Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa

International Journal of Nanomedicine, Apr 2014

Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa Chen-Hua Liu,1–3 Jia-Horng Kao1–3 1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 2Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; 3Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan Abstract: Asia is endemic for hepatitis C virus (HCV) infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma , and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α) in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR) rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1) infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B) genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients receiving PEG-IFN α plus ribavirin therapy are high, health care providers should judiciously determine the clinical usefulness of these novel agents on the basis of treatment duration, anticipated viral responses, patient tolerance, financial burdens, and drug accessibility. Keywords: PEG-IFN α, HCV, SVR, RGT, IL28B

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Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa

International Journal of Nanomedicine Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa Chen-Hua Liu 2 Jia-Horng Kao 2 0 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine , Taipei , Taiwan 1 Hepatitis Research Center, National Taiwan University Hospital , Taipei , Taiwan 2 Department of Internal Medicine, National Taiwan University Hospital , Taipei , Taiwan Asia is endemic for hepatitis C virus (HCV) infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma , and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α) in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR) rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1) infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B) genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients receiving PEG-IFN α plus ribavirin therapy are high, health care providers should judiciously determine the clinical usefulness of these novel agents on the basis of treatment duration, anticipated viral responses, patient tolerance, financial burdens, and drug accessibility. PEG-IFN α; HCV; SVR; RGT; IL28B - open access to scientific and medical research Introduction Hepatitis C virus (HCV) infection, the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and liver transplantation, affects ∼170 million people worldwide.1 It is estimated that approximately 20% of individuals who are infected with HCV will develop cirrhosis within 20–30 years, and that the risk of HCC development in these patients is 1%–4% per annum.2 The aim of HCV therapy is the eradication of HCV, and the current definition of successful treatment is sustained virologic response (SVR), referring to undetectable serum HCV RNA levels at 12 (SVR12) or 24 (SVR24) weeks after the cessation of antiviral therapy. The durability of viral response after achieving SVR has been confirmed by many observational studies, showing that over 98% of patients who achieve SVR can maintain non-viremic status after long-term posttreatment follow-up, regardless of HCV monoinfection, coinfection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV), alanine aminotransferase (ALT) levels, or patient ancestry.3,4 Compared to the development of conventional interferon alpha (IFN α) for the treatment of chronic HCV infection, which results in only 6%–19% of SVR after 24–48 weeks of treatment, the use of peginterferon alfa (PEG-IFN α) in combination with 81 ribavirin (RBV) has greatly improved the overall SVR rate to l-02 42%–52% in HCV genotypes 1/4 patients and 76%–82% in -Ju2 HCV genotype 2/3 patients, respectively.5–7 In addition, the 1no introduction of response-guided therapy (RGT), where the 270 optimized treatment duration is on the basis of early viral kinet..46 ics during the first 12 weeks of treatment, has further increased .957 the SVR rate to 70%–75%.8,9 Interestingly, the SVR rates of y3b Asian patients with HCV genotype 1 (HCV-1) infection receiv/om ing PEG-IFN α plus RBV combination therapy are higher than .scs those of Western HCV-1 patients. In contrast, the response rep rates between Asian and Western non-HCV-1 patients are ve comparable. The higher response rate in Asian HCV-1 patients .dow l.yn than in Western patients was explained by the discovery of w o ://w se human interleukin-28B (IL-28B) genetic polymorphisms ttsph launo (rs12979860 or rs8099917) that strongly affect the SVR rates om rse in HCV-1 patients receiving dual therapy of PEG-IFN α plus fr p ded roF RBV.10,11 Recently, the development of telaprevir (TVR) or loa boceprevir (BOC)-based triple therapy with PEG-IFN α plus now RBV further improved (...truncated)


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Chen-Hua Liu, Jia-Horng Kao. Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa, International Journal of Nanomedicine, 2014, pp. 2051-2067, DOI: 10.2147/IJN.S41822