The Neurobiology of Hepatic Encephalopathy

Despite significant recent breakthroughs, with rapid discoveries provided by the twentieth century, hepatic encephalopathy remains an ancestral enigma that accompanies the history of mankind. Much of this is due to the reductionist view that a single process would have primacy over others, with the emphasis on hyperammonemic theory being its greatest example. Since other factors, such as the intestinal microbiota composition, the synergism with neuroinflammation, and the role of glutamatergic and GABAergic tonus balance have been discovered, it has become clear that the traditional and linear view of scientific research allows the understanding of the initial state of multiple dysfunctional systems, but is unable to predict the overall behavior of the disease. As consequence, there is a lack of innovative interventions for controlled clinical trials, making its therapeutic management very limited. The objective of this chapter is to provide a general theoretical overview of the most relevant hypotheses and findings in the neurobiology of hepatic encephalopathy, and how its toxic, metabolic and immunological alterations affect the cellular metabolism and neurotransmission dynamics, causing its characteristic cognitive and motor manifestations

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.Universidade Estadual Paulista (UNESP) Botucatu School of MedicineUniversidade Federal do Rio de JaneiroUniversidade Estadual de CampinasUniversidade Federal de São Paulo (UNIFESP)Pontificia Universidade Catolica de São PauloUNIFESPSciEL

High rate of depression in patients with chronic hepatitis C / Taxa elevada de depressão em pacientes com hepatite C crônica

Objectives: To describe the frequency of depression in patients with hepatitis C (HCV) and relate to the biological variables and liver function. Methods: Cross-sectional, descriptive study with a quantitative approach, which assessed depression using the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and the association with biological and liver function variables in 85 patients HCV chronically infected indicated for direct-acting antiviral therapy (DAA) between May 2018 and May 2019. Results: Depression was detected in 47.1% of patients, predominantly mild depression (95%). However, depression occurred independently of biological characteristics, such as gender, age, education, associated comorbidities and liver function, such as degree of fibrosis and viral genotype. Conclusions: The frequency of depression was high in patients with HCV and had no statistical relationship with biological characteristics and liver function, suggesting that active search for depression could be a valuable strategy in managing these patients.Objetivos: Describir la frecuencia de depresión en pacientes con hepatitis C (VHC) y relacionarla con variables biológicas y función hepática. Métodos: Estudio descriptivo transversal con abordaje cuantitativo, que evaluó la depresión utilizando los criterios del Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-V) y la asociación con variables biológicas y de función hepática en 85 pacientes con VHC crónico indicados para tratamento com terapia antiviral de acción directo (AAD) entre mayo de 2018 y 2019. Resultados: Se detectó depresión en el 47,1% de los pacientes, predominantemente depresión leve (95%). Sin embargo, la depresión se produjo independientemente de las características biológicas, como el sexo, la edad, la educación, las comorbilidades asociadas y la función hepática, como el grado de fibrosis y el genotipo viral. Conclusiones: La frecuencia de depresión fue alta en pacientes con VHC y no tuvo relación estadística con características biológicas y función hepática, sugiriendo la búsqueda activa de depresión como estrategia en el manejo de estos pacientes.Objetivos: descrever a frequência de depressão em pacientes com hepatite C (HCV) e relacionar com as variáveis biológicas e função hepática. Métodos: estudo transversal, descritivo, de abordagem quantitativa, que avaliou a depressão utilizando os critérios do Manual de diagnóstico e estatístico de transtornos mentais (DSM-V) e a associação com as variáveis biológicas e de função hepática em 85 pacientes com HCV crônica indicados para a terapia antiviral de ação direta (DAA) entre maio de 2018 e 2019. Resultados: detectou-se depressão em 47,1% dos pacientes, predominantemente depressão leve (95%). Entretanto a depressão ocorreu de forma independente das características biológicas, como sexo, idade, escolaridade, comorbidades associadas e da função hepática, como grau de fibrose e genótipo viral. Conclusões: a frequência de depressão foi alta em pacientes com HCV e não teve relação estatística com as características biológicas e função hepática, sugerindo a busca ativa da depressão como estratégia na condução destes pacientes.

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10;

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%,

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

<p>Abstract</p> <p>Background</p> <p>Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.</p> <p>Methods</p> <p>This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.</p> <p>Discussion</p> <p>The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.</p> <p>Trial Registration</p> <p>Clinical Trials <a href="http://www.clinicaltrials.gov/ct2/show/NCT00970931">NCT00970931</a>.</p