N-acetyltransferase Gene Variants Involved in Pediatric Idiosyncratic Drug-Induced Liver Injury.

Idiosyncratic drug-induced liver injury (DILI) is a complex multifactorial disease in which the toxic potential of the drug, together with genetic and acquired factors and deficiencies in adaptive processes, which limit the extent of damage, may determine susceptibility and make individuals unique in their development of hepatotoxicity. In our study, we sequenced the exomes of 43 pediatric patients diagnosed with DILI to identify important gene variations associated with this pathology. The result showed the presence of two variations in the NAT2 gene: c.

Metabolomic Analysis of Pediatric Patients with Idiosyncratic Drug-Induced Liver Injury According to the Updated RUCAM.

Hepatotoxicity, a common adverse drug effect, has been extensively studied in adult patients. However, it is equally important to investigate this condition in pediatric patients to develop personalized treatment strategies for children. This study aimed to identify plasma biomarkers that characterize hepatotoxicity in pediatric patients through an observational case-control study.

Killer immunoglobulin-like receptor and cancer.

Introduction: Natural killer (NK) cells play an important role in defense against tumor cells. The development and function of NK cells is governed by a dynamic balance between inhibition and activation of cell surface receptors, including KIR receptors.

Patients And Method: A case-control study is carried out that compares a group of 46 children diagnosed with malignant diseases, the control group is made up of 82 healthy children.

[Killer immunoglobulin-like receptor and cancer].

Introduction: Natural killer (NK) cells play an important role in defense against tumor cells. The development and function of NK cells is governed by a dynamic balance between inhibition and activation of cell surface receptors, including KIR receptors.

Patients And Method: A case-control study is carried out that compares a group of 46 children diagnosed with malignant diseases, the control group is made up of 82 healthy children.

The relation between activator and inhibitor killer-cell immunoglobulin-like receptors and hepatotoxicity in oncological treatment.

Background: The molecular interactions between killer-cell immunoglobulin-like receptors (KIRs) and their related HLA class I ligands play a central role in regulating the responses of natural killer (NK) cells. Our study aim was to determine the role played by KIR genes and their HLA ligands in the genetic predisposition for the development of hepatotoxicity in children treated with chemotherapy for an oncological process.

Methods: The study group was composed of 22 children with cancer, being treated with chemotherapy at the Unit of Pediatric Oncology of the Maternity Hospital Virgen de las Nieves (Granada, Spain) and presenting signs of drug-induced liver injury (DILI).

[Chemotherapy-induced liver injury in children].

Introduction: Drug-induced liver injury due to chemotherapy is an important cause of morbidity in cancer patients, although its clinical manifestations are poorly understood.

Objective: The objective of the present study was to determine the characteristics (forms of presentation, severity, and type of injury) of hepatotoxicity due to chemotherapy in children treated for cancer.

Patients And Method: A total of 22 oncological patients were included in the study, after ruling out other causes of increased transaminases (infectious, metabolic, autoimmune, or hereditary), according to the CIOMS causality scale, it is concluded that it was a possible, probable or definite episode of hepatic injury by drugs.

Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment.

Aim: To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments.

Methods: Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), = 49; IFN-α + ribavirin (RBV), = 75; pegylated (peg) IFN-α + RBV, = 47; first-generation direct-acting antivirals (DAAs), = 13; and second-generation DAAs, = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR).

Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.

Introduction: Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients.

Analysis of Immunogenetic Factors in Idiosyncratic Drug-induced Liver Injury in the Pediatric Population.

Objectives: Idiosyncratic drug-induced liver injury is a multifactorial complex disease, in which the toxic potential of the drug, together with genetic and acquired factors and deficiencies in adaptive processes, which limit the extent of damage, can determine susceptibility, and make individuals unique in their development of hepatotoxicity. The aim of the present study is to analyse the genetic factors (human leukocyte antigen [HLA], cytokine polymorphisms, and killer cell immunoglobulin-like receptor [KIR] genotype) of children who experience an episode of drug-induced liver injury.

Patients And Methods: Prospective multicentre case-control study.

Effectiveness and safety of first-generation protease inhibitors in clinical practice: Hepatitis C virus patients with advanced fibrosis.

Aim: To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis.

Methods: Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-naïve (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings.

High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods.

Hepatitis C virus (HCV) is classified into seven major genotypes and 67 subtypes. Recent studies have shown that in HCV genotype 1-infected patients, response rates to regimens containing direct-acting antivirals (DAAs) are subtype dependent. Currently available genotyping methods have limited subtyping accuracy.

[The value of genetics in the era of hepatitis C triple therapy].

Despite the introduction of protease inhibitors (PI) in the treatment of hepatitis C, the sensitivity of interferon continues to be essential to achieve a sustained virological response (SVR) and to eradicate the viral infection. Currently, pegylated interferon (PEG-IFN) and ribavirin (RBV) are required to avoid selection of PI-resistance mutations. The likelihood of obtaining an SVR with dual therapy in treatment-naïve patients with genotype 1 infection varies from 40% to 50%.

Synergistic cytotoxicity of the poly (ADP-ribose) polymerase inhibitor ABT-888 and temozolomide in dual-drug targeted magnetic nanoparticles.

Background & Aims: Hepatocellular carcinoma (HCC) is associated with a poor prognosis because of a lack of effective treatment options. The objective of this study was to examine a new strategy for HCC treatment, namely the use of poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor (ABT-888) together with Temozolomide (TMZ) incorporated onto magnetic nanoparticles.

Methods: Magnetic Fe3 O4 /Fe cores were encapsulated within a silica shell to facilitate the simultaneous incorporation of ABT-888 and TMZ.

Melatonin reduces endothelin-1 expression and secretion in colon cancer cells through the inactivation of FoxO-1 and NF-κβ.

Melatonin is an indoleamine that is synthesised from tryptophan under the control of the enzymes arylalkylamine N-acetyltransferase (AA-NAT) and acetylserotonin methyltransferase (ASMT). Melatonin inhibits colon cancer growth in both in vivo and in vitro models; however, a precise mechanism responsible for inhibiting tumour growth has not been clearly described. Endothelin-1 (ET-1) is a peptide that acts as a survival factor in colon cancer, inducing cell proliferation, protecting carcinoma cells from apoptosis and promoting angiogenesis.

Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.

Importance of IL-10 and IL-6 during chronic hepatitis C genotype-1 treatment and their relation with IL28B.

Unlabelled: This paper investigates serum levels of interleukin 10 (IL-10) and interleukin 6 (IL-6) in patients with chronic hepatitis C genotype 1 (CHC-GT1), the relation of each with clinical and virological characteristics, how they affect the response to combined therapy and their relation with the IL28B polymorphisms rs12979860. Serum level expression and the polymorphism of IL-10, IL-6 and IL28B were determined in 138 CHC-GT1 patients, treated with pegylated interferon/ribavirin (pegIFN-α/RBV) for 48 weeks, in the following samples: baseline, week-12 (during treatment) and week-72 (post-treatment). 77 patients (56%) presented Sustained Virological Response (SVR) and 61 (44%) were non-SVR.

Aphorisms and short phrases as pieces of knowledge in the pedagogical framework of the andalusian school of public health.

Background: Bearing in mind the philosophical pedagogical significance of short phrases for the training of researchers in the health care ambit, we hence have studied the aphorisms and striking phrases expressed during the epidemiology course at the Andalusian School of Public Health.

Methods: Belonging to the qualitative type and applied through the establishment of a multidisciplinary focus group made up of ten post-graduated students, where one of them acted as a moderator. The collection of information lasted four months.

Plasma ribavirin trough concentrations during treatment of chronic hepatitis C in genotype-1 patients.

Goals: To investigate the correlation between virological response and plasma ribavirin trough concentrations (RBV Ctrough) during the full period of chronic hepatitis C (CHC) treatment.

Study: Multicenter prospective cohort study. Total 119 patients with CHC genotype-1 were treated with peginterferon alfa-2a (pegIFN) and RBV for 48 weeks.

Gender-related invasion differences associated with mRNA expression levels of melatonin membrane receptors in colorectal cancer.

Melatonin inhibits growth and invasive capacity of colon cancer cells in vitro through its membrane (MT1 and MT2) and/or nuclear receptors (RORα). Previous studies showed that this indoleamine is present in both the normal and colon cancer at similar levels. Therefore, we analyzed MT1, MT2, and RORα expression in tumor samples versus normal mucosa (NM) from patients suffering from colorectal cancer (CRC).

Importance of host genetic factors HLA and IL28B as predictors of response to pegylated interferon and ribavirin.

Objectives: Viral factors are considered the best predictors of response to treatment for chronic hepatitis C (CHC), but genetic factors are known to have an important role in this respect. This paper investigates the relationships among the host genetic factors HLA and IL28B, viral factors, and the outcome of combination therapy.

Methods: A multicenter retrospective cohort of 428 previously untreated CHC patients was treated with pegylated interferon/ribavirin (pegIFN/RBV) for 48 weeks.

Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV-infected children.

Unlabelled: The vertical transmission of hepatitis C virus (HCV-VT) is a major route of HCV infection in children, but the risk factors remain incompletely understood. This study analyzed the role of interleukin 28B (IL28B) in HCV-VT and in the spontaneous clearance of HCV among infected infants. Between 1991 and 2009, 145 mothers were recruited for this study: 100 were HCV-RNA+ve / human immunodeficiency virus negative (HIV-ve), with 128 children, and 33 were HCV-RNA-ve/HCV antibody+ve, with 43 children.

Inhibition of poly adenosine diphosphate-ribose polymerase decreases hepatocellular carcinoma growth by modulation of tumor-related gene expression.

Unlabelled: Hepatocellular carcinoma (HCC) is associated with a poor prognosis due to a lack of effective treatment options. In HCC a significant role is played by DNA damage and the inflammatory response. Poly (ADP-ribose) polymerase-1 (PARP-1) is an important protein that regulates both these mechanisms.

Quasispecies as predictive factor of rapid, early and sustained virological responses in chronic hepatitis C, genotype 1, treated with peginterferon-ribavirin.

Background: The relationship between the complexity of the hypervariable region 1 quasispecies of HCV and responsiveness to therapy is not completely clear.

Objective: To investigate the importance of quasispecies as a predictive factor of rapid (RVR), early (EVR) and sustained (SVR) virologic response.

Methods: Prospective analysis of 82 patients with chronic hepatitis C, genotype 1, treated with peginterferon alfa-2a and ribavirin.