When it comes to viral hepatitis, hepatitis C has become relatively boring since curative therapies have been so effective in treating the disease.
Managing HCV has essentially been reduced to identifying and linking patients to care. Although incredibly important, it lacks seductiveness. However, we recognize that when we can leave one disease space, it often allows for explosions in diagnostics and therapeutics in other places.
This month’s cover story brings that explosion of diagnostics and therapeutics to the forefront and focuses on how hepatitis B has become an interesting avenue to explore drug development.
The problem is, hepatitis B is already confusing for the average person. For hepatologists, or someone who specializes in either infectious diseases or hepatology with a focus in viral hepatitis, hepatitis B is not that difficult. But it often makes the average gastroenterologist, or someone who’s not as experienced with hepatitis B, a little nervous just trying to interpret the diagnostics and match the therapeutics appropriately.
There are a multitude of tests that you can order, and guidelines that you could try to follow. And although the guidelines have tried to be simple, it’s not as simple as just an active virus or agent.
Hepatitis C is relatively easy, but hepatitis B is harder. The guidelines are not consistent all across the board. There are subtle differences between the society’s, and physicians have to interpret the patient that is in front of them and match the appropriate therapy.
These therapies tend to be lifelong, whereas hepatitis C treatment is finite, which is easier for everyone to wrap their head around.
If we look ahead at the number of areas where therapeutics are being developed in hepatitis B, of which Ira M. Jacobson, MD, and Harry L.A. Janssen, MD, PhD, offer a snapshot, there is probably a company somewhere looking at every place in the replication process of hepatitis B as a potential therapeutic target.
Figuring out the ideal patient and therapy might take a little while. When several mechanisms exist, complexity is magnified by the ability to combine agents in different classes. Some of these ideas may work better as a combination therapy, and others might not be as effective in combination.
We originally looked at using two nucleosides for hepatitis B, and we recognized that using something like lamivudine and telbivudine together was not more effective than using either alone. Learning how to better pair the diagnostics to have predictive values is exciting, because we’re going to have things to experiment and learn about. But it is likely going to lead to a period of time where we don’t exactly know what we’re doing, and we might be doing things in a less than ideal fashion.
Of course, it is very early in the process, and even if one of these agents shows promise, the diagnostics to optimize its use may not be available. In the U.S., it’s relatively new that we can even quantify surface antigen which is very useful in predicting response to current anti-virals. When you haven’t been using a test very long, it’s hard for clinicians to understand how to incorporate it into their diagnostic algorithms. Many of these therapeutics are going to require more sophisticated diagnostics and different surrogates for response. The goal isn’t to control the virus, but rather, the goal is to decrease liver cancer and cirrhosis, liver complications, liver morbidity and liver mortality. There’s no conceivable reason to think suppressing a virus through a different action would lead to worse outcomes, but data are still going to be needed to be sure that these functional cures end up in the place that we would like them to be.
Nancy S. Reau, MD
The Richard B. Capps Chair of Hepatology
Division of Digestive Diseases and Nutrition
Rush Medical College
Associate Director of Organ Transplantation