Genetic variants associated with steatohepatitis and liver fibrosis in HIV-infected patients with NAFLD.

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver damage in people living with HIV (PLWHIV). Several studies have investigated candidate genes for susceptibility to NAFLD and to steatohepatitis. PNPLA3, TM6SF2, and MBOAT7-TMC4 have been reported to be associated with elevated ALT levels and the histologic parameters of nonalcoholic steatohepatitis and severity of fibrosis. Our objective was to analyze the relationship between PNPLA3, TM6SF2, and MBOAT7-TMC4 and steatosis, steatohepatitis, and liver fibrosis in PLWHIV with NAFLD. Method: A cohort of PLWHIV with persistently elevated aminotransferase levels and suspected NAFLD who underwent liver biopsy and determination of genetic variants was assessed at two large centers in Spain. All participants included in the current study were genotyped for rs738409 (PNPLA3), rs58542926 (TM6SF2), and rs641738 (MBOAT7-TMC4). Results: The study population comprised PLWHIV who were on stable antiretroviral therapy [7.7% women; median age, 49.3 years (44-53.4)]. The median CD4 count was 829 (650-980), 60% had metabolic syndrome, and 18.5% were diabetic. The median BMI was 28.9 (25.5-30.8). Patients with liver steatosis (any grade) vs. nonsteatosis tended to harbor the PNPLA3 G allele variant [57.6% vs. 16.7% (p = 0.09)], but not TM6SF2 or MBOAT7-TMC4 variants. However, those with steatohepatitis vs. nonsteatohepatitis significantly more frequently had the PNPLA3 G allele variant [69.4% vs. 39.1% (p < 0.05)] and the MBOAT7-TMC4 A allele variant [75% vs. 42% (p < 0.05)]. In our cohort, the TM6SF2 gene variant was not associated with steatosis or steatohepatitis. The PNPLA3 G allele variant was associated with steatohepatitis [OR 4.9 (1.3-18); p 0.02] and liver fibrosis [OR 4.3 (1.1-17.4); p 0.04], and the MBOAT7-TMC4 A allele variant was associated with steatohepatitis [OR 6.6 (1.6-27.6); p 0.01]. Conclusion: The PNPLA3 G allele variant and MBOAT7-TMC4 A allele variant were associated with steatohepatitis and liver fibrosis in PLWHIV with persistently elevated aminotransferases and NAFLD. We recommend routine genotyping for PNPLA3 and MBOAT7-TMC4 in PLWHIV with NAFLD to identify those at higher risk of progression.

Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens.

Background: Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH. Methods: This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results: Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75-1); CAP, 0.94 (0.88-1); FLI, 0.81 (0.58-1); HSI, 0.74 (0.62-0.87); and TyG, 0.75 (0.49-1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82-1), 0.96 (0.90-1), 0.97 (0.93-1), and 0.85 (0.68-1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97-1, P < .001) and 0.92 (0.77-1, P < .001). Conclusions: Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

Fermi Large Area Telescope as a Galactic Supernovae Axionscope.

In a Galactic core-collapse supernova (SN), axionlike particles (ALPs) could be emitted via the Primakoff process and eventually convert into γ rays in the magnetic field of the Milky Way. From a data-driven sensitivity estimate, we find that, for a SN exploding in our Galaxy, the Fermi Large Area Telescope (LAT) would be able to explore the photon-ALP coupling down to g_{aγ}≃2×10^{-13} GeV^{-1} for an ALP mass m_{a}≲10^{-9} eV. These values are out of reach of next generation laboratory experiments. In this event, the Fermi LAT would probe large regions of the ALP parameter space invoked to explain the anomalous transparency of the Universe to γ rays, stellar cooling anomalies, and cold dark matter. If no γ-ray emission were to be detected, Fermi-LAT observations would improve current bounds derived from SN 1987A by more than 1 order of magnitude.

Nódulos pulmonares múltiples bilaterales / Multiple bilateral pulmonary nodules

No disponible

Use of transient elastography (FibroScan®) for the noninvasive assessment of portal hypertension in HIV/HCV-coinfected patients.

The hepatic venous pressure gradient (HVPG) is the gold standard for assessing portal pressure and correlates with the occurrence of portal hypertension (PH)-related complications. Transient elastography (TE) is a new, highly accurate noninvasive technique, which enables us to evaluate hepatic fibrosis to detect advanced fibrosis and cirrhosis. We performed a hepatic haemodynamic study and TE in 38 HIV/HCV-coinfected patients. The association between HVPG and liver stiffness was assessed by linear regression. The diagnostic value of TE was assessed by receiver operating characteristic (ROC) curves. We considered clinically significant PH as an HVPG ≥ 10 mmHg and severe PH as an HVPG ≥ 12 mmHg. A total of 38 HIV/HCV-coinfected patients were included. Twenty-eight patients (73.7%) had clinically significant PH (HVPG ≥ 10 mmHg), and 23 (60.5%) of these had severe PH (HVPG ≥ 12 mmHg). We found a statistically significant association between liver stiffness (kPa) and HVPG (r(2) = 0.46, P < 0.001, straight line equation HVPG=7.4 + 0.204*TE). The areas under the ROC curves were 0.80 [95% confidence interval (CI), 0.64-0.97] and 0.80 (95% CI, 0.66-0.94) for the prediction of HVPG ≥ 10 and ≥ 12 mmHg, respectively. Our data suggest that TE can predict the presence of clinically significant and severe PH in HIV/HCV-coinfected patients.

Genotyping of a nosocomial outbreak of pandemic influenza A/H1N1 2009.

BACKGROUND: Epidemiological surveys have revealed outbreaks of pandemic influenza A (H1N1) 2009 in several different contexts. Molecular characterization of the influenza virus could help to provide a more accurate description of these outbreaks. OBJECTIVE: To genotype pandemic influenza A (H1N1) 2009 isolates from an epidemiologically defined nosocomial outbreak. STUDY DESIGN: We sequenced the neuraminidase (NA) and hemagglutinin (HA) influenza A (H1N1) 2009 genes from ten HIV-positive patients involved in an epidemiologically defined outbreak in the Clinical Microbiology and Infectious Diseases (CMID) Department. Sequences were aligned to search for specific genetic features of the involved strain. We also analyzed 37 unrelated influenza A (H1N1) 2009 cases from other hospital departments. All the sequences were used to obtain phylogenetic trees. RESULTS: Identical genotypic features were shared by nine of the 10 cases initially considered to be involved in the outbreak, but not by the remaining case. These features involved two silent mutations at N385 and V407 in the NA gene and three amino acid substitutions in the HA gene (D225E, A189T, and P300S). Searching for these substitutions in patients with influenza A (H1N1) 2009 hospitalized in other departments during the same period allowed us to identify an additional unsuspected immunocompetent case. The five outbreak-specific substitutions were absent in the remaining 36 unrelated controls. One of the substitutions (P300S) rendered detection of this variant by the CDC protocol inefficient. The other outbreak-specific substitutions (D225E and A189T) were identified at codons that have been analyzed in the context of virulence. CONCLUSIONS: Genotyping is essential to ensure a more accurate description of pandemic influenza A (H1N1) 2009 outbreaks.

Impact of liver steatosis on the correlation between liver stiffness and fibrosis measured by transient elastography in patients coinfected with human immunodeficiency virus and hepatitis C virus.

We assessed the effect of different hepatic conditions such as fibrosis, steatosis and necroinflammatory activity on liver stiffness as measured by transient elastography in HIV/HCV-coinfected patients. We studied all consecutive HIV/HCV-coinfected patients who underwent liver biopsy and elastography between January 2007 and December 2008. Liver fibrosis was staged following METAVIR Cooperative Study Group criteria. Steatosis was categorized according to the percentage of affected hepatocytes as low (≤10%), moderate (<25%) and severe (≥25%). A total of 110 patients were included. Fibrosis was distributed by stage as follows: F0, n = 13; F1, n = 47; F2, n = 29; F3, n = 18; and F4, n = 3. Liver biopsy revealed the presence of hepatic steatosis in 68 patients (low to moderate, n = 53; and severe n = 15). By univariate regression analysis, fibrosis, necroinflammatory activity, and the degree of steatosis were correlated with liver stiffness. However, in a multiple regression analysis, steatosis and fibrosis were the only independent variables significantly associated with liver stiffness. With a cut-off of 9.5 kPa to distinguish patients with F ≤ 2 from F ≥ 3, elastography led to a significantly higher number of misclassification errors (25%vs 5%; P = 0.014), most of which were false positives for F ≥ 3. Our study suggests that the correlation between liver stiffness and fibrosis as estimated by transient elastography may be affected by the presence of hepatic steatosis in HIV/HCV-coinfected patients.

[Inhaled anesthesia through a device for noninvasive continuous positive airway pressure ventilation for upper digestive endoscopy in pediatric patients]. / Anestesia inhalatoria mediante un dispositivo de ventilación no invasiva tipo "CPAP sin respirador" para endoscopia digestiva alta en pacientes pediátricos.

OBJECTIVE: The demand for sedation for pediatric diagnostic procedures performed outside operating rooms has increased considerably, but the ideal method to choose has been the subject of debate. The aim of this study was to assess the efficacy of using a device for continuous positive airway pressure, connected to a Mapleson D circuit and a nasopharyngeal tube as the interface, in order to ventilate and administer sevoflurane for upper digestive tract endoscopy in children. MATERIAL AND METHODS: Prospective cohort study of children undergoing upper digestive tract endoscopy. We recorded epidemiologic variables, heart rate, mean arterial pressure, arterial oxygen saturation and procedure-related adverse events before, during and 10 minutes after the procedure. Time spent in the recovery room was also recorded. The endoscopist asked the patients about their level of satisfaction and whether they had noticed any irritating smell or gas smell. RESULTS: Data was collected on 29 patients (17 boys, 12 girls) with a mean (SD) age of 4.2 (3.9) years. The mean duration of endoscopy was 15 (7) minutes. Arterial oxygen saturation below 92% during the procedure did not occur and the endoscopic exploration was completed satisfactorily with this technique in 28 patients (96%). All were discharged from the recovery room within 30 minutes. The endoscopist reported that the technique was considered satisfactory in all cases, although 2 children noted an anesthetic "gas" smell. CONCLUSIONS: A modified Mapleson D circuit and nasopharyngeal tube can be used effectively as an interface for noninvasive ventilation and administration of sevoflurane during upper digestive endoscopy in pediatric patients.

Comparison of transient elastography and liver biopsy for the assessment of liver fibrosis in HIV/hepatitis C virus-coinfected patients and correlation with noninvasive serum markers.

Transient elastography (FibroScan) is a novel, rapid and noninvasive technique to assess liver fibrosis. Our objective was to compare transient elastography (TE) and other noninvasive serum indexes as alternatives to liver biopsy in HIV/hepatitis C virus (HCV)-coinfected patients. The fibrosis stage (METAVIR Score), TE, the aspartate aminotransferase-to-platelet ratio index, the Forns fibrosis index, FIB-4 and HGM-2 indexes were assessed in 100 patients between January 2007 and January 2008. The diagnostic values were compared by calculating the area under the receiver operating characteristic curves (AUROCs). Using TE, the AUROC (95% CI) of liver stiffness was 0.80 (0.72-0.89) when discriminating between F 2, 0.93 (0.85-1.00) when discriminating between F 3 and 0.99 (0.97-1.00) when discriminating between F or= 3, the AUROCs of TE were significantly higher than those obtained with the other four noninvasive indexes. Based on receiver operating characteristic curves, three cutoff values were chosen to identify F or= 3 (>or=11 kPa) and F4 (>or=14 kPa). Using these best cutoff scores, the negative predictive value and positive predictive value were 81.1% and 70.2% for the diagnosis of F or= 3 and 100% and 57.1% for the diagnosis of F4. Thus, Transient elastography accurately predicted liver fibrosis and outperformed other simple noninvasive indexes in HIV/HCV-coinfected patients. Our data suggest that TE is a helpful tool for guiding therapeutic decisions in clinical practice.

Identification of liver fibrosis in HIV/HCV-coinfected patients using a simple predictive model based on routine laboratory data.

We constructed noninvasive models to predict significant fibrosis (F > or = 2) and advanced fibrosis (F > or = 3) among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients, naïve for anti-HCV treatment. A total of 296 patients with liver biopsy were randomly assigned to an estimation group (EG = 226; 70%) and a validation group (VG = 70; 30%). We developed the Hospital Gregorio Marañón (HGM)-1 index, based on platelet count, aspartate aminotransferase (AST) and glucose, to predict F > or = 2 and the HGM-2 index, based on platelet count, international normalized ratio, alkaline phosphatase and AST to predict F > or = 3. The area under the receiver operating characteristic curves (AUROCs) of the HGM-1 index for the EG and the VG were 0.807 and 0.712 respectively. The AUROCs of the HGM-2 index for the EG and the VG were 0.844 and 0.815 respectively. With the HGM-1 index applied to the VG, using best cutoff scores, the negative predictive value (NPV) to exclude F > or = 2 was 54.5% and the positive predictive value (PPV) to confirm F > or = 2 was 93.3%. With the HGM-2 index applied to the VG, using best cutoff scores, the NPV to exclude F > or = 3 was 92.3, and the PPV to confirm F > or = 3 was 64.3%. Thus, HGM-2 accurately predicted F > or = 3 among HIV/HCV-coinfected patients. HGM-1 was less accurate at predicting F > or = 2.