Inflammatory Bowel Disease as a Precondition for Stroke or TIA: A Matter of Crohn's Disease Rather than Ulcerative Colitis.

Abstract Background As a chronic systemic inflammation may be associated with an increased risk of vascular events, the aim of the present study was to assess the incidence of stroke and transient ischemic attack (TIA) in patients with inflammatory bowel disease over a period of 15 years. Methods This cohort study included patients for whom the initial diagnosis of an inflammatory bowel disease (IBD) (Crohn's disease: CD and ulcerative colitis: UC) was documented anonymously between 2000 and 2015 in 1,262 general practices in Germany. IBD patients were matched to patients without IBD using propensity scores based on age, sex, physician, co-diagnoses and co-therapies. Cox regression models w…

Validation of the simplified Animal Naming Test as primary screening tool for the diagnosis of covert hepatic encephalopathy

Diagnosis of covert hepatic encephalopathy (CHE) is time consuming in clinical practice. Recently, a new diagnostic tool - the simplified Animal Naming Test (S-ANT1) - was presented with promising results in an Italian cohort. The aim of the present study was to validate S-ANT1 in a cohort of cirrhotic patients from a German tertiary referral centre.143 cirrhotic patients and 37 healthy controls were enrolled. Hepatic encephalopathy (HE) grade 1 (HE1) was clinically diagnosed according to the West-Haven Criteria. Critical flicker frequency and Psychometric Hepatic Encephalopathy Score were used to detect minimal HE (MHE). All participants were additionally examined by S-ANT1.58 (40.6%) pati…

Predictors of advanced fibrosis in non-cirrhotic non-alcoholic fatty liver disease in Germany

BACKGROUND 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 ye…

Ein individualisiertes 8-wöchiges Sportprogramm verbessert bei Patienten mit NAFLD die hepatische Fibrose und Inflammation und steigert die Vielfalt des Mikrobioms

Adipokines and Endotoxemia Correlate with Hepatic Steatosis in Non-Alcoholic Fatty Liver Disease (NAFLD)

(1) Background: The etiology of non-alcoholic fatty liver disease (NAFLD) is multifactorial. Dietary composition has been implicated as a factor modulating intestinal barrier and could affect disease severity. The aim of this study was to evaluate dietary intake and markers of intestinal permeability in patients with NAFLD. (2) Methods: We enrolled 63 patients with NAFLD and compared them to age-matched controls. (3) Results: body mass index (BMI) and leptin to adiponectin ratio&mdash

Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes

Background: We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D). Methods: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by vibration-controlled transient elastography(VCTE) and AGILE 3+. The target conditions were advanced fibrosis, nonalcoholic steatohepatitis(NASH) and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of NITs individually or in sequential combination was assessed by area under receiver operating characteristic curve(AUROC) and by dec…

Impact of non-selective ß-blockers on hepatic encephalopathy in patients with liver cirrhosis

Non-selective β-blockers (NSBB) are frequently used for the treatment of portal hypertension and gastroesophageal varices in patients with liver cirrhosis; however prospective studies investigating the potential association between NSBB use and hepatic encephalopathy (HE) are still scarce. We investigated the potential association between NSBB use and the presence of covert HE (CHE) as well as the development of overt HE (OHE).224 patients with liver cirrhosis were included into this cohort study at two German centers and followed for a median of 364 days. CHE was diagnosed by pathological results in the PHES. Predictors for the presence of CHE or the development of OHE were analyzed using …

A young patient with type 2 diabetes associated non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma.

The rising prevalence of the metabolic syndrome has led to an increase of non-alcoholic fatty liver disease (NAFLD), and its progressive-inflammatory form called non-alcoholic steatohepatitis (NASH). In recent years, NAFLD and NASH have become major risk factors for developing liver cirrhosis and hepatocellular carcinoma (HCC). In this case, we report a 46-year-old patient with type 2 diabetes mellitus and metabolic comorbidities including obesity and arterial hypertension, who was referred because of rising liver enzymes. After clinical and diagnostic evaluation, the patient was diagnosed with NASH-associated liver cirrhosis, Child-Pugh stage B. A normal blood sugar level was difficult to …

Raised serum Interleukin-6 identifies patients with liver cirrhosis at high risk for overt hepatic encephalopathy

BACKGROUND 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 portosyste…

Non-alcoholic fatty liver disease increases the risk of incident chronic kidney disease

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease. Its role in the development of extrahepatic co-morbidities is under investigation. The impact of NAFLD on the development of chronic kidney disease (CKD) is incompletely understood. The aim of this study was to explore the potential contribution of NAFLD on CKD in Germany. METHODS: The Disease Analyzer Database covering 7.49 million cases in Germany was explored for patients diagnosed with NAFLD between 2000 and 2015 and was matched 1:1 to a cohort without NAFLD. Matching criteria included age, sex, physician, index year and co-diagnoses associated with CKD. The primary outcomes of thi…

Association between diabetes mellitus and hepatic encephalopathy in patients with cirrhosis

Background 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…

Epidemiology of hepatic encephalopathy in german hospitals – the EpHE study

Abstract Background Hepatic encephalopathy (HE) is a serious complication of liver cirrhosis. The proportion of patients with liver cirrhosis attending German hospitals suffering from HE is unknown. Methods In the first part of the study, data of 14 community hospitals and 5 university hospitals covering the years 2010 and 2011 were analyzed retrospectively for the DRG codes of liver cirrhosis and hepatic encephalopathy. In the second prospective part of the multicenter observational study, all patients with liver cirrhosis attending the departments of gastroenterology of 16 participating community hospitals within a study period of 3 months were included and screened for HE clinically acco…

Individualisierte Sportintervention bei Patienten mit nicht-alkoholischer Fettlebererkrankung (HELP-Studie)

Leberzirrhose bei NASH – eine unterschätzte Komplikation?

Health-related quality of life in patients with compensated and decompensated liver cirrhosis.

Compensated (Child-Pugh [CP] A) and decompensated (CP B/C) liver cirrhosis significantly differs in terms of impairment of health-related quality of life (HRQoL). However, sufficient data on potentially treatable factors associated with HRQoL in both stages of the disease are still lacking. Consequently, aims of this study were to determine differences in HRQoL between patients with compensated and decompensated liver cirrhosis and to identify potentially treatable factors associated with HRQoL.218 patients with liver cirrhosis were enrolled into this study. Chronic Liver Disease Questionnaire (CLDQ) was used to assess HRQoL. Covert hepatic encephalopathy (CHE) was diagnosed according to a …

Patterns of liver injury in COVID-19 - a German case series.

BACKGROUND: Reports of liver injury in patients with novel coronavirus disease 2019 (COVID-19) are emerging from China and the USA. A wide variety of liver function test abnormalities and few cases of severe liver failure have been reported. No data on the hepatic phenotype from Europe are available at current. METHODS: We report a case series of 44 consecutive patients hospitalized for COVID-19 in Germany. RESULTS: At the time of admission, aspartate aminotransferase greater than the upper limit of normal was present in 70%, while alanine aminotransferase was elevated in 15.8%. Markers of cholestatic liver injury were altered only in a minority of patients. During hospitalization, 31% and …

Prescription rates of common medications in patients with decompensated cirrhosis in Germany

Adequate pharmacological treatment is of pivotal importance to improve prognosis in patients with decompensated liver cirrhosis. We studied the adherence to recommended pharmacological treatments as secondary prevention in cirrhotic patients following a first decompensation in German primary care.Using the Disease Analyzer Database, the current study sample included patients with liver cirrhosis who had an initial diagnosis of a first decompensation event between 2015 and 2018 (index date) and a follow-up time of at least 6 months after the index date. Pharmacological treatments following the 6 months after the index date were studied.The study included 1538 patients with a first decompensa…

Prädiktion fortgeschrittener Fibrose bei Patienten mit nicht-alkoholischer Fettleber (NAFLD) – Vergleich von NAFLD fibrosis score (NFS), Fibrosis-4 (Fib-4) score und APRI

Association Between Serum Levels of Neurofilament Light Chains and Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis.

INTRODUCTION: Serum biomarkers for the diagnosis of minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis would be desirable. In this proof-of-concept study, we investigated the association between MHE and serum levels of neurofilament light chains (sNfL) in patients with liver cirrhosis. METHODS: sNfL were studied in patients with liver cirrhosis (with or without MHE) and controls (patients with ischemic stroke, transitory ischemic attack, and healthy individuals). MHE was diagnosed using the Psychometric Hepatic Encephalopathy Score. RESULTS: Patients with MHE showed higher sNfL than patients without MHE and controls. In multivariable analyses, higher sNfL were independent…

Liver injury in patients with severe acute respiratory syndrome coronavirus-2 infection: a systematic review and meta-analysis.

OBJECTIVE: Coronavirus disease-19 (COVID-19) infection is a global health threat. To inform the liver community on the potential relevance of COVID-19, we performed a systematic review and meta-analysis of published data on liver injury in patients with COVID-19 infection. METHODS: We searched PubMed and Google Scholar through 22 March according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled data were analyzed by using random-effects meta-analyses. RESULTS: A total of 14 studies combining data from 2.871 patients were identified. The prevalence of pre-existing liver disease was reported at 3.1%. The pooled prevalence of elevated aspartate aminot…

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

<b><i>Background/Aim:</i></b> Individual components of the metabolic syndrome (MS) such as obesity or diabetes mellitus impair the prognosis of patients with hepatocellular carcinoma (HCC) following curative treatment approaches or transarterial therapies. The aim of this retrospective study was to assess the impact of these factors on the overall survival (OS) of patients with advanced HCC treated with sorafenib. <b><i>Methods:</i></b> Univariate and multivariate analyses were performed to assess the impact of individual components of the MS on the OS of 152 consecutive patients with advanced HCC treated with sorafenib. <b><i>Resu…

Development and Validation of a Prognostic Score to Predict Covert Hepatic Encephalopathy in Patients With Cirrhosis.

Diagnosis of covert hepatic encephalopathy (CHE) is challenging and often neglected in clinical practice. The aim of this study was to develop an easy-to-perform score to predict CHE in patients with cirrhosis.For the development or validation cohort of the proposed clinical CHE score, 142 or 96 consecutive patients with cirrhosis were prospectively enrolled. The Psychometric Hepatic Encephalopathy Score was used to detect minimal hepatic encephalopathy. All patients were examined with the simplified animal naming test and were asked to complete the Chronic Liver Disease Questionnaire. We followed the TRIPOD guideline for development, validation, and reporting of the proposed score.The clin…

Impact of Non-Alcoholic Fatty Liver Disease on Metabolic Comorbidities in Type 2 Diabetes Mellitus.

Abstract Objective Type 2 Diabetes (T2D) is a major risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD). The published prevelance in epidemiological studies in this high risk population exceeds 70%. The aim of this analysis was to investigate the impact of NAFLD on T2D patients in Germany. Methods Using the Disease Analyzer Database (IQVIA), T2D patients with NAFLD diagnosed in Germany were matched to a cohort without NAFLD controlling for age, sex, physician, index year and metabolic comorbidities and assessed for their risk of developing myocardial infarction, stroke, peripheral arterial disease (PAD) or chronic kidney disease, as well as the type …

Fatty liver disease – A multifaceted disease with more than one name?

Management of hepatic encephalopathy in Germany: a survey among physicians

 Hepatic encephalopathy (HE) is a severe complication of liver cirrhosis with impairment of quality of life and prognosis. Management patterns among physicians have not been investigated yet. A questionnaire containing 17 questions was sent out to 1468 gastroenterologists and 120 general practitioners (GPs). It included questions regarding diagnostic, therapeutic, and management strategies used in patients with overt HE (OHE) and covert HE (CHE). The response rate was 12 % (n = 172) for gastroenterologists and 45 % (n = 54) for GPs. Of gastroenterologists, 26.7 % examine patients with an initial diagnosis of liver cirrhosis regarding HE. Gastroenterologists favored a combination of differen…

Nonalcoholic Fatty Liver Disease Increases the Risk of Anxiety and Depression.

Nonalcoholic fatty liver disease (NAFLD), depression, and anxiety disorders are frequent diseases, and data on mutual influence are inconsistent. The aim of this study was to explore the incidence of depression and anxiety in a large primary care cohort in Germany and to study the impact of NAFLD over a 10‐year time frame. Patients with NAFLD diagnosed between 2010 and 2015 were matched to a cohort without NAFLD controlling for age, sex, physician, index year, and Charlson comorbidity index. The primary outcome of the study was the incidence of depression, anxiety, and first prescription of antidepressant drugs. We compared 19,871 patients with NAFLD to 19,871 matched controls. Within 10 ye…

Editorial: stepwise risk stratification for both F3 and F4 in NAFLD patients-authors' reply.

Proton pump inhibitors increase risk of bone fractures in men with cirrhosis: a population-based study

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.To investigate whether PPI use predisposes patients with cirrhosis to bone fractures.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 regressi…

Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program

BACKGROUND Lifestyle modifications remain the cornerstone of treatment in non-alcoholic fatty liver disease (NAFLD). However, they requently fail related to the inability of patients to implement lasting changes. AIMS To evaluate the effects of a short, web-based, individualised exercise program on non-invasive markers of hepatic steatosis, inflammation and fibrosis. METHODS Patients with histologically confirmed NAFLD underwent an 8-week, web-based, individualised exercise program that contained bidirectional feedback. RESULTS Forty-four patients entered the study and 41 completed the assigned training goal (93.2%). In the completer population, 8 weeks of individualised exercise increased …

Letter: diabetes mellitus increases the risk of hepatic encephalopathy in patients with cirrhosis-authors’ reply

Entwicklung und Validierung des NAFLD Cirrhosis Score (NCS) zur Separierung von fortgeschrittener Fibrose und Zirrhose

Validation of the Clinical Frailty Scale for the Prediction of Mortality in Patients With Liver Cirrhosis

Introduction Frailty is a common but often underestimated complication in patients with liver cirrhosis. The Clinical Frailty Scale (CFS) allows the assessment of frailty within a short period of time but has only been investigated in a Canadian cohort of outpatients. The aim of the current study was to evaluate the ability of the CFS to predict mortality in outpatients and nonelectively hospitalized German patients. Methods Two hundred outpatients and 99 nonelectively hospitalized patients with liver cirrhosis were prospectively enrolled. Outpatients/inpatients were followed for a median of 364/28 days regarding the primary outcome of death or liver transplantation. Eighty-seven patients o…

Quality of life as a therapeutic objective in the management of hepatic encephalopathy and the potential role of rifaximin-α

Objective Quality of life (QoL) is impaired in patients with hepatic encephalopathy and rifaximin-α can improve QoL within 6 months. This study assessed the importance of QoL as a therapeutic objective in hepatic encephalopathy management; whether QoL is routinely assessed in hepatic encephalopathy patients in clinical practice and the role of rifaximin-α in this context. Methods A survey was conducted of healthcare professionals (HCPs) from Europe and Australia involved in hepatic encephalopathy management. HCPs rated the importance of a range of therapeutic objectives on a 1–7 Likert scale (1 = not at all important; 7 = extremely important). HCPs were also required to provide three patien…

Applicability and safety of discontinuous ADVanced Organ Support (ADVOS) in the treatment of patients with acute-on-chronic liver failure (ACLF) outside of intensive care.

Background ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis and holds promise to sustain liver function and recovery of patients with acute-on-chronic liver failure (ACLF). Previously, ADVOS was tested as continuous treatment for intensive care patients with liver failure. Data related to the applicability and safety as discontinuous treatment outside of ICU is not available. Aim Evaluation of ADVOS as discontinuous treatment for patients with ACLF outside intensive care unit and comparison with a matched historic cohort. Methods and results In this retrospective study, 26 patients with ACLF and the indication for renal replacement therapy related to HRS-AK…

Vitamin A deficiency is associated with disease severity in patients with liver cirrhosis

Outcome Prediction of Covert Hepatic Encephalopathy in Liver Cirrhosis: Comparison of Four Testing Strategies

INTRODUCTION: Despite the negative impact of covert hepatic encephalopathy on the outcome of patients with liver cirrhosis, data regarding the ability of different testing strategies to predict overt hepatic encephalopathy (OHE) development and mortality are limited. This study aimed to compare the ability of Psychometric Hepatic Encephalopathy Score (PHES), critical flicker frequency (CFF), simplified animal naming test (S-ANT1), and clinical covert hepatic encephalopathy (CCHE) score to predict OHE development and mortality. METHODS: A total of 224 patients with liver cirrhosis were tested with different testing strategies and prospectively followed up regarding clinically relevant outcom…

Clinical Frailty Scale for Risk Stratification in Patients with Sars-Cov-2 Infection

Predictive factors for adverse outcomes in patients with COVID-19 are urgently needed. Data related to the applicability of the Clinical Frailty Scale (CFS) for risk stratification in patients with COVID-19 are currently lacking. We investigated the ability of CFS to predict need for mechanical ventilation and the duration of hospital stays in European patients with COVID-19. In total, 42 patients with confirmed COVID-19 infection admitted to the University Medical Center Mainz between March 3 and April 15 2020 were included into this validation study and data were retrospectively analyzed. CFS was assessed at admission in all patients. Patients were followed for need for mechanical ventil…

Clinical Predictors for Poor Quality of Life in Patients With Covert Hepatic Encephalopathy.

Background Current EASL/AASLD guidelines recommend treatment of covert hepatic encephalopathy (HE) only in symptomatic patients, for example, in those with impaired quality of life or with affected driving abilities. Goals Because testing for impaired quality of life is time consuming, the aim of the present study was to identify simple clinical predictors for poor quality of life in patients with covert HE (CHE). Study In total, 139 cirrhotic in- and outpatients without a history of overt hepatic encephalopathy were enrolled. Diagnosis of HE grade 1 (HE1) was diagnosed clinically according to the West-Haven Criteria. Critical flicker frequency and the Psychometric Hepatic Encephalopathy Sc…

Editorial: covert hepatic encephalopathy-silent but serious. Authors’ reply

Response: Frailty Assessment in the Covid-19 Pandemic

Dear Editor, We would like to thank Ng Cheong Chung and colleagues for their important comment on our recent manuscript demonstrating the ability of the Clinical Frailty Scale (CFS) to predict the need for mechanical ventilation and duration of hospital stays in German patients with COVID-19.1 The authors raise important points and we take the opportunity to respond herein.2 Frailty is a complex condition that is characterized by the loss of functional reserve as well as a decline in cognitive function. The development of frailty in a patient is multifaceted—including body constitution and even …

Prospective evaluation of the impact of covert hepatic encephalopathy on quality of life and sleep in cirrhotic patients

BACKGROUND Minimal hepatic encephalopathy (HE) and HE grade 1 (HE1) according to the West Haven criteria have recently been grouped as one entity named-covert HE- (CHE). Data regarding the impact of CHE on health-related quality of life (HRQoL) and sleep quality are controversial. AIM First, to determine whether CHE affects HRQoL and sleep quality of cirrhotic patients and second, whether minimal HE (MHE) and HE1 affect HRQoL and sleep quality to a comparable extent. METHODS A total of 145 consecutive cirrhotic patients were enrolled. HE1 was diagnosed clinically according to the West Haven criteria. Critical flicker frequency and the Psychometric Hepatic Encephalopathy Score were used to d…

Letter: proton pump inhibitor use and bone fracture risk-a mechanistic point of view. Authors' reply

Vorsorgegastroskopie – lohnt sich das wirklich?

Die Vorsorgekoloskopie ist in Deutschland seit vielen Jahren fest etabliert und eine Erfolgsgeschichte. Erkrankungen mit malignem Potential sind auch im oberen Verdauungstrakt haufig anzutreffen. Zu nennen sind hier in erster Linie die gastroosophageale Refluxkrankheit (GERD) sowie die autoimmune (Typ A) und die bakterielle Gastritis (Typ B) hervorgerufen durch die Infektion mit Helicobacter pylori. Vergleichsweise selten sind dagegen intraepitheliale Neoplasien des Duodenums und die Zoeliakie, die zum T-Zell-Lymphom fuhren kann. Diese drei Regionen des oberen Verdauungstrakts konnen durch die „Vorsorgegastroskopie“, die korrekt Osophago-Gastro-Duodenoskopie (OGD) heist, beurteilt werden.

Proton Pump Inhibitors in Patients With Liver Cirrhosis: Evidence to Improve Their Battered Reputation.

Health-related Quality of Life in Nonalcoholic Fatty Liver Disease Associates With Hepatic Inflammation

Background & Aims Chronic liver disease has negative effects on health-related quality of life (HRQL). We analyzed data from the European non-alcoholic fatty liver disease (NAFLD) registry to assess the effects of NAFLD on HRQL. Methods We collected data from 304 patients (mean age, 52.3 ± 12.9 years) with histologically defined NAFLD enrolled prospectively into the European NAFLD Registry in Germany, the United Kingdom, and Spain. The chronic liver disease questionnaire (CLDQ) was completed within 6 months of liver biopsy collection. Results The mean CLDQ overall score was 5.0 ± 1.2, with the lowest score in the category fatigue (4.3 ± 1.6) and the highest scores for activity (5.4 ± 1.4). …

Symptom burden and treatment response in patients with primary biliary cholangitis (PBC) – real life data form Germany