Consultant hepatologist Professor John O’Grady at The London Clinic discusses the emergence of his field, and why we should all make ourselves familiar with the term ‘gamma GT.’ Words by Viel Richardson.
What is a hepatologist?
A specialist in liver disease. In the past, it was generally characterised as a subspecialty within gastroenterology, but over the past decade or so it has matured into its own specialty, driven by liver transplants and work on hepatitis C, which led to more people focusing on the liver as an entity in its own right.
What attracted you to the field?
During my training in Galway, a series of interesting liver cases came through while I was working in the gastroenterology department. These fascinated me and I decided I wanted to concentrate on this area. When I joined St James’s Hospital in Leeds in 1992, I was one of the first people in the UK to be appointed purely as a hepatologist.
What does the liver do?
It is the second most complex organ in the body. It receives most of the blood that leaves the intestines, so it deals with the nutrients the blood contains from the food that has been broken down during digestion. It stores some of them and converts the rest into other compounds that the body needs. It also filters out all of the bugs that may have entered the blood system from the gut. The digestion process produces ammonia, which ends up in the blood. The liver is extremely good at filtering that out.
The liver is also responsible for metabolising most drugs, either activating them to do their job or eliminating them from the body. The liver – along with the bile duct – is part of the biliary system, which plays an important role in draining toxins from the body. The liver is also significant for keeping our blood sugars balanced, and has a role in how the body deals with hormones, so it is a very complex and important organ.
What is a Fibroscan device?
The FibroScan is a quick, painless, non-invasive way of assessing liver health. Firstly, it scans for what we call fibrosis, which is the formation of scar tissue. If you cut yourself, the cut heals through the process of fibrosis, so it is a necessary function. However, long-term irritation of the liver may cause you to develop fibrosis around the areas of irritation. If this starts happening, you are in danger of developing cirrhosis, which is the most advanced form of fibrosis.
Secondly, the FibroScan reveals any fatty build up in the liver, which is often the beginning of liver issues. What makes it so important is that there are no outward signs when any of these systems begin to go wrong.
So, the scar tissue itself is not the issue, but its effect on the liver is?
Yes. The normal texture of the liver is quite soft, quite malleable. Once you’ve had a big meal, lots of blood is sent to the liver to be processed and it expands to cope with this extra demand. When fibrosis and cirrhosis occur, the excessive scar tissue reduces this elasticity. This means the liver cannot cope with the volume of blood it is receiving. The excess starts flowing into the body through blood vessels that are not designed to handle it, which can have two effects: it raises the pressure, which can lead to ruptures, and secondly, the untreated blood can have a serious impact if it flows into organs such as the brain.
What effects can poor liver function have on your general health?
There are three major things. First, the body has to work with blood that has been poorly processed, which can lead to a host of other problems. Secondly, it can create portal hypertension, which is the name for the increased pressure in veins caused when blood that should have been flowing to the liver flows elsewhere, and thirdly, cirrhosis can place you at greater risk of developing liver cancer.
Has liver disease treatment changed much in your time?
The huge change has been the rise in liver transplantation. I am very lucky that I came to the field very early on and have been able to see it develop. It has been a huge success and is a treatment for all the problems mentioned above. For individuals with end-stage liver disease, it really is fantastic.
Have there been pharmacological, rather than surgical, advances?
The biggest change has been the new development of antivirals for hepatitis C. Five years ago, if you came in with hepatitis C, your options were based on a drug called Interferon and patients had a 50-50 chance of responding to the treatment. The treatment took between six months and a year and there were a lot of unpleasant side-effects. Now, hepatitis C patients take a course of tablets for about 12 weeks, the drugs have more than a 90 per cent response rate and there are almost no side-effects. It’s a wonderful change.
What do you see as the biggest challenge the field is facing?
One of the greatest challenges for us as a profession is to dramatically increase levels of screening, because there are no outward symptoms until the disease is advanced. There is a blood test called gamma-glutamyl transferase (gamma GT), which bears the same relationship to liver disease as cholesterol does to heart disease. I would love to be in a position where the public are aware of and understand their gamma GT score in the way they understand their cholesterol levels.
If you had a silver bullet what would you aim it at?
It would be great to stop and then regress fibrosis once it has started. At the moment, we treat or manage the underlying cause, be it alcohol or non-alcohol related, and wait for the body’s defences to halt it. So, we are not treating the fibrosis itself, but trying to create the environment that would allow it to regress.
We would love to have a drug that attacks the fibrosis directly.
Where do you see the field in five years’ time?
The big thing we are working on is ways to stop fatty build-up in the liver, be that via alcohol or non-alcoholic causes. Fat is a very big factor in triggering fibrosis, and finding a way to stop it developing could significantly change the liver disease profile of the population. Of course, the big issue with liver disease is screening; if we can get on top of that, we could make significant inroads in public health terms.
What do you like best about what you do?
The excitement. Working with liver transplants has been wonderful. It is a real thrill to see patients who are healthy 30 years after their transplant. But I probably get my biggest kick engaging with excess alcohol users, getting a conversation going with them that they connect with. The problem with a lot of excessive alcohol drinkers is that they don’t get the right response from the medical profession and so don’t make any real progress. It is great when they engage, and work on the things I suggest. Seeing the difference, it makes to their lives is hugely satisfying.