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Louisiana HCV program cuts costs – and hassles
Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.
The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.
State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.
“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”
The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.
“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”
He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”
Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.
Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.
“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”
Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv
Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.
The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.
State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.
“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”
The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.
“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”
He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”
Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.
Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.
“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”
Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv
Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.
The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.
State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.
“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”
The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.
“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”
He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”
Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.
Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.
“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”
Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv
HCC surveillance after anti-HCV therapy cost effective only for patients with cirrhosis
For patients with hepatitis C virus (HCV)–related cirrhosis (F4), but not those with advanced fibrosis (F3), hepatocellular carcinoma (HCC) surveillance after a sustained virologic response (SVR) is cost effective, according to investigators.
Current international guidelines call for HCC surveillance among all patients with advanced fibrosis (F3) or cirrhosis (F4) who have achieved SVR, but this is “very unlikely to be cost effective,” reported lead author Hooman Farhang Zangneh, MD, of Toronto General Hospital and colleagues. “HCV-related HCC rarely occurs in patients without cirrhosis,” the investigators explained in Clinical Gastroenterology and Hepatology. “With cirrhosis present, HCC incidence is 1.4% to 4.9% per year. If found early, options for curative therapy include radiofrequency ablation (RFA), surgical resection, and liver transplantation.”
The investigators developed a Markov model to determine which at-risk patients could undergo surveillance while remaining below willingness-to-pay thresholds. Specifically, cost-effectiveness was assessed for ultrasound screenings annually (every year) or biannually (twice a year) among patients with advanced fibrosis (F3) or compensated cirrhosis (F4) who were aged 50 years and had an SVR. Relevant data were drawn from expert opinions, medical literature, and Canada Life Tables. Various HCC incidence rates were tested, including a constant annual rate, rates based on type of antiviral treatment (direct-acting and interferon-based therapies), others based on stage of fibrosis, and another that increased with age. The model was validated by applying it to patients with F3 or F4 fibrosis who had not yet achieved an SVR. All monetary values were reported in 2015 Canadian dollars.
Representative of current guidelines, the investigators first tested costs when conducting surveillance among all patients with F3 or F4 fibrosis with an assumed constant HCC annual incidence rate of 0.5%. Biannual ultrasound surveillance after SVR caught more cases of HCC still in a curable stage (78%) than no surveillance (29%); however, false-positives were relatively common at 21.8% and 15.7% for biannual and annual surveillance, respectively. The investigators noted that in the real world, some of these false-positives are not detected by more advanced imaging, so patients go on to receive unnecessary RFA, which incurs additional costs. Partly for this reason, while biannual surveillance was more effective, it was also more expensive, with an incremental cost-effectiveness ratio (ICER) of $106,792 per quality-adjusted life-years (QALY), compared with $72,105 per QALY for annual surveillance.
Including only patients with F3 fibrosis after interferon-based therapy, using an HCC incidence of 0.23%, biannual and annual ICERs rose to $484,160 and $204,708 per QALY, respectively, both of which exceed standard willingness-to-pay thresholds. In comparison, annual and biannual ICERs were at most $55,850 and $42,305 per QALY, respectively, among patients with cirrhosis before interferon-induced SVR, using an HCC incidence rate of up to 1.39% per year.
“These results suggest that biannual (or annual) HCC surveillance is likely to be cost effective for patients with cirrhosis, but not for patients with F3 fibrosis before SVR,” the investigators wrote.
Costs for HCC surveillance among cirrhosis patients after direct-acting antiviral-induced SVR were still lower, at $43,229 and $34,307 per QALY, which were far lower than costs for patients with F3 fibrosis, which were $188,157 and $111,667 per QALY.
Focusing on the evident savings associated with surveillance of patients with cirrhosis, the investigators tested two diagnostic thresholds within this population with the aim of reducing costs further. They found that surveillance of patients with a pretreatment aspartate aminotransferase to platelet ratio index (APRI) greater than 2.0 (HCC incidence, 0.89%) was associated with biannual and annual ICERs of $48,729 and $37,806 per QALY, respectively, but when APRI was less than 2.0 (HCC incidence, 0.093%), surveillance was less effective and more expensive than no surveillance at all. A similar trend was found for an FIB-4 threshold of 3.25.
Employment of age-stratified risk of HCC also reduced costs of screening for patients with cirrhosis. With this strategy, ICER was $48,432 per QALY for biannual surveillance and $37,201 per QALY for annual surveillance.
“These data suggest that, if we assume HCC incidence increases with age, biannual or annual surveillance will be cost effective for the vast majority, if not all, patients with cirrhosis before SVR,” the investigators wrote.
“Our analysis suggests that HCC surveillance is very unlikely to be cost effective in patients with F3 fibrosis, whereas both annual and biannual modalities are likely to be cost effective at standard willingness-to-pay thresholds for patients with cirrhosis compared with no surveillance,” the investigators wrote.
“Additional long-term follow-up data are required to help identify patients at highest risk of HCC after SVR to tailor surveillance guidelines,” the investigators concluded.
The study was funded by the Toronto Centre for Liver Disease. The investigators declared no conflicts of interest.
This story was updated on 7/12/2019.
SOURCE: Zangneh et al. Clin Gastroenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.018.
For patients with hepatitis C virus (HCV)–related cirrhosis (F4), but not those with advanced fibrosis (F3), hepatocellular carcinoma (HCC) surveillance after a sustained virologic response (SVR) is cost effective, according to investigators.
Current international guidelines call for HCC surveillance among all patients with advanced fibrosis (F3) or cirrhosis (F4) who have achieved SVR, but this is “very unlikely to be cost effective,” reported lead author Hooman Farhang Zangneh, MD, of Toronto General Hospital and colleagues. “HCV-related HCC rarely occurs in patients without cirrhosis,” the investigators explained in Clinical Gastroenterology and Hepatology. “With cirrhosis present, HCC incidence is 1.4% to 4.9% per year. If found early, options for curative therapy include radiofrequency ablation (RFA), surgical resection, and liver transplantation.”
The investigators developed a Markov model to determine which at-risk patients could undergo surveillance while remaining below willingness-to-pay thresholds. Specifically, cost-effectiveness was assessed for ultrasound screenings annually (every year) or biannually (twice a year) among patients with advanced fibrosis (F3) or compensated cirrhosis (F4) who were aged 50 years and had an SVR. Relevant data were drawn from expert opinions, medical literature, and Canada Life Tables. Various HCC incidence rates were tested, including a constant annual rate, rates based on type of antiviral treatment (direct-acting and interferon-based therapies), others based on stage of fibrosis, and another that increased with age. The model was validated by applying it to patients with F3 or F4 fibrosis who had not yet achieved an SVR. All monetary values were reported in 2015 Canadian dollars.
Representative of current guidelines, the investigators first tested costs when conducting surveillance among all patients with F3 or F4 fibrosis with an assumed constant HCC annual incidence rate of 0.5%. Biannual ultrasound surveillance after SVR caught more cases of HCC still in a curable stage (78%) than no surveillance (29%); however, false-positives were relatively common at 21.8% and 15.7% for biannual and annual surveillance, respectively. The investigators noted that in the real world, some of these false-positives are not detected by more advanced imaging, so patients go on to receive unnecessary RFA, which incurs additional costs. Partly for this reason, while biannual surveillance was more effective, it was also more expensive, with an incremental cost-effectiveness ratio (ICER) of $106,792 per quality-adjusted life-years (QALY), compared with $72,105 per QALY for annual surveillance.
Including only patients with F3 fibrosis after interferon-based therapy, using an HCC incidence of 0.23%, biannual and annual ICERs rose to $484,160 and $204,708 per QALY, respectively, both of which exceed standard willingness-to-pay thresholds. In comparison, annual and biannual ICERs were at most $55,850 and $42,305 per QALY, respectively, among patients with cirrhosis before interferon-induced SVR, using an HCC incidence rate of up to 1.39% per year.
“These results suggest that biannual (or annual) HCC surveillance is likely to be cost effective for patients with cirrhosis, but not for patients with F3 fibrosis before SVR,” the investigators wrote.
Costs for HCC surveillance among cirrhosis patients after direct-acting antiviral-induced SVR were still lower, at $43,229 and $34,307 per QALY, which were far lower than costs for patients with F3 fibrosis, which were $188,157 and $111,667 per QALY.
Focusing on the evident savings associated with surveillance of patients with cirrhosis, the investigators tested two diagnostic thresholds within this population with the aim of reducing costs further. They found that surveillance of patients with a pretreatment aspartate aminotransferase to platelet ratio index (APRI) greater than 2.0 (HCC incidence, 0.89%) was associated with biannual and annual ICERs of $48,729 and $37,806 per QALY, respectively, but when APRI was less than 2.0 (HCC incidence, 0.093%), surveillance was less effective and more expensive than no surveillance at all. A similar trend was found for an FIB-4 threshold of 3.25.
Employment of age-stratified risk of HCC also reduced costs of screening for patients with cirrhosis. With this strategy, ICER was $48,432 per QALY for biannual surveillance and $37,201 per QALY for annual surveillance.
“These data suggest that, if we assume HCC incidence increases with age, biannual or annual surveillance will be cost effective for the vast majority, if not all, patients with cirrhosis before SVR,” the investigators wrote.
“Our analysis suggests that HCC surveillance is very unlikely to be cost effective in patients with F3 fibrosis, whereas both annual and biannual modalities are likely to be cost effective at standard willingness-to-pay thresholds for patients with cirrhosis compared with no surveillance,” the investigators wrote.
“Additional long-term follow-up data are required to help identify patients at highest risk of HCC after SVR to tailor surveillance guidelines,” the investigators concluded.
The study was funded by the Toronto Centre for Liver Disease. The investigators declared no conflicts of interest.
This story was updated on 7/12/2019.
SOURCE: Zangneh et al. Clin Gastroenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.018.
For patients with hepatitis C virus (HCV)–related cirrhosis (F4), but not those with advanced fibrosis (F3), hepatocellular carcinoma (HCC) surveillance after a sustained virologic response (SVR) is cost effective, according to investigators.
Current international guidelines call for HCC surveillance among all patients with advanced fibrosis (F3) or cirrhosis (F4) who have achieved SVR, but this is “very unlikely to be cost effective,” reported lead author Hooman Farhang Zangneh, MD, of Toronto General Hospital and colleagues. “HCV-related HCC rarely occurs in patients without cirrhosis,” the investigators explained in Clinical Gastroenterology and Hepatology. “With cirrhosis present, HCC incidence is 1.4% to 4.9% per year. If found early, options for curative therapy include radiofrequency ablation (RFA), surgical resection, and liver transplantation.”
The investigators developed a Markov model to determine which at-risk patients could undergo surveillance while remaining below willingness-to-pay thresholds. Specifically, cost-effectiveness was assessed for ultrasound screenings annually (every year) or biannually (twice a year) among patients with advanced fibrosis (F3) or compensated cirrhosis (F4) who were aged 50 years and had an SVR. Relevant data were drawn from expert opinions, medical literature, and Canada Life Tables. Various HCC incidence rates were tested, including a constant annual rate, rates based on type of antiviral treatment (direct-acting and interferon-based therapies), others based on stage of fibrosis, and another that increased with age. The model was validated by applying it to patients with F3 or F4 fibrosis who had not yet achieved an SVR. All monetary values were reported in 2015 Canadian dollars.
Representative of current guidelines, the investigators first tested costs when conducting surveillance among all patients with F3 or F4 fibrosis with an assumed constant HCC annual incidence rate of 0.5%. Biannual ultrasound surveillance after SVR caught more cases of HCC still in a curable stage (78%) than no surveillance (29%); however, false-positives were relatively common at 21.8% and 15.7% for biannual and annual surveillance, respectively. The investigators noted that in the real world, some of these false-positives are not detected by more advanced imaging, so patients go on to receive unnecessary RFA, which incurs additional costs. Partly for this reason, while biannual surveillance was more effective, it was also more expensive, with an incremental cost-effectiveness ratio (ICER) of $106,792 per quality-adjusted life-years (QALY), compared with $72,105 per QALY for annual surveillance.
Including only patients with F3 fibrosis after interferon-based therapy, using an HCC incidence of 0.23%, biannual and annual ICERs rose to $484,160 and $204,708 per QALY, respectively, both of which exceed standard willingness-to-pay thresholds. In comparison, annual and biannual ICERs were at most $55,850 and $42,305 per QALY, respectively, among patients with cirrhosis before interferon-induced SVR, using an HCC incidence rate of up to 1.39% per year.
“These results suggest that biannual (or annual) HCC surveillance is likely to be cost effective for patients with cirrhosis, but not for patients with F3 fibrosis before SVR,” the investigators wrote.
Costs for HCC surveillance among cirrhosis patients after direct-acting antiviral-induced SVR were still lower, at $43,229 and $34,307 per QALY, which were far lower than costs for patients with F3 fibrosis, which were $188,157 and $111,667 per QALY.
Focusing on the evident savings associated with surveillance of patients with cirrhosis, the investigators tested two diagnostic thresholds within this population with the aim of reducing costs further. They found that surveillance of patients with a pretreatment aspartate aminotransferase to platelet ratio index (APRI) greater than 2.0 (HCC incidence, 0.89%) was associated with biannual and annual ICERs of $48,729 and $37,806 per QALY, respectively, but when APRI was less than 2.0 (HCC incidence, 0.093%), surveillance was less effective and more expensive than no surveillance at all. A similar trend was found for an FIB-4 threshold of 3.25.
Employment of age-stratified risk of HCC also reduced costs of screening for patients with cirrhosis. With this strategy, ICER was $48,432 per QALY for biannual surveillance and $37,201 per QALY for annual surveillance.
“These data suggest that, if we assume HCC incidence increases with age, biannual or annual surveillance will be cost effective for the vast majority, if not all, patients with cirrhosis before SVR,” the investigators wrote.
“Our analysis suggests that HCC surveillance is very unlikely to be cost effective in patients with F3 fibrosis, whereas both annual and biannual modalities are likely to be cost effective at standard willingness-to-pay thresholds for patients with cirrhosis compared with no surveillance,” the investigators wrote.
“Additional long-term follow-up data are required to help identify patients at highest risk of HCC after SVR to tailor surveillance guidelines,” the investigators concluded.
The study was funded by the Toronto Centre for Liver Disease. The investigators declared no conflicts of interest.
This story was updated on 7/12/2019.
SOURCE: Zangneh et al. Clin Gastroenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.018.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Mortality caused by chronic liver disease in setting of diabetes continues to rise
results from a large database analysis showed.
“While diabetes-related mortality has been reported to be decreasing due to improved awareness and management, our results highlight the need to better address NAFLD [nonalcoholic fatty liver disease] and end-stage liver disease among individuals with diabetes,” researchers led by Donghee Kim, MD, PhD, wrote in an article published in Clinical Gastroenterology and Hepatology.
In an effort to estimate the trends in chronic liver disease–related mortality among individuals with diabetes from 2007 to 2017 in the United States, Dr. Kim, of the division of gastroenterology and hepatology at Stanford (Calif.) University, and colleagues analyzed mortality records from the National Vital Statistic System database. They calculated age-specific mortality by dividing the number of deaths by the total U.S. census population for each year and standardized them according to age distribution of 2010 U.S. standard population. The researchers used joinpoint regression analysis to determine trends.
Of 2,686,590 individuals with diabetes identified, 48,761 had chronic liver disease as the underlying cause of death listed on the death certificate. Among individuals who had diabetes listed on their death certificate, the age-standardized mortality for cirrhosis and hepatocellular carcinoma as an underlying cause of death increased with an annual rate of 1.2% and 1.9%, respectively. Based on etiology, age-standardized mortality for hepatitis C and hepatitis B viral infections decreased at an annual rate of 4.4% and 5.1%, respectively. On the other hand, mortality among individuals with NAFLD and alcoholic liver disease increased at annual rates of 11.6% and 1.4%, respectively.
“When we defined chronic liver disease as an underlying or contributing cause of death among individuals with diabetes listed on the death certificate, the overall results remained similar,” the researchers wrote. They acknowledged certain limitations of the analysis, including the fact that using death certificates and ICD-10 codes “has the potential for misclassification and underestimation for diabetes and chronic liver disease–related mortality. However, the coding method has been constant over time, so it is unlikely to account for present trends. Increasing obesity and associated insulin resistance likely explain the link between diabetes and NAFLD and end-stage liver disease through hepatic inflammation and various proinflammatory cytokines.”
One of the study authors was supported by the National Institutes of Health. None of the other authors reported having relevant disclosures.
SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.
results from a large database analysis showed.
“While diabetes-related mortality has been reported to be decreasing due to improved awareness and management, our results highlight the need to better address NAFLD [nonalcoholic fatty liver disease] and end-stage liver disease among individuals with diabetes,” researchers led by Donghee Kim, MD, PhD, wrote in an article published in Clinical Gastroenterology and Hepatology.
In an effort to estimate the trends in chronic liver disease–related mortality among individuals with diabetes from 2007 to 2017 in the United States, Dr. Kim, of the division of gastroenterology and hepatology at Stanford (Calif.) University, and colleagues analyzed mortality records from the National Vital Statistic System database. They calculated age-specific mortality by dividing the number of deaths by the total U.S. census population for each year and standardized them according to age distribution of 2010 U.S. standard population. The researchers used joinpoint regression analysis to determine trends.
Of 2,686,590 individuals with diabetes identified, 48,761 had chronic liver disease as the underlying cause of death listed on the death certificate. Among individuals who had diabetes listed on their death certificate, the age-standardized mortality for cirrhosis and hepatocellular carcinoma as an underlying cause of death increased with an annual rate of 1.2% and 1.9%, respectively. Based on etiology, age-standardized mortality for hepatitis C and hepatitis B viral infections decreased at an annual rate of 4.4% and 5.1%, respectively. On the other hand, mortality among individuals with NAFLD and alcoholic liver disease increased at annual rates of 11.6% and 1.4%, respectively.
“When we defined chronic liver disease as an underlying or contributing cause of death among individuals with diabetes listed on the death certificate, the overall results remained similar,” the researchers wrote. They acknowledged certain limitations of the analysis, including the fact that using death certificates and ICD-10 codes “has the potential for misclassification and underestimation for diabetes and chronic liver disease–related mortality. However, the coding method has been constant over time, so it is unlikely to account for present trends. Increasing obesity and associated insulin resistance likely explain the link between diabetes and NAFLD and end-stage liver disease through hepatic inflammation and various proinflammatory cytokines.”
One of the study authors was supported by the National Institutes of Health. None of the other authors reported having relevant disclosures.
SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.
results from a large database analysis showed.
“While diabetes-related mortality has been reported to be decreasing due to improved awareness and management, our results highlight the need to better address NAFLD [nonalcoholic fatty liver disease] and end-stage liver disease among individuals with diabetes,” researchers led by Donghee Kim, MD, PhD, wrote in an article published in Clinical Gastroenterology and Hepatology.
In an effort to estimate the trends in chronic liver disease–related mortality among individuals with diabetes from 2007 to 2017 in the United States, Dr. Kim, of the division of gastroenterology and hepatology at Stanford (Calif.) University, and colleagues analyzed mortality records from the National Vital Statistic System database. They calculated age-specific mortality by dividing the number of deaths by the total U.S. census population for each year and standardized them according to age distribution of 2010 U.S. standard population. The researchers used joinpoint regression analysis to determine trends.
Of 2,686,590 individuals with diabetes identified, 48,761 had chronic liver disease as the underlying cause of death listed on the death certificate. Among individuals who had diabetes listed on their death certificate, the age-standardized mortality for cirrhosis and hepatocellular carcinoma as an underlying cause of death increased with an annual rate of 1.2% and 1.9%, respectively. Based on etiology, age-standardized mortality for hepatitis C and hepatitis B viral infections decreased at an annual rate of 4.4% and 5.1%, respectively. On the other hand, mortality among individuals with NAFLD and alcoholic liver disease increased at annual rates of 11.6% and 1.4%, respectively.
“When we defined chronic liver disease as an underlying or contributing cause of death among individuals with diabetes listed on the death certificate, the overall results remained similar,” the researchers wrote. They acknowledged certain limitations of the analysis, including the fact that using death certificates and ICD-10 codes “has the potential for misclassification and underestimation for diabetes and chronic liver disease–related mortality. However, the coding method has been constant over time, so it is unlikely to account for present trends. Increasing obesity and associated insulin resistance likely explain the link between diabetes and NAFLD and end-stage liver disease through hepatic inflammation and various proinflammatory cytokines.”
One of the study authors was supported by the National Institutes of Health. None of the other authors reported having relevant disclosures.
SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Formal weight loss programs improve NAFLD
For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.
The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues.
“Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine.“However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.
To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease.
The literature search returned 22 eligible studies involving 2,588 patients. The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I2 = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I2 = 94%), histologic NAFLD activity score (-0.92; I2= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I2 =0%), alanine aminotransferase (-9.81 U/L; I2= 97%), aspartate transaminase (-4.84 U/L; I2 = 96%), alkaline phosphatase (-5.53 U/L; I2 = 96%), and gamma-glutamyl transferase (-4.35 U/L; I2 = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.
“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”
“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.
The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.
SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at https://www.gastro.org/practice-guidance/practice-updates/obesity-practice-guide
For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.
The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues.
“Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine.“However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.
To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease.
The literature search returned 22 eligible studies involving 2,588 patients. The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I2 = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I2 = 94%), histologic NAFLD activity score (-0.92; I2= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I2 =0%), alanine aminotransferase (-9.81 U/L; I2= 97%), aspartate transaminase (-4.84 U/L; I2 = 96%), alkaline phosphatase (-5.53 U/L; I2 = 96%), and gamma-glutamyl transferase (-4.35 U/L; I2 = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.
“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”
“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.
The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.
SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at https://www.gastro.org/practice-guidance/practice-updates/obesity-practice-guide
For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.
The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues.
“Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine.“However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.
To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease.
The literature search returned 22 eligible studies involving 2,588 patients. The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I2 = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I2 = 94%), histologic NAFLD activity score (-0.92; I2= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I2 =0%), alanine aminotransferase (-9.81 U/L; I2= 97%), aspartate transaminase (-4.84 U/L; I2 = 96%), alkaline phosphatase (-5.53 U/L; I2 = 96%), and gamma-glutamyl transferase (-4.35 U/L; I2 = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.
“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”
“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.
The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.
SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at https://www.gastro.org/practice-guidance/practice-updates/obesity-practice-guide
FROM JAMA INTERNAL MEDICINE
Key clinical point: Major finding: Weight loss interventions were associated with significantly decreased alanine aminotransferase (-9.81 U/L; I2 = 97%).
Study details: A meta-analysis of randomized clinicals involving weight loss interventions for patients with nonalcoholic fatty liver disease (NAFLD).
Disclosures: The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.
Source: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.
Past studies have attempted to investigate the relationship between weight loss and nonalcoholic fatty liver disease (NAFLD), but they did so with various interventions and outcomes measures. Fortunately, the study by Dr. Koutoukidis and colleagues helps clear up this variability with a well-conducted systematic review. The results offer a convincing case that formal weight loss programs should be a cornerstone of NALFD treatment, based on improvements in blood, histologic, and radiologic biomarkers of liver disease. Since pharmacologic options for NAFLD are limited, these findings are particularly important.
Although the study did not reveal improvements in fibrosis or inflammation with weight loss, this is likely due to the scarcity of trials with histologic measures or long-term follow-up. Where long-term follow-up was available, weight loss was not maintained, disallowing clear conclusions. Still, other studies have shown that sustained weight loss is associated with improvements in fibrosis and mortality, so clinicians should feel encouraged that formal weight loss programs for patients with NAFLD likely have life-saving consequences.
Elizabeth Adler, MD and Danielle Brandman, MD , are with the University of California, San Francisco. Dr. Brandman reported financial affiliations with Conatus, Gilead, and Allergan. Their remarks are adapted from an accompanying editorial (JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2244 ).
AGA Clinical Practice Update: Coagulation in cirrhosis
Cirrhosis can involve “precarious” changes in hemostatic pathways that tip the scales toward either bleeding or hypercoagulation, experts wrote in an American Gastroenterological Association Clinical Practice Update.
Based on current evidence, clinicians should not routinely correct thrombocytopenia and coagulopathy in patients with cirrhosis prior to low-risk procedures, such as therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation, Jacqueline G. O’Leary, MD, of Dallas VA Medical Center and her three coreviewers wrote in Gastroenterology.
To optimize clot formation prior to high-risk procedures, and in patients with active bleeding, a platelet count above 50,000 per mcL is still recommended. However, it may be more meaningful to couple that platelet target with a fibrinogen level above 120 mg/dL rather than rely on the international normalized ratio (INR), the experts wrote. Not only does INR vary significantly depending on which thromboplastin is used in the test, but “correcting” INR with a fresh frozen plasma infusion does not affect thrombin production and worsens portal hypertension. Using cryoprecipitate to replenish fibrinogen has less impact on portal hypertension. “Global tests of clot formation, such as rotational thromboelastometry (ROTEM), thromboelastography (TEG), sonorheometry, and thrombin generation may eventually have a role in the evaluation of clotting in patients with cirrhosis but currently lack validated target levels,” the experts wrote.
They advised clinicians to limit the use of blood products (such as fresh frozen plasma and pooled platelet transfusions) because of cost and the risk of exacerbated portal hypertension, infection, and immunologic complications. For severe anemia and uremia, red blood cell transfusion (250 mL) can be considered. Platelet-rich plasma from one donor is less immunologically risky than a pooled platelet transfusion. Thrombopoietin agonists are “a good alternative” to platelet transfusion but require about 10 days for response. Alternative prothrombotic therapies include oral thrombopoietin receptor agonists (avatrombopag and lusutrombopag) to boost platelet count before an invasive procedure, antifibrinolytic therapy (aminocaproic acid and tranexamic acid) for persistent bleeding from mucosal oozing or puncture wounds. Desmopressin should only be considered for patients with comorbid renal failure.
For anticoagulation, the practice update recommends considering systemic heparin infusion for cirrhotic patients with symptomatic deep venous thrombosis (DVT) or portal vein thrombosis (PVT). However, the anti–factor Xa assay will not reliably monitor response if patients have low liver-derived antithrombin III (heparin cofactor). “With newly diagnosed PVT, the decision to intervene with directed therapy rests on the extent of the thrombosis, presence or absence of attributable symptoms, and the risk of bleeding and falls,” the experts stated.
Six-month follow-up imaging is recommended to assess anticoagulation efficacy. More frequent imaging can be considered for PVT patients considered at high risk for therapeutic anticoagulation. If clots do not fully resolve after 6 months of treatment, options including extending therapy with the same agent, switching to a different anticoagulant class, or receiving transjugular intrahepatic portosystemic shunt (TIPS). “The role for TIPS in PVT is evolving and may address complications like portal hypertensive bleeding, medically refractory clot, and the need for repeated banding after variceal bleeding,” the experts noted.
Prophylaxis of DVT is recommended for all hospitalized patients with cirrhosis. Vitamin K antagonists and direct-acting oral anticoagulants (dabigatran, apixaban, rivaroxaban, and edoxaban) are alternatives to heparin for anticoagulation of cirrhotic patients with either PVT and DVT, the experts wrote. However, DOACs are not recommended for most Child-Pugh B patients or for any Child-Pugh C patients.
No funding sources or conflicts of interest were reported.
SOURCE: O’Leary JG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.070.
Cirrhosis can involve “precarious” changes in hemostatic pathways that tip the scales toward either bleeding or hypercoagulation, experts wrote in an American Gastroenterological Association Clinical Practice Update.
Based on current evidence, clinicians should not routinely correct thrombocytopenia and coagulopathy in patients with cirrhosis prior to low-risk procedures, such as therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation, Jacqueline G. O’Leary, MD, of Dallas VA Medical Center and her three coreviewers wrote in Gastroenterology.
To optimize clot formation prior to high-risk procedures, and in patients with active bleeding, a platelet count above 50,000 per mcL is still recommended. However, it may be more meaningful to couple that platelet target with a fibrinogen level above 120 mg/dL rather than rely on the international normalized ratio (INR), the experts wrote. Not only does INR vary significantly depending on which thromboplastin is used in the test, but “correcting” INR with a fresh frozen plasma infusion does not affect thrombin production and worsens portal hypertension. Using cryoprecipitate to replenish fibrinogen has less impact on portal hypertension. “Global tests of clot formation, such as rotational thromboelastometry (ROTEM), thromboelastography (TEG), sonorheometry, and thrombin generation may eventually have a role in the evaluation of clotting in patients with cirrhosis but currently lack validated target levels,” the experts wrote.
They advised clinicians to limit the use of blood products (such as fresh frozen plasma and pooled platelet transfusions) because of cost and the risk of exacerbated portal hypertension, infection, and immunologic complications. For severe anemia and uremia, red blood cell transfusion (250 mL) can be considered. Platelet-rich plasma from one donor is less immunologically risky than a pooled platelet transfusion. Thrombopoietin agonists are “a good alternative” to platelet transfusion but require about 10 days for response. Alternative prothrombotic therapies include oral thrombopoietin receptor agonists (avatrombopag and lusutrombopag) to boost platelet count before an invasive procedure, antifibrinolytic therapy (aminocaproic acid and tranexamic acid) for persistent bleeding from mucosal oozing or puncture wounds. Desmopressin should only be considered for patients with comorbid renal failure.
For anticoagulation, the practice update recommends considering systemic heparin infusion for cirrhotic patients with symptomatic deep venous thrombosis (DVT) or portal vein thrombosis (PVT). However, the anti–factor Xa assay will not reliably monitor response if patients have low liver-derived antithrombin III (heparin cofactor). “With newly diagnosed PVT, the decision to intervene with directed therapy rests on the extent of the thrombosis, presence or absence of attributable symptoms, and the risk of bleeding and falls,” the experts stated.
Six-month follow-up imaging is recommended to assess anticoagulation efficacy. More frequent imaging can be considered for PVT patients considered at high risk for therapeutic anticoagulation. If clots do not fully resolve after 6 months of treatment, options including extending therapy with the same agent, switching to a different anticoagulant class, or receiving transjugular intrahepatic portosystemic shunt (TIPS). “The role for TIPS in PVT is evolving and may address complications like portal hypertensive bleeding, medically refractory clot, and the need for repeated banding after variceal bleeding,” the experts noted.
Prophylaxis of DVT is recommended for all hospitalized patients with cirrhosis. Vitamin K antagonists and direct-acting oral anticoagulants (dabigatran, apixaban, rivaroxaban, and edoxaban) are alternatives to heparin for anticoagulation of cirrhotic patients with either PVT and DVT, the experts wrote. However, DOACs are not recommended for most Child-Pugh B patients or for any Child-Pugh C patients.
No funding sources or conflicts of interest were reported.
SOURCE: O’Leary JG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.070.
Cirrhosis can involve “precarious” changes in hemostatic pathways that tip the scales toward either bleeding or hypercoagulation, experts wrote in an American Gastroenterological Association Clinical Practice Update.
Based on current evidence, clinicians should not routinely correct thrombocytopenia and coagulopathy in patients with cirrhosis prior to low-risk procedures, such as therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation, Jacqueline G. O’Leary, MD, of Dallas VA Medical Center and her three coreviewers wrote in Gastroenterology.
To optimize clot formation prior to high-risk procedures, and in patients with active bleeding, a platelet count above 50,000 per mcL is still recommended. However, it may be more meaningful to couple that platelet target with a fibrinogen level above 120 mg/dL rather than rely on the international normalized ratio (INR), the experts wrote. Not only does INR vary significantly depending on which thromboplastin is used in the test, but “correcting” INR with a fresh frozen plasma infusion does not affect thrombin production and worsens portal hypertension. Using cryoprecipitate to replenish fibrinogen has less impact on portal hypertension. “Global tests of clot formation, such as rotational thromboelastometry (ROTEM), thromboelastography (TEG), sonorheometry, and thrombin generation may eventually have a role in the evaluation of clotting in patients with cirrhosis but currently lack validated target levels,” the experts wrote.
They advised clinicians to limit the use of blood products (such as fresh frozen plasma and pooled platelet transfusions) because of cost and the risk of exacerbated portal hypertension, infection, and immunologic complications. For severe anemia and uremia, red blood cell transfusion (250 mL) can be considered. Platelet-rich plasma from one donor is less immunologically risky than a pooled platelet transfusion. Thrombopoietin agonists are “a good alternative” to platelet transfusion but require about 10 days for response. Alternative prothrombotic therapies include oral thrombopoietin receptor agonists (avatrombopag and lusutrombopag) to boost platelet count before an invasive procedure, antifibrinolytic therapy (aminocaproic acid and tranexamic acid) for persistent bleeding from mucosal oozing or puncture wounds. Desmopressin should only be considered for patients with comorbid renal failure.
For anticoagulation, the practice update recommends considering systemic heparin infusion for cirrhotic patients with symptomatic deep venous thrombosis (DVT) or portal vein thrombosis (PVT). However, the anti–factor Xa assay will not reliably monitor response if patients have low liver-derived antithrombin III (heparin cofactor). “With newly diagnosed PVT, the decision to intervene with directed therapy rests on the extent of the thrombosis, presence or absence of attributable symptoms, and the risk of bleeding and falls,” the experts stated.
Six-month follow-up imaging is recommended to assess anticoagulation efficacy. More frequent imaging can be considered for PVT patients considered at high risk for therapeutic anticoagulation. If clots do not fully resolve after 6 months of treatment, options including extending therapy with the same agent, switching to a different anticoagulant class, or receiving transjugular intrahepatic portosystemic shunt (TIPS). “The role for TIPS in PVT is evolving and may address complications like portal hypertensive bleeding, medically refractory clot, and the need for repeated banding after variceal bleeding,” the experts noted.
Prophylaxis of DVT is recommended for all hospitalized patients with cirrhosis. Vitamin K antagonists and direct-acting oral anticoagulants (dabigatran, apixaban, rivaroxaban, and edoxaban) are alternatives to heparin for anticoagulation of cirrhotic patients with either PVT and DVT, the experts wrote. However, DOACs are not recommended for most Child-Pugh B patients or for any Child-Pugh C patients.
No funding sources or conflicts of interest were reported.
SOURCE: O’Leary JG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.070.
FROM GASTROENTEROLOGY
Study finds differences for HCC in women
SAN DIEGO – Hepatocellular carcinoma is the third leading cause of cancer-related death in the United States and its incidence is increasing worldwide. While it affects men much more frequently than women, approximately 4 to 1, the differences in risk factors between men and women have never been studied.
At the annual Digestive Disease Week, Meaghan Phipps, MD, of New York–Presbyterian Hospital, described in a video interview how she and her colleagues set up a retrospective study of these differences in 5,327 patients at five large academic centers around the country. She and her colleagues found that women tended to present later, and with less severe disease, which was more likely to be treated with resection than transplantation. Women had better overall survival. Women were significantly more likely to present without cirrhosis and with nonalcoholic fatty liver disease than were men. Dr. Phipps noted that they did not characterize the women in their study by menopausal status, and suggested that this would be an important thing to look at in a future prospective study because it has long been thought that estrogen confers some protection against hepatocellular carcinoma.
SAN DIEGO – Hepatocellular carcinoma is the third leading cause of cancer-related death in the United States and its incidence is increasing worldwide. While it affects men much more frequently than women, approximately 4 to 1, the differences in risk factors between men and women have never been studied.
At the annual Digestive Disease Week, Meaghan Phipps, MD, of New York–Presbyterian Hospital, described in a video interview how she and her colleagues set up a retrospective study of these differences in 5,327 patients at five large academic centers around the country. She and her colleagues found that women tended to present later, and with less severe disease, which was more likely to be treated with resection than transplantation. Women had better overall survival. Women were significantly more likely to present without cirrhosis and with nonalcoholic fatty liver disease than were men. Dr. Phipps noted that they did not characterize the women in their study by menopausal status, and suggested that this would be an important thing to look at in a future prospective study because it has long been thought that estrogen confers some protection against hepatocellular carcinoma.
SAN DIEGO – Hepatocellular carcinoma is the third leading cause of cancer-related death in the United States and its incidence is increasing worldwide. While it affects men much more frequently than women, approximately 4 to 1, the differences in risk factors between men and women have never been studied.
At the annual Digestive Disease Week, Meaghan Phipps, MD, of New York–Presbyterian Hospital, described in a video interview how she and her colleagues set up a retrospective study of these differences in 5,327 patients at five large academic centers around the country. She and her colleagues found that women tended to present later, and with less severe disease, which was more likely to be treated with resection than transplantation. Women had better overall survival. Women were significantly more likely to present without cirrhosis and with nonalcoholic fatty liver disease than were men. Dr. Phipps noted that they did not characterize the women in their study by menopausal status, and suggested that this would be an important thing to look at in a future prospective study because it has long been thought that estrogen confers some protection against hepatocellular carcinoma.
REPORTING FROM DDW 2019
Early TIPS shows superiority to standard care for advanced cirrhosis with acute variceal bleeding
Early TIPS “should therefore be preferred to the current standard of care,” reported lead author Yong Lv, MD, of the Fourth Military Medical University in Xi’an, China, and colleagues, referring to standard pharmaceutical and endoscopic therapy.
“[The current standard] approach has improved patient outcomes,” the investigators wrote in the Lancet Gastroenterology & Hepatology. “However, up to 10%-20% of patients still experience treatment failure, requiring further intensive management. In such patients, [TIPS] is successful in achieving hemostasis in 90%-100% of patients. However, 6-week mortality remains high [35%-55%]. This is probably because the severity of the underlying liver disease has worsened and additional organ dysfunction may have occurred after several failed endoscopic therapy attempts.”
Previous studies have explored earlier intervention with TIPS; however, according to the investigators, these trials were inconclusive for various reasons. For example, uncovered stents and an out-of-date control therapy were employed in a trial by Monescillo et al., while a study by Garcia-Pagan et al. lacked a primary survival endpoint and has been criticized for selection bias. “Thus, whether early TIPS confers a survival benefit in a broader population remains to be assessed,” the investigators wrote.
To this end, the investigators screened 373 patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding. Of these, 132 were eligible for inclusion based on age, disease severity, willingness to participate, comorbidities, and other factors. Patients were randomized 2:1 to receive either early TIPS or standard therapy. Within 12 hours of hospital admission for the initial bleeding episode, all patients received vasoactive drugs or endoscopic band ligation and prophylactic antibiotics. Control patients continued vasoactive drugs for up to 5 days, followed by propranolol, which was titrated to reduce resting heart rate by 25% but not less than 55 beats per minute. Elective endoscopic band ligation was performed within 1-2 weeks of initial endoscopic treatment, then approximately every 2 weeks until variceal eradication, and additionally if varices reappeared. TIPS was allowed as rescue therapy. In contrast, patients in the TIPS group underwent the procedure with conscious sedation and local anesthesia within 72 hours of diagnostic endoscopy, followed by approximately 1 week of antibiotics and vasoactive drugs. TIPS revision with angioplasty or another stent placement was performed in the event of shunt dysfunction or reemergence of portal hypertensive complications. The final dataset contained 127 patients, as 3 were excluded after randomization because of exclusionary diagnoses, 1 withdrew consent, and 1 died before TIPS placement.
The primary endpoint was transplantation-free survival. The secondary endpoints were new or worsening ascites based on ultrasound score or sustained ascites necessitating paracentesis, failure to control bleeding or rebleeding, overt hepatic encephalopathy, other complications of portal hypertension, and adverse events.
After a median follow-up of 24 months, data analysis showed a survival benefit associated with early TIPS based on multiple measures. Out of 84 patients in the TIPS group, 15 (18%) died during follow-up, compared with 15 (33%) in the control group. Actuarial transplantation-free survival was also better with TIPS instead of standard therapy at 6 weeks (99% vs. 84%), 1 year (86% vs. 73%), and 2 years (79% vs. 64%). The hazard ratio for transplantation-free survival was 0.50 in favor of TIPS (P = .04). These survival advantages were maintained regardless of hepatitis B virus status or Child-Pugh/Model for End-Stage Liver Disease score.
Similarly to transplantation-free survival, patients treated with TIPS were more likely to be free of uncontrolled bleeding or rebleeding at 1 year (89% vs. 66%) and 2 years (86% vs. 57%). The associated hazard ratio for this outcome favored early TIPS (HR, 0.26; P less than .0001), and univariate and multivariate analysis confirmed an independent protective role. In further support of superiority over standard therapy, patients treated with TIPS were more likely than those in the control group to be free of new or worsening ascites at 1 year (89% vs. 57%) and 2 years (81% vs. 54%).
No significant intergroup differences were found for rates of overt hepatic encephalopathy, hepatic hydrothorax, hepatorenal syndrome, spontaneous bacterial peritonitis, hepatocellular carcinoma, serious adverse events, or nonserious adverse events. At 1 and 3 months, patients in the TIPS group had a slight increase of median bilirubin concentrations and median international normalized ratio; however, these values normalized after 6 months. A similar temporal pattern was observed in early TIPS patients with regard to median Model for End-Stage Liver Disease score.
“[The transplantation-free survival benefit of early TIPS] was probably related to better control of factors contributing to death, such as failure to control bleeding or rebleeding or new or worsening ascites, without increasing the frequency and severity of overt hepatic encephalopathy and other adverse events,” the investigators concluded. “This study provides direct evidence and greater confidence in the recommendations of current guidelines that early TIPS should be performed in high-risk patients without contraindications.
“Future studies addressing whether early TIPS can be equally recommended in Child-Pugh B and C patients are warranted,” the investigators added.
The study was funded by the National Key Technology R&D Program, Boost Program of Xijing Hospital, Optimized Overall Project of Shaanxi Province, and National Natural Science Foundation of China. The investigators reported no conflicts of interest.
SOURCE: Lv Y et al. Lancet Gastroenterol Hepatol. 2019 May 29. doi: 10.1016/S2468-1253(19)30090-1.
Although the paper published by Lv et al. supports early transjugular intrahepatic portosystemic shunt (TIPS) for some patients with cirrhosis and variceal bleeding, Dominique Thabut, MD, and Marika Rudler, MD, pointed out that this conclusion cannot be applied to all patients.
“First ... the landscape of cirrhosis with acute variceal bleeding in China is different from that in Europe,” they wrote. “Second, the authors chose to include patients with Child-Pugh B disease without active bleeding at endoscopy [the largest group of patients in this trial]; such patients are not often seen in Europe. Last, a survival benefit was only observed when the Child-Pugh B and Child-Pugh C patients were combined, with and without active bleeding. Hence, this study does not permit conclusions to be made for patients with Child-Pugh B disease.”
“Overall, the authors should be congratulated for tackling the much debated issue of preemptive TIPS,” Dr. Thabut and Dr. Rudler wrote. “There is now no doubt about the benefit of preemptive TIPS in patients with Child-Pugh C disease. The beneficial effects of preemptive TIPS on ascites should push us to consider this approach in all patients, in the absence of contraindication.”
Dr. Tabut and Dr. Rudler, of the Institute of Cardiometabolism and Nutrition, Paris, made their remarks in an accompanying editorial (Lancet Gastroenterol Hepatol. 2019 May 29. doi: 10.1016/S2468-1253[19]30172-4). They reported no conflicts of interest.
Although the paper published by Lv et al. supports early transjugular intrahepatic portosystemic shunt (TIPS) for some patients with cirrhosis and variceal bleeding, Dominique Thabut, MD, and Marika Rudler, MD, pointed out that this conclusion cannot be applied to all patients.
“First ... the landscape of cirrhosis with acute variceal bleeding in China is different from that in Europe,” they wrote. “Second, the authors chose to include patients with Child-Pugh B disease without active bleeding at endoscopy [the largest group of patients in this trial]; such patients are not often seen in Europe. Last, a survival benefit was only observed when the Child-Pugh B and Child-Pugh C patients were combined, with and without active bleeding. Hence, this study does not permit conclusions to be made for patients with Child-Pugh B disease.”
“Overall, the authors should be congratulated for tackling the much debated issue of preemptive TIPS,” Dr. Thabut and Dr. Rudler wrote. “There is now no doubt about the benefit of preemptive TIPS in patients with Child-Pugh C disease. The beneficial effects of preemptive TIPS on ascites should push us to consider this approach in all patients, in the absence of contraindication.”
Dr. Tabut and Dr. Rudler, of the Institute of Cardiometabolism and Nutrition, Paris, made their remarks in an accompanying editorial (Lancet Gastroenterol Hepatol. 2019 May 29. doi: 10.1016/S2468-1253[19]30172-4). They reported no conflicts of interest.
Although the paper published by Lv et al. supports early transjugular intrahepatic portosystemic shunt (TIPS) for some patients with cirrhosis and variceal bleeding, Dominique Thabut, MD, and Marika Rudler, MD, pointed out that this conclusion cannot be applied to all patients.
“First ... the landscape of cirrhosis with acute variceal bleeding in China is different from that in Europe,” they wrote. “Second, the authors chose to include patients with Child-Pugh B disease without active bleeding at endoscopy [the largest group of patients in this trial]; such patients are not often seen in Europe. Last, a survival benefit was only observed when the Child-Pugh B and Child-Pugh C patients were combined, with and without active bleeding. Hence, this study does not permit conclusions to be made for patients with Child-Pugh B disease.”
“Overall, the authors should be congratulated for tackling the much debated issue of preemptive TIPS,” Dr. Thabut and Dr. Rudler wrote. “There is now no doubt about the benefit of preemptive TIPS in patients with Child-Pugh C disease. The beneficial effects of preemptive TIPS on ascites should push us to consider this approach in all patients, in the absence of contraindication.”
Dr. Tabut and Dr. Rudler, of the Institute of Cardiometabolism and Nutrition, Paris, made their remarks in an accompanying editorial (Lancet Gastroenterol Hepatol. 2019 May 29. doi: 10.1016/S2468-1253[19]30172-4). They reported no conflicts of interest.
Early TIPS “should therefore be preferred to the current standard of care,” reported lead author Yong Lv, MD, of the Fourth Military Medical University in Xi’an, China, and colleagues, referring to standard pharmaceutical and endoscopic therapy.
“[The current standard] approach has improved patient outcomes,” the investigators wrote in the Lancet Gastroenterology & Hepatology. “However, up to 10%-20% of patients still experience treatment failure, requiring further intensive management. In such patients, [TIPS] is successful in achieving hemostasis in 90%-100% of patients. However, 6-week mortality remains high [35%-55%]. This is probably because the severity of the underlying liver disease has worsened and additional organ dysfunction may have occurred after several failed endoscopic therapy attempts.”
Previous studies have explored earlier intervention with TIPS; however, according to the investigators, these trials were inconclusive for various reasons. For example, uncovered stents and an out-of-date control therapy were employed in a trial by Monescillo et al., while a study by Garcia-Pagan et al. lacked a primary survival endpoint and has been criticized for selection bias. “Thus, whether early TIPS confers a survival benefit in a broader population remains to be assessed,” the investigators wrote.
To this end, the investigators screened 373 patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding. Of these, 132 were eligible for inclusion based on age, disease severity, willingness to participate, comorbidities, and other factors. Patients were randomized 2:1 to receive either early TIPS or standard therapy. Within 12 hours of hospital admission for the initial bleeding episode, all patients received vasoactive drugs or endoscopic band ligation and prophylactic antibiotics. Control patients continued vasoactive drugs for up to 5 days, followed by propranolol, which was titrated to reduce resting heart rate by 25% but not less than 55 beats per minute. Elective endoscopic band ligation was performed within 1-2 weeks of initial endoscopic treatment, then approximately every 2 weeks until variceal eradication, and additionally if varices reappeared. TIPS was allowed as rescue therapy. In contrast, patients in the TIPS group underwent the procedure with conscious sedation and local anesthesia within 72 hours of diagnostic endoscopy, followed by approximately 1 week of antibiotics and vasoactive drugs. TIPS revision with angioplasty or another stent placement was performed in the event of shunt dysfunction or reemergence of portal hypertensive complications. The final dataset contained 127 patients, as 3 were excluded after randomization because of exclusionary diagnoses, 1 withdrew consent, and 1 died before TIPS placement.
The primary endpoint was transplantation-free survival. The secondary endpoints were new or worsening ascites based on ultrasound score or sustained ascites necessitating paracentesis, failure to control bleeding or rebleeding, overt hepatic encephalopathy, other complications of portal hypertension, and adverse events.
After a median follow-up of 24 months, data analysis showed a survival benefit associated with early TIPS based on multiple measures. Out of 84 patients in the TIPS group, 15 (18%) died during follow-up, compared with 15 (33%) in the control group. Actuarial transplantation-free survival was also better with TIPS instead of standard therapy at 6 weeks (99% vs. 84%), 1 year (86% vs. 73%), and 2 years (79% vs. 64%). The hazard ratio for transplantation-free survival was 0.50 in favor of TIPS (P = .04). These survival advantages were maintained regardless of hepatitis B virus status or Child-Pugh/Model for End-Stage Liver Disease score.
Similarly to transplantation-free survival, patients treated with TIPS were more likely to be free of uncontrolled bleeding or rebleeding at 1 year (89% vs. 66%) and 2 years (86% vs. 57%). The associated hazard ratio for this outcome favored early TIPS (HR, 0.26; P less than .0001), and univariate and multivariate analysis confirmed an independent protective role. In further support of superiority over standard therapy, patients treated with TIPS were more likely than those in the control group to be free of new or worsening ascites at 1 year (89% vs. 57%) and 2 years (81% vs. 54%).
No significant intergroup differences were found for rates of overt hepatic encephalopathy, hepatic hydrothorax, hepatorenal syndrome, spontaneous bacterial peritonitis, hepatocellular carcinoma, serious adverse events, or nonserious adverse events. At 1 and 3 months, patients in the TIPS group had a slight increase of median bilirubin concentrations and median international normalized ratio; however, these values normalized after 6 months. A similar temporal pattern was observed in early TIPS patients with regard to median Model for End-Stage Liver Disease score.
“[The transplantation-free survival benefit of early TIPS] was probably related to better control of factors contributing to death, such as failure to control bleeding or rebleeding or new or worsening ascites, without increasing the frequency and severity of overt hepatic encephalopathy and other adverse events,” the investigators concluded. “This study provides direct evidence and greater confidence in the recommendations of current guidelines that early TIPS should be performed in high-risk patients without contraindications.
“Future studies addressing whether early TIPS can be equally recommended in Child-Pugh B and C patients are warranted,” the investigators added.
The study was funded by the National Key Technology R&D Program, Boost Program of Xijing Hospital, Optimized Overall Project of Shaanxi Province, and National Natural Science Foundation of China. The investigators reported no conflicts of interest.
SOURCE: Lv Y et al. Lancet Gastroenterol Hepatol. 2019 May 29. doi: 10.1016/S2468-1253(19)30090-1.
Early TIPS “should therefore be preferred to the current standard of care,” reported lead author Yong Lv, MD, of the Fourth Military Medical University in Xi’an, China, and colleagues, referring to standard pharmaceutical and endoscopic therapy.
“[The current standard] approach has improved patient outcomes,” the investigators wrote in the Lancet Gastroenterology & Hepatology. “However, up to 10%-20% of patients still experience treatment failure, requiring further intensive management. In such patients, [TIPS] is successful in achieving hemostasis in 90%-100% of patients. However, 6-week mortality remains high [35%-55%]. This is probably because the severity of the underlying liver disease has worsened and additional organ dysfunction may have occurred after several failed endoscopic therapy attempts.”
Previous studies have explored earlier intervention with TIPS; however, according to the investigators, these trials were inconclusive for various reasons. For example, uncovered stents and an out-of-date control therapy were employed in a trial by Monescillo et al., while a study by Garcia-Pagan et al. lacked a primary survival endpoint and has been criticized for selection bias. “Thus, whether early TIPS confers a survival benefit in a broader population remains to be assessed,” the investigators wrote.
To this end, the investigators screened 373 patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding. Of these, 132 were eligible for inclusion based on age, disease severity, willingness to participate, comorbidities, and other factors. Patients were randomized 2:1 to receive either early TIPS or standard therapy. Within 12 hours of hospital admission for the initial bleeding episode, all patients received vasoactive drugs or endoscopic band ligation and prophylactic antibiotics. Control patients continued vasoactive drugs for up to 5 days, followed by propranolol, which was titrated to reduce resting heart rate by 25% but not less than 55 beats per minute. Elective endoscopic band ligation was performed within 1-2 weeks of initial endoscopic treatment, then approximately every 2 weeks until variceal eradication, and additionally if varices reappeared. TIPS was allowed as rescue therapy. In contrast, patients in the TIPS group underwent the procedure with conscious sedation and local anesthesia within 72 hours of diagnostic endoscopy, followed by approximately 1 week of antibiotics and vasoactive drugs. TIPS revision with angioplasty or another stent placement was performed in the event of shunt dysfunction or reemergence of portal hypertensive complications. The final dataset contained 127 patients, as 3 were excluded after randomization because of exclusionary diagnoses, 1 withdrew consent, and 1 died before TIPS placement.
The primary endpoint was transplantation-free survival. The secondary endpoints were new or worsening ascites based on ultrasound score or sustained ascites necessitating paracentesis, failure to control bleeding or rebleeding, overt hepatic encephalopathy, other complications of portal hypertension, and adverse events.
After a median follow-up of 24 months, data analysis showed a survival benefit associated with early TIPS based on multiple measures. Out of 84 patients in the TIPS group, 15 (18%) died during follow-up, compared with 15 (33%) in the control group. Actuarial transplantation-free survival was also better with TIPS instead of standard therapy at 6 weeks (99% vs. 84%), 1 year (86% vs. 73%), and 2 years (79% vs. 64%). The hazard ratio for transplantation-free survival was 0.50 in favor of TIPS (P = .04). These survival advantages were maintained regardless of hepatitis B virus status or Child-Pugh/Model for End-Stage Liver Disease score.
Similarly to transplantation-free survival, patients treated with TIPS were more likely to be free of uncontrolled bleeding or rebleeding at 1 year (89% vs. 66%) and 2 years (86% vs. 57%). The associated hazard ratio for this outcome favored early TIPS (HR, 0.26; P less than .0001), and univariate and multivariate analysis confirmed an independent protective role. In further support of superiority over standard therapy, patients treated with TIPS were more likely than those in the control group to be free of new or worsening ascites at 1 year (89% vs. 57%) and 2 years (81% vs. 54%).
No significant intergroup differences were found for rates of overt hepatic encephalopathy, hepatic hydrothorax, hepatorenal syndrome, spontaneous bacterial peritonitis, hepatocellular carcinoma, serious adverse events, or nonserious adverse events. At 1 and 3 months, patients in the TIPS group had a slight increase of median bilirubin concentrations and median international normalized ratio; however, these values normalized after 6 months. A similar temporal pattern was observed in early TIPS patients with regard to median Model for End-Stage Liver Disease score.
“[The transplantation-free survival benefit of early TIPS] was probably related to better control of factors contributing to death, such as failure to control bleeding or rebleeding or new or worsening ascites, without increasing the frequency and severity of overt hepatic encephalopathy and other adverse events,” the investigators concluded. “This study provides direct evidence and greater confidence in the recommendations of current guidelines that early TIPS should be performed in high-risk patients without contraindications.
“Future studies addressing whether early TIPS can be equally recommended in Child-Pugh B and C patients are warranted,” the investigators added.
The study was funded by the National Key Technology R&D Program, Boost Program of Xijing Hospital, Optimized Overall Project of Shaanxi Province, and National Natural Science Foundation of China. The investigators reported no conflicts of interest.
SOURCE: Lv Y et al. Lancet Gastroenterol Hepatol. 2019 May 29. doi: 10.1016/S2468-1253(19)30090-1.
FROM THE LANCET GASTROENTEROLOGY & HEPATOLOGY
TEG-guided topped conventional transfusion in cirrhotic patients with variceal bleeding
For patients with cirrhosis, variceal bleeding, and severe coagulopathies, the use of thromboelastography (TEG) to guide transfusion decisions significantly reduced both transfusions and rates of late rebleeding, according to the results of a randomized, open-label trial.
“With the use of TEG, only 13.3% of patients received any blood product, as compared with all patients in the conventional transfusion group,” wrote Gyanranjan Rout, MD, and associates at the All India Institute of Medical Sciences, a tertiary care center in New Delhi. The rate of rebleeding at 6 weeks was more than two-thirds lower with TEG versus the comparator group. The findings were published in the Journal of Clinical Gastroenterology.
Mortality remains high in patients with hepatic cirrhosis and variceal bleeding. Rebleeding is a major concern for these patients, and guidelines disagree on how to correct their coagulopathies so that they can undergo endoscopic treatment of varices. TEG “provides a global assessment of various factors promoting coagulation [platelets and clotting factors] and anticoagulation [fibrinolysis] in a single test,” the researchers noted.
Hence, they randomly assigned 60 adults with hepatic cirrhosis, acute variceal bleeding based on the Baveno VI consensus criteria, and significant coagulopathy (less than 50,000 platelets per mm3 or international normalized ratio under 1.8) to either conventional or TEG-guided transfusion. TEG of fresh blood was performed within 6 hours of hospital admission by using a MonoTEM-A automated thromboelastometer (Framar Hemologix, Rome).
Patients in the TEG group whose blood samples took more than 15 minutes to start forming fibrin received fresh frozen plasma (5 mL/kg of ideal body weight based on the Devine formula). Those whose maximum amplitude (an indicator of clot strength) was less than 30 mm received three units of platelets. Conventionally transfused patients received the same dose of fresh frozen plasma if their international normalized ratio was under 1.8 and the same amount of platelets if their platelet count was under 50,000 per mm3.
The groups had comparable baseline endoscopic findings, international normalized ratios, and hemoglobin and platelet levels. In the TEG group, only four (13.3%) patients underwent blood product transfusions, compared with every patient in the comparator group (P less than .001). Initial endoscopy showed similar control of bleeding between groups. At 5 days, rebleeding was noted in one (3.3%) TEG patient and four (13.3%) conventional transfusion patients (P = .167). At 42 days, this difference reached statistical significance (10% vs. 36.7%; P = .012).
The 6-week mortality rates were 13.3% in the TEG group and 26.7% in the conventional transfusion group (P = .176). The lack of statistical significance “can be explained by the fact that our study was not adequately powered to address the difference in mortality between the two study arms,” the researchers wrote.
The study excluded patients with sepsis, a major reason for coagulopathy in patients with cirrhosis. It also did not assess fibrinogen levels, and no patient received cryoprecipitate. “Our study provides initial data [supporting] the concept that TEG may help to decrease unnecessary blood transfusion and may even decrease 6-week rebleeding rate,” the researchers concluded. “However, this needs to be validated in a larger cohort of patients.”
The investigators did not disclose funding sources. They reported having no conflicts of interest.
SOURCE: Rout G et al. J Clin Gastroenterol. 2019 Apr 17. doi: 10.1097/MCG.000000000000121.
For patients with cirrhosis, variceal bleeding, and severe coagulopathies, the use of thromboelastography (TEG) to guide transfusion decisions significantly reduced both transfusions and rates of late rebleeding, according to the results of a randomized, open-label trial.
“With the use of TEG, only 13.3% of patients received any blood product, as compared with all patients in the conventional transfusion group,” wrote Gyanranjan Rout, MD, and associates at the All India Institute of Medical Sciences, a tertiary care center in New Delhi. The rate of rebleeding at 6 weeks was more than two-thirds lower with TEG versus the comparator group. The findings were published in the Journal of Clinical Gastroenterology.
Mortality remains high in patients with hepatic cirrhosis and variceal bleeding. Rebleeding is a major concern for these patients, and guidelines disagree on how to correct their coagulopathies so that they can undergo endoscopic treatment of varices. TEG “provides a global assessment of various factors promoting coagulation [platelets and clotting factors] and anticoagulation [fibrinolysis] in a single test,” the researchers noted.
Hence, they randomly assigned 60 adults with hepatic cirrhosis, acute variceal bleeding based on the Baveno VI consensus criteria, and significant coagulopathy (less than 50,000 platelets per mm3 or international normalized ratio under 1.8) to either conventional or TEG-guided transfusion. TEG of fresh blood was performed within 6 hours of hospital admission by using a MonoTEM-A automated thromboelastometer (Framar Hemologix, Rome).
Patients in the TEG group whose blood samples took more than 15 minutes to start forming fibrin received fresh frozen plasma (5 mL/kg of ideal body weight based on the Devine formula). Those whose maximum amplitude (an indicator of clot strength) was less than 30 mm received three units of platelets. Conventionally transfused patients received the same dose of fresh frozen plasma if their international normalized ratio was under 1.8 and the same amount of platelets if their platelet count was under 50,000 per mm3.
The groups had comparable baseline endoscopic findings, international normalized ratios, and hemoglobin and platelet levels. In the TEG group, only four (13.3%) patients underwent blood product transfusions, compared with every patient in the comparator group (P less than .001). Initial endoscopy showed similar control of bleeding between groups. At 5 days, rebleeding was noted in one (3.3%) TEG patient and four (13.3%) conventional transfusion patients (P = .167). At 42 days, this difference reached statistical significance (10% vs. 36.7%; P = .012).
The 6-week mortality rates were 13.3% in the TEG group and 26.7% in the conventional transfusion group (P = .176). The lack of statistical significance “can be explained by the fact that our study was not adequately powered to address the difference in mortality between the two study arms,” the researchers wrote.
The study excluded patients with sepsis, a major reason for coagulopathy in patients with cirrhosis. It also did not assess fibrinogen levels, and no patient received cryoprecipitate. “Our study provides initial data [supporting] the concept that TEG may help to decrease unnecessary blood transfusion and may even decrease 6-week rebleeding rate,” the researchers concluded. “However, this needs to be validated in a larger cohort of patients.”
The investigators did not disclose funding sources. They reported having no conflicts of interest.
SOURCE: Rout G et al. J Clin Gastroenterol. 2019 Apr 17. doi: 10.1097/MCG.000000000000121.
For patients with cirrhosis, variceal bleeding, and severe coagulopathies, the use of thromboelastography (TEG) to guide transfusion decisions significantly reduced both transfusions and rates of late rebleeding, according to the results of a randomized, open-label trial.
“With the use of TEG, only 13.3% of patients received any blood product, as compared with all patients in the conventional transfusion group,” wrote Gyanranjan Rout, MD, and associates at the All India Institute of Medical Sciences, a tertiary care center in New Delhi. The rate of rebleeding at 6 weeks was more than two-thirds lower with TEG versus the comparator group. The findings were published in the Journal of Clinical Gastroenterology.
Mortality remains high in patients with hepatic cirrhosis and variceal bleeding. Rebleeding is a major concern for these patients, and guidelines disagree on how to correct their coagulopathies so that they can undergo endoscopic treatment of varices. TEG “provides a global assessment of various factors promoting coagulation [platelets and clotting factors] and anticoagulation [fibrinolysis] in a single test,” the researchers noted.
Hence, they randomly assigned 60 adults with hepatic cirrhosis, acute variceal bleeding based on the Baveno VI consensus criteria, and significant coagulopathy (less than 50,000 platelets per mm3 or international normalized ratio under 1.8) to either conventional or TEG-guided transfusion. TEG of fresh blood was performed within 6 hours of hospital admission by using a MonoTEM-A automated thromboelastometer (Framar Hemologix, Rome).
Patients in the TEG group whose blood samples took more than 15 minutes to start forming fibrin received fresh frozen plasma (5 mL/kg of ideal body weight based on the Devine formula). Those whose maximum amplitude (an indicator of clot strength) was less than 30 mm received three units of platelets. Conventionally transfused patients received the same dose of fresh frozen plasma if their international normalized ratio was under 1.8 and the same amount of platelets if their platelet count was under 50,000 per mm3.
The groups had comparable baseline endoscopic findings, international normalized ratios, and hemoglobin and platelet levels. In the TEG group, only four (13.3%) patients underwent blood product transfusions, compared with every patient in the comparator group (P less than .001). Initial endoscopy showed similar control of bleeding between groups. At 5 days, rebleeding was noted in one (3.3%) TEG patient and four (13.3%) conventional transfusion patients (P = .167). At 42 days, this difference reached statistical significance (10% vs. 36.7%; P = .012).
The 6-week mortality rates were 13.3% in the TEG group and 26.7% in the conventional transfusion group (P = .176). The lack of statistical significance “can be explained by the fact that our study was not adequately powered to address the difference in mortality between the two study arms,” the researchers wrote.
The study excluded patients with sepsis, a major reason for coagulopathy in patients with cirrhosis. It also did not assess fibrinogen levels, and no patient received cryoprecipitate. “Our study provides initial data [supporting] the concept that TEG may help to decrease unnecessary blood transfusion and may even decrease 6-week rebleeding rate,” the researchers concluded. “However, this needs to be validated in a larger cohort of patients.”
The investigators did not disclose funding sources. They reported having no conflicts of interest.
SOURCE: Rout G et al. J Clin Gastroenterol. 2019 Apr 17. doi: 10.1097/MCG.000000000000121.
FROM THE JOURNAL OF CLINICAL GASTROENTEROLOGY
Physical activity linked to less cirrhosis-related mortality
SAN DIEGO – People who were more physically active, including those who did strength training, had significantly reduced risks of cirrhosis-related and liver cancer–related mortality, based on 26 years of prospective data from 113,000 participants in the Nurses Health Study and the Health Professionals Follow-Up Study.
Adults in the highest quintile of physical activity in the study had a 73% lower risk for cirrhosis-related death than did those in the lowest quintile, according to researchers at Massachusetts General Hospital and Harvard Medical School, Boston, who presented the study findings at Digestive Disease Week 2019.
One of the researchers, Tracey Simon, MD, MPH, of Massachusetts General Hospital, Boston, broke down the major take-home messages from the study in this video interview.
For example, vigorous activity was not necessary to improve hepatic health, she said. Walking for 4 hours per week made a big difference.
Dr. Simon has no relevant financial disclosures.
SAN DIEGO – People who were more physically active, including those who did strength training, had significantly reduced risks of cirrhosis-related and liver cancer–related mortality, based on 26 years of prospective data from 113,000 participants in the Nurses Health Study and the Health Professionals Follow-Up Study.
Adults in the highest quintile of physical activity in the study had a 73% lower risk for cirrhosis-related death than did those in the lowest quintile, according to researchers at Massachusetts General Hospital and Harvard Medical School, Boston, who presented the study findings at Digestive Disease Week 2019.
One of the researchers, Tracey Simon, MD, MPH, of Massachusetts General Hospital, Boston, broke down the major take-home messages from the study in this video interview.
For example, vigorous activity was not necessary to improve hepatic health, she said. Walking for 4 hours per week made a big difference.
Dr. Simon has no relevant financial disclosures.
SAN DIEGO – People who were more physically active, including those who did strength training, had significantly reduced risks of cirrhosis-related and liver cancer–related mortality, based on 26 years of prospective data from 113,000 participants in the Nurses Health Study and the Health Professionals Follow-Up Study.
Adults in the highest quintile of physical activity in the study had a 73% lower risk for cirrhosis-related death than did those in the lowest quintile, according to researchers at Massachusetts General Hospital and Harvard Medical School, Boston, who presented the study findings at Digestive Disease Week 2019.
One of the researchers, Tracey Simon, MD, MPH, of Massachusetts General Hospital, Boston, broke down the major take-home messages from the study in this video interview.
For example, vigorous activity was not necessary to improve hepatic health, she said. Walking for 4 hours per week made a big difference.
Dr. Simon has no relevant financial disclosures.
REPORTING FROM DDW 2019
Study finds link between intrahepatic cholestasis of pregnancy and risk of NAFLD
Patients with intrahepatic cholestasis of pregnancy (ICP) were nearly six times more likely to have a diagnosis of nonalcoholic fatty liver disease (NAFLD) than were controls, results from a retrospective, single-center study demonstrated.
“If this connection is confirmed with future studies, intrahepatic cholestasis of pregnancy may prove a novel model through which to investigate bile acid metabolism in patients with fatty liver disease,” one of the study authors, Tatyana Kushner, MD, MSCE, said during a media briefing in advance of the annual Digestive Disease Week. “This could have implications for future management of fatty liver disease. Additionally, these findings suggest that ICP patients should be seen by a liver specialist because they may go on to develop chronic liver disease or may already have already existing underlying liver disease.”
ICP is characterized by a build-up of bile acids during pregnancy and is associated with an increased risk of negative fetal outcomes and fetal death if left untreated, said Dr. Kushner, of the division of liver diseases at the Icahn School of Medicine at Mount Sinai, New York. The most notable symptom during pregnancy is severe pruritus. In what is believed to be the first study of its kind, Dr. Kushner and colleagues set out to evaluate the association between ICP and NAFLD and associated metabolic risk factors, including obesity, dyslipidemia, hypertension, and diabetes. Between January and December of 2017, they drew from the electronic medical records of a New York City health system to identify 149 pregnancies complicated by ICP and compared them to a control group of 200 pregnancies without an ICP diagnosis. The researchers used Pearson’s chi-square or Fisher’s exact test and Wilcoxon rank-sum tests to evaluate association of ICP with categorical variables and continuous variables, respectively, and unadjusted odds ratios to compare the ICP and control groups for clinically significant outcomes.
The median age of the study population was 30 years, their mean body mass index was 27.5 kg/m2, and there was a higher proportion of Hispanic women in the ICP group, compared with the control group (75% vs. 62%, respectively). Dr. Kushner and colleagues found that Hispanic women were nearly twice as likely to be diagnosed with ICP than non-Hispanic women (OR, 1.90; 95% confidence interval, 1.87-3.03). However, patients in both the ICP and control groups were similar for median age (OR, 1.02; 95% CI, 0.99-1.06), nulliparity (OR, 0.79; 95% CI, 0.48-1.30), and prevalence of hepatitis C (OR, 1.35; 95% CI, 0.08-21.67). The two groups were also similar for certain metabolic risk factors, including prevalence of obesity (OR, 1.01; 95% CI, 0.62-1.61), hypertension (OR, 0.69; 95% CI, 0.31-1.52), hemoglobin A1c greater than 5.5% (OR, 0.80; 95% CI, 0.34-1.9), and total cholesterol above 200 mg/dL (OR, 4.15; 95% CI, 0.83-20.84). Median bile acid levels were 30.6 micromoles (interquartile range, 11.6, 32.7) in the ICP group.
Compared with patients in the control group, those in the ICP group had higher median levels of alanine aminotransferase (ALT) (32 vs. 16 U/L; P less than .0001), alkaline phosphatase (181 vs. 128 U/L; P less than .0001), and total bilirubin (0.5 vs. 0.35 mg/dL; P less than .0001). ICP patients were also more likely than their counterparts to have ALT levels above 50 U/L (two times the upper limit of normal; OR, 3.22; 95% CI, 1.48-7.03), a history of biliary disease (OR, 3.29; 95% CI, 1.39-7.80), and to have evidence of steatosis on liver imaging (OR, 4.69; 95% CI, 1.68-13.12). When the researchers evaluated a diagnosis of NAFLD based on ICD-10 codes or evidence of steatosis on liver imaging, ICP patients were significantly more likely to have a diagnosis of NAFLD than controls (OR, 5.7; 95% CI, 2.08-15.65).
“We recommend additional research to look at differences in NAFLD progression in women who had NAFLD and were later diagnosed with ICP, compared to women with NAFLD who did not go on to develop ICP, because that may be a reflection of the role that bile acid metabolism plays in these particular patients,” Dr. Kushner said.
Digestive Disease Week is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
The study’s primary author was Erica Monrose, MD. The researchers reported having no financial disclosures.
SOURCE: Monrose E et al. DDW 2019, Abstract Sa1562.
Patients with intrahepatic cholestasis of pregnancy (ICP) were nearly six times more likely to have a diagnosis of nonalcoholic fatty liver disease (NAFLD) than were controls, results from a retrospective, single-center study demonstrated.
“If this connection is confirmed with future studies, intrahepatic cholestasis of pregnancy may prove a novel model through which to investigate bile acid metabolism in patients with fatty liver disease,” one of the study authors, Tatyana Kushner, MD, MSCE, said during a media briefing in advance of the annual Digestive Disease Week. “This could have implications for future management of fatty liver disease. Additionally, these findings suggest that ICP patients should be seen by a liver specialist because they may go on to develop chronic liver disease or may already have already existing underlying liver disease.”
ICP is characterized by a build-up of bile acids during pregnancy and is associated with an increased risk of negative fetal outcomes and fetal death if left untreated, said Dr. Kushner, of the division of liver diseases at the Icahn School of Medicine at Mount Sinai, New York. The most notable symptom during pregnancy is severe pruritus. In what is believed to be the first study of its kind, Dr. Kushner and colleagues set out to evaluate the association between ICP and NAFLD and associated metabolic risk factors, including obesity, dyslipidemia, hypertension, and diabetes. Between January and December of 2017, they drew from the electronic medical records of a New York City health system to identify 149 pregnancies complicated by ICP and compared them to a control group of 200 pregnancies without an ICP diagnosis. The researchers used Pearson’s chi-square or Fisher’s exact test and Wilcoxon rank-sum tests to evaluate association of ICP with categorical variables and continuous variables, respectively, and unadjusted odds ratios to compare the ICP and control groups for clinically significant outcomes.
The median age of the study population was 30 years, their mean body mass index was 27.5 kg/m2, and there was a higher proportion of Hispanic women in the ICP group, compared with the control group (75% vs. 62%, respectively). Dr. Kushner and colleagues found that Hispanic women were nearly twice as likely to be diagnosed with ICP than non-Hispanic women (OR, 1.90; 95% confidence interval, 1.87-3.03). However, patients in both the ICP and control groups were similar for median age (OR, 1.02; 95% CI, 0.99-1.06), nulliparity (OR, 0.79; 95% CI, 0.48-1.30), and prevalence of hepatitis C (OR, 1.35; 95% CI, 0.08-21.67). The two groups were also similar for certain metabolic risk factors, including prevalence of obesity (OR, 1.01; 95% CI, 0.62-1.61), hypertension (OR, 0.69; 95% CI, 0.31-1.52), hemoglobin A1c greater than 5.5% (OR, 0.80; 95% CI, 0.34-1.9), and total cholesterol above 200 mg/dL (OR, 4.15; 95% CI, 0.83-20.84). Median bile acid levels were 30.6 micromoles (interquartile range, 11.6, 32.7) in the ICP group.
Compared with patients in the control group, those in the ICP group had higher median levels of alanine aminotransferase (ALT) (32 vs. 16 U/L; P less than .0001), alkaline phosphatase (181 vs. 128 U/L; P less than .0001), and total bilirubin (0.5 vs. 0.35 mg/dL; P less than .0001). ICP patients were also more likely than their counterparts to have ALT levels above 50 U/L (two times the upper limit of normal; OR, 3.22; 95% CI, 1.48-7.03), a history of biliary disease (OR, 3.29; 95% CI, 1.39-7.80), and to have evidence of steatosis on liver imaging (OR, 4.69; 95% CI, 1.68-13.12). When the researchers evaluated a diagnosis of NAFLD based on ICD-10 codes or evidence of steatosis on liver imaging, ICP patients were significantly more likely to have a diagnosis of NAFLD than controls (OR, 5.7; 95% CI, 2.08-15.65).
“We recommend additional research to look at differences in NAFLD progression in women who had NAFLD and were later diagnosed with ICP, compared to women with NAFLD who did not go on to develop ICP, because that may be a reflection of the role that bile acid metabolism plays in these particular patients,” Dr. Kushner said.
Digestive Disease Week is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
The study’s primary author was Erica Monrose, MD. The researchers reported having no financial disclosures.
SOURCE: Monrose E et al. DDW 2019, Abstract Sa1562.
Patients with intrahepatic cholestasis of pregnancy (ICP) were nearly six times more likely to have a diagnosis of nonalcoholic fatty liver disease (NAFLD) than were controls, results from a retrospective, single-center study demonstrated.
“If this connection is confirmed with future studies, intrahepatic cholestasis of pregnancy may prove a novel model through which to investigate bile acid metabolism in patients with fatty liver disease,” one of the study authors, Tatyana Kushner, MD, MSCE, said during a media briefing in advance of the annual Digestive Disease Week. “This could have implications for future management of fatty liver disease. Additionally, these findings suggest that ICP patients should be seen by a liver specialist because they may go on to develop chronic liver disease or may already have already existing underlying liver disease.”
ICP is characterized by a build-up of bile acids during pregnancy and is associated with an increased risk of negative fetal outcomes and fetal death if left untreated, said Dr. Kushner, of the division of liver diseases at the Icahn School of Medicine at Mount Sinai, New York. The most notable symptom during pregnancy is severe pruritus. In what is believed to be the first study of its kind, Dr. Kushner and colleagues set out to evaluate the association between ICP and NAFLD and associated metabolic risk factors, including obesity, dyslipidemia, hypertension, and diabetes. Between January and December of 2017, they drew from the electronic medical records of a New York City health system to identify 149 pregnancies complicated by ICP and compared them to a control group of 200 pregnancies without an ICP diagnosis. The researchers used Pearson’s chi-square or Fisher’s exact test and Wilcoxon rank-sum tests to evaluate association of ICP with categorical variables and continuous variables, respectively, and unadjusted odds ratios to compare the ICP and control groups for clinically significant outcomes.
The median age of the study population was 30 years, their mean body mass index was 27.5 kg/m2, and there was a higher proportion of Hispanic women in the ICP group, compared with the control group (75% vs. 62%, respectively). Dr. Kushner and colleagues found that Hispanic women were nearly twice as likely to be diagnosed with ICP than non-Hispanic women (OR, 1.90; 95% confidence interval, 1.87-3.03). However, patients in both the ICP and control groups were similar for median age (OR, 1.02; 95% CI, 0.99-1.06), nulliparity (OR, 0.79; 95% CI, 0.48-1.30), and prevalence of hepatitis C (OR, 1.35; 95% CI, 0.08-21.67). The two groups were also similar for certain metabolic risk factors, including prevalence of obesity (OR, 1.01; 95% CI, 0.62-1.61), hypertension (OR, 0.69; 95% CI, 0.31-1.52), hemoglobin A1c greater than 5.5% (OR, 0.80; 95% CI, 0.34-1.9), and total cholesterol above 200 mg/dL (OR, 4.15; 95% CI, 0.83-20.84). Median bile acid levels were 30.6 micromoles (interquartile range, 11.6, 32.7) in the ICP group.
Compared with patients in the control group, those in the ICP group had higher median levels of alanine aminotransferase (ALT) (32 vs. 16 U/L; P less than .0001), alkaline phosphatase (181 vs. 128 U/L; P less than .0001), and total bilirubin (0.5 vs. 0.35 mg/dL; P less than .0001). ICP patients were also more likely than their counterparts to have ALT levels above 50 U/L (two times the upper limit of normal; OR, 3.22; 95% CI, 1.48-7.03), a history of biliary disease (OR, 3.29; 95% CI, 1.39-7.80), and to have evidence of steatosis on liver imaging (OR, 4.69; 95% CI, 1.68-13.12). When the researchers evaluated a diagnosis of NAFLD based on ICD-10 codes or evidence of steatosis on liver imaging, ICP patients were significantly more likely to have a diagnosis of NAFLD than controls (OR, 5.7; 95% CI, 2.08-15.65).
“We recommend additional research to look at differences in NAFLD progression in women who had NAFLD and were later diagnosed with ICP, compared to women with NAFLD who did not go on to develop ICP, because that may be a reflection of the role that bile acid metabolism plays in these particular patients,” Dr. Kushner said.
Digestive Disease Week is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
The study’s primary author was Erica Monrose, MD. The researchers reported having no financial disclosures.
SOURCE: Monrose E et al. DDW 2019, Abstract Sa1562.
REPORTING FROM DDW 2019