RESUMO

Liver diseases preceding the occurrence of hepatocellular carcinoma (HCC) play a crucial role in the progression and establishment of HCC, a malignancy ranked as the third deadliest cancer worldwide. Late diagnosis, alongside ineffective treatment, leads patients to a poor survival rate. This scenario argues for seeking novel alternatives for detecting liver alterations preceding the early occurrence of HCC. Experimental studies have reported that ABCC3 protein increases within HCC tumors but not in adjacent tissue. Therefore, we analyzed ABCC3 expression in public databases and investigated the presence of ABCC3 and its isoforms in plasma, urine and its release in extracellular vesicles (EVs) cargo from patients bearing cirrhosis and HCC. The UALCAN and GEPIA databases were used to analyze the expression of ABCC3 in HCC. The results were validated in a case-control study including 41 individuals bearing cirrhosis and HCC, and the levels of ABCC3 in plasma and urine samples, as well as EVs, were analyzed by ELISA and western blot. Our data showed that ABCC3 expression was higher in HCC tissues than in normal tissues and correlated with HCC grade and stage. ABCC3 protein levels were highly increased in both plasma and urine and correlated with liver disease progression and severity. The isoforms MRP3A and MRP3B of ABCC3 were significantly increased in both EVs and plasma/urine of patients bearing HCC. ABCC3 expression gradually increases in HCC tissues, and its protein levels are increased in both plasma and urine of patients with cirrhosis and HCC. MRP3A and MRP3B isoforms have the potential to be prognostic biomarkers of HCC.

RESUMO

INTRODUCTION AND OBJECTIVES: Lower antibody (Ab) responses after SARS-CoV-2 vaccination have been reported in liver transplant (LT) recipients and those with chronic liver diseases (CLD). The role of a booster dose in those with poor responses to initial vaccination is not well defined. METHODS: In this prospective study, we determined antibody (Ab) response to spike protein after a booster dose in LT recipients and those with chronic liver diseases (CLD) with and without cirrhosis after they had a poor response to an initial standard regimen. RESULTS: Of the 80 patients enrolled, 45 had LT, and 35 had CLD (18 with cirrhosis). A booster dose was given at a median of 138.5 days after the completion of the standard regimen. After the booster dose, 58 (73%, 31 LT, 27 CLD) had good response (≥250 U/mL), and 22 (28%, 14 LT, and 8 CLD) had poor response (7 undetectable and 15 with low Ab levels). No patient had any serious adverse events. The antibody responses were lower in those who had undetectable Ab (80 U/mL) than those who had low levels of Ab (0.80-249 U/mL) after the standard vaccination regimen (42% vs. 87%, p=0.0001). The antibody responses after homologous and heterologous booster doses were similar. CONCLUSIONS: We have shown that a booster dose will enhance Ab responses in LT recipients and those with CLD who had poor responses after an initial vaccine regimen.

Assuntos

RESUMO

N6-methyladenosine (m6A) is the most thoroughly studied type of internal RNA modification, as this epigenetic modification is the most abundant in eukaryotic RNAs to date. This modification occurs in various types of RNAs and plays significant roles in dominant RNA-related processes, such as translation, splicing, export and degradation. These processes are catalyzed by three types of prominent enzymes: writers, erasers and readers. Increasing evidence has shown that m6A modification is vital for the regulation of gene expression, carcinogenesis, tumor progression and other abnormal changes, and recent studies have shown that m6A is important in the development of hepatocellular carcinoma (HCC). Herein, we summarize the nature and regulatory mechanisms of m6A modification, including its role in the pathogenesis of HCC and related chronic liver diseases. We also highlight the clinical significance and future strategies involving RNA m6A modifications in HCC.

Assuntos

RESUMO

In 2015 the European Association for the Study of Liver Diseases (EASL) and the Asociación Latinoamericana para el Estudio del Hígado (ALEH) published a guideline for the use of non-invasive markers of liver disease. At that time, this guideline focused on the available data regarding ultrasonic-related elastography methods. Since then, much has been published, including new data about XL probe use in transient elastography, magnetic resonance elastography, and non-invasive liver steatosis evaluation. In order to draw evidence-based guidance concerning the use of elastography for non-invasive assessment of fibrosis and steatosis in different chronic liver diseases, the Brazilian Society of Hepatology (SBH) and the Brazilian College of Radiology (CBR) sponsored a single-topic meeting on October 4th, 2019, at São Paulo, Brazil. The aim was to establish specific recommendations regarding the use of imaging-related non-invasive technology to diagnose liver fibrosis and steatosis based on the discussion of evidence-based topics by an organizing committee of experts. It was submitted online to all SBH and CBR members. The present document is the final version of the manuscript that supports the use of this new technology as an alternative to liver biopsy.

Assuntos

Assuntos

RESUMO

Sarcopenia is the loss of muscle mass and strength produced by aging or secondary to chronic diseases such as chronic liver disease (CLD). Although not all types of sarcopenia involve the same features, the most common are decreased fiber diameter and myosin heavy chain (MHC) levels, increased activity of ubiquitin-proteasome system (UPS) and reactive oxygen species (ROS). In this study, we aim to characterize the development of sarcopenia secondary to CLD induced by the hepatotoxin 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). For this purpose, four-months-old male C57BL6 mice were fed with normal diet or DDC supplemented diet for 6 weeks. Functional tests to evaluate muscle strength, mobility, and motor skills were performed in alive mice. The muscle strength in isolated gastrocnemius was also assayed via electrophysiological measurements. Morphometric measures of fibers' diameter, total and ubiquitinated protein levels of myosin heavy chain (MHC), E3 ubiquitin ligases, ROS, and oxidation-dependent modified proteins in gastrocnemius tissue were also determined. Our results demonstrated that mice fed the DDC diet developed muscle wasting as evidenced by a loss of muscle mass and decreased muscle strength. The muscles of mice fed with DDC diet have a decreased diameter of fibers and MHC levels, also as increased MuRF-1 and atrogin-1 protein levels, ROS levels, and oxidation-modified protein levels. Additionally, control and DDC mice have the same food and water intake as well as mobility. Our results demonstrate mice with CLD develop sarcopenia involving decreased levels of myofibrillar proteins, increased UPS, and oxidative stress, but not for impaired caloric intake or immobility.

Assuntos

RESUMO

PURPOSE OF REVIEW: The purpose of this study is to analyze the current evidence regarding the use of statins in patients with chronic liver disease and cirrhosis. RECENT FINDINGS: Chronic liver disease (CLD), cirrhosis, and its complications, including hepatocellular carcinoma (HCC), are significant public health problems. The use of statins in patients with CLD has been a matter of concern, and physicians are often reluctant to its prescription in these patients. This mainly relates to the potential occurrence of drug-induced liver injury. However, newer evidence from pre-clinical and clinical research has shown that statins are drugs with a potentially beneficial impact on the natural history of cirrhosis, on portal hypertension, and in HCC prevention. In this review, we summarize current evidence regarding the influence of statins in endothelial dysfunction in CLD, their ability to modulate hepatic fibrogenesis, and their vasoprotective effects in portal hypertension; we also focus on existing data about the impact of statins in cirrhosis development, progression, and complications and critically assess the current concerns about its use in patients with CLD.

Assuntos

RESUMO

El ultrasonido continúa siendo la primera investigación imaginológica en el estudio de los pacientes con hepatopatías crónicas, pues le permite al médico de asistencia, de manera rápida y eficaz, conocer el estado morfológico de los órganos involucrados y, además, mediante el estudio Doppler, valorar las características del flujo del sistema portal desde el punto de vista cuantitativo (velocidad del flujo) y cualitativo (permeabilidad y dirección del flujo así como la presencia de vasos de circulación colateral). Permite también evaluar todas las estructuras de la cavidad abdominal e investigar patologías asociadas, como es el caso del síndrome hepatorrenal. A favor de esta técnica están además; su bajo costo, fácil manejo, reproductibilidad y ausencia de intervensionismo, todo ello con alta sensibilidad y especificidad, superiores al de otras técnicas complejas de diagnóstico por imagen, como es la tomografía axial computarizada o la resonancia magnética nuclear. Con este trabajo nos proponemos realizar una revisión del tema y mostrar, mediante la literatura consultada y los resultados de nuestra experiencia, el valor del ultrasonido Doppler en el estudio de los pacientes con hepatopatías crónicas

Ultrasound (US) still is the first imaging research in the study of patients presenting with chronic liver diseases allowing to assistance physician to know in a fast and effective way the morphologic state of involved organs and also, be Doppler study, to evaluate the features of portal system flow from the quantitative point of view (flow speed) and the qualitative one (flow permeability and direction as well as the presence of collateral circulation vessels). Also allows to assess the structures of the abdominal cavity and to investigate the associated pathologies such as the hepatorenal syndrome. Favoring this technique are the following: its low cost, easy management, reproducibility and lack of interventions with a high sensitivity and specificity level superior to that of other complex techniques of imaging diagnosis by example, the computerized axial tomography (CAT) or the nuclear magnetic resonance (MNR)

Assuntos