Why is the hepatitis C virus (HCV) so difficult to kill?

The hepatitis C virus (HCV) infects millions of people worldwide. Patients are desperate for an effective treatment but medical professionals and the pharmaceutical industry have yet come up with the ideal one. There are two main reasons why HCV is so hard to kill.

First, HCV knocks out the host’s innate immunity. By constant mutation, HCV may be able to escape detection and elimination by the host’s immune system. [1] Therefore, it is almost impossible for the host to kill the virus without external help.

Second, HCV is highly mutable. HCV is an RNA virus and lacks proofreading ability as it replicates, therefore dozens of mutated forms arise. Even within an individual, slightly different genetic versions of HCV are present. According to WHO, there are at least 11 HCV genotypes identified throughout the world. The genotype is the strain of the virus to which patients were exposed when they were infected. [1]

The genotype generally does not affect the progression of liver diseases. However, it is of great clinical importance; different genotypes vary in their responsiveness to HCV treatments. For example, compared with genotype 1, patients with genotypes 2 and 3 are more likely to achieve a sustained virological response to interferon/ribavirin therapy. In addition, therapy duration also varies among different genotypes. Patients with genotypes 2 or 3 generally are treated with combination therapy for only 24 weeks, while patients with genotype 1 usually receive treatment for 48 weeks. [2]

Traditionally, combination therapy with interferon/ribavirin is recommended for HCV patients. Interferons do not directly kill the virus; instead they boost the immune system response to attack the virus. The success rate for such therapy is very low and often comes with unbearable side effects such as fever, headache and other flu-like symptoms. [3]

In recent years, new medications for HCV were developed. One of the most promising is Harvoni, a direct-acting antiviral (DAA) medication. Unlike interferon, DAAs directly inhibit the ability of HCV to replicate. Harvoni is a combination of two DAAs where one interferes with the reproduction of the virus’s genetic material, while the other interferes with a protein needed to complete the virus life cycle in the liver cell.

Although Harvoni claims to have high success rates in clinical studies, not many patients can afford it due to its extremely high cost. Moreover, a person could get infected again even after successful treatment. [4]

Despite the introduction of new drugs, treatment options for hepatitis C patients are still limited. If patients are unable to receive antiviral treatment due to genotype or financial reasons, or have tried and failed, they should shift their treatment focus to protecting liver function and reducing inflammation (ALT).