Alcohol-related liver disease (ARLD) is a major public health issue caused by excessive alcohol consumption. ARLD encompasses a wide range of chronic liver lesions, alcohol-related liver cirrhosis being the most severe and harmful state. Variations in the genes encoding the enzymes, which play an active role in ethanol metabolism, might influence alcohol exposure and hence be considered as risk factors of developing cirrhosis.
View Article and Find Full Text PDFUnlabelled: Background. Nutritional deficiencies may aggravate the course of chronic hepatitis C (CHC). Our aim has been to perform a comprehensive analysis of body composition and nutritional deficiencies in CHC patients in non-cirrhotic and compensated cirrhotic stages to correlate the detected deficiencies with the fibrosis stage.
View Article and Find Full Text PDFInsulin resistance (IR) is found in chronic hepatitis C (CHC) more frequently than in other chronic liver diseases.Prospective cross-sectional study to evaluate a wide multitest panel to identify factors related with IR in CHC and their possible interactions.In 76 patients with CHC we performed a series of routine laboratory analysis as well as specifically designed serum biochemical tests [retinol, retinol-binding protein 4 (RBP4), 25-OH vitamin D, Vitamin E, lipopolysaccharide-binding protein (LBP), interleukin-6 (IL-6), and cystatin C].
View Article and Find Full Text PDFHepatitis C virus infection is a major health burden affecting 130-170 million people worldwide. Approximately 10-30% of those with chronic hepatitis C will progress to cirrhosis over 20-30 years. The development of new direct-acting antivirals has changed the management of the disease, allowing efficacious Interferon-free therapies superior to prior treatment regimens with minimal side effects, even in some subgroups previously thought to be difficult to cure such as cirrhotic patients.
View Article and Find Full Text PDFUnlabelled: Matrix metalloproteinases (MMPs) participate in tissue repair after acute injury, but also participate in cancer by promoting a protumorigenic microenvironment. Previously, we reported on a key role for MMP10 in mouse liver regeneration. Herein, we investigated MMP10 expression and function in human hepatocellular carcinoma (HCC) and diethylnitrosamine (DEN)-induced mouse hepatocarcinogenesis.
View Article and Find Full Text PDFBackground And Aims: Vitamin D exerts immunomodulatory effects on the host response against infection with hepatitis C virus (HCV). This study was performed to assess the putative influence of polymorphisms in vitamin D-related genes on the response to antiviral therapy in patients with chronic hepatitis C (CHC).
Methods: Single nucleotide polymorphisms (SNPs) in CYP27B-1260 gene promoter (rs10877012AC) and in vitamin D receptor (VDR) gene rs2228570TC, rs1544410CT, rs7975232AC and rs731236AT were analyzed in a cohort of 238 Caucasian CHC patients treated with pegylated interferon (Peg-IFN) plus ribavirin (RBV).
In addition to the known effects on drug metabolism and response, functional polymorphisms of genes coding for xenobiotic-metabolizing enzymes (XME) play a role in cancer. Genes coding for XME act as low-penetrance genes and confer modest but consistent and significant risks for a variety of cancers related to the interaction of environmental and genetic factors. Consistent evidence supports a role for polymorphisms of the cytochrome P450 CYP2C9 gene as a protecting factor for colorectal cancer susceptibility.
View Article and Find Full Text PDFBackground: Vitamin D has immunomodulatory properties, exerts an anti-hepatitis C virus (HCV) effect in vitro and improves response to interferon-based therapy in patients with chronic hepatitis C (CHC). Low serum levels of 25(OH) vitamin D [25(OH)D] are frequently found in CHC patients and seem to be related to more advanced stages of liver fibrosis. The study aims to establish the incidence of vitamin D deficiency in Spanish patients with CHC, its possible relation with features of liver damage and with the IL28B gene polymorphism, and the immediate effect of vitamin D therapy on CHC-related analytical variables.
View Article and Find Full Text PDFBackground: Serum levels of cystatin C, an endogenous inhibitor of cysteine proteases, provide an alternative method to creatinine-based criteria for measuring glomerular filtration rate. Preliminary data suggested that serum cystatin C levels parallel with the stage of liver fibrosis in chronic liver disorders. Our aim has been to evaluate the possible role of serum cystatin C as a marker of liver fibrosis in hepatitis C virus (HCV)-induced chronic liver disease.
View Article and Find Full Text PDFObjective: Sorafenib is the standard treatment of patients with advanced hepatocellular carcinoma, regardless of the liver functional reserve. We present a single institutional series of Child-Pugh A and Child-Pugh B patients treated with sorafenib with the aim to establish the efficacy and safety of sorafenib in patients of daily clinical conditions and to compare these results between Child-Pugh A and Child-Pugh B patients.
Materials And Methods: A total of 51 patients were treated with sorafenib 400 mg/12 h until disease progression or unacceptable toxicity.
Background/aims: Polymorphism at the IL28B gene may modify the course of hepatitis C virus (HCV) chronic infection. Our aim was to study the influence of IL28B rs12979860 gene polymorphism on the biochemistry and pathology of HCV-induced disease in the clinical course from mild chronic hepatitis C to hepatocellular carcinoma.
Methods: We have determined the rs12979860 single nucleotide polymorphism (SNP) upstream IL28B gene in two groups of patients with HCV-induced chronic liver disease: 1) 268 patients (159 men) with biopsy-proven chronic hepatitis C, to analyse its relation with biochemical, virological and histological features; and 2) 134 patients (97 men) with HCV-related hepatocellular carcinoma.
Objective: Toll-like receptor 4 (TLR4) signalling participates in the innate immune response against hepatitis C virus (HCV) infection. TLR4 gene polymorphisms may influence the risk of HCV-induced hepatocellular carcinoma (HCC). This is a single-centre-based study designed to analyse the distribution of several TLR4 gene single nucleotide polymorphisms in healthy controls and in patients chronically infected with HCV, with and without HCC.
View Article and Find Full Text PDFBackground And Aim: Polymorphisms at the interleukin-28B (IL28B) gene predict therapeutic response in chronic hepatitis C virus genotype 1 (CHC-1) infection. The aim of the present study was to establish whether a unique single-nucleotide polymorphism (SNP) represents the whole predictive value of the IL28B haplotype for sustained viral response (SVR) and primary non-response (PNR).
Methods: SNP rs12979860 and rs8099917 were determined by TaqMan assays in 110 CHC-1 Caucasian patients treated with pegylated interferon plus ribavirin.
Aims: To detect differences in the frequency of the known nonsynonymous CYP2W1 polymorphisms between colorectal cancer patients and healthy subjects.
Materials & Methods: The study group consisted of 150 colorectal patients and 263 controls. The presence of five nonsynonymous CYP2W1 polymorphisms was analyzed by novel amplification-restriction methods.
Background And Aims: more than half of patients with genotype 1 chronic hepatitis C (CHC) do not achieve a sustained viral response (SVR) to current antiviral therapy due to primary non-response, relapse or intolerance. Factors related to each of these unfavorable outcomes are different and the last two may be partially prevented. Our aim was to identify basal criteria to predict the risk of primary failure.
View Article and Find Full Text PDFObjective: Liver biopsy is an invasive procedure and new surrogate markers to assess fibrosis are needed. We performed a comparative external evaluation of nine non-invasive scores of liver fibrosis and tried to identify other potential biochemical markers of low-stage liver fibrosis in chronic hepatitis C (CHC).
Material And Methods: We included 429 previously untreated consecutive patients from a single centre who underwent a liver biopsy between January 1999 and April 2009.
Objective: To analyse the possible influence of a non-synonymous single nucleotide polymorphism (SNP) of the histamine-degrading enzyme diamine oxidase (DAO) on genetic susceptibility to Crohn's disease (CD).
Material And Methods: In this prospective, case-control study, 210 unrelated Caucasian consecutive CD patients were recruited at the Inflammatory Bowel Disease Unit of a single tertiary centre (Hospital Clínico San Carlos) in Madrid, Spain. A total of 261 healthy volunteers from the same geographic area were also recruited and matched with patients.
Rev Esp Enferm Dig
January 2009
Background: Hyperferritinemia is often found in patients with chronic hepatitis C (CHC) and is predictive of poorer response to antiviral therapy.
Objective: To investigate changes in ferritinemia during and after antiviral therapy.
Patients And Methods: serum ferritin levels were measured in 262 CHC patients (163 males, mean age 48.
Objective: The current guidelines recommend maintenance of combined therapy for hepatitis C virus (HCV) genotype-1 chronic hepatitis when HCV-RNA is undetectable or < or = 2 log10 of baseline after 12 weeks of therapy. The aim of this study was to investigate whether the probability of obtaining sustained viral (SVR) response is similar when HCV-RNA is undetectable or is present at < or = 2 log10 level after 12 weeks of therapy.
Material And Methods: Retrospective analysis was carried out in 208 HCV genotype-1 chronic hepatitis patients treated with pegylated interferon and ribavirin with available data on HCV viral load after 12 weeks of therapy and definite data on the results of therapy.
Unlabelled: Treatment response remains suboptimal for many patients with chronic hepatitis C, particularly those with genotype 1 and high levels of viremia. The efficacy of high-dose regimens of peginterferon alpha-2a and ribavirin was compared with conventional dose regimens in patients with features predicting poor treatment responses. Eligible treatment-naïve adults with genotype 1 infection, hepatitis C virus (HCV) RNA > 800,000 IU/mL and body weight > 85 kg were randomized to double-blind treatment with peginterferon alpha-2a at 180 or 270 microg/week plus ribavirin at 1,200 or 1,600 mg/day for 48 weeks (four regimens were evaluated).
View Article and Find Full Text PDFThe common single-nucleotide polymorphism (SNP) rs3802842 at 11q23.1 has recently been reported to be associated with risk of colorectal cancer (CRC). To examine this association in detail we genotyped rs3802842 in eight independent case-control series comprising a total of 10 638 cases and 10 457 healthy individuals.
View Article and Find Full Text PDFPolymorphic N-acetyl transferases (NAT) 1 and 2 are involved in detoxification of xenobiotic arylamines and hydralazines. These common environmental chemicals may be related to the pathogenesis of many spontaneous disorders, mainly malignancies, but also disimmune or degenerative diseases, for which a polygenic predisposition has been suggested. Hence, polymorphic NAT genes (NAT2 has been the most studied one) may be low-penetrance risk genes for some of these disorders.
View Article and Find Full Text PDFIntroduction: nearly all the data on the efficacy of combined antiviral therapy on chronic hepatitis C genotype 4 have been obtained in countries of Middle East. Genotype 4 is quite unusual in Spain. We report our experience in a group of Spanish patients treated with homogeneous criteria.
View Article and Find Full Text PDFTo identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls.
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