Hepatitis C: What have been our successes so far?

[MUSIC] I'm Dr. Sheila Feigh, Senior U.S. Clinical Lead in the BMJ Knowledge Center. And I'm very pleased to have with us today Dr. Jawad Ahmad, Professor of Medicine in the Division of Liver Diseases at the Mount Sinai Hospital in New York. And the author of our BMJ Best Practice, hepatitis C topic. We'll be discussing some of the issues surrounding its treatment. Welcome to Dr. Ahmad. Thank you Sheila, very happy to be here. So let's start with some background. Who gets hepatitis C? What are some of the risk factors? And how do you diagnose it in practice? So hepatitis C is really a viral illness that's spread through tainted blood. So if you injected drugs or if you've received blood transfusion from tainted blood, then you're at risk of hepatitis C. Now the blood supply is obviously screened in all the developed world. But if you had a transfusion prior to 1990, then you were at risk for hepatitis C. But the majority of patients that we see particularly in the U.S. are from injection drug use. And how do you diagnose this? How is it usually picked up in clinical practice? So you have to have an index of suspicion. And in fact, in the United States, all baby boomers should be tested because the incidence is high enough. A baby boomer is someone born between 1945 and 1965. But obviously if patients have risk factors for hepatitis C, such as injection drug use. And there are some others that really should be tested as well. So for instance, if you have ever been incarcerated, if you're in any kind of institution, those patients have a higher incidence. So there should be a high index of suspicion. The test is very straightforward. It's a hepatitis C antibody test. And if that's positive, that implies that you have been exposed to hepatitis C. And just because of the way your immune system works against hepatitis C, if you've been exposed to hepatitis C, there's about a 70% chance that you still have hepatitis C. So if the antibody test is positive, that implies you've been exposed. And then you'll do a confirmatory test, which is a hepatitis C RNA test to show that you actually have active hepatitis C. So in general, the antibody is not protective. It indicates active infection. So yes, the antibody is not protective at all. It implies prior exposure to hepatitis C. But because it's difficult to get rid of hepatitis C when you get exposed to it, the majority of patients that have a positive hepatitis C antibody will have active hepatitis C. And in fact, after successful treatment, even then the antibodies can still be positive. So what is a population that should be treated? Should we be treating everybody with hepatitis C and Y? So there's a very interesting question. And there are lots of political and financial implications for that as well. In the United States, over the last year or two, pretty much everyone who has a evidence of hepatitis C infection should be treated. And the reasoning behind that is that there is about a 15, maybe even 20% chance that if you have hepatitis C that's untreated, you will go on to develop cirrhosis. And the complications of cirrhosis, such as portal eye pretension, sometimes leading a liver trasmap, but also liver cancer. In fact, we've seen a large increase in liver cancer over the last 20, 30 years of which at least half is due to the hepatitis C epidemic. So the quick answer to who should get treated for hepatitis C is pretty much everyone. What's the currently recommended treatment? So this is where there's been another huge success story in the last about five years in the development of what we call direct antiviral agents. So historically, it was very difficult to treat hepatitis C required treatment with interferon and riboviron, which was a combination of drugs that had a lot of side effects and weren't very successful. Now we have drugs that are oral drugs that work in several ways against viral replication. But unlike with hepatitis B, they cause viral eradication. So they are used usually only in a three month course. And there's 95% chance that they will eradicate the hepatitis C from the patient. Does the genotype matter in prognosis and the treatment recommendations? So in terms of prognosis, not so much any genotype can cause bad disease. It used to be very important because some of the genotypes really responded very well to interferon and the main genotypes particularly in the United States did not. And we've almost got to the stage. And in fact, there will be new drugs being approved, at least in the United States in the next actually few months, that will be pan-genotypic, meaning they will lead to viral eradication irrelevant of genotype. Now we still check because it does have some implications sometimes in terms of how likely you are to get rid of the hepatitis C. So genotype is still checked. But I suspect in about two or three years, the genotype with hepatitis C will be irrelevant. And you won't need to check it because there will be a treatment that will eradicate hepatitis C irrelevant of the genotype. Let's move on to some issues following treatment with direct acting agents. Can patients who have been successfully treated get re-infected with hepatitis C? Yes. So this is what I tell patients all the time that yes, even though you have been-- this is a viral infection, you think, OK, I've been treated successfully. And I have an antibody against it that does not mean that you are protected against reinfection. So yes, even though you've been successful treated, you can get re-infected. Should patients be re-treated when current direct acting antiviral drugs have failed? Are there options for people with resistance? Yes. So we are seeing that now. The current treatments are actually very successful. So the number of patients that do not respond or have a viral breakthrough because of resistance, actually, is very small. What will happen is that it'll be a case-by-case basis. And in fact, you can order a resistance panel to see, OK, why did the patient develop or not respond? Which kind of resistance do they have? Very occasionally, there will be a patient that is resistant to all the current therapies. And those patients will have to wait until we have better combinations, which will come very soon. Particularly what you would do in that situation is order a resistance panel and see what they're resistant to and then try an alternative drug. And we have, as I mentioned, several different drugs. And we will have even more in the next few months. Is relapse seen after successful treatment? No, so that's that version never occurs. Very occasionally, you can have a patient that you treat. They become a hepatitis C RNA negative. And you check it several months later, it's still negative. And then nine or 10 months later, it becomes positive. Obviously, you have to think about reinfection, which is the more likely reason why the hepatitis C reappears after successful treatment. But very occasionally, you can get a rate late relapse. What about people who already have advanced liver disease related to hepatitis C infection? People with decompensated cirrhosis or people on the liver transplant waiting list? Should they be treated? So this is a little bit of a complicated question. The answer is usually yes. The current drugs, the oral direct antiviral agents, they really do not have a lot of side effects with a couple of exceptions. So that even patients with decompensated cirrhosis, or patients on the transplant waiting list, can get treated to eradicate the hepatitis C. And it becomes a little bit of an issue. And because the way liver transplant works in the United States, and same in Europe, is that it's based on a scoring system that measures how sick patients are. And if you have to be sick to get transplanted, if you successfully treat hepatitis C in some patients, they may actually improve a little bit. So it reduces the chances of actually getting transplanted. So you have to take it a little bit on a case-by-case basis. But in general, if the patient is not too sick and not too decompensated, you have a chance of treating that patient. So hopefully they can avoid the need for liver transplant. And obviously in those patients, particularly with decompensated cirrhosis, they're also at risk for hepatocelular carcinoma. So if you eradicate the hepatitis C, theoretically, you should reduce the risk of them developing a hepatocelular carcinoma. I'm going to finish up with a follow-up to the success story so far. You mentioned the new direct acting agents that most people being treated and even more drugs on the horizon. But we're such a long-term trajectory necessary to evaluate the benefits of antiviral treatment. The main question is, the successful treatment of hepatitis C in fact, can reduce the risk of liver cancer and cirrhosis? Theoretically, yes, would be the answer. The problem, as you mentioned, is that these are the disease that causes problems over many, many years. So for you to see an improvement should also take a long time. There has been some literature recently looking at this and it's been a little bit controversial. But I would anticipate what we will see will be, as we have seen with hepatitis B, that when you have successful treatment that's been available for 15 or 20 years and enough people have been treated, then you will start seeing that the risk of cirrhosis, or the number of patients with cirrhosis from hepatitis C and a paddocelular carcinoma from hepatitis C, will start dropping. We're not seeing it yet, but these drugs have essentially just been available for a few years. But I would anticipate that, yes, successful treatment of hepatitis C will reduce the risk of cirrhosis and the risk of a paddocelular carcinoma. Many thanks to you and to our listeners to find out more, click the link in the podcast information to sign up to a free trial of the MJBest Practice where you can visit the hepatitis C topic for more details. We also have a podcast about hepatitis B in the SoundCloud playlist. Thank you very much.