0000000000273451
AUTHOR
Miguel A. Serra
showing 28 related works from this author
Plasma concentrations of nitric oxide and asymmetric dimethylarginine in human alcoholic cirrhosis.
2004
The liver plays a prominent role in the metabolism of asymmetric dimethyl-l-arginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase. This study was designed to determine whether plasma levels of ADMA and NO production are altered in patients with compensated and decompensated alcoholic cirrhosis.Plasma levels of l-arginine, ADMA, symmetric dimethylarginine (SDMA) and NO (nitrite plus nitrate, NOx) were measured in nine patients with compensated alcoholic cirrhosis (Child-Pugh A) and 11 patients with advanced cirrhosis (Child-Pugh B-C). Seven healthy volunteers served as controls.ADMA and NOx concentrations in decompensated cirrhosis were higher than in the compensated group a…
Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease
2021
Traditional histological evaluation for grading liver disease severity is based on subjective and semi-quantitative scores. We examined the relationship between digital pathology analysis and corresponding scoring systems for the assessment of hepatic necroinflammatory activity. A prospective, multicenter study including 156 patients with chronic liver disease (74% nonalcoholic fatty liver disease-NAFLD, 26% chronic hepatitis-CH etiologies) was performed. Inflammation was graded according to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network system and METAVIR score. Whole-slide digital image analysis based on quantitative (I-score: inflammation ratio) and morphometric (C-sco…
Interferon decreases serum lipid peroxidation products of hepatitis C patients
1994
Abstract Thiobarbituric acid reactive substances (TBARS) concentration in serum has been determined in healthy subjects and in patients suffering acute hepatitis and chronic cases of hepatitis C. Treatment with interferon of the chronic active hepatitis C patients, 5 × 10 6 U three times a week during 2 months, led in those patients whose SGPT activity normalized in serum, to a concomitant decrease in serum TBARS content. The possible theoretical involvement of peroxidation and antioxidants in this beneficial effect of interferon in hepatitis C patients is discussed. The results presented confirm the value of TBARS as laboratory test in the management of liver diseases and as a useful tool …
The PHES battery does not detect all cirrhotic patients with early neurological deficits, which are different in different patients.
2017
Background and aims The psychometric hepatic encephalopathy score (PHES) is the “gold standard” for minimal hepatic encephalopathy (MHE) diagnosis. Some reports suggest that some cirrhotic patients “without” MHE according to PHES show neurological deficits and other reports that neurological alterations are not homogeneous in all cirrhotic patients. This work aimed to assess whether: 1) a relevant proportion of cirrhotic patients show neurological deficits not detected by PHES; 2) cirrhotic patients with mild neurological deficits are a homogeneous population or may be classified in sub-groups according to specific deficits. Methods Cirrhotic patients “without” (n = 56) or “with” MHE (n = 4…
Minimal hepatic encephalopathy is associated with expansion and activation of CD4+CD28−, Th22 and Tfh and B lymphocytes
2017
AbstractPeripheral inflammation acts synergistically with hyperammonemia in inducing neurological alterations in cirrhotic patients with minimal hepatic encephalopathy (MHE). We hypothesized that appearance of MHE would be associated to some specific qualitative change in peripheral inflammation. The aim of this work was to characterize the changes in peripheral inflammation associated to appearance of MHE. We analyzed it by immunophenotyping and cytokine profile analysis, in cirrhotic patients without or with MHE and controls. The main alterations associated specifically with MHE are: 1) increased activation of all subtypes of CD4+ T-lymphocytes, with the increased expression of CD69; 2) i…
Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies.
2010
Among the different processes occurring during the evolution of liver disease, fibrosis has a predominant role. Liver fibrosis mechanisms are fairly constant irrespective of the underlying etiology. Cirrhosis is the end-stage of this reaction. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. The aim of this study was to demonstrate the applicability of 1H high resolution magic angle spinning (HR-MAS) NMR spectroscopy in the biochemical profile determination of human liver needle biopsy samples for the characterization of metabolic alterations related to the sever…
Tratamiento de la hepatitis C en grupos de pacientes especiales
2014
Resumen El plan de tratamiento de la hepatitis cronica C en las poblaciones especiales varia en funcion de la comorbilidad y las evidencias de tratamiento existentes. En los pacientes con coinfeccion por virus de la hepatitis C y virus de la inmunodeficiencia humana, los resultados del tratamiento con biterapia (interferon pegilado mas ribavirina) son pobres. En los pacientes infectados por virus de genotipo 1, la terapia triple (biterapia mas boceprevir o telaprevir) ha duplicado la tasa de respuesta, pero los inhibidores de la proteasa pueden interactuar con algunos farmacos antirretrovirales y provocan mas efectos adversos. Estos inconvenientes no los presentan los nuevos antivirales dir…
A single transient episode of hyperammonemia induces long-lasting alterations in protein kinase A.
2007
A single transient episode of hyperammonemia induces long-lasting alterations in protein kinase A. Am J Physiol Gastrointest Liver Physiol 292: G305-G314,2007; doi:10.1152/ajpgi.00100.2006.-Hepatic encephalopathy in patients with liver disease is associated with poor prognosis. This could be due to the induction by the transient episode of hepatic encephalopathy of long-lasting alterations making patients more susceptible. We show that a single transient episode of hyperammonemia induces long-lasting alterations in signal transduction. The content of the regulatory subunit of the protein kinase dependent on cAMP (PKA-RI) is increased in erythrocytes from cirrhotic patients. This increase is…
Cirrhotic patients with minimal hepatic encephalopathy have increased capacity to eliminate superoxide and peroxynitrite in lymphocytes, associated w…
2018
Patients with minimal hepatic encephalopathy (MHE) show increased oxidative stress in blood. We aimed to assess whether MHE patients show alterations in different types of blood cells in (a) basal reactive oxygen and nitrogen species levels; (b) capacity to metabolise these species. To assess the mechanisms involved in the altered capacity to metabolise these species we also analysed: (c) peroxynitrite formation and d) peroxynitrite reaction with biological molecules. Levels of reactive oxygen and nitrogen species were measured by flow cytometry in blood cell populations from cirrhotic patients with and without MHE and controls, under basal conditions and after adding generators of superoxi…
High efficacy and safety of triple therapy in HCV genotype 1 and moderate fibrosis: a multicenter study of clinical practice in Spain.
2015
Background and rational. Telaprevir-based therapy (TBT) has been extensively evaluated in clinical trials. So we designed a study to compare the efficacy and safety of TBT between patients with moderate fibrosis and those suffering from advanced fibrosis in clinical practice. A multicenter observational and ambispective study was conducted. It included 582 patients with chronic hepatitis C genotype 1, 214 with fibrosis F2, and 368 with F3/F4 (F3: 148; F4: 220). Results. The mean patient age was 55 years, 67% male. Type of prior response was 22% naive, 57% relapsers, and 21% partial/null responders, 69% had high viral load (> 800,000 IU/mL). HCV genotypes were 1a (19%), 1b (69%), and 1 (12%)…
Serum and ascitic fluid bacterial DNA: a new independent prognostic factor in noninfected patients with cirrhosis.
2008
We tested the hypothesis that the presence of bacterial DNA (bactDNA) in ascitic fluid and serum is associated with decreased survival in patients with cirrhosis. In a prospective, multicenter study, we analyzed the clinical evolution of 156 patients with cirrhosis and ascites (first or recurrence) with lower than 250 polymorphonuclear cells (PMN)/L, negative ascites bacteriological culture, and absence of other bacterial infections being admitted for evaluation of largevolume paracentesis, according to the presence of bactDNA at admission. Survival, causes of death, and successive hospital admissions were determined during a 12-month follow-up period. BactDNA was detected in 48 patients. T…
Focal cortical damage parallels cognitive impairment in minimal hepatic encephalopathy
2012
Little attention has been paid to cortical integrity in patients with minimal hepatic encephalopathy (MHE), although cognitive functions affected in early stages of liver disease are mainly allocated in different neocortical structures. Here we used cortical surface-based analysis techniques to investigate if patterns of cortical thinning accompany the mildest form of HE. To aim this goal, cortical thickness obtained from high-resolution 31 magnetic resonance imaging (MRI) was measured in patients with no MHE (NMHE), MHE, and healthy controls. Further correlation analyses were performed to examine whether scores in the critical flicker frequency (CFF) test, and blood ammonia levels accounte…
Serum nitrotyrosine and psychometric tests as indicators of impaired fitness to drive in cirrhotic patients with minimal hepatic encephalopathy
2013
BACKGROUND & AIMS: Cirrhotic patients with minimal hepatic encephalopathy (MHE) show impaired driving ability and increased vehicle accidents. The neurological deficits contributing to impair driving and the underlying mechanisms are poorly understood. Early detection of driving impairment would help to reduce traffic accidents in MHE patients. It would be therefore useful to have psychometric or biochemical parameters reflecting driving impairment. The aims of this work were as follows: (i) to shed light on the neurological deficits contributing to impair driving; (ii) to assess whether some psychometric test or biochemical parameter is a good indicator of driving impairment. METHODS: We a…
Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests
2013
AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention we…
Let's End HepC: modelling public health epidemiological policies applied to Hepatitis C in Spain
2022
Background: The WHO has defined international targets toward the elimination of hepatitis C by 2030. Most countries cannot be on track to achieve this goal unless many challenges are surpassed. The Let's End HepC (LEHC) tool aims to contribute to the control of hepatitis C. The innovation of this tool combines the modelling of public health policies (PHP) focused on hepatitis C with epidemiological modelling of the disease, obtaining a unique result that allows to forecast the impact of policy outcomes. The model was applied to several countries, including Spain.Methods: To address the stated objective, we applied the “Adaptive Conjoint Analysis” for PHP decision-making and Markov Chains in…
Patients with minimal hepatic encephalopathy show impaired mismatch negativity correlating with reduced performance in attention tests
2012
Attention deficit is an early event in the cognitive impairment of patients with minimal hepatic encephalopathy (MHE). The underlying mechanisms remain unclear. Mismatch negativity (MMN) is an auditory event-related potential that reflects an attentional trigger. Patients with schizophrenia show impaired attention and cognitive function, which are reflected in altered MMN. We hypothesized that patients with MHE, similarly to those with schizophrenia, should show MMN alterations related with attention deficits. The aims of this work were to assess whether (1) MMN is altered in cirrhotic patients with MHE, compared to those without MHE, (2) MMN changes in parallel with performance in attentio…
Increased protein kinase A regulatory subunit content and cGMP binding in erythrocyte membranes in liver cirrhosis
2003
Abstract Background/Aims : Patients with liver disease show increased plasma cGMP and decreased intracellular cGMP in lymphocytes. The initial aim of this work was to assess whether decreased intracellular cGMP and increased plasma cGMP may be due to increased ATP-dependent release of cGMP from cells. The results obtained led to a new aim: to identify and quantify a protein responsible for the increased cGMP binding found in erythrocyte membranes from patients with liver disease. Methods : ATP-dependent cGMP transport was determined in inside-out vesicles from erythrocyte membranes. cGMP-binding proteins were isolated from the membranes and identified by MALDI-TOF peptide mass fingerprint. …
Pegylated alpha-interferon-2a plus ribavirin compared with pegylated alpha-interferon-2b plus ribavirin for initial treatment of chronic hepatitis C …
2008
Background and aim We assessed whether the two regimens of pegylated alpha-interferon-2b (PEG-IFN-alpha2b) plus ribavirin and pegylated alpha-interferon-2a (PEG-IFN-alpha2a) plus ribavirin showed differences in terms of sustained virological response, withdrawal due to side-effects and dose adjustment requirements in the treatment of naive chronic hepatitis C virus (HCV) patients. Methods A prospective non-randomized, open-label comparison was made of naive HCV-infected patients undergoing standard 24- or 48-week treatment with two PEG-IFN combined with weight-based dosing regimen of ribavirin (PEG-IFN-alpha2a/ribavirin, n = 91; PEG-IFN-alpha2b/ribavirin, n = 92). Results Sustained virologi…
Accumulation of Symmetric Dimethylarginine in Hepatorenal Syndrome
2005
In patients with cirrhosis, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and possibly symmetric dimethylarginine (SDMA) have been linked to the severity of the disease. We investigated whether plasma levels of dimethylarginines and NO are elevated in patients with hepatorenal syndrome (HRS), compared with patients with cirrhosis without renal failure (no-HRS). Plasma levels of NO, ADMA, SDMA, and l-arginine were measured in 11 patients with HRS, seven patients with no-HRS, and six healthy volunteers. SDMA concentration in HRS was higher than in no-HRS and healthy subjects (1.47 ± 0.25 vs. 0.38 ± 0.06 and 0.29 ± 0.04 μM, respectively; P < 0.05). ADMA and NOx concentrations were…
Miliary tuberculosis infection during hepatitis C treatment with sofosbuvir and ledipasvir plus ribavirin
2017
Chronic hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. In the last 5 years, treatment for HCV infection has experienced a marked development. In 2014, the use of ledipasvir/sofosbuvir with or without concomitant weight-based ribavirin was approved with a very significant increase in the sustained virological response. However, new side effects have been associated. We report the first case of an HCV infected patient treated for 12 wk with the combination of sofosbuvir/ledipasvir plus ribavirin who developed a miliary tuberculosis (TB) infection while on therapy. The patient was a 65-year-old woman, who referred malaise, asthenia, hyporexia, 7…
Changing prevalence, clinical features, and outcome of acute hepatitis in Spain (1982-2003)
2006
Background: Diagnostic and preventive measures have contributed to a change in the epidemiology of acute hepatitis. The purpose of the present paper was to assess the changing prevalence of acute hepatitis from 1982 to 2003. Methods: Trends in the epidemiology, clinical findings, and outcome of acute viral hepatitis from 1982 to 2003 were examined. A total of 548 episodes of acute hepatitis diagnosed between 1982 and 2003, the clinical course of which was monitored up to the year 2003, were included. Annual changes as well as for the intervals 1982–1992 and 1993–2003 were compared. Results: Severe infections occurred in 1.3% of cases, with a mortality of 0.6%, with progression into chron…
Serum malondialdehyde: possible use for the clinical management of chronic hepatitis C patients
1998
Serum lipid peroxidation products are increased in inflammatory liver disease and, as we previously reported, also in chronic hepatitis C. We have performed a specific assay of malondialdehyde, the reported most abundant product of lipid peroxidation, in serum of twenty four chronic hepatitis C patients, before, during, and after interferon treatment. Liver biopsies were performed in each patient before and after interferon treatment. The results show higher serum malondialdehyde values in chronic hepatitis C patients than healthy subjects (n = 68) before interferon treatment (p < .001). Mean value of serum malondialdehyde levels after interferon treatment was significantly lower than befor…
Correlation of nitric oxide and atrial natriuretic peptide changes with altered cGMP homeostasis in liver cirrhosis.
2005
: Background: Cyclic GMP (cGMP) concentration is increased in plasma of patients with liver cirrhosis. Three possible mechanisms may contribute: increased cGMP synthesis by soluble (activated by nitric oxide), or particulate (activated by atrial natriuretic peptide (ANP)) guanylate cyclase or increased release from cells. Aim: The aim of this work was to analyze the possible contributors to increased plasma cGMP and to assess whether changes in the parameters of the system vary with the degree of liver disease (Child Pugh score) or by the presence of ascites. Methods: We measured cGMP in plasma and lymphocytes, soluble guanylate cyclase activation by nitric oxide in lymphocytes, nitrates an…
Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (C…
2019
Background and aims Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r +/- DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. Material and methods Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and toler…
SARS-CoV-2 vs. Hepatitis Virus Infection Risk in the Hemodialysis Population: What Should We Expect?
2021
Since the dramatic rise of the coronavirus infection disease 2019 (COVID-19) pandemic, patients receiving dialysis have emerged as especially susceptible to this infection because of their impaired immunologic state, chronic inflammation and the high incidence of comorbidities. Although several strategies have thus been implemented to minimize the risk of transmission and acquisition in this population worldwide, the reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence varies across studies but is higher than in the general population. On the contrary, the screening for hepatitis viruses (HBV and HCV) has seen significant improvements in recent years, with va…
Altered postural control and stability in cirrhotic patients with minimal hepatic encephalopathy correlate with cognitive deficits
2017
Background & Aims: Cognitive dysfunction in cirrhotic patients with minimal hepatic encephalopathy (MHE) is associated with falls. Alterations in postural control and stability could contribute to increase falls risk in these patients. We aimed to assess whether postural control and direction-specific limits of stability are altered in cirrhotic patients with MHE compared to patients without MHE and controls. We also assessed if alterations in postural control correlate with neurological impairment and/or blood biomarkers. Methods: Posturography analysis, attention Stroop test and bimanual and visuo-motor coordination tests were performed in 18 controls, 19 patients with cirrhosis without M…
Análisis coste-utilidad de la triple terapia con telaprevir en pacientes con hepatitis C no tratados previamente
2014
Introducción: En España, con una prevalencia del 2,5%, la hepatitis C (VHC) se asocia a una elevada morbi-mortalidad. El tratamiento combinado de telaprevir y peginterferon/ribavirina ([T/PR]) es eficaz en pacientes con VHC-G1. El objetivo primario de este estudio fue evaluar la relación coste-utilidad (RCUI) de [T/PR] versus peginterferon alfa 2a/ribavirina ([PR]) en pacientes naïve VHC-G1, según el grado de fibrosis y bajo la perspectiva del sistema sanitario español. Metodología: La eficacia y la incidencia de efectos adversos (EAs) se obtuvieron de los estudios ADVANCE y OPTIMIZE. La estimación de los costes de monitorización, de manejo de EAs y de la enfermedad por estados de salud (€,…
Análisis coste-utilidad de la triple terapia con telaprevir en pacientes con hepatitis C no tratados previamente
2014
Introducción: En España, con una prevalencia del 2,5%, la hepatitis C (VHC) se asocia a una elevada morbi-mortalidad. El tratamiento combinado de telaprevir y peginterferon/ribavirina ([T/PR]) es eficaz en pacientes con VHC-G1. El objetivo primario de este estudio fue evaluar la relación coste-utilidad (RCUI) de [T/PR] versus peginterferon alfa 2a/ribavirina ([PR]) en pacientes naïve VHC-G1, según el grado de fibrosis y bajo la perspectiva del sistema sanitario español. Metodología: La eficacia y la incidencia de efectos adversos (EAs) se obtuvieron de los estudios ADVANCE y OPTIMIZE. La estimación de los costes de monitorización, de manejo de EAs y de la enfermedad por estados de salud (,…