The Hepatitis C Virus (HCV) is a major global public health concern. It is a serious and complex bloodborne virus which manifests itself through complications of the liver. If left untreated, it can cause significant and potentially fatal damage, possible hepatic carcinoma and other complications leading to transplantation. The World Health Organization (WHO) estimates that 150 million people worldwide were chronically infected with HCV in 2011. The virus is responsible for 350,000 deaths globally with 10,000 – 16,500 deaths each year in the United States. Up to 90% of those infected with hepatitis C do not clear the virus and become chronically infected. In the United States, nearly 4 million people are chronically infected. The HCV virus is most commonly detected in people who are 40-60 years of age, reflecting higher rates of infection during the 1970’s – 1980’s. Recently, both the Centers for Disease Control and Prevention (CDC) and the U.S. Preventive Service Task Force have encouraged HCV screening among baby boomers (those born between 1945-1965).
Treatment modalities for HCV have advanced incredibly in the last 25 years since HCV infection was identified in 1989. We witnessed the first approved treatment with Interferon (IFN-a) in 1991, then seven years later, Ribavirin (an antiviral) was approved in combination with Interferon. Both of these drugs were revolutionary at the time because they inhibited viral replication. However, although this was an incredible advancement there were several side effects such as fatigue, flu-like symptoms and depression. Additionally, the body’s response to IFN-a, was not as efficient and effective as some had hoped. A decade would pass until we had an improved delivery method of Interferon. Pegylated Interferon (IFN-a) was introduced in 2001 and resulted in the interferon’s ability to stay in the body longer. However, the side effects in treatment still persisted.
Fortunately, HCV treatment regimens saw a breakthrough in 2011 when the first direct-acting agents were approved in combination with Interferon and Ribavirin for genotype 1 HCV infection. “We are now going to get into an era of using combinations of direct-acting antivirals”, said Luis Balart, MD, chief of gastroenterology and hepatology at Tulane University School of Medicine, in New Orleans. In December of 2013, the United Stated Food and Drug Administration (FDA) approved sofosbuvir (a nucleotide polymerse inhibitor of the HCV NS5B enzyme), as part of the first ever Interferon (IFN) free regimen for HCV. This was a major breakthrough because those who were not eligible for interferon due to contraindications now had a mode of treatment. Sobosbuvir was approved for use in combination with ribavirin for adults with HCV genotypes 2 or 3, and in combination with pegylated interferon (PEG-IFN) and ribavirin (RBV) for adults with HCV genotypes 1 or 4. This drug approval came several weeks after the approval of Simeprevir (a HCV NS3/4A protease inhibitor) which treated patients with HCV genotype 1 in combination with PEG-IFN and Ribavirin.
Despite the fact that the current standard of care for genotype 1 includes combination of PEG-IFN and ribavirin, the approval of these two new drugs represents a shift in the treatment paradigm for patients with chronic hepatitis C. These two types of Direct Acting Antivirals (DAA’s) are playing a role in bringing about important therapeutic advances, particularly for IFN-free treatment modalities.
In the next 6 months to five years, a number of new DAA’s are expected to receive the FDA approval for hepatitis C. According to Donald Jensen, MD, director of the Center for Liver Disease at the University of Chicago, “Five to 10 new HCV treatment regimens currently stand a good chance of being submitted for FDA approval in the next few years”. These new treatment modalities have a high sustained virologic response (SVR) rates, meaning that they have a high success rate. Not only are they effective at treating HCV but they are given in shorter duration with minimal side effects when compared to IFN based treatments. Moreover, the traditional risk factors thought to portend poor outcomes in HCV patients ( past treatment responses, gender, high baseline HCV RNA, advanced fibrosis/cirrhosis, and genotype-IL28B- non CC genotype) may have no effect with the new DAA agents.
“There are multiple, oral, interferon (IFN) free DAA regimens in late stage clinical trials with high SVR rates” said Mark Sulkowski, MD, Medical Director of the Viral Hepatitis Center in the Divisions of Infectious Diseases and Gastroenterology & Hepatology at Johns Hopkins School of Medicine, in Baltimore. These include the Gilead-based regimen of sofosbuvir plus ledipasvir, with or without GS-9669; Abb Vie’s ABT 450/r plus ABT267 and ABT333; Boehringer Ingelheim’s faldaprevir plus deleobuvir, with or without PPI-668; Janssen’s simeprivir and samatasvir plus TMC647055/r; Merick’s MK 8742 plus MK 5172; Bristol-Myers Squibb’s daclatasvir plus asunaprevir and/or with BMS 791325. Not to mention the already filed and awaiting FDA’s “stamp of approval” for several DAA’s that will be on the market within the next 6 – 12 months
These new DAA’s can be classified into three groups: protease inhibitors, polymerase inhibitors and NS5A inhibitors. All of the new agents target specific processes of the HCV life cycle. The treatment strategy involving these new agents is to include drugs that attack at least two different HCV targets in a single regimen. The challenge for the clinician will be to scrutinize the drug combinations and select the best regimen, such as assessing whether some populations may benefit from 8 or 24 weeks of therapy or the addition of ribavirin. However, the bottom line is that an extremely simple, safe, and effective therapy for HCV genotype 1 infection is here. Given the dramatic advances in the treatment of HCV infection, identification of patients with hepatitis C may provide an opportunity to cure patients and greatly reduce the health care burden associated with the complications of liver disease.
Finally, it is important to remember to ask your gastroenterologist if there are any new treatment options that are right for you. Gastro Health has been a long time leader in hepatitis treatment and expects to offer these new treatment combinations in the near future. At Gastro Health we remain up to date with current and future treatment remedies and offer quarterly support groups in order to effectively care for you and those you love.