Liver fibrosis in HCV monoinfected and HIV/HCV coinfected patients: dysregulation of matrix metalloproteinases (MMPs) and their tissue inhibitors TIMPs and effect of HCV protease inhibitors

An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to liver fibrosis in patients with hepatitis C (HCV) infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD). Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline) in patients receiving dual as well as triple direct-acting antivirals (DAA) anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation

VI Seminario di studio. Salute globale e scenari attuali. Nuovi contributi di ricerca. Istituto Superiore di Sanità. Roma, 16 aprile 2015. Riassunti

Esiste un bisogno crescente di chiare evidenze scientifiche che possano supportare le politiche per la salute. Questo vale per una serie di aspetti che vanno dai protocolli diagnostici applicati alle malattie trasmissibili, agli approcci terapeutici, agli studi epidemiologici, alla definizione e identificazione dei determinanti della salute con partico lare riguardo alle situazioni di grave diseguaglianza, alle contaminazioni ambientali, alla relazione tra malattia e diritti così come alla relazione tra malattia e diritto. L’obiettivo del Dottorato di Ricerca in Malattie Infettive, Microbiologia e Scienze della Salute è proprio quello di fornire momenti di crescita, finalizzati alla formazione di nuovi ricercatori, nel campo delle malattie infettive, della microbiologia, della parassitologia, della sanità pubblica e medicina sociale, nella medicina legale e nelle scienze forensi. L’obiettivo di questo sesto appuntamento, nell’ambito della collaborazione tra Istituto Superiore di Sanità e l’Università̀ Sapienza di Roma, con i dottorandi è proprio quello di fornire una cornice il più possibile unitaria a un quadro complesso di ricerche di base e applicate nell’ambito degli obiettivi del dottorato.There is a growing need for clear scientific evidence that can support health policies. This applies to a number of issues including diagnostic protocols applied to communicable diseases, therapeutic approaches, epidemiological studies, the definition and identification of the health determinants (with particular reference to situations of severe inequality), environmental contamination, the relationship between disease and rights as well as the relationship between disease and law. The objective of the PhD Program in Infectious Diseases, Microbiology and Health Sciences is precisely to provide moments of intellectual growth, aimed at the trai ning of new researchers in the field of infectious diseases, microbiology, parasitology, public health and social medicine, in forensic medicine and forensic sciences. The objective of the sixth meeting with graduate students, part of the collaboration between the Italian National Institute of Health, and the Sapienza University of Rome, is precisely to provide a frame as unitary as possible to a complex picture of basic and applied research within the objectives of the doctorat

Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV

Tailored health literacy interventions for people with deafness and hearing loss: an ongoing systematic review

Worldwide, deafness and disabling hearing loss (DHL) are estimated to be among the five major causes of disability. Health literacy (HL) is a well- established social determinant of health. DHL people have lower HL and lower health outcomes than non-hearing disabled counterparts. To inform a pilot national-based project on appropriate HL interventions for people with DHL, we aimed to explore scholarly articles through a systematic review

Have We New Therapeutic Strategies in the Treatment of Renovascular Nephropathy?

Renal artery stenosis (RAS) is a cause of hypertension and ischemic nephropathy. The incidence of this disorder is probably less than 1% in patients with mild hypertension, but rises to as high as 10 to 40% in patients with acute, severe or refractory hypertension. Significant RAS can be caused by atheromatous plaques, or due to fibromuscular dysplasia (FMD). Atherosclerotic lesions are present in almost 7% of adults older than 65 years and up to 50% of patients presenting with diffuse atherosclerotic disease. In contrast to atherosclerosis, FMD most often affects women under the age of 50 and typically involves the distal main renal artery or the intrarenal branches. The optimal treatment for RAS is not yet established. Based on recent trials, we reviewed the literature on pharmacological and endovascular treatment of atherosclerotic RAS and ischemic nephropathy

Nephroangiosclerosis and Its Pharmacological Approach

Nephroangiosclerosis (NAS) is a major cause of progressive renal insufficiency. Hypertension is very important in the causation of NAS but other factors such as race, age, metabolic variables, and genetics play a pathogenic and prognostic role. A multifactorial treatment strategy, including antihypertensive, lipid-lowering and anti-platelet agents, could improve cardiovascular and renal outcomes in patients with vascular nephropathy