To describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance.
Cirrhotic ...patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model.
We enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure–SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29–18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93–5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28–1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73–4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48–4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12–0.73; p 0.008).
MDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.
Abstract Background The main limiting factor to major hepatic resections is the amount of the future liver remnant (FLR). Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy ...(ALPPS) is a procedure which induces a rapid hypertrophy of the FLR in patients with non-resectable liver tumours. Methods ALPPS is a surgical technique of in-situ splitting of the liver along the main portal scissura or the right side of the falciform ligament, in association with portal vein ligation in order to induce a rapid hypertrophy of the left FLR. Results The median FLR volume increase was 18.7% within one week after the first step and 38.6% after the second step. At the first step the median operating time was 300 min, blood transfusions were not required in any case, median blood loss was 150 cc. At the second step median operating time was 180 min, median blood loss was 50 cc, none of the patients required intra-operative blood. All patients are alive at a median follow up of 9 months. Conclusions This novel strategy seems to be feasible even in the context of a cirrhotic liver, and demonstrates the capacity to reach a sufficient FLR within a shorter interval of time.
•The liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype, independently from HCV infection.•An enrichment of PD-1+Vγ9Vδ2 T-cells was observed both in the peripheral blood ...and in the liver of HCVpos patients.•HCV induced a dysregulation in IFN-γ production by intrahepatic Vγ9Vδ2 T-cells by mantaining their anti-HCV activity.
Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction.
Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCVpos) and in HCV-negative (HCVneg) subjects. Phenotypic and functional analysis was performed by flow cytometry. Anti-HCV activity was analyzed by using an in vitro autologous liver culture system.
Independently from HCV infection, the liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype. In contrast, an enrichment of PD-1 expressing Vγ9Vδ2 T-cells was observed both in the peripheral blood and in the liver of HCVpos patients, probably due to a persistent antigenic stimulation. Moreover, a lower frequency of IFN-γ producing Vγ9Vδ2 T-cells was observed in the liver of HCVpos patients, suggesting a functional impairment in the cytokine production in HCVpos liver. Despite this hypo-responsiveness, intrahepatic Vγ9Vδ2 T-cells are able to exert an anti-HCV activity after specific stimulation.
Altogether, our data show that HCV infection induced a dysregulation of intrahepatic Vγ9Vδ2 T cells that maintain their anti-HCV activity after specific stimulation. A study aimed to evaluate the mechanisms of the antiviral activity may be useful to identify new pathways able to improve Vγ9Vδ2 T-cells intrahepatic function during HCV infection.
The objective of this study is to identify a simplified rapid screening and linkage-to-care model for HCV among PWUD.
The study stems from a collaborative project bringing together two local Italian ...Centers for Drug Addiction and the Hepatology-Infectious Diseases Department of Lazzaro Spallanzani. A research physician analyzed the available medical records seeking to identify HCV and HIV infected patients in care in the addiction centers. Between March 2018 and January 2020 subjects were selected from among a cohort of 720 PWUD in the two Centers' care. The study comprises three steps: first, screening for HCVAb; second, the linkage to care; third, clinical assessment to treatment. The research physician recruited patients for the first two steps directly in their local addiction center. The third step was conducted in the Spallanzani. The characteristics of those subjects who adhered to the three-step study program were then compared to those of the non-adhering PWUD.
194 were known HCVAb positive patients. Of the 505 PWUD in the care of the two Centers eligible for screening, 364 were enrolled in the study. 144 resulted HCVAb positive. 269 were tested for HCVRNA. 101 underwent a full assessment. 96 patients started antiviral therapy with DAA. Patients who refused first step screening were older patients and mainly heroin users; in the second step, almost all the HIV/HCV co-infected patients agreed to a viremia test; in the third step all the HIV/HCV co-infected patients refused HCV treatment.
The study suggests an on-site specialist approach conducted directly in the addiction centers themselves starting from screening; it can bring the goal of HCV PWUD microelimination closer.
Integrase drug resistance monitoring deserves attention because of the increasing number of patients being treated with integrase strand-transfer inhibitors. Therefore, we evaluated the integrase ...genotyping success rate at low-level viraemia (LLV, 51-1000 copies/mL) and resistance in raltegravir-failing patients.
An integrase genotypic resistance test (GRT) was performed on 1734 HIV-1 samples collected during 2006-13. Genotyping success rate was determined according to the following viraemia levels: 51-500, 501-1000, 1001-10 000, 10 001-100 000 and >100 000 copies/mL. The reproducibility of integrase GRT was evaluated in 41 plasma samples processed in duplicate in two reference centres. The relationship between LLV and resistance prevalence was evaluated in a subset of 120 raltegravir-failing patients.
Overall, the integrase genotyping success rate was 95.7%. For viraemia levels 51-500 and 501-1000 copies/mL, the rate of success was 82.1% and 94.0%, respectively. GRT was reproducible, producing sequences with a high similarity and an equal resistance profile regardless of the sequencing centre or viraemia level. Resistance was detected both at LLV and at viraemia >1000 copies/mL (51-500 copies/mL = 18.2%; 501-1000 = 37.5%; 1001-10 000 = 53.7%; 10 001-100 000 = 30.0%; and >100 000 = 30.8%). At viraemia ≤500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL.
Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.
Summary
What is known and objective
The second‐generation direct‐acting antivirals represented the first major turning point for the eradication of HCV infection in almost all settings of patients. ...However, no data were available on use in gastro‐resected patients.
Case description
We report on a gastrectomized patient with chronic hepatitis C infection. She was treated with sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks, with measurement of blood levels of the drugs. She obtained sustained virological response at week 12 and 24 without dose adjustment.
What is new and conclusion
This case report can provide information useful for clinical practice in this set of patients and can open new perspectives in evaluating actual SOF/LDV bioavailability.
We describe the first reported case of treatment with direct antiviral agents in a gastrotomized patient. This report can provide information useful for clinical practice in this set of patients and can open new perspectives in evaluating Sofosbuvir/Ledipasvir bioavailability.
Objectives
We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir‐boosted protease inhibitor.
...Methods
Data from 206 drug‐naïve and 327 PI‐experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined.
Results
DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug‐naïve and PI‐experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug‐naïve patients >500 000 HIV‐1 RNA copies/mL: median interquartile range (IQR) 6.1 (5.1–10.3) months; 100 000–500 000 copies/mL: median (IQR) 4.9 (3.8–6.1) months; <100 000 copies/mL: median (IQR) 3.9 (3.5–4.8) months; P < 0.001 and in PI‐experienced patients ≥100 000 copies/mL: median (IQR) 7.2 (5.7–11.6) months; <100 000 copies/mL: median (IQR) 2.8 (2.4–3.3) months; P < 0.001. In PI‐experienced patients, the probability of VR was higher for higher viraemia levels (22.3% for ≥100 000 copies/ml vs. 9.7% for <100 000 copies/mL; P = 0.007). Baseline resistance did not affect the virological response. At failure, a high percentage of patients maintained virus susceptible to all PIs (drug‐naïve: 95%; PI‐experienced: 80%). Despite being used more often in patients with more complex requirements, DRV600 performed as well as DRV800.
Conclusions
In clinical practice, use of DRV/r (with its flexible dosage) results in high rates of virological response. These data support the use of PI/r in patients whose characteristics require potent drugs with a high genetic barrier.
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