@article{RauBuggischMaussetal.2022,
  author    = {Rau, Monika and Buggisch, Peter and Mauss, Stefan and Boeker, Klaus H. W. and Klinker, Hartwig and M{\"u}ller, Tobias and Stoehr, Albrecht and Schattenberg, J{\"o}rn M. and Geier, Andreas},
  title     = {Prognostic impact of steatosis in the clinical course of chronic HCV infection-Results from the German Hepatitis C-Registry},
  series = {PLoS ONE},
  volume    = {17},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0264741},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300549},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{StrunzVuilleDitBilleFoxetal.2022,
  author    = {Strunz, Patrick-Pascal and Vuille-Dit-Bille, Raphael N. and Fox, Mark R. and Geier, Andreas and Maggiorini, Marco and Gassmann, Max and Fruehauf, Heiko and Lutz, Thomas A. and Goetze, Oliver},
  title     = {Effect of high altitude on human postprandial \(^{13}\)C-octanoate metabolism, intermediary metabolites, gastrointestinal peptides, and visceral perception},
  series = {Neurogastroenterology and Motility},
  volume    = {34},
  journal   = {Neurogastroenterology and Motility},
  number    = {3},
  doi       = {10.1111/nmo.14225},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259611},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{MetznerHerzogHeckeletal.2022,
  author    = {Metzner, Valentin and Herzog, Gloria and Heckel, Tobias and Bischler, Thorsten and Hasinger, Julia and Otto, Christoph and Fassnacht, Martin and Geier, Andreas and Seyfried, Florian and Dischinger, Ulrich},
  title     = {Liraglutide + PYY\(_{3-36}\) combination therapy mimics effects of Roux-en-Y bypass on early NAFLD whilst lacking-behind in metabolic improvements},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {3},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11030753},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255244},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{JohnFranckAlAouaetal.2022,
  author    = {John, Katharina and Franck, Martin and Al Aoua, Sherin and Rau, Monika and Huber, Yvonne and Schattenberg, Joern M. and Geier, Andreas and Bahr, Matthias J. and Wedemeyer, Heiner and Schulze-Osthoff, Klaus and Bantel, Heike},
  title     = {Non-invasive detection of fibrotic NASH in NAFLD patients with low or intermediate FIB-4},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {15},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11154394},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281824},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{LeyhEhmerRoessleretal.2022,
  author    = {Leyh, Catherine and Ehmer, Ursula and Roessler, Daniel and Philipp, Alexander B. and Reiter, Florian P. and Jeliazkova, Petia and Jochheim, Leonie S. and Jeschke, Matthias and Hammig, Janina and Ludwig, Johannes M. and Theysohn, Jens M. and Geier, Andreas and Lange, Christian M.},
  title     = {Sorafenib versus lenvatinib-based sequential systemic therapy for advanced hepatocellular carcinoma: a real-world analysis},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {8},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14081975},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270765},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}