Article

Zeuzem, S. Interferon-based therapy for chronic hepatitis C: current and future perspectives. Nat Clin Pract Gastroenterol Hepatol. 5, 610-622

Department of Medicine, JW Goethe University Hospital, Frankfurt, Germany.
Nature Clinical Practice Gastroenterology &#38 Hepatology (Impact Factor: 5.33). 11/2008; 5(11):610-22. DOI: 10.1038/ncpgasthep1274
Source: PubMed

ABSTRACT

Pegylated interferon alpha (peginterferon alpha) plus ribavirin is the current mainstay of treatment for patients with chronic HCV infection. When peginterferon alpha plus ribavirin is administered for the standard duration, a sustained virological response is achieved in around 50% of patients infected with HCV genotype 1 and around 80% of patients infected with HCV genotype 2 or 3. Data now suggest that treatment duration can be shortened or lengthened depending on baseline viral load and/or early on-treatment viral kinetics, offering the prospect of individualizing therapy further to improve response or to prevent treatment from being unnecessarily extended. Further efforts to optimize therapy are likely to involve the use of new anti-HCV agents, several of which are currently in the early stages of development. These agents include HCV protease inhibitors (particularly those against NS3-4A protease), HCV polymerase inhibitors (including both nucleoside and non-nucleoside analogs) and cyclophilin inhibitors. These compounds will be used, at least initially, in combination with peginterferon alpha plus ribavirin, extending the pivotal role of interferon-based therapy in the management of chronic hepatitis C.

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    • "It is estimated that 20% of persons with untreated chronic HCV infections will progress to cirrhosis and 15% of individuals with cirrhosis will develop hepatocellular carcinoma within 5 years (Davis et al., 2010). While peginterferon and ribavirin (PR) therapy of HCV infection allows for a sustained virologic response (SVR) in about 40–50% of genotype 1-infected patients and in 80–90% of those infected with genotypes 2 or 3 (Zeuzem, 2008; McHutchison et al., 2009), other treatments are available. The new standard of care for genotype 1 is combination therapy with PR in combination with boceprevir or telaprevir. "
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    ABSTRACT: We investigated the frequency of RAVs among patients failing to achieve SVR in two clinical trials. We also investigated the impact of interferon responsiveness on RAVs and specific baseline RAVs relationship with boceprevir treatment failure. Data are from 1020 patients enrolled into either SPRINT-2 or RESPOND-2; patients received a 4-week PR lead-in prior to receiving boceprevir or placebo. RAVs were analyzed via population-based sequence analysis of the NS3 protease gene (success rate of >90% at a virus level of ≥10,000IU/mL) RESULTS: The high SVR rate in patients who received boceprevir resulted in a low rate of RAVs; 7% was detected at baseline in all patients, which rose to 15% after treatment. However, RAVs were detected in 53% of patients that failed to achieve SVR, which declined to 22.8% 6-14 months following cessation of boceprevir therapy. Baseline RAVs alone were not predictive of virologic outcome; poor interferon responsiveness was highly predictive of non-SVR. RAVs were more frequently detected in poor interferon responders. We detected no association between the presence of baseline amino acid variants at boceprevir resistance-associated loci and outcome in the context of good IFN response.
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    • "Nonetheless, while 80% of patients infected with either HCV genotype 2 or 3 reach sustained viral response (SVR) under pegIFN/ RBV combination therapy, only 45e50% of HCV genotype 1 infected patients achieve SVR [12]. Recently, the SOC treatment of genotype 1 infected patients has markedly advanced by including this combination with one of two clinically approved direct-acting antivirals (DAAs), telaprevir or boceprevir. "
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    • "It remains to be studied whether the rate of decrease of serum HCV RNA titers continues after day-14 in the Pioglitazone group. If the effects of Pioglitazone on in HCV genotype 4 RNA titers would continue at the same rate as for the first 2 weeks, it would achieve a clinically significant decrease of ∼1 log10 in HCV RNA titers by week-12, an important predictive timeline for a sustained virological response in HCV treatments [16]. Given the relative safety of Pioglitazone administration [9],[17], it could be, as a co-adjuvant, a valuable therapeutic effect for difficult to treat HCV genotype 4-infected patients. "
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    ABSTRACT: Insulin resistance (IR) is induced by chronic hepatitis C virus (HCV) genotypes 1 and 4 infections. It is not known whether drugs that affect IR such as Pioglitazone and Prednisone also affect serum HCV RNA titers independently of PEG-Interferon-α2/ribavirin treatment. The primary aim was to assess whether Pioglitazone by improving IR and/or inflammation decreases HCV viral load independently of standard of care HCV treatment. A secondary aim was to assess whether Prednisone, a drug that induces insulin resistance and stimulates HCV viral entry and replication in replicon culture systems, increases HCV viral load in this population.
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