Metabolic syndrome and obesity are the cornerstones of liver fibrosis in HIV-monoinfected patients

Background: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease have become a common finding in HIV-infected patients. However, the severity, risk factors and pathogenesis of liver fibrosis in this population have been poorly documented. Objectives: To assess the impact of MetS on liver fibrosis and analyze the association between MetS, liver fibrosis and markers of adipose tissue and macrophage activation. Methods: In a matched cohort of HIV-1-monoinfected patients with and without MetS, after exclusion of other causes of liver disease, we assessed liver stiffness measurement and measured levels of serum adipokines, homeostasis model assessment index and soluble CD163 (sCD163) and CD14 as markers of fat, insulin resistance and macrophage/monocyte activation, respectively. Results: A total of 468 HIV-monoinfected individuals were enrolled; 405 (203 with MetS/202 without MetS) were analyzed. Patients with MetS were older and 49% had insulin resistance. The prevalence of significant liver fibrosis (≥F2) was higher in patients with MetS [25.1%, 95% confidence interval (19.3–31.2)] compared with those without MetS [7.9%, (4.6–12.5), P < 0.0001]. In multivariable analysis, obesity [odds ratio: 3.9 (95% CI 2.1–7.1)] and homeostasis model assessment [1.1 (1.06–1.2)] were independent factors of significant fibrosis and remained associated after adjustment on MetS. Serum levels of adipokines and sCD163 were significantly associated with the degree of liver fibrosis. When adjusted on MetS, leptin and sCD163 remained strongly associated with fibrosis/cirrhosis, whereas HIV parameters and antiretroviral therapy were not. Conclusion: In HIV-monoinfected patients, MetS is an important risk factor of liver fibrosis. Adipose tissue and macrophage activation might be key players in the development of liver fibrosis but the exact mechanisms need to be elucidated

Integrating field, textural, and geochemical monitoring to track eruption triggers and dynamics: a case study from Piton de la Fournaise

The 2014 eruption at Piton de la Fournaise (PdF), La Réunion, which occurred after 41 months of quiescence, began with surprisingly little precursory activity and was one of the smallest so far observed at PdF in terms of duration (less than 2 days) and volume (less than 0.4  ×  106 m3). The pyroclastic material was composed of golden basaltic pumice along with fluidal, spiny iridescent and spiny opaque basaltic scoria. Density analyses performed on 200 lapilli reveal that while the spiny opaque clasts are the densest (1600 kg m−3) and most crystalline (55 vol. %), the golden pumices are the least dense (400 kg m−3) and crystalline (8 vol. %). The connectivity data indicate that the fluidal and golden (Hawaiian-like) clasts have more isolated vesicles (up to 40 vol. %) than the spiny (Strombolian-like) clasts (0–5 vol. %). These textural variations are linked to primary pre-eruptive magma storage conditions. The golden and fluidal fragments track the hotter portion of the melt, in contrast to the spiny fragments and lava that mirror the cooler portion of the shallow reservoir. Exponential decay of the magma ascent and output rates through time revealed depressurization of the source during which a stratified storage system was progressively tapped. Increasing syn-eruptive degassing and melt–gas decoupling led to a decrease in the explosive intensity from early fountaining to Strombolian activity. The geochemical results confirm the absence of new input of hot magma into the 2014 reservoir and confirm the emission of a single shallow, differentiated magma source, possibly related to residual magma from the November 2009 eruption. Fast volatile exsolution and crystal–melt separation (second boiling) were triggered by deep pre-eruptive magma transfer and stress field change. Our study highlights the possibility that shallow magma pockets can be quickly reactivated by deep processes without mass or energy (heat) transfer and produce hazardous eruptions with only short-term elusive precursors.</p

Effectiveness and Safety of Interferon-Free Direct-Acting Antiviral Hepatitis C Virus Therapy in HIV/Hepatitis C Virus Coinfected Individuals: Results From a Pan-European Study

Objectives: To investigate the effectiveness, safety, and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/hepatitis C virus (HCV) coinfected individuals in Europe. Methods: All HIV/HCV coinfected individuals in the EuroSIDA study that started interferon free DAA treatment between January 6, 2014, and January 3, 2018, with >= 12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result >= 12 weeks after stopping treatment (SVR12). Logistic regression was used to explore factors associated with SVR12. Results: 1042 individuals started interferon-free DAA treatment after 1/6/2014 and were included, 862 (82.2%) had a known response to treatment, and 789 [91.5%, 95% confidence interval (CI): 89.7 to 93.4] of which achieved SVR12. There were no differences in SVR12 across regions of Europe (P = 0.84). After adjustment, the odds of achieving SVR12 was lower in individuals that received sofosbuvir/simeprevir +/- ribavirin (RBV) [adjusted odds ratio 0.21 (95% CI: 0.08 to 0.53)] or ombitasvir/paritaprevir/dasabuvir +/- RBV [adjusted odds ratio 0.46 (95% CI: 0.22 to 1.00)] compared with sofosbuvir/ledipasvir +/- RBV. Forty-three (4.6%) individuals had one or more components of their HCV regimen stopped early, most commonly because of toxicity (n = 14); of these 14, 11 were treated with ribavirin. Increased bilirubin was the most common grade 3 or 4 laboratory adverse event (n = 15.3%) and was related to treatment with atazanavir and ribavirin. Conclusions: Our findings from real-world data on HIV/HCV coinfected individuals across Europe show DAA treatment is well tolerated and that high rates of SVR12 can be achieved in all regions of Europe.Peer reviewe

Long-term Durability of Immune Responses After Hepatitis A Vaccination Among HIV-Infected Adults

Background.  Vaccination provides long-term immunity to hepatitis A virus (HAV) among the general population, but there are no such data regarding vaccine durability among human immunodeficiency virus (HIV)–infected adults