Dr Kwo: The direct-acting antiviral agents tackle the replication proteins for the hepatitis C virus, and there are three broad classes that we have been able to assemble to allow cure in most people. The first class of DAAs emerged in 2011 and are the protease inhibitors that interfere with the protein processing and synthesis pathway for the hepatitis C virus. We have a single polymerase inhibitor that is still commonly in use, sofosbuvir. This interferes with direct replication of HCV. And most recently, there is a very interesting inhibitor called an NS5A inhibitor, which helps retard the hepatitis C virus as it replicates and in the virus release. When we combine these direct-acting antiviral agents either as couplets or trios, we can achieve extraordinarily high cure rates in virtually all hepatitis C populations, including those populations that we have historically deemed very difficult to cure.

 

Dr Kwo: Optimization means delivering the largest number of treatment options to the widest population. For treatment strategies in large populations, such as in China in parts of the country that have not yet seen the universal benefits of hepatitis C therapies, it will be important that simple, straightforward combinations of therapy are made available that have few drug-drug interactions and few side effects. Fortunately, all of the oral therapies that have been approved now have really simplified their approach in this regard compared to the older interferon days. All of them can be taken with very few precautions, although one must be aware of potential drug-drug interactions even though there are very few that are problematic. In emerging markets, we have to be careful with some supplements and herbs that are commonly used. These drug-drug interactions involving these supplements are not well known, and I suspect the most common strategy will be to simply stop them. But by allowing the greatest number of people who are diagnosed with hepatitis C the opportunity to take the approved therapies or the therapies that are reimbursed in that particular area, we should be able to get cure rates or sustained responses rates that are the same as the sustained response rates that we see in the registration trials (which are close to 100%). Real world data shows that you can get very close to these levels of efficacy when properly implemented, and there is no reason why developing countries cannot do that as well.

 

Dr Kwo: The good news is if you are diagnosed with hepatitis C and you don’t have cirrhosis (and even if you have cirrhosis that is compensated), your treatment options are many, and the chances that you will be cured are extraordinarily high. When physicians start using the DAAs and discuss this with patients, the important thing to communicate is that cure is expected. It is no long IF you get cured. It is now, if we do this correctly, you should be cured. There are still some challenging populations though that require careful management. For instance: decompensated cirrhosis patients; those that have developed ascites; those where it is determined they have hepatitis C only because they developed decompensated liver disease. These are individuals who have to be carefully managed by liver specialists, because, even though the chances of achieving a sustained response are good, there are still going to be issues of risk for liver cancer and issues with portal hypertension varices that will require long-term management. So we need to make sure that the liver disease is managed just as well as the viral infection. The other special populations like dialysis and HIV-HCV co-infection are manageable and can be treated effectively. Finally, in Asia, the last important aspect is that there is a lot of hepatitis B as well, and that these DAAs can (although rarely) reactivate hepatitis B. That is an important issue particularly for the Asian region, that as we treat more and more hepatitis C cases that they are adequately evaluated for hepatitis B to prevent reactivation.

 

Dr Kwo: What can we do and how realistic is it to pursue global eradication of hepatitis C? The answer is that it is quite realistic, but to do it, multiple strategies will have to be employed. First, if you are diagnosed with hepatitis C in any part of the world, you need to be linked to someone who can treat you successfully and cure you. Secondly, we are going to have to treat people who we have historically not treated. These are people who inject drugs and people with other high-risk behaviors, who we would typically not treat, yet they are the individuals spreading the virus. We need to be getting this population the help they need for harm reduction, but also treated. Many of the patients we readily treat with advanced or end-stage liver disease are less likely to be spreading the virus than the younger individuals. We need to be aware of the demographics of hepatitis C. Not only do we have a cohort of older people (for example, in Japan and to a lesser degree in the United States), but there are also younger generations acquiring hepatitis C. We need to be able to find those individuals. There are few chronic diseases that we can actually cure without a vaccine by giving a finite course of therapy and thereby prevent the morbidity and mortality. For instance, there is no pill that will stop heart disease. There is no pill that will stop hypertension. When left untreated, hepatitis C causes tremendous morbidity and mortality, and the ultimate solution for some would be a liver transplant. These are complications that a global eradication strategy can prevent if successfully implemented, leaving our liver-related resources open for use in other chronic liver diseases.