Effect of ß-Mannanase Addition during Whole Pigs Fattening on Production Yields and Intestinal Health.

The presence of ß-mannans in feed can produce a futile and chronic immune stimulation in fattening pigs. In this trial, a 1-4-endo-D-ß-mannanase was added to the feed (HC) during growth and fattening (0.03% of Hemicell HT) and physical performance and pathological data were recorded, and intestinal integrity and immune activation were studied by molecular biomarkers, compared to a control group (CON). The treatment diet was reduced in energy content by 40 Kcal/kg NE. From each group, 113 and 112 animals housed in 8 pens were individually identified and weighed three times: at 7th, 63rd and 116th days in feed. The FCR was calculated for groups of two pens and ADG individually. There was no difference in ADG (CON = 0.836, HC = 0.818) nor in FCR between groups (p = 0.486). During growth, there was a higher frequency of normal feces in HC and there were also no differences in the frequency of gastric lesions. A significant increase in Claudin, Occludin, IFN-γ and IL8 was observed in the CON in feces and a significant decrease in IL-6 in HC. In tissues, there were differences for IL-12p40, TNF-alpha in jejunum (increased CON) and TGF-ß in ileum and jejunum, (decreased HC). The economic performance was EUR 4.7 better in the treated group. In conclusion, the addition of 1-4-endo-D-ß--mannanase to the feed with a 1.6% reduction in net energy compared to the control, allowed the animals to perform as well as the animals on the higher energy diet, with lower prevalence of diarrhea.

Increased expression of MNK1b, the spliced isoform of MNK1, predicts poor prognosis and is associated with triple-negative breast cancer.

MAP kinase interacting kinases (MNKs) modulate the function of oncogene eukaryotic initiation factor 4E (eIF4E) through phosphorylation, which is necessary for oncogenic transformation. MNK1 gives rise to two mRNAs and thus two MNK1 isoforms, named MNK1a and MNK1b. MNK1b, the splice variant of human MNK1a, is constitutively active and independent of upstream MAP kinases. In this study, we have analyzed the expression of both MNK1 isoforms in 69 breast tumor samples and its association with clinicopathologic/prognostic characteristics of breast cancer. MNK1a and MNK1b expression was significantly increased in tumors relative to the corresponding adjacent normal tissue (p < 0.001). In addition, MNK1b overexpression was found in most of the triple-negative tumors and was associated with a shorter overall and disease-free survival time. Overexpression of MNK1b in MDA-MB-231 cells induced an increase in the expression of the MCL1 antiapoptotic protein and promoted proliferation, invasion and colony formation. In conclusion, a high expression level of MNK1b protein could be used as a marker of poor prognosis in breast cancer patients and it could be a therapeutic target in triple-negative tumors.

Changes in the response to treatment against chronic hepatitis C between 1999 and 2015: data from a prospective cohort.

BACKGROUND: The drug options and strategies for treatment against hepatitis C virus (HCV) infection have changed considerably in the last few years. The aim of this study was to compare the changes in the proportion of nonresponders and patients who achieved a sustained virologic response (SVR) from 1999 to 2015 in one single cohort. PATIENTS AND METHODS: A total of 522 patients treated against chronic hepatitis C were included prospectively. The time periods were 1999-2002 [interferon (IFN)/ribavirin (RBV)], 2002-2009 (pegylated-IFN/RBV), 2010-2011 (use of IL28B genotype), 2012-2014 (pegylated-IFN/RBV/direct-acting antivirals) and 2015 (IFN-free direct-acting antiviral-based therapy). RESULTS: The numbers of nonresponders in the study periods in chronological order were as follows: 14 (40%), 76 (21.3%), 7 (8%), 10 (13%), and 0; P=1.1×10 and r=0.837. The corresponding numbers of patients who achieved SVR were 9 (25.7%), 14 (40.9%), 44 (50.6%), 51 (66.2%), and 64 (90.1%), P=3.3×10 and r=0.997. Characteristics that may impair SVR, such as advanced fibrosis, genotype 1 infection, HIV coinfection, or treatment experience, did not decrease in the last time periods. CONCLUSION: The proportion of nonresponders was significantly reduced using the IL28B genotype as a predictive tool and direct-acting antivirals further improved treatment outcome. Concomitantly, the rates of SVR showed a linear increase.

Chemokine (C-C Motif) Receptor 2 Mediates Dendritic Cell Recruitment to the Human Colon but Is Not Responsible for Differences Observed in Dendritic Cell Subsets, Phenotype, and Function Between the Proximal and Distal Colon.

BACKGROUND & AIMS: Most knowledge about gastrointestinal (GI)-tract dendritic cells (DC) relies on murine studies where CD103+ DC specialize in generating immune tolerance with the functionality of CD11b+/- subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon. METHODS: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing. RESULTS: Colonic DC identified were myeloid (mDC, CD11c+CD123-) and further divided based on CD103 and SIRPα (human analog of murine CD11b) expression. CD103-SIRPα+ DC were the major population and with CD103+SIRPα+ DC were CD1c+ILT3+CCR2+ (although CCR2 was not expressed on all CD103+SIRPα+ DC). CD103+SIRPα- DC constituted a minor subset that were CD141+ILT3-CCR2-. Proximal colon samples had higher total DC counts and fewer CD103+SIRPα+ cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4+CD45RA+ T-cells. However, DC and DC-invoked T-cell expression of mucosal homing markers (ß7, CCR9) was lower for proximal DC. CCR2 was expressed on circulating CD1c+, but not CD141+ mDC, and mediated DC recruitment by colonic culture supernatants in transwell assays. Proximal colon DC produced higher levels of cytokines. Mucosal microbiota profiling showed a lower microbiota load in the proximal colon, but with no differences in microbiota composition between compartments. CONCLUSIONS: Proximal colonic DC subsets differ from those in distal colon and are more mature. Targeted immunotherapy using DC in T-cell mediated GI tract inflammation may therefore need to reflect this immune compartmentalization.

Characterization of MNK1b DNA Aptamers That Inhibit Proliferation in MDA-MB231 Breast Cancer Cells.

Elevated expression levels of eukaryotic initiation factor 4E (eIF4E) promote cancer development and progression. MAP kinase interacting kinases (MNKs) modulate the function of eIF4E through the phosphorylation that is necessary for oncogenic transformation. Therefore, pharmacologic MNK inhibitors may provide a nontoxic and effective anticancer strategy. MNK1b is a truncated isoform of MNK1a that is active in the absence of stimuli. Using in vitro selection, high-affinity DNA aptamers to MNK1b were selected from a library of ssDNA. Selection was monitored using the enzyme-linked oligonucleotide assay (ELONA), and the selected aptamer population was cloned and sequenced. Four groups of aptamers were identified, and the affinities of one representative for rMNK1b were determined using ELONA and quantitative polymerase chain reaction. Two aptamers, named apMNK2F and apMNK3R, had a lower Kd in the nmol/l range. The secondary structure of the selected aptamers was predicted using mFold, and the QGRS Mapper indicated the presence of potential G-quadruplex structures in both aptamers. The selected aptamers were highly specific against MNK1, showing higher affinity to MNK1b than to MNK1a. Interestingly, both aptamers were able to produce significant translation inhibition and prevent tumor cell proliferation and migration and colony formation in breast cancer cells. These results indicate that MNK1 aptamers have an attractive therapeutic potential.

Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection.

BACKGROUND: Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients. PATIENTS AND METHODS: This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 µg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control. RESULTS: Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events. CONCLUSIONS: No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01529073.

Progression of liver stiffness predicts clinical events in HIV/HCV-coinfected patients with compensated cirrhosis.

BACKGROUND: Our objective was to assess the predictive value of the changes of liver stiffness (LS) for clinical outcome in HIV/HCV-coinfected patients with compensated liver cirrhosis and a LS value < 40 kPa. METHODS: Prospective cohort of 275 HIV/HCV-coinfected patients with cirrhosis, no previous liver decompensation (LD) and LS < 40 kPa. The time from diagnosis to LD and/or hepatocellular carcinoma (HCC) and the predictors of this outcome were evaluated. Significant progression of LS was defined as an increase ≥ 30 % over the baseline value at any time during the follow-up. RESULTS: After a median (Q1-Q3) follow-up of 32 (20-48) months, 19 (6.9 %, 95 % CI: 3.8 %-9.9 %) patients developed a first LD and/or HCC. At the end of the follow-up, 247 (90 %) patients had undergone a further LS examination. Of them, 77 (31 %) patients had a significant progression of LS. The mean (SD) survival time free of LD and/or HCC was 67 (3) and 77 (1) months in patients with or without significant progression of LS (p = 0.01). Significant progression of LS was an independent predictor of LD and/or HCC (Adjusted Hazard Ratio 4.63; 95 % confidence interval: 1.34-16.02; p = 0.015). CONCLUSIONS: Significant progression of LS is associated with a higher risk of clinical events in HIV/HCV-coinfected patients with compensated cirrhosis and LS < 40 kPa.

Cambios en la prevalencia y distribución genotípica de la coinfección por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana / Prevalence and genotype distribution changes in hepatitis C virus co-infection among human immunodeficiency virus-infected patients

INTRODUCCIÓN: La prevalencia de hepatitis C es menor en los nuevos casos de pacientes infectados por VIH en España. El uso creciente del tratamiento frente al VHC podría haber cambiado la distribución genotípica del VHC. El objetivo de este estudio fue analizar los cambios en la prevalencia de la coinfección por VHC y en la distribución genotípica del VHC en pacientes infectados por VIH. Métodos Estudio de prevalencia seriada. Se incluyeron todos los pacientes infectados por VIH que acudieron a las consultas de un hospital de Andalucía entre septiembre de 2008 y febrero de 2009 (primer periodo) y entre enero y junio de 2013 (segundo periodo).Resultados Se incluyeron 520 y 651 pacientes en el primer y segundo periodos, respectivamente. El factor de riesgo de infección por VHC en el primer y segundo periodo fue: UDVP 319 (61%) vs. 348 (53%); contacto heterosexual, 111 (21%) vs. 135 (21%); homosexual, 76 (15%) vs. 114 (22%) (p = 0,006). La prevalencia de anti-VHC por periodos fue del 69% vs. el 58% (p=<0,001), y la de ARN-VHC detectable fue 49% vs. 37% (p=<0,001). En ambos periodos, la distribución genotípica fue: 1, 137 (60%) vs. 138 (59%); 3, 45 (20%) vs. 42 (18%); 4, 42 (18%) vs. 47 (20%) (p = 0,881). CONCLUSIONES: La prevalencia de infección por el VHC ha disminuido en los pacientes infectados por VIH en nuestro medio, incluyendo tanto la exposición al virus como la infección activa, en los últimos 5 años. Sin embargo, la distribución de los genotipos del VHC no ha cambiado

BACKGROUND: The prevalence of hepatitisC is decreasing among new diagnoses of HIV/HCV coinfection in Spain. The increasing use of the HCV treatment could have changed the HCV genotype distribution. The aim of this study is to analyze changes in the prevalence of HCV coinfection and in HCV genotype distribution among HIV-infected patients. METHODS: A serial cross-sectional study was conducted that included all HIV-infected patients who attended the Outpatient Clinic of a hospital in Andalusia, between September 2008 and February 2009 (first period), and between January 2013 and June 2013 (second period). RESULTS: A total of 520 and 651 patients were included in the first and second period, respectively. The risk factors of HCV infection in the first vs. second period were: IDU, 319 (61%) vs. 348 (53%); heterosexual contact, 111 (21%) vs. 135 (21%); homosexual men, 76 (15%) vs. 114 (22%) (P=.006). The prevalence of HCV antibody per period was: 358 (69%) vs. 380 (58%) (P=<.001), and for the HCV-RNA was 255 (49%) vs. 240 (37%) (P=<.001). In both periods, the HCV genotype distribution was: 1, 137 (60%) vs. 138 (59%); 3, 45 (20%) vs. 42 (18%); 4, 42 (18%) vs. 47 (20%) (P=.881). CONCLUSIONS: The prevalence of HCV infection in HIV-infected patients has decreased in our area, including overall exposure to HCV virus and active infection during the last 5 years. However, the HCV genotype distribution has not changed

[Prevalence and genotype distribution changes in hepatitis C virus co-infection among human immunodeficiency virus-infected patients]. / Cambios en la prevalencia y distribución genotípica de la coinfección por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND: The prevalence of hepatitisC is decreasing among new diagnoses of HIV/HCV coinfection in Spain. The increasing use of the HCV treatment could have changed the HCV genotype distribution. The aim of this study is to analyze changes in the prevalence of HCV coinfection and in HCV genotype distribution among HIV-infected patients. METHODS: A serial cross-sectional study was conducted that included all HIV-infected patients who attended the Outpatient Clinic of a hospital in Andalusia, between September 2008 and February 2009 (first period), and between January 2013 and June 2013 (second period). RESULTS: A total of 520 and 651 patients were included in the first and second period, respectively. The risk factors of HCV infection in the first vs. second period were: IDU, 319 (61%) vs. 348 (53%); heterosexual contact, 111 (21%) vs. 135 (21%); homosexual men, 76 (15%) vs. 114 (22%) (P=.006). The prevalence of HCV antibody per period was: 358 (69%) vs. 380 (58%) (P=<.001), and for the HCV-RNA was 255 (49%) vs. 240 (37%) (P=<.001). In both periods, the HCV genotype distribution was: 1, 137 (60%) vs. 138 (59%); 3, 45 (20%) vs. 42 (18%); 4, 42 (18%) vs. 47 (20%) (P=.881). CONCLUSIONS: The prevalence of HCV infection in HIV-infected patients has decreased in our area, including overall exposure to HCV virus and active infection during the last 5 years. However, the HCV genotype distribution has not changed.

DNA aptamers selectively target Leishmania infantum H2A protein.

Parasites of the genus Leishmania produce leishmaniasis which affects millions people around the world. Understanding the molecular characteristics of the parasite can increase the knowledge about the mechanisms underlying disease development and progression. Thus, the study of the molecular features of histones has been considered of particular interest because Leishmania does not condense the chromatin during mitosis and, consequently, a different role for these proteins in the biology of the parasite can be expected. Furthermore, the sequence divergences in the amino and in the carboxy-terminal domains of the kinetoplastid core histones convert them in potential diagnostic and/or therapeutics targets. Aptamers are oligonucleotide ligands that are selected in vitro by their affinity and specificity for the target as a consequence of the particular tertiary structure that they are able to acquire depending on their sequence. Development of high-affinity molecules with the ability to recognize specifically Leishmania histones is essential for the progress of this kind of study. Two aptamers which specifically recognize Leishmania infantum H2A histone were cloned from a previously obtained ssDNA enriched population. These aptamers were sequenced and subjected to an in silico analysis. ELONA, slot blot and Western blot were performed to establish aptamer affinity and specificity for LiH2A histone and ELONA assays using peptides corresponding to overlapped sequences of LiH2A were made mapping the aptamers:LiH2A interaction. As "proofs of concept", aptamers were used to determine the number of parasites in an ELONA platform and to purify LiH2A from complex mixtures. The aptamers showed different secondary structures among them; however, both of them were able to recognize the same peptides located in a side of the protein. In addition, we demonstrate that these aptamers are useful for LiH2A identification and also may be of potential application as diagnostic system and as a laboratory tool with purification purpose.

Interobserver concordance in controlled attenuation parameter measurement, a novel tool for the assessment of hepatic steatosis on the basis of transient elastography.

BACKGROUND: The combination of transient elastometry with a controlled attenuation parameter (CAP) is available to evaluate hepatic steatosis (HS) along with liver stiffness. AIMS: To assess the concordance of CAP measurements between two independent observers in patients infected by HIV and/or hepatitis virus, as well as to determine the concordance of classification of the grade of HS using two cut-off values. MATERIALS AND METHODS: In a cross-sectional prospective study, CAP-enabled transient elastometry acquisitions were performed by two independent observers in patients with HIV or hepatitis virus infection. The interobserver concordance between the CAP examinations was assessed using the intraclass correlation coefficient and the concordance in the classification of patients in the grades of HS was characterized using the κ index. RESULTS: A total of 118 patients were included. Twenty (17%) patients were HIV monoinfected, 44 (37.3%) were hepatitis C virus monoinfected, and 52 (44%) had HIV/hepatitis C virus coinfection. The median (Q1-Q3) of the absolute difference of CAP values between the two observers was 20 (10-41) dB/m. The overall intraclass correlation coefficient was 0.84 (95% confidence interval: 0.77-0.88). The corresponding figures for liver stiffness measurements were 0.9 (0.4-2.6) kPa and 0.96 (95% confidence interval: 0.94-0.97). The κ indexes for the concordance of classification for the presence of HS, cut-off of 215 dB/m, and significant HS, cut-off of 252 dB/m, were 0.53 and 0.62, respectively. CONCLUSION: The determination of HS by means of CAP in HIV and/or hepatitis virus infection represents an observer-independent and easily performable method. However, the use of cut-off values for the classification of patients is suboptimal.

No influence of antiretroviral therapy on the mutation rate of the HCV NS5B polymerase in HIV/HCV-coinfected patients.

OBJECTIVES: To assess the impact of antiretroviral treatment (ART), including nucleoside analogues retrotranscriptase inhibitors (NRTIs), on the mutation rate of hepatitis C virus (HCV) NS5B polymerase and on the ratio of substitution at synonymous and nonsynonymous sites (dN/dS) this polymerase in HIV/HCV-coinfected patients. PATIENTS AND METHODS: Sixty-one patients on defined ART were included in this study. The NS5B polymerase of HCV was sequenced at baseline and after at least two years of ART. The mutation rate and the dN/dS were calculated at both times. RESULTS: The NS5B gene from forty-nine (80.3%) patients including; 19 HCV-1a (38.8%), 13 HCV-1b (26.5%), 8 HCV-3a (16.3%) and 9 HCV-4d (18.4%), could be sequenced. Thirty-two (65.3%) patients received non-nucleoside analogues and 41 (83.7%) received protease inhibitor. The mean estimated substitution rates at baseline and at the end of follow-up were from 1.38 to 3.5×10(-3)substitution/site/year (s/s/y) and from 1.39 to 3.18×10(-3)s/s/y, respectively, varying according to HCV genotype. All HCV genotypes at baseline and the end time point had values of dN/dS <1. At the end of follow-up, most of sites experienced negative selection and positive selection occurred only in a few sites. CONCLUSION: The mutation rate of NS5B in HIV/HCV-coinfected patients is within the range previously reported in studies in HCV-monoinfected patients. Additionally, the use of ART, including NRTIs, in these patients does not affect neither mutation rate nor the dN/dS of the HCV NS5B protein, suggesting that its use would not generate new resistance mutants to the polymerase inhibitors of HCV.

eIF4F complex disruption causes protein synthesis inhibition during hypoxia in nerve growth factor (NGF)-differentiated PC12 cells.

Poor oxygenation (hypoxia) influences important physiological and pathological situations, including development, ischemia, stroke and cancer. Hypoxia induces protein synthesis inhibition that is primarily regulated at the level of initiation step. This regulation generally takes place at two stages, the phosphorylation of the subunit α of the eukaryotic initiation factor (eIF) 2 and the inhibition of the eIF4F complex availability by dephosphorylation of the inhibitory protein 4E-BP1 (eukaryotic initiation factor 4E-binding protein 1). The contribution of each of them is mainly dependent of the extent of the oxygen deprivation. We have evaluated the regulation of hypoxia-induced translation inhibition in nerve growth factor (NGF)-differentiated PC12 cells subjected to a low oxygen concentration (0.1%) at several times. Our findings indicate that protein synthesis inhibition occurs primarily by the disruption of eIF4F complex through 4E-BP1 dephosphorylation, which is produced by the inhibition of the mammalian target of rapamycin (mTOR) activity via the activation of REDD1 (regulated in development and DNA damage 1) protein in a hypoxia-inducible factor 1 (HIF1)-dependent manner, as well as the translocation of eIF4E to the nucleus. In addition, this mechanism is reinforced by the increase in 4E-BP1 levels, mainly at prolonged times of hypoxia.

Interobserver concordance in the assessment of liver fibrosis in HIV/HCV-coinfected patients using transient elastometry.

OBJECTIVES: Although the reproducibility of transient elastometry (TE) in hepatitis C virus (HCV)-monoinfected patients seems to be high, this may not be the case in HIV/HCV-coinfected patients because of different degrees of steatosis and/or inflammation. This study was aimed to determine the interobserver concordance of TE measurements in HIV/HCV-coinfected patients. METHODS: A total of 188 patients were evaluated in a cross-sectional, prospective study in two hospitals. The interobserver variability of TE results and the rate of unequal classification of significant fibrosis (cutoff value = 7.2 kPa) and cirrhosis (cutoff value = 14.6 kPa) for two observers were evaluated. RESULTS: The values of liver stiffness (LS) for two observers highly correlated [intraclass correlation index = 0.976; 95% confidence interval (CI): 0.968-0.982]. The kappa indexes for the concordance of patient classification were 0.60 for significant fibrosis and 0.89 for cirrhosis. Using two cutoff points to diagnose or rule out significant fibrosis (LS >or=9 kPa or <6 kPa) yielded a kappa index of 0.96, but 46% of patients were not classified. Covariables that influenced the interobserver agreement were a high interquartile range in the determination (adjusted odd ratio: 0.189; 95% CI: 0.087-0.411; P = 0.001) and elevated levels of triglycerides (adjusted odd ratio: 1.004; 95% CI: 1.000-1.008; P = 0.031). CONCLUSION: TE measurement is an observer-independent method to evaluate LS in HIV/HCV coinfected patients. The concordance of the classification of mild-to-severe fibrosis is good and for the diagnosis of cirrhosis is excellent. Lower interquartile ranges and triglyceride levels lead to a higher interobserver agreement.

Liver stiffness as a predictor of esophageal varices requiring therapy in HIV/hepatitis C virus-coinfected patients with cirrhosis.

BACKGROUND: Liver stiffness (LS) measured by transient elastometry is associated with portal pressure in hepatitis C virus (HCV)-monoinfected patients and could predict the presence of esophageal varices in these subjects. The aim of this study was to assess the ability of LS to predict esophageal varices requiring preventive therapy for bleeding in HIV/HCV-coinfected patients. METHODS: One hundred two HIV/HCV-coinfected patients with liver cirrhosis (LS >or= 14 kPa) underwent an upper gastrointestinal endoscopy (UGE) examination. The diagnostic performance of LS for esophageal varices requiring therapy (>or=F2 or F1 with red signs or Child-Pugh-Turcotte class C) was assessed by receiver operating receptor characteristic curves. RESULTS: Nineteen patients (19%) harbored varices requiring therapy. LS in patients with and without varices needing treatment was 48 (33-71) kPa and 32 (18-48) kPa (P = 0.004). The area under the receptor operating characteristic curve (95% confidence interval) of LS for the occurrence of varices that should be treated was 0.71 (0.60 to 0.82). There was no cutoff level of LS with good positive predictive value for the presence of varices requiring therapy, but LS of 21 kPa had a negative predictive value of 100%. Twenty-six percent of patients with LS measurement and UGE showed LS <21 KPa. CONCLUSIONS: LS is higher in HIV/HCV-coinfected patients with cirrhosis who show esophageal varices requiring therapy than in those who do not. A cutoff value of LS of 21 kPa could be useful to identify patients with very low probability of varices at risk for bleeding. UGE for screening could be spared in these patients until LS increases above 21 kPa.

Application of transient elastometry to differentiate mild from moderate to severe liver fibrosis in HIV/HCV co-infected patients.

BACKGROUND/AIMS: Transient elastometry (TE) is accurate for detecting cirrhosis (F=4) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. However, this procedure is less precise to differentiate mild (F < or = 1) from moderate to severe (F > or = 2) fibrosis using the cut-off value of 7.2kPa, a level previously proposed by some authors. Because of this, we elaborated and validated cut-off values of liver stiffness (LS) to better discriminate F < or = 1 from F > or = 2 in HIV/HCV co-infected subjects to aid therapy decisions. METHODS: One hundred and ninety-seven co-infected patients with liver biopsy and TE measurement, without prior therapy against HCV infection, were included. RESULTS: To diagnose F < or = 2, a cut-off of 9.0kPa showed a positive predictive value of 87%. To discard F > or = 2, a cut-off of 6.0kPa showed a negative predictive value of 90%. Considering all the patients, 61 (31%) patients yielded LS values < or = 6.0kPa and 81 (41%) patients showed LS values > or = 9.0kPa. There were no severe classification errors as the NPV of L < or = S6.0kPa for F > or = 3 was 100% and the NPV LS > or = 9.0kPa for F=0 was also 100%. CONCLUSIONS: The usefulness of TE can be enhanced using two different cut-off values to identify patients with F < or = 1 and F > or = 2.