So the viruses themselves are probably in general, not directly, cytopathic. And by that, I mean that you can have large amounts of the virus in a cell, in the hepatocyte or liver cell, without that liver cell being damaged in any way. So it’s not the presence of the virus, which actually causes the damage, in general; it’s the body’s response to the damage, which is the key component in causation of liver injury. And what the immune system, what everybody’s immune system, is designed to do is to identify and to discriminate and to then eliminate foreign proteins.
So that when a cell, a liver cell in this case, is infected with hepatitis virus, then some of the viral proteins should eventually make their way to the surface of that cell and be exposed to the exterior. So that the immune system can come along and have a sniff and decide whether there’s any foreign proteins in the cell. And if the immune system comes along and detects a viral protein, and recognises that as being a foreign protein, then a sequence of events should follow, where the immune system leads to the destruction of the infected hepatocyte. So it’s actually designed to eliminate the factories of the virus.
That’s a key component in elimination of the infection or otherwise other aspects of the immune response, which are important as well. But the key thing is that the hepatitis and the liver damage are due to the immune system’s recognition of an infected cell and then the elimination of that cell.
OK. So, without knowledge of the epidemiology of infection, and there are people who may have reason to believe that they’re at risk of being a carrier of Hepatitis So here I think we’re talking about, mainly about, well people who have put themselves at risk in some way, or have been at risk in some way, and therefore are keen to find out whether they might be a carrier. In some parts of the world, the prevalence of hepatitis carriage is so high that just being a member of that population is sufficient to encourage you to be tested.
For instance, if we look at the first-generation Pakistani community in England, then we know that the prevalence of hepatitis carriage in that community is the same as the prevalence in their country of origin, in their region of origin. So that we’ve got a good idea, then, that there’s about a 1 in 20 chance that a British first-generation Pakistani would be a carrier of hepatitis, a 1 in 20 chance. So that’s a sufficient risk that that person should consider getting themselves tested. If you’ve ever injected drugs in the past, then you should seriously consider getting yourself tested for Hepatitis C infection.
And there are public health campaigns all over the world which are encouraging people who may have a history– often 30 years ago and often briefly– but if they’ve got any history of injecting drug use, then Hepatitis C infection is a distinct possibility. And the treatments are so good for chronic hepatitis now, but it’s important that people are diagnosed at a pre-symptomatic stage, even if they’ve got serious liver damage because death from liver disease can be prevented with good anti-viral therapy.
Acute hepatitis, in general, requires no anti-viral therapy. So the majority of people who get acute hepatitis will find they have a self-limiting and resolving illness. So anti-virals are not used in that setting. We usually just observe the patient to make sure that the liver damage does not get so severe. And anticipate recovery in the majority. So the treatment of viral hepatitis is really targeted towards people who are carriers of the infection. Remember, it’s carriers that have the chronic liver damage, and it’s the chronic liver damage that goes on to cirrhosis, liver failure, and liver cancer.
The reason to treat the chronic hepatitis– and here we’re talking about Hepatitis B and Hepatitis C infection– is that if you can eliminate the virus or suppress the virus effectively and indefinitely, then you prevent further liver damage. Now for Hepatitis B, the paradigm is very much that of HIV treatment, in that our anti-virals that we use are very good at suppressing, but not very good at eliminating infection. So for the large majority of patients treated for Hepatitis B, we aim to suppress the virus to undetectable levels, and having done that, we’re confident that disease progression is prevented, and that recovery will start to occur.
The treatment paradigm for Hepatitis C is completely different from Hepatitis B and from HIV because it’s a short duration of therapy which aims to completely eliminate infection. And if you completely eliminate infection, then we see that same sequence of events– we prevent progression, we start to see a regression of liver damage, and we can be confident that the person we have treated will not suffer consequences of cirrhosis, like liver failure in the future.
Hepatitis C treatment presently has been revolutionised because we’re going through a period where there’s been very active drug development and the drugs are incredibly effective against Hepatitis C. And some of them have been licenced quite recently in many countries around the world. The real challenge now is to make sure that the additional drugs come through, and that we can afford to treat patients with these anti-virals. That’s going to be one of the major challenges, I think, during the next 5 to 10 years– affordability rather than efficacy.
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