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  • 1
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    Online Resource
    Predictors of advanced fibrosis in non‐cirrhotic non‐alcoholic fatty liver disease in Germany
    Wiley ; 2018
    In:  Alimentary Pharmacology & Therapeutics Vol. 48, No. 10 ( 2018-11), p. 1109-1116
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 48, No. 10 ( 2018-11), p. 1109-1116
    Abstract: Advanced fibrosis has been established as the most important predictor of overall mortality in patients with non‐alcoholic fatty liver disease ( NAFLD ). In contrast to cirrhosis, advanced, non‐cirrhotic NAFLD is difficult to identify and data from Germany are lacking. Aim To identify clinical factors associated with advanced, non‐cirrhotic fibrosis. Methods Patients were recruited in the prospectively enrolling European NAFLD Registry. Clinical characteristics and the performance of non‐invasive surrogate scores compared with vibration‐controlled transient elastography are reported. Results Two hundred and sixty‐one patients with non‐cirrhotic NAFLD on liver biopsy (mean age 51 years, equal sex distribution) were included. The prevalence of stage 3 fibrosis on liver biopsy was 15.7%. These patients were significantly older (57 vs 50 years, P   〈  0.01), had a higher body mass index (32.3 vs 30.5, P   〈  0.05), and more frequent arterial hypertension (78% vs 50%, P  = 0.001) and type 2 diabetes (61% vs 24.1%, P   〈  0.001). On multivariate logistic regression, diabetes ( OR  = 4.68, 95% CI 2.17‐10.10) and hypertension ( OR  = 2.91, 95% CI 1.12‐7.18) were independent predictors of advanced fibrosis. Comedication included metformin in 50% and insulin in 33% of patients with diabetes. Despite the presence of cardiovascular risk factors, the use of statins was low. Liver stiffness measurement identified advanced fibrosis with an AUROC of 0.81 (95% CI 0.72‐0.91). The performance of NAFLD fibrosis score, Fibrosis‐4, and AST to platelet ratio index were lower with AUCs of 0.74, 0.71, and 0.67, respectively. Conclusions The prevalence of metabolic comorbidities in a German population with non‐cirrhotic biopsy‐proven NAFLD is high. While the examined scores exhibit an acceptable specificity, liver stiffness measurement appeared to be superior to blood‐based non‐invasive surrogate scores in ruling out advanced fibrosis.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.2018.48.issue-10
    DOI: 10.1111/apt.14976
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2003094-0
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  • 2
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    Raised serum Interleukin‐6 identifies patients with liver cirrhosis at high risk for overt hepatic encephalopathy
    Wiley ; 2019
    In:  Alimentary Pharmacology & Therapeutics Vol. 50, No. 10 ( 2019-11), p. 1112-1119
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 50, No. 10 ( 2019-11), p. 1112-1119
    Abstract: Systemic inflammation is a driving force for the development of hepatic encephalopathy and recent studies demonstrated that elevated Interleukin‐6 (IL‐6) serum levels are associated with the presence of minimal hepatic encephalopathy in patients with liver cirrhosis. Aim To test the hypothesis that IL‐6 is a suitable marker to identify patients with liver cirrhosis at high risk for the development of overt hepatic encephalopathy. Methods 201 patients were included into this prospective cohort study and were followed for a mean time of 322 days. Covert hepatic encephalopathy was diagnosed according to the West‐Haven criteria (hepatic encephalopathy grade 1) and with the portosystemic encephalopathy (PSE) test. Results The cumulative incidence of overt hepatic encephalopathy was higher in patients with IL‐6 levels above the median of 9 pg/mL than in patients with IL‐6 levels at or below the median (35.6% vs 1.9%, P   〈  .001). After adjustment for covert hepatic encephalopathy, history of overt hepatic encephalopathy, C‐reactive protein (CRP) and model for end‐stage liver disease (MELD), IL‐6 levels above the median remained independently associated with the development of overt hepatic encephalopathy. The predictive performance of IL‐6 regarding the development of overt hepatic encephalopathy during the next 180 days (AUROC, 0.931) was numerically higher than that of MELD (AUROC, 0.841) or CRP (AUROC, 0.835). In patients without prior overt hepatic encephalopathy, the predictive performance of IL‐6 (AUROC, 0.966) was even significantly higher than that of MELD (AUROC 0.843) or CRP (AUROC 0.850). The ideal cut‐off for IL‐6 in this setting was 23.5 pg/mL with a sensitivity and specificity of 89.3% and 89.5% respectively. Conclusion IL‐6 serum levels are closely linked to the development of overt hepatic encephalopathy in patients with liver cirrhosis.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.v50.10
    DOI: 10.1111/apt.15515
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2003094-0
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  • 3
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    Sonographic assessment of low muscle quantity identifies mortality risk during COVID‐19: a prospective single‐centre study
    Wiley ; 2022
    In:  Journal of Cachexia, Sarcopenia and Muscle Vol. 13, No. 1 ( 2022-02), p. 169-179
    Details
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley, Vol. 13, No. 1 ( 2022-02), p. 169-179
    Abstract: Assessment of muscle quantity by sonographic muscle indices could help identify patients at risk for fatal outcome during coronavirus disease‐2019 (COVID‐19). The aim of this study was to explore sonographic muscle indices as predictors of COVID‐19 outcome and to test the feasibility of sonographic muscle measurement in an isolation context. Methods Muscle indices, derived from the psoas muscle or thigh muscles, were quantified by sonography in a cohort of patients without COVID‐19 to obtain reference values for low muscle quantity. Gender‐specific median of different muscle indices were defined as threshold value for low muscle quantity. The prognostic relevance of low muscle quantity, was prospectively explored in two cohorts of hospitalized COVID‐19 patients. Optimal muscle index cutoff values predictive for 30 day mortality during COVID‐19 were determined by receiver operating characteristic‐area under the curve and Youden index calculation. Muscle quantity and known prognostic factors of COVID‐19 were analysed by multivariable log‐regression. Results Compared with other muscle indices, the psoas muscle area index (PMAI) showed the most favourable characteristics to predict outcome of COVID‐19 disease. Sonographic morphometry of patients without COVID‐19 ( n  = 136) revealed a gender‐specific median for PMAI (male: 291.1 mm 2 /m 2 , female 260.6 mm 2 /m 2 ) as threshold value of low muscle quantity. Subsequently, COVID‐19 patients (Cohort I: n  = 58; Cohort II: n  = 55) were prospectively assessed by bedside sonography. The studied COVID‐19 patients developed a critical course of disease in 22.4% (Cohort I: n  = 13/58) and 34.5% (Cohort II: n  = 20/55). Mortality rate reached 12.1% (Cohort I: n  = 7/58) and 20.0% (Cohort I: n  = 11/55) within 30 days of follow up. COVID‐19 patients with a PMAI below the gender‐specific median showed a higher 30 day mortality in both COVID‐19 cohorts (log rank, P   〈  0.05). The optimal PMAI cutoff value (206 mm 2 /m 2 ) predicted 30 day mortality of hospitalized COVID‐19 patients with a sensitivity of 72% and specificity of 78.5% (receiver operating characteristic‐area under the curve: 0.793, 95% confidence interval 0.671–0.914, P  = 0.008). Multivariable log‐regression analysis of PMAI, age, gender, BMI and comorbidities confirmed an independent association of low PMAI with 30 day mortality of COVID‐19 patients ( P  = 0.018). Conclusions Sonographic morphometry provides reliable muscle quantification under hygienic precautions and allows risk stratification of patients with COVID‐19.
    Type of Medium: Online Resource
    ISSN: 2190-5991 , 2190-6009
    URL: Issue
    URL: Article
    DOI: 10.1002/jcsm.v13.1
    DOI: 10.1002/jcsm.12862
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2586864-0
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  • 4
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    Overexpression of Bcl‐3 inhibits the development of marginal zone B cells
    Wiley ; 2014
    In:  European Journal of Immunology Vol. 44, No. 2 ( 2014-02), p. 545-552
    Details
    In: European Journal of Immunology, Wiley, Vol. 44, No. 2 ( 2014-02), p. 545-552
    Abstract: The transcription factor Bcl‐3 functions as a proto‐oncogene via regulation of cell proliferation and apoptosis. Bcl‐3 is an atypical member of the IκB family and plays a central role in the immune response through interactions with the NF‐κB subunits p50 and p52. To investigate the impact of Bcl‐3 on B‐cell maturation and regulation, we generated mice that overexpress Bcl‐3 specifically in B cells. Interestingly, these mice lack marginal zone B cells and exhibit a significant reduction in the number of B‐1 B cells. Further, B cells from these mice are impaired in their proliferative capacity. Our data demonstrate that the overexpression of the transcription factor Bcl‐3 inhibits germinal center formation, marginal zone B‐cell development, and affects the B‐1 B‐cell compartment.
    Type of Medium: Online Resource
    ISSN: 0014-2980 , 1521-4141
    URL: Issue
    URL: Article
    DOI: 10.1002/eji.v44.2
    DOI: 10.1002/eji.201343655
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 1491907-2
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  • 5
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    Association between diabetes mellitus and hepatic encephalopathy in patients with cirrhosis
    Wiley ; 2020
    In:  Alimentary Pharmacology & Therapeutics Vol. 52, No. 3 ( 2020-08), p. 527-536
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 52, No. 3 ( 2020-08), p. 527-536
    Abstract: Diabetes mellitus may lead to increased serum ammonia and systemic inflammation thereby promoting hepatic encephalopathy (HE). Aim To investigate the potential association between diabetes mellitus/glycaemic control and the presence of covert HE as well as the development of overt HE in a prospective setting. Methods A total of 240 patients with liver cirrhosis were included into this prospective cohort study and followed for a median of 17 months. Covert HE was diagnosed by pathological results in the Portosystemic Hepatic Encephalopathy Score. Predictors for the presence of covert HE or the development of overt HE were analysed using logistic regression or Cox‐regression models. Results At study inclusion, 65 patients (27.1%) presented with diabetes mellitus and covert HE was detected in 33.3%. Patients with diabetes mellitus had a more preserved liver function as compared to patients without diabetes mellitus (MELD 9 vs 10; P  = 0.043). In regression analyses after adjustment for confounders, diabetes mellitus was independently associated with the presence of covert HE at study inclusion and the development of overt HE during follow‐up. These associations were confirmed in separate propensity‐score‐weighted regression models. In subgroup analyses, patients with worse glycaemic control (HbA1c 〉 = 6.5%) had a pronounced risk for covert HE (OR 2.264, 95% CI 1.002‐5.118) and overt HE (HR 4.116, 95% CI 1.791‐9.459). Conclusions Diabetes mellitus may associate with higher risk for the presence of covert HE and the development of overt HE in patients with liver cirrhosis. Adequate glycaemic control may be a potential target to attenuate this important complication.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.v52.3
    DOI: 10.1111/apt.15915
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 6
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    Guidelines are silver, but a multidisciplinary team discussion may be golden?
    Wiley ; 2018
    In:  Liver International Vol. 38, No. 9 ( 2018-09), p. 1550-1551
    Details
    In: Liver International, Wiley, Vol. 38, No. 9 ( 2018-09), p. 1550-1551
    Abstract: See Article on Page 1624
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    URL: Article
    DOI: 10.1111/liv.2018.38.issue-9
    DOI: 10.1111/liv.13936
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2124684-1
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  • 7
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    Survival analysis of proposed BCLC ‐B subgroups in hepatocellular carcinoma patients
    Wiley ; 2015
    In:  Liver International Vol. 35, No. 2 ( 2015-02), p. 591-600
    Details
    In: Liver International, Wiley, Vol. 35, No. 2 ( 2015-02), p. 591-600
    Abstract: The BCLC ‐staging system is used to facilitate treatment decisions in patients with hepatocellular carcinoma ( HCC ). Owing to the observed clinical heterogeneity of the intermediate stage BCLC ‐B, a subclassification was proposed taking Child–Pugh score and extended criteria for transplantation into account. Analysis of the prognostic significance of a proposed subclassification of the BCLC ‐B score in a European cohort of HCC patients. Methods Eight hundred and eighty four consecutive HCC patients were retrospectively analysed. Patients with stage BCLC ‐B were grouped according to the proposed subclassification. Baseline patient and tumour characteristics, therapy and overall survival were analysed. Results Two hundred and fifty four patients with stage BCLC ‐B were classified as B1/B2/B3 and B4 in 16.1/56.7/7.9 and 19.3%. OS compared between adjacent subgroups (B1 vs. B2, B2 vs. B3, B3 vs. B4) did not reach statistical significance. Groupwise comparison showed significant differences between B1 vs. B3 ( P  = 0.035), B1 vs. B4 ( P  = 0.006) and B2 vs. B4 ( P   〈  0.0001). OS was significantly improved in patients undergoing OLT ( P   〈  0.0001). Cox regression showed no significant influence of the BCLC ‐B substage on survival. Conclusions No significant survival differences between subgroups were found in the retrospective analysis. We could not confirm the BCLC ‐B subclassification to be prognostically meaningful in our cohort. As liver function and therapy influenced survival in this study, a more refined BCLC ‐B subclassification has the potential to be a useful tool to better stratify treatment decisions. Further studies in larger collectives with homogenous staging and treatment strategies are warranted to confirm the prognostic significance of the proposed subclassifications.
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    URL: Article
    DOI: 10.1111/liv.2015.35.issue-2
    DOI: 10.1111/liv.12696
    Language: English
    Publisher: Wiley
    Publication Date: 2015
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  • 8
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    Application of patient‐derived liver cancer cells for phenotypic characterization and therapeutic target identification
    Wiley ; 2019
    In:  International Journal of Cancer Vol. 144, No. 11 ( 2019-06), p. 2782-2794
    Details
    In: International Journal of Cancer, Wiley, Vol. 144, No. 11 ( 2019-06), p. 2782-2794
    Abstract: What's new? More and more people are affected by primary liver cancer but therapeutic progress is hampered by the phenotypic and molecular diversity within the tumor. To tackle this issue, the authors established multiple patient‐specific cell lines from freshly resected liver tumors and showed that they retained key oncogenic mutations, copy number alterations and gene expression signatures from the primary tumor. These cell lines facilitate direct exploration of therapeutic targets and may expedite drug discovery and individualized approaches to liver cancer treatment.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    URL: Article
    DOI: 10.1002/ijc.v144.11
    DOI: 10.1002/ijc.32026
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 218257-9
    detail.hit.zdb_id: 1474822-8
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  • 9
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    Proton pump inhibitors increase risk of bone fractures in men with cirrhosis: a population‐based study
    Wiley ; 2020
    In:  Alimentary Pharmacology & Therapeutics Vol. 52, No. 6 ( 2020-09), p. 1042-1050
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 52, No. 6 ( 2020-09), p. 1042-1050
    Abstract: Bone fractures are a frequent complication in patients with cirrhosis. Proton pump inhibitors (PPIs) are among the most frequently prescribed medications and may impair bone quality and quantity. Aims To investigate whether PPI use predisposes patients with cirrhosis to bone fractures. Methods We performed a population‐based case‐control study exploring a sample of patients with cirrhosis derived from the Disease Analyzer database. In total, 1795 cirrhotic patients with fractures were compared to 10 235 cirrhotic patients without fractures. PPI use overall and the cumulative PPI dose 5 years prior to the index date were analysed. To estimate the association between PPI use and fractures, logistic regression analyses were performed taking cofounding factors into consideration. Results PPI use was more frequently seen in cirrhotic patients with fractures compared to controls (67.0% vs 53.4%, P   〈  0.001). In regression analyses, PPI use was associated with bone fractures after adjusting for important confounders (OR 1.34, 95% CI 1.20‐1.51, P   〈  0.001). Importantly, the strongest effect of PPIs on bone fractures was seen in men and patients below 70 years of age. On further sensitivity analyses, we observed a dose‐dependent effect for all PPIs with the strongest effect in cirrhotic patients receiving a dose of 〉 50 000 mg during the 5 years prior to index date (OR 1.63, 95% CI 1.32‐2.03). Conclusions PPI use was associated with bone fractures in a dose‐dependent fashion in patients with cirrhosis. PPI use in these patients should be based on a careful risk‐benefit assessment.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.v52.6
    DOI: 10.1111/apt.16008
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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