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Myeloperoxidase elevated in HCV-related liver cancer
Myeloperoxidase (MPO) expression was significantly higher in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) cases when compared with cirrhotic patients, according to a study of 59 patients with HCV-related liver disease.
HCV is the main cause of liver disease, wrote Mohamed Abdel-Hamed, MD, of Minia University in Egypt, and his colleagues. In addition, HCV is associated with significant oxidative stress, which has been identified as a significant metabolic pathway culminating in hepatic cirrhosis, liver failure, and liver cancer. Thus the researchers studied the role of MPO, an oxidative enzyme released at sites of inflammation, in the possible etiology of HCV-related liver cancer.
The patients were divided into two groups, 25 with HCC and 34 with chronic liver diseases with cirrhosis. All patients were examined immunohistochemically to demonstrate the expression of myeloperoxidase, according to the report published in Meta Gene.
Subjects with HCC showed markedly increased MPO expression when compared with MPO expression in hepatocytes of subjects with liver cirrhosis, who mostly showed a mild degree of expression. In addition, no mild expression of MPO was detected in the subjects with HCC. These findings were highly statistically significant (P less than .0001), according to Dr. Abdel-Hamed and his colleagues.
“The present study showed that marked expression of MPO plays an important role in the pathogenesis of HCV-associated HCC,” the authors stated. “This study could provide valuable, predictive parameters that can be used clinically in the prognosis of HCC patients.”
The authors did not report any disclosures.
SOURCE: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.
Myeloperoxidase (MPO) expression was significantly higher in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) cases when compared with cirrhotic patients, according to a study of 59 patients with HCV-related liver disease.
HCV is the main cause of liver disease, wrote Mohamed Abdel-Hamed, MD, of Minia University in Egypt, and his colleagues. In addition, HCV is associated with significant oxidative stress, which has been identified as a significant metabolic pathway culminating in hepatic cirrhosis, liver failure, and liver cancer. Thus the researchers studied the role of MPO, an oxidative enzyme released at sites of inflammation, in the possible etiology of HCV-related liver cancer.
The patients were divided into two groups, 25 with HCC and 34 with chronic liver diseases with cirrhosis. All patients were examined immunohistochemically to demonstrate the expression of myeloperoxidase, according to the report published in Meta Gene.
Subjects with HCC showed markedly increased MPO expression when compared with MPO expression in hepatocytes of subjects with liver cirrhosis, who mostly showed a mild degree of expression. In addition, no mild expression of MPO was detected in the subjects with HCC. These findings were highly statistically significant (P less than .0001), according to Dr. Abdel-Hamed and his colleagues.
“The present study showed that marked expression of MPO plays an important role in the pathogenesis of HCV-associated HCC,” the authors stated. “This study could provide valuable, predictive parameters that can be used clinically in the prognosis of HCC patients.”
The authors did not report any disclosures.
SOURCE: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.
Myeloperoxidase (MPO) expression was significantly higher in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) cases when compared with cirrhotic patients, according to a study of 59 patients with HCV-related liver disease.
HCV is the main cause of liver disease, wrote Mohamed Abdel-Hamed, MD, of Minia University in Egypt, and his colleagues. In addition, HCV is associated with significant oxidative stress, which has been identified as a significant metabolic pathway culminating in hepatic cirrhosis, liver failure, and liver cancer. Thus the researchers studied the role of MPO, an oxidative enzyme released at sites of inflammation, in the possible etiology of HCV-related liver cancer.
The patients were divided into two groups, 25 with HCC and 34 with chronic liver diseases with cirrhosis. All patients were examined immunohistochemically to demonstrate the expression of myeloperoxidase, according to the report published in Meta Gene.
Subjects with HCC showed markedly increased MPO expression when compared with MPO expression in hepatocytes of subjects with liver cirrhosis, who mostly showed a mild degree of expression. In addition, no mild expression of MPO was detected in the subjects with HCC. These findings were highly statistically significant (P less than .0001), according to Dr. Abdel-Hamed and his colleagues.
“The present study showed that marked expression of MPO plays an important role in the pathogenesis of HCV-associated HCC,” the authors stated. “This study could provide valuable, predictive parameters that can be used clinically in the prognosis of HCC patients.”
The authors did not report any disclosures.
SOURCE: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.
FROM META GENE
Key clinical point:
Major finding: Hepatocellular carcinoma subjects showed a marked increase of myeloperoxidase expression when compared with subjects with liver cirrhosis (P less than .0001).
Study details: An immunohistochemical analysis of 59 patients infected with hepatitis C virus.
Disclosures: The authors did not report any disclosures.
Source: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.
Opiate use tied to hepatitis C risk in youth
SAN FRANCISCO – A new study indicates young adults with opioid use disorder are seldom screened for hepatitis C virus infections; yet 11% of the subjects with opioid use disorder who were tested had been exposed to hepatitis C, and 6.8% had evidence of chronic hepatitis C infection.
Overall, 2.5% (6,812 subjects) of all subjects received hepatitis C testing and 122 (1.8%) tested positive. Based on health records, 23,345 had an ICD-9 code for any illicit drug use and 8.9% of those (2,090) were tested for HCV infection. Of the 933 subjects with an ICD-9 code for opioid use disorder, 35% were tested for HCV.
The results suggest that a group at significant risk of hepatitis C – those with opioid use disorder – is being overlooked in public health efforts to control the disease.
Clinicians may presume, “Oh, you just take opioids orally, you don’t inject drugs,” but oral opiate users can progress to intravenous drug use, Donna Futterman, MD, director of clinical pediatrics, Montefiore Medical Center, and professor of clinical pediatrics at Albert Einstein College of Medicine, both in New York, said during the press conference at the annual scientific meeting on infectious diseases.
Guidelines call for testing for hepatitis C only in individuals with known injected drug use, among other risk factors, but the research suggests that this significantly underestimates the population of teenagers and young adults who are at risk. Many who take opiates go on to use injectable drugs.
Another surprise finding in the study was that only 10.6% of those tested for hepatitis C had also been screened for human immunodeficiency virus (HIV).
The reasons for the low frequency of screening are likely complex, including lack of time, discomfort between the physician and patient, and concerns over privacy and stigma, according to Dr. Epstein, who emphasized the importance of communication to overcome such barriers.
“As a pediatrician, I try to be as open as possible with patients and let them know that anything they tell me is confidential. I start out discussing less private issues, things that are easier to talk about,” Dr. Epstein said.
But the results of the study also suggest that preconceived notions may be holding clinicians back from testing. “How can you test for hepatitis C and not think HIV?” Dr. Futterman said. “What is that differentiator in providers’ heads that makes them focus on one thing and not the other?”
SAN FRANCISCO – A new study indicates young adults with opioid use disorder are seldom screened for hepatitis C virus infections; yet 11% of the subjects with opioid use disorder who were tested had been exposed to hepatitis C, and 6.8% had evidence of chronic hepatitis C infection.
Overall, 2.5% (6,812 subjects) of all subjects received hepatitis C testing and 122 (1.8%) tested positive. Based on health records, 23,345 had an ICD-9 code for any illicit drug use and 8.9% of those (2,090) were tested for HCV infection. Of the 933 subjects with an ICD-9 code for opioid use disorder, 35% were tested for HCV.
The results suggest that a group at significant risk of hepatitis C – those with opioid use disorder – is being overlooked in public health efforts to control the disease.
Clinicians may presume, “Oh, you just take opioids orally, you don’t inject drugs,” but oral opiate users can progress to intravenous drug use, Donna Futterman, MD, director of clinical pediatrics, Montefiore Medical Center, and professor of clinical pediatrics at Albert Einstein College of Medicine, both in New York, said during the press conference at the annual scientific meeting on infectious diseases.
Guidelines call for testing for hepatitis C only in individuals with known injected drug use, among other risk factors, but the research suggests that this significantly underestimates the population of teenagers and young adults who are at risk. Many who take opiates go on to use injectable drugs.
Another surprise finding in the study was that only 10.6% of those tested for hepatitis C had also been screened for human immunodeficiency virus (HIV).
The reasons for the low frequency of screening are likely complex, including lack of time, discomfort between the physician and patient, and concerns over privacy and stigma, according to Dr. Epstein, who emphasized the importance of communication to overcome such barriers.
“As a pediatrician, I try to be as open as possible with patients and let them know that anything they tell me is confidential. I start out discussing less private issues, things that are easier to talk about,” Dr. Epstein said.
But the results of the study also suggest that preconceived notions may be holding clinicians back from testing. “How can you test for hepatitis C and not think HIV?” Dr. Futterman said. “What is that differentiator in providers’ heads that makes them focus on one thing and not the other?”
SAN FRANCISCO – A new study indicates young adults with opioid use disorder are seldom screened for hepatitis C virus infections; yet 11% of the subjects with opioid use disorder who were tested had been exposed to hepatitis C, and 6.8% had evidence of chronic hepatitis C infection.
Overall, 2.5% (6,812 subjects) of all subjects received hepatitis C testing and 122 (1.8%) tested positive. Based on health records, 23,345 had an ICD-9 code for any illicit drug use and 8.9% of those (2,090) were tested for HCV infection. Of the 933 subjects with an ICD-9 code for opioid use disorder, 35% were tested for HCV.
The results suggest that a group at significant risk of hepatitis C – those with opioid use disorder – is being overlooked in public health efforts to control the disease.
Clinicians may presume, “Oh, you just take opioids orally, you don’t inject drugs,” but oral opiate users can progress to intravenous drug use, Donna Futterman, MD, director of clinical pediatrics, Montefiore Medical Center, and professor of clinical pediatrics at Albert Einstein College of Medicine, both in New York, said during the press conference at the annual scientific meeting on infectious diseases.
Guidelines call for testing for hepatitis C only in individuals with known injected drug use, among other risk factors, but the research suggests that this significantly underestimates the population of teenagers and young adults who are at risk. Many who take opiates go on to use injectable drugs.
Another surprise finding in the study was that only 10.6% of those tested for hepatitis C had also been screened for human immunodeficiency virus (HIV).
The reasons for the low frequency of screening are likely complex, including lack of time, discomfort between the physician and patient, and concerns over privacy and stigma, according to Dr. Epstein, who emphasized the importance of communication to overcome such barriers.
“As a pediatrician, I try to be as open as possible with patients and let them know that anything they tell me is confidential. I start out discussing less private issues, things that are easier to talk about,” Dr. Epstein said.
But the results of the study also suggest that preconceived notions may be holding clinicians back from testing. “How can you test for hepatitis C and not think HIV?” Dr. Futterman said. “What is that differentiator in providers’ heads that makes them focus on one thing and not the other?”
REPORTING FROM ID WEEK 2018
Key clinical point: By focusing solely on injectable drug users, clinicians may miss many others who are at risk for hepatitis C infection.
Major finding: Among those with opiate use disorder, 11% tested positive for hepatitis C.
Study details: Survey of 269,124 teenagers and young adults visiting U.S. Federally Qualified Health Centers.
Disclosures: Dr. Epstein and Dr. Futterman have reported no conflicts of interest.
Cirrhosis study finds no link between screening, liver cancer mortality
In a case-control study of patients with cirrhosis, screening for hepatocellular carcinoma up to 4 years prior to diagnosis was not associated with lower mortality.
Similar proportions of cases and controls underwent screening with abdominal ultrasonography, serum alpha-fetoprotein (AFP) testing, or both, reported Andrew M. Moon, MD, MPH, of the University of North Carolina at Chapel Hill, and his associates. “There was also no difference in receipt of these screening tests within 1, 2, or 3 years prior to the index date,” they wrote. The report was published in Gastroenterology. The findings “[suggest] that either these screening tests or the currently available treatments [for liver cancer], or both, are suboptimal and need to be improved.”
Because cirrhosis significantly increases the risk of hepatocellular carcinoma, the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver recommend screening cirrhotic patients every 6 months with abdominal ultrasonography with or without concomitant serum AFP. But nonliver societies have not endorsed this approach, citing a lack of high-quality data. One problem is that studies have compared patients whose liver cancer was diagnosed by screening with those diagnosed after they became symptomatic, which creates a lead-time bias that inherently favors screening, Dr. Moon and his associates noted.
To help fill the evidence gap, they identified 238 patients from the Veterans Affairs health care system who had died of hepatocellular carcinoma between 2013 and 2015 and who had been diagnosed with cirrhosis at least 4 years beforehand. They compared these cases with an equal number of patients with cirrhosis who had been in VA care for a similar amount of time and had not died of hepatocellular carcinoma. Cases and controls were matched by etiology of cirrhosis, year that cirrhosis was diagnosed, race, age, sex, Model for End-Stage Liver Disease score, and VA medical center. The researchers identified screening tests by reviewing blinded medical charts.
There were no significant differences in the proportions of cases and controls who underwent screening ultrasonography (52.9% versus 54.2%, respectively), screening serum AFP (74.8% versus 73.5%), either test (81.1% versus 79.4%), or both tests (46.6% versus 48.3%) within 4 years of the index date or the matched control. The result was similar after potential confounders were controlled for and when examining shorter time frames of 1, 2, and 3 years.
It was unlikely that these results reflect delayed diagnosis of liver cancer or a lack of treatment within the VA system, the experts wrote. A total of 51.3% of cases were diagnosed with Milan criteria, which exceeds the proportion in the national Surveillance, Epidemiology, and End Results registry, they noted. None of the fatal cases underwent liver transplantation, but 66.8% received other treatments for liver cancer.
Funders included the National Institutes of Health and the Veterans Affairs Clinical Science Research & Development. The investigators reported having no conflicts of interest.
SOURCE: Moon AM et al. Gastroenterology. 2018 Jul 5. doi: 10.1053/j.gastro.2018.06.079.
In a case-control study of patients with cirrhosis, screening for hepatocellular carcinoma up to 4 years prior to diagnosis was not associated with lower mortality.
Similar proportions of cases and controls underwent screening with abdominal ultrasonography, serum alpha-fetoprotein (AFP) testing, or both, reported Andrew M. Moon, MD, MPH, of the University of North Carolina at Chapel Hill, and his associates. “There was also no difference in receipt of these screening tests within 1, 2, or 3 years prior to the index date,” they wrote. The report was published in Gastroenterology. The findings “[suggest] that either these screening tests or the currently available treatments [for liver cancer], or both, are suboptimal and need to be improved.”
Because cirrhosis significantly increases the risk of hepatocellular carcinoma, the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver recommend screening cirrhotic patients every 6 months with abdominal ultrasonography with or without concomitant serum AFP. But nonliver societies have not endorsed this approach, citing a lack of high-quality data. One problem is that studies have compared patients whose liver cancer was diagnosed by screening with those diagnosed after they became symptomatic, which creates a lead-time bias that inherently favors screening, Dr. Moon and his associates noted.
To help fill the evidence gap, they identified 238 patients from the Veterans Affairs health care system who had died of hepatocellular carcinoma between 2013 and 2015 and who had been diagnosed with cirrhosis at least 4 years beforehand. They compared these cases with an equal number of patients with cirrhosis who had been in VA care for a similar amount of time and had not died of hepatocellular carcinoma. Cases and controls were matched by etiology of cirrhosis, year that cirrhosis was diagnosed, race, age, sex, Model for End-Stage Liver Disease score, and VA medical center. The researchers identified screening tests by reviewing blinded medical charts.
There were no significant differences in the proportions of cases and controls who underwent screening ultrasonography (52.9% versus 54.2%, respectively), screening serum AFP (74.8% versus 73.5%), either test (81.1% versus 79.4%), or both tests (46.6% versus 48.3%) within 4 years of the index date or the matched control. The result was similar after potential confounders were controlled for and when examining shorter time frames of 1, 2, and 3 years.
It was unlikely that these results reflect delayed diagnosis of liver cancer or a lack of treatment within the VA system, the experts wrote. A total of 51.3% of cases were diagnosed with Milan criteria, which exceeds the proportion in the national Surveillance, Epidemiology, and End Results registry, they noted. None of the fatal cases underwent liver transplantation, but 66.8% received other treatments for liver cancer.
Funders included the National Institutes of Health and the Veterans Affairs Clinical Science Research & Development. The investigators reported having no conflicts of interest.
SOURCE: Moon AM et al. Gastroenterology. 2018 Jul 5. doi: 10.1053/j.gastro.2018.06.079.
In a case-control study of patients with cirrhosis, screening for hepatocellular carcinoma up to 4 years prior to diagnosis was not associated with lower mortality.
Similar proportions of cases and controls underwent screening with abdominal ultrasonography, serum alpha-fetoprotein (AFP) testing, or both, reported Andrew M. Moon, MD, MPH, of the University of North Carolina at Chapel Hill, and his associates. “There was also no difference in receipt of these screening tests within 1, 2, or 3 years prior to the index date,” they wrote. The report was published in Gastroenterology. The findings “[suggest] that either these screening tests or the currently available treatments [for liver cancer], or both, are suboptimal and need to be improved.”
Because cirrhosis significantly increases the risk of hepatocellular carcinoma, the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver recommend screening cirrhotic patients every 6 months with abdominal ultrasonography with or without concomitant serum AFP. But nonliver societies have not endorsed this approach, citing a lack of high-quality data. One problem is that studies have compared patients whose liver cancer was diagnosed by screening with those diagnosed after they became symptomatic, which creates a lead-time bias that inherently favors screening, Dr. Moon and his associates noted.
To help fill the evidence gap, they identified 238 patients from the Veterans Affairs health care system who had died of hepatocellular carcinoma between 2013 and 2015 and who had been diagnosed with cirrhosis at least 4 years beforehand. They compared these cases with an equal number of patients with cirrhosis who had been in VA care for a similar amount of time and had not died of hepatocellular carcinoma. Cases and controls were matched by etiology of cirrhosis, year that cirrhosis was diagnosed, race, age, sex, Model for End-Stage Liver Disease score, and VA medical center. The researchers identified screening tests by reviewing blinded medical charts.
There were no significant differences in the proportions of cases and controls who underwent screening ultrasonography (52.9% versus 54.2%, respectively), screening serum AFP (74.8% versus 73.5%), either test (81.1% versus 79.4%), or both tests (46.6% versus 48.3%) within 4 years of the index date or the matched control. The result was similar after potential confounders were controlled for and when examining shorter time frames of 1, 2, and 3 years.
It was unlikely that these results reflect delayed diagnosis of liver cancer or a lack of treatment within the VA system, the experts wrote. A total of 51.3% of cases were diagnosed with Milan criteria, which exceeds the proportion in the national Surveillance, Epidemiology, and End Results registry, they noted. None of the fatal cases underwent liver transplantation, but 66.8% received other treatments for liver cancer.
Funders included the National Institutes of Health and the Veterans Affairs Clinical Science Research & Development. The investigators reported having no conflicts of interest.
SOURCE: Moon AM et al. Gastroenterology. 2018 Jul 5. doi: 10.1053/j.gastro.2018.06.079.
FROM GASTROENTEROLOGY
Key clinical point: Among patients with cirrhosis, screening for hepatocellular carcinoma was not associated with reductions in liver cancer mortality.
Major finding: Similar proportions of cases and controls were screened by abdominal ultrasonography, serum alpha-fetoprotein, or both up to 4 years before the index date and even after researchers controlled for relevant confounders.
Study details: A matched case-control study of 476 patients from the Veterans Affairs health care system.
Disclosures: Funders included the National Institutes of Health and the Veterans Affairs Clinical Science Research & Development. The investigators reported no conflicts of interest.
Source: Moon AM et al. Gastroenterology. 2018 Jul 5. doi: 10.1053/j.gastro.2018.06.079.
Transition to noninjected drug use lowers risk of HCV infection
A protective effect was seen with regard to hepatitis C virus (HCV) transmission among individuals who “reversed transitioned” to noninjected drug use and in persons who used noninjected drugs in addition to injecting, according to an interview study of 846 drug users.
Data were collected between January 2007 and December 2017 as part of a long-running study of persons entering Mount Sinai Beth Israel drug detoxification and methadone maintenance programs, reported Don C. Des Jarlais, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues.
Among the 846 individuals studied, men comprised 79%; 41% were white, 15% African American, and 40% Hispanic, with a mean age of 35 years. They were all currently persons who injected drugs (PWID), according to the report published in Drug and Alcohol Dependence.
A total of 97 persons (11%) “reverse transitioned” back to noninjected drug use, according to the researchers; this reverse transitioning was strongly associated with lower HCV positivity, compared with those who continued injecting (30% vs. 47%, respectively; P less than .005).
There was a substantial difference in the HCV prevalence between PWID who reported noninjected use of heroin (43%) versus PWID who did not report noninjected use of heroin (53%) (P = .005).
Distributive needle sharing was common in HCV seropositives who were injecting cocaine in the 6 months prior to the interview: 28% of the HCV seropositives injecting cocaine reported distributive sharing versus 14% of the HCV seropositives not injecting cocaine (P = .001).
“Harm reduction for PWID has been largely defined in terms of ‘safer injection,’ using sterile injection equipment, proper preparation of the injecting site, etc. We would like to suggest that harm reduction for PWID be broadened to include reverse transitions back to exclusive noninjecting use and frequent substitution of noninjecting for injecting use,” the investigators suggested.
The study was funded by the U.S. National Institute on Drug Abuse. The authors reported that they had no conflicts of interest.
SOURCE: Des Jarlais DC et al. Drug Alcohol Depend. 2018 Sep 12. doi: 10.1016/j.drugalcdep.2018.07.034.
A protective effect was seen with regard to hepatitis C virus (HCV) transmission among individuals who “reversed transitioned” to noninjected drug use and in persons who used noninjected drugs in addition to injecting, according to an interview study of 846 drug users.
Data were collected between January 2007 and December 2017 as part of a long-running study of persons entering Mount Sinai Beth Israel drug detoxification and methadone maintenance programs, reported Don C. Des Jarlais, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues.
Among the 846 individuals studied, men comprised 79%; 41% were white, 15% African American, and 40% Hispanic, with a mean age of 35 years. They were all currently persons who injected drugs (PWID), according to the report published in Drug and Alcohol Dependence.
A total of 97 persons (11%) “reverse transitioned” back to noninjected drug use, according to the researchers; this reverse transitioning was strongly associated with lower HCV positivity, compared with those who continued injecting (30% vs. 47%, respectively; P less than .005).
There was a substantial difference in the HCV prevalence between PWID who reported noninjected use of heroin (43%) versus PWID who did not report noninjected use of heroin (53%) (P = .005).
Distributive needle sharing was common in HCV seropositives who were injecting cocaine in the 6 months prior to the interview: 28% of the HCV seropositives injecting cocaine reported distributive sharing versus 14% of the HCV seropositives not injecting cocaine (P = .001).
“Harm reduction for PWID has been largely defined in terms of ‘safer injection,’ using sterile injection equipment, proper preparation of the injecting site, etc. We would like to suggest that harm reduction for PWID be broadened to include reverse transitions back to exclusive noninjecting use and frequent substitution of noninjecting for injecting use,” the investigators suggested.
The study was funded by the U.S. National Institute on Drug Abuse. The authors reported that they had no conflicts of interest.
SOURCE: Des Jarlais DC et al. Drug Alcohol Depend. 2018 Sep 12. doi: 10.1016/j.drugalcdep.2018.07.034.
A protective effect was seen with regard to hepatitis C virus (HCV) transmission among individuals who “reversed transitioned” to noninjected drug use and in persons who used noninjected drugs in addition to injecting, according to an interview study of 846 drug users.
Data were collected between January 2007 and December 2017 as part of a long-running study of persons entering Mount Sinai Beth Israel drug detoxification and methadone maintenance programs, reported Don C. Des Jarlais, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues.
Among the 846 individuals studied, men comprised 79%; 41% were white, 15% African American, and 40% Hispanic, with a mean age of 35 years. They were all currently persons who injected drugs (PWID), according to the report published in Drug and Alcohol Dependence.
A total of 97 persons (11%) “reverse transitioned” back to noninjected drug use, according to the researchers; this reverse transitioning was strongly associated with lower HCV positivity, compared with those who continued injecting (30% vs. 47%, respectively; P less than .005).
There was a substantial difference in the HCV prevalence between PWID who reported noninjected use of heroin (43%) versus PWID who did not report noninjected use of heroin (53%) (P = .005).
Distributive needle sharing was common in HCV seropositives who were injecting cocaine in the 6 months prior to the interview: 28% of the HCV seropositives injecting cocaine reported distributive sharing versus 14% of the HCV seropositives not injecting cocaine (P = .001).
“Harm reduction for PWID has been largely defined in terms of ‘safer injection,’ using sterile injection equipment, proper preparation of the injecting site, etc. We would like to suggest that harm reduction for PWID be broadened to include reverse transitions back to exclusive noninjecting use and frequent substitution of noninjecting for injecting use,” the investigators suggested.
The study was funded by the U.S. National Institute on Drug Abuse. The authors reported that they had no conflicts of interest.
SOURCE: Des Jarlais DC et al. Drug Alcohol Depend. 2018 Sep 12. doi: 10.1016/j.drugalcdep.2018.07.034.
FROM DRUG AND ALCOHOL DEPENDENCE
Key clinical point: Encouraging reverse transitioning to noninjected drug use could help persons who injected drugs lower their risk of hepatitis C virus infection.
Major finding: Reverse transitioning was strongly associated with lower hepatitis C virus positivity, compared with continued drug injection (P less than .005).
Study details: An interview study of 846 drug users.
Disclosures: The study was funded by the U.S. National Institute on Drug Abuse. The authors reported that they had no conflicts of interest.
Source: Des Jarlais DC et al. Drug Alcohol Depend. 2018 Sep 12. doi: 10.1016/j.drugalcdep.2018.07.034.
Women, older patients at greater risk of more aggressive PBC
A large, real-world study of primary biliary cholangitis has revealed that patients who are female, older, or have other autoimmune diseases are likely to have a more progressed and aggressive disease profile.
In the Journal of Clinical Gastroenterology, researchers reported the findings of a medical records database study involving 15,875 patients with primary biliary cholangitis (PBC) – previously known as primary biliary cirrhosis – a chronic, autoimmune form of liver disease.
Overall, more than one-third of patients (38.3%) had high levels of alkaline phosphatase – a marker for treatment nonresponse, defined as at least 1.5 times the upper limit of the normal range, which is also an indicator of adverse outcomes and of progression to high-risk liver disease.
These patients were more likely to be female, less likely to be insured by Medicaid, and more likely to have been diagnosed more than 1 year ago than patients whose alkaline phosphatase levels were not high. They were also more likely to be older, from the Midwest or Southern regions of the United States, have cirrhosis, or have other autoimmune diseases such as Sjögren’s syndrome and RA.
Patients with high alkaline phosphatase also showed higher aminotransferase and bilirubin, more cirrhosis, pruritus, and jaundice, but lower albumin.
Conversely, male patients had a higher incidence of cirrhosis, the study found. Other factors independently associated with cirrhosis included older age, having Medicaid insurance, having high alkaline phosphatase, and certain autoimmune conditions including type 1 diabetes, autoimmune hepatitis, and ulcerative colitis.
In patients with cirrhosis, the authors saw higher serum levels of AST and bilirubin, but lower albumin and platelets.
Zobair M. Younossi, MD, from the Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, Virginia, and his coauthors said the results suggest many patients with PBC have progressed further in their condition than previously thought.
“This implies that a heightened focus on these patients with a goal toward treating more optimally should be considered to reduce their probability of disease progression,” they wrote. “Once cirrhosis develops, adverse patient outcomes such as increased mortality and adverse health care system outcomes such as excessive resource utilization increases substantially.”
The authors noted that most patients were female and white – consistent with previous reports of PBC – but the mean age of 60 years was older than expected.
“Our data suggest that PBC patients may be getting older and this could have major implications for Medicare,” they wrote. The study also examined how patients used health care resources, and found those with alkaline phosphatase levels more than 1.5 times the upper range of normal had significantly higher use. For example, they had significantly more all-cause and disease-related visits to the doctor and more use of outpatient resources for all causes.
They also had significantly more cumulative days of treatment with ursodeoxycholic acid – the standard treatment for PBC – at 528.4 days, compared with 41.6 days in individuals without high alkaline phosphatase levels. However they were no more likely to undergo imaging procedures.
Patients with cirrhosis were also more likely to have higher levels of health care utilization, compared with patients without cirrhosis, particularly use of outpatient services, inpatient stays, and ED visits. The authors also noted that patients with Medicaid but not Medicare had a higher rate of abdominal procedures.
Given that more advanced disease and presence of cirrhosis were both major drivers of increased health care use, the authors called for better identification and treatment of these patients. “This should not only potentially improve patients’ long-term outcomes but also aid in the reduction or delay of conceivably costly health resource utilization,” they wrote.
Two authors declared research funding or consulting fees from the pharmaceutical industry, and one author was an employee of Intercept Pharmaceuticals. No other conflicts of interest were declared.
SOURCE: Younossi ZM et al. J Clin Gastroenterol. 2018 Aug 24. doi: 10.1097/MCG.0000000000001120.
A large, real-world study of primary biliary cholangitis has revealed that patients who are female, older, or have other autoimmune diseases are likely to have a more progressed and aggressive disease profile.
In the Journal of Clinical Gastroenterology, researchers reported the findings of a medical records database study involving 15,875 patients with primary biliary cholangitis (PBC) – previously known as primary biliary cirrhosis – a chronic, autoimmune form of liver disease.
Overall, more than one-third of patients (38.3%) had high levels of alkaline phosphatase – a marker for treatment nonresponse, defined as at least 1.5 times the upper limit of the normal range, which is also an indicator of adverse outcomes and of progression to high-risk liver disease.
These patients were more likely to be female, less likely to be insured by Medicaid, and more likely to have been diagnosed more than 1 year ago than patients whose alkaline phosphatase levels were not high. They were also more likely to be older, from the Midwest or Southern regions of the United States, have cirrhosis, or have other autoimmune diseases such as Sjögren’s syndrome and RA.
Patients with high alkaline phosphatase also showed higher aminotransferase and bilirubin, more cirrhosis, pruritus, and jaundice, but lower albumin.
Conversely, male patients had a higher incidence of cirrhosis, the study found. Other factors independently associated with cirrhosis included older age, having Medicaid insurance, having high alkaline phosphatase, and certain autoimmune conditions including type 1 diabetes, autoimmune hepatitis, and ulcerative colitis.
In patients with cirrhosis, the authors saw higher serum levels of AST and bilirubin, but lower albumin and platelets.
Zobair M. Younossi, MD, from the Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, Virginia, and his coauthors said the results suggest many patients with PBC have progressed further in their condition than previously thought.
“This implies that a heightened focus on these patients with a goal toward treating more optimally should be considered to reduce their probability of disease progression,” they wrote. “Once cirrhosis develops, adverse patient outcomes such as increased mortality and adverse health care system outcomes such as excessive resource utilization increases substantially.”
The authors noted that most patients were female and white – consistent with previous reports of PBC – but the mean age of 60 years was older than expected.
“Our data suggest that PBC patients may be getting older and this could have major implications for Medicare,” they wrote. The study also examined how patients used health care resources, and found those with alkaline phosphatase levels more than 1.5 times the upper range of normal had significantly higher use. For example, they had significantly more all-cause and disease-related visits to the doctor and more use of outpatient resources for all causes.
They also had significantly more cumulative days of treatment with ursodeoxycholic acid – the standard treatment for PBC – at 528.4 days, compared with 41.6 days in individuals without high alkaline phosphatase levels. However they were no more likely to undergo imaging procedures.
Patients with cirrhosis were also more likely to have higher levels of health care utilization, compared with patients without cirrhosis, particularly use of outpatient services, inpatient stays, and ED visits. The authors also noted that patients with Medicaid but not Medicare had a higher rate of abdominal procedures.
Given that more advanced disease and presence of cirrhosis were both major drivers of increased health care use, the authors called for better identification and treatment of these patients. “This should not only potentially improve patients’ long-term outcomes but also aid in the reduction or delay of conceivably costly health resource utilization,” they wrote.
Two authors declared research funding or consulting fees from the pharmaceutical industry, and one author was an employee of Intercept Pharmaceuticals. No other conflicts of interest were declared.
SOURCE: Younossi ZM et al. J Clin Gastroenterol. 2018 Aug 24. doi: 10.1097/MCG.0000000000001120.
A large, real-world study of primary biliary cholangitis has revealed that patients who are female, older, or have other autoimmune diseases are likely to have a more progressed and aggressive disease profile.
In the Journal of Clinical Gastroenterology, researchers reported the findings of a medical records database study involving 15,875 patients with primary biliary cholangitis (PBC) – previously known as primary biliary cirrhosis – a chronic, autoimmune form of liver disease.
Overall, more than one-third of patients (38.3%) had high levels of alkaline phosphatase – a marker for treatment nonresponse, defined as at least 1.5 times the upper limit of the normal range, which is also an indicator of adverse outcomes and of progression to high-risk liver disease.
These patients were more likely to be female, less likely to be insured by Medicaid, and more likely to have been diagnosed more than 1 year ago than patients whose alkaline phosphatase levels were not high. They were also more likely to be older, from the Midwest or Southern regions of the United States, have cirrhosis, or have other autoimmune diseases such as Sjögren’s syndrome and RA.
Patients with high alkaline phosphatase also showed higher aminotransferase and bilirubin, more cirrhosis, pruritus, and jaundice, but lower albumin.
Conversely, male patients had a higher incidence of cirrhosis, the study found. Other factors independently associated with cirrhosis included older age, having Medicaid insurance, having high alkaline phosphatase, and certain autoimmune conditions including type 1 diabetes, autoimmune hepatitis, and ulcerative colitis.
In patients with cirrhosis, the authors saw higher serum levels of AST and bilirubin, but lower albumin and platelets.
Zobair M. Younossi, MD, from the Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, Virginia, and his coauthors said the results suggest many patients with PBC have progressed further in their condition than previously thought.
“This implies that a heightened focus on these patients with a goal toward treating more optimally should be considered to reduce their probability of disease progression,” they wrote. “Once cirrhosis develops, adverse patient outcomes such as increased mortality and adverse health care system outcomes such as excessive resource utilization increases substantially.”
The authors noted that most patients were female and white – consistent with previous reports of PBC – but the mean age of 60 years was older than expected.
“Our data suggest that PBC patients may be getting older and this could have major implications for Medicare,” they wrote. The study also examined how patients used health care resources, and found those with alkaline phosphatase levels more than 1.5 times the upper range of normal had significantly higher use. For example, they had significantly more all-cause and disease-related visits to the doctor and more use of outpatient resources for all causes.
They also had significantly more cumulative days of treatment with ursodeoxycholic acid – the standard treatment for PBC – at 528.4 days, compared with 41.6 days in individuals without high alkaline phosphatase levels. However they were no more likely to undergo imaging procedures.
Patients with cirrhosis were also more likely to have higher levels of health care utilization, compared with patients without cirrhosis, particularly use of outpatient services, inpatient stays, and ED visits. The authors also noted that patients with Medicaid but not Medicare had a higher rate of abdominal procedures.
Given that more advanced disease and presence of cirrhosis were both major drivers of increased health care use, the authors called for better identification and treatment of these patients. “This should not only potentially improve patients’ long-term outcomes but also aid in the reduction or delay of conceivably costly health resource utilization,” they wrote.
Two authors declared research funding or consulting fees from the pharmaceutical industry, and one author was an employee of Intercept Pharmaceuticals. No other conflicts of interest were declared.
SOURCE: Younossi ZM et al. J Clin Gastroenterol. 2018 Aug 24. doi: 10.1097/MCG.0000000000001120.
FROM THE JOURNAL OF CLINICAL GASTROENTEROLOGY
Key clinical point: Women, older individuals, and patients with other autoimmune diseases are more likely to have worse primary biliary cholangitis (PBC).
Major finding: More than one-third of patients with PBC have high levels of alkaline phosphatase.
Study details: An analysis of medical records for 15,875 patients with PBC.
Disclosures: Two authors declared research funding or consulting fees from the pharmaceutical industry; one author was an employee of Intercept Pharmaceuticals. No other conflicts of interest were declared.
Source: Younossi ZM et al. J Clin Gastroenterol. 2018 August 24. doi: 10.1097/MCG.0000000000001120.
Outpatient costs soar for Medicare patients with chronic hepatitis B
The average cost of outpatient care for Medicare recipients with chronic hepatitis B (CH-B) rose by 400% from 2005 to 2014, according to investigators.
Inpatient costs also increased, although less dramatically, reported lead author Min Kim, MD, of the Inova Fairfax Hospital Center for Liver Diseases in Falls Church, Virginia, and her colleagues. The causes of these spending hikes may range from policy changes and expanded screening to an aging immigrant population.
“According to the National Health and Nutrition Examination Survey, from 1988 to 2012 most people with CH-B in the United States were foreign born and accounted for up to 70% of all CH-B infections,” the authors wrote in the Journal of Clinical Gastroenterology. “The Centers for Disease Control [and Prevention] estimates that Asians, who comprise 5% of the U.S. population, account for 50% of all chronic CH-B infections.” Despite these statistics, the clinical and economic impacts of an aging immigrant population are unknown. The investigators therefore assessed patient characteristics associated with increased 1-year mortality and the impact of demographic changes on Medicare costs.
The retrospective study began with a random sample of Medicare beneficiaries from 2005 to 2014. From this group, 18,603 patients with CH-B were identified by ICD-9 codes V02.61, 070.2, 070.3, 070.42, and 070.52. Patients with ICD-9-CM codes of 197.7, 155.1, or 155.2 were excluded, as were records containing insufficient information about year, region, or race. Patients were analyzed collectively and as inpatients (n = 6,550) or outpatients (n = 13,648).
Cost of care (per patient, per year) and 1-year mortality were evaluated. Patient characteristics included age, sex, race/ethnicity, geographic region, type of Medicare eligibility, length of stay, Charlson comorbidity index, presence of decompensated cirrhosis, and/or hepatocellular carcinoma (HCC).
Most dramatically, outpatient charges rose more than 400% during the study period, from $9,257 in 2005 to $47,864 in 2014 (P less than .001). Inpatient charges increased by almost 50%, from $66,610 to $94,221 (P less than .001). (All values converted to 2016 dollars.)
Although the increase in outpatient costs appears seismic, the authors noted that costs held steady from 2005 to 2010 before spiking dramatically, reaching a peak of $58,450 in 2013 before settling down to $47,864 the following year. This spike may be caused by changes in screening measures and policies. In 2009, the American Association for the Study of Liver Diseases expanded screening guidelines to include previously ineligible patients with CH-B, and in 2010, the Centers for Medicare & Medicaid Services expanded ICD-9 and ICD-10 codes for CH-B from 9 to 25.
“It seems plausible that the increase in CH-B prevalence, and its associated costs, might actually be a reflection of [these factors],” the authors noted. Still, “additional studies are needed to clarify this observation.”
Turning to patient characteristics, the authors reported that 1-year mortality was independently associated most strongly with decompensated cirrhosis (odds ratio, 3.02) and hepatocellular carcinoma (OR, 2.64). In comparison with white patients, Asians were less likely to die (OR, 0.47).
“It is possible that this can be explained through differences in transmission mode and disease progression of CH-B between these two demographics,” the authors wrote. “A majority of Asian Medicare recipients with CH-B likely acquired it perinatally and did not develop significant liver disease. In contrast, whites with CH-B generally acquired it in adulthood, increasing the chance of developing liver disease.”
Over the 10-year study period, Medicare beneficiaries with CH-B became more frequently Asian and less frequently male. While the number of outpatient visits and average Charlson comorbidity index increased, decreases were reported for length of stay, rates of 1-year mortality, hospitalization, and HCC – the latter of which is most closely associated with higher costs of care.
The investigators suggested that the decreased incidence of HCC was caused by “better screening programs for HCC and/or more widespread use of antiviral treatment for CH-B.”
“Although advances in antiviral treatment have effectively reduced hospitalization and disease progression,” the authors wrote, “vulnerable groups – especially immigrants and individuals living in poverty – present an important challenge for better identification of infected individuals and their linkage to care. In this context, it is vital to target these cohorts to reduce further mortality and resource utilization, as well as optimize long-term public health and financial benefits.”
Study funding was provided by Seattle Genetics. One coauthor reported compensation from Gilead Sciences, AbbVie, Intercept Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb.
SOURCE: Kim M et al. J Clin Gastro. 2018 Aug 13. doi: 10.1097/MCG.0000000000001110.
The average cost of outpatient care for Medicare recipients with chronic hepatitis B (CH-B) rose by 400% from 2005 to 2014, according to investigators.
Inpatient costs also increased, although less dramatically, reported lead author Min Kim, MD, of the Inova Fairfax Hospital Center for Liver Diseases in Falls Church, Virginia, and her colleagues. The causes of these spending hikes may range from policy changes and expanded screening to an aging immigrant population.
“According to the National Health and Nutrition Examination Survey, from 1988 to 2012 most people with CH-B in the United States were foreign born and accounted for up to 70% of all CH-B infections,” the authors wrote in the Journal of Clinical Gastroenterology. “The Centers for Disease Control [and Prevention] estimates that Asians, who comprise 5% of the U.S. population, account for 50% of all chronic CH-B infections.” Despite these statistics, the clinical and economic impacts of an aging immigrant population are unknown. The investigators therefore assessed patient characteristics associated with increased 1-year mortality and the impact of demographic changes on Medicare costs.
The retrospective study began with a random sample of Medicare beneficiaries from 2005 to 2014. From this group, 18,603 patients with CH-B were identified by ICD-9 codes V02.61, 070.2, 070.3, 070.42, and 070.52. Patients with ICD-9-CM codes of 197.7, 155.1, or 155.2 were excluded, as were records containing insufficient information about year, region, or race. Patients were analyzed collectively and as inpatients (n = 6,550) or outpatients (n = 13,648).
Cost of care (per patient, per year) and 1-year mortality were evaluated. Patient characteristics included age, sex, race/ethnicity, geographic region, type of Medicare eligibility, length of stay, Charlson comorbidity index, presence of decompensated cirrhosis, and/or hepatocellular carcinoma (HCC).
Most dramatically, outpatient charges rose more than 400% during the study period, from $9,257 in 2005 to $47,864 in 2014 (P less than .001). Inpatient charges increased by almost 50%, from $66,610 to $94,221 (P less than .001). (All values converted to 2016 dollars.)
Although the increase in outpatient costs appears seismic, the authors noted that costs held steady from 2005 to 2010 before spiking dramatically, reaching a peak of $58,450 in 2013 before settling down to $47,864 the following year. This spike may be caused by changes in screening measures and policies. In 2009, the American Association for the Study of Liver Diseases expanded screening guidelines to include previously ineligible patients with CH-B, and in 2010, the Centers for Medicare & Medicaid Services expanded ICD-9 and ICD-10 codes for CH-B from 9 to 25.
“It seems plausible that the increase in CH-B prevalence, and its associated costs, might actually be a reflection of [these factors],” the authors noted. Still, “additional studies are needed to clarify this observation.”
Turning to patient characteristics, the authors reported that 1-year mortality was independently associated most strongly with decompensated cirrhosis (odds ratio, 3.02) and hepatocellular carcinoma (OR, 2.64). In comparison with white patients, Asians were less likely to die (OR, 0.47).
“It is possible that this can be explained through differences in transmission mode and disease progression of CH-B between these two demographics,” the authors wrote. “A majority of Asian Medicare recipients with CH-B likely acquired it perinatally and did not develop significant liver disease. In contrast, whites with CH-B generally acquired it in adulthood, increasing the chance of developing liver disease.”
Over the 10-year study period, Medicare beneficiaries with CH-B became more frequently Asian and less frequently male. While the number of outpatient visits and average Charlson comorbidity index increased, decreases were reported for length of stay, rates of 1-year mortality, hospitalization, and HCC – the latter of which is most closely associated with higher costs of care.
The investigators suggested that the decreased incidence of HCC was caused by “better screening programs for HCC and/or more widespread use of antiviral treatment for CH-B.”
“Although advances in antiviral treatment have effectively reduced hospitalization and disease progression,” the authors wrote, “vulnerable groups – especially immigrants and individuals living in poverty – present an important challenge for better identification of infected individuals and their linkage to care. In this context, it is vital to target these cohorts to reduce further mortality and resource utilization, as well as optimize long-term public health and financial benefits.”
Study funding was provided by Seattle Genetics. One coauthor reported compensation from Gilead Sciences, AbbVie, Intercept Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb.
SOURCE: Kim M et al. J Clin Gastro. 2018 Aug 13. doi: 10.1097/MCG.0000000000001110.
The average cost of outpatient care for Medicare recipients with chronic hepatitis B (CH-B) rose by 400% from 2005 to 2014, according to investigators.
Inpatient costs also increased, although less dramatically, reported lead author Min Kim, MD, of the Inova Fairfax Hospital Center for Liver Diseases in Falls Church, Virginia, and her colleagues. The causes of these spending hikes may range from policy changes and expanded screening to an aging immigrant population.
“According to the National Health and Nutrition Examination Survey, from 1988 to 2012 most people with CH-B in the United States were foreign born and accounted for up to 70% of all CH-B infections,” the authors wrote in the Journal of Clinical Gastroenterology. “The Centers for Disease Control [and Prevention] estimates that Asians, who comprise 5% of the U.S. population, account for 50% of all chronic CH-B infections.” Despite these statistics, the clinical and economic impacts of an aging immigrant population are unknown. The investigators therefore assessed patient characteristics associated with increased 1-year mortality and the impact of demographic changes on Medicare costs.
The retrospective study began with a random sample of Medicare beneficiaries from 2005 to 2014. From this group, 18,603 patients with CH-B were identified by ICD-9 codes V02.61, 070.2, 070.3, 070.42, and 070.52. Patients with ICD-9-CM codes of 197.7, 155.1, or 155.2 were excluded, as were records containing insufficient information about year, region, or race. Patients were analyzed collectively and as inpatients (n = 6,550) or outpatients (n = 13,648).
Cost of care (per patient, per year) and 1-year mortality were evaluated. Patient characteristics included age, sex, race/ethnicity, geographic region, type of Medicare eligibility, length of stay, Charlson comorbidity index, presence of decompensated cirrhosis, and/or hepatocellular carcinoma (HCC).
Most dramatically, outpatient charges rose more than 400% during the study period, from $9,257 in 2005 to $47,864 in 2014 (P less than .001). Inpatient charges increased by almost 50%, from $66,610 to $94,221 (P less than .001). (All values converted to 2016 dollars.)
Although the increase in outpatient costs appears seismic, the authors noted that costs held steady from 2005 to 2010 before spiking dramatically, reaching a peak of $58,450 in 2013 before settling down to $47,864 the following year. This spike may be caused by changes in screening measures and policies. In 2009, the American Association for the Study of Liver Diseases expanded screening guidelines to include previously ineligible patients with CH-B, and in 2010, the Centers for Medicare & Medicaid Services expanded ICD-9 and ICD-10 codes for CH-B from 9 to 25.
“It seems plausible that the increase in CH-B prevalence, and its associated costs, might actually be a reflection of [these factors],” the authors noted. Still, “additional studies are needed to clarify this observation.”
Turning to patient characteristics, the authors reported that 1-year mortality was independently associated most strongly with decompensated cirrhosis (odds ratio, 3.02) and hepatocellular carcinoma (OR, 2.64). In comparison with white patients, Asians were less likely to die (OR, 0.47).
“It is possible that this can be explained through differences in transmission mode and disease progression of CH-B between these two demographics,” the authors wrote. “A majority of Asian Medicare recipients with CH-B likely acquired it perinatally and did not develop significant liver disease. In contrast, whites with CH-B generally acquired it in adulthood, increasing the chance of developing liver disease.”
Over the 10-year study period, Medicare beneficiaries with CH-B became more frequently Asian and less frequently male. While the number of outpatient visits and average Charlson comorbidity index increased, decreases were reported for length of stay, rates of 1-year mortality, hospitalization, and HCC – the latter of which is most closely associated with higher costs of care.
The investigators suggested that the decreased incidence of HCC was caused by “better screening programs for HCC and/or more widespread use of antiviral treatment for CH-B.”
“Although advances in antiviral treatment have effectively reduced hospitalization and disease progression,” the authors wrote, “vulnerable groups – especially immigrants and individuals living in poverty – present an important challenge for better identification of infected individuals and their linkage to care. In this context, it is vital to target these cohorts to reduce further mortality and resource utilization, as well as optimize long-term public health and financial benefits.”
Study funding was provided by Seattle Genetics. One coauthor reported compensation from Gilead Sciences, AbbVie, Intercept Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb.
SOURCE: Kim M et al. J Clin Gastro. 2018 Aug 13. doi: 10.1097/MCG.0000000000001110.
FROM THE JOURNAL OF CLINICAL GASTROENTEROLOGY
Key clinical point: Outpatient care for patients with chronic hepatitis B is becoming more expensive; the trend may be tied to an aging immigrant population.
Major finding: The average Medicare charge for outpatient care per patient increased from $9,257 in 2005 to $47,864 in 2014 (P less than .001).
Study details: A retrospective study involving 18,603 Medicare recipients with chronic hepatitis B who filed claims between 2005 and 2014.
Disclosures: Study funding was provided by the Beatty Center for Integrated Research. One coauthor reported compensation from Gilead Sciences, AbbVie, Intercept Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb.
Source: Kim M et al. J Clin Gastro. 2018 Aug 13. doi: 10.1097/MCG.0000000000001110.
Even modest alcohol use may worsen NAFLD
Patients with nonalcoholic fatty liver disease who consumed modest quantities of alcohol had significantly less improvement in steatosis and significantly lower odds of resolution of nonalcoholic steatohepatitis, compared with nondrinkers, according to the results of a longitudinal cohort study published in the Clinical Gastroenterology and Hepatology.
Modest drinkers also had significantly less improvement in their AST levels, compared with nondrinkers, said Veeral Ajmera, MD, of the University of California, San Diego, and his associates. “Importantly, our results suggest that cessation of alcohol use may mitigate these changes,” they wrote. Clinicians should consider the spectrum of nonalcoholic fatty liver disease (NAFLD), and especially nonalcoholic steatohepatitis (NASH), when making recommendations about alcohol use. “More advanced NAFLD severity may warrant counseling against [even] modest alcohol use.”
More than one in three adults in the United States has NAFLD and about two-thirds drink alcohol, almost always in moderation, the researchers noted. Modest alcohol use has been linked to decreased cardiovascular risk, which is particularly relevant because patients with NAFLD tend to have risk factors for cardiovascular disease. Results from at least two cross-sectional studies also suggest modest drinkers with NAFLD have less severe histology, including less NASH and fibrosis. However, modest drinkers tend to be more physically active, with lower body mass indices, higher physical activity levels, and less obesity, which are potential confounders. To better understand the effects of modest alcohol consumption on NAFLD, the researchers studied adults with NAFLD who participated in studies conducted by the multicenter NASH Clinical Research Network.
The 285 participants were typically aged in their late 40s, female, white, and obese, with an average body mass index of 34.7 kg/m2. In all, 168 participants (59%) reported consuming up to two drinks per day, while 41% abstained from alcohol use. During an average of 47 months between biopsies (standard deviation, 26 months), nondrinkers averaged a 0.49 reduction in steatosis grade, significantly more than that of modest drinkers (reduction, 0.30; P = .04). Nondrinkers also had a greater decrease in mean AST level (7 U/L), compared with drinkers (2 U/L; P = .04).
A total of 64% of patients were classified as having definite NASH, 19% had NAFLD without NASH, and 17% had borderline NASH. At baseline, 23% of patients did not have fibrosis, 32% had stage 1 fibrosis, 21% had stage 2, 21% had stage 3, and 3% had stage 4. Modest drinkers were more likely to be white and were less likely to be diagnosed with definitive NASH at baseline. After controlling for these potential confounders, modest drinkers had significantly lower odds of NASH resolution, compared with nondrinkers (adjusted odds ratio, 0.32; 95% confidence interval, 0.11-0.92; P = .04).
“[The] presence of NASH has consistently been shown to predict increased risk for fibrosis progression, and therefore, our finding of less NASH resolution among consistent modest drinkers is clinically relevant,” the investigators wrote. “Although we were unable to assess the association between modest alcohol consumption and cardiovascular risk, we did not see any significant changes in measured metabolic risk factors with known associations with cardiovascular disease including low-density lipoprotein and high-density lipoprotein cholesterol and insulin resistance.”
Funders of the study included the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Advancing Translational Sciences, the Advanced/Transplant Hepatology Fellowship, the American Association for the Study of Liver Diseases Foundation, and the Intramural Research Program of the National Institutes of Health.
SOURCE: Ajmera V et al. Clin Gastroenterol Hepatol. 2018 Mar 14. doi: 10.1016/j.cgh.2018.01.026.
Patients with nonalcoholic fatty liver disease who consumed modest quantities of alcohol had significantly less improvement in steatosis and significantly lower odds of resolution of nonalcoholic steatohepatitis, compared with nondrinkers, according to the results of a longitudinal cohort study published in the Clinical Gastroenterology and Hepatology.
Modest drinkers also had significantly less improvement in their AST levels, compared with nondrinkers, said Veeral Ajmera, MD, of the University of California, San Diego, and his associates. “Importantly, our results suggest that cessation of alcohol use may mitigate these changes,” they wrote. Clinicians should consider the spectrum of nonalcoholic fatty liver disease (NAFLD), and especially nonalcoholic steatohepatitis (NASH), when making recommendations about alcohol use. “More advanced NAFLD severity may warrant counseling against [even] modest alcohol use.”
More than one in three adults in the United States has NAFLD and about two-thirds drink alcohol, almost always in moderation, the researchers noted. Modest alcohol use has been linked to decreased cardiovascular risk, which is particularly relevant because patients with NAFLD tend to have risk factors for cardiovascular disease. Results from at least two cross-sectional studies also suggest modest drinkers with NAFLD have less severe histology, including less NASH and fibrosis. However, modest drinkers tend to be more physically active, with lower body mass indices, higher physical activity levels, and less obesity, which are potential confounders. To better understand the effects of modest alcohol consumption on NAFLD, the researchers studied adults with NAFLD who participated in studies conducted by the multicenter NASH Clinical Research Network.
The 285 participants were typically aged in their late 40s, female, white, and obese, with an average body mass index of 34.7 kg/m2. In all, 168 participants (59%) reported consuming up to two drinks per day, while 41% abstained from alcohol use. During an average of 47 months between biopsies (standard deviation, 26 months), nondrinkers averaged a 0.49 reduction in steatosis grade, significantly more than that of modest drinkers (reduction, 0.30; P = .04). Nondrinkers also had a greater decrease in mean AST level (7 U/L), compared with drinkers (2 U/L; P = .04).
A total of 64% of patients were classified as having definite NASH, 19% had NAFLD without NASH, and 17% had borderline NASH. At baseline, 23% of patients did not have fibrosis, 32% had stage 1 fibrosis, 21% had stage 2, 21% had stage 3, and 3% had stage 4. Modest drinkers were more likely to be white and were less likely to be diagnosed with definitive NASH at baseline. After controlling for these potential confounders, modest drinkers had significantly lower odds of NASH resolution, compared with nondrinkers (adjusted odds ratio, 0.32; 95% confidence interval, 0.11-0.92; P = .04).
“[The] presence of NASH has consistently been shown to predict increased risk for fibrosis progression, and therefore, our finding of less NASH resolution among consistent modest drinkers is clinically relevant,” the investigators wrote. “Although we were unable to assess the association between modest alcohol consumption and cardiovascular risk, we did not see any significant changes in measured metabolic risk factors with known associations with cardiovascular disease including low-density lipoprotein and high-density lipoprotein cholesterol and insulin resistance.”
Funders of the study included the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Advancing Translational Sciences, the Advanced/Transplant Hepatology Fellowship, the American Association for the Study of Liver Diseases Foundation, and the Intramural Research Program of the National Institutes of Health.
SOURCE: Ajmera V et al. Clin Gastroenterol Hepatol. 2018 Mar 14. doi: 10.1016/j.cgh.2018.01.026.
Patients with nonalcoholic fatty liver disease who consumed modest quantities of alcohol had significantly less improvement in steatosis and significantly lower odds of resolution of nonalcoholic steatohepatitis, compared with nondrinkers, according to the results of a longitudinal cohort study published in the Clinical Gastroenterology and Hepatology.
Modest drinkers also had significantly less improvement in their AST levels, compared with nondrinkers, said Veeral Ajmera, MD, of the University of California, San Diego, and his associates. “Importantly, our results suggest that cessation of alcohol use may mitigate these changes,” they wrote. Clinicians should consider the spectrum of nonalcoholic fatty liver disease (NAFLD), and especially nonalcoholic steatohepatitis (NASH), when making recommendations about alcohol use. “More advanced NAFLD severity may warrant counseling against [even] modest alcohol use.”
More than one in three adults in the United States has NAFLD and about two-thirds drink alcohol, almost always in moderation, the researchers noted. Modest alcohol use has been linked to decreased cardiovascular risk, which is particularly relevant because patients with NAFLD tend to have risk factors for cardiovascular disease. Results from at least two cross-sectional studies also suggest modest drinkers with NAFLD have less severe histology, including less NASH and fibrosis. However, modest drinkers tend to be more physically active, with lower body mass indices, higher physical activity levels, and less obesity, which are potential confounders. To better understand the effects of modest alcohol consumption on NAFLD, the researchers studied adults with NAFLD who participated in studies conducted by the multicenter NASH Clinical Research Network.
The 285 participants were typically aged in their late 40s, female, white, and obese, with an average body mass index of 34.7 kg/m2. In all, 168 participants (59%) reported consuming up to two drinks per day, while 41% abstained from alcohol use. During an average of 47 months between biopsies (standard deviation, 26 months), nondrinkers averaged a 0.49 reduction in steatosis grade, significantly more than that of modest drinkers (reduction, 0.30; P = .04). Nondrinkers also had a greater decrease in mean AST level (7 U/L), compared with drinkers (2 U/L; P = .04).
A total of 64% of patients were classified as having definite NASH, 19% had NAFLD without NASH, and 17% had borderline NASH. At baseline, 23% of patients did not have fibrosis, 32% had stage 1 fibrosis, 21% had stage 2, 21% had stage 3, and 3% had stage 4. Modest drinkers were more likely to be white and were less likely to be diagnosed with definitive NASH at baseline. After controlling for these potential confounders, modest drinkers had significantly lower odds of NASH resolution, compared with nondrinkers (adjusted odds ratio, 0.32; 95% confidence interval, 0.11-0.92; P = .04).
“[The] presence of NASH has consistently been shown to predict increased risk for fibrosis progression, and therefore, our finding of less NASH resolution among consistent modest drinkers is clinically relevant,” the investigators wrote. “Although we were unable to assess the association between modest alcohol consumption and cardiovascular risk, we did not see any significant changes in measured metabolic risk factors with known associations with cardiovascular disease including low-density lipoprotein and high-density lipoprotein cholesterol and insulin resistance.”
Funders of the study included the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Advancing Translational Sciences, the Advanced/Transplant Hepatology Fellowship, the American Association for the Study of Liver Diseases Foundation, and the Intramural Research Program of the National Institutes of Health.
SOURCE: Ajmera V et al. Clin Gastroenterol Hepatol. 2018 Mar 14. doi: 10.1016/j.cgh.2018.01.026.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Consider counseling patients with more advanced nonalcoholic fatty liver disease to avoid alcohol.
Major finding: Compared with nondrinkers, patients who reported modest alcohol use had significantly less improvement in steatosis and significantly lower odds of resolution of nonalcoholic steatohepatitis (P = .04 for both comparisons).
Study details: A longitudinal cohort study of 285 adults with nonalcoholic fatty liver disease with paired biopsy specimens obtained an average of 4 years apart.
Disclosures: Funders of the study included the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Advancing Translational Sciences, the Advanced/Transplant Hepatology Fellowship, the American Association for the Study of Liver Diseases Foundation, and the Intramural Research Program of the National Institutes of Health.
Source: Ajmera V et al. Clin Gastroenterol Hepatol. 2018 Mar 14. doi: 10.1016/j.cgh.2018.01.026.
Avatrombopag cut procedure-related transfusions in patients with thrombocytopenia, chronic liver disease
Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).
These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.
The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 109 per liter, and 40 mg if their baseline platelet count was 40-50 x 109 per liter. Procedures were scheduled for 10-13 days after treatment initiation.
“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 109 platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).
Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 109 per liter, and they all remained asymptomatic, the investigators said.
Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.
SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.
Thrombocytopenia in cirrhosis is frequent and multifactorial and includes sequestration in the spleen, reduced liver-derived thrombopoietin, bone marrow toxicity, and autoimmunity towards platelets. Severe thrombocytopenia (less than 50/nL) is rare in cirrhotic patients, but when it occurs may prevent required procedures from being performed or require platelet transfusions, which are associated with significant risks.
Previous attempts to increase platelets in cirrhotic patients with thrombopoietin agonists were halted because of increased frequency of portal vein thrombosis and hepatic decompensation.
Now avatrombopag has been specifically licensed with a 5-day regimen to increase platelets prior to elective interventions in severely thrombocytopenic (less than 50/nL) patients with chronic liver disease with a seemingly better safety profile than earlier treatments and good efficacy. The patient groups studied in the licensing trial had slightly milder but not significantly different liver disease, compared with those in the eltrombopag studies. The key difference was a pretreatment requirement of a portal vein flow of more than 10 cm/sec prior to enrollment, which likely reduced the risk of portal vein thrombosis. It is important that providers ready to use avatrombopag are aware of this.
Importantly, no data are currently available for patients with a Model for End-Stage Liver Disease score greater than 24, and very limited data are available for patients with Child B and Child C cirrhosis.
Given this limitation, careful judgment will be needed; a pretreatment portal vein flow may be advisable, though not a label requirement.
An observational study, NCT03554759, in patients with chronic liver disease and thrombocytopenia is ongoing and will further confirm the likely safety of avatrombopag.
Hans L. Tillmann, MD, is a clinical associate professor, East Carolina University, Greenville, and staff physician, Greenville (N.C.) VA Health Care Center. He has no relevant conflicts of interest.
Thrombocytopenia in cirrhosis is frequent and multifactorial and includes sequestration in the spleen, reduced liver-derived thrombopoietin, bone marrow toxicity, and autoimmunity towards platelets. Severe thrombocytopenia (less than 50/nL) is rare in cirrhotic patients, but when it occurs may prevent required procedures from being performed or require platelet transfusions, which are associated with significant risks.
Previous attempts to increase platelets in cirrhotic patients with thrombopoietin agonists were halted because of increased frequency of portal vein thrombosis and hepatic decompensation.
Now avatrombopag has been specifically licensed with a 5-day regimen to increase platelets prior to elective interventions in severely thrombocytopenic (less than 50/nL) patients with chronic liver disease with a seemingly better safety profile than earlier treatments and good efficacy. The patient groups studied in the licensing trial had slightly milder but not significantly different liver disease, compared with those in the eltrombopag studies. The key difference was a pretreatment requirement of a portal vein flow of more than 10 cm/sec prior to enrollment, which likely reduced the risk of portal vein thrombosis. It is important that providers ready to use avatrombopag are aware of this.
Importantly, no data are currently available for patients with a Model for End-Stage Liver Disease score greater than 24, and very limited data are available for patients with Child B and Child C cirrhosis.
Given this limitation, careful judgment will be needed; a pretreatment portal vein flow may be advisable, though not a label requirement.
An observational study, NCT03554759, in patients with chronic liver disease and thrombocytopenia is ongoing and will further confirm the likely safety of avatrombopag.
Hans L. Tillmann, MD, is a clinical associate professor, East Carolina University, Greenville, and staff physician, Greenville (N.C.) VA Health Care Center. He has no relevant conflicts of interest.
Thrombocytopenia in cirrhosis is frequent and multifactorial and includes sequestration in the spleen, reduced liver-derived thrombopoietin, bone marrow toxicity, and autoimmunity towards platelets. Severe thrombocytopenia (less than 50/nL) is rare in cirrhotic patients, but when it occurs may prevent required procedures from being performed or require platelet transfusions, which are associated with significant risks.
Previous attempts to increase platelets in cirrhotic patients with thrombopoietin agonists were halted because of increased frequency of portal vein thrombosis and hepatic decompensation.
Now avatrombopag has been specifically licensed with a 5-day regimen to increase platelets prior to elective interventions in severely thrombocytopenic (less than 50/nL) patients with chronic liver disease with a seemingly better safety profile than earlier treatments and good efficacy. The patient groups studied in the licensing trial had slightly milder but not significantly different liver disease, compared with those in the eltrombopag studies. The key difference was a pretreatment requirement of a portal vein flow of more than 10 cm/sec prior to enrollment, which likely reduced the risk of portal vein thrombosis. It is important that providers ready to use avatrombopag are aware of this.
Importantly, no data are currently available for patients with a Model for End-Stage Liver Disease score greater than 24, and very limited data are available for patients with Child B and Child C cirrhosis.
Given this limitation, careful judgment will be needed; a pretreatment portal vein flow may be advisable, though not a label requirement.
An observational study, NCT03554759, in patients with chronic liver disease and thrombocytopenia is ongoing and will further confirm the likely safety of avatrombopag.
Hans L. Tillmann, MD, is a clinical associate professor, East Carolina University, Greenville, and staff physician, Greenville (N.C.) VA Health Care Center. He has no relevant conflicts of interest.
Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).
These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.
The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 109 per liter, and 40 mg if their baseline platelet count was 40-50 x 109 per liter. Procedures were scheduled for 10-13 days after treatment initiation.
“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 109 platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).
Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 109 per liter, and they all remained asymptomatic, the investigators said.
Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.
SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.
Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).
These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.
The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 109 per liter, and 40 mg if their baseline platelet count was 40-50 x 109 per liter. Procedures were scheduled for 10-13 days after treatment initiation.
“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 109 platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).
Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 109 per liter, and they all remained asymptomatic, the investigators said.
Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.
SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.
FROM GASTROENTEROLOGY
Key clinical point: Once-daily treatment with oral avatrombopag significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures.
Major finding: In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).
Study details: ADAPT-1 and ADAPT-2, international, randomized, double-blind, placebo-controlled, phase III trials.
Disclosures: Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, BMS, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.
Source: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.
Prealbumin level predicts outcomes for HCC resection
Preoperative prealbumin levels independently predicted survival after curative liver resection for hepatocellular carcinoma (HCC) in a recent multicenter, retrospective study.
By contrast, preoperative albumin levels did not predict long-term overall or relapse-free survival in the analysis, which was reported by Tian Yang, MD, and Feng Shen, MD, along with their coinvestigators, in the journal HPB.
Those findings suggest that serum prealbumin is superior to the widely used serum albumin level as a marker of nutritional status and liver function in this setting, according to Dr. Yang and Dr. Shen, who are with the department of hepatobiliary surgery at Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
“The importance of preoperative prealbumin level in predicting long-term prognosis after liver resection for HCC should be given adequate attention by hepatic surgeons,” they wrote in their report.
The retrospective analysis included a total of 1,483 patients with HCC newly diagnosed at one of six medical institutions in China during 2001-2014. Of those patients, 1,046 (71%) had normal prealbumin levels (above 170 mg/L) measured within a week before surgery, while the remaining 437 (29%) had low prealbumin levels.
Overall survival was a mean of 72 months for the low prealbumin group versus 99 months for the normal prealbumin group (P less than .001), with a corresponding 5-year overall survival of 31% versus 43%, respectively, investigators reported
Likewise, relapse-free survival was a mean of 56 months for the low prealbumin group versus 77 months for the normal prealbumin groups (P less than .001), with 5-year relapse-free survival rates of 20% and 28%, respectively.
In multivariable Cox-regression analyses, the hazard ratios of low preoperative prealbumin level for risk of decreased overall survival and for risk of decreased relapse-free survival were 1.45 (95% confidence interval, 1.24-1.70) and 1.28 (95% CI, 1.10-1.48), respectively.
By contrast, preoperative albumin level was not an independent predictor of either overall or relapse-free survival in multivariate analyses, according to investigators.
Despite these findings, it remains controversial as to which marker is more accurate as a measure of nutritional status, investigators wrote in their report.
While albumin is more commonly used in clinical practice, they explained, multiple studies have shown prealbumin is more specific and sensitive in evaluating protein malnutrition and liver function.
The present study, although retrospective, is multicenter, has a large sample size, and includes adequately long follow-up. Nevertheless, further studies will be required to determine whether prealbumin could replace albumin for assessments of nutritional status and liver function after curative liver resection for HCC, investigators concluded.
The research was supported in part by the National Natural Science Foundation of China and the Shanghai Pujiang Program. Dr. Yang, Dr. Shen, and their coauthors had no conflicts of interest to disclose.
SOURCE: Li J-D et al. HPB (Oxford). 2018 Aug 3. doi: 10.1016/j.hpb.2018.06.1803.
Preoperative prealbumin levels independently predicted survival after curative liver resection for hepatocellular carcinoma (HCC) in a recent multicenter, retrospective study.
By contrast, preoperative albumin levels did not predict long-term overall or relapse-free survival in the analysis, which was reported by Tian Yang, MD, and Feng Shen, MD, along with their coinvestigators, in the journal HPB.
Those findings suggest that serum prealbumin is superior to the widely used serum albumin level as a marker of nutritional status and liver function in this setting, according to Dr. Yang and Dr. Shen, who are with the department of hepatobiliary surgery at Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
“The importance of preoperative prealbumin level in predicting long-term prognosis after liver resection for HCC should be given adequate attention by hepatic surgeons,” they wrote in their report.
The retrospective analysis included a total of 1,483 patients with HCC newly diagnosed at one of six medical institutions in China during 2001-2014. Of those patients, 1,046 (71%) had normal prealbumin levels (above 170 mg/L) measured within a week before surgery, while the remaining 437 (29%) had low prealbumin levels.
Overall survival was a mean of 72 months for the low prealbumin group versus 99 months for the normal prealbumin group (P less than .001), with a corresponding 5-year overall survival of 31% versus 43%, respectively, investigators reported
Likewise, relapse-free survival was a mean of 56 months for the low prealbumin group versus 77 months for the normal prealbumin groups (P less than .001), with 5-year relapse-free survival rates of 20% and 28%, respectively.
In multivariable Cox-regression analyses, the hazard ratios of low preoperative prealbumin level for risk of decreased overall survival and for risk of decreased relapse-free survival were 1.45 (95% confidence interval, 1.24-1.70) and 1.28 (95% CI, 1.10-1.48), respectively.
By contrast, preoperative albumin level was not an independent predictor of either overall or relapse-free survival in multivariate analyses, according to investigators.
Despite these findings, it remains controversial as to which marker is more accurate as a measure of nutritional status, investigators wrote in their report.
While albumin is more commonly used in clinical practice, they explained, multiple studies have shown prealbumin is more specific and sensitive in evaluating protein malnutrition and liver function.
The present study, although retrospective, is multicenter, has a large sample size, and includes adequately long follow-up. Nevertheless, further studies will be required to determine whether prealbumin could replace albumin for assessments of nutritional status and liver function after curative liver resection for HCC, investigators concluded.
The research was supported in part by the National Natural Science Foundation of China and the Shanghai Pujiang Program. Dr. Yang, Dr. Shen, and their coauthors had no conflicts of interest to disclose.
SOURCE: Li J-D et al. HPB (Oxford). 2018 Aug 3. doi: 10.1016/j.hpb.2018.06.1803.
Preoperative prealbumin levels independently predicted survival after curative liver resection for hepatocellular carcinoma (HCC) in a recent multicenter, retrospective study.
By contrast, preoperative albumin levels did not predict long-term overall or relapse-free survival in the analysis, which was reported by Tian Yang, MD, and Feng Shen, MD, along with their coinvestigators, in the journal HPB.
Those findings suggest that serum prealbumin is superior to the widely used serum albumin level as a marker of nutritional status and liver function in this setting, according to Dr. Yang and Dr. Shen, who are with the department of hepatobiliary surgery at Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
“The importance of preoperative prealbumin level in predicting long-term prognosis after liver resection for HCC should be given adequate attention by hepatic surgeons,” they wrote in their report.
The retrospective analysis included a total of 1,483 patients with HCC newly diagnosed at one of six medical institutions in China during 2001-2014. Of those patients, 1,046 (71%) had normal prealbumin levels (above 170 mg/L) measured within a week before surgery, while the remaining 437 (29%) had low prealbumin levels.
Overall survival was a mean of 72 months for the low prealbumin group versus 99 months for the normal prealbumin group (P less than .001), with a corresponding 5-year overall survival of 31% versus 43%, respectively, investigators reported
Likewise, relapse-free survival was a mean of 56 months for the low prealbumin group versus 77 months for the normal prealbumin groups (P less than .001), with 5-year relapse-free survival rates of 20% and 28%, respectively.
In multivariable Cox-regression analyses, the hazard ratios of low preoperative prealbumin level for risk of decreased overall survival and for risk of decreased relapse-free survival were 1.45 (95% confidence interval, 1.24-1.70) and 1.28 (95% CI, 1.10-1.48), respectively.
By contrast, preoperative albumin level was not an independent predictor of either overall or relapse-free survival in multivariate analyses, according to investigators.
Despite these findings, it remains controversial as to which marker is more accurate as a measure of nutritional status, investigators wrote in their report.
While albumin is more commonly used in clinical practice, they explained, multiple studies have shown prealbumin is more specific and sensitive in evaluating protein malnutrition and liver function.
The present study, although retrospective, is multicenter, has a large sample size, and includes adequately long follow-up. Nevertheless, further studies will be required to determine whether prealbumin could replace albumin for assessments of nutritional status and liver function after curative liver resection for HCC, investigators concluded.
The research was supported in part by the National Natural Science Foundation of China and the Shanghai Pujiang Program. Dr. Yang, Dr. Shen, and their coauthors had no conflicts of interest to disclose.
SOURCE: Li J-D et al. HPB (Oxford). 2018 Aug 3. doi: 10.1016/j.hpb.2018.06.1803.
FROM HPB
Key clinical point: Preoperative prealbumin levels independently predicted survival after curative liver resection for HCC, while preoperative albumin levels did not.
Major finding: The hazard ratios of low preoperative prealbumin level for risk of decreased overall survival and for risk of decreased relapse-free survival were 1.45 (95% confidence interval, 1.24-1.70) and 1.28 (95% CI, 1.10-1.48), respectively.
Study details: Retrospective analysis that included 1,483 patients with HCC newly diagnosed at one of six institutions in China during 2001-2014.
Disclosures: The research was supported in part by the National Natural Science Foundation of China and the Shanghai Pujiang Program. The study authors had no conflicts of interest to disclose.
Source: Li J-D et al. HPB (Oxford). 2018 Aug 3. doi: 10.1016/j.hpb.2018.06.1803.
Prepare for ‘the coming tsunami’ of NAFLD
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