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Foundations of Artificial Intelligence in Hepatology: What a Clinician Needs to Know.

This review focuses on foundational knowledge about artificial intelligence (AI) in hepatology, exploring how AI, including machine learning and deep learning, leverages large-scale clinical data to transform the diagnosis, risk assessment, prognostication, and management of liver diseases. Online resources are described to offer fundamental AI knowledge and essential technical skills and to facilitate clinician participation across the entire AI lifecycle, ensuring they contribute not only as end users but also in development and deployment. Unlike traditional statistical approaches that prioritize interpretable parameters and clinical insight, AI focuses on maximizing predictive accuracy by identifying complex, often non-linear patterns using high-dimensional data, albeit often at the cost of model interpretability. AI is demonstrating clinical utility in liver histopathology and radiological imaging, significantly improving detection accuracy for cirrhosis, clinically significant portal hypertension, and hepatocellular carcinoma. Beyond diagnostics, AI-driven prediction models are emerging to provide personalized risk stratification for the development of liver-related complications and treatment guidance, based on complex data including longitudinal laboratory results, comorbidities, and co-medication use to monitor disease progression and therapy response. The field is rapidly expanding into novel areas such as analyzing patient-reported outcomes, genomic data, and real-time liver function monitoring, offering deeper mechanistic insights alongside clinical tools. Despite the potential to revolutionize hepatology practice and research, successful integration into routine care faces challenges. These include seamless workflow integration with existing electronic health records, establishing clear liability frameworks, and guaranteeing protection of patient privacy. Addressing these hurdles requires collaborative efforts from clinicians, researchers, and regulators to develop best practices and governance. Understanding the transformative capabilities, current applications, emerging frontiers, and essential implementation considerations is crucial for clinicians navigating the evolving AI landscape and responsibly utilizing its power for improved patient outcomes.

PROBAST+AI

[Perspectives of clinical biochemistry in hepatology].

In a survey the trend of the biochemical investigations in hepatology is analysed. Together with the histologic diagnosis the function of the liver parenchyma must be determined, in which cases tolerance tests which do not only determine the function of the liver parenchyma, but also the changed functions of other organs are of importance. On the basis of own findings is shown that the ammonia metabolism in patients with hepatic encephalopathy is also disturbed in musculature. In the serum of patients with decompensated liver cirrhosis a factor could be isolated which apart from the inhibition of the utilisation of glucose has also another metabolic effect. In future we might expect an intensified search for such active metabolites. Investigations concerning the salicylaemia in patients with liver cirrhosis and experimental findings about changes of the O-demethylase activity in the fatty degeneration of the liver show the great significance of the pharmacokinetic analyses in the clinical hepatology.

Ammonia

[Hepatologic dispensaire for blood donors].

By means of hepatological examinations of 119 blood donors who became conspicuous by liver screenings in 57 cases we could prove an adipose degeneration without, in 16 cases a fatty degeneration of the liver without, in 9 cases an adipose degeneration with and in 15 cases a fatty degeneration of the liver with mesenchymal reaction. Only 9 blood donors had normal liver findings. 90% of the punctured blood donors had an overweight up to a maximum of 35 kg in comparison to the ideal weight. 30% of the punctured patients admitted a clearly increased daily consumption of alcoholic beverages. By means of repeated punctures on 24 blood donors after 8 to 32 months after an adequate consultation in three cases a normalisation and in eight cases an improvement of the liver findings could be proved. In 13 cases the findings remained unchanged, also the anamnestic and clinical findings corresponded to this. In 2 blood donors by means of a threefold liver puncture in the observation period of 48 months also a clear retrogression of the liver findings was proved. With this was also connected the reduction of overweight and the avoiding of alcohol. Thus our investigations confirmed that overweight and abuse of alcohol are essential factors for the development of a fatty degeneration of the liver. Of an infectious hepatitis reported in the anamnesis in 10 blood donors histologically in no case residues were established. Thus the liver dispensary is of great importance for the care of blood donors who become conspicuous by screening tests. On the one hand the importance is referred to the blood donor himself, on the other hand to the group of donors. Blood donors taken out of the group could again be included in the special group, when after the exclusion of known noxae the retrogression of unspecific liver changes took place.

Adolescent

[The effectivity of long-term treatment of porphyria cutanea tarda from a hepatological viewpoint].

34 Patients with an ascertained porphyria cutanea tarda who underwent a long-term therapy a comprehensive internal and hepatological diagnosis was made. In these cases for the first time the estimation of the intrahepatic distribution of enzymes and its comparison with the serum enzymes were also performed. The liver histology allowed a division of our patients into three groups, in which cases the reactive hepatitides prevailed and a conspicuously large proportion of normal histological findings were present. The comparison of all data got with the literature made the conclusion possible that the phlebotomy therapy as well as the care in a special dispensary for years lead to very favourable results on liver and skin.

Bloodletting

Toward AI Virtual Cells for Hepatology: Representation, Generation, Dynamics, and Intervention in Single-Cell Models.

``Single-cell and spatial atlases describe the healthy and diseased liver at high resolution, including lobular hepatocyte zonation, fibrotic macrophage-stellate niches, cholangiocyte reactions, immune remodeling, and hepatocellular carcinoma ecosystems. These maps show where cell states occur but do not, by themselves, predict whether liver injury will progress or how the liver will respond to an untested drug, toxicant, or genetic perturbation. In this review, we organize current approaches toward an AI Virtual Cell (AIVC) for the liver into three complementary modeling routes. Generative models represent cell states, dynamics and transport models infer state transitions, and pretrained or foundation models test whether learned representations transfer across donors, etiologies, disease stages, and platforms. Perturbation-response prediction serves as a cross-cutting assessment of whether these layers can predict responses to untested genetic, chemical, inflammatory, or metabolic interventions. Available evidence can be categorized as direct liver validation, liver-included benchmarks, general single-cell evidence, and conceptual applications. Published models demonstrate individual components, including atlas integration, inferred trajectories, transferable representations, and retrospective response programs. However, these models do not constitute a prospectively validated liver simulator. At minimum, evaluation should include donor-, etiology-, stage-, platform-, and perturbation-level hold-outs. Model performance should be reported using response direction, recovery of differentially expressed genes and rare states, and calibrated uncertainty. Claims about tissue- or function-level prediction additionally require independent spatial, histologic, metabolic, and functional readouts. Near-term use should prioritize experiment selection and hypothesis generation, whereas clinical decision support remains a longer-term objective.

AI Virtual Cell

[Hepatology and immunology].

Immunologic diseases of the liver are exogenous mostly initiated by virus or endogenous initiated by autoaggression. All virus-induced kinds of hepatitis are due to an immune response against inocculated hepatocytes. Therefore the hepatitis is limited to the period of complete elimination of virus-infected cells. A strong immune response therefore corresponds with an acute and short hepatitis whilest a weak immune response develops a chronic hepatitis. In contrast, autoimmune hepatitis based on a disorder of the immune system with some genetic background is always unlimited. Each cirrhosis developing from immunologic hepatitis is also an immunologic disease; a special variant is the autoimmune primary biliary cirrhosis. All in all, the number of immunologic liver diseases surmounts the remaining liver diseases due to intoxication of metabolic disorders.

Antibodies, Viral

[New aspects of clinical hepatology (author's transl)].

Studies of the enzymes participating in the urea cycle and urine synthesis in the liver punctate show that typical changes occur in the enzyme pattern during chronic liver diseases which yield new starting points for the diagnostic classification and prognostic assessment. From studies on the metabolism of the bile acids it appears that, among the conditions for cholestasis, a fetal snythetic pathway for the bile acids with primary side chain oxidation of the cholesterol is followed, and intrahepatic monohydroxy-bile acids are formed. The pathogenetic significance of these bile acids for cholestasis is discussed.

Argininosuccinate Synthase

The physiologic basis for clearance measurements in hepatology.

Three hepatic clearance regimes (flow-limited, general, and enzyme-limited) can be defined from a model of hepatic perfusion-elimination relationships. Substances that can be used for clearance measurements can thus be classified into three categories according to the relation between their kinetic elimination constants (Vmax, Km) and hepatic blood flow. The pathophysiologic and clinical importance of the clearance regimes is discussed with special emphasis on the effect of changes in hepatic blood flow and liver function. The criteria for choosing test substances within each regime are stated. This choice depends on the object of study for a clearance measurement (blood flow, drug elimination, liver function). Only the enzyme-limited clearance regime is suited for direct assessment of quantitative liver function ('true clearance'), while the other regimes depend more or less on blood flow.

Animals