Success of antiviral therapy in chronic hepatitis C infection relates to functional status of myeloid dendritic cells.

Chronic hepatitis C infection poses a major global health predicament and appears to be potent threat to mankind. The treatment in wide use is interferon/ribavirin combination therapy which is generally effective in about 60-70 per cent of patients carrying genotype 3 and causes significant morbidity. The response to therapy is largely guided by limited number of factors such as genotype of virus, rapid virological response, ethnicity, pre-therapy viral load, etc. While involvement of host genetic factors has been a major focus of research in playing an important role in the outcome of disease, the role of immune system cannot be marginalized. Poor cellular trafficking and suboptimal T cell responses in liver, the hall marks of chronic hepatitis C virus infection, might be attributed to defective antigen presentation. Various immunological factors, both innate and adaptive, play role in the pathogenesis of the disease and become dysfunctional in active disease. Recent reports suggest the major impact of functional and numerical status of dendritic cells in deciding the fate of antiviral therapy. In this review we take a look at the involvement of dendritic cells in playing an important role in the response to therapy.

A randomized trial of 24 versus 48 weeks of peginterferon a-2a plus ribavirin in Egyptian patients with hepatitis C virus genotype 4 and rapid viral response.

Background and aim: Little data is available regarding the 24-week therapy with pegylated interferon and ribavirin in Egyptian patients with hepatitis C virus (HCV) genotype 4 infection. We aimed to investigate the efficacy of 24-week versus 48-week peginterferon a-2a plus ribavirin therapy in patients with HCV genotype 4 infection with with rapid virological response. Methods: This trial included 102 patients with HCV genotype 4 infection and low viral load. They were treated with peginterferon a-2a (180 μg/week) plus ribavirin. Patients (87/102) with a rapid virological response were randomized for a total treatment duration of 24 weeks (group A: 43) or 48 weeks (group B:44). Virological responses (EVR: early virological response, EOTR: end of treatment response, and SVR: sustained virological response) were assessed for each group. Results: In group A, EVR was achieved in 37/43 (84%) patients, while EOTR was achieved in 34/43 (79%) patients and SVR in 30/43 (70%) patients. In group B, on the other hand EVR was achieved in 38/44 (84%) patients, while EOTR was achieved in 35/44 (80%) patients and SVR in 32/44 (73%) patients. No significant difference in SVR rates was observed between the two groups. The rate of adverse events was higher in group B, with lower adherence rates than group A. Conclusions: In patients with chronic HCV genotype 4 infection with rapid virological response and low viral loads, a 24-week peginterferon a-2a plus ribavirin therapy is as effective as a 48-week therapy with lower rate of adverse events.

Nuevos avances en el manejo de la hepatitis C / Current advances in hepatitis C treatment

La hepatitis por virus C constituye un problema de salud importante en México. El diagnóstico de poblaciones de alto riesgo es esencial dada la probabilidad de desarrollar enfermedad crónica, cirrosis, descompensación de la cirrosis y la consecuente necesidad de un trasplante hepático o de desarrollar carcinoma hepatocelular. Actualmente, el tratamiento de elección establecido (TEE) incluye interferón pegilado y ribavirina, los cuales han mostrado una tasa de respuesta de alrededor de 57 por ciento en el caso del genotipo 1, el más prevalente en México. Sabemos que entre 30 y 60 por ciento de la población no muestra una respuesta viral sostenida (RVS) o curación. Por lo tanto, en este artículo se revisan las estrategias terapéuticas existentes para optimizar el tratamiento, y se describen también las estrategias de tratamiento para el futuro. Eventualmente, será posible adicionar una o dos moléculas de los nuevos antivirales que actúan directamente (AAD) sobre áreas específicas del virus al TEE. Cada una de ellas cuenta con mecanismo de acción diferente y se está contemplando la posibilidad de una terapéutica libre de interferón después del año 2015.

Infection by hepatitis C virus constitutes an important health problem in Mexico. Diagnosis of high-risk population is essential given the probability of developing chronic disease, cirrhosis and cirrhosis decompensation, likely leading to the need of a liver transplant and/or the development of hepatocellular carcinoma. Currently, the standard of care (SOC) treatment includes pegylated interferon and ribavirin, which have shown an approximately 57 percent rate response in genotype 1, the most prevalent in Mexico. It is known that between 30 and 60 percent of the infected population does not show a sustained virological response or cure. Therefore, in this article, we review existing therapeutic strategies in order to optimize the treatment. Future treatment strategies are also described. Eventually, it will be possible to add one or two molecules of the new directly acting antiviral drugs, to the SOC treatment. Each of them has a different action mechanism, and we are envisioning the possibility of an interferon-free therapy after 2015.

24 Weeks Treatment with Pegylated Interferon Alfa Plus Ribavirin May Be Possible in Genotype 1 Chronic Hepatitis C Patients with Rapid Virological Response Who Have Low Pretreatment Viremia / 대한소화기학회지

BACKGROUND/AIMS: The standard treatment for chronic hepatitis C infected with hepatitis C virus (HCV) genotype 1 is a combination of pegylated interferon alfa and ribavirin over a 48 weeks period. It is unclear if 24 weeks treatment is possible for patients showing a rapid virological response (RVR) without compromising the sustained virological response (SVR) in Korea. METHODS: Between June 2005 and September 2008, among patients chronically infected with the HCV genotype 1 who were treated with pegylated interferon alfa subcutaneously once weekly plus ribavirin based on body weight, 55 patients who had low pretreatment viral load (<600,000 IU/mL) and RVR were enrolled. A total of 55 patients were divided into 24 weeks treatment group (n=29) and the standard treatment group (n=26). The HCV RNA was quantitatively assessed before treatment, and after 12 weeks of treatment, and also qualitatively assessed after 4 weeks of treatment, at end of treatment (24 weeks), and 24 weeks after end of treatment. RVR was defined as undetectable HCV RNA at the 4 weeks of treatment. RESULTS: Among the 55 patients, SVR was achieved in 100% (29/29) of the patients in 24 weeks treatment and 96.2% (25/26) of the patients in the standard treatment (p=0.473). CONCLUSIONS: HCV genotype 1 infected patients with a low baseline HCV RNA concentration who become HCV RNA negative at week 4 may be treated for 24 weeks without compromising sustained virlolgical response. However, an additional trial will be needed to optimize the treatment duration.