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  • 1
    Online Resource
    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
    Online Resource
    Online Resource
    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
    Online Resource
    Online Resource
    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
    detail.hit.zdb_id: 2003094-0
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  • 4
    Online Resource
    Online Resource
    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
    detail.hit.zdb_id: 2003094-0
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  • 5
    Online Resource
    Online Resource
    Letter: diabetes mellitus increases the risk of hepatic encephalopathy in patients with cirrhosis—authors’ reply
    Wiley ; 2020
    In:  Alimentary Pharmacology & Therapeutics Vol. 52, No. 7 ( 2020-10), p. 1258-1258
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 52, No. 7 ( 2020-10), p. 1258-1258
    Abstract: LINKED CONTENT This article is linked to Labenz et al and Liu et al papers. To view these articles, visit https://doi.org/10.1111/apt.15915 and https://doi.org/10.1111/apt.16015
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.v52.7
    DOI: 10.1111/apt.16018
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2003094-0
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  • 6
    Online Resource
    Online Resource
    Novel inhibitors in development for hepatocellular carcinoma
    Informa UK Limited ; 2010
    In:  Expert Opinion on Investigational Drugs Vol. 19, No. 5 ( 2010-05), p. 615-629
    Details
    In: Expert Opinion on Investigational Drugs, Informa UK Limited, Vol. 19, No. 5 ( 2010-05), p. 615-629
    Type of Medium: Online Resource
    ISSN: 1354-3784 , 1744-7658
    URL: Article
    DOI: 10.1517/13543781003767418
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2010
    detail.hit.zdb_id: 2030114-5
    SSG: 15,3
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