Dificultades en el diagnóstico de los pacientes con enfermedad de Wilson en la práctica clínica: experiencia de 15 casos

Background

Wilson disease (WD) is an inherited disorder that causes copper (Cu) accumulation, leading to mainly liver, neurological and/or psychiatric manifestations. In the absence of some of the typical features, diagnosis of WD is difficult and is based on the combination of clinical, biochemical and genetic testing. The aim of this study was to illustrate the complexity of the approach to WD in daily clinical practice.

Methods

We retrospectively analyzed the medical records of patients with WD, including the clinical presentation, histological and biochemical findings, and follow up after treatment. We also carried out genetic testing, and the Leipzig diagnostic score was applied.

Results

We included 15 patients. Four were symptomatic, with liver (n = 1), neurological (n = 1), psychiatric (n = 1) and mixed clinical manifestations (n = 1), and 11 were presymptomatic, with elevated transaminases (n = 8) and family study (n = 3).We observed Kayser-Fleischer ring in 2 patients, both without neurologic symptoms.Ceruloplasmin ≤5 mg/dL was present in 73%, and 24-hour urinary Cu > 100 μg in 40%. Liver Cu was > 250 μg/g.d.t. in 85% of the patients. The final diagnosis of WD was given by genetic testing (ATP7B gene mutations) in 5 patients with minimal disease features, including one symptomatic patient (psychiatric symptoms). We identified 5 previously reported mutations (p.M645R, p.R827W, p.H1069Q, p.P768L and p.G869R) and 3 unpublished mutations (p.L1313R, p.I1311T and p.A1179D); the most frequent mutation was p.M645R.After treatment, biochemical parameters (transaminases, urinary cooper) and symptoms improved, except in patients with neurological and psychiatric manifestations.

Conclusions

Our series illustrates the important role of genetic testing in the diagnosis of WD. The identification of the p.M645R mutation in most of our patients should be kept in mind in the molecular analysis of the ATP7B gene in our region.     

Tratamiento de la hepatitis crónica B antígeno e positiva con antivirales orales: experiencia y resultados en la práctica clínica

Introduction

Due to globalization and migratory movements, HBeAg+ chronic hepatitis B is becoming increasingly important in Spain.

Objective

To analyze the epidemiological features, progression, and treatment response to oral antiviral agents (OA) in HBeAg+ chronic hepatitis B patients in our area.

Material and methods

We analyzed 436 patients with chronic hepatitis B infection followed up at the Ramón y Cajal Hospital from 1990 to June 2012.

Results

Sixty-five patients (14.9%) had HBeAg+ chronic hepatitis B. Seven patients in the immunotolerant phase were not treated, while the remaining 58 received treatment.Four patients were excluded: two due to severe acute hepatitis, one due to hepatitis C virus coinfection and another because of a Delta virus coinfection. Of the remaining 54 patients, 19 received interferon with or without OA, and 35 received only OA. Two patients treated for less than 1 month were not included in the analysis. The analysis was finally performed in 33 patients. The mean duration of treatment was 46.81 months (6-138). Lamivudine was the most frequently prescribed drug (39.39%) followed by tenofovir (24.24%) and entecavir (21.21%). The mean age was 42.08 ± 14 years and 75.75% (25/33) of the patients were male. Nineteen of 33 patients (57.57%) achieved seroconversion to anti-HBe, and 27.27% (9/33) showed clearance of HBsAg. There was no evidence of HBsAg reversion after a mean follow-up of 35.6 months. There were 8 cases of resistance in 7 patients: 7 to lamivudine and 1 to adefovir.

Conclusions

Approximately 15% of chronic hepatitis B patients in our area are HBeAg+. Treatment with OA achieves a high seroconversion rate (57.57%) and a considerable percentage of HBsAg clearance (27.27%).     

Medicina de sistemas: una nueva visión de la práctica clínica

Most respiratory diseases are considered complex diseases as their susceptibility and outcomes are determined by the interaction between host-dependent factors (genetic factors, comorbidities, etc.) and environmental factors (exposure to microorganisms or allergens, treatments received, etc.)     

Protección contra el daño miocárdico por isquemia-reperfusión en la práctica clínica

Even when reperfusion therapy is applied as early as possible, survival and quality of life are compromised in a considerable number of patients with ST-segment elevation acute myocardial infarction. Some cell death following transient coronary occlusion occurs during reperfusion, due to poor handling of calcium in the sarcoplasmic reticulum-mitochondria system, calpain activation, oxidative stress, and mitochondrial failure, all promoted by rapid normalization of intracellular pH. Various clinical trials have shown that infarct size can be limited by nonpharmacological strategies—such as ischemic postconditioning and remote ischemic conditioning—or by drugs—such as cyclosporine, insulin, glucagon-like peptide-1 agonists, beta-blockers, or stimulation of cyclic guanosine monophosphate synthesis. However, some clinical studies have yielded negative results, largely due to a lack of consistent preclinical data or a poor design, especially delayed administration. Large-scale clinical trials are therefore necessary, particularly those with primary clinical variables and combined therapies that consider age, sex, and comorbidities, to convert protection against reperfusion injury into a standard treatment for patients with ST-segment elevation acute myocardial infarction.