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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.
Study examines the world of alcohol use
Considerable variations were seen in alcohol consumption. In 2016, males overall consumed more than twice as many standard drinks per day as females: 1.70 versus 0.73. Alcohol consumption in those aged 15-95 years was highest in the top quintile of countries according to sociodemographic development for both males (2.9 drinks per day) and females (1.9) and lowest in the bottom quintile of countries for males (1.4) and the second-lowest quintile for females (0.3), Max G. Griswold, MA, of the University of Washington, Seattle, and his associates said in the Lancet.
Denmark had the highest prevalence of current drinkers of any country for both males (97%) and females (95%) in 2016; Pakistan was lowest for males (0.8%) and Bangladesh was lowest for females (0.3%). The United States had a prevalence of 72% for males and 60% for females, along with consumption rates of 3.2 drinks per day for males and 1.9 for females. Alcohol-related diseases caused 6.7% of male deaths and 2.3% of female deaths in the United States, both close to the global numbers of 6.8% for males and 2.2% for females, the investigators said.
The analysis, conducted within the framework of the Global Burden of Diseases, Injuries, and Risk Factors Study, showed that even a single alcoholic drink a day increases the risk of developing 1 of the 23 alcohol-related health problems by 0.5% a year for people aged 15-95 years, which translates into a rate of 918 per 100,000 population, compared with 914 per 100,000 for nondrinkers. Consuming two drinks a day raises the risk to 7%, which would be an incidence of 977 per 100,000, and those who have five drinks a day increase their risk by 37%, which works out to 1,252 people per 100,000 who would develop an alcohol-related disease, Mr. Griswold and his associates said.
In an editorial comment, Robyn Burton, PhD, of King’s College London and Nick Sheron, MD, of the University of Southampton (England), wrote that “the conclusions of the study are clear and unambiguous: Alcohol is a colossal global health issue and small reductions in health-related harms at low levels of alcohol intake are outweighed by the increased risk of other health-related harms, including cancer. … These diseases of unhealthy behaviors, facilitated by unhealthy environments and fueled by commercial interests putting shareholder value ahead of the tragic human consequences, are the dominant health issue of the 21st century. The solutions are straightforward: Increasing taxation creates income for hard-pressed health ministries, and reducing the exposure of children to alcohol marketing has no downsides.”
The study was funded by the Bill and Melinda Gates Foundation. Mr. Griswold did not have any conflicts to disclose, but six of his several hundred coauthors did make such disclosures.
SOURCE: Griswold MG et al. Lancet. 2018 Aug 23. doi: 10.1016/S0140-6736(18)31310-2.
Considerable variations were seen in alcohol consumption. In 2016, males overall consumed more than twice as many standard drinks per day as females: 1.70 versus 0.73. Alcohol consumption in those aged 15-95 years was highest in the top quintile of countries according to sociodemographic development for both males (2.9 drinks per day) and females (1.9) and lowest in the bottom quintile of countries for males (1.4) and the second-lowest quintile for females (0.3), Max G. Griswold, MA, of the University of Washington, Seattle, and his associates said in the Lancet.
Denmark had the highest prevalence of current drinkers of any country for both males (97%) and females (95%) in 2016; Pakistan was lowest for males (0.8%) and Bangladesh was lowest for females (0.3%). The United States had a prevalence of 72% for males and 60% for females, along with consumption rates of 3.2 drinks per day for males and 1.9 for females. Alcohol-related diseases caused 6.7% of male deaths and 2.3% of female deaths in the United States, both close to the global numbers of 6.8% for males and 2.2% for females, the investigators said.
The analysis, conducted within the framework of the Global Burden of Diseases, Injuries, and Risk Factors Study, showed that even a single alcoholic drink a day increases the risk of developing 1 of the 23 alcohol-related health problems by 0.5% a year for people aged 15-95 years, which translates into a rate of 918 per 100,000 population, compared with 914 per 100,000 for nondrinkers. Consuming two drinks a day raises the risk to 7%, which would be an incidence of 977 per 100,000, and those who have five drinks a day increase their risk by 37%, which works out to 1,252 people per 100,000 who would develop an alcohol-related disease, Mr. Griswold and his associates said.
In an editorial comment, Robyn Burton, PhD, of King’s College London and Nick Sheron, MD, of the University of Southampton (England), wrote that “the conclusions of the study are clear and unambiguous: Alcohol is a colossal global health issue and small reductions in health-related harms at low levels of alcohol intake are outweighed by the increased risk of other health-related harms, including cancer. … These diseases of unhealthy behaviors, facilitated by unhealthy environments and fueled by commercial interests putting shareholder value ahead of the tragic human consequences, are the dominant health issue of the 21st century. The solutions are straightforward: Increasing taxation creates income for hard-pressed health ministries, and reducing the exposure of children to alcohol marketing has no downsides.”
The study was funded by the Bill and Melinda Gates Foundation. Mr. Griswold did not have any conflicts to disclose, but six of his several hundred coauthors did make such disclosures.
SOURCE: Griswold MG et al. Lancet. 2018 Aug 23. doi: 10.1016/S0140-6736(18)31310-2.
Considerable variations were seen in alcohol consumption. In 2016, males overall consumed more than twice as many standard drinks per day as females: 1.70 versus 0.73. Alcohol consumption in those aged 15-95 years was highest in the top quintile of countries according to sociodemographic development for both males (2.9 drinks per day) and females (1.9) and lowest in the bottom quintile of countries for males (1.4) and the second-lowest quintile for females (0.3), Max G. Griswold, MA, of the University of Washington, Seattle, and his associates said in the Lancet.
Denmark had the highest prevalence of current drinkers of any country for both males (97%) and females (95%) in 2016; Pakistan was lowest for males (0.8%) and Bangladesh was lowest for females (0.3%). The United States had a prevalence of 72% for males and 60% for females, along with consumption rates of 3.2 drinks per day for males and 1.9 for females. Alcohol-related diseases caused 6.7% of male deaths and 2.3% of female deaths in the United States, both close to the global numbers of 6.8% for males and 2.2% for females, the investigators said.
The analysis, conducted within the framework of the Global Burden of Diseases, Injuries, and Risk Factors Study, showed that even a single alcoholic drink a day increases the risk of developing 1 of the 23 alcohol-related health problems by 0.5% a year for people aged 15-95 years, which translates into a rate of 918 per 100,000 population, compared with 914 per 100,000 for nondrinkers. Consuming two drinks a day raises the risk to 7%, which would be an incidence of 977 per 100,000, and those who have five drinks a day increase their risk by 37%, which works out to 1,252 people per 100,000 who would develop an alcohol-related disease, Mr. Griswold and his associates said.
In an editorial comment, Robyn Burton, PhD, of King’s College London and Nick Sheron, MD, of the University of Southampton (England), wrote that “the conclusions of the study are clear and unambiguous: Alcohol is a colossal global health issue and small reductions in health-related harms at low levels of alcohol intake are outweighed by the increased risk of other health-related harms, including cancer. … These diseases of unhealthy behaviors, facilitated by unhealthy environments and fueled by commercial interests putting shareholder value ahead of the tragic human consequences, are the dominant health issue of the 21st century. The solutions are straightforward: Increasing taxation creates income for hard-pressed health ministries, and reducing the exposure of children to alcohol marketing has no downsides.”
The study was funded by the Bill and Melinda Gates Foundation. Mr. Griswold did not have any conflicts to disclose, but six of his several hundred coauthors did make such disclosures.
SOURCE: Griswold MG et al. Lancet. 2018 Aug 23. doi: 10.1016/S0140-6736(18)31310-2.
FROM THE LANCET
Barriers loom for HCV care in young people who inject drugs
Young adults who inject drugs and are infected with hepatitis C virus “face unique barriers to HCV testing, counseling, and treatment,” according to Margie R. Skeer, ScD, of Tufts University, Boston, and her fellow researchers.
Dr. Skeer and her colleagues found five themes in 24 in-depth interviews with people aged 22-30 years who inject drugs and have HCV infection. At the time of the interviews, none of the patients had received the newer HCV treatment regimens (Drug Alcohol Depend. 2018 Sep 1;190:246-54).
These themes captured the knowledge of and experience of HCV along the continuum of care:
1. Deservingness of HCV treatment and stigma.
2. Dissatisfaction with provider interactions.
3. Perceived lack of referral to treatment and care continuity.
4. Disincentives around HCV treatment for PWID.
5. Perceived need for treatment.
The interviewees were largely uninformed about HCV prior to diagnosis and reported learning more about the virus after their diagnosis. They also tended to affirm the belief that they did not deserve treatment. They felt stigmatized by insurance companies and clinicians, thereby reducing their engagement in the care continuum. And, at the time, insurance companies enforced “sobriety” restrictions dictating the length of time patients had to be off drugs before qualifying for HCV treatment. In the words of one interviewee: “[Caregivers] have a big stigma when it comes to addicts. ... Their whole demeanor changes. They rush you, they slam things, they are very impatient with you, and it is very saddening to see.”
Interviewees reported no or incomplete referrals or being given pamphlets and flyers. They reported little follow-up as to whether they sought additional care, and experienced a lack of confidence from medical professionals that they could be counted on to adhere to an HCV treatment regimen.
Interviewees stated that injection drug use and HCV are inevitably linked, and that IV drug users will eventually contract HCV infections.
“Hep C’s no big deal, Hep C’s like the common cold for the junkie. ... It might take 5 years away from your, you know, life but, you know, we’re not even gonna live that long anyways, so who cares about it anyway,” remarked a 28-year old woman, who was not currently injecting drugs.
The study authors said there is an increased need to provide patient-oriented care for young injection drug users and described the potential benefits of some insurance companies reducing their sobriety and disease severity restrictions.
“Reducing stigma among healthcare professionals, which cuts across the different levels of the HCV care continuum, improving referral patterns and continuity of care, better informing people about their HCV status through patient-oriented testing and disclosure experiences, and reducing perceptions of personal responsibility for disease are crucial next steps to increasing treatment as prevention,” Dr. Skeer and her colleagues concluded.
The authors reported that they had no conflicts of interest.
AGA patient materials can help your patients better understand and manage living with hepatitis C. Learn more at patient.gastro.org.
Young adults who inject drugs and are infected with hepatitis C virus “face unique barriers to HCV testing, counseling, and treatment,” according to Margie R. Skeer, ScD, of Tufts University, Boston, and her fellow researchers.
Dr. Skeer and her colleagues found five themes in 24 in-depth interviews with people aged 22-30 years who inject drugs and have HCV infection. At the time of the interviews, none of the patients had received the newer HCV treatment regimens (Drug Alcohol Depend. 2018 Sep 1;190:246-54).
These themes captured the knowledge of and experience of HCV along the continuum of care:
1. Deservingness of HCV treatment and stigma.
2. Dissatisfaction with provider interactions.
3. Perceived lack of referral to treatment and care continuity.
4. Disincentives around HCV treatment for PWID.
5. Perceived need for treatment.
The interviewees were largely uninformed about HCV prior to diagnosis and reported learning more about the virus after their diagnosis. They also tended to affirm the belief that they did not deserve treatment. They felt stigmatized by insurance companies and clinicians, thereby reducing their engagement in the care continuum. And, at the time, insurance companies enforced “sobriety” restrictions dictating the length of time patients had to be off drugs before qualifying for HCV treatment. In the words of one interviewee: “[Caregivers] have a big stigma when it comes to addicts. ... Their whole demeanor changes. They rush you, they slam things, they are very impatient with you, and it is very saddening to see.”
Interviewees reported no or incomplete referrals or being given pamphlets and flyers. They reported little follow-up as to whether they sought additional care, and experienced a lack of confidence from medical professionals that they could be counted on to adhere to an HCV treatment regimen.
Interviewees stated that injection drug use and HCV are inevitably linked, and that IV drug users will eventually contract HCV infections.
“Hep C’s no big deal, Hep C’s like the common cold for the junkie. ... It might take 5 years away from your, you know, life but, you know, we’re not even gonna live that long anyways, so who cares about it anyway,” remarked a 28-year old woman, who was not currently injecting drugs.
The study authors said there is an increased need to provide patient-oriented care for young injection drug users and described the potential benefits of some insurance companies reducing their sobriety and disease severity restrictions.
“Reducing stigma among healthcare professionals, which cuts across the different levels of the HCV care continuum, improving referral patterns and continuity of care, better informing people about their HCV status through patient-oriented testing and disclosure experiences, and reducing perceptions of personal responsibility for disease are crucial next steps to increasing treatment as prevention,” Dr. Skeer and her colleagues concluded.
The authors reported that they had no conflicts of interest.
AGA patient materials can help your patients better understand and manage living with hepatitis C. Learn more at patient.gastro.org.
Young adults who inject drugs and are infected with hepatitis C virus “face unique barriers to HCV testing, counseling, and treatment,” according to Margie R. Skeer, ScD, of Tufts University, Boston, and her fellow researchers.
Dr. Skeer and her colleagues found five themes in 24 in-depth interviews with people aged 22-30 years who inject drugs and have HCV infection. At the time of the interviews, none of the patients had received the newer HCV treatment regimens (Drug Alcohol Depend. 2018 Sep 1;190:246-54).
These themes captured the knowledge of and experience of HCV along the continuum of care:
1. Deservingness of HCV treatment and stigma.
2. Dissatisfaction with provider interactions.
3. Perceived lack of referral to treatment and care continuity.
4. Disincentives around HCV treatment for PWID.
5. Perceived need for treatment.
The interviewees were largely uninformed about HCV prior to diagnosis and reported learning more about the virus after their diagnosis. They also tended to affirm the belief that they did not deserve treatment. They felt stigmatized by insurance companies and clinicians, thereby reducing their engagement in the care continuum. And, at the time, insurance companies enforced “sobriety” restrictions dictating the length of time patients had to be off drugs before qualifying for HCV treatment. In the words of one interviewee: “[Caregivers] have a big stigma when it comes to addicts. ... Their whole demeanor changes. They rush you, they slam things, they are very impatient with you, and it is very saddening to see.”
Interviewees reported no or incomplete referrals or being given pamphlets and flyers. They reported little follow-up as to whether they sought additional care, and experienced a lack of confidence from medical professionals that they could be counted on to adhere to an HCV treatment regimen.
Interviewees stated that injection drug use and HCV are inevitably linked, and that IV drug users will eventually contract HCV infections.
“Hep C’s no big deal, Hep C’s like the common cold for the junkie. ... It might take 5 years away from your, you know, life but, you know, we’re not even gonna live that long anyways, so who cares about it anyway,” remarked a 28-year old woman, who was not currently injecting drugs.
The study authors said there is an increased need to provide patient-oriented care for young injection drug users and described the potential benefits of some insurance companies reducing their sobriety and disease severity restrictions.
“Reducing stigma among healthcare professionals, which cuts across the different levels of the HCV care continuum, improving referral patterns and continuity of care, better informing people about their HCV status through patient-oriented testing and disclosure experiences, and reducing perceptions of personal responsibility for disease are crucial next steps to increasing treatment as prevention,” Dr. Skeer and her colleagues concluded.
The authors reported that they had no conflicts of interest.
AGA patient materials can help your patients better understand and manage living with hepatitis C. Learn more at patient.gastro.org.
FROM DRUG AND ALCOHOL DEPENDENCE
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.
Model finds spontaneous HCV clearance higher than previous estimates
Up to 40% of hepatitis C virus (HCV)–infected individuals clear their infection spontaneously, based on the results of a new mathematical model of HCV transmission and clearance, according to a report published online in the International Journal of Infectious Diseases.
Houssein H. Ayoub, PhD, of Cornell University, New York, and his colleagues conducted a study on HCV clearance. Previous estimates using empirical data indicated that the HCV clearance rate was about 25% after and acute infection duration of 16.5 weeks, according to Dr. Ayoub and his colleagues.
They developed a model to describe HCV transmission and a virus clearance rate (fclearance), defined as the proportion of HCV-infected persons who spontaneously clear their infection after the acute stage. The rest of the infected population (1–fclearance) become chronically infected and positive for both HCV antibodies and HCV RNA.This was estimated by fitting the model to probability-based and nationally representative, population-based data from Egypt (2008 and 2015), and the U.S. National Health and Nutrition Examination Surveys (NHANES A and NHANES B) data. Their model showed that fclearance was related to the HCV viremic rate approximately as fclearance = 1.16 x (1–HCV viremic rate). The HCV viremic rate was defined as the proportion of individuals who were positive for HCV antibodies and HCV RNA out of all who were positive for HCV antibodies positive, regardless of RNA status, as measured in a cross-sectional survey.
Antibody prevalence in Egypt was estimated at 14.7% in 2008 and 10.0% in 2015, while the viremic rate was assessed as 67.1% and 70.2%, respectively. For the United States, the pooled antibody prevalence from the NHANES A data between 1999 and 2012 was an estimated 1.4% and the pooled viremic rate was estimated at around 74%. The NHANES B data used as the denominator for HCV viremic rate both individuals confirmed as HCV Ab positive and those with an undetermined HCV antibody status. (NHANES laboratory procedures can provide this added information because of their subsequent testing of undetermined HCV antibody results for HCV RNA positivity.) This change to the formula yielded a viremic rate of 64.6%.
They found that fclearance was an estimated at 39.9% and 33.5% for Egypt in 2008 and 2015, respectively, and 29.6% and 49.9% for NHANES A and NHANES B, respectively.
“Empirical measures from longitudinal cohort studies may have underestimated the ability of the host immune system to clear HCV infection. This finding may have also implications for our understanding of the biological determinants of HCV spontaneous clearance. It may hint that a strategy for HCV vaccine development could be a vaccine that does not necessarily prevent infection, but modulates immune response towards conditions that increase the capacity of the host immune system to clear HCV infection spontaneously,” the researchers concluded.
The study was funded by the Qatar National Research Fund and Cornell University. The authors reported no conflicts of interest.
SOURCE: Ayoub HH et al. Int J Infect Dis. 2018 Jul 18. doi: 10.1016/j.ijid.2018.07.013.
Up to 40% of hepatitis C virus (HCV)–infected individuals clear their infection spontaneously, based on the results of a new mathematical model of HCV transmission and clearance, according to a report published online in the International Journal of Infectious Diseases.
Houssein H. Ayoub, PhD, of Cornell University, New York, and his colleagues conducted a study on HCV clearance. Previous estimates using empirical data indicated that the HCV clearance rate was about 25% after and acute infection duration of 16.5 weeks, according to Dr. Ayoub and his colleagues.
They developed a model to describe HCV transmission and a virus clearance rate (fclearance), defined as the proportion of HCV-infected persons who spontaneously clear their infection after the acute stage. The rest of the infected population (1–fclearance) become chronically infected and positive for both HCV antibodies and HCV RNA.This was estimated by fitting the model to probability-based and nationally representative, population-based data from Egypt (2008 and 2015), and the U.S. National Health and Nutrition Examination Surveys (NHANES A and NHANES B) data. Their model showed that fclearance was related to the HCV viremic rate approximately as fclearance = 1.16 x (1–HCV viremic rate). The HCV viremic rate was defined as the proportion of individuals who were positive for HCV antibodies and HCV RNA out of all who were positive for HCV antibodies positive, regardless of RNA status, as measured in a cross-sectional survey.
Antibody prevalence in Egypt was estimated at 14.7% in 2008 and 10.0% in 2015, while the viremic rate was assessed as 67.1% and 70.2%, respectively. For the United States, the pooled antibody prevalence from the NHANES A data between 1999 and 2012 was an estimated 1.4% and the pooled viremic rate was estimated at around 74%. The NHANES B data used as the denominator for HCV viremic rate both individuals confirmed as HCV Ab positive and those with an undetermined HCV antibody status. (NHANES laboratory procedures can provide this added information because of their subsequent testing of undetermined HCV antibody results for HCV RNA positivity.) This change to the formula yielded a viremic rate of 64.6%.
They found that fclearance was an estimated at 39.9% and 33.5% for Egypt in 2008 and 2015, respectively, and 29.6% and 49.9% for NHANES A and NHANES B, respectively.
“Empirical measures from longitudinal cohort studies may have underestimated the ability of the host immune system to clear HCV infection. This finding may have also implications for our understanding of the biological determinants of HCV spontaneous clearance. It may hint that a strategy for HCV vaccine development could be a vaccine that does not necessarily prevent infection, but modulates immune response towards conditions that increase the capacity of the host immune system to clear HCV infection spontaneously,” the researchers concluded.
The study was funded by the Qatar National Research Fund and Cornell University. The authors reported no conflicts of interest.
SOURCE: Ayoub HH et al. Int J Infect Dis. 2018 Jul 18. doi: 10.1016/j.ijid.2018.07.013.
Up to 40% of hepatitis C virus (HCV)–infected individuals clear their infection spontaneously, based on the results of a new mathematical model of HCV transmission and clearance, according to a report published online in the International Journal of Infectious Diseases.
Houssein H. Ayoub, PhD, of Cornell University, New York, and his colleagues conducted a study on HCV clearance. Previous estimates using empirical data indicated that the HCV clearance rate was about 25% after and acute infection duration of 16.5 weeks, according to Dr. Ayoub and his colleagues.
They developed a model to describe HCV transmission and a virus clearance rate (fclearance), defined as the proportion of HCV-infected persons who spontaneously clear their infection after the acute stage. The rest of the infected population (1–fclearance) become chronically infected and positive for both HCV antibodies and HCV RNA.This was estimated by fitting the model to probability-based and nationally representative, population-based data from Egypt (2008 and 2015), and the U.S. National Health and Nutrition Examination Surveys (NHANES A and NHANES B) data. Their model showed that fclearance was related to the HCV viremic rate approximately as fclearance = 1.16 x (1–HCV viremic rate). The HCV viremic rate was defined as the proportion of individuals who were positive for HCV antibodies and HCV RNA out of all who were positive for HCV antibodies positive, regardless of RNA status, as measured in a cross-sectional survey.
Antibody prevalence in Egypt was estimated at 14.7% in 2008 and 10.0% in 2015, while the viremic rate was assessed as 67.1% and 70.2%, respectively. For the United States, the pooled antibody prevalence from the NHANES A data between 1999 and 2012 was an estimated 1.4% and the pooled viremic rate was estimated at around 74%. The NHANES B data used as the denominator for HCV viremic rate both individuals confirmed as HCV Ab positive and those with an undetermined HCV antibody status. (NHANES laboratory procedures can provide this added information because of their subsequent testing of undetermined HCV antibody results for HCV RNA positivity.) This change to the formula yielded a viremic rate of 64.6%.
They found that fclearance was an estimated at 39.9% and 33.5% for Egypt in 2008 and 2015, respectively, and 29.6% and 49.9% for NHANES A and NHANES B, respectively.
“Empirical measures from longitudinal cohort studies may have underestimated the ability of the host immune system to clear HCV infection. This finding may have also implications for our understanding of the biological determinants of HCV spontaneous clearance. It may hint that a strategy for HCV vaccine development could be a vaccine that does not necessarily prevent infection, but modulates immune response towards conditions that increase the capacity of the host immune system to clear HCV infection spontaneously,” the researchers concluded.
The study was funded by the Qatar National Research Fund and Cornell University. The authors reported no conflicts of interest.
SOURCE: Ayoub HH et al. Int J Infect Dis. 2018 Jul 18. doi: 10.1016/j.ijid.2018.07.013.
FROM THE INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
Key clinical point: The hepatitis C virus clearance rate was 39.9% and 33.5% for Egypt in 2008 and 2015, respectively, and 29.6% and 49.9% for two U.S. populations.
Major finding: A new model of HCV-infected persons indicates that up to 40% clear their infection spontaneously, higher than earlier estimates.
Study details: A mathematical model was developed to describe HCV transmission and clearance based on nationally representative population data for Egypt and the United States.
Disclosures: The study was funded by the Qatar National Research Fund and Cornell University. The authors reported no conflicts of interest.
Source: Ayoub HH et al. Int J Infect Dis. 2018 Jul 18. doi: 10.1016/j.ijid.2018.07.013.
FDA approves lenvatinib for HCC
Approval was based on a noninferiority trial of 954 patients with previously untreated, metastatic or unresectable HCC, comparing treatment with lenvatinib to sorafenib, according to an FDA statement.
Lenvatinib was found noninferior but not statistically superior to sorafenib for overall survival (hazard ratio, 0.92; 95% confidence interval, 0.79-1.06). Median overall survival was 13.6 months for patients in the lenvatinib arm, compared with 12.3 months for patients in the sorafenib arm.
The most common adverse reactions with lenvatinib were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea.
The recommended lenvatinib dosages are 12 mg orally once daily in patients weighing 60 kg or greater actual body weight or 8 mg orally once daily in patients weighing less than 60 kg actual body weight, the FDA said.
Lenvatinib is marketed as Lenvima by Eisai.
Approval was based on a noninferiority trial of 954 patients with previously untreated, metastatic or unresectable HCC, comparing treatment with lenvatinib to sorafenib, according to an FDA statement.
Lenvatinib was found noninferior but not statistically superior to sorafenib for overall survival (hazard ratio, 0.92; 95% confidence interval, 0.79-1.06). Median overall survival was 13.6 months for patients in the lenvatinib arm, compared with 12.3 months for patients in the sorafenib arm.
The most common adverse reactions with lenvatinib were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea.
The recommended lenvatinib dosages are 12 mg orally once daily in patients weighing 60 kg or greater actual body weight or 8 mg orally once daily in patients weighing less than 60 kg actual body weight, the FDA said.
Lenvatinib is marketed as Lenvima by Eisai.
Approval was based on a noninferiority trial of 954 patients with previously untreated, metastatic or unresectable HCC, comparing treatment with lenvatinib to sorafenib, according to an FDA statement.
Lenvatinib was found noninferior but not statistically superior to sorafenib for overall survival (hazard ratio, 0.92; 95% confidence interval, 0.79-1.06). Median overall survival was 13.6 months for patients in the lenvatinib arm, compared with 12.3 months for patients in the sorafenib arm.
The most common adverse reactions with lenvatinib were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea.
The recommended lenvatinib dosages are 12 mg orally once daily in patients weighing 60 kg or greater actual body weight or 8 mg orally once daily in patients weighing less than 60 kg actual body weight, the FDA said.
Lenvatinib is marketed as Lenvima by Eisai.
Hot topics
K. Rajender Reddy, MD, discussed the management of hepatitis B virus reactivation (HBVr), which can occur in the setting of treatment with immunosuppressive or direct-acting antiviral agents, HIV, or organ transplant. He discussed the mechanisms by which HBVr occurs despite serologic evidence of viral clearance, and he reviewed the American Gastroenterological Association Institute’s 2015 Clinical Decision Support Tool on managing HBVr. In patients treated with anti-TNF therapy, HBVr was seen almost exclusively in HBsAg+ patients and not HBsAg–/anti-HBc+ patients. Data supports HBV screening prior to starting anti–tumor necrosis factor therapy and prophylactic antiviral therapy for HBsAg-positive patients, Dr. Reddy explained.
Allison R. Schulman, MD, MPH then discussed endoscopic bariatric therapy for obesity. When he spoke about gastric interventions, he said that, although space-occupying devices have been shown to reduce weight and resolve comorbidities, they are more likely to be removed early because of intolerance and can be associated with serious adverse events (in less than 0.1%). He also said that endoscopic sleeve gastroplasty has been associated with significant weight loss and a beneficial effect on comorbidities and aspiration therapy has been associated with a 20%-25% total body weight loss over 1-2 years. With regard to small-bowel interventions, Dr. Schulman discussed sleeves and liners, mucosal resurfacing therapy, anastomosis and enteral diversion, and flow-altering therapy, none of which are Food and Drug Administration–approved. Endoscopic bariatric therapy options of both types fill a gap between medications and surgery, Dr. Schulman concluded, and are reversible, repeatable, and cost-effective and can be used in combination.
Neil H. Stollman, MD, AGAF, reviewed the role of fecal microbial transplantation (FMT) in gastrointestinal disorders and the variety of ways in which FMT can be administered. One of its main uses is for recurrent Clostridium difficile infection (rCDI); this is the only indication for which the FDA will not require an investigational new drug permit. Dr. Stollman discussed current guidelines for FMT and said that systematic reviews have demonstrated that FMT has an overall cure rate of 85%-90% for rCDI with no or few adverse events. He recommended not resuming vancomycin after FMT and not retesting for rCDI unless the patient has suggestive symptoms. Currently, he noted, more than 180 clinical trials are studying the efficacy of FMT in other diseases, including inflammatory bowel disease, irritable bowel syndrome, and liver disease.
Fasiha Kanwal, MD, MSHS, AGAF, who is editor in chief of Clinical Gastroenterology and Hepatology, presented the top three clinical papers published in that journal or in the journal Gastroenterology. The first paper, titled “Chromoendoscopy for surveillance in ulcerative colitis and Crohn’s disease: A systematic review of randomized trials” (Clin Gastroenterol Hepatol. 2017 Nov;15[11]:1684-97), found that chromoendoscopy identifies more patients with dysplasia when compared with standard-definition, white-light endoscopy. There was no direct evidence, however, of an effect on all-cause or cancer-specific mortality.
The second paper, “Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis” (Clin Gastroenterol Hepatol. 2017 Dec;15[12]:1950-6), showed that both agents were generally well tolerated and that they were equally effective in patients who had responded completely to standard therapy but could not tolerate it. In nonresponders to standard therapy, tacrolimus was more effective.
Dr. Kanwal’s study entitled, “Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents” (Gastroenterology. 2017 Oct;153[4]:996-1005) was the third paper. This study found that sustained virologic response (SVR) resulted in a considerable reduction in the risk of HCC. However, the absolute risk of HCC was high in some patients who achieved sustained virologic response, including about 40% who had already progressed to cirrhosis, she said.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2018. Dr. Chang is the vice-chief of the Vatche and Tamar Manounkian division of digestive diseases, the program director of University of California, Los Angeles, GI fellowship program, the codirector of G. Oppenheimer Center for Neurobiology of Stress and Resilience, and a professor of medicine at UCLA. She is on the advisory board for Synergy, IM HealthSciences, and Salix; an adviser for Metameconnect.com and ModifyHealth; and a speaker for Allergan and Takeda.
K. Rajender Reddy, MD, discussed the management of hepatitis B virus reactivation (HBVr), which can occur in the setting of treatment with immunosuppressive or direct-acting antiviral agents, HIV, or organ transplant. He discussed the mechanisms by which HBVr occurs despite serologic evidence of viral clearance, and he reviewed the American Gastroenterological Association Institute’s 2015 Clinical Decision Support Tool on managing HBVr. In patients treated with anti-TNF therapy, HBVr was seen almost exclusively in HBsAg+ patients and not HBsAg–/anti-HBc+ patients. Data supports HBV screening prior to starting anti–tumor necrosis factor therapy and prophylactic antiviral therapy for HBsAg-positive patients, Dr. Reddy explained.
Allison R. Schulman, MD, MPH then discussed endoscopic bariatric therapy for obesity. When he spoke about gastric interventions, he said that, although space-occupying devices have been shown to reduce weight and resolve comorbidities, they are more likely to be removed early because of intolerance and can be associated with serious adverse events (in less than 0.1%). He also said that endoscopic sleeve gastroplasty has been associated with significant weight loss and a beneficial effect on comorbidities and aspiration therapy has been associated with a 20%-25% total body weight loss over 1-2 years. With regard to small-bowel interventions, Dr. Schulman discussed sleeves and liners, mucosal resurfacing therapy, anastomosis and enteral diversion, and flow-altering therapy, none of which are Food and Drug Administration–approved. Endoscopic bariatric therapy options of both types fill a gap between medications and surgery, Dr. Schulman concluded, and are reversible, repeatable, and cost-effective and can be used in combination.
Neil H. Stollman, MD, AGAF, reviewed the role of fecal microbial transplantation (FMT) in gastrointestinal disorders and the variety of ways in which FMT can be administered. One of its main uses is for recurrent Clostridium difficile infection (rCDI); this is the only indication for which the FDA will not require an investigational new drug permit. Dr. Stollman discussed current guidelines for FMT and said that systematic reviews have demonstrated that FMT has an overall cure rate of 85%-90% for rCDI with no or few adverse events. He recommended not resuming vancomycin after FMT and not retesting for rCDI unless the patient has suggestive symptoms. Currently, he noted, more than 180 clinical trials are studying the efficacy of FMT in other diseases, including inflammatory bowel disease, irritable bowel syndrome, and liver disease.
Fasiha Kanwal, MD, MSHS, AGAF, who is editor in chief of Clinical Gastroenterology and Hepatology, presented the top three clinical papers published in that journal or in the journal Gastroenterology. The first paper, titled “Chromoendoscopy for surveillance in ulcerative colitis and Crohn’s disease: A systematic review of randomized trials” (Clin Gastroenterol Hepatol. 2017 Nov;15[11]:1684-97), found that chromoendoscopy identifies more patients with dysplasia when compared with standard-definition, white-light endoscopy. There was no direct evidence, however, of an effect on all-cause or cancer-specific mortality.
The second paper, “Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis” (Clin Gastroenterol Hepatol. 2017 Dec;15[12]:1950-6), showed that both agents were generally well tolerated and that they were equally effective in patients who had responded completely to standard therapy but could not tolerate it. In nonresponders to standard therapy, tacrolimus was more effective.
Dr. Kanwal’s study entitled, “Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents” (Gastroenterology. 2017 Oct;153[4]:996-1005) was the third paper. This study found that sustained virologic response (SVR) resulted in a considerable reduction in the risk of HCC. However, the absolute risk of HCC was high in some patients who achieved sustained virologic response, including about 40% who had already progressed to cirrhosis, she said.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2018. Dr. Chang is the vice-chief of the Vatche and Tamar Manounkian division of digestive diseases, the program director of University of California, Los Angeles, GI fellowship program, the codirector of G. Oppenheimer Center for Neurobiology of Stress and Resilience, and a professor of medicine at UCLA. She is on the advisory board for Synergy, IM HealthSciences, and Salix; an adviser for Metameconnect.com and ModifyHealth; and a speaker for Allergan and Takeda.
K. Rajender Reddy, MD, discussed the management of hepatitis B virus reactivation (HBVr), which can occur in the setting of treatment with immunosuppressive or direct-acting antiviral agents, HIV, or organ transplant. He discussed the mechanisms by which HBVr occurs despite serologic evidence of viral clearance, and he reviewed the American Gastroenterological Association Institute’s 2015 Clinical Decision Support Tool on managing HBVr. In patients treated with anti-TNF therapy, HBVr was seen almost exclusively in HBsAg+ patients and not HBsAg–/anti-HBc+ patients. Data supports HBV screening prior to starting anti–tumor necrosis factor therapy and prophylactic antiviral therapy for HBsAg-positive patients, Dr. Reddy explained.
Allison R. Schulman, MD, MPH then discussed endoscopic bariatric therapy for obesity. When he spoke about gastric interventions, he said that, although space-occupying devices have been shown to reduce weight and resolve comorbidities, they are more likely to be removed early because of intolerance and can be associated with serious adverse events (in less than 0.1%). He also said that endoscopic sleeve gastroplasty has been associated with significant weight loss and a beneficial effect on comorbidities and aspiration therapy has been associated with a 20%-25% total body weight loss over 1-2 years. With regard to small-bowel interventions, Dr. Schulman discussed sleeves and liners, mucosal resurfacing therapy, anastomosis and enteral diversion, and flow-altering therapy, none of which are Food and Drug Administration–approved. Endoscopic bariatric therapy options of both types fill a gap between medications and surgery, Dr. Schulman concluded, and are reversible, repeatable, and cost-effective and can be used in combination.
Neil H. Stollman, MD, AGAF, reviewed the role of fecal microbial transplantation (FMT) in gastrointestinal disorders and the variety of ways in which FMT can be administered. One of its main uses is for recurrent Clostridium difficile infection (rCDI); this is the only indication for which the FDA will not require an investigational new drug permit. Dr. Stollman discussed current guidelines for FMT and said that systematic reviews have demonstrated that FMT has an overall cure rate of 85%-90% for rCDI with no or few adverse events. He recommended not resuming vancomycin after FMT and not retesting for rCDI unless the patient has suggestive symptoms. Currently, he noted, more than 180 clinical trials are studying the efficacy of FMT in other diseases, including inflammatory bowel disease, irritable bowel syndrome, and liver disease.
Fasiha Kanwal, MD, MSHS, AGAF, who is editor in chief of Clinical Gastroenterology and Hepatology, presented the top three clinical papers published in that journal or in the journal Gastroenterology. The first paper, titled “Chromoendoscopy for surveillance in ulcerative colitis and Crohn’s disease: A systematic review of randomized trials” (Clin Gastroenterol Hepatol. 2017 Nov;15[11]:1684-97), found that chromoendoscopy identifies more patients with dysplasia when compared with standard-definition, white-light endoscopy. There was no direct evidence, however, of an effect on all-cause or cancer-specific mortality.
The second paper, “Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis” (Clin Gastroenterol Hepatol. 2017 Dec;15[12]:1950-6), showed that both agents were generally well tolerated and that they were equally effective in patients who had responded completely to standard therapy but could not tolerate it. In nonresponders to standard therapy, tacrolimus was more effective.
Dr. Kanwal’s study entitled, “Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents” (Gastroenterology. 2017 Oct;153[4]:996-1005) was the third paper. This study found that sustained virologic response (SVR) resulted in a considerable reduction in the risk of HCC. However, the absolute risk of HCC was high in some patients who achieved sustained virologic response, including about 40% who had already progressed to cirrhosis, she said.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2018. Dr. Chang is the vice-chief of the Vatche and Tamar Manounkian division of digestive diseases, the program director of University of California, Los Angeles, GI fellowship program, the codirector of G. Oppenheimer Center for Neurobiology of Stress and Resilience, and a professor of medicine at UCLA. She is on the advisory board for Synergy, IM HealthSciences, and Salix; an adviser for Metameconnect.com and ModifyHealth; and a speaker for Allergan and Takeda.
Liver cancer death rates down for Asians and Pacific Islanders
Liver cancer death rates are dropping for Asians/Pacific Islanders, but that is the exception to a larger trend, according to the National Center for Health Statistics.
The age-adjusted death rate for liver cancer is down 22% among Asian or Pacific Islander adults aged 25 years and older since the turn of the century, falling from 17.5 per 100,000 population in 2000 – when it was the highest of the four racial/ethnic groups included in the report – to 13.6 per 100,000 in 2016, by which time it was just middle of the pack, the NCHS reported.
That shift resulted as much from increases for the other groups as from the decreased rate for Asians/Pacific Islanders. White adults were dying of liver cancer at a 48% higher rate in 2016 (9.0 per 100,000) than they were in 2000 (6.1), blacks saw their death rate go from 9.5 to 13.6 – a 43% increase – and the rate for Hispanics rose by 27% from 2000 (11.5) to 2016 (14.6), said Jiaquan Xu, MD, of the NCHS mortality statistics branch.
The adjusted death rate from liver cancer for all adults went from 7.2 per 100,000 in 2000 to 10.3 in 2016 for an increase of 43%. Over that period, the rate for men was always at least twice as high as it was for women: It rose from 10.5 per 100,000 for men and 4.9 for women in 2000 to 15.0 for men and 6.3 for women in 2016, Dr. Xu said based on data from the mortality files of the National Vital Statistics System.
Geographically, the District of Columbia had the highest rate at 16.8 per 100,000 in 2016, followed by Louisiana (13.8), Hawaii (12.7), and Mississippi and New Mexico (12.4 each). Vermont’s rate of 6.0 was the lowest in the country, with Maine second at 7.4, Montana third at 7.7, and Utah and Nebraska tied for fourth at 7.8, according to Dr. Xu.
Liver cancer death rates are dropping for Asians/Pacific Islanders, but that is the exception to a larger trend, according to the National Center for Health Statistics.
The age-adjusted death rate for liver cancer is down 22% among Asian or Pacific Islander adults aged 25 years and older since the turn of the century, falling from 17.5 per 100,000 population in 2000 – when it was the highest of the four racial/ethnic groups included in the report – to 13.6 per 100,000 in 2016, by which time it was just middle of the pack, the NCHS reported.
That shift resulted as much from increases for the other groups as from the decreased rate for Asians/Pacific Islanders. White adults were dying of liver cancer at a 48% higher rate in 2016 (9.0 per 100,000) than they were in 2000 (6.1), blacks saw their death rate go from 9.5 to 13.6 – a 43% increase – and the rate for Hispanics rose by 27% from 2000 (11.5) to 2016 (14.6), said Jiaquan Xu, MD, of the NCHS mortality statistics branch.
The adjusted death rate from liver cancer for all adults went from 7.2 per 100,000 in 2000 to 10.3 in 2016 for an increase of 43%. Over that period, the rate for men was always at least twice as high as it was for women: It rose from 10.5 per 100,000 for men and 4.9 for women in 2000 to 15.0 for men and 6.3 for women in 2016, Dr. Xu said based on data from the mortality files of the National Vital Statistics System.
Geographically, the District of Columbia had the highest rate at 16.8 per 100,000 in 2016, followed by Louisiana (13.8), Hawaii (12.7), and Mississippi and New Mexico (12.4 each). Vermont’s rate of 6.0 was the lowest in the country, with Maine second at 7.4, Montana third at 7.7, and Utah and Nebraska tied for fourth at 7.8, according to Dr. Xu.
Liver cancer death rates are dropping for Asians/Pacific Islanders, but that is the exception to a larger trend, according to the National Center for Health Statistics.
The age-adjusted death rate for liver cancer is down 22% among Asian or Pacific Islander adults aged 25 years and older since the turn of the century, falling from 17.5 per 100,000 population in 2000 – when it was the highest of the four racial/ethnic groups included in the report – to 13.6 per 100,000 in 2016, by which time it was just middle of the pack, the NCHS reported.
That shift resulted as much from increases for the other groups as from the decreased rate for Asians/Pacific Islanders. White adults were dying of liver cancer at a 48% higher rate in 2016 (9.0 per 100,000) than they were in 2000 (6.1), blacks saw their death rate go from 9.5 to 13.6 – a 43% increase – and the rate for Hispanics rose by 27% from 2000 (11.5) to 2016 (14.6), said Jiaquan Xu, MD, of the NCHS mortality statistics branch.
The adjusted death rate from liver cancer for all adults went from 7.2 per 100,000 in 2000 to 10.3 in 2016 for an increase of 43%. Over that period, the rate for men was always at least twice as high as it was for women: It rose from 10.5 per 100,000 for men and 4.9 for women in 2000 to 15.0 for men and 6.3 for women in 2016, Dr. Xu said based on data from the mortality files of the National Vital Statistics System.
Geographically, the District of Columbia had the highest rate at 16.8 per 100,000 in 2016, followed by Louisiana (13.8), Hawaii (12.7), and Mississippi and New Mexico (12.4 each). Vermont’s rate of 6.0 was the lowest in the country, with Maine second at 7.4, Montana third at 7.7, and Utah and Nebraska tied for fourth at 7.8, according to Dr. Xu.
Real-time microarrays can simultaneously detect HCV and HIV-1, -2 infections
The use of TaqMan Array Card (TAC) microarrays has been extended to permit simultaneous detection of HIV-1, HIV-2, and five hepatitis viruses from a small amount of extracted nucleic acid, according to a study by Timothy C. Granade, MD, and his colleagues at the Centers for Disease Control and Prevention, Atlanta.
This is particularly important for dealing with HIV-infected individuals, because HIV-1 and HIV-2 require different treatment interventions, and approximately one-third of HIV-infected patients have been found to be coinfected with hepatitis C or hepatitis B, according to the study report, published in the Journal of Virological Methods (J Virol Methods. 2018 Sep;259:60-5).
HIV-1-positive plasma samples from a variety of subtypes as well as whole blood specimens were confirmed for HIV-1-infection serologically or by nucleic amplification methods. HIV-2 whole blood and plasma specimens were also obtained.
TAC cards contained one positive control, one negative control, three HIV-1 replicates, and two HIV-2 replicates. In addition, the five common hepatitis viruses (A-E) were each replicated three times on each card. The cards were used to test the RNA isolates obtained from the various samples.
Ninety-five of the 104 known HIV-1-positive specimens were assayed positive using TAC; 23 of 26 HIV-2-seeded specimens were detectable using TAC and no cross-reactivity was seen between HIV-1-positive and HIV-2-positive specimens.
Eighteen of the HIV-1-positive specimens were also reactive in triplicate for HCV; three of the HIV-1-positive specimens were reactive to HBV and one specimen was reactive to HIV-1, HBV, and HCV.
“The TAC assay could be invaluable in large-scale screening environments or in surveying local outbreaks such as the recent HIV cluster found in Indiana. Many of these individuals were later determined to be infected with hepatitis C. The use of TAC could shorten the time to identifying and confirming such cases and permit the detection of multiple blood-borne infections in a single test. Application of TAC technology to general population surveillance could identify problem areas for both HIV prevention and intervention efforts in a variety of global environs,” the researchers concluded.
The authors were employed by the Centers for Disease Control and Prevention, Atlanta, which funded the study.
The use of TaqMan Array Card (TAC) microarrays has been extended to permit simultaneous detection of HIV-1, HIV-2, and five hepatitis viruses from a small amount of extracted nucleic acid, according to a study by Timothy C. Granade, MD, and his colleagues at the Centers for Disease Control and Prevention, Atlanta.
This is particularly important for dealing with HIV-infected individuals, because HIV-1 and HIV-2 require different treatment interventions, and approximately one-third of HIV-infected patients have been found to be coinfected with hepatitis C or hepatitis B, according to the study report, published in the Journal of Virological Methods (J Virol Methods. 2018 Sep;259:60-5).
HIV-1-positive plasma samples from a variety of subtypes as well as whole blood specimens were confirmed for HIV-1-infection serologically or by nucleic amplification methods. HIV-2 whole blood and plasma specimens were also obtained.
TAC cards contained one positive control, one negative control, three HIV-1 replicates, and two HIV-2 replicates. In addition, the five common hepatitis viruses (A-E) were each replicated three times on each card. The cards were used to test the RNA isolates obtained from the various samples.
Ninety-five of the 104 known HIV-1-positive specimens were assayed positive using TAC; 23 of 26 HIV-2-seeded specimens were detectable using TAC and no cross-reactivity was seen between HIV-1-positive and HIV-2-positive specimens.
Eighteen of the HIV-1-positive specimens were also reactive in triplicate for HCV; three of the HIV-1-positive specimens were reactive to HBV and one specimen was reactive to HIV-1, HBV, and HCV.
“The TAC assay could be invaluable in large-scale screening environments or in surveying local outbreaks such as the recent HIV cluster found in Indiana. Many of these individuals were later determined to be infected with hepatitis C. The use of TAC could shorten the time to identifying and confirming such cases and permit the detection of multiple blood-borne infections in a single test. Application of TAC technology to general population surveillance could identify problem areas for both HIV prevention and intervention efforts in a variety of global environs,” the researchers concluded.
The authors were employed by the Centers for Disease Control and Prevention, Atlanta, which funded the study.
The use of TaqMan Array Card (TAC) microarrays has been extended to permit simultaneous detection of HIV-1, HIV-2, and five hepatitis viruses from a small amount of extracted nucleic acid, according to a study by Timothy C. Granade, MD, and his colleagues at the Centers for Disease Control and Prevention, Atlanta.
This is particularly important for dealing with HIV-infected individuals, because HIV-1 and HIV-2 require different treatment interventions, and approximately one-third of HIV-infected patients have been found to be coinfected with hepatitis C or hepatitis B, according to the study report, published in the Journal of Virological Methods (J Virol Methods. 2018 Sep;259:60-5).
HIV-1-positive plasma samples from a variety of subtypes as well as whole blood specimens were confirmed for HIV-1-infection serologically or by nucleic amplification methods. HIV-2 whole blood and plasma specimens were also obtained.
TAC cards contained one positive control, one negative control, three HIV-1 replicates, and two HIV-2 replicates. In addition, the five common hepatitis viruses (A-E) were each replicated three times on each card. The cards were used to test the RNA isolates obtained from the various samples.
Ninety-five of the 104 known HIV-1-positive specimens were assayed positive using TAC; 23 of 26 HIV-2-seeded specimens were detectable using TAC and no cross-reactivity was seen between HIV-1-positive and HIV-2-positive specimens.
Eighteen of the HIV-1-positive specimens were also reactive in triplicate for HCV; three of the HIV-1-positive specimens were reactive to HBV and one specimen was reactive to HIV-1, HBV, and HCV.
“The TAC assay could be invaluable in large-scale screening environments or in surveying local outbreaks such as the recent HIV cluster found in Indiana. Many of these individuals were later determined to be infected with hepatitis C. The use of TAC could shorten the time to identifying and confirming such cases and permit the detection of multiple blood-borne infections in a single test. Application of TAC technology to general population surveillance could identify problem areas for both HIV prevention and intervention efforts in a variety of global environs,” the researchers concluded.
The authors were employed by the Centers for Disease Control and Prevention, Atlanta, which funded the study.
FROM THE JOURNAL OF VIROLOGICAL METHODS
Deaths from liver disease surged in U.S. since 1999
Cirrhosis mortality showed a sharp rise beginning in 2009, with a 3.6% annual increase driven entirely by a surge in alcoholic cirrhosis among young people aged 25-34 years, Elliot B. Tapper, MD, and Neehar D. Parikh, MD, reported in the BMJ. The uptick in hepatocellular carcinoma, however, was gradual and consistent, with a 2% annual increase felt mostly in older people, wrote Dr. Tapper and Dr. Parikh, both at the University of Michigan, Ann Arbor.
“The increasing mortality due to cirrhosis and hepatocellular carcinoma speaks to the expanding socioeconomic impact of liver disease,” the colleagues wrote. “Adverse trends in liver-related mortality are particularly unfortunate given that in most cases the liver disease is preventable. Understanding the factors associated with mortality due to these conditions will inform how best to allocate resources.”
The study extracted its data from the Vital Statistic Cooperative and the Centers for Disease Control and Prevention. The investigators not only examined raw mortality numbers, but analyzed them for demographic and geographic trends, in analyses that controlled for age.
Cirrhosis
During the study period, 460,760 patients died from cirrhosis (20,661 in 1999 and 34,174 in 2016, an increase of 65.4%).
Men were twice as likely to die from cirrhosis. Young people aged 25-34 years had the highest rate of increase (3.7% over the entire period and 10.5% from 2009 to 2016). This was directly driven by parallel increases in both alcohol use disorder and alcohol-related liver diseases, which increased by about 16% and 10%, respectively, in this group.
Native Americans had the highest mortality rate (25.8 per 100,000) followed by whites (12.7 per 100,000). “Notably, by 2016, cirrhosis accounted for 6.3% [up from 4.3% in 2009] and 7% [up from 5.8% in 2009] of deaths for Native Americans aged 25-34 and 35 or more, respectively,” and 2.3% of all deaths among adults aged 25-34 years, the authors wrote.
The increases were largely felt in the southern and western states (about 13 per 100,000 in each region). The greatest increases occurred in Kentucky (6.8%), New Mexico (6%), Arkansas (5.7%), Indiana (5%), and Alabama (5%). There was a statistically significant 1.2% decrease in deaths from cirrhosis in Maryland.
Hepatocellular carcinoma
Hepatocellular carcinoma accounted for 136,442 deaths during the study period (5,112 in 1999 and 11,073 in 2016 – an increase of 116.6%). This represented an average annual increase of 2%.
Men were four times more likely to die from hepatocellular carcinoma. The increase manifested mostly in older people, decreasing in those younger than 55 years. Mortality was highest among Asians and Pacific Islanders (6 per 100,000), followed by blacks (4.94 per 100,000).
The increases were largely felt in western states, with an overall increase of 4.2 per 100,000.
“Many of the same states with worsening cirrhosis-related mortality also experienced worsening mortality from hepatocellular carcinoma, including Oregon and Iowa,” the authors wrote. But mortality from the disease also increased significantly in Arizona (5.1%), Kansas (4.3%), Kentucky (4%), and Washington (3.9%).
“Potential explanations supported by these data include increasing early detection of hepatocellular carcinoma, application of curative or locoregional therapies, and, because hepatitis B is the principal cause of hepatocellular carcinoma worldwide and among Asian Americans, effectiveness of vaccination programs and the efficacy of antiviral therapy for hepatitis B in preventing the development of hepatocellular carcinoma.”
However, they noted, “it is unclear how these trends are, or will be, affected by direct-acting antivirals for hepatitis C virus ... eradication of hepatitis C virus will prevent the development of cirrhosis and its complications, potentially changing these trends in the next 5-10 years. However, therapy for hepatitis C viral infection cannot modify the statistically significant trends observed related to alcohol or the expected increase in the burden of nonalcoholic fatty liver disease.”
Neither author had any financial disclosure relevant to the work.
SOURCE: Tapper EB et al. BMJ 2018;362:k2817.
Cirrhosis mortality showed a sharp rise beginning in 2009, with a 3.6% annual increase driven entirely by a surge in alcoholic cirrhosis among young people aged 25-34 years, Elliot B. Tapper, MD, and Neehar D. Parikh, MD, reported in the BMJ. The uptick in hepatocellular carcinoma, however, was gradual and consistent, with a 2% annual increase felt mostly in older people, wrote Dr. Tapper and Dr. Parikh, both at the University of Michigan, Ann Arbor.
“The increasing mortality due to cirrhosis and hepatocellular carcinoma speaks to the expanding socioeconomic impact of liver disease,” the colleagues wrote. “Adverse trends in liver-related mortality are particularly unfortunate given that in most cases the liver disease is preventable. Understanding the factors associated with mortality due to these conditions will inform how best to allocate resources.”
The study extracted its data from the Vital Statistic Cooperative and the Centers for Disease Control and Prevention. The investigators not only examined raw mortality numbers, but analyzed them for demographic and geographic trends, in analyses that controlled for age.
Cirrhosis
During the study period, 460,760 patients died from cirrhosis (20,661 in 1999 and 34,174 in 2016, an increase of 65.4%).
Men were twice as likely to die from cirrhosis. Young people aged 25-34 years had the highest rate of increase (3.7% over the entire period and 10.5% from 2009 to 2016). This was directly driven by parallel increases in both alcohol use disorder and alcohol-related liver diseases, which increased by about 16% and 10%, respectively, in this group.
Native Americans had the highest mortality rate (25.8 per 100,000) followed by whites (12.7 per 100,000). “Notably, by 2016, cirrhosis accounted for 6.3% [up from 4.3% in 2009] and 7% [up from 5.8% in 2009] of deaths for Native Americans aged 25-34 and 35 or more, respectively,” and 2.3% of all deaths among adults aged 25-34 years, the authors wrote.
The increases were largely felt in the southern and western states (about 13 per 100,000 in each region). The greatest increases occurred in Kentucky (6.8%), New Mexico (6%), Arkansas (5.7%), Indiana (5%), and Alabama (5%). There was a statistically significant 1.2% decrease in deaths from cirrhosis in Maryland.
Hepatocellular carcinoma
Hepatocellular carcinoma accounted for 136,442 deaths during the study period (5,112 in 1999 and 11,073 in 2016 – an increase of 116.6%). This represented an average annual increase of 2%.
Men were four times more likely to die from hepatocellular carcinoma. The increase manifested mostly in older people, decreasing in those younger than 55 years. Mortality was highest among Asians and Pacific Islanders (6 per 100,000), followed by blacks (4.94 per 100,000).
The increases were largely felt in western states, with an overall increase of 4.2 per 100,000.
“Many of the same states with worsening cirrhosis-related mortality also experienced worsening mortality from hepatocellular carcinoma, including Oregon and Iowa,” the authors wrote. But mortality from the disease also increased significantly in Arizona (5.1%), Kansas (4.3%), Kentucky (4%), and Washington (3.9%).
“Potential explanations supported by these data include increasing early detection of hepatocellular carcinoma, application of curative or locoregional therapies, and, because hepatitis B is the principal cause of hepatocellular carcinoma worldwide and among Asian Americans, effectiveness of vaccination programs and the efficacy of antiviral therapy for hepatitis B in preventing the development of hepatocellular carcinoma.”
However, they noted, “it is unclear how these trends are, or will be, affected by direct-acting antivirals for hepatitis C virus ... eradication of hepatitis C virus will prevent the development of cirrhosis and its complications, potentially changing these trends in the next 5-10 years. However, therapy for hepatitis C viral infection cannot modify the statistically significant trends observed related to alcohol or the expected increase in the burden of nonalcoholic fatty liver disease.”
Neither author had any financial disclosure relevant to the work.
SOURCE: Tapper EB et al. BMJ 2018;362:k2817.
Cirrhosis mortality showed a sharp rise beginning in 2009, with a 3.6% annual increase driven entirely by a surge in alcoholic cirrhosis among young people aged 25-34 years, Elliot B. Tapper, MD, and Neehar D. Parikh, MD, reported in the BMJ. The uptick in hepatocellular carcinoma, however, was gradual and consistent, with a 2% annual increase felt mostly in older people, wrote Dr. Tapper and Dr. Parikh, both at the University of Michigan, Ann Arbor.
“The increasing mortality due to cirrhosis and hepatocellular carcinoma speaks to the expanding socioeconomic impact of liver disease,” the colleagues wrote. “Adverse trends in liver-related mortality are particularly unfortunate given that in most cases the liver disease is preventable. Understanding the factors associated with mortality due to these conditions will inform how best to allocate resources.”
The study extracted its data from the Vital Statistic Cooperative and the Centers for Disease Control and Prevention. The investigators not only examined raw mortality numbers, but analyzed them for demographic and geographic trends, in analyses that controlled for age.
Cirrhosis
During the study period, 460,760 patients died from cirrhosis (20,661 in 1999 and 34,174 in 2016, an increase of 65.4%).
Men were twice as likely to die from cirrhosis. Young people aged 25-34 years had the highest rate of increase (3.7% over the entire period and 10.5% from 2009 to 2016). This was directly driven by parallel increases in both alcohol use disorder and alcohol-related liver diseases, which increased by about 16% and 10%, respectively, in this group.
Native Americans had the highest mortality rate (25.8 per 100,000) followed by whites (12.7 per 100,000). “Notably, by 2016, cirrhosis accounted for 6.3% [up from 4.3% in 2009] and 7% [up from 5.8% in 2009] of deaths for Native Americans aged 25-34 and 35 or more, respectively,” and 2.3% of all deaths among adults aged 25-34 years, the authors wrote.
The increases were largely felt in the southern and western states (about 13 per 100,000 in each region). The greatest increases occurred in Kentucky (6.8%), New Mexico (6%), Arkansas (5.7%), Indiana (5%), and Alabama (5%). There was a statistically significant 1.2% decrease in deaths from cirrhosis in Maryland.
Hepatocellular carcinoma
Hepatocellular carcinoma accounted for 136,442 deaths during the study period (5,112 in 1999 and 11,073 in 2016 – an increase of 116.6%). This represented an average annual increase of 2%.
Men were four times more likely to die from hepatocellular carcinoma. The increase manifested mostly in older people, decreasing in those younger than 55 years. Mortality was highest among Asians and Pacific Islanders (6 per 100,000), followed by blacks (4.94 per 100,000).
The increases were largely felt in western states, with an overall increase of 4.2 per 100,000.
“Many of the same states with worsening cirrhosis-related mortality also experienced worsening mortality from hepatocellular carcinoma, including Oregon and Iowa,” the authors wrote. But mortality from the disease also increased significantly in Arizona (5.1%), Kansas (4.3%), Kentucky (4%), and Washington (3.9%).
“Potential explanations supported by these data include increasing early detection of hepatocellular carcinoma, application of curative or locoregional therapies, and, because hepatitis B is the principal cause of hepatocellular carcinoma worldwide and among Asian Americans, effectiveness of vaccination programs and the efficacy of antiviral therapy for hepatitis B in preventing the development of hepatocellular carcinoma.”
However, they noted, “it is unclear how these trends are, or will be, affected by direct-acting antivirals for hepatitis C virus ... eradication of hepatitis C virus will prevent the development of cirrhosis and its complications, potentially changing these trends in the next 5-10 years. However, therapy for hepatitis C viral infection cannot modify the statistically significant trends observed related to alcohol or the expected increase in the burden of nonalcoholic fatty liver disease.”
Neither author had any financial disclosure relevant to the work.
SOURCE: Tapper EB et al. BMJ 2018;362:k2817.
FROM BMJ
Key clinical point: Deaths from cirrhosis and hepatocellular carcinoma have surged in the United States since 1999.
Major finding: Liver cirrhosis mortality increased by 65% and hepatocellular carcinoma mortality by about 117%.
Study details: The study extracted data from the National Vital Statistics database and the CDC.
Disclosures: Neither author had relevant financial disclosures.
Source: Tapper EB et al. BMJ 2018;362:k2817.