of aminotransferases and IgG) by 6 months, and more than 20% develop side effects that require discontinuation. In addition, current medications have high rates of relapse after discontinuation. Evidence of second- and third-line treatments is mainly built on real-world studies without control groups. In addition, people with AIH experience symptoms that affect their well-being, such as fatigue, depression, anxiety, cognitive dysfunction and mood changes. Several gaps in AIH management persist, including a lack of validated questionnaires to capture specific symptoms and complaints, lack of recognized endpoints for clinical trials supported by regulatory agencies, and special AIH populations are understudied and outcomes beyond liver enzymes are underrepresented. In this review, we provide a detailed appraisal of current gaps in the management, discuss special populations, and recent advancements of new agents for AIH, summarizing evidence regarding how these agents could reduce the side effects of current treatment, potentially improving the quality of life of people living with AIH.

Seronegative autoimmune hepatitis (SnAIH) lacks detectable conventional autoantibodies (ANA, SMA, anti-LKM, anti-LC1, and anti-SLA/LP), posing diagnostic challenges. Increasing evidence suggests SnAIH in adults reflects limitations in autoantibody detection rather than a distinct variant. We systematically re-evaluated all biopsy-proven SnAIH cases in a large international multicenter AIH cohort using standardized testing. Among 760 patients with baseline liver biopsy, 52 (6.8%) were initially classified as SnAIH. Forty-three lacked complete autoantibody testing, most commonly anti-SLA/LP. After comprehensive re-evaluation, only 9 patients (1.18%) fulfilled criteria for true SnAIH. All presented acutely with markedly elevated transaminases (median ALT 16.1 × ULN); five had elevated IgG levels. Histology suggestive of autoimmune-like drug-induced liver injury was observed in four cases. All but one relapsed after treatment withdrawal, and 42.9% failed to normalize ALT at six months. In conclusion, SnAIH is rare (~1%), highlighting the importance of standardized, comprehensive autoantibody testing and re-testing according to the guidelines.

Background The optimal duration of antibiotic prophylaxis in cirrhotic patients with variceal bleeding remains debated. Current guidelines (EASL, AASLD, Baveno VII) recommend 5-7 days of antibiotics, largely based on pre-2010 studies. While ceftriaxone reduces mortality, rebleeding, and infections, prolonged use may increase antimicrobial resistance, hospital length of stay, and costs. We evaluated whether shorter or on-demand antibiotic strategies are comparable to standard prophylaxis. Aim This systematic review and meta-analysis compared standard prophylaxis (5–7 days) with shorter (<5 days) or on-demand strategies. Primary outcomes were rebleeding and bacterial infections. Secondary outcomes included length of stay, infection subtypes, bilirubin at admission, and all-cause mortality. Results Thirteen studies including 2,194 patients were analyzed; ten were RCT’s and three were retrospective studies. Heterogeneity was high (I2 >50%). The pooled OR in favor of standard treatment strategies was 1.22 [95% CI:0.64–2.32] for rebleeding and 1.53 [0.66–3.54] for bacterial infections. Recent studies reported lower risk estimates than earlier studies. Meta-regression showed a downward trend in infection risk over time (p ≤0.0001). Secondary outcomes did not differ significantly. Conclusion Although pooled estimates numerically favored standard prophylaxis, recent evidence suggests that alternative strategies may be as effective. While this generates the hypothesis that current guideline recommendations may no longer reflect modern practice, the prevailing uncertainty emphasizes the need for new and adequately powered randomized trials before clinical practice can be definitively altered.

Background and Aims: Remote monitoring (RM) enables out-of-hospital surveillance and may benefit patients with liver cirrhosis. However, implementation in routine liver cirrhosis care is limited, most likely due to the lack of conclusive data on clinical effectiveness. This systematic review aims to analyze the quality of evidence regarding the effect of RM tools on disease outcomes for liver cirrhosis. Methods: This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review included studies of RM interventions per the World Health Organization’s definition in patients with liver cirrhosis reporting at least 1 liver disease-related outcome. Retrospective or cross-sectional studies were excluded. Risk of bias was assessed using the Cochrane Risk Of Bias Tool for Randomized Trials and the Newcastle-Ottawa Scale for other study types. RM development quality was evaluated against the V3+ framework. Results: One randomized controlled trial, 4 prospective cohorts with controls, and 7 prospective studies without controls were identified (n = 12; 636 patients; 17,680 studies screened). All studies with controls reported lower hospital readmissions in the RM groups. Interventions included smartphone applications, with or without additional measurement instruments, and automated calls. RM development quality varied substantially, with multiple RM interventions not reporting on verification (n = 6), usability (n = 4), or analytical validation (n = 5). The identified evidence informed the synthesis of a proposal framework to harmonize future RM research. Conclusion: Although studies show clinical benefits of RM tools in liver cirrhosis, evidence is limited by the (inherent) heterogeneity in interventions, design, and outcomes, and quality of the RM development process. This review emphasizes the need for consensus on RM monitoring frameworks and high-quality data to inform better clinical decision-making.

BACKGROUND:Optimal care delivery for primary biliary cholangitis (PBC) has become challenging due to new therapies and more individualized biochemical treatment goals. AIM:To evaluate uptake of ursodeoxycholic acid (UDCA) and second-line therapy (SLT) in a nationwide PBC cohort and identify factors associated with suboptimal therapeutical management. METHODS:The Dutch PBC Cohort Study is a retrospective study including every identifiable patient with PBC in the Netherlands from 1990 onwards. Use of UDCA and SLT was assessed among patients in clinical follow-up on 1 January 2019. Biochemical response was defined as alkaline phosphatase (ALP) and aspartate aminotransferase (AST) ≤ 1.5 × ULN and total bilirubin (TB) ≤ ULN. SLT included off-label fibrates, budesonide and/or obeticholic acid (not reimbursed). RESULTS:In total, 2638 patients with PBC were included; median age was 64.0 (IQR 55.0-72.0) years, 2361 (89.5%) were female and 2143 (81.2%) were treated in a non-academic center. Overall, 2532 (96.0%) patients used UDCA. The recommended UDCA dose of ≥ 13 mg/kg/day was used by 1363/2205 (61.8%). Age (aOR 1.01, 95% CI 1.00-1.02, p = 0.02), body weight (aOR 1.04, 95% CI 1.03-1.05, p < 0.01) and biochemical response (aOR 1.35, 95% CI 1.09-1.67, p = 0.01) were associated with UDCA dosage < 13 mg/kg/day. Among patients with an incomplete response, 101/638 (15.8%) were prescribed SLT. Younger age, female sex, treatment in an academic centre and higher levels of ALP and AST were positively associated with use of SLT. CONCLUSIONS:During recent years, UDCA was insufficiently dosed in Dutch patients with PBC. The results indicate that first-line treatment can be optimized, especially in those with a biochemical response and higher body weight.