Showing papers by "Raffaele Bruno published in 2008"
TL;DR: Screening for underlying viral hepatitis coinfection and the provision of management and treatment recommendations for patients with chronic viral hepatitis are of great importance in preventing, as far as possible, the development of liver disease.
Abstract: Objectives
With the decline in HIV-associated morbidity and mortality following the introduction of highly active antiretroviral therapy (HAART), liver disease has emerged as a major cause of death in HIV/hepatitis B virus (HBV) and HIV/hepatitis C virus (HCV) coinfected persons. Therefore, screening for underlying viral hepatitis coinfection and the provision of management and treatment recommendations for patients with chronic viral hepatitis are of great importance in preventing, as far as possible, the development of liver disease. With the introduction of new agents for the treatment of hepatitis B and increased knowledge of how best to manage hepatitis C, an update of current guidelines for management of HBV and HCV coinfection with HIV is warranted.
Summary
Clearly, all HIV-infected patients should be screened for hepatitis A, B and C, taking into account shared pathways of transmission. Patients who are seronegative for hepatitis A and B should be considered for vaccination. In HIV-infected patients with chronic hepatitis B, the first important differentiation is whether HAART is required or not. In the setting of stable HIV infection, with no need for HAART, several treatment options are available, namely treatment with interferon, early initiation of HAART, or selective non-HIV active anti-HBV nucleoside therapy, with the aim of achieving undetectable HBV DNA levels. In most cases, undetectable HBV DNA can only be achieved with combination therapy.
With regard to hepatitis C, individualized tailoring of the duration of HCV therapy is advisable, taking into account rapid or delayed virological response. In patients who do not achieve at least a 2 log drop in HCV RNA at week 12, treatment can be terminated because of the low probability of achieving sustained virological response. Overall, with the currently available treatment algorithms, HCV can be eradicated in over 50% of patients. Therefore, HCV therapy should be considered and discussed with the patient if an indication for HCV therapy (elevated liver enzymes, positive HCV RNA and >F1 fibrosis) is present.
Conclusions
Management of underlying hepatitis B and/or C in patients with HIV infection is of great importance in preventing liver disease-associated morbidity and mortality.
253 citations
TL;DR: The data suggest that the important discrepancies observed in the evolutionary rates of HBV genotypes A and D may reflect different population dynamics of their epidemics and show the usefulness of phylodynamic studies in reconstructing the history of epidemics due to highly variable DNA viruses, and in evaluating the long-term efficacy of prophylactic measures.
39 citations
Journal Article•
TL;DR: A better knowledge of adaptive immune mechanisms, cytokine alteration, interference with host defense mechanisms, and the "cross-talk" among the viruses will improve the understanding of the pathogenetic mechanism and provide the opportunity to cure this disease.
Abstract: The coinfection of HIV and HCV has become a pathology with several distinctive characteristics. Pathogenesis of liver damage in patients with HIV and HCV coinfection is complex and multifactorial. It derives from a balance of factors which interact among themselves in a dynamic way. The reasons for the accelerated course of HIV/HCV coinfection are mainly related to two principal causes: the persistence of HCV, which depends upon alterations of cell-mediated immunity, and the activation of the immune system towards secretion of proinflammatory and profibrotic cytokines. This review will first focus on the characteristics of both these immune-mediated mechanisms, and then their implication on fibrogenesis as well as on other pathogenetic mechanisms, such as interactions between viruses and the deficit of protective mechanisms. A better knowledge of adaptive immune mechanisms, cytokine alteration, interference with host defense mechanisms, and the "cross-talk" among the viruses will improve the understanding of the pathogenetic mechanism and provide the opportunity to cure this disease.
23 citations
TL;DR: This is the largest series of HIV‐infected patients with chronic hepatitis C due to HCV‐4 treated with pegIFN plus RBV examined so far and the results show that HCV4 behaves similarly to HCv‐1, and these patients should be considered as difficult to treat population.
Abstract: Summary. Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA 2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm3; 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3–F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01–0.7) and EVR (OR: 7.08; 95% CI: 1.8–27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.
17 citations
10 citations
Journal Article•
TL;DR: Viremia was more frequent in IDUs and, conversely, was less common in HBsAg-positive patients, and this genotype was associated with greater serum HCV RNA levels.
Abstract: Background. Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. Methods. All HCV antibody (Ab)-positive patients with HIV infection in the EuroSIDA cohort who had stored samples were tested for serum HCV RNA, and HCV genotyping was done for subjects with viremia. Logistic regression was used to identify variables associated with spontaneous HCV clearance and HCV genotype 1. Results. Of 1940 HCV Ab-positive patients, 1496 (77%) were serum HCV RNA positive. Injection drug users (IDUs) were less likely to have spontaneously cleared HCV than were homosexual men (20% vs. 39%; adjusted odds ratio [aOR], 0.36 [95% confidence interval {CI }, 0.24 - 0.53]), whereas patients positive for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4, respectively. A greater HCV RNA level was associated with a greater chance of being infected with HCV genotype 1 (aOR, 1.60 per 1 log higher [95% CI, 1.36-1.88]). Conclusions. More than three-quarters of the HIV- and HCV Ab-positive patients in EuroSIDA showed active HCV replication. Viremia was more frequent in IDUs and, conversely, was less common in HBsAg-positive patients. Of the patients with HCV viremia analyzed, 53% were found to carry HCV genotype 1, and this genotype was associated with greater serum HCV RNA levels.
6 citations
TL;DR: In this article, the authors evaluated the cost-effectiveness of peginterferon α-2a plus ribavirin versus peginTERferon β-2b plus ribvirin in the treatment of chronic hepatitis C in HIV-HCV co-infection.
Abstract: Introduction: The objective of this study was to evaluate the cost-effectiveness of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin in the treatment of chronic hepatitis C in HIV-HCV co-infection. Methods: We used a pre-existent Markov model of disease progression in which two cohorts of patients received peginterferon α-2a plus ribavirin or peginterferon α-2b plus ribavirin for 48 weeks and were followed for their expected lifetimes. The reference patient was a 40-year-old man or woman. The sustained virological response (SVR) with peginterferon α-2a plus ribavirin and peginterferon α-2b plus ribavirin, were taken from two different publications. Utilities and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs in 2005 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was conducted from the perspective of the Italian National Health Service. Results: For the two cohorts, expected life-years with peginterferon α-2a plus ribavirin versus peginterferon α-2a plus ribavirin were respectively 24.47 and 23.71 years. Quality-adjusted life years for peginterferon α-2a plus ribavirin were 12.93, and 12.49 for peginterferon α-2b plus ribavirin. The expected cost was € 19,858 with peginterferon α-2a plus ribavirin and €19,983 with peginterferon α-2b plus ribavirin. Conclusion: This economic evaluation suggests that peginterferon α-2a plus ribavirin is a dominant strategy versus peginterferon α-2b plus ribavirin for treatment of adults with HIV-HCV co-infection, under some assumptions regarding treatment effectiveness and model structure.
5 citations
TL;DR: This work has shown that infection with HIV exacerbates the natural history of chronic HBV and HCV infection, and in prospective studies, HIV/ HCV coinfection is associated with a high mortality in patients infected with HIV.
Abstract: Progressive chronic liver disease associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a leading cause of morbidity and mortality in patients infected with HIV. As many as onethird of HIV-infected individuals are coinfected with HCV, and 10%– 45% of these patients will die from complications associated with HCV-related liver disease. Numerous studies have shown that infection with HIV exacerbates the natural history of chronic HBV and HCV infection. Increased rates of liver fibrosis and progression to end-stage liver disease (ESLD) have been well documented in HIVinfected individuals coinfected with HBV and/or HCV. In prospective studies, HIV/ HCV coinfection is associated with a
4 citations
4 citations