Investigating VEGF. miR-145-3p, and miR-101-3p Expression in Patients with Cholangiocarcinoma.

INTRODUCTION: Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer. Several factors, such as epigenetic changes in promoter genes, gene expression, and microRNAs (miR), can contribute to genomic instability in cancer. This study aimed at evaluating the expression of VEGF, miRs 145-3p, and 101-3p in patients with CCA and their potential as biomarkers for diagnosis and prognosis of CCA. MATERIAL AND METHODS: Sixty two patients were studied. Out of these 62 patients, 41 cases had confirm CCA and 21 cases had hepatopathies complications. The RNA was extracted from a paraffined tissue block, and then the synthesis of cDNA was performed. The analysis of the expression of VEGF, miR-145-3p, and miR-101-3p was carried out by polymerase chain reaction in real time.  Results: The findings revealed that miRs 145-3p and 101-3p were under expressed in the case group compared to the control group (0.46; 0.17; P = 0.0001, respectively). VEGF was overexpressed in the case group compared to the control group (11.8; P = 0.0001). An increase in miR-145-3p expression level was observed in patients with perihilar CCA compared to those with distal CCA (0.51 ± 0.41; 0.17 ± 0.13; P = 0.0698). Survival rate analysis showed that 41.9% of patients with intrahepatic CCA and 31.5% of patients with extrahepatic CCA were free from death within 11 months, leading to a significant difference (P> 0.05). CONCLUSION: The underexpression of miRNAs, tumor suppressors, the overexpression of VEGF, smoking, and aging were associated with CCA based on our findings. It seems that the reduced expression of the studies miRNAs and increased expression of VEGF can contribute to a decrease in survival rate of patients with tumor in their intrahepatic bile ducts.

Application of the Validated Social Assessment Instrument for Liver Transplantation Candidates.

The use of appropriate instruments for social assessment in health aims at both the participation of the subject and effectiveness in resolving demands. The objective of this study was to characterize the population assessed by the Validated Social Assessment Instrument and its implications; a descriptive, documental study with participant and dialectical observation. The data survey were taken from the social assessments applied from July 2020 to June 2021 in a transplant center in northwestern São Paulo state in Brazil. Descriptive statistics were performed. The 65 social evaluations of candidates for liver transplantation (LTx) have presented the following sociodemographic characteristics: male sex (n = 47; 72.3%); mean age of 55.05 years (range: 24-75 years old); with a partner (n = 50; 76.9%); low education level (n = 30; 46.2%); and coming from the state of São Paulo (n = 54; 83.1). Of those evaluated, 48 candidates (74%) were professionally inactive and 37 (56.9%) received assistance or social security benefits; 62 (95.4%) had a family caregiver; 61 (93.9%) had a resolutive compliance family response; 57 (87.7%) had facilitated accessibility; 59 (90.8%) met satisfactory housing standards; and 60 (92.3%) had full acceptance for LTx. The 65 candidates' (100%) social opinions were favorable, and 21 (32.3%) had some limitations and required further assistance. All of them received basic and specific social orientations, and 25 (38.5%) required social referrals. The variables have allowed a view at the totality of the social being in addition to widening the subject's participation in order to identify the real demands and facilitate the monitoring of actions, thus contributing for favorable conditions for treatment.

Evaluation of drug-induced liver injury as etiology for acute liver failure in Brazil.

INTRODUCTION AND OBJECTIVES: Little is known about the etiology of acute liver failure (ALF) in Latin America. The objective of this paper is to investigate the main etiologies of ALF in Brazil, including Drug Induced Liver Injury (DILI) using stringent causality criteria. PATIENTS OR MATERIAL AND METHODS: All the cases of individuals who underwent liver transplantation (LT) in 12 centers in Brazil for ALF were reviewed. When DILI was stated as the cause of ALF, causality criteria were applied on site by the main investigator in order to rule out other etiologies. RESULTS: 325 individuals had ALF mainly for unknown reasons (34%), DILI (27%) and AIH (18%). Reassessment of the 89 cases of DILI, using stringent causality criteria, revealed that in only 42 subjects could DILI be confirmed as the cause of ALF. Acetaminophen (APAP) toxicity (n = 3) or DILI due to herbal and dietary supplements (HDS) (n = 2) were not commonly observed. CONCLUSIONS: Undetermined etiology and DILI are the main causes of ALF in Brazil. However, APAP toxicity and DILI due to HDS are mostly uncommon.

Clinical and laboratorial profiles of dengue virus infection in kidney transplant recipients: Report of a single center.

Dengue infection (DI) is the most important arboviral infection in the world. The majority of immunocompetent patients will have asymptomatic or mild infections, but the degree of dengue severity in kidney transplant recipients (KTx) is unknown. In this study, we report the clinical profile and outcomes of 39 dengue cases in KTx. From a total of 1,186 KTx outpatients in follow-up we reviewed clinical and laboratory records of 60 (5%) patients admitted with suspected DI initially screened by NS-1, IgM, and when possible, multiplex nested PCR. The prevalence of DI in KTx was 3% (39/1,118), with symptoms leading to hospital admission being fever, myalgia, malaise, and headache. Laboratory tests showed leucopenia, thrombocytopenia, and liver enzyme elevation. DI was confirmed by positivity of NS-1 (33%), IgM (69%), and/or RT-PCR (59%). Twenty-three patients (59%) had dengue with warning signs, and 15% had severe dengue, 2 of them with a fatal course. Acute graft dysfunction occurred in 59% (mean nadir serum creatinine: 2.9 ± 2.6mg/dL), 4 of them requiring dialysis. CMV coinfection diagnosed in 19% of the cases and patients was associated with worse clinical presentation. Our results suggest that KTx with DI presented initial physical and laboratorial profile similar to the general population. However, DI in KTx seems to have a higher risk for graft dysfunction, severe dengue, and death. Because CMV coinfection aggravates the DI clinical presentation and recovery, it must be evaluated in all cases.

Clinical, Epidemiological and Histopathological Aspects in Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation

Background: Hepatocellular Carcinoma (HCC) is the primary liver cancer with high incidence and mortality rates. Currently one of the major etiologies for liver disease, HCC and liver transplantation is nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the epidemiological, histopathological and clinical aspects of HCC transplant patients, with emphasis on NAFLD etiology. Methods: This study included all HCC patients submitted to liver transplantation from 2010 to 2016 of the University Reference Center. The analyzed variables were age, gender, ethnicity, causes that led to liver transplantation, alpha-fetoprotein (AFP) dosage, histological aspects, recurrence, survival and NAFLD. Results: A total of 60 patients were included in the study being 80% men with a mean age of 58.3 ± 10.6 years. All patients were cirrhotic. The causes that led to the transplantation were the presence of the hepatitis C virus (HCV) (56.6% of the patients), an association of the virus with alcohol (20%), the presence of the hepatitis B virus (HBV) (20%), alcoholic liver disease (ALD) (50.9%) and NAFLD (25%). Of the latter, eight were diagnosed pre-transplantation and seven were NAFLD carriers without a previous diagnosis. Regarding the Edmondson-Steiner histological classification, 58.5% of the patients were classified as grade ≤ II. Conclusions: There is predominance of male patients with a mean age of 58.3 years. Degree ≤ II is the most frequent to the Edmondson-Steiner histological classification in the evaluated casuistic. HCV, ALD and NAFLD is the most common etiological agents found in the study. The (high) underestimated prevalence of NAFLD in the pre-transplanted patients is due to the fact that all patients presented cirrhosis, masking NAFLD signals.

Hepatocellular Carcinoma: a Comprehensive Review of Biomarkers, Clinical Aspects, and Therapy

Hepatocellular carcinoma (HCC) is a cause of several deaths related to cancer worldwidely. In early stage, curative treatments such as surgical resection, liver transplant and local ablation can improve the patient ´s survival. However, the disease is detected in advanced stage; moreover some available therapies are restricted to palliative care and local treatment. Early detections of HCC and adequate therapy are crucial to increase survival as well as to improve the patient´s quality of life. Therefore, researchers have been investigating molecular biomarkers with high sensibility and reliability as Golgi 73 protein (GP73), Glypican-3 (GPC3), Osteopontin (OPN), microRNAs and others. MicroRNAs can regulate important pathways on carcinogenesis, as tumor angiogenesis and progression. So, they can be considered as possible markers of prognosis in HCC, and therapeutic target for this tumor type. In this review, we discuss the recent advances related to the cause (highlighting the main risk factors), treatment, biomarkers, clinic aspects, and outcome in hepatocellular carcinoma.

VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF) involved in angiogenesis process. The aim of this study was to evaluate the association of VEGF-A (C936T and A1154G) with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1), 117 with cirrhosis (G2), and 127 controls (G3). Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild-type genotype of both polymorphisms prevailed (P > 0.05). In G1, 23% of the patients died, with no relation to genetic profile (P > 0.05). Increased VEGF level was observed in G1 and G3, related to the mutant allele of VEGF-C936T and VEGF-A1154G, respectively, and compared with the wild-type genotype (P = 0.0285; P = 0.0284, resp.) as well as G1 versus G2 and G3 for VEGF-C936T and G1 versus G2 for VEGF-A1154G (P < 0.05 for both). In conclusion, there is a relationship between mutant alleles of VEGF-C936T and VEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC.