Only about 40% of patients with HCV genotype 1 infection (the most common genotype in North America) achieve sustained virologic response with pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy (Zeuzem 2011; Alkhouri 2012). Therefore, rigorous research efforts are aimed at developing more effective treatment strategies.
Direct-acting Antivirals (DAAs)
Telaprevir and boceprevir, direct-acting antivirals (DAAs) that inhibit HCV replication, received FDA approval in 2011. They are used in combination with pegylated interferon plus ribavirin to treat chronic genotype 1 HCV infection (Kim 2012; Feret 2011).
In chronic HCV-infected patients who had either not been treated or for who conventional treatment was unsuccessful, adding telaprevir to pegylated interferon plus ribavirin therapy resulted in significantly higher sustained virologic response rates (Jacobson 2011; Zeuzem 2011).
The rate of chronic HCV infection is notably high in the African American population (CDC 2012b). Research showed when telaprevir was used in combination with pegylated interferon plus ribavirin in African Americans, the sustained virologic response rate was 61% versus 25% without telaprevir (American College of Gastroenterology 2011).
Additional evidence indicates using telaprevir may shorten treatment time (Sherman 2011). Being able to shorten treatment duration is extremely important, as some patients stop complying with treatment over time or may need to stop treatment due to adverse events (Lo Re 2011; Kim 2012). If prolonged exposure to these therapies can be minimized, this might encourage patient compliance.
Adding boceprevir to pegylated interferon plus ribavirin treatment has also yielded major improvements in sustained virologic response rates (Poordad 2011). In previously untreated patients, treatment with boceprevir plus pegylated interferon plus ribavirin therapy yielded high sustained virologic response rates in most patients at 28 weeks; boceprevir was also found to be safe and effective for up to 48 weeks (when necessary). Having a 4-week lead-in period of pegylated interferon plus ribavirin treatment before adding boceprevir yielded a better sustained virologic response as well as decreased viral breakthrough and relapse over a 48-week duration (Kwo 2010).
Limitations of DAAs include a greater frequency of adverse events than pegylated interferon plus ribavirin (Ghany 2011), complex dosing regimen (Lo Re 2011), potential for drug-drug interactions (Ghany 2011), and the emergence of treatment-resistant HCV strains (Sarrazin 2010; Kim 2012; Susser 2009; Kuntzen 2008). Also, neither drug is equally effective against all HCV genotypes. New therapies are being developed to address a broader range of genotypes (Shiffman 2012).
Metformin: More than a Diabetes Drug
Life Extension has been reporting on the benefits of metformin for years. New research indicates metformin, normally used to treat diabetes, may be a useful therapy for HCV patients. In vitro data suggests metformin may have a suppressive effect on HCV replication (Nakashima 2011). In women with HCV genotype 1 infection who were found to exhibit insulin resistance, taking metformin in addition to standard HCV therapy resulted in a doubled sustained virologic response and greater decrease in viral load compared to placebo in the first 12 weeks of treatment (del Campo 2010). A number of other clinical studies have also shown improved sustained virologic response rates among insulin-resistant HCV patients receiving metformin in addition to standard therapy (Yu 2012; Romero-Gómez 2009). Metformin use was also correlated with a significantly better prognosis among 99 diabetic HCV patients with cirrhosis. Compared to non-use, metformin treatment was associated with an 81% reduction in risk of hepatocellular carcinoma and a 78% reduction of liver-related death or need for liver transplant (Nkontchou 2011).
Ezetimibe: A cholesterol-lowering Drug that Inhibits HCV Viral Entry
New findings reveal certain cholesterol medications may be useful in HCV treatment. Niemann-Pick C1-like 1 (NPC1L1) receptors are important mediators of cholesterol absorption in the human body. Interestingly, scientists recently found NPC1L1 receptors also help the HCV virus enter cells.
The cholesterol drug ezetimibe specifically targets NPC1L1 receptors. Researchers tested its effects on HCV and found it inhibits infection by all major HCV genotypes. Moreover, in mice with human liver grafts, ezetimibe slowed the establishment of HCV genotype 1b infection. These findings represent a breakthrough discovery by identifying an entry factor for HCV and revealing a new treatment target (Sainz 2012).
In a 2012 Phase II study, patients were treated with an investigational interferon-free therapy (combination of protease inhibitor BI 201335 and polymerase inhibitor BI 207127) with and without ribavirin and for varying treatment durations. Treatment for 28 weeks resulted in a viral cure in nearly 82% of patients with HCV genotypes 1a CC and 1b infection, the most common genotypes in Asia and Europe. Moreover, 68% of all patients in the study achieved a viral cure, including individuals with genotype 1a non-CC, which is normally very difficult to treat. If proven to be a viable treatment option, interferon-free therapy would eliminate interferon’s side effects. This, in turn, would potentially encourage patient compliance (Zeuzem 2012).
HCV Vaccination on the Horizon
A February 2012 report states Michael Houghton, one of the scientists who discovered HCV in 1989, developed a vaccine from a strain of HCV. The results have been overwhelmingly positive—patients who received this vaccine produced antibodies that neutralized all known strains of HCV, a feat previously thought impossible given the virulence of HCV. Although further testing will be needed, and it would likely take five to seven years before the vaccine could receive approval, preliminary findings are encouraging (Hanlon 2012).
Life Extension has been reporting on the benefits of thymosin alpha-1 since the early 1980s. This immune-boosting agent has been studied for its potential role in treating cancer and viral hepatitis. Study results suggest thymosin alpha-1 in addition to pegylated interferon plus ribavirin treatment may improve the efficacy of treatment in patients who were previously not responsive to therapy (Poo 2008; Baek 2007). Other study findings have indicated taking thymosin in addition to standard HCV treatment might lower the rate of relapse (Ciancio 2010). Moreover, thymosin alpha-1 shows promise as a potential adjuvant therapy in difficult-to-treat patients with HCV, but more studies are needed (Sherman 2010). In another trial among 552 hepatitis C patients who were non-responders to standard care, addition of two 1.6 mg subcutaneous injections of thymosin alpha-1 per week to pegylated interferon plus ribavirin for 48 weeks resulted in a 41% sustained virologic response compared to 26% in placebo recipients (Ciancio 2012).