Hepatitis C (HCV) is an infection that primarily affects the liver. In the majority of persons, HCV infection becomes chronic and if left untreated can cause numerous outcomes, including cirrhosis and liver cancer. HCV-related end-stage liver disease is the leading cause of liver transplantation in the United States.
Chronic HCV affects nearly four million Americans, and it is estimated that 75 percent of people with chronic infection were born between 1945 and 1965. The risks of cirrhosis and cancer are higher in older individuals and those who have been infected for a longer period of time.
Historically, the backbone of treatment has been a combination of two drugs.
- Interferon is a drug that activates the immune system to interfere, through different pathways, with production of the virus in infected cells.
- Ribavirin is a drug that changes the genetic material of the virus and blocks reproduction in cells. Also, it is thought to activate the immune system in order to destroy infected cells.
Prior to 2011, treatment with the combination of these two drugs for 48 weeks cured approximately 40 percent of patients with genotype 1 infection, the most difficult-to-treat form of HCV. However, treatment produced significant side effects (flu-like symptoms, fatigue, depression, anemia, rash), and could complicate other conditions, such as diabetes and thyroid disease.
Poor tolerability forced many patients to discontinue treatment early and lowered their chances of cure. The need for more effective and better tolerated therapies has led researchers and doctors to develop and study classes of drugs that target HCV directly (Direct Acting Antivirals, or DAAs).
- Protease inhibitors (PIs) include agents like telaprevir, boceprevir and the recently approved simeprevir. Any one of these drugs combined with interferon and ribavirin (triple therapy) improves cure rates and, in some cases, can shorten treatment duration from 48 weeks to 24-28 weeks. Cure rates with triple therapy can be as high as 70 to 80 percent in patients with genotype 1 chronic HCV. However, because the PIs are indicated with interferon and ribavirin, actual cure rates depend on factors such as race/ethnicity and stage of disease. Finally, the PIs have unique side effect profiles and can interact with numerous drugs, causing unwanted side effects.
- Recent FDA-approval of sofosbuvir, a nucleotide analog, supports treatment for patients with genotype 1 and non-genotype 1 chronic HCV. It will shorten treatment duration to 12 weeks when combined with interferon and ribavirin. Furthermore, for some patients, it will allow for an all oral, non-interferon regimen. Sofosbuvir-containing regimens improve cure rates up to approximately 90 percent.
Clinical trials conducted at Columbia University’s Center for Liver Disease and Transplantation currently study the effectiveness and safety of different interferon-free combinations. These combinations include potent agents that are well tolerated and have fewer interactions with other drugs. When these treatments become available, providers will be able to offer effective and well tolerated therapies to a greater number of patients. The long-term goal of treatment, which is HCV eradication with effective and safe drug combinations, will help to reduce complications from HCV-related liver disease, including cirrhosis and liver cancer, as well as the need for liver transplantation.