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The prevalence of fatty liver disease has increased significantly in Germany in recent years. With an estimated 18 million German citizens being affected, it is now among the most prevalent diseases. Furthermore, it is also considered a relevant and independent risk factor for other common cardiovascular diseases such as heart attack or stroke. Finally, diabetes mellitus promotes the development of and an unfavorable course of fatty liver disease. Given the high prevalence and complications, the German healthcare system is reaching its limits.Therefore, close coordination of all healthcare providers and specialists involved in the treatment of these patients is essential. In an expert consensus involving private practice and hospital doctors from the fields of gastroenterology, endocrinology, cardiology, general practitioners and laboratory physicians, as well as in close coordination with patient representatives, we have designed a concept for the care of these patients in the German healthcare system. Necessary developments are also addressed. In addition to being useful as a practical guideline, this should also support health policy work, especially in the development of practical care solutions at the medical level., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem. Understanding the immunological processes in the liver during the development and progression of fatty liver disease to fatty liver inflammation (NASH), liver cirrhosis or hepatocellular carcinoma (HCC) can be used to better understand the disease, identify clinically relevant subgroups and therapeutic approaches. The interaction between innate and acquired immune systems seems to be of great importance. This review article highlights the various immunological processes in NAFLD leading up to progression to HCC, organized according to the major cell groups of the innate and acquired immune systems., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Competing Interests: Die Interessenerklärungen aller Expert*innen sind im Anhang aufgeführt.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), or non-alcoholic fatty liver disease (NAFLD), is a common disease that is diagnosed through manual evaluation of liver biopsies, an assessment that is subject to high interobserver variability (IBV). IBV can be reduced using automated methods., Objectives: Many existing computer-based methods do not accurately reflect what pathologists evaluate in practice. The goal is to demonstrate how these differences impact the prediction of hepatic steatosis. Additionally, IBV complicates algorithm validation., Materials and Methods: Forty tissue sections were analyzed to detect steatosis, nuclei, and fibrosis. Data generated from automated image processing were used to predict steatosis grades. To investigate IBV, 18 liver biopsies were evaluated by multiple observers., Results: Area-based approaches yielded more strongly correlated results than nucleus-based methods (⌀ Spearman rho [ρ] = 0.92 vs. 0.79). The inclusion of information regarding tissue composition reduced the average absolute error for both area- and nucleus-based predictions by 0.5% and 2.2%, respectively. Our final area-based algorithm, incorporating tissue structure information, achieved a high accuracy (80%) and strong correlation (⌀ Spearman ρ = 0.94) with manual evaluation., Conclusion: The automatic and deterministic evaluation of steatosis can be improved by integrating information about tissue composition and can serve to reduce the influence of IBV., (© 2024. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) is of increasing prevalence globally. While lifestyle modifications are recommended, many patients do not succeed to achieve significant and maintained weight loss from lifestyle and as such there is a high unmet need for pharmacotherapy in this group. Comparable to other metabolic diseases including diabetes and dyslipidaemia, a high proportion of patients will likely benefit from permanent pharmacological therapy. Currently there are many compounds with different mechanisms of action in clinical development including metabolic, anti-inflammatory and anti-fibrotic drugs. A number of phase 3 clinical trials are currently ongoing including Elafibranor, a dual PPAR α/δ agonist, Cenicriviroc, a CCR2/CCR5 chemokine antagonist, the nuclear bile acid receptor FXR agonist obeticholic acid, Aramchol, a fatty acid bile acid conjugate that modulates SCD-1, and Resmetrion, a liver-specific THR-β agonist. Further studies with promising pathophysiological mechanisms of action, e. g. the ASK-1 inhibitor Selonsertib or the caspase inhibitor Emricasan have shown negative results. However, some are being further evaluated in combination therapies. The complex pathophysiology of the disease, which combines inflammation, metabolism and fibrosis, has led to the fact that even combinations of several substances are investigated with different modes of action. This review summarizes pivotal clinical trials for patients with NASH in the absence of cirrhosis which are recruiting in the fall of 2019., Competing Interests: (Forschungs-)Unterstützung: Gilead Sciences.Honorar oder Beratungskosten: Allergan, Galmed, Genfit, Gilead Sciences, Intercept Pharmaceuticals, IQVIA, Madrigal, Novartis, Pfizer, Roche, Siemens Healthineers., (© Georg Thieme Verlag KG Stuttgart · New York.)

Non-alcoholic fatty liver disease (NAFLD) is mainly treated with caloric restriction and consecutive weight reduction. Protein, in exchange for starch and sugar as well as monounsaturated and long chain omega-3-fatty acids and prebiotic β-glucan, are thought to be supportive.In a randomized controlled intervention study, two different dietary concepts were tested regarding effects on intrahepatic lipid content as well as on biochemical parameters in patients with a body-mass-index (BMI) > 30 kg/m 2 and signs of fatty liver disease. The intervention group (IG, n = 17) received a commercially available formula diet supplemented with oats fibers. The control group (CG, n = 19) received a comparably restricted diet (approx. 1000 kcal/d) according to the "low glycemic and insulinemic diet" method.After twelve weeks, both interventions resulted into a reduction of BMI (IG: 33.8 ± 2.9 to 29.3 ± 2.5 kg/m 2 , CG: 33.7 ± 2.8 to 30.1 ± 3.2 kg/m 2 , both p < 0.001), as well as an improvement of liver and other metabolic functions. The hepatorenal index decreased in both groups, however, this reduction was more pronounced in the IG than in the CG (end of the study: 1.1 ± 0.2 vs. 1.9 ± 0.3, p < 0.05). A reduction of blood pressure only occurred in the IG (systolic from 136 ± 15 mmHg to 122 ± 11 mmHg, diastolic from 89 ± 9 mmHg to 79 ± 11 mmHg, both p < 0.01).In conclusion, we found that both dietetic interventions were similarly effective regarding weight reduction, but the formula diet with oats fibers was more effective regarding the reduction of intrahepatic lipid content and blood pressure than the control diet., Competing Interests: Frau Anna Schweinlin ist bei der ZKES GmbH als wissenschaftliche Mitarbeiterin beschäftigt. Herr Prof. Dr. med. Stephan C. Bischoff ist Geschäftsführer der ZKES GmbH. Frau Melanie Teutsch ist in der medizinisch-wissenschaftlichen Abteilung der Bodymed AG tätig. Herr Dr. med. Hardy Walle ist Gründer und Vorstandsvorsitzender der Bodymed AG. Die ZKES GmbH hat die vorliegende Studie im Auftrag der Bodymed AG durchgeführt., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Cirrhosis is a common disease with high morbidity and mortality. In industrialised countries, the most common causes of cirrhosis are the alcoholic liver disease, non-alcoholic fatty liver disease and chronic viral hepatitis. Cirrhosis is often diagnosed late, as it can be asymptomatic for a long time. Therefore, hepatopathy screening in high-risk patients and fibrosis surveillance using the ultrasound, in the presence of a chronic hepatopathy are essential. A liver biopsy is necessary to confirm the diagnosis. With optimal therapy, in some cases, cirrhosis is preventable and potentially reversible in others. In the stage of decompensation, typically characterised by ascites, patients often die from recurrent infections or hepatocellular carcinoma unless cured by liver transplantation. The prevention and treatment of complications as well as the evaluation of a transplant require cooperation with a centre hospital., Competing Interests: Es bestehen keine Interessenskonflikte., (© 2023 Aerzteverlag medinfo AG.)

Non-alcoholic steatohepatitis (NASH) is the progressive entity of non-alcoholic fatty liver disease (NAFLD) and characterised by increased inflammatory activity, potentially resulting in liver fibrosis and ultimately cirrhosis. NASH activity and hepatic fibrosis are the prognosis determinating risk factors - rational stepwise diagnostic approaches are urgently needed as therapeutic options beyond lifestyle modifications are limited., Competing Interests: Frank Tacke erhält eine Forschungsförderung durch Allergan, BMS, Inventiva sowie Gilead und übt eine Beratungs- und Vortragstätigkeit für Allergan, Gilead, Abbvie, Alnylam, BMS, Intercept, Falk, Inventiva, Pfizer, Novartis, Novo Nordisk, Merz und Sanofi aus. Frank Tacke ist Koordinator der deutschen NAFLD-Leitlinie (DGVS) sowie designierter Koordinator der europäischen NAFLD-Leitlinie. Tobias Püngel wird im Rahmen des BIH Clinician Scientist Programm gefördert., (Thieme. All rights reserved.)

Background: Sarcopenia is a progressive and generalized disorder of the skeletal musculature that involves the loss of skeletal muscle mass and function. Patients with chronic liver disease frequently have sarcopenia in advanced stages of the disease; however, there is an increased prevalence of sarcopenia not only in liver cirrhosis but also in earlier stages of disease, e.g., in non-alcoholic fatty liver disease (NAFLD)., Results: Sarcopenia is an independent prognostic risk factor for morbidity and mortality in patients with liver cirrhosis. The pathogenesis of sarcopenia is multifactorial and in chronic liver diseases a lower oral energy intake, altered ammonia metabolism, hormonal imbalances and a chronic low-grade inflammatory state are important. When the screening test is positive, determination of the muscle strength, e.g., measurement of hand grip strength, is recommended for the diagnostic approach. Lower muscle strength leads to further measurement of muscle mass to confirm the diagnosis of sarcopenia. In patients with chronic liver disease abdominal imaging by computed tomography or magnetic resonance imaging is particularly suitable for this. The severity of sarcopenia is classified by the physical performance. Therapeutic strategies for the treatment of sarcopenia include nutritional therapy as well as exercise therapy., Conclusion: Patients with chronic liver diseases frequently have sarcopenia. This is an independent prognostic risk factor. Therefore, sarcopenia should be considered in the diagnostics and therapeutic approaches., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Nonalcoholic fatty liver disease (NAFLD) is nowadays the leading cause of chronic liver disease worldwide and shows a strong association with the metabolic syndrome. The NAFLD is a systemic disease associated with a plethora of extrahepatic manifestations and comorbidities, such as type 2 diabetes, obesity and dyslipidemia. These extrahepatic disorders are related either to secondary effects of the associated obesity or to pathophysiological effects of insulin resistance in NAFLD. The three most common causes of the observed increased morbidity and mortality associated with NAFLD are cardiovascular diseases, liver diseases, such as cirrhosis, and cancer. In this overview, cardiovascular diseases, type 2 diabetes mellitus and chronic kidney diseases in connection with NAFLD are discussed as examples, as well as tumor entities, in particular colon cancer, lung diseases (obstructive sleep apnea), endocrine diseases (hypothyroidism) and systemic phenomena associated with NAFLD (e.g. iron overload and thrombophilia). In addition to focusing on the pathogenesis of these extrahepatic manifestations, the clinical implications are highlighted. So far there are no drugs approved for the indication NAFLD in Germany. The new NAFLD S2k guidelines offer a way out of the current "therapeutic nihilism". Diagnostic and therapeutic algorithms based on the metabolic comorbidities and the stage of fibrosis are designed with practical relevance and can be used in everyday medical practice. Therefore, clear basic measures and drug recommendations can be given for NAFLD depending on the comorbidities and stage of fibrosis., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. In Germany, the prevalence in the adult population is estimated at 24 % and the incidence is increasing. Prognostically, the distinction between early and advanced stages of the disease is important. In particular, the extent of scarring considered as liver fibrosis is of prognostic significance. Patients with advanced fibrosis and cirrhosis show increased mortality. Liver fibrosis develops as a consequence of a persistent inflammation of the liver tissue over time. Since inflammation and fibrosis are histological features, liver biopsy is considered the reference method in the diagnosis of NAFLD. More recently, non-invasive diagnostic methods for staging (of fibrosis) and grading (activity) of the disease are being developed and validated. The current review summarizes new developments in non-invasive liver diagnostics., Competing Interests: JMS: Beratungstätigkeit: BMS, Boehringer Ingelheim, Echosens, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Madrigal, Nordic Bioscience, Novartis, Pfizer, Roche, Sanofi, Siemens Healthcare GmbH, Zydus. Finanzierung wissenschaftlicher Untersuchungen: Gilead Sciences. Vortragshonorare: Falk Foundation MSD Sharp & Dohme GmbH.MM gibt keinen Interessenkonflikt an., (Thieme. All rights reserved.)

Clinical guidelines are essential in implementing and maintaining nationwide stage-specific diagnostic and therapeutic standards. In 2015, the first German expert consensus guideline defined the evidence for epidemiology, pathogenesis, diagnosis and treatment of non-alcoholic fatty liver diseases in adults and children. The German S2k-guideline used an approved development process with de novo literature research since 2010, international guideline adaptation, or good clinical practice. Other recent evidence-based national guidelines and current references were included., (© Georg Thieme Verlag KG Stuttgart · New York.)

Research over the last two decades has highlighted the major role played by the gut microbiota in health and disease, including chronic liver diseases. The liver and intestine communicate via the portal vein, biliary system, and mediators in the circulation (gut-liver axis). Microbes in the intestine are involved in the maintenance of liver homeostasis. Conversely, alterations in the normal composition or diversity of the gut microbiome-a condition called dysbiosis-can also serve as a source of pathogens and molecules that contribute to the onset or progression of chronic liver diseases, like non-alcoholic fatty liver disease. Through the increased production of bacteria-derived ethanol, altered bile acid metabolism, altered production of short-chain fatty acids, greater abundance of lipopolysaccharide (LPS) containing Gram-negative bacteria and an increased intestinal permeability, dysbiosis impacts metabolic pathways and inflammatory processes. However, the clinical relevance of specific gut microbial alterations associated with chronic liver diseases remains unclear. This review discusses how microbes and their products contribute to liver disease pathogenesis and how targeting the microbiota might be used for therapeutic approaches., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Non-alcoholic fatty liver disease is the most common chronic liver disease in Europe and in the USA with rising prevalence. Patients with a metabolic syndrome (diabetes mellitus, obesity, dyslipidemia) are patients at risk with the highest prevalence for NAFLD. Progression from a non-alcoholic fatty liver (NAFL) to a non-alcoholic steatohepatitis (NASH) occurs in 5-20% of patients with the potential to develop a liver fibrosis/cirrhosis. NASH patients and NAFLD patients with higher fibrosis should be identified because they are at risk of a higher mortality. A specific treatment for NASH is not available at the moment. Therefore, the treatment of risk factors and metabolic syndrome has high priority., (© Georg Thieme Verlag KG Stuttgart · New York.)

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Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Up to 40% of all adults worldwide are overweight or obese. Besides the established obesity-related comorbidities, such as type 2 diabetes mellitus, hypertension or NAFLD (non-alcoholic fatty liver disease), the focus of interest is shifting towards the influence of increased body weight as a risk factor for the development of malignant diseases. For more than 20 different types of malignancies, interactions between increased body weight and cancer risk have been established. Pathophysiological influences of obesity on carcinogenesis are diverse, including factors such as chronic inflammation, hyperinsulinaemia and insulin resistance, various changes in growth factor and changes in sex hormones. In cohorts of visceral oncology patients, malignancies such as colorectal carcinomas, hepatocellular carcinomas, adenocarcinomas of the pancreas, oesophageal and gastric carcinomas are also linked to an increased disease risk with increasing body weight. Since obesity must be considered a preventable or at least treatable cause of cancer, this review examines the influence of obesity in the field of visceral oncology, examining the effects of obesity on tumour prevalence, prevention and diagnostic testing, as well as its influence on treatment and prognosis. Furthermore, this review explores the current evidence on the influence of bariatric surgery on the prevalence of these obesity associated tumours. For example, in the case of colorectal carcinomas, the evidence base following bariatric surgery is mixed, painting an inhomogeneous picture. On the other hand, significantly lower prevalence of pancreatic adenocarcinoma and hepatocellular carcinomas is to be noted. The latter effect can be explained by the decrease in non-alcoholic fatty liver disease (NAFLD) associated with weight loss. Despite the justified concern that bariatric procedures (especially gastric sleeve resection) lead to increased prevalence of malignancies of the oesophageal junction, the currently available epidemiological data does not seem to identify a relevant increase in the incidence of these malignancies., Competing Interests: Hospitationshaus für Medtronic (geplant und vertraglich vereinbart, aber noch nicht gestartet, daher bisher keinerlei Vergütung), (Thieme. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent chronic liver diseases with a rising incidence in industrial countries. This is accompanied by an increased prevalence for NAFLD-associated liver cirrhosis and an increased risk for developing hepatocellular carcinoma. The current gold standard in the diagnostics is a liver biopsy. The histopathological evaluation is performed through semiquantitative scoring. To optimize the standardization and quantification of the existing scoring systems, in the coming years procedures with artificial intelligence, such as deep learning models could be used. Fields of application could be the supplementation of conventional histopathological diagnostics, the identification of new predictive parameters for estimating the prognosis and the prediction of a possible response to treatment., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Competing Interests: Die Interessenerklärungen aller Expert*innen sind im Leitlinienreport aufgeführt.

Cirrhosis is a common disease with high morbidity and mortality. In industrialised countries, the most common causes of cirrhosis are the alcoholic liver disease, non-alcoholic fatty liver disease and chronic viral hepatitis. Cirrhosis is often diagnosed late, as it can be asymptomatic for a long time. Therefore, hepatopathy screening in high-risk patients and fibrosis surveillance using the ultrasound, in the presence of a chronic hepatopathy are essential. A liver biopsy is necessary to confirm the diagnosis. With optimal therapy, in some cases, cirrhosis is preventable and potentially reversible in others. In the stage of decompensation, typically characterised by ascites, patients often die from recurrent infections or hepatocellular carcinoma unless cured by liver transplantation. The prevention and treatment of complications as well as the evaluation of a transplant require cooperation with a centre hospital. [ABSTRACT FROM AUTHOR]

Introduction: Non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent causes of chronic liver disease. Currently, therapeutic options for NAFLD patients are limited, but new pharmacologic agents are being investigated in the course of clinical trials. Because most of these studies are focusing on patients with fibrosis stages II and III (according to Kleiner), non-invasive identification of patients with intermediate fibrosis stages (II and III) is of increasing interest., Aims: Evaluation of NAFLD Fibrosis Score (NFS) and liver stiffness measurement (LSM) for prediction of fibrosis stages II/III., Methods: Patients with histologically confirmed NAFLD diagnosis were included in the study. All patients underwent a clinical and laboratory examination as well as a LSM prior to liver biopsy. Predictive value of NFS and LSM with respect to identification of fibrosis stages II/III was assessed., Results: 134 NAFLD patients were included and analyzed. Median age was 53 (IQR 36 - 60) years, 55 patients (41 %) were female. 82 % of our patients were overweight/obese with typical aspects of metabolic syndrome. 84 patients (66 %) had liver fibrosis, 42 (50 %) advanced fibrosis. LSM and NFS correlated with fibrosis stage (r = 0.696 and r = 0.685, respectively; p < 0.01 for both). NFS values between -2.0 and + 0.5, and LSM values between 8 and 22kPa were associated with fibrosis stages II/III. If both criteria were met, probability of fibrosis stage II/III was 61 %. If none of the two criteria was met, chance for fibrosis stage II/III was only 6 % (negative predictive value 94 %)., Conclusion: Combination of LSM and NFS enables identification of patients with significant probability of fibrosis stage II/III. Accordingly, these tests, especially in combination, may be a suitable screening tool for fibrosis stages II/III in NAFLD. The use of these non-invasive methods might also help to avoid unnecessary biopsies., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background:  Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in Germany. In the long term, there is an increased risk of developing liver cirrhosis and subsequent diseases. Epidemiologic studies on NAFLD prevalence in Germany are scarce. The aim of the study was to assess administrative incidence and prevalence or, more specifically, the number of patients diagnosed with NAFLD in the period from 2008 to 2018., Methods:  Analyses are based on administrative data of a large statutory health insurance fund. All individuals who were insured in the year of analysis and in the three-year pre-observation period were included (between 1.7-2 million insured per analysis year). NAFLD-patients were identified using relevant ICD-10 codes (K76.0 und K75.8)., Results:  In 2018, 4.66 % of insured persons had a NAFLD diagnosis, 0.87 % were diagnosed first-time. Diagnoses of nonalcoholic steatohepatitis (NASH) were comparatively rare (0.09 %). Data show an uptake of NAFLD diagnoses over time. The number of incident cases per year has hardly changed. Patients with diseases of the metabolic syndrome had an increased chance of being diagnosed with NAFLD., Conclusion:  It becomes evident that NAFLD is frequently diagnosed in everyday medical practice, although data from population-based studies suggest an even higher prevalence., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Competing Interests: Die Autorin erhielt Zuwendungen von folgenden Firmen für Vorträge und/oder Beratung: Abbvie, Bristol Myers Squibb, Falk Foundation, Gilead, Intercept, Merz, Norgine, Pfizer. In Bezug auf diesen Text bestehen aus Sicht der Autorin keine signifikanten Interessenkonflikte.