MR elastography can replace a piecemeal approach to liver health
October 04, 2017
By Dr. Amy Salinas
MR elastography (MRE) has seen an increased role in noninvasively staging liver fibrosis since its introduction in 2009, with demand for the technology surging in 2017. Now, with multiparametric MRE on the horizon, radiology may soon offer a more efficient, comprehensive clinical pathway for liver health assessment.
For years, the gold standard for assessing advanced liver fibrosis – which is the primary clinical indication for initiating therapy in most liver disease patients – had been liver biopsy. Costly and uncomfortable, the accuracy of this invasive test is limited by the fact that it assesses only a small sample of liver tissue. The accuracy of ultrasound-based methods such as transient elastography is also affected by limited sampling volume and a high failure rate in obese patients. When magnetic resonance elastography (MRE) was introduced clinically nearly a decade ago, patients looking for more confidence in their diagnosis were eager to learn more. For the first time ever, they could see the degree of fibrosis across their entire liver, all without pain.
Background
Approved by the FDA in 2009, MRE was once only available as an add-on for new scanner purchases. However, since the major MR vendors (GE Healthcare, Siemens Healthineers, Philips) started offering MRE as an upgrade for older machines as well, the availability of MRE has skyrocketed. According to the manufacturer Resoundant Inc., there are now over 800 clinical MRE installations worldwide, with over 300 in the U.S. alone.
Technically speaking, MRE is an entirely new imaging modality, as it represents a quantitative technique for measuring the mechanical properties of tissue. Since many diseases can alter the stiffness of tissue in different ways, MRE uses very low frequency sound waves to create tiny movements in the tissue or organ being studied. As the sound waves pass through the region of interest, a special MR algorithm then analyzes the movements to determine the overall stiffness of the tissue being studied. The result is a color-coded map, called an elastogram, of the organ or tissue being studied, where blue/purple areas correspond to soft tissue and orange/red areas correspond to stiff tissue. In general, I find it to be one of the most intuitive and patient-friendly results to include in my report – especially when it adds virtually no additional time in the scanner for the patient.
MR elastography for liver fibrosis staging
Over the past 10 years, as the burden of chronic liver disease has exploded, there have been well-documented strengths and weaknesses among the noninvasive options for staging liver disease. Blood serum-based markers generally lack the sensitivity required, especially at moderate levels of fibrosis. The same is found for ultrasound-based elastography techniques, whose performance also becomes suboptimal in obese patients and those with ascites. Because payers often require multiple strategies before approving liver therapies, clinicians have often come to rely on a combination of tests to assess liver fibrosis stage – resulting in a piecemeal approach to diagnosis where costs and inconvenience to the patient can quickly grow.
However, MRE has enabled clinicians and patients to overcome many of the technical issues with other noninvasive options – and in my view has helped fuel demand for the technology as a "one-stop shop" for liver assessment. MRE has a very low failure rate (< 4%), and performs equally as well in obese patients as those with BMIs < 30, which is a contraindication for a lower-tech, one-dimensional technique called transient elastography (Fibroscan, Echosens, Paris).
Most importantly, in dozens of clinical studies, MRE has demonstrated the highest sensitivity for detecting advanced fibrosis and cirrhosis (0.94 sensitivity for MRE versus 0.86 for transient elastography, according to a recent meta-analysis compiled by the American Gastroenterological Association). Correctly identifying patients at this acute stage of disease progression is critical, as a missed diagnosis can put the patient at risk for liver-related mortality or liver transplant (average total weighted costs of $1.4 million per transplant). In a sample population of 1,000 patients with a prevalence for advanced fibrosis of 30 percent, an MRE-based approach to staging liver fibrosis would reduce the false negative rate by more than half (14 percent to 6.3 percent), over relying on transient elastography alone.
An MRE model for liver fibrosis can also reduce HCV treatment costs
The development of a direct-acting antiviral (DAA) treatment for Hepatitis C virus (HCV) is one of the great medical stories of our time. However, the cost of the treatment plans have resulted in a rationing of sorts. In the U.S., patients must typically wait until they exhibit advanced fibrosis to quality for treatment. But new studies have shown that waiting for advanced fibrosis to manifest may actually be more costly, as the efficacy of expensive DAAs for HCV treatment is significantly better when initiated at earlier stages of fibrosis.
In a “treat earlier” scenario, patients have been found to require fewer weeks to achieve sustained virologic response (SVR), and the overall SVR success rate is significantly higher when initiated at a mild fibrotic stage (reducing the need to re-treat). By shortening the cycle time and improving the cure rate, a “treat earlier” strategy would not only save billions over the next 10 years, but also help meet the calls of the patient community to avoid waiting until advanced disease has set in. The missing element in this preferable clinical model, however, is the current diagnostic model. By only relying on one-dimensional transient elastography, clinicians lack the diagnostic capability to confidently diagnose at these stages.
With MRE, however, clinicians would be able to consider treatment at an earlier stage of disease progression. MRE is capable of distinguishing among earlier stages of fibrosis with a very high level of sensitivity, bringing the “treat earlier” model closer to a reality. This type of model would result in systemic savings that outweigh the marginal increase of an MRE scan by a factor of 100. That would net billions of dollars in savings over a population model – all while meeting the calls of patients to avoid an acute stage of disease in order to qualify for treatment.
For health systems and practices looking for strategies that can help control overall costs, MRE is a "poster child" for improved outcomes at lower resource utilization. As a radiologist, it is one of my favorite examples of the value of advanced imaging.
The future of MRE
The future of MR elastography is extremely bright for liver disease patients. Looking beyond fibrosis staging alone, multiparametric MRE may soon add additional capabilities, including assessment of inflammation, in the same exam. If a traditional workup for hepatocellular carcinoma (HCC) is also included, referring clinicians now have everything they need to diagnose and manage a patient with suspected liver disease. This “hepatogram”, as some have dubbed it, represents the emergence of one of the most clinically efficient patient management strategies in recent years. Not far from now, the standard of care for suspected liver disease patients may begin with a patient’s hepatologist saying, “let’s get you a hepatogram and then go from there.”
From a population perspective, the emergence and proliferation of MRE couldn’t have arrived at a better time. The clinical and economic burden of chronic liver diseases is enormous. As around 3.5 million HCV patients begin to navigate toward a cure, clinicians, pharmaceutical companies and epidemiologists are turning their attention to an emerging disease threat, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD affects an estimated 25 percent to 30 percent of the population, with about 10 percent to 15 percent of those patients going on to develop NASH. Due to the comorbidity with obesity (which is a source of high technical failure for other noninvasive diagnostics), and the need for an assessment of steatosis and inflammation, multiparametric MRE is poised to become the optimal diagnostic pathway for patients and providers. As such, it will be great to see radiology offering clinicians and patients an innovative and comprehensive solution to a complex set of diseases.
About the author: Dr. Amy Salinas is a private practice radiologist at Austin Radiological Associates, which was among the earliest adopters of MR elastography for liver fibrosis assessment. She received her medical doctorate at Georgetown University School of Medicine, and completed her radiology residency and abdominal imaging fellowship at the University of California San Francisco.
MR elastography (MRE) has seen an increased role in noninvasively staging liver fibrosis since its introduction in 2009, with demand for the technology surging in 2017. Now, with multiparametric MRE on the horizon, radiology may soon offer a more efficient, comprehensive clinical pathway for liver health assessment.
For years, the gold standard for assessing advanced liver fibrosis – which is the primary clinical indication for initiating therapy in most liver disease patients – had been liver biopsy. Costly and uncomfortable, the accuracy of this invasive test is limited by the fact that it assesses only a small sample of liver tissue. The accuracy of ultrasound-based methods such as transient elastography is also affected by limited sampling volume and a high failure rate in obese patients. When magnetic resonance elastography (MRE) was introduced clinically nearly a decade ago, patients looking for more confidence in their diagnosis were eager to learn more. For the first time ever, they could see the degree of fibrosis across their entire liver, all without pain.
Background
Approved by the FDA in 2009, MRE was once only available as an add-on for new scanner purchases. However, since the major MR vendors (GE Healthcare, Siemens Healthineers, Philips) started offering MRE as an upgrade for older machines as well, the availability of MRE has skyrocketed. According to the manufacturer Resoundant Inc., there are now over 800 clinical MRE installations worldwide, with over 300 in the U.S. alone.
Technically speaking, MRE is an entirely new imaging modality, as it represents a quantitative technique for measuring the mechanical properties of tissue. Since many diseases can alter the stiffness of tissue in different ways, MRE uses very low frequency sound waves to create tiny movements in the tissue or organ being studied. As the sound waves pass through the region of interest, a special MR algorithm then analyzes the movements to determine the overall stiffness of the tissue being studied. The result is a color-coded map, called an elastogram, of the organ or tissue being studied, where blue/purple areas correspond to soft tissue and orange/red areas correspond to stiff tissue. In general, I find it to be one of the most intuitive and patient-friendly results to include in my report – especially when it adds virtually no additional time in the scanner for the patient.
MR elastography for liver fibrosis staging
Over the past 10 years, as the burden of chronic liver disease has exploded, there have been well-documented strengths and weaknesses among the noninvasive options for staging liver disease. Blood serum-based markers generally lack the sensitivity required, especially at moderate levels of fibrosis. The same is found for ultrasound-based elastography techniques, whose performance also becomes suboptimal in obese patients and those with ascites. Because payers often require multiple strategies before approving liver therapies, clinicians have often come to rely on a combination of tests to assess liver fibrosis stage – resulting in a piecemeal approach to diagnosis where costs and inconvenience to the patient can quickly grow.
However, MRE has enabled clinicians and patients to overcome many of the technical issues with other noninvasive options – and in my view has helped fuel demand for the technology as a "one-stop shop" for liver assessment. MRE has a very low failure rate (< 4%), and performs equally as well in obese patients as those with BMIs < 30, which is a contraindication for a lower-tech, one-dimensional technique called transient elastography (Fibroscan, Echosens, Paris).
Most importantly, in dozens of clinical studies, MRE has demonstrated the highest sensitivity for detecting advanced fibrosis and cirrhosis (0.94 sensitivity for MRE versus 0.86 for transient elastography, according to a recent meta-analysis compiled by the American Gastroenterological Association). Correctly identifying patients at this acute stage of disease progression is critical, as a missed diagnosis can put the patient at risk for liver-related mortality or liver transplant (average total weighted costs of $1.4 million per transplant). In a sample population of 1,000 patients with a prevalence for advanced fibrosis of 30 percent, an MRE-based approach to staging liver fibrosis would reduce the false negative rate by more than half (14 percent to 6.3 percent), over relying on transient elastography alone.
An MRE model for liver fibrosis can also reduce HCV treatment costs
The development of a direct-acting antiviral (DAA) treatment for Hepatitis C virus (HCV) is one of the great medical stories of our time. However, the cost of the treatment plans have resulted in a rationing of sorts. In the U.S., patients must typically wait until they exhibit advanced fibrosis to quality for treatment. But new studies have shown that waiting for advanced fibrosis to manifest may actually be more costly, as the efficacy of expensive DAAs for HCV treatment is significantly better when initiated at earlier stages of fibrosis.
In a “treat earlier” scenario, patients have been found to require fewer weeks to achieve sustained virologic response (SVR), and the overall SVR success rate is significantly higher when initiated at a mild fibrotic stage (reducing the need to re-treat). By shortening the cycle time and improving the cure rate, a “treat earlier” strategy would not only save billions over the next 10 years, but also help meet the calls of the patient community to avoid waiting until advanced disease has set in. The missing element in this preferable clinical model, however, is the current diagnostic model. By only relying on one-dimensional transient elastography, clinicians lack the diagnostic capability to confidently diagnose at these stages.
With MRE, however, clinicians would be able to consider treatment at an earlier stage of disease progression. MRE is capable of distinguishing among earlier stages of fibrosis with a very high level of sensitivity, bringing the “treat earlier” model closer to a reality. This type of model would result in systemic savings that outweigh the marginal increase of an MRE scan by a factor of 100. That would net billions of dollars in savings over a population model – all while meeting the calls of patients to avoid an acute stage of disease in order to qualify for treatment.
For health systems and practices looking for strategies that can help control overall costs, MRE is a "poster child" for improved outcomes at lower resource utilization. As a radiologist, it is one of my favorite examples of the value of advanced imaging.
The future of MRE
The future of MR elastography is extremely bright for liver disease patients. Looking beyond fibrosis staging alone, multiparametric MRE may soon add additional capabilities, including assessment of inflammation, in the same exam. If a traditional workup for hepatocellular carcinoma (HCC) is also included, referring clinicians now have everything they need to diagnose and manage a patient with suspected liver disease. This “hepatogram”, as some have dubbed it, represents the emergence of one of the most clinically efficient patient management strategies in recent years. Not far from now, the standard of care for suspected liver disease patients may begin with a patient’s hepatologist saying, “let’s get you a hepatogram and then go from there.”
Dr. Amy Salinas
About the author: Dr. Amy Salinas is a private practice radiologist at Austin Radiological Associates, which was among the earliest adopters of MR elastography for liver fibrosis assessment. She received her medical doctorate at Georgetown University School of Medicine, and completed her radiology residency and abdominal imaging fellowship at the University of California San Francisco.