Health values of patients coinfected with HIV/hepatitis C: are two viruses worse than one?

OBJECTIVES: We sought to assess health values of patients coinfected with HIV/hepatitis C (HCV) and compare them with those of patients singly infected with HIV or HCV and to characterize and assess the relationship of clinical and nonhealth-related factors with health values. SUBJECTS: We studied a total of 203 subjects infected with HIV, HCV, or both. MEASURES: We assessed rating scale (RS), time tradeoff (TTO), and standard gamble (SG) values, and we explored associations of health values with the Mental Component Summary (MCS) and Physical Component Summary (PCS) of the SF-12; number of bothersome symptoms from the HIV Symptoms Index; spirituality, as assessed by the Functional Assessment of Chronic Illness Therapy, Spiritual Well-being scale; as well as with a number of demographic, clinical, and psychosocial characteristics. RESULTS: Of the 203 subjects, 59 (29%) had HIV monoinfection, 69 (34%) had HCV monoinfection, and 75 (37%) were coinfected. The mean (SD) health values for the cohort were: RS = 0.69 (0.23), TTO= 0.88 (0.24), and SG = 0.78 (0.30). Infection type was related, albeit differently, to TTO values (mean values for patients with coinfection = 0.82; HIV = 0.91; and HCV = 0.91 [P < 0.05]) and SG values (coinfection = 0.77; HIV = 0.70; and HCV = 0.87; P < 0.05). In multivariable models, RS scores were significantly associated with sexual orientation, PCS scores, MCS scores, symptoms, and spirituality (adjusted R = 0.61); TTO with symptoms and spirituality (adjusted R = 0.23); and SG with infection type, PCS scores, and symptoms (adjusted R = 0.24). CONCLUSIONS: Health values and their correlates varied by method of assessment. Health values appear to be driven more by symptoms, health status, and spirituality than by number of viral infections.     

Pegylated IFN-α2b plus ribavirin for treatment-naive patients coinfected with HCV and HIV

Since 1995, after the generalization of highly active antiretroviral therapy (HAART), HCV coinfection in patients with HIV has become a clinical problem of first magnitude. In fact, currently, HCV coinfection is the primary cause of morbi–mortality of AIDS patients in many hospitals. As a consequence, a significant number of clinical trials have been carried out during the past 8–10 years on HCV/HIV-coinfected patients, and have been coincident that the use of pegylated interferon (PEG-IFN) plus ribavirin should be now the gold standard for treating these patients. Various prospective, randomized studies have reached the conclusion that PEG-IFN-α_2b plus ribavirin achieves HCV cure rates in approximately 50% of all patients, together with important clinical consequences, since hepatic illness progression stops or even reverts. Although adverse events are extremely common with this combined treatment, it is also true that their handling by experts means that only 10–15% of patients must abandon treatment.     

Telaprevir: a new hope in the treatment of chronic hepatitis C?

More than 180 million people worldwide have chronic hepatitis C (CHC) virus infection, a major cause of liver cirrhosis and its life-threatening complications including liver failure, portal hypertension, and hepatocellular carcinoma. With the current standard of care of pegylated interferon-alpha and ribavirin (PEG-IFN-α/RBV), the chances of sustained viral clearance or “cure” are only 40%–50% for genotype 1 infection, which is the most common genotype in western populations. Consequently, there has been a drive to develop new agents specifically targeting essential components of the viral life cycle, such as the hepatitis C virus (HCV) NS3/4A serine protease. Perhaps the most advanced HCV protease inhibitor in clinical development is telaprevir, which has been shown to improve treatment outcomes when combined with PEG-IFN-α/RBV in genotype 1 infection, and is currently undergoing phase 3 study. In this review, we summarize the pharmacology, pharmacokinetics, and results of phase 1 and 2 clinical trials of telaprevir, and discuss the likely role of this agent in the future management of CHC.     

Pegylated IFN-α2a and ribavirin in the treatment of hepatitis C

Chronic hepatitis C is a major worldwide health problem with an estimated prevalence of 1.6–2%. The prognosis of chronic hepatitis C depends on the rate of fibrosis progression which, over a 20–30-year time span, may determine the risk of developing cirrhosis and its complications, namely hepatocellular carcinoma, liver decompensation, hepatic encefalopathy and espohageal variceal bleeding. The only therapeutic measure able to halt this progressive process is HCV eradication by interferon (IFN)-based therapies. HCV clearance benefits patients with chronic hepatitis C, by preventing the progression to cirrhosis, as well as those with established cirrhosis, by effectively reducing the risk of liver-related complications. The latest innovation in anti-HCV treatment has been the pegylation of the IFN molecule through the attachment of one or more polyethylene glycols to the IFN molecule, drastically modifying the immunological, pharmacokinetic and pharmacodynamic properties of the drug. Following the demonstration of a more potent antiviral effect in terms of sustained virological response rates in Phase III randomized trials, pegylated IFN coupled with ribavirin has become the standard of care for chronic hepatitis C. Currently, two forms of pegylated IFN exist (α2a and α2b), which differ significantly in terms of pharmacokinetics and dynamics, is whether these peculiarities translate into different efficacy rates being still being debated.     

PegIFN-α2a for the treatment of chronic hepatitis B and C: a 10-year history

Chronic HBV and HCV are progressive diseases leading to cirrhosis and liver transplantation. Persistent viral eradication or suppression can positively affect the natural course of the infection, by preventing disease progression. Since its introduction more than 30 years ago, IFN-α has represented the foundation of HBV and, lately, anti-HCV treatment. Pegylation of the IFN-α molecule (PegIFN-α2a) has provided improvements in both efficacy and administration schedule, thus becoming part of the standard-of-care regimen for HCV and HBV therapy in the last 10 years. Currently, treatment of finite duration with PegIFN-α2a may achieve a sustained virological response off-treatment and HBsAg seroconversion. PegIFN-α2a will most likely remain the backbone of HCV treatment for the next few years, despite the availability of direct-acting antivirals that are expected to improve cure rates. However, many efforts are concentrated on developing new compounds, with the goal of administrating all oral regimens and eliminating PegIFN from anti-HCV treatment.     

Is positivity for hepatitis C virus antibody predictive of lower risk of death in COVID-19 patients with cirrhosis?

Liver injury has been reported in coronavirus disease 2019 (COVID-19) cases but the impact of pre-existing liver damage and related etiology have not been completely elucidated. Our research interests include the potential reciprocal influence of COVID-19 and pre-existing liver damage related to hepatitis C virus (HCV) infection, in particular. To this end, we have evaluated three cohorts of patients admitted at three Italian hospitals during the coronavirus pandemic; these included 332 patients with COVID-19 and 1527 patients with HCV who were from established real-world antiviral treatment study cohorts (sofosbuvir/velpatasvir), with either liver disease (various severities; n = 1319) or cirrhosis (n = 208). Among the COVID-19 patients, 10 had cirrhosis (3%), including 7 of metabolic origin and 3 of viral origin. Mortality among the COVID-19 patients was 27.1%, with 70% of those with cirrhosis of metabolic etiology having died. Cirrhosis, older age, low white blood cell count and lymphocyte count being identified as risk predictors of death [odds ratio (OR) = 13.7, 95% confidence interval (CI): 2.59-83.01, P = 0.006; OR = 1.05, 95%CI: 1.03-1.08, P = 0.0001; OR = 1.09, 95%CI: 1.36-1.16, P = 0.001; OR = 0.61, 95%CI: 0.39-0.93, P = 0.023, respectively]. In the two cohorts of HCV patients, COVID-19 diagnosis was made in 0.07% of those with liver disease and 1% of those with cirrhosis. Thus, the prevalence of HCV antibodies among COVID-19-infected patients was comparable to that currently reported for the general population in Italy. Amongst the COVID-19 patients, pre-existing metabolic cirrhosis appears to be associated with higher mortality, while HCV antibodies may be suggestive of “protection” against COVID-19.     

Early viral kinetics: a novel guide for optimal dosing frequency of pegylated interferon-α-2a in HIV/HCV-coinfected patients

The success rate in HCV treatment of HIV/HCV-coinfected patients is still unsatisfactory and new strategies are required to improve the effectiveness of current regimens and eventually optimize the oncoming new antiviral drugs. This article assesses the findings of a recently published paper comparing pharmacokinetics, pharmacodynamics and HCV decay with twice-weekly dosing of pegylated IFN-α-2a versus the standard weekly dosing, and weight-based ribavirin. A more rapid HCV-RNA decline was observed in the twice-weekly pegylated interferon arm and associated with a higher induction of interferon-stimulated genes, despite a similar pharmacokynetic profile between the two dosing schedules. This promising novel therapeutic approach to improve sustained virologic response in difficult-to-treat populations is discussed in relation to the key findings of the article.     

Early viral kinetics: a novel guide for optimal dosing frequency of pegylated interferon-α-2a in HIV/HCV-coinfected patients

Evaluation of: Murphy AA, Herrmann E, Osinusi AO et al. Twice-weekly pegylated interferon-α-2a and ribavirin results in superior viral kinetics in HIV/hepatitis C virus coinfected patients compared with standard therapy. AIDS 25, 1179–1187 (2011).

The success rate in HCV treatment of HIV/HCV-coinfected patients is still unsatisfactory and new strategies are required to improve the effectiveness of current regimens and eventually optimize the oncoming new antiviral drugs. This article assesses the findings of a recently published paper comparing pharmacokinetics, pharmacodynamics and HCV decay with twice-weekly dosing of pegylated IFN-α-2a versus the standard weekly dosing, and weight-based ribavirin. A more rapid HCV-RNA decline was observed in the twice-weekly pegylated interferon arm and associated with a higher induction of interferon-stimulated genes, despite a similar pharmacokynetic profile between the two dosing schedules. This promising novel therapeutic approach to improve sustained virologic response in difficult-to-treat populations is discussed in relation to the key findings of the article.     

Hepatocellular carcinoma in a patient with human immunodeficiency virus and hepatitis B virus coinfection: an emerging problem?

Infections with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) have similar risk factors and routes of transmission. It is estimated that 64 to 84% of HIV-infected individuals have positive markers for anti-HBc antibodies, with the chronic HBV infection rate approaching 16%. There is, however, a paucity of information on HBV/HIV coinfection, and its clinical implications remain unclear. We review the literature and report our recent experience with a 44-year-old man with HBV/HIV coinfection who developed metastatic hepatocellular carcinoma despite quiescent HBV and HIV disease courses. Highly active antiretroviral therapy has revolutionized HIV disease. As a result, morbidity and mortality from other underlying chronic, non-HIV-related diseases, such as the HBV infection and hepatocellular carcinoma reported here, will likely continue to increase in the HIV-infected patient population.     

White matter fiber tracking in patients with space-occupying lesions of the brain: a new technique for neurosurgical planning?

The technique of fiber tracking based on diffusion tensor imaging offers the unique possibility of localizing the white matter pathways of the brain in vivo. In patients with cerebral tumors or space-occupying lesions of the brain, these pathways are often damaged or significantly displaced. Knowledge of the exact location of the lesion with respect to clinically eloquent white matter pathways is of great value to the neurosurgeon in planning the appropriate surgical strategy. We present here preliminary findings using the fiber tracking technique in four patients with space-occupying lesions and discuss the potential and limitations of the technique for lesion localization and neurosurgical planning.     

Fibrin,the preferred scaffold for cell transplantation after myocardial infarction? An old molecule with a new life

Fibrin is a topical haemostat, sealant and tissue glue, which consists of concentrated fibrinogen and thrombin. It has broad medical and research uses. Recently, several studies have shown that engineered patches comprising mixtures of biological or synthetic materials and progenitor cells showed therapeutic promise for regenerating damaged tissues. In that context, fibrin maintains cell adherence at the site of injury, where cells are required for tissue repair, and offers a nurturing environment that protects implanted cells without interfering with their expected benefit. Here we review the past, present and future uses of fibrin, with a focus on its use as a scaffold material for cardiac repair. Fibrin patches filled with regenerative cells can be placed over the scarring myocardium; this methodology avoids many of the drawbacks of conventional cell‐infusion systems. Advantages of using fibrin also include extraction from the patient's blood, an easy readjustment and implantation procedure, increase in viability and early proliferation of delivered cells, and benefits even with the patch alone. In line with this, we discuss the numerous preclinical studies that have used fibrin–cell patches, the practical issues inherent in their generation, and the necessary process of scaling‐up from animal models to patients. In the light of the data presented, fibrin stands out as a valuable biomaterial for delivering cells to damaged tissue and for promoting beneficial effects. However, before the fibrin scaffold can be translated from bench to bedside, many issues must be explored further, including suboptimal survival and limited migration of the implanted cells to underlying ischaemic myocardium. Copyright © 2016 John Wiley & Sons, Ltd.