TY - JOUR A1 - Rau, Monika A1 - Buggisch, Peter A1 - Mauss, Stefan A1 - Boeker, Klaus H. W. A1 - Klinker, Hartwig A1 - Müller, Tobias A1 - Stoehr, Albrecht A1 - Schattenberg, Jörn M. A1 - Geier, Andreas T1 - Prognostic impact of steatosis in the clinical course of chronic HCV infection-Results from the German Hepatitis C-Registry JF - PLoS ONE N2 - Background Liver steatosis is often observed in chronic HCV infection and associated to genotype or comorbidities. NAFLD is an important risk factor for end-stage liver disease. We aimed to analyse the course of NAFLD as a concomitant disease in a cohort of HCV patients. Methods The German Hepatitis C-Registry is a national multicenter real-world cohort. In the current analysis, 8789 HCV patients were included and separated based on the presence of steatosis on ultrasound and/or histology. Fibrosis progression was assessed by transient elastography (TE), ultrasound or non-invasive surrogate scores. Results At the time of study inclusion 12.3% (n = 962) of HCV patients presented with steatosis (+S) (higher rate in GT-3). Diabetes mellitus was more frequent in GT-1 patients. HCV patients without steatosis (-S) had a slightly higher rate of fibrosis progression (FP) over time (30.3%) in contrast to HCV patients +S (26%). This effect was mainly observed in GT-3 patients (34.4% vs. 20.6%). A larger decrease of ALT, AST and GGT from baseline to FU-1 (4–24 weeks after EOT) was found in HCV patients (without FP) +S compared to -S. HCV patients -S and with FP presented more often metabolic comorbidities with a significantly higher BMI (+0.58kg/m\(^{2}\)) compared to patients -S without FP. This was particularly pronounced in patients with abnormal ALT. Conclusion Clinically diagnosed steatosis in HCV patients does not seem to contribute to significant FP in this unique cohort. The low prevalence of steatosis could reflect a lower awareness of fatty liver in HCV patients, as patients -S and with FP presented more metabolic risk factors. KW - steatosis KW - HCV infection KW - liver Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300549 VL - 17 IS - 6 ER - TY - JOUR A1 - Strunz, Patrick-Pascal A1 - Vuille-Dit-Bille, Raphael N. A1 - Fox, Mark R. A1 - Geier, Andreas A1 - Maggiorini, Marco A1 - Gassmann, Max A1 - Fruehauf, Heiko A1 - Lutz, Thomas A. A1 - Goetze, Oliver T1 - Effect of high altitude on human postprandial \(^{13}\)C-octanoate metabolism, intermediary metabolites, gastrointestinal peptides, and visceral perception JF - Neurogastroenterology and Motility N2 - Objective At high altitude (HA), acute mountain sickness (AMS) is accompanied by neurologic and upper gastrointestinal symptoms (UGS). The primary aim of this study was to test the hypothesis that delayed gastric emptying (GE), assessed by \(^{13}\)C-octanoate breath testing (OBT), causes UGS in AMS. The secondary aim was to assess post-gastric mechanisms of OBT, which could confound results under these conditions, by determination of intermediary metabolites, gastrointestinal peptides, and basal metabolic rate. Methods A prospective trial was performed in 25 healthy participants (15 male) at 4559 m (HA) and at 490 m (Zurich). GE was assessed by OBT (428 kcal solid meal) and UGS by visual analogue scales (VAS). Blood sampling of metabolites (glucose, free fatty acids (FFA), triglycerides (TG), beta-hydroxyl butyrate (BHB), L-lactate) and gastrointestinal peptides (insulin, amylin, PYY, etc.) was performed as well as blood gas analysis and spirometry. Statistical analysis: variance analyses, bivariate correlation, and multilinear regression analysis. Results After 24 h under hypoxic conditions at HA, participants developed AMS (p < 0.001). \(^{13}\)CO\(_{2}\) exhalation kinetics increased (p < 0.05) resulting in reduced estimates of gastric half-emptying times (p < 0.01). However, median resting respiratory quotients and plasma profiles of TG indicated that augmented beta-oxidation was the main predictor of accelerated \(^{13}\)CO\(_{2}\)-generation under these conditions. Conclusion Quantification of \(^{13}\)C-octanoate oxidation by a breath test is sensitive to variation in metabolic (liver) function under hypoxic conditions. \(^{13}\)C-breath testing using short-chain fatty acids is not reliable for measurement of gastric function at HA and should be considered critically in other severe hypoxic conditions, like sepsis or chronic lung disease. KW - acute hypobaric hypoxia KW - beta-oxidation KW - gastric emptying KW - stable isotope breath tests Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259611 VL - 34 IS - 3 ER - TY - JOUR A1 - Leyh, Catherine A1 - Ehmer, Ursula A1 - Roessler, Daniel A1 - Philipp, Alexander B. A1 - Reiter, Florian P. A1 - Jeliazkova, Petia A1 - Jochheim, Leonie S. A1 - Jeschke, Matthias A1 - Hammig, Janina A1 - Ludwig, Johannes M. A1 - Theysohn, Jens M. A1 - Geier, Andreas A1 - Lange, Christian M. T1 - Sorafenib versus lenvatinib-based sequential systemic therapy for advanced hepatocellular carcinoma: a real-world analysis JF - Cancers N2 - The optimal treatment sequence of tyrosine kinase inhibitor (TKI)-based therapy in patients with hepatocellular carcinoma (HCC) remains unclear. Therefore, sequential systemic therapy after first-line therapy with sorafenib or lenvatinib was compared in a retrospective real-world cohort. In total, 164 patients with HCC were included. Child B cirrhosis was present in 26 patients (16.5%), whereas 132 patients (83.5%) had preserved liver function. In total, 72 patients (44%) discontinued systemic therapy after first-line therapy while 51 (31%) and 31 (19%) patients received 2 or more treatment lines. Most notably, median overall survival (mOS) was influenced by liver functional status and patient performance status at the beginning of first-line therapy. Patients receiving a sequential therapy regimen had significantly longer mOS compared to patients that discontinued systemic therapy after omitting first-line treatment. The choice of the initial TKI did not impact mOS. A clear deterioration of liver function could be observed during the course of TKI-based treatment. KW - hepatocellular carcinoma KW - systemic therapy KW - tyrosine-kinase inhibitor Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270765 SN - 2072-6694 VL - 14 IS - 8 ER - TY - JOUR A1 - John, Katharina A1 - Franck, Martin A1 - Al Aoua, Sherin A1 - Rau, Monika A1 - Huber, Yvonne A1 - Schattenberg, Joern M. A1 - Geier, Andreas A1 - Bahr, Matthias J. A1 - Wedemeyer, Heiner A1 - Schulze-Osthoff, Klaus A1 - Bantel, Heike T1 - Non-invasive detection of fibrotic NASH in NAFLD patients with low or intermediate FIB-4 JF - Journal of Clinical Medicine N2 - Background: Non-alcoholic steatohepatitis (NASH) and fibrosis are the main prognostic factors in non-alcoholic fatty liver disease (NAFLD). The FIB-4 score has been suggested as an initial test for the exclusion of progressed fibrosis. However, increasing evidence suggests that also NASH patients with earlier fibrosis stages are at risk of disease progression, emphasizing the need for improved non-invasive risk stratification. Methods: We evaluated whether the apoptosis biomarker M30 can identify patients with fibrotic NASH despite low or intermediate FIB-4 values. Serum M30 levels were assessed by ELISA, and FIB-4 was calculated in an exploration (n = 103) and validation (n = 100) cohort of patients with histologically confirmed NAFLD. Results: The majority of patients with low FIB-4 (cut-off value < 1.3) in the exploration cohort revealed increased M30 levels (>200 U/L) and more than 80% of them had NASH, mostly with fibrosis. NASH was also detected in all patients with intermediate FIB-4 (1.3 to 2.67) and elevated M30, from which ~80% showed fibrosis. Importantly, in the absence of elevated M30, most patients with FIB-4 < 1.3 and NASH showed also no fibrosis. Similar results were obtained in the validation cohort. Conclusions: The combination of FIB-4 with M30 enables a more reliable identification of patients at risk for progressed NAFLD and might, therefore, improve patient stratification. KW - apoptosis KW - biomarker KW - fibrosis KW - FIB-4 KW - NAFLD KW - NASH KW - keratin-18 KW - M30 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281824 SN - 2077-0383 VL - 11 IS - 15 ER - TY - JOUR A1 - Metzner, Valentin A1 - Herzog, Gloria A1 - Heckel, Tobias A1 - Bischler, Thorsten A1 - Hasinger, Julia A1 - Otto, Christoph A1 - Fassnacht, Martin A1 - Geier, Andreas A1 - Seyfried, Florian A1 - Dischinger, Ulrich T1 - Liraglutide + PYY\(_{3-36}\) combination therapy mimics effects of Roux-en-Y bypass on early NAFLD whilst lacking-behind in metabolic improvements JF - Journal of Clinical Medicine N2 - Background: Treatment options for NAFLD are still limited. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), has been shown to improve metabolic and histologic markers of NAFLD. Glucagon-like-peptide-1 (GLP-1) analogues lead to improvements in phase 2 clinical trials. We directly compared the effects of RYGB with a treatment using liraglutide and/or peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) in a rat model for early NAFLD. Methods: Obese male Wistar rats (high-fat diet (HFD)-induced) were randomized into the following treatment groups: RYGB, sham-operation (sham), liraglutide (0.4 mg/kg/day), PYY\(_{3-36}\) (0.1 mg/kg/day), liraglutide+PYY\(_{3-36}\), and saline. After an observation period of 4 weeks, liver samples were histologically evaluated, ELISAs and RNA sequencing + RT-qPCRs were performed. Results: RYGB and liraglutide+PYY\(_{3-36}\) induced a similar body weight loss and, compared to sham/saline, marked histological improvements with significantly less steatosis. However, only RYGB induced significant metabolic improvements (e.g., adiponectin/leptin ratio 18.8 ± 11.8 vs. 2.4 ± 1.2 in liraglutide+PYY\(_{3-36}\)- or 1.4 ± 0.9 in sham-treated rats). Furthermore, RNA sequencing revealed a high number of differentially regulated genes in RYGB treated animals only. Conclusions: The combination therapy of liraglutide+PYY\(_{3-36}\) partly mimics the positive effects of RYGB on weight reduction and on hepatic steatosis, while its effects on metabolic function lack behind RYGB. KW - liraglutide KW - GLP-1 KW - peptide tyrosine tyrosine (PYY) KW - peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) KW - RYGB KW - gastric bypass KW - obesity KW - NASH KW - NAFLD Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-255244 SN - 2077-0383 VL - 11 IS - 3 ER -