Telaprevir for Retreatment of HCV Infection

BACKGROUND: Up to 60% of patients with hepatitis C virus (HCV) genotype 1 infection don’t have a sustained virologic response to therapy with peginterferon alfa plus ribavirin.

METHODS: during this randomized, phase 3 trial, we evaluated the addition of telaprevir to peginterferon alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response. a complete of 663 patients were assigned to at least one of three groups: the T12PR48 group, which received telaprevir for 12 weeks and peginterferon plus ribavirin for a complete of 48 weeks; the lead-in T12PR48 group, which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a complete of 48 weeks; and therefore the control group (PR48), which received peginterferon plus ribavirin for 48 weeks. the first end point was the speed of sustained virologic response, which was defined as undetectable HCV RNA 24 weeks after the last planned dose of a study drug. [1]

Natural history of HCV infection

Chronic hepatitis C virus (HCV) infection affects 170 million individuals worldwide. These individuals are in danger of developing both hepatological and non-hepatological manifestations. HCV is typically only fatal when it results in cirrhosis, the ultimate stage of liver fibrosis. Therefore, an estimate of fibrosis progression represents a crucial surrogate end-point for the evaluation of the vulnerability of a private patient. In untreated patients, the median expected time to cirrhosis is 30 years; 33% of patients have an expected median time to cirrhosis of but 20 years and 31% will only reach cirrhosis after quite 50 years, if ever. Several factors are related to fibrosis progression rate: duration of infection, age, male gender, consumption of alcohol, HIV co-infection and low CD4 count. Non-hepatological manifestations are frequent with quite 70% of HCV patients experiencing fatigue or a minimum of one extrahepatic clinical manifestation involving primarily the joints, skin and muscles. [2]

Treatment of HCV Infection by Targeting MicroRNA

BACKGROUND: the steadiness and propagation of hepatitis C virus (HCV) depends on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen may be a locked nucleic acid–modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 during a highly stable heteroduplex, thereby inhibiting its function.

METHODS: during this phase 2a study at seven international sites, we evaluated the security and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection. The patients were randomly assigned to receive five weekly subcutaneous injections of miravirsen at doses of three mg, 5 mg, or 7 mg per kilogram of weight or placebo over a 29-day period. They were followed until 18 weeks after randomization. [3]

HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules

The combined regulation of a network of inhibitory and activating T cell receptors could also be a critical step within the development of chronic HCV infection. Ex vivo HCV MHC class I + II tetramer staining and bead-enrichment was performed with baseline and longitudinal PBMC samples of a cohort of patients with acute, chronic and spontaneously resolved HCV infection to assess the expression pattern of the co-inhibitory molecule TIGIT along side PD-1, BTLA, Tim-3, also as OX40 and CD226 (DNAM-1) of HCV-specific CD4+ T cells, and during a subset of patients of HCV-specific CD8+ T cells. [4]

Impact of Chronic HCV Infection on Treatment Outcome of Patients with Non-Hodgkin’s Lymphoma

Background: hepatitis C virus (HCV) may be a hepatotropic and potentially lymphotropic virus. Chronic HCV infection could be involved within the pathogenesis of non-Hodgkin’s lymphoma (NHL). Aim: to work out the prevalence of HCV infection in patients with NHL and its effect on treatment outcome. Methods: during this retrospective study, 2 hundred patients presented with NHL were screened for chronic HCV infection by detecting anti-HCV antibody then further confirmation with real-time polymerase chain reaction for HCV-RNA. We compared treatment response, hepatotoxicity, relapse-free survival (RFS) and overall survival (OS) consistent with HCV infection (NHL with negative HCV RNA group and NHL with positive HCV RNA group). [5]

Reference

[1] Zeuzem, S., Andreone, P., Pol, S., Lawitz, E., Diago, M., Roberts, S., Focaccia, R., Younossi, Z., Foster, G.R., Horban, A. and Ferenci, P., 2011. Telaprevir for retreatment of HCV infection. New England Journal of Medicine, 364(25), (Web Link)

[2] Poynard, T., Ratziu, V., Benhamou, Y., Opolon, P., Cacoub, P. and Bedossa, P., 2000. Natural history of HCV infection. Best Practice & Research Clinical Gastroenterology, 14(2), (Web Link)

[3] Janssen, H.L., Reesink, H.W., Lawitz, E.J., Zeuzem, S., Rodriguez-Torres, M., Patel, K., van der Meer, A.J., Patick, A.K., Chen, A., Zhou, Y. and Persson, R., 2013. Treatment of HCV infection by targeting microRNA. New England Journal of Medicine, 368(18), (Web Link)

[4] HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules
Christin Ackermann, Maike Smits, Robin Woost, Johanna M. Eberhard, Sven Peine, Silke Kummer, Matthias Marget, Thomas Kuntzen, William W. Kwok, Ansgar W. Lohse, Thomas Jacobs, Tobias Boettler & Julian Schulze zur Wiesch
Scientific Reports volume 9, (Web Link)

[5] Sayed Tharwa, E.-, Abdelsameea, E., Yousri, M. and A. Shehata, M. (2018) “Impact of Chronic HCV Infection on Treatment Outcome of Patients with Non-Hodgkin’s Lymphoma”, Journal of Cancer and Tumor International, 7(2), (Web Link)

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