Chronic liver disease is affecting millions worldwide and presents major global challenges. Researchers Nina Tirnitz-Parker and John Olynyk discuss what’s being done to understand, prevent and combat liver disease and cancer.
Chronic liver disease is one of the most rapidly growing causes of death worldwide. Current treatments for liver cancer are limited and only prolong life by only months.
In this episode, Associate Professor Nina Tirnitz-Parker from Curtin University’s Liver Disease and Regeneration Group and Professor John Olynyk, Director of Research Development at Fiona Stanley Hospital, explain what liver disease is, and what the future holds for its prevention and treatment.
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You can read the full transcript for the episode here.
Intro: This is the future of where experts share their vision of the future and how their work is helping shape it for the better.
David: I'm David Blayney. Many of us will know someone who has succumbed to liver cancer. It's one of the most rapidly growing causes of death worldwide, but unfortunately by the time liver cancer is diagnosed, it's usually incurable with current treatments, prolonging life by only months with me today to discuss the quest to cure liver disease and liver cancer is associate professor Nina Tirnitz-Parker, who heads the liver disease and regeneration group at Curtin university and her research partner and the director of research development at Fiona Stanley hospital, Professor John Olynyk.
Dr John Olynyk: Morning.
David: To start with you, John, I guess a bit of background. What's the difference between liver cancer and liver disease?
Dr John Olynyk: So currently I work as the head of gastroenterology and hepatology at Fiona Stanley Hospital and I've been working in the field of liver disease and gastroenterology further 30 years now. Liver disease is very common, has been increasing in terms of its prevalence in the community and the knowledge that people in the community have about it, for a long time. Liver disease, basically just means your liver isn't working right for some reason. Many people with liver disease have absolutely no symptoms whatsoever, so they can be walking around feeling completely well and yet have a very scarred liver. Conversely, some people can feel very unwell with it. So there's a huge range of manifestations. So you don't have to look sick to have liver disease. The commonest causes of liver disease would be what we call nonalcoholic fatty liver disease. In other words, obesity related liver disease. And that globally now is the most common liver disease. So it's again a lifestyle manifestation of obesity and weight gain.
David: Is it just because we're living longer that we, you know, we tend to to sort of get cleaned up by these sorts of diseases, which we wouldn't have gotten younger, or is it is it due to our lifestyle?
Dr John Olynyk: A combination of both. So, uh, we are living longer, yes. And so we're living long enough for whatever nasty things we take into our bodies or due to our bodies to have some sequelae. But also there's a lot of other factors driving these things. So it's not just what we eat and watching too much TV. It's genetics, it's what our parents have done, the effect that that's had on us as we're developing and then it's all the exposures after we're born, be it diet, lifestyle, that ultimately manifest as this, and so for fatty liver disease, it's a combination of all of the above. The treatment therefore is not any one individual thing. It has to cut across the board of all the things that contribute to it and then if you have liver disease long enough, the liver is quite an intelligent organ. It tries to fix itself and in the process of fixing itself, ultimately at some point it may get it wrong and that's when we end up with cancer as a complication of that process.
David: Why does it take so long for us to detect liver cancer?
Dr John Olynyk: Because again, the liver disease itself, which is a requirement, can be very subtle and have no symptoms and then the cancer itself - just in the same way as for example, breast cancer - you might only realize you've got breast cancer if you find a lump. It's not because you felt unwell or looked any different until it's very late in the disease. Same with bowel cancer. That's why we have screening for it because we know symptoms are not a very good way of diagnosing it and so, in the community walking around, people won't expect that they've got liver cancer, especially in the early, most treatable sorts of phases. It's only they'll look unwell when it's very advanced and by then we've lost the battle.
David: And we don't usually screen people for liver cancer in the same way that we do for bowel cancer or for breast cancer. Is that right?
Dr John Olynyk: In a general sense in the community, no, but if we know that you have chronic liver disease and you've got what we call cirrhosis or advanced scarring of the liver, then we will recommend people to have an ultrasound every six months, and possibly some blood tests as well, to keep an eye on the liver to detect the earliest stages of something going wrong in the form of a cancer.
David: Nina, you're quite heavily involved in research in this space. I understand you recently got an NHMRC grant to do some research. What's it about?
Dr Nina Tirnitz-Parker: I did and John Olynyk is also part of that. It's an international collaboration we have with the Center for Regenerative Medicine in Edinburgh in Scotland and QMR Burkholder in Brisbane and it's looking at two forms of liver cancer. One is hepatocellular carcinoma, the most common form, especially in Australia, and the other one is Colandra carcinoma or cancer of the bile ducts. And our research looks at how we can target certain cells in that process of liver disease and tell them to induce regeneration as opposed to liver disease progression to cancer. So we want to understand how these cells talk to each other. We want to decode their language and pretty much make them do what we want them to do.
Dr Nina Tirnitz-Parker: The project itself focuses on a certain pathway that we discovered to play a major role in liver disease progression and we want to find ways to actually inhibit that sort of language that the cells use to talk to each other. So there are certain ways - we want to develop what's called small molecule inhibitors. Certain ways like antibodies where you can target certain cells and block that activity if you like. And yeah, we've taken it to a step where we are almost in a phase one clinical trial phase. So we want to establish the foundation for the research to take that pretty much from bench to bedside. So that's the pipeline.
David: And that would involve some sort of pharmaceutical, treatment or how ...
Dr Nina Tirnitz-Parker: Eventually, yes. So we are not there yet. We need to first establish the mechanisms. We really need to understand what's going on before we risk the health of a patient. So there are certain steps that we need to do first. We look at cells in isolation where we know exactly what's going on. Then we need to test what we think has an effect in a bigger system. So we look into - let's say - something called a precision organ slices, where we can have little organ systems and we can look at the cells in their natural environment without risking the health of a patient. So it's actually possible to take a little piece of liver, slice it into many different mini organ systems. In the mini organ systems we can test different ranges of drugs, different combinations, different concentrations, and determine what really made the best effect without any side effects. So we can test this outside the body before we have to risk the health of a patient, which is quite exciting and a very powerful technique.
David: So what's on the horizon with respect to research in liver disease? What do we need to learn?
Dr Nina Tirnitz-Parker: So John and I worked together as a clinical and sort of fundamental research team because we actually look at those things. So what is most important to work on? What would make the best difference? The biggest difference for a patient? And at the moment we pretty much work towards 'prevention is better than cure'. So we would like to identify, let's say, biomarkers, which is a molecule so we can identify in the blood of a patient or in the tissue. So say you go to the doctor, say you have a blood sample taken, we would like to take that sample and look at sort of the signature of molecules that are in there, to have a fingerprint of that patient and say, does that tell us whether a patient will develop liver cancer? Or do they need to be put in a higher surveillance group?
Dr Nina Tirnitz-Parker: What can we actually predict from that sort of signature? We also need to identify all the mechanisms better, how it actually develops, and not only what predicts it, but identify pathways that we can interfere with. At the moment, we are in a very exciting time in liver cancer research because a lot of technologies have just become available. For example, previously you could look at sequencing, which means you decode the language of cells. So how the genes are transcribed. And you could only do that for whole tissue pieces. And just very recently, the technique was developed to actually look at this in a much higher resolution. So you can look at a single cell level and we are involved in a few projects in collaboration with the Harry Perkins Institute for medical research. And we are actually looking at the profile of individual cells and how they talk to other cells and how we can target those cells. And we identify new cell populations every day in our analysis. And it's a really exciting time.
David: John treatment options right now for liver cancer and chronic liver disease are relatively limited. Why are these options limited?
Dr John Olynyk: Okay, so if you look at it, it depends again who you're talking about. So if you're talking about a population, the sorts of treatments we do at a population level are by necessity very different to what an individual patient gets because of cost, availability and things. So treatments need to be designed to layer into all levels of society. So out there in the community, for liver disease probably the most effective strategies are those related to the lifestyle inducing elements of this. So obesity and weight - things designed to treat that - alcohol, exposure to chronic viral hepatitis and everything from needle control to not using drugs or sharing needles, et cetera. So they're all the things that are community level.
Dr John Olynyk: Once you get to a patient, the diseases we can treat fairly effectively now are chronic viral hepatitis, where we've got good drugs for both hepatitis B and hepatitis C. So in hepatitis C it's curable and hepatitis B, it's controllable. However, once you turn up with alcohol-related liver disease or nonalcoholic fatty liver disease, to the point where you're presenting to a hospital and unwell, there's very little we can do. We do try and get people to stop alcohol and we have programs with that, but often that's easier said than done and fatty liver disease, the same sort of thing happens. So we'll often end up seeing people who've just incubated whatever disease process is going on all their lives and then turn up with a clinical problem. Either they're unwell, they look unwell, they've got a complication of chronic liver disease or they've got liver cancer.
Dr John Olynyk: And once you get cancer, the problem is that for most people they've got a degree of severe scarring or impairment of the way the liver works anyway. So, and as most people know, if you have liver disease or kidney disease or heart disease, that dramatically impedes the ability to take drugs, which could kill cancer cells and use them safely. So that's the first thing in patients with liver disease - you can't use nasty drugs because the liver can't clear them properly and you'll end up harming the patient rather than the cancer. So chemo is very limited. There are new drugs coming along, but to be honest, they're more in a palliating, life extending mode rather than a curative mode. Cures for liver cancer, that is, we found the abnormality and can remove it, less than 10 to 20% of people in a curative mode. So the majority of people who will turn up now with the world's second commonest cancer, that causes years of life lost, we'll be going into, 'we're going to try and extend their life and quality of life rather than cure them' type mode.
Dr John Olynyk: So that's why if you think about it, by 2030, of all the people in the world with chronic liver disease, the majority of them, when they die, because of the chronic liver disease, will die because of liver cancer, not because of their liver just failing and not working. So there's going to be a dramatic change in the way we as a community experience and see liver disease over the next 10 to 20 years.
David: How are we doing in terms of population health in this area? I understand, you know, personally I was vaccinated against hep A and hep B under the childhood vaccination program. How things trending and we're getting better in this area, or are we getting less and less healthy?
Dr John Olynyk: So viral hepatitis, hepatitis B, universal vaccination, that's a standard of care, just as it is for many viruses and it's a preventable disease. So, everything we do that can prevent something is well worth doing. There's good data on that. Alcohol, again, it's an issue in our community. It is globally. And, unfortunately, no matter what we tend to do, we will always see and experience alcohol-related liver disease. Nutrition - and the fatty liver disease, which is now the commonest - that starts almost after birth. It's not the problem just of the person who's got it in adult life. It actually incubates during whenever mothers are pregnant with their children, because there's genetic and other lifestyle things that contribute to the risk. There's early life nutrition, so for example, if you're breastfed for the first six months of life without introducing solid foods, you have a much lower risk of fatty liver disease. And in fact, a lot of other metabolic things. So there's a whole raft of things. And then we get to the people like me who work in a hospital who see that pointy tip of an iceberg of people who come in.
Dr John Olynyk: We'd rather not be seeing that, and that's where Nina's research comes in - to try and prevent this whole cascade going wrong. Because the reason we live with liver disease is, our liver can repair itself. And so we just need to get the balance right where the good stuff happens, i.e. the liver fixes itself and keeps us healthy, as long as we can, but try and avoid the bed sequelae, which is the cancer development, which is really getting the language right between the cells, which is where Nina's targeting all that work.
David: Nina, could you tell us about the Lions Lotus PhD scholarship?
Dr Nina Tirnitz-Parker: We received very generous support from the Lions Cancer Institute. They were interested in supporting a PhD scholarships scheme. That's not the first one that they've supported. They've teamed up with the Cancer Council of Western Australia and two Curtin University students receive top-up scholarships this year already, working on different areas of cancer research. So one is in cancer and palliative care and the other one is an immunologist. So different aspects of cancer research are supported. And I approached them with an idea earlier this year to see how we can possibly attract the best student to cover three-and-a-half years of PhD studies, just to kickstart that scheme. But we plan for the student to get a government-funded scholarship because we will only select the best student possible, that already has the runs on the board to really be competitive for those government scholarships. And then we only take 10,000 out of that pot instead of 30,000.
Dr Nina Tirnitz-Parker: So if I can fill that gap on a yearly basis with my fundraising, then we can make it an in-perpetuity scheme, which would be exciting because then you don't have to plan for three and a half years. You can really look at the big ticket items and say, what can we do within 10 years of our research? How can we drive this and really have a meaningful, impactful change in the research field? So, currently fundraising around a trip coming up to Antarctica to fill that yearly gap of 10,000, so we can make it an in-perpetuity scheme.
David: What are you doing in Antarctica?
Dr Nina Tirnitz-Parker: That is part of a program called Homeward Bound. It's an international leadership program for women in STEM. So STEM stands for science, technology, engineering, maths and medicine. And I guess I represent science and medicine. It's a program that was designed by an Australian group actually, but now it's global and it's supposed to equip a thousand women over 10 years with skills and allowed a voice to fight for what is close to their heart and to inform policy and come up with strategies that secure a positive future for our planet basically.
Dr Nina Tirnitz-Parker: So there's very different aspects that go into that program. So there's people from space shuttle engineer to conservationist to medical researchers and the Arctictica trip is a retreat. So what's better than a retreat in Antarctica? I guess we can focus for four weeks on what is important, we can collaborate and we have scientific programs. And around that trip, there's a lot of media attention because it's an all female expedition. I'm in the fourth cohort with actually six other people from Perth - two other Curtin people are in the cohort - and around the trip I'll fundraise for the Lions Lotus PhD scholarship, but also for the PNE Scholarship, which is a scholarship scheme focused on pancreatic cancer research, because that's something that's also close to my heart. So if anyone is interested to support this, they can contact Curtin University and the Curtin Foundation will look after those funds and make sure that they go directly to our research and support those students that work in our research program.
David: And if there's anyone listening, anyone who knows a smart student, or if they themselves reckon they're pretty switched on, what should they do?
Dr Nina Tirnitz-Parker: If they're interested, it will be advertised very soon on the Curtin University website. I think it is already advertised, but you can't yet apply for it because I planned to set it up first and get it known out there to be able to really select from a big pool of students. So we advertising very soon. I think the first student will be able to start in 2020 or 2021. We will not just throw the money away. We are really waiting for top people to come along that are enthusiastic and want to make a big difference. And the PNE Scholarship will be set up around the same time. So whether they're interested in liver cancer research or pancreatic cancer research, there's some exciting things happening at Curtin.
David: Well, I think that's a very good place to wrap up this discussion. Thank you very much, Nina and John for sharing your insights and all the best for your research and for your trip to Antarctica.
Dr Nina Tirnitz-Parker: Thank you for having us.
Dr John Olynyk: Yeah.
David: And that brings us to the end of this episode. You've been listening to The Future Of podcast powered by Curtin University. If you have any questions about today's topic, please feel free to get in touch by following the links in the show notes. Bye for now.