A hepatitis C patient* with genotype 3 wrote to me. He cleared hepatitis C two weeks in to his sofosbuvir and ribavirin treatment. He wondered if he could stop taking the medications now that hepatitis C was no longer detectable. His primary concern was that the drugs would damage his liver. I am so glad he asked this question, because if he wonders if he should continue, chances are others are wondering too. He had the courage and insight to ask before taking action.
My answer: It is critical to stay on hepatitis C treatment unless advised to stop by his medical provider. These new drugs are game changers. They are powerful, effective, and easier to take. However, they can cause drug resistance, a potentially serious issue we have not had until recently.
Sofosbuvir (Sovaldi) is a polymerase inhibitor and classified as a direct-acting antiviral agent (DAA). Simeprevir (Olysio), boceprevir (Victrelis), and telaprevir (Incivek) are protease inhibitors, and also DAAs. The use of DAAs for hepatitis C treatment is an exciting development as it dramatically improves the odds of reaching the goal of sustained virologic response (SVR) or viral cure for patients. Between reduced treatment lengths and fewer side effects, DAAs are saving lives.
Basic Theory and the New Hepatitis C Drugs
To understand viral resistance, let’s review basic evolution, specifically Darwin’s theory of survival of the fittest. Darwin noticed that sometimes the weakest members of a species died off before they could reproduce. Simultaneously, the strongest survived, passing on their genes to future generations.
Here is an example of Darwin’s theory: Imagine that you have a roach infestation. You try stomping on them but the fast ones scurry away. The swiftest roaches survive and have speedy offspring. You try organic pesticides, but that just kills off the weakest roaches; again, the strongest roaches reproduce. Finally, you resort to the most potent poisons available, but a few of the toughest roaches manage to escape. When they reproduce, their babies inherit the resilient genes of their parents and they are resistant to these strong insecticides. All future generations are likely to be resistant to these poisons, leaving you with a new infestation of roaches and no way to kill them.
If you are going to get every roach, you need to apply constant aggressive anti-roach measures and you need to get every single roach. You can’t let up, because if you do, the strongest will reproduce and then you will be fighting the toughest bugs. You have to keep killing the roaches even if you think they are dead, because if a few have any breath left in them, they will make more baby roaches that will mature into Super Roaches. They will be so strong, that nothing can kill them—and they will outlive even a nuclear war.
DAAs, such as sofosbuvir, apply constant pressure to hepatitis C by directly targeting the virus and interfering with its ability to reproduce. Viruses require healthy cells in order to replicate and DAAs hinder the process. Sofosbuvir disables an enzyme (the polymerase enzyme) necessary for hepatitis C replication. As long as you are taking your medication as directed, hepatitis C is being assaulted.
You keep the pressure on even long after hepatitis C is undetectable. Genotype 3 is especially strong, so it has the longest genotype-determined treatment at 24 weeks. Some patients with advanced liver disease may even need 48 weeks of treatment. The good news is that sofosbuvir has a low risk of resistance.
The reason we take these drugs is to eliminate hepatitis C, restore the liver, and reclaim health. It’s not a picnic to be on hepatitis C treatment, but it is a short-term inconvenience compared to living with hepatitis C. We are on these drugs to save our livers and our lives.
*Note: Some details were changed to disguise the identity of the patient referred to in this blog.