Objective:Liver diseases represent a major global health burden. Growth Differentiation Factor 15 (GDF-15), a stress-induced cytokine, has been suggested to protect against fibrosis progression through neuro-metabolic-immunologic pathways and to regulate energy and lipid homeostasis, potentially influencing hepatic steatosis. This study evaluated the role of GDF-15 in steatosis and fibrosis, considering prior liver injury, alcohol intake, insulin resistance, and obesity. Design and methods:In this retrospective cohort study, 626 participants from a large population-based cohort were analyzed. Associations of baseline GDF-15, alcohol intake, FIB-4 score, and metabolic risk factors with hepatic steatosis and fibrosis over 6 years were examined using linear regression models. Results:In participants with elevated baseline FIB-4, the interaction of GDF-15 and FIB-4 was positively associated with follow-up liver stiffness (β = 0.47, p = 0.045). Interactions between GDF-15 and higher alcohol intake (3rd/4th quantiles) were negatively associated with stiffness (β = -1.68, p = 0.002; β = -1.43, p = 0.038). GDF-15 was positively associated with follow-up steatosis (β = 37.14, p = 0.006). Higher HOMA-IR (3rd/4th quantile) was linked to increased steatosis (β = 31.15, p = 0.032; β = 38.15, p = 0.023), whereas interactions of HOMA-IR × GDF-15 were inversely associated (β = -38.98, p = 0.008; β = -38.54, p = 0.019), suggesting a protective modulation. Conclusions:GDF-15 appears to modulate hepatic steatosis and fibrosis in individuals with metabolic or lifestyle risk factors, supporting its potential as a therapeutic target and warranting further investigation of the neuro-metabolic-immunologic axis.

OBJECTIVE:The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, underscoring the need for tools to stratify individual risk of disease progression. We evaluated whether logistic regression models augmented by deep learning-based predictions (DLPs) can improve the B-mode ultrasound-based identification of at-risk MASLD, defined as patients with increased fibrosis risk. METHODS:We retrospectively analyzed 205 patients with a total of 636 ultrasound images. We developed a model that reproduces the LSM-based dichotomous fibrosis risk classification using clinical parameters and ultrasound image-derived deep learning pipelines. Patients were classified by same-day liver stiffness measurement (LSM) (<8 kPa: low fibrosis risk; ≥8 kPa: increased fibrosis risk). We assessed the incremental value of DLPs when added to the parameters sex, age, BMI, diabetes mellitus type 2 status and the fibrosis-4 score (FIB-4) based on accuracy, AUROC, and related statistics. RESULTS:The logistic regression model combining the clinical parameters and the DLPs achieved acceptable performance with an AUROC of 0.73 and a test accuracy of 68%. The same model without DLPs showed an AUROC of 0.72 and a test accuracy of 61%. Including FIB-4 improved performance further (AUROC 0.92, accuracy 88%). Models based solely on image data demonstrated limited diagnostic performance. CONCLUSION:B-mode ultrasound provides a weak fibrosis-related signal, yielding limited diagnostic performance. Meaningful discrimination required the incorporation of clinical parameters, with FIB-4 offering the greatest improvement among the parameters assessed. Deep learning predictions added only modest incremental value. Prospective validation is needed to clarify clinical utility.

Abstract:Metabolic dysfunction-associated steatotic liver disease (MASLD) has undergone a major conceptual shift from a steatosis-centred condition to a disease spectrum, in which advanced fibrosis is the major prognostic determinant. It affects up to one-third of the adult population but remains asymptomatic in the majority of patients. Therefore, the efficient identification of at-risk individuals is a central clinical task. Non-invasive tests increasingly complement histological staging and are embedded in sequential diagnostic algorithms. In particular, FIB-4, as a first-line screening tool followed by vibration-controlled transient elastography for liver stiffness assessment, has been adopted by expert recommendations and clinical guidelines. Abstract:These non-invasive tests have proven relevance to clinical endpoints beyond risk stratification and indications for MASLD-specific therapy. However, dynamic changes and their prognostic implications during treatment require further prospective evaluation. This review summarizes the current diagnostic strategies for MASLD and discusses their implementation in the German healthcare context.

INTRODUCTION AND OBJECTIVES:Treatment response of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) is assessed after 12 months by Paris II criteria. In the German PBC registry, individuals were stratified into adequate and inadequate Paris II responders. We analyzed the concordance between clinical judgement and formal Paris II classification. PATIENTS AND METHODS:Physician-assessed UDCA treatment response was compared to formal Paris II criteria (alkaline phosphatase (ALP) or aspartate-aminotransferase (AST) >1.5 x ULN or bilirubin >1 mg/dL). RESULTS:10/130 (8%) cases were misclassified as inadequate UDCA responders, 44/253 (17%) as adequate responders despite not meeting Paris II criteria. Incorrectly classified responders occurred in 26% versus 13% of individuals at secondary and tertiary centers (p = 0.0141). At secondary centers, 86% of misclassified responders had ALP >1.5 × ULN and 5% had bilirubin >1 mg/dL, compared with 32% and 27% at tertiary centers. ALP levels >1.5 x ULN occurred significantly more often at secondary centers (p = 0.0005). At secondary centers, ALP levels at diagnosis were higher in misclassified versus correctly classified responders (3.6 ± 3.0 x ULN vs. 1.7 ± 0.9 x ULN, p < 0.001) and remained higher after 12 months of therapy (2.3 ± 1.2 vs. 0.9 ± 0.3 × ULN, p < 0.001). CONCLUSIONS:Clinical judgement and Paris II classification differ in 20% of patients. Higher baseline ALP levels and kinetics may lead to misclassification. This may result in withholding of second line treatments in these patients.

Background Conventional ultrasound is widely used in abdominal imaging but remains limited by operator dependency, non-standardized documentation, and a restricted field of view. Tomographic three-dimensional ultrasound combined with multiscan stitching may overcome some of these limitations by generating standardized large-volume datasets that allow retrospective multiplanar review. This pilot study evaluated the technical feasibility of multiscan three-dimensional ultrasound for large-volume abdominal imaging in phantoms, healthy volunteers, and selected patients with liver disease. Methods A multiscan stitching algorithm was first assessed under controlled conditions using standardized ultrasound phantoms to evaluate volume reconstruction, seam continuity, and artifact formation. The method was then prospectively applied in 22 healthy volunteers and 22 patients with focal or chronic parenchymal liver disease. Conventional ultrasound served as the reference for image quality and completeness of organ depiction. Additional phantom and proof-of-concept torso examinations were performed to explore potential future use cases. Results In phantom experiments, adjacent three-dimensional ultrasound volumes could be successfully merged, with preserved margin continuity when acquisition was performed under standardized conditions and with sufficient overlap. In healthy volunteers, three-dimensional ultrasound enabled large-area abdominal and liver coverage, although image quality was lower than conventional B-mode ultrasound and varied depending on the scan protocol. In patients, focal liver lesions and characteristic features of diffuse liver disease were visualized in reconstructed datasets. The best balance between image quality and organ coverage was achieved with acquisition strategies using fewer, well-aligned adjacent volumes. Stitching-related artifacts, respiratory motion, transducer pressure, and tracking-related limitations were identified as relevant technical challenges. Conclusion Multiscan tomographic three-dimensional ultrasound is technically feasible for generating standardized large-volume abdominal ultrasound datasets in phantoms, healthy volunteers, and selected patients under favourable examination conditions. The approach may support retrospective examiner-independent review, structured documentation, telemedical assessment, and future image-analysis workflows. However, the findings remain exploratory and system-specific. Quantitative validation of geometric accuracy, diagnostic performance, reproducibility, and robustness in larger and more heterogeneous patient cohorts is required before broader clinical implementation. Trial registration The study was registered in the German Clinical Trials Register (DRKS00016736 05/2019).

Obesity and type 2 diabetes (T2DM) are major risk factors for hepatic steatosis. Diet or bariatric surgery can reduce liver volume, fat content, and inflammation. However, little is known about their effects on liver function, as evaluated here using the LiMAx test. In the MetaSurg study (RCT on the effects of different Roux-en-Y gastric bypass (RYGB) limb lengths on diabetes remission in patients with BMI ≥ 27 to ≤ 60 kg/m2 and T2DM; trial registration: DRKS00007810, German Clinical Trials Register Freiburg), 24 consecutive patients underwent liver function (LiMAx) and imaging assessments (MRI, transient elastography; TE) before and after diet and surgery. Two weeks before surgery, the patients received a hypocaloric protein-rich diet. Nine of 18 patients had a pathologic LiMAx value (≤ 315 µg/kg/h) at baseline. After two weeks of diet, LiMAx values improved (p = 0.01, paired t test, n = 15). LiMAx values further recovered six months after RYGB (p = 0.01, paired t test, n = 15), which was accompanied by decreased liver volumes (p = 0.005, paired t test, n = 10), proton density fat fraction (p = 0.003, paired t test, n = 12), and TE measurements (p = 0.032, paired t test, n = 14). The need for medical diabetes treatment decreased from 100 to 35

Guidelines on primary biliary cholangitis (PBC) recommend therapy with 13–15 mg/kg ursodeoxycholic acid (UDCA) and assessment of treatment response after 12 months. We evaluated to which extent these recommendations are followed in newly diagnosed patients. The German PBC Registry recruited three subgroups: Adequate or inadequate UDCA treatment responders (Paris II criteria) and newly diagnosed patients (<6 months prior to recruitment). We focus on newly diagnosed patients with UDCA monotherapy. 82 patients were recruited (43 at 12 tertiary and 39 at 9 secondary centers) thereof 22% with cirrhosis. Individuals with cirrhosis were older (71 ± 9 vs. 55 ± 14 years, p<0.001) and presented more frequently with diabetes mellitus (44% vs. 13%, p=0.0054) and arterial hypertension (78% vs. 42%, p=0.0076) compared to cases without cirrhosis. 12 months follow-up data were available in 62 patients. UDCA underdosing (<13 mg/kg/d) occurred in 47% and 74% of cases (p=0.013) at tertiary and secondary care at treatment initiation and in 29% and 73% (p=0.002) after 12 months, respectively. Paris II criteria were achieved in 74% and a deep UDCA response (alkaline phosphatase < ULN and bilirubin < 0.6 × ULN) in 32% of cases. Newly diagnosed PBC patients include a substantial proportion of late presenters with cirrhosis. UDCA dosage is suboptimal in many cases. Time point of diagnosis and UDCA dosage should be improved.

BACKGROUND:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease. Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of MASLD, can lead to fibrosis and cirrhosis. The incidence and burden of MASH in Germany are expected to double by 2030, while diagnostic and management challenges persist. Expert consensus on diagnostic strategies and treatment modalities in MASLD and MASH is required. OBJECTIVES:The panel aimed to gather insights and consensus on the diagnostic pathway and current treatment modalities for MASH in Germany. METHODS:A three-round web-based survey, integrating Delphi panel methodology with a standard survey, was conducted from February to May 2024 to reach consensus on predefined questions. The survey involved 12 gastroenterology, diabetology and/or hepatology specialists in Germany. RESULTS:The Delphi panel revealed that ~75% of MASH patients in Germany remain undiagnosed. Non-invasive measures, such as fibrosis scores (values from clinical and imaging tests to assess fibrosis), liver enzyme tests and liver stiffness measurement, were primary methods for diagnosing and monitoring MASH patients. Lifestyle modifications were the primary management strategy, given the absence of approved pharmacological treatments for MASH. The panel also highlighted significant challenges in managing MASH, including the lack of approved medications and the difficulty in sustaining lifestyle changes. CONCLUSIONS:The survey underscores the substantial underdiagnosis of MASH and the reliance on non-invasive diagnostic methods in Germany. The lack of approved treatments necessitates a focus on lifestyle modifications and comorbidity management. The Delphi panel's insights call for enhanced screening, early detection and standardised algorithms to improve patient outcomes.

Conventional ultrasound (conUS) is operator-dependent, limiting reproducibility. Tomographic three-dimensional ultrasound processing (t3DUS) offers a potential solution by creating standardised data volumes similar to cross-sectional imaging. However, since abdominal organs often extend beyond the transducers’ angle of view, combining multiple adjacent volumes is necessary. First, the feasibility of applying a volume-stitching algorithm (PIUR Imaging, Vienna, Austria) to t3DUS images was evaluated using a standardised ultrasound phantom. Then, t3DUS was prospectively assessed in healthy volunteers and patients with liver diseases, comparing its image quality and diagnostic value to conUS. Finally, t3DUS was applied to a neonatal torso to explore potential use cases. Precise alignment of adjacent 3D image volumes on the ultrasound phantom yielded excellent results. In 22 healthy subjects and 22 patients with focal or parenchymal liver diseases, up to four adjacent abdominal scans were seamlessly merged into a continuous 3D volume, effectively illustrating both focal liver lesions and diffuse liver disease characteristics. The tomographic images from the neonatal ultrasound torso further underlined the imaging capabilities of t3DUS. In conclusion, tomographic acquisition and data processing techniques for abdominal ultrasound images are feasible and provides standardised, examiner-independent image datasets. However, technical optimisation and simplification of the acquisition process are necessary.

INTRODUCTION AND OBJECTIVES:Pruritus is a frequent and burdensome symptom in patients with primary biliary cholangitis (PBC), significantly affecting quality of life. Despite its clinical relevance, data on the prevalence and management, particularly across different levels of healthcare, remain limited. We aimed to assess prevalence, severity, and treatment of pruritus in PBC patients across secondary and tertiary care. PATIENTS AND METHODS:Within the German PBC registry, the intensity and management of pruritus were assessed cross-sectionally by treating physicians using a standardized 4-point verbal rating scale (absent, mild, moderate, severe), as well as by analyzing prescribed antipruritic medications. RESULTS:Pruritus was reported in 23 % (n = 120/515) of patients and classified as mild, moderate, or severe in 59 (49 %), 41 (34 %), and 20 (17 %) cases, respectively. The prevalence of pruritus was 27 % (n = 96/360) for tertiary versus 16 % (n = 24/155) for secondary care (p = 0.006). Moderate or severe pruritus was observed in 13.3 % (n = 48/360) of patients at tertiary centers compared to 8.4 % (n = 13/155) at secondary centers (p = 0.137). Antipruritic therapies were used in only 22.5 % (n = 27/120) patients with pruritus, with bezafibrate being the most frequently prescribed medication (63 %, n = 17/27). Patients with pruritus were more likely to receive antipruritic therapies in tertiary than secondary care: 26 % (n = 25/96) vs. 8 % (n = 2/24) (p = 0.098). CONCLUSIONS:Pruritus in patients with PBC is common and under-treated in the real-world scenario. Assessment and management vary by healthcare level, highlighting the need for standardized care and greater awareness of treatment options across all settings.