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…

Hepatitis viruses: live and let die.

Viral hepatitis is a diffuse inflammatory reaction of the liver caused by hepatotropic viruses. Among the hepatitis viruses, only hepatitis B virus and hepatitis C virus are able to persist in the host and cause chronic hepatitis. In the course of persistent infection, inflammation forms the pathogenetic basis of chronic hepatitis that can lead to nodular fibrosis, which can progress to cirrhosis and, eventually, hepatocellular carcinoma (HCC). Of the different antiviral defense systems employed by the host, apoptosis significantly contributes to the prevention of viral replication, dissemination, and persistence. Pathomorphologic studies have shown acidophilic bodies and hepatocyte dropout…

O100 : The hepatic microenvironment induces a CSC phenotype and determines the prognosis of HCC patients

Pathogenic lipid‐binding antiphospholipid antibodies are associated with severity of COVID‐19

Abstract Background Coronavirus disease 19 (COVID‐19)–associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome—microvascular thrombosis, stroke, and venous and pulmonary clots—are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID‐19 patients, but their association with the clinical course of COVID‐19 remains unproven. Objectives To analyze the presence and relevance of lipid‐binding aPL in hospitalized COVID‐19 patients. Methods Two cohorts of 53 and 121 patients from a single center hospitalized for PCR‐proven severe acute respiratory syndro…

Sorafenib perpetuates cellular anti-cancer effector functions by modulating the cross talk between macrophages and natural killer cells.

Alternatively polarized macrophages (Mϕ) shape the microenvironment of hepatocellular carcinoma (HCC) and temper anticancer immune responses. We investigated if sorafenib alters the HCC microenvironment by restoring classical macrophage polarization and triggering tumor-directed natural killer (NK) cell responses. In vivo experiments were conducted with sorafenib (25 mg/kg)-treated C57BL/6 wildtype as well as hepatitis B virus (HBV) and lymphotoxin transgenic mice with and without HCC. Monocyte-derived Mϕ or tumor-associated macrophages (TAM) isolated from HCC tissue were treated with sorafenib (0.07-5.0 μg/mL) and cocultured with autologous NK cells. Mϕ and NK cell activation was analyzed …

Interferon- and ribavirin-free therapy with new direct acting antivirals (DAA) for chronic hepatitis C improves vascular endothelial function.

Abstract Introduction Chronic Hepatitis C virus infection (HCV) is associated with extrahepatic manifestations and an increased prevalence in cardiovascular disease. New direct acting antivirals (DAA) have revolutionized HCV treatment with high rates of sustained virological response (SVR). Recently it was demonstrated, that SVR reduces morbidity and overall mortality more than can be solely explained by hepatic effects, suggesting that treatment with DAA also affects cardiovascular disease. The aim of this pilot study was to identify possible underlying mechanisms behind the HCV-associated cardiovascular mortality reported by others. Methods and results 20 HCV patients (10 genotype GT1, 10…

Hepatitis C virus re-infection: new perspectives

Hepatitis C virus (HCV) re-infection of the liver graft has been recognized to be one of the most important factors that determines prognosis and outcome after liver transplantation in HCV-positive patients. Graft loss due to recurrent HCV re-cirrhosis and subsequent hepatic decompensation, which is the predominant cause of death among transplant recipients, reflects the prognostic significance of HCV re-infection. Despite better overall outcome after liver transplantation, the prognosis of HCV-infected patients has not improved during the last two decades. Recent data suggest that increased liver donor age and intensified immunosuppression of transplant patients are the most important cont…

Hepatitis B virus-specific T-cell responses during IFN administration in a small cohort of chronic hepatitis B patients under nucleos(t)ide analogue treatment.

The effect of pegylated interferon-α (IFN) add-on therapy on HBV-specific T-cell responses was evaluated in 12 patients with stable, undetectable hepatitis B virus (HBV) load under nucleos(t)ide analogue therapy. Peripheral blood mononuclear cells were isolated at week 0, 4, 8, 12, 24 and 48 of IFN add-on therapy. Quantity and quality of circulating HBV S- and core-specific CD4 and CD8 T cells were analysed ex vivo by flow cytometry. HBV S- and core-specific CD4 T-cell numbers modestly increased within 8 weeks of IFN administration (P = 0.0391 and P = 0.0195), whereas HBV-specific CD8 T cells in general showed only minor changes under IFN add-on therapy. Functionality of HBV-specific CD4 bu…

Portal vein infiltration in patients with hepatocellular carcinoma: The relevance of correct classification.

e15651 Background: Portal vein invasion (PVI) is has a significant impact on the prognosis of patients with hepatocellular carcinoma (HCC). Patients with PVI are classified as stage C in the BCLC score and systemic therapy is recommended. Patients with minor PVI are frequently misclassified due to radiological challenges in determining malignant PVI or non-adherence to guidelines. The concept of resection or TACE in limited PVI is sometimes followed with the assumption of a negligible influence on survival. Aim of this study is the reevaluation of PVI and the analysis of the impact of a misclassification. Methods: 763 patients with HCC of a total of 1413 were extracted from the clinical re…

Risk Factors in Patients With Rapid Recurrent Hepatitis C Virus–Related Cirrhosis Within 1 Year After Liver Transplantation

Abstract Background Recurrent cirrhosis (RC) due to pretransplant underlying disease leads to organ failure and subsequent death after orthotopic liver transplantation (OLT). RC occurs in up to 30% of patients with recurrent hepatitis C (HCV) within 5 years after OLT. We sought to identify early risk factors for rapid RC within the first year after OLT in HCV-positive patients. Methods Among 404 liver transplanted patients at the University of Mainz between 1998 and 2008, 90 were HCV-RNA positive. To identify predictive factors for rapid RC, we compared HCV-positive patients with advanced fibrosis stages within 1 year after OLT ( n = 13) with these without RC at 5 years after OLT ( n = 23).…

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 …

Epidemiologie und Auswirkungen bakterieller Infektionen bei stationären Patienten mit Leberzirrhose

Improved prediction of survival by a risk factor-integrated inflammatory score in Sorafenib treated hepatocellular carcinoma

Background and aims Inflammation affects progression of hepatocellular carcinoma (HCC). We therefore postulate that systemic inflammatory markers could help to predict prognosis in HCC patients receiving sorafenib therapy. Methods Overall survival (OS) of HCC patients receiving palliative sorafenib treatment was correlated with the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and the modified GPS (mGPS) along with clinicopathological parameters. Predictors of OS were assessed by multivariable Cox regression and receiver operating characteristics and area under the curve (ROC-AUC) analyses.…

Evidence for the utility of cfDNA plasma concentrations to predict disease severity in COVID-19

AbstractCOVID-19 is a pandemic caused by the highly infective SARS-CoV-2. There is a need for biomarkers not only for overall prognosis but also for predicting the response to treatments and thus for improvements in the clinical management of patients with COVID-19. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker in the assessment of various disease conditions. The aim of this retrospective and observational pilot study was to examine the potential value of cfDNA plasma concentrations as a correlative biomarker in hospitalized COVID-19 patients. Lithium-Heparin plasma samples were obtained from twenty-one COVID-19 patients during hospitalization in the University Medi…

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…

COVID-19 as a Potential Trigger for Immune Thrombotic Thrombocytopenic Purpura and Reason for an Unusual Treatment: A Case Report

AbstractImmune thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder characterized by severely reduced activity of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) due to autoantibodies. This leads to the development of pathogenic multimers of VWF, causing a thrombotic microangiopathy with decreased number of platelets, hemolysis, and life-threatening tissue ischemia of mostly brain, heart, and kidneys. Standard treatment of iTTP involves daily plasma exchange to remove ultra large multimers of VWF, inhibitors, substituting ADAMTS13, and the accompaniment of an immunosuppressive …

Consensus interferon and ribavirin for patients with chronic hepatitis C and failure of previous interferon-alpha therapy.

BACKGROUND The efficacy of consensus interferon (CIFN), a synthetic IFN with optimised in vitro activity, was assessed in chronic hepatitis C virus (HCV) patients who had failed the pretreatment with interferon-alpha (IFNalpha) and ribavirin. METHODS One hundred and three patients after non-response (n=69) or relapse (n=34) to IFNalpha+/-ribavirin were randomly assigned to high-dose induction (CIFN 27-->9 microg daily for 24 weeks, 9 microg t.i.w. for 24 weeks) or low-dose treatment (CIFN 18 microg t.i.w. for 12 weeks, 9 microg t.i.w. for 36 weeks); each with ribavirin 800 mg/day. Follow-up was 24 weeks. RESULTS Non-responder patients treated with high-dose induction had higher early virolo…

Construction of Recombinant Adenoviruses that Produce Infectious Hepatitis B Virus

Metabolic syndrome and its association with fatty liver disease after orthotopic liver transplantation

The metabolic syndrome (MetS) might contribute to morbidity after orthotopic liver transplantation (OLT). For this reason, we searched for MetS-associated risk factors and analyzed the link with nonalcoholic fatty liver disease (NAFLD) in OLT recipients. De novo MetS affected 32.9% of our cohort (n = 170) within 2 years after OLT. Multivariate analysis identified glycosylated hemoglobin (HbA1c) levels ≥5% [odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.56-8.13, P = 0.003], diabetes mellitus (OR = 4.31, CI = 1.69-10.99, P = 0.002), and arterial hypertension (OR = 4.59, CI = 1.46-14.49, P = 0.009) as independent risk factors for de novo MetS. MetS incidence correlated with steroid do…

High pretreatment static and dynamic alpha‐fetoprotein values predict reduced overall survival in hepatocellular carcinoma

Abstract Background Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha‐fetoprotein (AFP) is a well‐established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static AFP values is limited and the clinical potential is a matter of ongoing scientific discussion. Objective We here evaluated the prognostic impact of pretreatment static and dynamic AFP variables on overall survival of hepatocellular carcinoma patients in a Western cohort. Methods Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenber…

Ablation of c-FLIP in hepatocytes enhances death-receptor mediated apoptosis and toxic liver injury in vivo

Background & Aims Apoptosis is crucially involved in acute and chronic liver injury, including viral, cholestatic, toxic, and metabolic liver disease. Additionally, dysregulation of apoptosis signaling pathways has been implicated in hepatocarcinogenesis. The most prominent members of the apoptosis-mediating tumor necrosis factor receptor superfamily are the TNF-R1 (CD120a) and the CD95 (Apo-1/Fas) receptor. Although extensively studied, the intracellular signaling events in hepatocytes are only incompletely understood. Methods To examine the role of the caspase-8 homolog cellular FLICE-inhibitory protein (c-FLIP) in liver injury, we generated mice with hepatocyte specific deletion of c-FLI…

Differential diagnosis of human hepatitis

There is a variety of differential diagnoses of acute and chronic human hepatitis regularly seen in clinical praxis. Risk factor assessment for specific entities provides important information and should guide individual diagnostic procedures. Liver screening tests often remain the first indicator for hepatic pathologies and should include quantification of liver enzymes, liver function parameters and cholestatic parameters. Nevertheless, virus serology should always be done during further laboratory evaluation. To estimate the parenchymal liver damage and to exclude biliary obstruction or hepatic lesions an abdominal ultrasound scan is essential. A liver biopsy may complete the diagnostic …

Immune Control in Hepatocellular Carcinoma Development and Progression: Role of Stromal Cells

Immune control of hepatocellular carcinoma (HCC) is executed by effector immune cells, which efficiently eliminate malignant transformed cells. However, progression of HCC clearly documents failure of tumor immune control, which led to the concept of immune subversion by the tumor environment. Particularly tumor-associated stromal cells cooperate within an inflammatory network, which is responsible for immune privilege. The stromal cell composition matures during tumor growth and is derived from surrounding noncancerous tissue or from circulating cells recruited to the tumor site. Therefore, immunosuppressive stromal cells represent heterogeneous cell lineages, including myeloid cells, lymp…

Facing the dawn of immunotherapy for hepatocellular carcinoma.

In this study, administration of tremelimumab was accompanied by a tolerable toxicity profile, most frequently including skin rash (65%), fatigue (55%), and anorexia (50%). During the initial course of tremilimumab, a transient increase of serum transaminase activity was observed. Hepatotoxicity did not impair liver function, even in the context of Child-Pugh B cirrhosis and hepatitis C. Therapy was stopped in 3 patients before tumor response evaluation was completed due to tremilimumab-related diarrhea or clinical deterioration, which was not associated with the treatment regimen. The relevance of this study is strengthened by the inclusion of HCC patients, showing hepatitis C associated c…

Early changes in dynamic biomarkers of liver fibrosis in hepatitis C virus-infected patients treated with sofosbuvir

Abstract Background Chronic hepatitis C is a major cause of liver-associated mortality caused by decompensated cirrhosis and hepatocellular carcinoma. With the approval of sofosbuvir, therapeutic efficacy has markedly increased. Early changes in non-invasive biomarkers of liver fibrosis under effective antiviral therapy are widely unknown. Aim To evaluate early changes of fibrosis markers determined by enhanced liver fibrosis (ELF) scores and liver stiffness measurement (FibroScan®) in patients treated with sofosbuvir. Methods A total of 32 hepatitis C patients treated prospectively with sofosbuvir were included. The ELF-panel and FibroScan measurements were performed at baseline, week 4, e…

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…

Survival analysis of proposed BCLC-B subgroups in hepatocellular carcinoma patients

Background & Aims The BCLC-staging system is used to facilitate treatment decisions in patients with hepatocellular carcinoma (HCC). Owing to the observed clinical heterogeneity of the intermediate stage BCLC-B, a subclassification was proposed taking Child–Pugh score and extended criteria for transplantation into account. Analysis of the prognostic significance of a proposed subclassification of the BCLC-B score in a European cohort of HCC patients. Methods Eight hundred and eighty four consecutive HCC patients were retrospectively analysed. Patients with stage BCLC-B were grouped according to the proposed subclassification. Baseline patient and tumour characteristics, therapy and overall …

T cells engineered to express a T-cell receptor specific for glypican-3 to recognize and kill hepatoma cells in vitro and in mice

Background & Aims Cancer therapies are being developed based on our ability to direct T cells against tumor antigens. Glypican-3 (GPC3) is expressed by 75% of all hepatocellular carcinomas (HCC), but not in healthy liver tissue or other organs. We aimed to generate T cells with GPC3-specific receptors that recognize HCC and used them to eliminate GPC3-expressing xenograft tumors grown from human HCC cells in mice. Methods We used mass spectrometry to obtain a comprehensive peptidome from GPC3-expressing hepatoma cells after immune-affinity purification of human leukocyte antigen (HLA)-A2 and bioinformatics to identify immunodominant peptides. To circumvent GPC3 tolerance resulting from feta…

Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins

Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity in targeting phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and/or aPL against cardiolipin and/or β2-glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. aPL production is thought to be triggered by–among other factors–viral infections, though infection-associated aPL have mostly been considered non-pathogenic. Recently, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acu…

Docetaxel as Salvage Therapy in Highly Pretreated and Drug Resistant Gastrointestinal Carcinomas

Introduction Despite many efforts to develop new chemotherapies for metastatic upper gastrointestinal (GI) cancer, overall prognosis continues to be fatal, particularly in gastric and pancreatic cancer. Many of these patients deserve second-or third-line treatment after failure of first-line chemotherapy. Therefore, we analysed toxicity and response rate of weekly docetaxel after failed upfront regimes in these upper GI cancer patients. Patients and Methods Between 2001 and 2006, 18 patients received docetaxel based regimes (35 mg/m2 weekly) after informed consent. Response rates were determined using RECIST criteria or tumor progression if clinically evident. Toxicities were graded based o…

Current progress in immunotherapy of hepatocellular carcinoma

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…

Die Leberfunktion vor Lebertransplantation bestimmt das Überleben nach Lebertransplantation beim hepatozellulären Karzinom

Acute organ failure following the loss of anti-apoptotic cellular FLICE-inhibitory protein involves activation of innate immune receptors

Apoptosis signaling is involved in both physiological tissue homeostasis and acute and chronic diseases. The role of regulatory apoptosis signaling molecules and their organ-specific functions are less defined. Therefore, we investigated the loss of the anti-apoptotic cellular FLICE-inhibitory protein (cFLIP) and the mechanisms of the resulting lethal organ failure in vivo using inducible knockout mice. These were generated by crossing floxed cFLIP mice to a tamoxifen inducible Rosa26-creERT2 mouse strain. Death following global loss of cFLIP resulted from liver failure, accumulation of M1-polarized macrophages and accompanying hepatic cell death and inflammation. Apoptosis was also promine…

Safety and immunogenicity of the therapeutic vaccine TG1050 in chronic hepatitis B patients: a phase 1b placebo-controlled trial

Funding: Transgène; International audience; Treatment of chronic hepatitis B (CHB) typically requires life-long administration of drugs. Cohort and pre-clinical studies have established the link between a functional T-cell-mounted immunity and resolution of infection. TG1050 is an adenovirus 5-based vaccine that expresses HBV polymerase and domains of core and surface antigen and has shown immunogenicity and antiviral effects in mice. We performed a phase 1 clinical trial to assess safety and explore immunogenicity and early efficacy of TG1050 in CHB patients. This randomized, double blind, placebo-controlled study included two sequential phases: one single dose cohort (SD, n = 12) and one …

Efficacy of an escalating dose regimen of pegylated interferon ?-2a plus ribavirin in the early phase of HCV reinfection after liver transplantation

We evaluated the safety and efficacy of an escalating dose regimen of pegylated interferon alpha-2a (PEG-IFN(alpha-2a)) and ribavirin in the early phase of recurrent hepatitis C after orthotopic liver transplantation (OLT). In this prospective study, 26 patients transplanted for hepatitis C virus cirrhosis with recurrent hepatitis C were treated 3.4 +/- 3.6 months after OLT and compared with an untreated historical control. PEG-IFN(alpha-2a) was initiated as monotherapy, following stepwise dose escalation up to 180 mug/week and the addition of ribavirin up to 1200 mg/day or maximally tolerated doses for 48 weeks. In the intent-to-treat analysis, 38% showed an early virological response (EVR…

Sarcopenia as prognostic factor for survival after orthotopic liver transplantation

Background and aim Body composition has emerged as a prognostic factor for end-stage liver disease. We therefore investigated muscle mass, body fat and other clinical-pathological variables as predictors of posttransplant survival. Methods A total of 368 patients, who underwent orthotopic liver transplantation (OLT) at our institution, were assessed prior to OLT and followed for a median of 9.0 years (range 2.0-10.0 years) after OLT. Psoas, erector spinae and the combined paraspinal muscle area, as well as the corresponding indices normalized by body-height squared, were quantified by a lumbar (L3) cross-sectional computed tomography. In addition, absolute body fat and bone density were est…

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…

Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

AIM: To investigate the efficacy and safety of cape-citabine plus irinotecan ± bevacizumab in advanced or metastatic colorectal cancer patients. METHODS: Forty six patients with previously untreated, locally-advanced or metastatic colorectal cancer (mCRC) were recruited between 2001-2006 in a prospective open-label phase II trial, in German community-based outpatient clinics. Patients received a standard capecitabine plus irinotecan (CAPIRI) or CAPIRI plus bevacizumab (CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of > grade 2 toxicity. The treatment choice of bevacizumab was at the discretion of the physician. The primary endpoints were respon…

EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes

The hepatitis B virus (HBV) is a major causative agent of chronic liver disease and subsequent liver cirrhosis worldwide. The reduced sensitivity of virus-infected liver cells to apoptosis may play a role in the failure to remove virus-infected cells and eventually promote viral chronicity. The purpose of our study was to investigate whether survival factors induced during compensatory liver regeneration may protect hepatocytes against apoptosis. We evaluated the serum levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in HBV-infected patients and found significant increases in HGF and EGF in patients with active virus infection. In primary human hepatocytes we show …

No Evidence for Classic Thrombotic Microangiopathy in COVID-19

Background: Coronavirus disease-2019 (COVID-19) triggers systemic infection with involvement of the respiratory tract. There are some patients developing haemostatic abnormalities during their infection with a considerably increased risk of death. Materials and Methods: Patients (n = 85) with SARS-CoV-2 infection attending the University Medical Center, Mainz, from 3 March to 15 May 2020 were retrospectively included in this study. Data regarding demography, clinical features, treatment and laboratory parameters were analyzed. Twenty patients were excluded for assessment of disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) due to lack of laboratory data. Resu…