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Introduction: A substantial interobserver variation in the differential diagnosis of hyperplastic polyps (HPs) and sessile or traditional serrated adenomas (SSAs/TSAs) has been described. Methods: The aim of this study is to determine the magnitude of reclassification of HPs and associated factors after pathological reassessment of specimens from screening and surveillance colonoscopies, and to estimate its consequences for follow-up recommendations. Results: Among 1694 screening and surveillance colonoscopies, a total of 536 polyps were initially diagnosed as HPs and remained unchanged in 88.5 % ( n = 474), whereas 7.6 ( n = 41) and 1.1 % ( n = 6) were reclassified as SSA and TSA, respectively. Compared to definite HPs, SSAs were found more frequently in men than in women (82.9 vs. 61.2 %, p < 0.05), and in individuals ≥65.0 years (51.2 vs. 31.6 %, p = 0.05). Also, more SSAs were >5 mm in size (36.6 vs. 6.3 %, p < 0.05) and were localized in the proximal colon (31.7 vs. 11.8 %, p < 0.05). In a mixed model analysis, age ≥65.0 years (OR 4.13, 95 % CI 1.22-14.2), snare polypectomy (OR 23.6, 95 % CI 4.86-115), and coincident advanced adenomas (OR 7.56, 95 % CI 1.31-43.5) were significantly ( p < 0.05) associated with reclassification to SSAs. Only 0.53 % of patients had received false recommendations for follow-up visits based on the incorrect HP diagnosis. A c.1799T>A, p.V600E BRAF mutation was detected in 21.9 % ( n = 9) of reclassified SSAs. Conclusion: Considering these factors may be helpful in serrated lesions that are difficult to allocate. Incorrect recommendations regarding control colonoscopy intervals due to misdiagnosed HPs can explain only a small fraction of interval colorectal cancers. [ABSTRACT FROM AUTHOR]

Alcohol‐associated liver disease is the primary cause of liver‐related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic hepatitis represents the most acute and severe manifestation of alcohol‐associated liver disease and is characterized by a rapid onset of jaundice with progressive inflammatory liver injury, worsening of portal hypertension, and an increased risk for multiorgan failure in patients with excessive alcohol consumption. Severe alcoholic hepatitis is associated with a poor prognosis and high short‐term mortality. During the COVID‐19 pandemic, rates of alcohol‐associated hepatitis have increased significantly, underscoring that it is a serious and growing health problem. However, adequate management of alcohol‐associated hepatitis and its complications in everyday clinical practice remains a major challenge. Currently, pharmacotherapy is limited to corticosteroids, although these have only a moderate effect on reducing short‐term mortality. In recent years, translational studies deciphering key mechanisms of disease development and progression have led to important advances in the understanding of the pathogenesis of alcoholic hepatitis. Emerging pathophysiology‐based therapeutic approaches include anti‐inflammatory agents, modifications of the gut‐liver axis and intestinal dysbiosis, epigenetic modulation, antioxidants, and drugs targeting liver regeneration. Concurrently, evidence is increasing that early liver transplantation is a safe treatment option with important survival benefits in selected patients with severe alcoholic hepatitis not responding to medical treatment. This narrative review describes current pathophysiology and management concepts of alcoholic hepatitis, provides an update on emerging treatment options, and focuses on the need for holistic and patient‐centred treatment approaches to improve prognosis. [ABSTRACT FROM AUTHOR]

Background: Cronkhite-Canada syndrome is a rare disease of unknown etiology and the optimal treatment for this syndrome is unknown.Case Presentation: We present the case of a man who at the age of 66.0 years was diagnosed with Cronkhite-Canada syndrome (CCS). In addition to watery diarrhea, alopecia, and a complete loss of toenails and fingernails, the patient had been suffering from dysgeusia and rapid weight loss of more than 10.0 kg within a few months. The patient had recently incurred a distal radius fracture. During the initial endoscopy an extensive polyposis of the stomach and jejunum was found. The diagnosis of CCS was made and after initiation of a steroid therapy his diarrhea improved immediately. A discontinuation of the steroid therapy was not possible and mesalazine (1000 mg t.i.d.) was added to prednisolone (10.0 mg/d). This therapy led to a remission within 6.0 months with weight gain and normalization of serum albumin levels. The prednisolone dose was reduced to 7.5 mg/d. During the following year, the steroids could be further reduced and nails had regrown again. Within three years, all polyps had disappeared and the steroid therapy was finished while the dosage of mesalazine was reduced in a stepwise fashion. Four years later, the mesalazine was stopped and more than 14.0 years after the initial diagnosis the patient is still in complete remission without any treatment.Conclusion: The optimal treatment for CCS is unknown. In our case, the initial combination therapy of corticosteroids plus mesalazine followed by a mesalazine monotherapy has led to a remarkable long-lasting remission with complete resolution of all intestinal polyps. [ABSTRACT FROM AUTHOR]

A letter to the editor about the article "ACE Inhibitors after Myocardial Infarction," in the September 3, 1992 issue is presented.

In this cross-sectional study, we hypothesized that a high dietary ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids could be associated with an altered gut bacterial composition and with the disease severity in patients with nonalcoholic fatty liver disease (NAFLD). A total of 101 NAFLD patients were included in the study, of which 63 underwent a liver biopsy. All 101 patients completed a 14-day food and activity record. Ebispro 2016 professional software was used to calculate individual macronutrients and micronutrients consumed. Patients were grouped into 3 quantiles (Q) according to a low (Q1: <6.1, n = 34), moderate (Q2: 6.1-7.8, n = 33), or high (Q3: >7.8, n = 34) dietary n-6/n-3 ratio. Stool samples were analyzed using 16S rRNA gene sequencing. Spearman correlation coefficients and principal coordinate analysis were used to detect differences in the bacterial composition of the gut microbiota. The median dietary n-6/n-3 ratio of all patients was 6.7 (range, 3.1-14.9). No significant associations between the dietary n-6/n-3 ratio and the gut microbiota composition or disease severity were observed. However, the abundance of specific bacteria such as Catenibacterium or Lactobacillus ruminis were found to be positively correlated and the abundance of Clostridium were negatively correlated with dietary n-6 fatty acid intake. The results indicate that a high dietary n-6/n-3 ratio is probably not a highly relevant factor in the pathogenesis of human NAFLD. Further studies are needed to clarify the importance of interactions between gut bacterial taxa and n-6 fatty acids in the pathophysiology of NAFLD. Patients with nonalcoholic fatty liver disease consume a high proportion of dietary omega-6 polyunsaturated fatty acids (n-6 PUFAs). We did not detect significant associations between a high dietary n-6/n-3 PUFA ratio and histological disease severity or the gut microbiota composition. On the other hand, we could observe correlations between the dietary n-6 PUFA intake and the abundance of specific gut bacterial taxa. Only bacterial taxa with highly significant correlations are displayed (P <.01). [Display omitted] [ABSTRACT FROM AUTHOR]

Studies investigating the gut-liver axis have largely focused on bacteria, whereas little is known about commensal fungi. We characterized fecal fungi in patients with non-alcoholic fatty liver disease (NAFLD) and investigated their role in a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis. We performed fungal internal transcribed spacer 2 sequencing using fecal samples from 78 patients with NAFLD, 16 controls and 73 patients with alcohol use disorder. Anti- Candida albicans (C. albicans) IgG was measured in blood samples from 17 controls and 79 patients with NAFLD. Songbird, a novel multinominal regression tool, was used to investigate mycobiome changes. Germ-free mice were colonized with feces from patients with non-alcoholic steatohepatitis (NASH), fed a Western diet for 20 weeks and treated with the antifungal amphotericin B. The presence of non-obese NASH or F2-F4 fibrosis was associated with a distinct fecal mycobiome signature. Changes were characterized by an increased log-ratio for Mucor sp./ Saccharomyces cerevisiae (S. cerevisiae) in patients with NASH and F2-F4 fibrosis. The C. albicans/S. cerevisiae log-ratio was significantly higher in non-obese patients with NASH when compared with non-obese patients with NAFL or controls. We observed a different fecal mycobiome composition in patients with NAFLD and advanced fibrosis compared to those with alcohol use disorder and advanced fibrosis. Plasma anti- C. albicans IgG was increased in patients with NAFLD and advanced fibrosis. Gnotobiotic mice, colonized with human NASH feces and treated with amphotericin B were protected from Western diet-induced steatohepatitis. Non-obese patients with NAFLD and more advanced disease have a different fecal mycobiome composition to those with mild disease. Antifungal treatment ameliorates diet-induced steatohepatitis in mice. Intestinal fungi could be an attractive target to attenuate NASH. Non-alcoholic fatty liver disease is one of the most common chronic liver diseases and is associated with changes in the fecal bacterial microbiome. We show that patients with non-alcoholic fatty liver disease and more severe disease stages have a specific composition of fecal fungi and an increased systemic immune response to Candida albicans. In a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis, we show that treatment with antifungals reduces liver damage. [Display omitted] • More advanced disease severity in non-alcoholic fatty liver disease is associated with a specific composition of fecal fungi. • Changes are particularly present in non-obese patients. • Systemic antibodies against Candida albicans are increased in patients with non-alcoholic fatty liver disease and advanced fibrosis. • Antifungals protect germ-free fecal microbiome-humanized mice from Western diet-induced steatohepatitis. [ABSTRACT FROM AUTHOR]

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/m2: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Acute decompensation (AD) in patients with liver cirrhosis is associated with a dramatic deterioration in prognosis. Immediate initiation of appropriate recompensation measures is essential to improve patient's outcome, although objective parameters for evaluating the success of recompensation are still lacking. Spleen stiffness measurements (SSM) have emerged as promising non-invasive tool to assess clinically significant portal hypertension (CSPH), which is the main driver of acute decompensation. However, while SSM accurately predicts CSPH and its complication, currently no data are available on its diagnostic performance during recompensation. This pilot-study aimed at evaluating changes in spleen stiffness following the initiation of recompensation measures in cirrhotic patients hospitalized due to AD., Methods: In this prospective pilot-study, 60 patients with cirrhosis showing AD were included. Liver stiffness measurements (LSM) and SSM were performed on admission and repetitive SSM on day 3 and 5, respectivele, during recompensation measures. A cohort of patients ( n  = 10) with compensated cirrhosis served as control., Results: A total of 36 data sets from the originally enrolled 60 patients were eligible for final analysis. On admission, patients with AD revealed a significantly increased spleen stiffness compared to the control group (70.51 vs. 29.06 kPa, p  < 0.0001). Following the initiation of recompensation measures SSM revealed a significant reduction in spleen stiffness compared to the baseline assessment on day 3 (-18.5 kPa, -21.53%; p  = 0.0002) with no further decrease on day 5 (-17.63 kPa, -21.23%; p  = 0.0326)., Conclusion: Repetitive SSM seems to be a useful non-invasive clinical marker to assess the effectiveness of recompensation measures in cirrhotic patients with AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gülcicegi, Hannemann, Bürger, Allo, Dittmann, Martin, Jaspers, Holzapfel, Chon, Lang, Goeser, Steffen and Kasper.)

Background: Sub-Saharan Africa is one of the regions in the world with the highest numbers of uncontrolled hypertension as well as people living with HIV/AIDS (PLHIV). However, the association between hypertension and antiretroviral therapy is controversial., Methods: Participant demographics, medical history, laboratory values, WHO clinical stage, current medication, and anthropometric data were recorded at study entry and during study visits at 1, 3, 6 months, and every 6 months thereafter until month 36. Patients who stopped or changed their antiretroviral therapy (tenofovir, lamivudine, efavirenz) were censored on that day. Office blood pressure (BP) was categorized using ≥ 2 measurements on ≥ 2 occasions during the first three visits. Factors associated with systolic and mean BP were analyzed using bivariable and multivariable multilevel linear regression., Results: 1,288 PLHIV (751 females, 58.3%) could be included and 832 completed the 36 months of observation. Weight gain and a higher BP level at study entry were associated with an increase in BP (p < 0.001), while female sex (p < 0.001), lower body weight at study entry (p < 0.001), and high glomerular filtration rate (p = 0.009) protected against a rise in BP. The rate of uncontrolled BP remained high (73.9% vs. 72.1%) and despite indication treatment, adjustments were realized in a minority of cases (13%)., Conclusion: Adherence to antihypertensive treatment and weight control should be addressed in patient education programs at centers caring for PLHIV in low-resources settings like Malawi. Together with intensified training of medical staff to overcome provider inertia, improved control rates of hypertension might eventually be achieved., Trial Registration: NCT02381275., (© 2023. The Author(s).)

Background and Aims: Hepatocellular carcinoma (HCC) surveillance in patients at risk is strongly recommended and usually performed by ultrasound (US) semiannually with or without alfa-fetoprotein (AFP) measurements. Quality parameters except for surveillance intervals have not been strictly defined. We aimed to evaluate surveillance success and risk factors for surveillance failure., Methods: Patients with ≥1 US prior to HCC diagnosis performed at four tertiary referral hospitals in Germany between 2008 and 2019 were retrospectively analyzed. Surveillance success was defined as HCC detection within Milan criteria., Results: Only 47% of 156 patients, median age 63 (interquartile range: 57-70) years, 56% male, and 96% with cirrhosis, received recommended surveillance modality and interval. Surveillance failure occurred in 29% and was significantly associated with lower median model for end-stage liver disease (MELD) score odds ratio (OR) 1.154, 95% confidence interval (CI): 1.027-1.297, p =0.025) and HCC localization within right liver lobe (OR: 6.083, 95% CI: 1.303-28.407, p =0.022), but not with AFP ≥200 µg/L. Patients with surveillance failure had significantly more intermediate/advanced tumor stages (93% vs. 6%, p <0.001), fewer curative treatment options (15% vs. 75%, p <0.001) and lower survival at 1 year (54% vs. 75%, p =0.041), 2 years (32% vs. 57%, p =0.019) and 5 years (0% vs. 16%, p =0.009). Alcoholic and non-alcoholic fatty liver disease (OR: 6.1, 95% CI: 1.7-21.3, p =0.005) and ascites (OR: 3.9, 95% CI: 1.2-12.6, p =0.021) were independently associated with severe visual limitations on US., Conclusions: US-based HCC surveillance in patients at risk frequently fails and its failure is associated with unfavorable patient-related outcomes. Lower MELD score and HCC localization within right liver lobe were significantly associated with surveillance failure., Competing Interests: MB has obtained travel support from Pfizer. FF, PR, GA, HMS, JG, DN, MR, LL, FK, MN, PH, CS have no conflict of interests related to this publication., (© 2023 Authors.)

Purpose of Review: Patients with non-alcoholic fatty liver disease (NAFLD), often considered as the hepatic manifestation of the metabolic syndrome, represent a population at high cardiovascular risk and frequently suffer from atherogenic dyslipidemia. This article reviews the pathogenic interrelationship between NAFLD and dyslipidemia, elucidates underlying pathophysiological mechanisms and focuses on management approaches for dyslipidemic patients with NAFLD., Recent Findings: Atherogenic dyslipidemia in patients with NAFLD results from hepatic and peripheral insulin resistance along with associated alterations of hepatic glucose and lipoprotein metabolism, gut dysbiosis, and genetic factors. Since atherogenic dyslipidemia and NAFLD share a bi-directional relationship and are both major driving forces of atherosclerotic cardiovascular disease (ASCVD) development, early detection and adequate treatment are warranted. Thus, integrative screening and management programs are urgently needed. A stepwise approach for dyslipidemic patients with NAFLD includes (i) characterization of dyslipidemia phenotype, (ii) individual risk stratification, (iii) definition of treatment targets, (iv) lifestyle modification, and (v) pharmacotherapy if indicated., (© 2022. The Author(s).)

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., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

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.

Bacteria, archaeae, fungi and viruses of the intestinal microbiome play an important role as symbionts in the complex human ecosystem. Parasites, which account for about 40 % of the earth's biodiversity, depend on hosts to complete their life cycle. This article explains how they use them and which signalling pathways play a role in this, using toxoplasmosis and malaria as examples. The parasitic manipulation hypothesis is based on impressive observations in the wild and under laboratory conditions, especially in invertebrates. For the assumption of an adaptive manipulation, every step from the genotype, the translated messenger, and its source via the used signalling pathways to the altered host behaviour must be proven. The assumption of an adaptive manipulation of humans by T. gondii in the sense of a cause-effect relationship is not proven. Alternative explanations include the inflammatory and immunological processes on the host side, which change the neuronal signal transduction as concomitant symptoms of an infection. Even without confirmation of parasitic manipulation in humans, it could be worthwhile to further investigate the observed associations in order to develop new possibilities for diagnosis and therapy, e. g. for schizophrenia., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

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., (Published by Elsevier Inc.)

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.

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.

Aging, physical activity, bodyweight and diet are well established risk factors for cardiovascular disease. For all of these factors a great impact on the intestinal microbiome has been described. The current review will discuss available data regarding the role of the gut microbiome in regulating blood pressure, vascular function and its possible contribution to atherosclerosis and heart failure., Competing Interests: Die Autoren haben Reisekostenerstattungen und Vortragshonorare von der Hypertonie Akademie der Deutschen Gesellschaft für Hypertonie und Prävention erhalten., (© Georg Thieme Verlag KG Stuttgart · New York.)

Clinical guidelines are essential in implementing and maintaining nationwide stage-specific diagnostic and therapeutic standards. In 2015, the first German expert consensus guideline defined the evidence for epidemiology, pathogenesis, diagnosis and treatment of non-alcoholic fatty liver diseases in adults and children. The German S2k-guideline used an approved development process with de novo literature research since 2010, international guideline adaptation, or good clinical practice. Other recent evidence-based national guidelines and current references were included., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aberrant activation of plasmacytoid dendritic cells (pDCs) with excessive production of interferon alpha (IFNα) represents one of the hallmarks of immune activation during chronic phase of human immunodeficiency virus (HIV) infection. A number of studies have shown that disruption of mucosal integrity in the gut is a cause of persistent immune activation. However, little is known about the role that pDCs play in this process, and our current understanding comes from the simian immunodeficiency virus macaque model. Thus, in the present study we sought to investigate the frequency and function of pDCs in peripheral blood and gut samples from HIV-infected individuals before and 6 months after initiation of antiretroviral therapy (ART). We show that circulating pDCs were depleted in ART-naive HIV+ patients, and upregulated the gut-homing receptor CD103 compared with uninfected controls. By converse, pDCs accumulated in the terminal ileum of ART-naive HIV individuals compared with controls. Baseline levels of IFNα production and markers of immune activation in gut samples of ART-naive HIV subjects were elevated. All these parameters declined after 6 months of ART. Our results suggest that in chronic HIV infection, pDCs migrate from peripheral blood to the gut-associated lymphatic tissue, where they may contribute to immune activation.

Background and Aim: Current methods for visualization of the blood vasculature, biliary tree and for isolation of vital cholangiocytes are afflicted with a plethora of technical difficulties, especially in mice. In this project, we propose a novel, reliable and straightforward alternative technique for histological demonstration of blood- and biliary systems and derivation of vital cholangiocytes., Methods: Intravital retrograde perfusion of bile ducts was performed in twenty wild type mice. Liver and gallbladder were exposed by median laparotomy. Using a venous catheter, the gallbladder was cannulated, a few millimeters of the liver edge were cropped to allow free outflow of the perfusate, and carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) solution was retrogradely infused. Thereafter, formaldehyde solution was either injected through the same catheter, or the liver was immediately dissociated into a single-cell suspension for FACS-analysis. Intravital perfusion of the vascular system was performed in ten Lewis rats by direct intra-arterial injection of CFDA-SE into the abdominal aorta. The specificity and sensitivity of CFDA-SE labeling was controlled using Indian ink or cytokeratin 19 immunohistochemistry respectively., Results: Upon histomorphological analysis of cryo- and paraffin sections, strong fluorescence was noted in large and small bile ducts throughout the entire liver and in the vascular system after infusion of the CFDA-SE solution. In preliminary FACS-experiments, we succeeded in separating cholangiocytes based on combined CFDA-SE-staining and cell size., Conclusions: Visualization of liver architecture and the isolation of cholangiocytes is feasible using a fast and cost-effective method of retrograde perfusion and vital fluorescent labeling of mouse bile duct epithelium and vascular endothelium with CFDA-SE.

Background/aims: Ribavirin has favorable immune-modulating effects in patients with hepatitis C. Therefore, a ribavirin monotherapy preceding the combination of peginterferon plus ribavirin may be beneficial. We conducted a pilot study with a sequential regimen using a reduced dosage of peginterferon-alfa 2b in patients with chronic hepatitis C and normal transaminases., Methodology: Twenty patients (17 genotype 1, 3 genotype 2/3) were treated with ribavirin for 4 wk followed by ribavirin plus peginterferon-alfa 2b 100 microg for 4 wk and ribavirin plus peginterferon-alfa 2b 50 microg for 44 wk. TH1-cytokines interferon-gamma and interleukin-2, and TH2-cytokines interleukin-4 and interleukin-10 were measured in the supernatant from PHA-stimulated lymphocytes., Results: Sustained viral response defined as negative HCV-RNA after follow up was 50%, 41%, and 100% for all patients, genotype 1, and genotype 2/3, resp. The increase in interferon-gamma following ribavirin monotherapy was significantly higher for patients with sustained viral response., Conclusions: The sustained viral response rate of this pilot study using ribavirin priming and reduced peginterferon dosage is in line with previous trials using standard treatment regimens for chronic hepatitis C. Our data stress the positive impact of the ribavirin-induced TH2-TH1 cytokine shift at least in patients with normal ALT. Larger clinical studies with ribavirin priming seem warranted.