Hepatitis C and Cardiovascular Risk

Conflicting results have been produced regarding the association between chronic hepatitis C virus (HCV) infection and coronary artery disease, including heart attacks and strokes. It was found in a study about the relationship between HCV infection and risk for incident (newly emerging) coronary artery disease. HCV-positive patients were less likely to have arterial hypertension, dyslipidemias, and diabetes than persons without HCV. HCV-positive patients were more likely to smoke cigarettes and abuse alcohol or drugs. Compared with participants without HCV, patients with HCV had lower mean plasma levels of total cholesterol , low-density lipoprotein (LDL) cholesterol, and triglycerides .

In a multivariate analysis, HCV infection was associated with a 25% higher risk for coronary artery disease. Classic risk factors (older age, hypertension, smoking, diabetes, dyslipidemias) were associated with a higher risk for coronary artery disease. In contrast, nonwhite ethnicity and female sex were associated with a lower risk. It was concluded that people infected with HCV are at increased risk for coronary artery disease despite having fewer other cardiovascular risk factors.

(Butt A, Xiaoqiang W, Budoff M, et al. Hepatitis C virus infection and the risk of coronary disease. Program and abstracts of the 48th ICAAC/46th IDSA; October 25-28, 2008; Washington, DC. Abstract V-4219)

The Difficulties of Acute HCV-Infection Diagnosis

Most individuals infected with hepatitis C virus (HCV) fail to clear virus at the acute stage, becoming chronically infected, with consequent significant risks of progressive liver disease, cirrhosis and hepatocellular carcinoma. Treatment of chronic HCV with combination pegylated-interferon (PEG-IFN) and ribavirin achieves sustained virological response (SVR) rates of 42-52% of patients infected with HCV genotype 1 and 76-82% of those with genotype 2/3. In contrast, much higher SVR rates (e.g. >97%) have been reported when treating acute HCV infection with PEG-IFN, irrespective of the infecting genotype. It would thus seem preferable to treat HCV infection at the acute stage rather than waiting for the infection to become chronic.

The problem is the diagnosis of acute HCV infection is not straightforward. Detection of anti-HCV IgM does not distinguish acute from chronic infection. Genome or antigen detection techniques provide information on the current infection status of an individual, but do not indicate when infection may have taken place. One possible laboratory approach to diagnosis of acute infection would be to demonstrate sero- or genoconversion in serial samples, but practically, it is difficult to obtain regular repeat samples in high-risk individuals such as injecting drug users (IDUs). Clinical approaches to diagnosis are also flawed. Only a small minority of acute infections are symptomatic. Even in patients presenting with acute hepatitis C, the majority of whom are already anti-HCV positive, one cannot be certain that illness is due to recent infection with HCV rather than another inter-current cause in a chronically infected patient.
(J Viral Hepat. 2008;15(12):871-877)

HIV and Methicillin-resistant Staphylococcus Aureus (MRSA)

HIV-infected patients could increase the risk for Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection, including bloodstream infection. A study reported that the incidence of methicillin resistant Staphylococcus aureus (MRSA) bacteraemia increased significantly in HIV-infected patients from 2000 to 2004. Injection drug use (IDU), end-stage renal disease (ESRD) and CD4 count <200 cells/μL were independent predictors for incident MRSA bacteraemia, while ESRD was more common in patients with MRSA bacteraemia than methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. IDU, ESRD and CD4 count <200 cells/μL factors may serve as important clinical markers of MRSA likelihood in decisions regarding initial antimicrobial management.

Initial antimicrobial therapy for presumed sepsis in HIV-infected patients may require agents active against MRSA, including vancomycin, linezolid and, in nonpulmonary infections, daptomycin, particularly in patients with risk factors for MRSA bacteraemia.

(HIV Med. 2008;9(10):858-862)

The Role of Viral Infections in Type 1 Diabetes

A number of epidemiological studies support the hypothesis that viral infections play a causative role in type 1 diabetes. However, systematic review of control studies published between 1966 and 2002 has shown no convincing evidence for or against an association between type 1 diabetes and the prime candidate for infectious cause, Coxsackievirus B　(CVB). In animal models for type 1 diabetes, solid evidence supporting an inductive role for viruses is faced with just as solid evidence supporting a protective effect of viral infections. For example, based on mouse studies alone, there is no doubt that association between viruses and type 1 diabetes is extremely complex: while belonging to the same enteroviral group, CVB3 and CVB4 have opposing effects on type 1 diabetes in the same mouse model. Thus, the reason for current failure to associate a particular virus with induction of autoimmune diabetes likely is that such an association might be impossible to make. Certain viruses might be capable of inducing diabetes and others of preventing diabetes, and type 1 diabetes inducers might be capable of preventing disease under certain conditions. This will depend of course on the nature of the considered virus, but also on the state of advancement of autoimmunity at the time of infection. A given viral infection could thus be an essential disease precipitator once required predisposing events have occurred, but could on the other hand disrupt accumulation of these events.

Most important is the indication from animal studies that modulation of autoimmunity during viral infection does not depend merely on inherent properties of the virus, but also significantly on intrinsic factors of the host. The close interplay between the two will dictate whether enhancement or abrogation of autoimmune diabetes occurs. While molecular mimicry might activate autoreactive T-cells, it could also segregate these cells away from the islets and/or induce the activation of protective Tregs. While inflammatory cytokines might promote bystander activation of APCs and autoreactive T-cells, infection could occur at a time where inflammation will induce the relocation or demise of these cells. Whereas β-cell lysis and presentation of islet antigen might promote activation of autoreactive T-cells, it could also suppress the function of these cells by promoting Treg activity. Whereas repeated/sustained infections might lead to the accumulation of autoreactive T-cells within the memory pool, they could also induce suppressor mechanisms that will hinder autoimmunity.
(Diabetes. 2008;57(11):2863-2871)