Liver diseases represent an unrecognized but exploding epidemic and a rapidly increasing cause of chronic disease and health-care utilization in Canada. For example, about 1 in 3 Canadian adults and 1 in 10 children have fatty liver disease not caused by alcohol intake. These numbers are much higher when limited to the 50% of Canadians who are obese, of whom three-quarters have fatty liver disease. While this disease initially has no symptoms, up to a quarter of these people will have their health deteriorate as they develop serious liver symptoms that can ultimately progress into liver cancer or complete liver failure. Currently, there is no readily accessible diagnostic test that can determine when fatty liver disease will progress to something more dangerous. When progression does occur, it is usually detected so late that the only treatment option is a liver transplant. Given the growing obesity epidemic, particularly among children and teenagers, the long term implications for individual health and the impact on the health care system are grave.
Assessment of Liver Fat
The only method currently available to assess liver fat content is needle biopsy, which is invasive, painful, costly, not very reliable, and carries significant risks for the patient. The problems with biopsy are so significant that the National Institutes of Health (NIH) in the USA has stated that “one of the roadblocks to therapeutic studies in … fatty liver disease is the need to perform liver biopsies …”. The liver imaging research group is part of an international industrial-academic partnership that is developing methods of assessing liver fat with MRI. With support from GE Healthcare and Canadian funding agencies, the team is now testing their techniques in patients with various forms of fatty liver disease. Their ultimate goal is to show that our non-invasive MRI fat measurement technique is as good as, or better than, the invasive liver biopsy and can therefore replace this unreliable and costly method of diagnosis. This could significantly increase the ability to monitor this burgeoning disease epidemic, not to mention improving the lives of patients who currently must undergo a needle biopsy.
Assessment of Liver Iron
Excessive amounts of iron can be deposited in the liver as a result of a number of relatively common genetic diseases, as well as a result of multiple blood transfusions (e.g. following major surgery). This excess iron can impair liver function, and if left untreated can result in liver failure. In patients with iron-overload, but no liver fat, MRI is the gold standard for measurement of liver iron content. However, many patients with fatty liver disease also have significant iron deposition in the liver. While existing MRI techniques can detect and possibly measure liver fat or iron-overload in isolation, no non-invasive method exists for accurately determining fat fraction and iron concentration simultaneously, because the effects of fat and iron on the MRI image can cancel out the other. This leaves a painful and expensive liver needle biopsy as the only option for diagnosis. The team is currently developing an extension of their MRI fat measurement technique that will also allow measurement of liver iron content, even in the presence of significant liver fat. Their ultimate goal is to improve this MRI technique until it is capable of eliminating needle biopsies in another large group or patients.
Monitoring of Disease Treatment
There are very few options for treating patients with fat and/or iron deposition in the liver. This is due in large part to the inability to use needle biopsy to closely monitor the iron and fat content of patients being treated with new therapies. The poor reliability of biopsy, not to mention the risks to the patient, preclude using repeated biopsies to see if a patients liver iron or fat content is actually responding to therapy. This group is just now starting to investigate the use of our MRI techniques as an alternative to biopsy to monitor patients’ response to treatment. Widespread use of the techniques being developed at Western/Robarts could significantly accelerate the development of treatments for these liver afflictions.
The development of new liver imaging techniques has taken on renewed priority in recent years, due to the recognition of the widespread nature of these diseases and the need to develop liver fat and iron assessment that will accelerate development of new drugs and therapies that promise to reduce the impact of liver disease. We are developing the next generation of MRI techniques for use in animal studies and clinical trials. Over the next decade, imaging will play a pivotal role in the development of effective new treatments for liver disease.