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NEW ORLEANS – Zobair M. Younossi, MD, declared at the annual meeting of the American College of Physicians.
The massive growth in nonalcoholic fatty liver disease (NAFLD) is being fueled to a great extent by the related epidemics of obesity and type 2 diabetes mellitus. While the overall prevalence of NAFLD worldwide is 24%, almost three-quarters of patients with NAFLD are obese. And the prevalence of NAFLD in individuals with T2DM was 58% in a recent meta-analysis of studies from 20 countries conducted by Dr. Younossi and his coinvestigators.
“The prevalence of NAFLD in U.S. kids is about 10%. This is of course part of the coming tsunami because our kids are getting obese, diabetic, and they’re going to have problems with NASH [nonalcoholic steatohepatitis],” said Dr. Younossi, a gastroenterologist who is professor and chairman of the department of medicine at the Inova Fairfax (Va.) campus of Virginia Commonwealth University.
NASH is the form of NAFLD that has the strongest prognostic implications. It can progress to cirrhosis, liver failure, or hepatocellular carcinoma. As Dr. Younossi and his coworkers have shown (Hepat Commun. 2017 Jun 6;1[5]:421-8), it is associated with a significantly greater risk of both liver-related and all-cause mortality than that of non-NASH NAFLD, although NAFLD also carries an increased risk of cardiovascular disease, the leading cause of death in that population.
In addition to highlighting the enormous clinical, economic, and quality-of-life implications of the NAFLD epidemic, Dr. Younossi offered practical tips on how busy primary care physicians can identify patients in their practice who have high-risk NAFLD. They have not done a very good job of this to date. That’s possibly due to lack of incentive, since in 2018 there is no approved drug for the treatment of NASH. He cited one representative retrospective study in which only about 15% of patients identified as having NAFLD received a recommendation for lifestyle modification involving diet and exercise, which is the standard evidence-based treatment, albeit admittedly difficult to sustain. And only 3% of patients with advanced liver fibrosis were referred to a specialist for management.
“So NAFLD is common, but its recognition and doing something about it is quite a challenge,” Dr. Younossi observed.
He argued that patients who have NASH deserve to know it because of its prognostic implications and also so they can have the chance to participate in one of the roughly two dozen ongoing clinical trials of potential therapies, some of which look quite promising. All of the trials required a liver biopsy as a condition for enrollment. Plus, once a patient is known to have stage 3 fibrosis, it’s time to start screening for hepatocellular carcinoma and esophageal varices.
The scope of the epidemic
NASH is the most rapidly growing indication for liver transplantation in the United States, with most of the increase coming from the baby boomer population. NASH is now the second most common indication for placement on the wait list. Meanwhile, liver transplantation due to the consequences of hepatitis C, the No. 1 indication, is declining as a result of the spectacular advances in medical treatment introduced a few years ago. It’s likely that in coming years NASH will take over the top spot, according to Dr. Younossi.
He was coauthor of a recent study that modeled the estimated trends for the NAFLD epidemic in the United States through 2030. The forecast is that the prevalence of NAFLD among adults will climb to 33.5% and the proportion of NAFLD categorized as NASH will increase from 20% at present to 27%. Moreover, this will result in a 168% jump in the incidence of decompensated cirrhosis, a 137% increase in the incidence of hepatocellular carcinoma, and a 178% increase in liver-related mortality, which will account for an estimated 78,300 deaths in 2030 (Hepatology. 2018 Jan;67[1]:123-33).
Practical ways to identify high-risk patients
The best noninvasive means of detecting NAFLD is by ultrasound showing a fatty liver. Often the condition is detected as an incidental finding on abdominal ultrasound ordered for another reason. Elevated liver enzymes can be a tipoff as well. Of course, alcoholic liver disease and other causes must be excluded.
But what’s most important is to identify patients with NASH. It’s a diagnosis made by biopsy. However, it is unthinkable to perform liver biopsies in the entire vast population with NAFLD, so there is a great deal of interest in developing noninvasive diagnostic modalities that can help zero in on the subset of high-risk NAFLD patients who should be considered for referral for liver biopsy.
One useful clue is the presence of comorbid metabolic syndrome in patients with NAFLD. It confers a substantially higher mortality risk – especially cardiovascular mortality – than does NAFLD without metabolic syndrome. Dr. Younossi and his coinvestigators have shown in a study of 3,613 NAFLD patients followed long-term that those with one component of the metabolic syndrome – either hypertension, central obesity, increased fasting plasma glucose, or hyperlipidemia – had 8- and 16-year all-cause mortality rates of 4.7% and 11.9%, nearly double the 2.6% and 6% rates in NAFLD patients with no elements of the metabolic syndrome.
Moreover, the magnitude of risk increased with each additional metabolic syndrome condition: a 3.57-fold increased mortality risk in NAFLD patients with two components of metabolic syndrome, a 5.87-fold increase in those with three, and a 13.09-fold increase in NAFLD patients with all four elements of metabolic syndrome (Medicine [Baltimore]. 2018 Mar;97[13]:e0214. doi: 10.1097/MD.0000000000010214).
Dr. Younossi was a member of the American Association for the Study of Liver Disease expert panel that developed the latest practice guidance regarding the diagnosis and management of NAFLD (Hepatology. 2018 Jan;67[1]:328-57). He said that probably the best simple noninvasive scoring system for the detection of NASH with advanced fibrosis is the NAFLD fibrosis score, which is easily calculated using laboratory values and clinical parameters already in a patient’s chart.
A more sophisticated serum biomarker test known as ELF, or the Enhanced Liver Fibrosis test, combines serum levels of hyaluronic acid, tissue inhibitor of metalloproteinase I, and procollagen amino terminal peptide.
“ELF is a very, very good test. It’s approved in Europe and I suspect it will be in the U.S. within the next year or so,” said Dr. Younossi.
The most exciting noninvasive tests, however, involve imaging that measures liver stiffness, which provides a fairly accurate indication of the degree of scarring in the organ. There are two methods available: vibration wave transient elastography and magnetic resonance elastography.
Transient elastography using the FibroScan device is commercially available in the United States. “It’s a good test, very easy to do, noninvasive. I have a couple of these machines, and we use them all the time,” the gastroenterologist said.
MR elastography provides superior accuracy, but access is an issue.
“At our institution you sometimes have to wait for weeks to get an outpatient MRI, so if you have hundreds of patients with fatty liver disease it makes things difficult. So in our practice we use transient elastography,” he explained.
Both imaging modalities also measure the amount of fat in the liver.
Dr. Younossi uses transient elastography in patients who don’t have type 2 diabetes or frank insulin resistance. If the FibroScan score is 7 kiloPascals or more, he considers liver biopsy, since that’s the threshold for detection of earlier, potentially reversible stage 2 fibrosis. If, however, a patient has diabetes or insulin resistance along with a NAFLD fibrosis score suggesting a high possibility of fibrosis, he sends that patient for liver biopsy, since those endocrinologic disorders are known to be independent risk factors for mortality in the setting of NAFLD.
Dr. Younossi reported having no financial conflicts of interest regarding his presentation.
NEW ORLEANS – Zobair M. Younossi, MD, declared at the annual meeting of the American College of Physicians.
The massive growth in nonalcoholic fatty liver disease (NAFLD) is being fueled to a great extent by the related epidemics of obesity and type 2 diabetes mellitus. While the overall prevalence of NAFLD worldwide is 24%, almost three-quarters of patients with NAFLD are obese. And the prevalence of NAFLD in individuals with T2DM was 58% in a recent meta-analysis of studies from 20 countries conducted by Dr. Younossi and his coinvestigators.
“The prevalence of NAFLD in U.S. kids is about 10%. This is of course part of the coming tsunami because our kids are getting obese, diabetic, and they’re going to have problems with NASH [nonalcoholic steatohepatitis],” said Dr. Younossi, a gastroenterologist who is professor and chairman of the department of medicine at the Inova Fairfax (Va.) campus of Virginia Commonwealth University.
NASH is the form of NAFLD that has the strongest prognostic implications. It can progress to cirrhosis, liver failure, or hepatocellular carcinoma. As Dr. Younossi and his coworkers have shown (Hepat Commun. 2017 Jun 6;1[5]:421-8), it is associated with a significantly greater risk of both liver-related and all-cause mortality than that of non-NASH NAFLD, although NAFLD also carries an increased risk of cardiovascular disease, the leading cause of death in that population.
In addition to highlighting the enormous clinical, economic, and quality-of-life implications of the NAFLD epidemic, Dr. Younossi offered practical tips on how busy primary care physicians can identify patients in their practice who have high-risk NAFLD. They have not done a very good job of this to date. That’s possibly due to lack of incentive, since in 2018 there is no approved drug for the treatment of NASH. He cited one representative retrospective study in which only about 15% of patients identified as having NAFLD received a recommendation for lifestyle modification involving diet and exercise, which is the standard evidence-based treatment, albeit admittedly difficult to sustain. And only 3% of patients with advanced liver fibrosis were referred to a specialist for management.
“So NAFLD is common, but its recognition and doing something about it is quite a challenge,” Dr. Younossi observed.
He argued that patients who have NASH deserve to know it because of its prognostic implications and also so they can have the chance to participate in one of the roughly two dozen ongoing clinical trials of potential therapies, some of which look quite promising. All of the trials required a liver biopsy as a condition for enrollment. Plus, once a patient is known to have stage 3 fibrosis, it’s time to start screening for hepatocellular carcinoma and esophageal varices.
The scope of the epidemic
NASH is the most rapidly growing indication for liver transplantation in the United States, with most of the increase coming from the baby boomer population. NASH is now the second most common indication for placement on the wait list. Meanwhile, liver transplantation due to the consequences of hepatitis C, the No. 1 indication, is declining as a result of the spectacular advances in medical treatment introduced a few years ago. It’s likely that in coming years NASH will take over the top spot, according to Dr. Younossi.
He was coauthor of a recent study that modeled the estimated trends for the NAFLD epidemic in the United States through 2030. The forecast is that the prevalence of NAFLD among adults will climb to 33.5% and the proportion of NAFLD categorized as NASH will increase from 20% at present to 27%. Moreover, this will result in a 168% jump in the incidence of decompensated cirrhosis, a 137% increase in the incidence of hepatocellular carcinoma, and a 178% increase in liver-related mortality, which will account for an estimated 78,300 deaths in 2030 (Hepatology. 2018 Jan;67[1]:123-33).
Practical ways to identify high-risk patients
The best noninvasive means of detecting NAFLD is by ultrasound showing a fatty liver. Often the condition is detected as an incidental finding on abdominal ultrasound ordered for another reason. Elevated liver enzymes can be a tipoff as well. Of course, alcoholic liver disease and other causes must be excluded.
But what’s most important is to identify patients with NASH. It’s a diagnosis made by biopsy. However, it is unthinkable to perform liver biopsies in the entire vast population with NAFLD, so there is a great deal of interest in developing noninvasive diagnostic modalities that can help zero in on the subset of high-risk NAFLD patients who should be considered for referral for liver biopsy.
One useful clue is the presence of comorbid metabolic syndrome in patients with NAFLD. It confers a substantially higher mortality risk – especially cardiovascular mortality – than does NAFLD without metabolic syndrome. Dr. Younossi and his coinvestigators have shown in a study of 3,613 NAFLD patients followed long-term that those with one component of the metabolic syndrome – either hypertension, central obesity, increased fasting plasma glucose, or hyperlipidemia – had 8- and 16-year all-cause mortality rates of 4.7% and 11.9%, nearly double the 2.6% and 6% rates in NAFLD patients with no elements of the metabolic syndrome.
Moreover, the magnitude of risk increased with each additional metabolic syndrome condition: a 3.57-fold increased mortality risk in NAFLD patients with two components of metabolic syndrome, a 5.87-fold increase in those with three, and a 13.09-fold increase in NAFLD patients with all four elements of metabolic syndrome (Medicine [Baltimore]. 2018 Mar;97[13]:e0214. doi: 10.1097/MD.0000000000010214).
Dr. Younossi was a member of the American Association for the Study of Liver Disease expert panel that developed the latest practice guidance regarding the diagnosis and management of NAFLD (Hepatology. 2018 Jan;67[1]:328-57). He said that probably the best simple noninvasive scoring system for the detection of NASH with advanced fibrosis is the NAFLD fibrosis score, which is easily calculated using laboratory values and clinical parameters already in a patient’s chart.
A more sophisticated serum biomarker test known as ELF, or the Enhanced Liver Fibrosis test, combines serum levels of hyaluronic acid, tissue inhibitor of metalloproteinase I, and procollagen amino terminal peptide.
“ELF is a very, very good test. It’s approved in Europe and I suspect it will be in the U.S. within the next year or so,” said Dr. Younossi.
The most exciting noninvasive tests, however, involve imaging that measures liver stiffness, which provides a fairly accurate indication of the degree of scarring in the organ. There are two methods available: vibration wave transient elastography and magnetic resonance elastography.
Transient elastography using the FibroScan device is commercially available in the United States. “It’s a good test, very easy to do, noninvasive. I have a couple of these machines, and we use them all the time,” the gastroenterologist said.
MR elastography provides superior accuracy, but access is an issue.
“At our institution you sometimes have to wait for weeks to get an outpatient MRI, so if you have hundreds of patients with fatty liver disease it makes things difficult. So in our practice we use transient elastography,” he explained.
Both imaging modalities also measure the amount of fat in the liver.
Dr. Younossi uses transient elastography in patients who don’t have type 2 diabetes or frank insulin resistance. If the FibroScan score is 7 kiloPascals or more, he considers liver biopsy, since that’s the threshold for detection of earlier, potentially reversible stage 2 fibrosis. If, however, a patient has diabetes or insulin resistance along with a NAFLD fibrosis score suggesting a high possibility of fibrosis, he sends that patient for liver biopsy, since those endocrinologic disorders are known to be independent risk factors for mortality in the setting of NAFLD.
Dr. Younossi reported having no financial conflicts of interest regarding his presentation.
NEW ORLEANS – Zobair M. Younossi, MD, declared at the annual meeting of the American College of Physicians.
The massive growth in nonalcoholic fatty liver disease (NAFLD) is being fueled to a great extent by the related epidemics of obesity and type 2 diabetes mellitus. While the overall prevalence of NAFLD worldwide is 24%, almost three-quarters of patients with NAFLD are obese. And the prevalence of NAFLD in individuals with T2DM was 58% in a recent meta-analysis of studies from 20 countries conducted by Dr. Younossi and his coinvestigators.
“The prevalence of NAFLD in U.S. kids is about 10%. This is of course part of the coming tsunami because our kids are getting obese, diabetic, and they’re going to have problems with NASH [nonalcoholic steatohepatitis],” said Dr. Younossi, a gastroenterologist who is professor and chairman of the department of medicine at the Inova Fairfax (Va.) campus of Virginia Commonwealth University.
NASH is the form of NAFLD that has the strongest prognostic implications. It can progress to cirrhosis, liver failure, or hepatocellular carcinoma. As Dr. Younossi and his coworkers have shown (Hepat Commun. 2017 Jun 6;1[5]:421-8), it is associated with a significantly greater risk of both liver-related and all-cause mortality than that of non-NASH NAFLD, although NAFLD also carries an increased risk of cardiovascular disease, the leading cause of death in that population.
In addition to highlighting the enormous clinical, economic, and quality-of-life implications of the NAFLD epidemic, Dr. Younossi offered practical tips on how busy primary care physicians can identify patients in their practice who have high-risk NAFLD. They have not done a very good job of this to date. That’s possibly due to lack of incentive, since in 2018 there is no approved drug for the treatment of NASH. He cited one representative retrospective study in which only about 15% of patients identified as having NAFLD received a recommendation for lifestyle modification involving diet and exercise, which is the standard evidence-based treatment, albeit admittedly difficult to sustain. And only 3% of patients with advanced liver fibrosis were referred to a specialist for management.
“So NAFLD is common, but its recognition and doing something about it is quite a challenge,” Dr. Younossi observed.
He argued that patients who have NASH deserve to know it because of its prognostic implications and also so they can have the chance to participate in one of the roughly two dozen ongoing clinical trials of potential therapies, some of which look quite promising. All of the trials required a liver biopsy as a condition for enrollment. Plus, once a patient is known to have stage 3 fibrosis, it’s time to start screening for hepatocellular carcinoma and esophageal varices.
The scope of the epidemic
NASH is the most rapidly growing indication for liver transplantation in the United States, with most of the increase coming from the baby boomer population. NASH is now the second most common indication for placement on the wait list. Meanwhile, liver transplantation due to the consequences of hepatitis C, the No. 1 indication, is declining as a result of the spectacular advances in medical treatment introduced a few years ago. It’s likely that in coming years NASH will take over the top spot, according to Dr. Younossi.
He was coauthor of a recent study that modeled the estimated trends for the NAFLD epidemic in the United States through 2030. The forecast is that the prevalence of NAFLD among adults will climb to 33.5% and the proportion of NAFLD categorized as NASH will increase from 20% at present to 27%. Moreover, this will result in a 168% jump in the incidence of decompensated cirrhosis, a 137% increase in the incidence of hepatocellular carcinoma, and a 178% increase in liver-related mortality, which will account for an estimated 78,300 deaths in 2030 (Hepatology. 2018 Jan;67[1]:123-33).
Practical ways to identify high-risk patients
The best noninvasive means of detecting NAFLD is by ultrasound showing a fatty liver. Often the condition is detected as an incidental finding on abdominal ultrasound ordered for another reason. Elevated liver enzymes can be a tipoff as well. Of course, alcoholic liver disease and other causes must be excluded.
But what’s most important is to identify patients with NASH. It’s a diagnosis made by biopsy. However, it is unthinkable to perform liver biopsies in the entire vast population with NAFLD, so there is a great deal of interest in developing noninvasive diagnostic modalities that can help zero in on the subset of high-risk NAFLD patients who should be considered for referral for liver biopsy.
One useful clue is the presence of comorbid metabolic syndrome in patients with NAFLD. It confers a substantially higher mortality risk – especially cardiovascular mortality – than does NAFLD without metabolic syndrome. Dr. Younossi and his coinvestigators have shown in a study of 3,613 NAFLD patients followed long-term that those with one component of the metabolic syndrome – either hypertension, central obesity, increased fasting plasma glucose, or hyperlipidemia – had 8- and 16-year all-cause mortality rates of 4.7% and 11.9%, nearly double the 2.6% and 6% rates in NAFLD patients with no elements of the metabolic syndrome.
Moreover, the magnitude of risk increased with each additional metabolic syndrome condition: a 3.57-fold increased mortality risk in NAFLD patients with two components of metabolic syndrome, a 5.87-fold increase in those with three, and a 13.09-fold increase in NAFLD patients with all four elements of metabolic syndrome (Medicine [Baltimore]. 2018 Mar;97[13]:e0214. doi: 10.1097/MD.0000000000010214).
Dr. Younossi was a member of the American Association for the Study of Liver Disease expert panel that developed the latest practice guidance regarding the diagnosis and management of NAFLD (Hepatology. 2018 Jan;67[1]:328-57). He said that probably the best simple noninvasive scoring system for the detection of NASH with advanced fibrosis is the NAFLD fibrosis score, which is easily calculated using laboratory values and clinical parameters already in a patient’s chart.
A more sophisticated serum biomarker test known as ELF, or the Enhanced Liver Fibrosis test, combines serum levels of hyaluronic acid, tissue inhibitor of metalloproteinase I, and procollagen amino terminal peptide.
“ELF is a very, very good test. It’s approved in Europe and I suspect it will be in the U.S. within the next year or so,” said Dr. Younossi.
The most exciting noninvasive tests, however, involve imaging that measures liver stiffness, which provides a fairly accurate indication of the degree of scarring in the organ. There are two methods available: vibration wave transient elastography and magnetic resonance elastography.
Transient elastography using the FibroScan device is commercially available in the United States. “It’s a good test, very easy to do, noninvasive. I have a couple of these machines, and we use them all the time,” the gastroenterologist said.
MR elastography provides superior accuracy, but access is an issue.
“At our institution you sometimes have to wait for weeks to get an outpatient MRI, so if you have hundreds of patients with fatty liver disease it makes things difficult. So in our practice we use transient elastography,” he explained.
Both imaging modalities also measure the amount of fat in the liver.
Dr. Younossi uses transient elastography in patients who don’t have type 2 diabetes or frank insulin resistance. If the FibroScan score is 7 kiloPascals or more, he considers liver biopsy, since that’s the threshold for detection of earlier, potentially reversible stage 2 fibrosis. If, however, a patient has diabetes or insulin resistance along with a NAFLD fibrosis score suggesting a high possibility of fibrosis, he sends that patient for liver biopsy, since those endocrinologic disorders are known to be independent risk factors for mortality in the setting of NAFLD.
Dr. Younossi reported having no financial conflicts of interest regarding his presentation.
REPORTING FROM ACP INTERNAL MEDICINE