Dr.Devanshi Seth Heavy Drinking and Liver Cirrhosis Interview

Dr.Devanshi Seth Heavy Drinking and Liver Cirrhosis Interview

The US government is investing $2.5 million in a Sydney-based study to determine the role of genetics in alcoholic liver disease. The study, should lead to better diagnosis and treatment of the condition - a silent epidemic that costs $3.8 billion a year in Australia alone.

"We still do not understand why only a proportion of moderate to heavy drinkers get liver cirrhosis," says Dr Devanshi Seth, from the Royal Prince Alfred (RPA) Hospital's Drug Health Services and the Centenary Institute who conceived and now leads the project.

"Nothing so far has been able to explain the unpredictability of why some people get cirrhosis and others who drink equal amounts don't," she says.

She and her colleagues will soon start testing the genes of hundreds of Sydney-siders and thousands of others in six countries with the support of the grant from the US National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH).

"Apart from alcohol consumption, several contributory factors, including diet, lifestyle, mental health, viral infection and gender, influence the risk of developing cirrhosis," Dr Seth says. There is evidence that genes influence the development and progression of this disease.

"We hope that by analysing the genes in a large international group comprising thousands of drinkers we can detect the genetic risks that predispose some drinkers to get alcoholic liver cirrhosis."

Like other multi-factorial diseases, alcoholic liver cirrhosis is controlled by a number of genes, each of which makes a small overall contribution. Previous genetic searches have been inconclusive because the studies performed to date have generally been too small to yield definitive results.

"The lack of specific markers for diagnosis and effective treatment compound the burden of the disease. That is why this research is so important," says Dr Seth. "The results will help us identify and treat the people most at risk from drinking."

While the disease has been predominantly seen among men over 50 years of age, it is becoming more frequent worldwide among younger adults and young women.

"This study is an important addition to Centenary's liver research effort," says Professor Mathew Vadas Executive Director of the Centenary Institute.

"Alcoholic liver disease is the leading cause of alcohol related death and contributes to 50% of the total burden of liver disease and to 15% of liver transplants," he says.

Dr Seth leads several other projects on alcoholic liver disease in collaboration with Professors Haber and Geoff McCaughan at the RPA and Centenary Institute.

Their group is one of few groups comprehensively addressing issues related to alcohol, ranging from genetics, to clinical, biomedical, molecular, mental health co-morbidities through to treatment approaches.

"We frequently look at the social costs to the community, such as violence and vehicle accidents, but we are not looking enough at the direct damage to the drinkers themselves. Health problems related to alcohol, especially chronic effects, are often overlooked because alcohol is so culturally embedded in our society," says Dr Seth

Dr Seth formed the GenomALC Consortium to conduct this large study with Australian colleagues as well as clinicians and researchers from the USA, UK, Germany, Switzerland and France.

"In Sydney, we will recruit hundreds of participants over the next three years through the clinics at four hospitals - Royal Prince Alfred, Liverpool, Concord and Fairfield. Half our group will have cirrhosis and the other half, the control group, will have been heavy drinkers for 10 years but be free of liver disease."

A pilot feasibility study for recruitment at these hospitals has already been undertaken through funding from Lion Nathan's Alcohol Health and Research Grant Scheme.

Interview with Dr.Devanshi Seth

Question: What is Liver Cirrhosis?

Dr.Devanshi Seth: If you damage your skin, for example, there is a scar formation (if there is a deep tissue entry) if it is a minor injury the skin will heal and you can't see a scar but if it is slightly deeper tissue entry then it will leave a scar on the skin, that scaring is what is happening inside the liver tissue. When people drink alcohol, 90% of the alcohol is metabolised through the liver and the liver is the major organ for detoxification. The liver is damaged all the time from different things, the liver does heal and regenerate but if you continue to damage the liver the damage will be far greater than the regeneration of the liver and that leaves a scar. When you have a scar on the skin, the skin is harder which similarity happens to the liver tissue as well and the blood vessels become constricted.


Question: What are the symptoms of Liver Cirrhosis?

Dr.Devanshi Seth: Symptoms are mostly evident at the later stages of Liver Cirrhosis which is an issue because people don't understand that they have damage to the liver. The liver has the greatest capacity to regenerate, if you cut two-thirds of the liver it can regenerate back to almost normal size. People do not understand or do not realise that the damage is done until it is too late.


Question: Is there a treatment for Liver Cirrhosis?

Dr.Devanshi Seth: At the late stages of Liver Cirrhosis there are not many treatment options; it is either liver transplant or mortality.


Question:How can we prevent Liver Cirrhosis?

Dr.Devanshi Seth: Some people are more susceptible to a moderate amount of drinking and we want total abstinence as far as possible. One or two drinks a day, three times a week is still okay but any more than the recommended guidelines is really not good. Alcohol experts actually say that not even a little bit of alcohol is good for you because it is a chemical toxin.


Question: Can you talk about how the study, funded by the US government, will help Australians?

Dr.Devanshi Seth: We still don't understand why people who drink alcohol to moderate or excessive levels get liver cirrhosis and worldwide this is a big problem because 50% of liver disease hospital admissions are due to alcoholic liver disease and there is no treatment for alcoholic liver disease. When you ask people to abstain from alcohol they will often say "my friends drink and they do not have liver disease" and things like that.

It is difficult to tell people they are susceptible to Liver Cirrhosis if they are a heavy drinker because we do not have any scientific basis for that, so far. We do have an indication that there are genetic basis for people being more susceptible or resistant to alcohol Liver Cirrhosis. This is one of the first larger studies, worldwide and we should be able to get an indication of whether there are genetic factors involved and what these genetic factors are. I hope we can manage this disease better and advise patients if they are more susceptible to getting alcoholic liver disease that they should stop drinking or cut down drinking. The study is important, worldwide, not just in Australia.


Question: Can you talk about what is involved in this study?

Dr.Devanshi Seth: The study will proceed by recruiting people who are drinking to excessive levels; these people have presented themselves at the liver clinic or an alcoholic clinic so they already understand that there is some kind of issue whether it is liver or not. We have organised a questionnaire that asks if they would like to be a part of the study. If they consent we ask them questions about their alcohol history, such as 'how long have you been drinking?', 'do you have any liver damage that you know of' and 'do you smoke'. We also do a blood test to find their genotype which becomes the basis of the genetic study. We calculate data about weight, age and muscle mass that we can correlate back to the results we get from the study.

In Sydney we are recruiting people from four major hospitals including the Royal Prince Albert Hospital, Liverpool Hospital, Fairfield Hospital and the Concord Hospital.


Question: What role do you play in this study?

Dr.Devanshi Seth: I am the leader of the study, worldwide. I look after the whole project and coordinate the study to ensure everything is happening on time and basic protocols are followed. I make sure that the data collection is good whilst also conductingresearch.


Question:What results are you expecting to see from the study?

Dr.Devanshi Seth: I am hoping that we find some genetic practice that will aid us in understanding more about Liver Cirrhosis. The genetic factors will help us because it is a worldwide study and we are more than likely to find something that is a common factor between people. This is the first step.


Interview by Brooke Hunter