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Akute gastrointestinale Notfälle zählen zu den häufigsten Vorstellungsgründen in der Notaufnahme. Liegt als Hauptsymptom ein akuter Abdominalschmerz vor, wird dies klinisch als „akutes Abdomen“ bezeichnet, dem viele mögliche Ursachen (z. B. gastroduodenale Ulkuskrankheit, akute Pankreatitis, Divertikulitis) zugrunde liegen können. Hepatologische Notfälle umfassen das akute Leberversagen und das akut-auf-chronische Leberversagen. Aufgrund der Vielzahl möglicher Differenzialdiagnosen mit variabler klinischer Begleitsymptomatik stellt eine rasche Diagnosestellung der zugrunde liegenden Ätiologie gastrointestinaler sowie hepatologischer Notfälle im klinischen Alltag oftmals eine große Herausforderung dar und erfordert ein strukturiertes Vorgehen sowie die umgehende Einleitung adäquater Therapiemaßnahmen, um das Mortalitätsrisiko der Betroffenen zu reduzieren.

•A pathophysiologic rationale supports chemokine receptor (CCR) inhibition in COVID-19•This randomised controlled human trial assessed CCR inhibitor CVC in COVID-19•Data document efficient CCR2/CCR5 inhibition through CCL2/4 elevation in CVC treated patients.•CVC was safe and well tolerated by COVID-19 patients.

Die Forschung der letzten zwei Jahrzehnte hat die wichtige Rolle der Darmmikrobiota für Gesundheit und Krankheit, einschließlich chronischer Lebererkrankungen, deutlich gemacht. Darm und Leber kommunizieren über die Pfortader, das biliäre System und Mediatoren im Blutkreislauf („Darm-Leber-Achse“). Die Mikroben im Darm sind an der Aufrechterhaltung der Homöostase in der Leber beteiligt. Andererseits können Veränderungen in der normalen Zusammensetzung oder Vielfalt des Darmmikrobioms – die sogenannte Dysbiose – auch als Quelle für Krankheitserreger und Moleküle dienen, die zum Auftreten oder Fortschreiten chronischer Lebererkrankungen wie der nichtalkoholischen Fettlebererkrankung beitragen. Durch eine erhöhte Produktion von bakteriellem Ethanol, einen veränderten Gallensäurestoffwechsel, eine veränderte Produktion kurzkettiger Fettsäuren, eine gesteigerte Anzahl von endotoxinhaltigen gramnegativen Bakterien sowie eine erhöhte intestinale Permeabilität beeinflusst eine Dysbiose Stoffwechsel- und Entzündungsprozesse. Die klinische Bedeutung spezifischer Veränderungen des Darmmikrobioms im Zusammenhang mit chronischen Lebererkrankungen ist noch unklar. In dieser Übersichtsarbeit wird erörtert, wie die Darmmikrobiota und ihre Produkte zur Pathogenese von Lebererkrankungen beitragen und wie eine gezielte Manipulation der Darmmikrobiota für therapeutische Ansätze genutzt werden könnte.

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Norursodeoxycholic acid is an orally administered side chain-shortened homologue of ursodeoxycholic acid that undergoes hepatic enrichment with hepatoprotective, anti-inflammatory, and antifibrotic activity. We assessed the efficacy of two doses of norursodeoxycholic acid versus placebo for the treatment of non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the western world. The excess mortality in NAFLD patients is strongly related to extrahepatic comorbidities. Recently, an association between NAFLD and chronic kidney disease (CKD) has been reported in various populations. Methods: Based on the IQVIA Disease Analyzer database, this retrospective study examined two cohorts from Germany matched for sex, age, index year, annual visit frequency, hypertension, and diabetes, including 92,225 patients with and without NAFLD. The incidence of CKD was assessed as a function of NAFLD using Cox regression models. Results: A total of 92,225 NAFLD patients as well as 92,225 patients without NAFLD were included into analyses. CKD was diagnosed in 19.1% vs. 11.1% of patients with and without NAFLD within the 10 years observation period (p< 0.001). Cox regression confirmed a significant association between NAFLD and CKD with a hazard ratio (HR) of 1.80 (95%CI: 1.73–1.86, p< 0.001). Subgroup analyses revealed that this association was most pronounced in the age group of 18 to 50 years (HR: 2.13, 95%CI: 1.91–2.37, p< 0.001) and among female NAFLD patients (HR 1.85, 95%CI: 1.76–1.95, p< 0.001). Conclusions: The results of this study confirm a significantly increased risk of developing CKD in a large, real-world cohort of adult NAFLD patients in Germany. Interdisciplinary care of NAFLD patients, which is currently gaining importance worldwide, should be considered to include systematic measures for prevention and/or early detection of CKD with the aim of minimizing long-term renal complications.

Non-alcoholic fatty liver disease (NAFLD) is frequent among obese individuals with metabolic syndrome. Variants PNPLA3p.I148M, TM6SF2p.E167K and MBOAT7rs641738 are associated with higher liver fat contents. Here we analyzed 63 biopsied non-obese, non-diabetic patients with NAFLD (39 men, age: 20–72 years) recruited within the German NAFLD CSG program. The frequencies of the PNPLA3, TM6SF2and MBOAT7polymorphisms were compared with the remaining patients in the NAFLD CSG cohort and with a control population (n= 174). Serum CK18-M30 was measured by ELISA. In non-obese NAFLD patients, the frequency of the PNPLA3p.I148M allele (74.6%), but not of the TM6SF2or MBOAT7polymorphisms, was significantly (P< 0.05) higher as compared to the other patients in the NAFLD CSG cohort (54.9%) or controls (40.2%). The presence of the minor PNPLA3p.I148M risk allele increased the risk of developing NAFLD (OR = 3.29, P< 0.001) and was associated with higher steatosis, fibrosis, and serum CK18-M30 levels (all P< 0.05). According to the population attributable fraction (PAF), 49.8% of NAFLD cases could be eliminated if the PNPLA3mutation was absent. The MBOAT7polymorphism was more frequent (P= 0.019) in patients with severe hepatic steatosis. In conclusion, PNPLA3, and to a lesser extent, MBOAT7variants are associated with NAFLD risk and modulate liver injury in non-obese patients without diabetes.

The PNPLA3p.I148M, TM6SF2p.E167K, and MBOAT7rs641738 variants represent genetic risk factors for nonalcoholic fatty liver disease (NAFLD). Here we investigate if these polymorphisms modulate both steatosis and fibrosis in patients with NAFLD. We recruited 515 patients with NAFLD (age 16–88 years, 280 female patients). Liver biopsies were performed in 320 patients. PCR-based assays were used to genotype the PNPLA3, TM6SF2, and MBOAT7variants. Carriers of the PNPLA3and TM6SF2risk alleles showed increased serum aspartate aminotransferase and alanine transaminase activities (P< 0.05). The PNPLA3genotype was associated with steatosis grades S2–S3 (P< 0.001) and fibrosis stages F2–F4 (P< 0.001). The TM6SF2genotype was associated with steatosis (P= 0.003) but not with fibrosis (P> 0.05). The MBOAT7variant was solely associated with increased fibrosis (P= 0.046). In the multivariate model, variants PNPLA3(P= 0.004) and TM6SF2(P= 0.038) were associated with steatosis. Fibrosis stages were affected by the PNPLA3(P= 0.042) and MBOAT7(P= 0.021) but not by the TM6SF2polymorphism (P> 0.05). The PNPLA3, TM6SF2, and MBOAT7variants are associated with increased liver injury. The TM6SF2variant seems to modulate predominantly hepatic fat accumulation, whereas the MBOAT7polymorphism is linked to fibrosis. The PNPLA3polymorphism confers risk of both increased steatosis and fibrosis.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging from simple fatty liver to steatohepatitis, fibrosis, and cirrhosis. We aimed to analyze the diagnostic performance and clinical utility of simple noninvasive tests alone or in combination for the detection of advanced fibrosis in patients with NAFLD.

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For almost a decade, systemic therapy of advanced hepatocellular carcinoma (HCC) was limited to the tyrosine kinase inhibitor (TKI) sorafenib. Different agents including checkpoint inhibitors, TKIs and anti-VEGFR antibodies demonstrated efficacy in treatment. For the first time, the combination of atezolizumab and bevacizumab, a first-line treatment that is superior to the current standard was identified, potentially changing the way we treat HCC. In this review, we summarize current data on systemic treatment of patients with advanced HCC, focusing on combination therapies comprising immune checkpoint inhibitors, TKIs and locoregional therapies. We elucidate findings from recent trials and discuss such challenges as the lack of predictive biomarkers for identification of subgroups that will benefit from novel treatment strategies.

For almost a decade, systemic therapy of advanced hepatocellular carcinoma (HCC) was limited to the tyrosine kinase inhibitor (TKI) sorafenib. Different agents including checkpoint inhibitors, TKIs and anti-VEGFR antibodies demonstrated efficacy in treatment. For the first time, the combination of atezolizumab and bevacizumab, a first-line treatment that is superior to the current standard was identified, potentially changing the way we treat HCC. In this review, we summarize current data on systemic treatment of patients with advanced HCC, focusing on combination therapies comprising immune checkpoint inhibitors, TKIs and locoregional therapies. We elucidate findings from recent trials and discuss such challenges as the lack of predictive biomarkers for identification of subgroups that will benefit from novel treatment strategies.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Most patients present with advanced or metastatic HCC at diagnosis and face a dismal prognosis. Tyrosine kinases are the gold standard treatment for this disease but yield limited survival benefits. Immune checkpoint inhibitors that augment adaptive immunity have been tested in HCC. Complex interactions between tumor cells, lymphocytes and the tumor environment determine the efficacy of such immunotherapies. Innate immune mechanisms – known drivers of liver disease progression in pre-HCC conditions such as fibrosis or cirrhosis – may either support or counteract tumor-related immune activation. In this review, we will highlight current concepts of the role of the innate immune system in hepatocarcinogenesis and discuss their relevance for translation into clinics.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Most patients present with advanced or metastatic HCC at diagnosis and face a dismal prognosis. Tyrosine kinases are the gold standard treatment for this disease but yield limited survival benefits. Immune checkpoint inhibitors that augment adaptive immunity have been tested in HCC. Complex interactions between tumor cells, lymphocytes and the tumor environment determine the efficacy of such immunotherapies. Innate immune mechanisms – known drivers of liver disease progression in pre-HCC conditions such as fibrosis or cirrhosis – may either support or counteract tumor-related immune activation. In this review, we will highlight current concepts of the role of the innate immune system in hepatocarcinogenesis and discuss their relevance for translation into clinics.

Supplemental Digital Content is available in the text