[Show abstract][Hide abstract] ABSTRACT: Antiviral treatment with pegIFN/RBV decreases ANC and CD4+ cell count. An association between neutropenia, a low CD4+ cell count and infections has not been demonstrated so far in HIV-HCV coinfected patients.
The incidence, type, and severity of infections were recorded in 85 HIV-HCV coinfected and 164 monoinfected patients receiving pegIFN/RBV for 48 weeks. ANC and CD4+ cell count were assessed every 4 weeks during therapy.
The incidence of infections was significantly higher in HIV-HCV than HCV-Mono (38% vs. 15%; p = 0.001). Types of infections: pneumonia (n = 16/n = 24), bacteraemia/sepsis (n = 5/n = 2), skin infections (n = 15/n = 12), urinary tract infections (n = 4/n = 1), OIs (n = 10/n = 1). The incidence of neutropenia grade 1, 2 3 or 4 was similar in HIV-HCV and HCV-Mono, respectively. The incidence of infections was not associated with neutropenia (HCV-Mono: p = 0.584; HIV-HCV: p = 0.23) or with CD4+ cell counts <200/μL (HIV-HCV: p = 0.29). OIs occurred more often in HIV-HCV patients with CD4+ cell count <200/μL (p = 0.024).
Up to 38% and 15% of HIV-HCV coinfected and HCV-monoinfected patients develop infections during pegIFN+RBV therapy but without any correlation to neutropenia. Antibacterial prophylaxis/treatment should be considered early in HIV-HCV coinfected patients developing CD4+ cell counts <200/μL during antiviral therapy as these patients have an increased risk of OIs.
The Journal of infection 03/2012; 65(2):142-9. · 4.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Single nucleotide polymorphisms (SNPs) in IL28B and serum levels of interferon γ inducible protein 10 (IP-10) predict outcomes of antiviral therapy in patients with chronic hepatitis C. We associated IL28B SNPs rs12979860 and rs8099917, along with serum levels of IP-10, with outcomes of patients with acute hepatitis C (AHC).
We studied 120 patients with AHC (64 male; 37 ± 16 years old) and 96 healthy individuals (controls). The IL28B SNPs rs12979860 and rs8099917 were detected using real-time polymerase chain reaction; serum concentrations of IP-10 were measured by enzyme-linked immunosorbent assays of 62 patients with AHC.
Hepatitis C virus was cleared spontaneously from 59 patients (49.2%). The IL28B rs12979860 C/C genotype was more frequent among patients with AHC than controls (62.5% vs 39.6%; P < .001) and among patients with spontaneous clearance than those without (74.6% vs 51.7%; P = .02) (positive predictive value, 60.3%). Patients with IL28B rs12979860 C/C more frequently developed jaundice (53.2% vs 27.6%; P = .022) than carriers of the T allele. The median level of IP-10 was lower among patients with AHC and spontaneous clearance (764 [113-2470] pg/mL) than those without spontaneous clearance (1481 [141-4412] pg/mL; P = .006). Based on receiver operating characteristic analysis, 540 pg/mL IP-10 was set as the cutoff for patients most likely to have spontaneous clearance (positive predictive value, 71.4%; negative predictive value, 65.9%). Including data on IP-10 levels increased the ability of the IL28B rs12979860 C/C to identify patients most likely to have spontaneous clearance (83% of those who had an IP-10 level <540 pg/mL and 32% who had an IP-10 level >540 pg/mL) (P < .01).
The combination of serum level of IP-10 and SNPs in IL28B can identify patients with AHC who are most likely to undergo spontaneous clearance and those in need of early antiviral therapy.
[Show abstract][Hide abstract] ABSTRACT: Pegylated interferon-alpha2/ribavirin (peg-IFN/RBV) is the standard of care (SOC) for patients with chronic hepatitis C (CHC) infection. Currently, direct-acting antiviral agents (DAAs) are evaluated in clinical trials. The aim of this study was to compare baseline characteristics and sustained virologic response (SVR) rates in patients included in clinical trials to those receiving SOC. Medical records of all 503 treatment-naïve patients with CHC, genotype (GT) 1, referred over a 4-year period (January 2006-December 2009) were reviewed. Only 310 of 503 (62%) patients received antiviral therapy, 141 were enrolled in randomized, controlled trials ("study patients"; 101 in DAA studies), and 169 received SOC. At baseline, viral load and platelet count were higher and bilirubin was lower in study patients than in SOC patients. History of psychiatric disorders was more common in SOC patients (43 [25%] versus study patients with 18 [13%]; P < 0.01). Liver biopsy was obtained in 98% of study patients, but only in 59% of SOC patients. Twenty-nine (21%) and 40 (40%) study and SOC patients, respectively, had advanced fibrosis (F3/4; P = 0.001). By intent-to-treat analysis, SVR rates were higher in DAAs (64%; 95% confidence interval [CI]: 53.4-74.4) than in SOC patients (46%; 95% CI: 37.9-53.7; P < 0.01), but not different when calculated on a treated-per-protocol (TPP) basis. Interleukin (IL)28B GT was equally distributed in both cohorts. By chance, more patients treated with IFN/RBV had rs12979860 C/C-GT (up to 44%) than DAA-treated patients. If analyzed according to the IL28B polymorphism, TPP SVR rates did not reach statistically significant differences among study and SOC patients. CONCLUSIONS: Baseline characteristics slightly favored study patients, but IL28B GT and treatment adherence were the most important factors determining outcome. Thus, the applicability of the results of controlled studies has to be tested in a "real-world" setting.
[Show abstract][Hide abstract] ABSTRACT: The incidence of hypoxic liver injury, most commonly referred to as hypoxic hepatitis (HH), is up to 10% in critically ill patients. In the majority of cases, HH occurs as a consequence of haemodynamic impairment following cardiogenic or septic shock. A marked, dramatic increase in the aminotransferase levels in a setting of cardiocirculatory failure is the key characteristic of HH. HH may contribute to several complications such as hepatopulmonary syndrome and hypoglycaemia. The overall mortality after the onset of HH is approximately 50-60% within 1 month. We report a case of severe HH that was successfully bridged using the Molecular Adsorbent Recirculating System. In addition to the possible effects of extracorporeal liver support devices, the recognition of HH and therapy of the underlying disease that led to the occurrence of HH is of central importance.
Liver international: official journal of the International Association for the Study of the Liver 09/2011; 31 Suppl 3:19-23. · 3.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Single nucleotide polymorphisms (SNPs) in the gene that encodes interleukin (IL)-28B predict response of patients with chronic hepatitis C to antiviral therapy. We investigated the roles of polymorphisms rs12979860 and rs8099917 on the early virologic response of treatment-naïve patients.
SNPs were identified by real-time polymerase chain reaction analysis of samples from 682 patients (genotype [GT]1=372, GT2/3=208, GT4=102) who were treated with 180 μg pegylated interferon-α2a and 400 or 800 mg (GT2/3, depending on the protocol) or 1000-1200 mg (GT1/4) ribavirin/day. The duration of treatment was 24 (GT2/3) or 24-72 weeks (GT1/4).
Patients with C/C also had higher rates of rapid virologic response (RVR) (GT1, 38.3% vs 11.6%; GT4, 76.5% vs 23.5%; both P<.001) and sustained virologic responses (SVRs) (GT1, 79.1% vs 43.2%; GT4, 85.3% vs 44.1%; both P<.001). In patients with GT2/3, the RVR was more frequent in carriers of C/C (75.3% vs 52.6%, P<.01), but SVR rates were similar between those with C/C and T (80.5% vs 74.4%, P=.31). Results for rs8099917 were comparable. The positive predictive value of rs12979860 C/C for SVR was higher than that of rs8099917 T/T (80.5% vs 71.6%). Overall, RVR was the best predictor of SVR. In patients who did not have GT1, IL28B polymorphisms did not affect the SVR if RVR data were included in the multivariate analysis.
An early virologic response to pegylated interferon and ribavirin is more likely among carriers of rs12979860 C/C and rs8099917 T/T, which might underlie their high rates of SVR. Determination of the IL28B genotype and whether patients have an RVR might be used in future studies of patients with hepatitis C virus genotype 1 or 4.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 04/2011; 9(4):344-350.e2. · 5.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Khat is a drug widely used in the Horn of Africa and the Arabian Peninsula. Khat leaves contain, among other substances, the psychoactive alkaloid cathinone, which induce central nervous system stimulation leading to euphoria, hyperactivity, restlessness, and insomnia. However, it also could cause psychological adverse effects such as lethargy, sleepiness, psychoses, and depression necessitating pharmacologic treatment. Here we report the case of a 35-year-old man from Somalia who became unconscious and developed aspiration pneumonia and subsequent ARDS after excessive consumption of khat leaves. His unconsciousness was possibly caused by the sleepiness developed after khat consumption and a benzodiazepine intake by the patient himself. Thus, khat-induced adverse effects should not primarily be treated pharmacologically, but patients should be urged to quit khat consumption in order to eliminate or, at least, reduce the severity of present psychological adverse effects.
[Show abstract][Hide abstract] ABSTRACT: Levels of von Willebrand factor antigen (vWF-Ag) increase during combination antiviral therapy of chronic hepatitis C (CHC). The present study investigates the association between these changes in vWF-Ag levels and response to treatment.
Changes in levels of vWF-Ag on antiviral combination treatment in 184 patients with CHC genotype 1 or 4 infections were measured prospectively and effect on response was studied.
High on-treatment levels of vWF-Ag were associated with relapse (P<0.01) and low on-treatment levels with sustained virological response (SVR). Receiver operating characteristic curve analysis showed that vWF-Ag levels of <300% at week 12 of therapy have a positive predictive value (PPV) of 78% for SVR. In early virological response (EVR) patients, the PPV of vWF-Ag levels <300% at week 12 was 74%. An even higher PPV of 88% in complete EVRs (undetectable HCV RNA at week 12) was observed for the same cutoff value at week 12.
On-treatment levels of vWF-Ag can be utilized as an additional predictive marker for response to antiviral therapy. This is especially relevant in EVR patients because EVR alone only has a PPV of 58-72% on SVR, which increased to 74%, when factoring in vWF-Ag levels <300% at week 12, and to 88% in complete EVRs; therefore, measurement of vWF-Ag levels at week 12 is helpful. EVR patients that are above the cutoff values for vWF-Ag that make SVR very probable might profit from an extension of therapy to 72 weeks.
[Show abstract][Hide abstract] ABSTRACT: Artificial Toll-like receptor 7/8 (TLR7/8) ligands can endow plasmacytoid dendritic cells (pDCs) with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-dependent lytic properties. Keeping in mind that ssRNA serves as natural TLR7/8 ligand, we searched for TRAIL-expressing cells in persons infected with HIV and identified TRAIL+ pDCs in HIV-1 viremic persons, but not in nonviremic and healthy persons. TRAIL expression on pDCs was directly correlated with individual viral loads. Conversely, HIV-1 viremia was found to be associated with the up-regulation of the apoptosis-transmitting receptor TRAIL R1 on activated CD4+ T cells. As a consequence, the latter became susceptible to TRAIL-dependent pDC-mediated killing. In contrast, initiation of antiretroviral therapy led to the up-regulation of apoptosis-inhibiting TRAIL R4 on CD4+ T cells, which subsequently became resistant against pDC-mediated cellular injury. Definition of pDCs as killers of CD4+ T cells implies a new mechanism of disease progression in HIV infection.