Reversibility of structural and functional alterations of hepatic encephalopathy.

Hepatic Encephalopathy (HE) is a frequent complication of chronic liver disease. Type C HE mainly appears in episodes; only seldom chronic persistent forms occur. HE can lead to hospitalization and it has a huge impact on the health related quality of life.

Long-Term Follow-Up of Neuropsychiatric Symptoms After Sustained Virological Response to Interferon-Free and Interferon-Based Hepatitis C Virus Treatment.

Chronic hepatitis C virus (HCV) infection can be associated with neuropsychiatric symptoms like fatigue and cognitive impairment, independent of the liver status. The present study aims to assess changes in the pattern and extent of neuropsychological symptoms after successful treatment with interferon (IFN)-based and IFN-free therapy. HCV-infected patients who underwent neuropsychological assessment in previous studies were invited to a follow-up examination.

Assessment of cognitive functioning after living kidney donation: A cross-sectional pilot study.

Background: Chronic kidney disease (CKD) has emerged as a risk factor for cognitive impairment. Living kidney donation results in reduction of the donors' renal function. This is considered acceptable in general but possible associations with cognitive function have not yet been studied.

Brain metabolic and microstructural alterations associated with hepatitis C virus infection, autoimmune hepatitis and primary biliary cholangitis.

Background And Aims: Neuropsychiatric symptoms in hepatitis C (HCV) patients resemble those of patients with autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC), whilst the mechanisms behind them are unknown. Here we looked for cerebral metabolic and/or microstructural alterations in patients with HCV, AIH or PBC as possible causes behind these symptoms.

Methods: Patients with HCV infection (n = 17), AIH (n = 14) or PBC (n = 11) and age-adjusted healthy controls (n = 18) underwent brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and psychometric assessment of memory and attention.

[Neuroprotective treatment of tauopathies].

Tau pathology is now considered to be the main cause of a wide spectrum of neurodegenerative diseases, which are collectively referred to as tauopathies. These include primary tauopathies, in which tau plays the main role in the pathogenesis as well as secondary tauopathies, such as Alzheimer's disease, in which amyloid beta also plays a substantial role in the disease process in addition to the tau pathology. Primary tauopathies include progressive supranuclear palsy, corticobasal degeneration, Pick's disease and rare hereditary tauopathies, which are referred to as frontotemporal lobar degeneration with microtubule-associated protein tau (MAPT) mutation.

Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.

Purpose: Calcineurin inhibitors (CNI) can cause long-term impairment of brain function. Possible pathomechanisms include alterations of the cerebral immune system. This study used positron emission tomography (PET) imaging with the translocator protein (TSPO) ligand F-GE-180 to evaluate microglial activation in liver-transplanted patients under different regimens of immunosuppression.

Reliable quantification of F-GE-180 PET neuroinflammation studies using an individually scaled population-based input function or late tissue-to-blood ratio.

Purpose: Tracer kinetic modeling of tissue time activity curves and the individual input function based on arterial blood sampling and metabolite correction is the gold standard for quantitative characterization of microglia activation by PET with the translocator protein (TSPO) ligand F-GE-180. This study tested simplified methods for quantification of F-GE-180 PET.

Methods: Dynamic F-GE-180 PET with arterial blood sampling and metabolite correction was performed in five healthy volunteers and 20 liver-transplanted patients.

Brain function and metabolism in patients with long-term tacrolimus therapy after kidney transplantation in comparison to patients after liver transplantation.

Background: About 50% of the patients 5-7 years after kidney transplantation show impairment of memory, attention and executive function. Tacrolimus frequently induces neurological complications in the first few weeks after transplantation. Furthermore, tacrolimus treatment is associated with impaired cognitive function in the long-term in patients after liver transplantation.

Impact of immunosuppressive therapy on brain derived cytokines after liver transplantation.

Background: While acute neurotoxic side effects of calcineurin inhibitors (CNI) are well-known, data upon long-term effects on brain structure and function are sparse. We hypothesize that long-term CNI therapy affects the neuroimmune system, thereby, increasing the risk of neurodegeneration. Here, we measured the impact of CNI therapy on plasma levels of brain- and T cell-derived cytokines in a cohort of patients after liver transplantation (LT).

Quantitative magnetic resonance imaging indicates brain tissue alterations in patients after liver transplantation.

Purpose: To investigate cerebral microstructural alterations in patients treated with calcineurin inhibitors (CNI) after orthotopic liver transplantation (OLT) using quantitative magnetic resonance imaging (qMRI) and a cross-sectional study design.

Methods: Cerebral qMRI was performed in 85 patients in a median 10 years after OLT compared to 31 healthy controls. Patients were treated with different dosages of CNI or with a CNI-free immunosuppression (CNI-free: n = 19; CNI-low: n = 36; CNI-standard: n = 30).

Cerebral metabolite alterations in patients with posttransplant encephalopathy after liver transplantation.

Background: In the first weeks after liver transplantation about 30% of the patients develop a posttransplant encephalopathy. A posttransplant encephalopathy comprises metabolic-toxic caused symptoms such as disorientation, confusion, hallucinations, cognitive dysfunction and seizures. We hypothesize that alterations of cerebral metabolites before liver transplantation predispose posttransplant encephalopathy development after liver transplantation.

Hepatic Encephalopathy Is Reversible in the Long Term After Liver Transplantation.

Cognitive dysfunction caused by hepatic encephalopathy (HE) improves within the first year after liver transplantation (LT). However, cognitive restitution seems to be incomplete in a subset of patients and after LT a new-onset cognitive decline was described. Data about the longterm development of cognitive function after liver transplantation (LT) are sparse.

Cognitive impairment after liver transplantation: residual hepatic encephalopathy or posttransplant encephalopathy?

Liver transplantation (LT) represents the definitive treatment for end-stage liver disease. Cognitive impairment following LT is frequent, referred to as postliver transplant encephalopathy (PLTE). LT removes the underlying chronic liver disease, and until recently hepatic encephalopathy (HE) was assumed to be fully reversible after LT.

Brain metabolic alterations in patients with long-term calcineurin inhibitor therapy after liver transplantation.

Background: Calcineurin inhibitor (CNI) neurotoxicity after liver transplantation might be due to impairment of the cerebral metabolism.

Aims: To investigate CNI-related alterations of brain metabolite distributions and associations between cognitive function and brain metabolism in patients with long-term CNI treatment after liver transplantation.

Methods: Eighty-two patients (19 CNI free, 34 CNI low-dose and 29 standard-dose CNI immunosuppression) 10 years after liver transplantation and 32 adjusted healthy controls underwent nonlocalised brain phosphorus magnetic resonance spectroscopy (MRS) and single voxel proton MRS in the parietal white matter to estimate brain metabolite contents.

Neuropsychiatric symptoms in hepatitis C patients resemble those of patients with autoimmune liver disease but are different from those in hepatitis B patients.

Chronic fatigue, mood alterations and cognitive impairment are frequent accessory symptoms of HCV infection. Fatigue and mood alterations have also been observed in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but not in hepatitis B virus (HBV)-infection, thus indicating an autoimmune response as possible cause of HCV infection-associated encephalopathy. Data, however, are sparse.

Systemic inflammation and immune cell phenotypes are associated with neuro-psychiatric symptoms in patients with chronic inflammatory liver diseases.

Background & Aims: Chronic inflammatory liver diseases are frequently associated with neuropsychiatric and cognitive dysfunctions. We hypothesized that symptomatic patients may show altered levels of soluble inflammatory mediators (SIMs) as well as changes in immune cell phenotypes.

Methods: A comprehensive immune-phenotyping including investigation of 50 SIMs as well as ex-vivo phenotypes of NK-cells, CD3+, CD4+, CD8+ and regulatory T cells in 40 patients with viral and autoimmune chronic liver diseases was performed.

Longterm calcineurin inhibitor therapy and brain function in patients after liver transplantation.

Calcineurin inhibitors (CNIs) frequently induce neurological complications early after orthotopic liver transplantation (OLT). We hypothesize that longterm CNI therapy after OLT causes dose-dependent cognitive dysfunction and alteration of brain structure. In this study, 85 OLT patients (20 with CNI-free, 35 with CNI low-dose, and 30 with standard-dose CNI immunosuppression) underwent psychometric testing and cerebral magnetic resonance imaging approximately 10 years after OLT to assess brain function and structural brain alterations.

Hepatic encephalopathy before and neurological complications after liver transplantation have no impact on the employment status 1 year after transplantation.

Aim: To investigate the impact of hepatic encephalopathy before orthotopic liver transplantation (OLT) and neurological complications after OLT on employment after OLT.

Methods: One hundred and fourteen patients with chronic liver disease aged 18-60 years underwent neurological examination to identify neurological complications, neuropsychological tests comprising the PSE-Syndrome-Test yielding the psychometric hepatic encephalopathy score, the critical flicker frequency and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), completed a questionnaire concerning their occupation and filled in the short form 36 (SF-36) to assess health-related quality of life before OLT and 12 mo after OLT, if possible. Sixty-eight (59.

Cerebral white matter lesions in patients with cirrhosis - causative for hepatic encephalopathy or bystanders?

Background & Aims: Focal white matter lesions mimicking microvascular lesions were connected to the development of hepatic encephalopathy (HE) in patients with cirrhosis. This study aims to assess the relationship between cerebrovascular risk factors and the prevalence and extent of these lesions in patients with cirrhosis, as well as their impact upon cognitive function.

Methods: 55 cirrhotic patients underwent neurological examination, psychometric testing and magnetic resonance imaging.

Central nervous system complications after liver transplantation: common but mostly transient phenomena.

Although central nervous system complications (CNSCs) are common after orthotopic liver transplantation (OLT), standardized prospective studies are still lacking. This prospective study was aimed at determining the incidence of CNSCs, describing their clinical presentations, and establishing predicting factors. One hundred thirty-six adult patients who underwent OLT at Hannover Medical School between December 2008 and June 2011 were included.

The temporal dynamics of plasma fractalkine levels in ischemic stroke: association with clinical severity and outcome.

Background: The chemokine fractalkine (CX3CL1, FKN) is involved in neural-microglial interactions and is regarded as neuroprotective according to several in vivo studies of inflammatory and degenerative states of the brain. Recently, an association with outcome in human ischemic stroke has been proposed. In this study, we aimed to investigate the temporal pattern of FKN levels in acute ischemic stroke in relation to stroke severity and outcome.

New-onset cognitive dysfunction impairs the quality of life in patients after liver transplantation.

Patients after orthotopic liver transplantation (OLT) may show cognitive dysfunction. To date, it has not been clear whether this dysfunction is due to residual hepatic encephalopathy (HE) or new-onset cognitive disturbances. Just as little is known about the course and clinical significance.

Active at night, sleepy all day--sleep disturbances in patients with hepatitis C virus infection.

Background & Aims: More than 50% of patients with chronic hepatitis C with only mild liver disease complain about chronic fatigue, daytime sleepiness and poor sleep quality. The aim of the present study was to characterize and objectify the sleep disturbances in hepatitis C virus-infected patients.

Methods: Twenty-five women who had been infected with hepatitis C virus contaminated anti-D immunoglobulin in 1978/79 and 22 age-matched female healthy controls underwent actigraphy over a period of 5 days to measure motor activity and thereby sleep-wake-rhythm and in addition completed questionnaires for depression, health-related quality of life, fatigue and sleep, and a sleep diary.

Modulation of neural activation following treatment of hepatic encephalopathy.

Objective: To measure changes in psychometric state, neural activation, brain volume (BV), and cerebral metabolite concentrations during treatment of minimal hepatic encephalopathy.

Methods: As proof of principle, 22 patients with well-compensated, biopsy-proven cirrhosis of differing etiology and previous minimal hepatic encephalopathy were treated with oral l-ornithine l-aspartate for 4 weeks. Baseline and 4-week clinical review, blood chemistry, and psychometric evaluation (Psychometric Hepatic Encephalopathy Score and Cognitive Drug Research Score) were performed.