Publications by authors named "Philipp Kasper"

35 Publications

24-h-Ambulatory Blood Pressure Monitoring in Sub-Saharan Africa: Hypertension Phenotypes and Dipping Patterns in Malawian HIV+ Patients on Antiretroviral Therapy.

Glob Heart 2021 13;16(1):67. Epub 2021 Oct 13.

Clinic for Gastroenterology and Hepatology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, DE.

Background: Cardiovascular disease and especially hypertension are a growing problem among people living with HIV (PLHIV) on antiretroviral therapy (ART) in sub-Saharan Africa.

Objectives: As robust data on hypertension phenotypes associated with distinct cardiovascular risks among PLHIV are limited, we aimed to assess the frequency of white-coat (WCH), masked (MH) hypertension, and blood pressure dipping-patterns in a group of Malawian PLHIV.

Methods: As part of the prospective Lighthouse-Tenofovir-Cohort-Study, we analyzed clinical, laboratory and 24-h-ambulatory blood pressure monitoring (ABPM) data of PLHIV from urban Lilongwe with treated or untreated hypertension or raised office blood pressure (OBP) during routine study-visits.

Results: 118 PLHIV were included and data of 117 participants could be analyzed. Twenty-four-hour ABPM normotension was found in a total of 73 PLHIV including 14/37 on antihypertensive treatment (37.8%). Using strict definitions, i.e. normal OBP plus normal mean BP for all periods of ABPM, controlled hypertension was found in only 4/37 (10.8%) PLHIV on antihypertensive treatment while true normotension was observed in 10/24 untreated patients (41.7%) with previously diagnosed hypertension and 22/56 patients (39.3%) without a medical history of hypertension. WCH with normal BP during all periods of 24-h-ABPM was identified in 12/64 OBP-hypertensive PLHIV (18.8%), primarily in patients with grade 1 hypertension (11/41 patients; 26.8%). MH was found in 17/53 PLHIV with OBP-normotension (32.1%), predominantly in patients with high normal BP (11/20 patients; 55%). The estimated glomerular filtration rate tended to be lower in MH compared to strictly defined normotensive PLHIV (92.0±20.4 vs. 104.8±15.7 ml/min/m²). 64.1 percent of PLHIV (59.5% with 24-h hypertension and 66.7% with 24-h normotension) had abnormal systolic dipping.

Conclusion: The high prevalence of WCH and MH with signs of early renal end-organ damage and an abnormal dipping in approximately 2/3 of PLHIV warrants further investigation as these factors may contribute to the increased cardiovascular risk in PLHIV in resource-limited settings like Malawi.

Clinical Trial Registration: https://clinicaltrials.gov (NCT02381275), registered March 6th, 2015.
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http://dx.doi.org/10.5334/gh.945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516010PMC
October 2021

[Management of acutely decompensated liver cirrhosis in emergency and critical care medicine].

Med Klin Intensivmed Notfmed 2021 Oct 12. Epub 2021 Oct 12.

Klinik für Akut- und Notfallmedizin, St.-Antonius-Hospital Eschweiler, Eschweiler, Deutschland.

Acute decompensation in patients with liver cirrhosis is characterized by the development of ascites, gastrointestinal bleeding, hepatic encephalopathy, or bacterial infection and is often accompanied by further extrahepatic organ dysfunction. Since critically ill patients with decompensated cirrhosis have a high mortality risk, rapid identification and treatment of the triggering event of decompensation (e.g., infection, hemorrhage, drugs) as well as specific measures for the treatment of concomitant extrahepatic organ dysfunctions are essential in order to improve the patient's prognosis and to prevent the development of acute-on-chronic liver failure (ACLF).
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http://dx.doi.org/10.1007/s00063-021-00876-3DOI Listing
October 2021

[Cirrhotic cardiomyopathy].

Dtsch Med Wochenschr 2021 Aug 20;146(16):1070-1076. Epub 2021 Aug 20.

A cirrhotic cardiomyopathy (CCM) can be observed in patients with end-stage liver disease and is characterized by a systolic and/or diastolic dysfunction in the absence of pre-existing heart diseases. While the cardiac dysfunction is often masked at rest, it typically manifests itself during cardiovascular challenges such as hypovolemia, physical stress, or sepsis. The diagnosis of CCM is challenging and predominantly based on echocardiographic measurements to identify subclinical cardiac dysfunction. Additional diagnostic criteria include electrophysiological abnormalities such as QT-interval prolongation, an abnormal chronotropic or inotropic response to stress, elevated cardiac biomarkers such as natriuretic peptides, and structural cardiac abnormalities like left atrium enlargement. There is no specific therapy for CCM. Supportive measures and regular cardiac evaluation of high-risk patients and transplant candidates are important to reduce the risks associated with invasive procedures and treatments.
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http://dx.doi.org/10.1055/a-1321-9523DOI Listing
August 2021

Maternal Exercise Mediates Hepatic Metabolic Programming via Activation of AMPK-PGC1α Axis in the Offspring of Obese Mothers.

Cells 2021 05 19;10(5). Epub 2021 May 19.

Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.

Maternal obesity is associated with an increased risk of hepatic metabolic dysfunction for both mother and offspring and targeted interventions to address this growing metabolic disease burden are urgently needed. This study investigates whether maternal exercise (ME) could reverse the detrimental effects of hepatic metabolic dysfunction in obese dams and their offspring while focusing on the AMP-activated protein kinase (AMPK), representing a key regulator of hepatic metabolism. In a mouse model of maternal western-style-diet (WSD)-induced obesity, we established an exercise intervention of voluntary wheel-running before and during pregnancy and analyzed its effects on hepatic energy metabolism during developmental organ programming. ME prevented WSD-induced hepatic steatosis in obese dams by alterations of key hepatic metabolic processes, including activation of hepatic ß-oxidation and inhibition of lipogenesis following increased AMPK and peroxisome-proliferator-activated-receptor-γ-coactivator-1α (PGC-1α)-signaling. Offspring of exercised dams exhibited a comparable hepatic metabolic signature to their mothers with increased AMPK-PGC1α-activity and beneficial changes in hepatic lipid metabolism and were protected from WSD-induced adipose tissue accumulation and hepatic steatosis in later life. In conclusion, this study demonstrates that ME provides a promising strategy to improve the metabolic health of both obese mothers and their offspring and highlights AMPK as a potential metabolic target for therapeutic interventions.
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http://dx.doi.org/10.3390/cells10051247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158724PMC
May 2021

Combined analysis of gut microbiota, diet and PNPLA3 polymorphism in biopsy-proven non-alcoholic fatty liver disease.

Liver Int 2021 07 7;41(7):1576-1591. Epub 2021 May 7.

Department of Hepatology and Gastroenterology, Charité University Medicine, Campus Virchow Clinic and Campus Charité Mitte, Berlin, Germany.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) is a global health burden. Risk factors for disease severity include older age, increased body mass index (BMI), diabetes, genetic variants, dietary factors and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unknown.

Methods: In this cross-sectional study, we performed 16S gene sequencing using fecal samples, collected dietary intake, PNPLA3 gene variants and clinical and liver histology parameters in a well-described cohort of 180 NAFLD patients. Principal component analyses were used for dimensionality reduction of dietary and microbiota data. Simple and multiple stepwise ordinal regression analyses were performed.

Results: Complete data were available for 57 NAFLD patients. In the simple regression analysis, features associated with the metabolic syndrome had the highest importance regarding liver disease severity. In the multiple regression analysis, BMI was the most important factor associated with the fibrosis stage (OR per kg/m : 1.23, 95% CI 1.10-1.37, P < .001). The PNPLA3 risk allele had the strongest association with the histological grade of steatosis (OR 5.32, 95% CI 1.56-18.11, P = .007), followed by specific dietary patterns. Low abundances of Faecalibacterium, Bacteroides and Prevotella and high abundances of Gemmiger were associated with the degree of inflammation, ballooning and stages of fibrosis, even after taking other cofactors into account.

Conclusions: BMI had the strongest association with histological fibrosis, but PNPLA3 gene variants, gut bacterial features and dietary factors were all associated with different histology features, which underscore the multifactorial pathogenesis of NAFLD.
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http://dx.doi.org/10.1111/liv.14899DOI Listing
July 2021

Acute gastric outlet obstruction due to an impacted gallstone: the Bouveret's syndrome.

BMJ Case Rep 2021 Mar 16;14(3). Epub 2021 Mar 16.

Department of Acute and Emergency Care, Sankt Antonius-Hospital Eschweiler, Eschweiler, North Rhine-Westphalia, Germany.

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http://dx.doi.org/10.1136/bcr-2021-242301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970255PMC
March 2021

Hypertension in NAFLD: An uncontrolled burden.

J Hepatol 2021 05 22;74(5):1258-1260. Epub 2021 Jan 22.

University of Cologne, Faculty of Medicine and University Hospital Cologne, Clinic for Gastroenterology and Hepatology, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Hypertension Center, Cologne, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2021.01.019DOI Listing
May 2021

Spontaneous cholecystocutaneous fistula: an uncommon complication of acute cholecystitis.

BMJ Case Rep 2020 Dec 15;13(12). Epub 2020 Dec 15.

Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, Cologne, North Rhine Westphalia, Germany.

A 78-year-old man presented to the hospital with acute right upper quadrant pain, fever and nausea. A focused abdominal ultrasound and abdominal CT scan were performed demonstrating an acute calculous cholecystitis with gallbladder perforation. Although a CT-guided cholecystostomy was performed and a pericholecystic abscess was relieved promptly, the patient developed a cholecystocutaneous fistula in the right hypochondriac region. A cholecystocutaneous fistula is an extremely rare complication that may occur in patients with acute calculous or acalculous cholecystitis, chronic gallstone disease, gallbladder carcinoma or prior hepatobiliary surgery.
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http://dx.doi.org/10.1136/bcr-2020-238063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745323PMC
December 2020

Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming.

Sci Rep 2020 09 22;10(1):15424. Epub 2020 Sep 22.

Department of Pediatrics and Adolescent Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Robert-Koch Str. 16, Building 44a, 50931, Cologne, Germany.

Maternal exercise (ME) during pregnancy has been shown to improve metabolic health in offspring and confers protection against the development of non-alcoholic fatty liver disease (NAFLD). However, its underlying mechanism are still poorly understood, and it remains unclear whether protective effects on hepatic metabolism are already seen in the offspring early life. This study aimed at determining the effects of ME during pregnancy on offspring body composition and development of NAFLD while focusing on proteomic-based analysis of the hepatic energy metabolism during developmental organ programming in early life. Under an obesogenic high-fat diet (HFD), male offspring of exercised C57BL/6J-mouse dams were protected from body weight gain and NAFLD in adulthood (postnatal day (P) 112). This was associated with a significant activation of hepatic AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα) and PPAR coactivator-1 alpha (PGC1α) signaling with reduced hepatic lipogenesis and increased hepatic β-oxidation at organ programming peak in early life (P21). Concomitant proteomic analysis revealed a characteristic hepatic expression pattern in offspring as a result of ME with the most prominent impact on Cholesterol 7 alpha-hydroxylase (CYP7A1). Thus, ME may offer protection against offspring HFD-induced NAFLD by shaping hepatic proteomics signature and metabolism in early life. The results highlight the potential of exercise during pregnancy for preventing the early origins of NAFLD.
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http://dx.doi.org/10.1038/s41598-020-72022-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508970PMC
September 2020

[Hepatic dysfunction in sepsis].

Med Klin Intensivmed Notfmed 2020 Oct 28;115(7):609-619. Epub 2020 Jul 28.

Klinik für Akut- und Notfallmedizin, St.-Antonius-Krankenhaus Eschweiler, Eschweiler, Deutschland.

Sepsis represents a life-threatening condition that frequently accompanies acute hepatic dysfunction. As a result of systemic inflammation, immune dysregulation, and microcirculatory derangements, different types of liver dysfunction can occur, such as hypoxic hepatitis, sepsis-associated cholestasis, or liver failure. A very serious and late sequela is secondary sclerosing cholangitis of the critically ill patient. Clinical management of sepsis-related liver dysfunction includes the rapid identification and treatment of the suspected underlying infection, hemodynamic stabilization to improve hepatic perfusion, and the optimization of oxygen delivery to the liver. Despite maximum efforts in supportive treatment, the outcome of patients with sepsis or septic shock and concomitant severe hepatic dysfunction remains very poor.
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http://dx.doi.org/10.1007/s00063-020-00707-xDOI Listing
October 2020

NAFLD and cardiovascular diseases: a clinical review.

Clin Res Cardiol 2021 Jul 21;110(7):921-937. Epub 2020 Jul 21.

Department of Gastroenterology and Hepatology, Faculty of Medicine, and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.

Non-alcoholic fatty liver DISEASE (NAFLD) is the most common chronic liver disease in Western countries and affects approximately 25% of the adult population. Since NAFLD is frequently associated with further metabolic comorbidities such as obesity, type 2 diabetes mellitus, or dyslipidemia, it is generally considered as the hepatic manifestation of the metabolic syndrome. In addition to its potential to cause liver-related morbidity and mortality, NAFLD is also associated with subclinical and clinical cardiovascular disease (CVD). Growing evidence indicates that patients with NAFLD are at substantial risk for the development of hypertension, coronary heart disease, cardiomyopathy, and cardiac arrhythmias, which clinically result in increased cardiovascular morbidity and mortality. The natural history of NAFLD is variable and the vast majority of patients will not progress from simple steatosis to fibrosis and end stage liver disease. However, patients with progressive forms of NAFLD, including non-alcoholic steatohepatitis (NASH) and/or advanced fibrosis, as well as NAFLD patients with concomitant types 2 diabetes are at highest risk for CVD. This review describes the underlying pathophysiological mechanisms linking NAFLD and CVD, discusses the role of NAFLD as a metabolic dysfunction associated cardiovascular risk factor, and focuses on common cardiovascular manifestations in NAFLD patients.
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http://dx.doi.org/10.1007/s00392-020-01709-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238775PMC
July 2021

Intestinal Virome Signature Associated With Severity of Nonalcoholic Fatty Liver Disease.

Gastroenterology 2020 11 9;159(5):1839-1852. Epub 2020 Jul 9.

Department of Medicine, University of California San Diego, La Jolla, California; Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California; Center for Innovative Phage Applications and Therapeutics, University of California San Diego, La Jolla, California. Electronic address:

Background & Aims: Alterations in the gut microbiome have been associated with the severity of nonalcoholic fatty liver disease (NAFLD). Previous studies focused exclusively on the bacteria in the microbiome; we investigated changes in the viral microbiome (virome) in patients with NAFLD.

Methods: In a prospective, cross-sectional, observational study, we extracted RNA and DNA virus-like particles from fecal samples from 73 patients with NAFLD: 29 patients had an NAFLD Activity Score (NAS) of 0-4, 44 patients had an NAS of 5-8 or liver cirrhosis (LCI), 37 patients had F0-F1 fibrosis, and 36 patients had F2-F4 fibrosis. As controls, 9 individuals without liver disease and 13 patients with mild primary biliary cholangitis were included in the analysis. We performed shotgun metagenomic sequencing of virus-like particles.

Results: Patients with NAFLD and NAS 5-8/LCI had a significant decrease in intestinal viral diversity compared with patients with NAFLD and NAS 0-4 or control individuals. The presence of more advanced NAFLD was associated with a significant reduction in the proportion of bacteriophages compared with other intestinal viruses. Using multivariate logistic regression analysis with leave-1-out cross validation, we developed a model, including a viral diversity index and simple clinical variables, that identified patients with NAS 5-8/LCI with an area under the curve of 0.95 (95% confidence interval, 0.91-0.99) and F2-F4 fibrosis with an area under the curve of 0.88 (95% confidence interval, 0.80-0.95). Addition of data on viral diversity significantly improved multivariate models, including those based on only clinical parameters or bacterial diversity.

Conclusions: In a study of fecal viromes from patients with NAFLD and control individuals, we associated histologic markers of NAFLD severity with significant decreases in viral diversity and proportion of bacteriophages. We developed a model based on fecal viral diversity and clinical data that identifies patients with severe NAFLD and fibrosis more accurately than models based only on clinical or bacterial data.
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http://dx.doi.org/10.1053/j.gastro.2020.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404510PMC
November 2020

Detection rates for adenomas, serrated polyps and clinically relevant serrated polyps can be easily estimated by individually calculated detection rate ratios.

Scand J Gastroenterol 2020 Jun 11;55(6):745-751. Epub 2020 Jun 11.

Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Adenoma detection rate (ADR) is a key quality indicator for colonoscopy; however, it is cumbersome to obtain. We investigated if detection rates (DRs) for adenomas, serrated polyps (SPs) and clinically relevant SP (crSPDR) can be accurately estimated by individualized DR ratios (DRRs) in a multicenter primary colonoscopy screening cohort of average-risk individuals. DRRs were calculated by dividing DRs for a certain polyp entity by polyp detection rate (PDR) for each endoscopist individually on the basis of his/her first 50 (DRR) and 100 (DRR) consecutive colonoscopies. DRs were estimated for each endoscopist by multiplying his/her DRR for a certain polyp entity with his/her PDR of subsequent colonoscopies in groups of 50 (DRR) and 100 (DRR) consecutive colonoscopies. Estimated and actual DRs were compared. Estimated DRs showed a strong correlation with actual DRs for adenomas ( = 0.86 and 0.87; each < .001), SPs ( = 0.85 and 0.91; each < .001) and crSPs ( = 0.82 and 0.86; each < .001) using DRRs derived from first 50 and 100 consecutive colonoscopies. Corresponding root mean square error (RMSE) between individual estimated and actual DRs using DRR and DRR was 5.3(±4.6)% and 4.5(±4.8)% for adenomas, 5.2(±4.1)% and 3.9(±2.8)% for SP, 3.1(±3.1)% and 2.8(±2.5)% for crSP, respectively. RMSE was not significantly different between DRR and DRR for ADR ( = .445), SPDR ( = .178) and crSP ( = .544). DR for all relevant polyp entities can be accurately estimated by using individual DRRs. This approach may enable endoscopists to easily track their performance measures in daily routine.
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http://dx.doi.org/10.1080/00365521.2020.1774643DOI Listing
June 2020

Prediction of advanced fibrosis in non-alcoholic fatty liver disease using gut microbiota-based approaches compared with simple non-invasive tools.

Sci Rep 2020 06 10;10(1):9385. Epub 2020 Jun 10.

University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany.

Liver fibrosis is the major determinant of liver related complications in patients with non-alcoholic fatty liver disease (NAFLD). A gut microbiota signature has been explored to predict advanced fibrosis in NAFLD patients. The aim of this study was to validate and compare the diagnostic performance of gut microbiota-based approaches to simple non-invasive tools for the prediction of advanced fibrosis in NAFLD. 16S rRNA gene sequencing was performed in a cohort of 83 biopsy-proven NAFLD patients and 13 patients with non-invasively diagnosed NAFLD-cirrhosis. Random Forest models based on clinical data and sequencing results were compared with transient elastography, the NAFLD fibrosis score (NFS) and FIB-4 index. A Random Forest model containing clinical features and bacterial taxa achieved an area under the curve (AUC) of 0.87 which was only marginally superior to a model without microbiota features (AUC 0.85). The model that aimed to validate a published algorithm achieved an AUC of 0.71. AUC's for NFS and FIB-4 index were 0.86 and 0.85. Transient elastography performed best with an AUC of 0.93. Gut microbiota signatures might help to predict advanced fibrosis in NAFLD. However, transient elastography achieved the best diagnostic performance for the detection of NAFLD patients at risk for disease progression.
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http://dx.doi.org/10.1038/s41598-020-66241-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286895PMC
June 2020

High Protein Intake Is Associated With Histological Disease Activity in Patients With NAFLD.

Hepatol Commun 2020 May 26;4(5):681-695. Epub 2020 Mar 26.

Department of Gastroenterology and Hepatology Faculty of Medicine University of Cologne University Hospital Cologne Cologne Germany.

Overconsumption of carbohydrates and lipids are well known to cause nonalcoholic fatty liver disease (NAFLD), while the role of nutritional protein intake is less clear. In Western diet, meat and other animal products are the main protein source, with varying concentrations of specific amino acids. Whether the amount or composition of protein intake is associated with a higher risk for disease severity has not yet been examined. In this study, we investigated associations of dietary components with histological disease activity by analyzing detailed 14-day food records in a cohort of 61 patients with biopsy-proven NAFLD. Furthermore, we used 16S ribosomal RNA gene sequencing to detect associations with different abundances of the gut microbiota with dietary patterns. Patients with definite nonalcoholic steatohepatitis (NAFLD activity score of 5-8 on liver biopsy) had a significantly higher daily relative intake of protein compared with patients with a NAFLD activity score of 0-4 (18.0% vs. 15.8% of daily protein-based calories, = 0.018). After adjustment for several potentially confounding factors, a higher protein intake (≥17.3% of daily protein-based calories) remained associated with definite nonalcoholic steatohepatitis, with an odds ratio of 5.09 (95% confidence interval 1.22-21.25, = 0.026). This association was driven primarily by serine, glycine, arginine, proline, phenylalanine, and methionine. A higher protein intake correlated with a lower abundance and an altered abundance of several other bacterial taxa. A high protein intake was independently associated with more active and severe histological disease activity in patients with NAFLD. Further studies are needed to investigate the potential harmful role of dietary amino acids on NAFLD, with special attention to meat as their major source.
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http://dx.doi.org/10.1002/hep4.1509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193126PMC
May 2020

Phenotyping non-alcoholic fatty liver disease by the gut microbiota: Ready for prime time?

J Gastroenterol Hepatol 2020 Nov 30;35(11):1969-1977. Epub 2020 Apr 30.

University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany.

Background And Aim: Several studies observed alterations in the gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD). However, analyzed patient populations and methods strongly differ among these studies. The aim of this study was to prove the reproducibility of published results and to provide a detailed overview of all findings in our NAFLD cohort using next generation sequencing methods.

Methods: The individual taxonomic microbiota composition of fecal samples from 90 NAFLD patients and 21 healthy controls was analyzed using 16S rRNA gene sequencing. Study participants were grouped according to their disease stage and compared regarding their gut microbiota composition. Studies were identified from PubMed listed publications, and the results were compared with the findings in our cohort.

Results: Results from 13 identified studies were compared with our data. A decreased abundance of the Bacteroidetes and Ruminococcaceae as well as an increased abundance of Lactobacillaceae and Veillonellaceae and Dorea were the most frequently reported changes among NAFLD patients in 4/13, 5/13, 4/13, 2/13, and 3/13 studies, respectively. Even though these alterations in the gut microbiota composition were also observed in our patient cohort, the majority of published differences could not be reproduced, neither in our own nor in other NAFLD cohort studies.

Conclusion: Despite repeatedly reproduced abundance patterns of specific bacteria, the heterogeneous study results did not reveal a consistent disease specific gut microbiota signature. Further prospective studies with homogenous patient cohorts and standardized methods are necessary to phenotype NAFLD by the gut microbiota.
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http://dx.doi.org/10.1111/jgh.15071DOI Listing
November 2020

Ambulatory Blood Pressure Monitoring in PLHIV in Malawi: Preliminary Findings.

J Acquir Immune Defic Syndr 2020 07;84(3):e11-e14

Clinic for Gastroenterology and Hepatology, University Hospital of Cologne, Cologne, Germany.

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http://dx.doi.org/10.1097/QAI.0000000000002336DOI Listing
July 2020

Cholestatic hepatitis with concomitant nephrotic syndrome due to late syphilis in an immunocompetent 32-year-old man.

BMJ Case Rep 2020 Feb 5;13(2). Epub 2020 Feb 5.

Department of Gastroenterology and Hepatology, University of Cologne, Cologne, North Rhine Westphalia, Germany.

A 32-year-old man was referred to our clinic for evaluation of abnormal liver function tests and concurrent proteinuria. Physical examination revealed a maculopapular rash, involving the trunk and palms, and multiple 'moth-eaten' patches of alopecia. After a prolonged diagnostic work-up a hepatitis with concomitant nephrotic syndrome due to secondary syphilis was diagnosed. Treatment with benzylpenicillin led to complete clinical recovery. Syphilis is a re-emerging infectious disease with heterogeneous clinical presentation that should be considered in the differential diagnosis of inexplicable simultaneous liver and kidney dysfunction in patients with high-risk sexual behaviour.Syphilis is a re-emerging infectious disease with heterogeneous clinical presentation that should be considered in the differential diagnosis of inexplicable simultaneous liver and kidney dysfunction in patients with high-risk sexual behaviour.
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http://dx.doi.org/10.1136/bcr-2019-232615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021109PMC
February 2020

[mTOR-induced pneumonitis in a 72-year-old patient after heart transplantation].

Dtsch Med Wochenschr 2020 02 4;145(3):189-194. Epub 2020 Feb 4.

Klinik III für Innere Medizin, Herzzentrum der Universität zu Köln.

History: A 72-year-old heart transplant recipient presented to the hospital with progressive dyspnea. His immunosuppressive therapy was switched to the mTOR-inhibitor everolimus. A few months before, due to a progressive decline in renal function. Primarily, a community-acquired pneumonia was suspected and an empiric antibiotic therapy was initiated. Despite antimicrobial treatment, an acute respiratory distress syndrome developed and mechanical ventilation became necessary.

Investigations: During the following extensive diagnostic a transbronchial lung biopsy was performed and histological analysis revealed a drug induced lung injury.

Diagnosis: Based on the clinical and histological findings an everolimus induced pneumonitis was suspected.

Treatment And Course: The drug was immediately discontinued and a high-dose steroid treatment was started, resulting in a significant improvement of respiratory function.

Conclusion: Everolimus-related interstitial pneumonitis represents a rare but important adverse effect of everolimus in immunosuppressed patients. Recognition of everolimus induced pneumonitis is of high clinical relevance and should be considered in all patients on everolimus presenting with respiratory symptoms of unknown origin.
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http://dx.doi.org/10.1055/a-1008-7206DOI Listing
February 2020

Hepatocellular carcinoma surveillance with liver imaging is not associated with improved survival.

Scand J Gastroenterol 2020 Feb 28;55(2):222-227. Epub 2020 Jan 28.

Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.

International guidelines recommend hepatocellular carcinoma (HCC) surveillance with ultrasound in high-risk patients with chronic liver diseases. However, there is low-strength evidence about the effects on mortality. The aim of our study was to assess the impact of surveillance on the clinical course and survival of HCC patients seen at a tertiary referral center in Germany. We retrospectively evaluated the data of 401 HCC patients, who presented to our clinic between 1997 and 2015. Two groups were compared regarding patient and disease outcomes: one group included patients who received at least two ultrasound examinations for surveillance purposes prior to first diagnosis ( = 111). The other group consisted of patients with HCC at first presentation without foregoing HCC surveillance ( = 290). Median follow-up in the surveillance group was 76 months (range 4-310 months). Patients in the surveillance group had smaller median tumor sizes (3.5 cm vs. 4.5 cm;  < .001), fulfilled more often Milan criteria (64% vs. 42%;  < .001) and received more often liver transplantation (27% vs. 9%,  < .001) when compared with the non-surveillance group. However, HCC surveillance was not associated with an improved survival (14 months in the surveillance group vs. 12 months in the non-surveillance group,  = .375), hazard ratio regarding overall mortality for the surveillance group: 0.80 (95% CI: 0.62-1.04,  = .09). HCC surveillance with ultrasound led to the detection of earlier disease stages but was not significantly associated with improved survival. Further prospective and long-term studies are needed to clarify benefits and harms of HCC surveillance programs on mortality.
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http://dx.doi.org/10.1080/00365521.2020.1718747DOI Listing
February 2020

Ileal intubation is not associated with higher detection rate of right-sided conventional adenomas and serrated polyps compared to cecal intubation after adjustment for overall adenoma detection rate.

BMC Gastroenterol 2019 Nov 15;19(1):190. Epub 2019 Nov 15.

Department for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, Kerpener Strasse 62, 50937, Cologne, Germany.

Background: High cecal intubation rate (CIR) is associated with significant improved adenoma detection rate (ADR), however, self-reported CIR may be overestimated and inadequate documentation of cecal intubation is associated with a lower polyp detection rate compared to clear documentation. We aimed to investigate if ileal intubation may be associated with higher detection rates (DR) for right-sided conventional adenomas (cAD) and serrated polyps (SP) compared to cecal intubation in a large screening colonoscopy cohort.

Material And Methods: Retrospective analysis of individuals ≥50 years with average risk for colorectal cancer (CRC) who underwent screening colonoscopy between 01/01/2012 and 14/12/2016 at a tertiary academic hospital and six community-based private practices. Exclusion criteria were conditions with increased risk for CRC (e.g. inflammatory bowel disease, history of CRC, hereditary cancer syndromes), previous colonoscopy at the same institution, and incomplete procedures. Right-sided colon was defined as caecum and ascending colon.

Results: 4.138 individuals were analysed (mean age 62 years, 52.1% female). DR for right-sided cADs and SPs were significantly higher after ileal compared to cecal intubation in univariate (12.5% vs. 6.8%, p < 0.001, and 6.3% vs. 3.3%, p < 0.001), but not in multivariate analysis (OR 1.025, 95%-CI 0.639-1.646, p = 0.918, and OR 0.937, 95%-CI 0.671-1.309, p = 0.704). DRs did not differ between ileal and cecal intubation for endoscopists with ADR ≥25 and < 25%, respectively. ADR ≥25% was significantly associated with ileal intubation (OR 21.862, 95%-CI 18.049-26.481, p < 0.001).

Conclusion: Ileal intubation may not provide any benefit over cecal intubation concerning the detection of cADs and SPs in the right-sided colon.
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http://dx.doi.org/10.1186/s12876-019-1111-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858714PMC
November 2019

Assessing guideline adherence in patients with non-variceal upper gastrointestinal bleeding receiving antiplatelet and anticoagulant therapy.

Scand J Gastroenterol 2019 Nov 13;54(11):1357-1363. Epub 2019 Nov 13.

Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Non-variceal upper gastrointestinal bleeding (NVUGIB) occurs frequently and is associated with a significant morbidity and mortality, especially in patients receiving antiplatelet or anticoagulant therapy (APT and ACT, respectively). We aimed to evaluate adherence to guideline recommendations published by European Society of Gastrointestinal Endoscopy (ESGE). Retrospective analysis of patients with NVUGIB und prior exposition to APT or ACT at a single university hospital between 01 January 2016 and 31 December 2017. 270 patients were identified (70.4% male, median age 72 years). 6/17 (35.3%) patients receiving APT for primary cardiovascular prophylaxis, 39/71 (54.9%) and 35 (49.3%) patients receiving APT for secondary cardiovascular prophylaxis (using strict and liberal definition, respectively) and 13/25 (52%) patients receiving dual antiplatelet therapy (DAPT) were not managed according to current recommendations. Management of ACT for secondary thromboembolic prophylaxis did not follow guideline recommendations in 59/93 (63.4%) and 34/93 (36.6%) patients (using strict and liberal definition, respectively). 23.7% of patients with NVUGIB were exposed to combined APT and ACT for whom no guideline recommendations exist. Mortality for any reason was twice as high in patients who were not managed according to guideline recommendations (18.8% vs. 8% using strict definition, 20.5% vs. 10.2% using liberal definition), which did not remain significant after adjusting for comorbidities, whereas cardiovascular events were observed at similar rates. A significant number of patients with NVUGIB receiving APT or ACT is not managed according to current ESGE guideline recommendations. Strategies to implement these guidelines into daily practice need to be developed.
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http://dx.doi.org/10.1080/00365521.2019.1688384DOI Listing
November 2019

[Hepatic dysfunction in patients with cardiogenic shock].

Med Klin Intensivmed Notfmed 2019 Oct 19;114(7):665-676. Epub 2019 Sep 19.

Klinik III für Innere Medizin, Herzzentrum, Universität zu Köln, Köln, Deutschland.

Cardiogenic shock is a life-threatening condition that is frequently associated with acute hepatic dysfunction. Due to low cardiac output resulting in end-organ hypoperfusion and hypoxia, different types of liver dysfunction can develop, such as hypoxic hepatitis or acute liver failure. A very serious and late sequela is the secondary sclerosing cholangitis in critically patients. Clinical management of acute hepatic dysfunction involves the stabilization of cardiac output to improve hepatic perfusion and the optimization of liver oxygenation. However, despite maximum efforts in supportive treatment, the outcome of patients with cardiogenic shock and concomitant hepatic dysfunction remains poor.
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http://dx.doi.org/10.1007/s00063-019-00618-6DOI Listing
October 2019

Fatal disseminated enterovirus infection in a patient with follicular lymphoma undergoing obinutuzumab maintenance therapy.

Eur J Haematol 2019 Sep 18;103(3):268-271. Epub 2019 Jun 18.

Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Critical Care Medicine, University of Cologne, Cologne, Germany.

Follicular lymphoma is the most common subtype of the indolent non-Hodgkin lymphomas. Treatment usually consists of immuno-chemotherapy and results in long-lasting remissions in most cases. Progression-free survival with the second-generation anti-CD20 antibody obinutuzumab was shown to be better than with rituximab when given in combination with either bendamustine or anthracycline-based chemotherapy. Although treatment is generally well tolerated without an excessive rate of toxicities, there appear to be slightly more adverse events with obinutuzumab than with rituximab. Here, we report the case of a 45-year-old female patient that was diagnosed with a disseminated enterovirus infection while undergoing maintenance therapy with obinutuzumab after induction treatment with the combination of bendamustine and rituximab. Enterovirus RNA was detected in the blood, the cerebrospinal fluid, and the colon. A therapy with intravenous immunoglobulins was initiated since the patient presented with a severe treatment-related immunosuppression indicated by hypogammaglobulinemia. Nonetheless, she eventually died from the enterovirus infection without evidence of lymphoma progression. This case underscores that clinicians should be aware of rare but potentially fatal infectious complications related to treatment protocols containing anti-CD20 antibodies.
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http://dx.doi.org/10.1111/ejh.13278DOI Listing
September 2019

Oesophageal and scaly skin lesions associated with chronic cholestatic liver disease.

Gut 2019 11 16;68(11):1960-2018. Epub 2019 Mar 16.

Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.

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http://dx.doi.org/10.1136/gutjnl-2019-318502DOI Listing
November 2019

Jejunal varices as a rare cause of recurrent gastrointestinal bleeding in a 74-year-old man with extrahepatic portal hypertension after pancreato-biliary surgery.

BMJ Case Rep 2019 Mar 14;12(3). Epub 2019 Mar 14.

Department of Gastroenterology and Hepatology, University Hospital of Cologne, Cologne, North Rhine-Westphalia, Germany.

A 74-year-old man presented to our hospital with recurrent lower gastrointestinal bleeding. His past medical history was remarkable for a duodenal papilla carcinoma and he underwent a pylorus-preserving pancreaticoduodenectomy 4 years before. During diagnostic work-up a severe portal vein stenosis after surgery and multiple dilated intramural jejunal varices, which formed as collateral pathways could be detected. Based on these findings, the recurrent haemorrhages were considered to be due to repeated rupturing and bleeding of jejunal varices. Therapeutically, the portal vein stenosis was treated with endovascular stent placement leading to a reduction in prestenotic portal pressure. During follow-up no further episodes of gastrointestinal bleeding were observed. Bleeding from jejunal varices is a very rare cause of gastrointestinal haemorrhages and represents a diagnostic and therapeutic challenge. However, it should be considered in differential diagnosis of obscure recurrent gastrointestinal haemorrhages in patients with a history of hepato-pancreato-biliary surgery.
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http://dx.doi.org/10.1136/bcr-2018-228527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424255PMC
March 2019

Alterations in ERBB2 and BRCA and microsatellite instability as new personalized treatment options in small bowel carcinoma.

BMC Gastroenterol 2019 Feb 4;19(1):21. Epub 2019 Feb 4.

Institute of Pathology, University of Cologne, Cologne, Germany.

Background: Carcinomas of the small bowel are rare tumors usually with dismal prognosis. Most recently, some potentially treatable molecular alterations were described. We emphasize the growing evidence of individualized treatment options in small bowel carcinoma.

Methods: We performed a DNA- based multi-gene panel using ultra-deep sequencing analysis (including 14 genes with up to 452 amplicons in total; KRAS, NRAS, HRAS, BRAF, DDR2, ERBB2, KEAP1, NFE2L2, PIK3CA, PTEN, RHOA, BRCA1, BRCA2 and TP53) as well as an RNA-based gene fusion panel including ALK, BRAF, FGFR1, FGFR2, FGFR3, MET, NRG1, NTRK1, NTRK2, NTRK3, RET and ROS1 on eleven formalin fixed and paraffin embedded small bowel carcinomas. Additionally, mismatch-repair-deficiency was analyzed by checking the microsatellite status using the five different mononucleotide markers BAT25, BAT26, NR-21, NR-22 and NR-27 and loss of mismatch repair proteins using four different markers (MLH1, MSH6, MSH2, PMS2).

Results: In five out of eleven small bowel carcinomas we found potentially treatable genetic alterations. Three patients demonstrated pathogenic (class 5) BRCA1 or BRCA2 mutations - one germline-related in a mixed neuroendocrine-non neuroendocrine neoplasm (MiNEN). Two additional patients revealed an activating ERBB2 mutation or PIK3CA mutation. Furthermore two tumors were highly microsatellite-instable (MSI-high), in one case associated to Lynch-syndrome. We did not find any gene fusions.

Conclusion: Our results underscore, in particular, the relevance of potentially treatable molecular alterations (like ERBB2, BRCA and MSI) in small bowel carcinomas. Further studies are needed to proof the efficacy of these targeted therapies in small bowel carcinomas.
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http://dx.doi.org/10.1186/s12876-019-0942-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360678PMC
February 2019

Hyperplastic polyps and nonadvanced adenomas, but not advanced polypoid lesions, are detected more frequently in the presence of colonic diverticula during screening colonoscopies.

Z Gastroenterol 2018 Dec 10;56(12):1475-1480. Epub 2018 Dec 10.

Department of Gastroenterology and Hepatology, University Hospital Cologne, Germany.

Hintergrund:  Die bisher veröffentlichte Studienlage zur Assoziation von Kolondivertikeln und kolorektalen Polypen einschließlich des kolorektalen Karzinoms (KRK) ist konträr. Ziel der Studie war es, die Assoziation für sämtliche relevanten histologischen Polypensubtypen, d. h. hyperplastische Polypen (HP), sessil und traditionell serratierte Adenome (SSA und TSA), klinisch relevante serratierte Polypen (krSP), tubuläre Adenome und fortgeschrittene Adenome in einer ausschließlichen Vorsorgekoloskopie-Kohorte zu untersuchen.

Material Und Methoden:  Wir führten eine retrospektive Analyse von Personen ≥ 50 Jahre und einem durchschnittlichen Risiko für ein KRK, die eine Vorsorgekoloskopie zwischen dem 01.01.2012 und dem 14.12.2016 in einer Universitätsklinik und 6 gastroenterologischen Schwerpunktpraxen erhalten haben, durch. Ausschlusskriterien waren Erkrankungen mit einem erhöhten KRK-Risiko (z. B. chronisch-entzündliche Darmerkrankungen, KRK in der Vorgeschichte, hereditäre Karzinomsyndrome), eine vorherige Koloskopie und eine unvollständige Untersuchung.

Ergebnisse:  4196 Koloskopien wurden eingeschlossen (mittleres Alter 63,4 Jahre, Standardabweichung ± 7,6 Jahre, 48,6 %). Bei Vorliegen von Divertikeln zeigten sich nach Adjustierung für Alter und Geschlecht erhöhte Odds-Ratios (OR) für den Nachweis von HP im gesamten (OR 1,340, 95 %-Konfidenzintervall 1,133 - 1,584, p = 0,001) und im distalen Kolon (OR 1,459, 95 %-KI 1,208 - 1,763, p < 0,001) sowie von tubulären Adenomen im distalen Kolon (OR 1,355, 95 %-KI 1,144 - 1,604, p < 0,001). Die mittlere Polypenanzahl pro Untersuchung mit dem Nachweis von mindestens einem Polypensubtypen unterschied sich nicht zwischen beiden Gruppen.

Schlussfolgerung:  Die Untersucher sollten beim Vorliegen einer Divertikulose wachsam für den Nachweis von vor allem distal gelegenen Adenomen sein.
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http://dx.doi.org/10.1055/a-0755-2448DOI Listing
December 2018

Postoperative granulomatous peritonitis mimicking abdominal tuberculosis.

Clin Case Rep 2018 Sep 25;6(9):1810-1814. Epub 2018 Jul 25.

Department I of Internal Medicine University Hospital of Cologne Cologne Germany.

Granulomatous peritonitis represents a rare postoperative complication that should be considered as important differential diagnosis in all patients who present to the hospital with abdominal pain, abdominal tenderness, and fever after abdominal surgery. Clinical distinction from abdominal tuberculosis remains a diagnostic challenge and requires thorough histopathological and microbiological examination.
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http://dx.doi.org/10.1002/ccr3.1724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132106PMC
September 2018

Varioliform gastritis: an unusual endoscopic finding.

Ann Gastroenterol 2018 Jul-Aug;31(4):520. Epub 2018 May 25.

Department of Gastroenterology and Hepatology (Philipp Kasper, Tobias Goeser), University Hospital of Cologne, Germany.

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http://dx.doi.org/10.20524/aog.2018.0279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033768PMC
May 2018
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