Liver Disease

From 2007 to 2017, the age-standardized cirrhosis and hepatocellular carcinoma–related mortality among individuals with diabetes in the United States increased 1.2% and 1.9% each year, respectively, 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.

[email protected]

SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.

From 2007 to 2017, the age-standardized cirrhosis and hepatocellular carcinoma–related mortality among individuals with diabetes in the United States increased 1.2% and 1.9% each year, respectively, 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.

[email protected]

SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.

From 2007 to 2017, the age-standardized cirrhosis and hepatocellular carcinoma–related mortality among individuals with diabetes in the United States increased 1.2% and 1.9% each year, respectively, 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.

[email protected]

SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.

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

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.

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.

[email protected]

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.

[email protected]

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.

[email protected]

For patients with advanced cirrhosis and acute variceal bleeding, early treatment with transjugular intrahepatic portosystemic shunt (TIPS) appears to improve transplantation-free survival, according to investigators.

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.

For patients with advanced cirrhosis and acute variceal bleeding, early treatment with transjugular intrahepatic portosystemic shunt (TIPS) appears to improve transplantation-free survival, according to investigators.

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.

For patients with advanced cirrhosis and acute variceal bleeding, early treatment with transjugular intrahepatic portosystemic shunt (TIPS) appears to improve transplantation-free survival, according to investigators.

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.

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.

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.

[email protected]

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.

[email protected]

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.

[email protected]

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 A_1c 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.

[email protected]

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 A_1c 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.

[email protected]

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 A_1c 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.

[email protected]

SOURCE: Monrose E et al. DDW 2019, Abstract Sa1562.

LOS ANGELES – More than 20 years ago, Roy Taylor, MD, began working to further understand the pathogenesis of hepatic insulin resistance in people with type 2 diabetes. It became clear that the main determinant was the amount of fat in the liver.

Vidyard Video

“If you reduced the amount of fat, the resistance went down,” Dr. Taylor, professor of medicine and metabolism at Newcastle University (England), said at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “We had a very clear picture of what might be controlling this awful matter of fasting glucose being too high.”

Then, Dr. Taylor read a study from Caterina Guidone, MD, and colleagues in Italy, which found that 1 week after patients with type 2 diabetes underwent gastric bypass surgery, their fasting plasma glucose levels became normal (Diabetes. 2006;55[7]:2025-31). “I was sitting at my desk and I thought, ‘This really changes type 2 diabetes,’ ” Dr. Taylor said. “It set in process a series of thoughts as to what was controlling what.”

This inspired ongoing work that Dr. Taylor termed the “twin-cycle hypothesis,” which postulates that chronic calorie excess leads to accumulation of liver fat, which spills over into the pancreas (Diabetologia. 2008;51[10]:1781-9).

“People with type 2 diabetes have been in positive calorie balance for a number of years,” he said. “That’s going to lead to an excess of fat in the body, and liver fat levels tend to rise with increasing body weight. If a person has normal insulin sensitivity in muscle tissue, then dealing with a meal is quite easy. Some 30 years ago, we showed using MR spectroscopy that you will have stored the carbohydrate from your breakfast in muscle, to the extent of about one-third of your breakfast, and the peak will be about 5 hours after breakfast. If you had your corn flakes at seven in the morning, by noon there will be peak in muscle, nicely stored away. However, if you happen to be insulin resistant in muscle, that doesn’t happen. There’s only one other pathway that the body can use, and that’s lipogenesis. The body can turn this very toxic substance [glucose] into safe storage [fat]. A lot of that happens in the liver. This means that people with insulin resistance tend to build up liver fat more rapidly than others.”

To test the twin-cycle hypothesis, Dr. Taylor and colleagues launched an 8-week study known as Counterpoint, which set out to induce negative calorie balance using a very low–calorie diet – about one-quarter of an average person’s daily food intake – in 11 people with diabetes (Diabetologia. 2011;54[10]:2506-14). The diet included consuming three packets of liquid formula food each day (46.4% carbohydrate, 32.5% protein, and 20.1% fat; plus vitamins, minerals, and trace elements), supplemented with portions of nonstarchy vegetables such that total energy intake was about 700 calories a day.

“On a liquid-formula diet, hunger is not a problem after the first 36 hours,” Dr. Taylor said. “This is one of the best-kept secrets of the obesity field. Our low-calorie diet was designed as something that people would be able to do in real life. We included nonstarchy vegetables to keep the bowels happy. That was important. It also fulfilled another point. People didn’t want just a liquid diet. They missed the sensation of chewing.”

The researchers also developed three-point Dixon MRI to measure pancreas and liver triacylglycerol content. “The pancreas was particularly challenging, and the full resources of the magnetic resonance physics team were needed to crack the technical problems,” he said.

After just 1 week of restricted energy intake, the fasting plasma glucose level normalized in the diabetic group, going from 9.2 to 5.9 mmol/L (P = .003), while insulin suppression of hepatic glucose output improved from 43% to 74 % (P = .003). By week 8, pancreatic triacylglycerol decreased from 8.0% to 1.1% (P = .03), and hepatic triacylglycerol content fell from 12.8% to 2.9% (P = .003).

“Within 7 days, there was a 30% drop in liver fat, and hepatic insulin resistance had disappeared,” Dr. Taylor said. “This is not a significant change – it’s a disappearance. For one individual, the amount of fat in the liver decreased from 36% to 2%. In fact, 2% [fat in the liver] was the average in the whole group. But what was simply amazing was the change in first-phase insulin response. It gradually increased throughout the 8 weeks of the study to become similar to the normal control group. We knew right away that a low-calorie diet would start correcting this central abnormality of type 2 diabetes.”

After the results from Counterpoint were published, Dr. Taylor received a “tsunami” of emails from researchers and from members of the public. “Some of the medical experts said it was a flash in the pan – interesting, but not relevant,” he said. “People with diabetes learned of it by the media, and it was talked about as a crash diet, which is unfortunate. First, it wasn’t a crash diet. This diet has to be very carefully planned, and people need to think about it in advance. They need to talk about it with their nearest and dearest, because it’s the spouse, the partner, the friends who will be supporting the individual through this journey. That’s critically important. People don’t eat as isolated individuals, they often eat as a family. We’re not talking about cure. We’re talking about reversal of the processes underpinning diabetes, with the aim of achieving remission.”

Dr. Taylor created a website devoted to providing information for clinicians and patients about the low-calorie diet and other tips on how to reverse type 2 diabetes. Soon afterward, he started to receive emails from people telling him about their experiences with the diet. “In the comfort of their own kitchens these people had lost the same amount of weight as in our trial subjects – about 33 pounds,” Dr. Taylor said. “Most of them had gotten rid of their type 2 diabetes. This was not something artificial as part of a research project. This was something that real people would do if the motivation was strong enough.”

To find out if the results from the Counterpoint study were sustainable, Dr. Taylor and his associates launched the Counterbalance study in 30 patients with type 2 diabetes who had a positive calorie imbalance and whom the researchers followed for 6 months. The 8-week diet consisted of consuming three packets of liquid formula a day comprising 43.0% carbohydrates, 34.0% protein, and 19.5% fat, as well as up to 240 g of nonstarchy vegetables (Diabetes Care. 2016;39[5]:808-15). “This was followed for a 6-month period of normal eating: Eating whatever foods they liked but in quantities to keep their weight steady,” Dr. Taylor explained. “These people gained no weight over the 6-month follow-up period. They achieved normalization of liver fat, and it remained normal.”

The patients’ hemoglobin A_1c levels fell from an average of 7.1% at baseline to less than 6.0%, and stayed at less than 6.0%. Patients who didn’t respond tended to have a longer duration of diabetes. Their beta cells had fallen to a level beyond that capable of recovery. “So the durability of the return to normal metabolic function was not in question, at least up to 6 months,” he said. “This study also gave us the opportunity to look at changes in pancreas fat. Was it likely that the liver fat was driving the pancreas fat? Yes.”

During the weight-loss period, the researchers found that there was the same degree of reduction of pancreas fat in the Counterbalance study as there’d been in the Counterpoint study. “Remarkably, it decreased slightly during the 6 months of follow-up,” Dr. Taylor said. “Those changes were significant. Type 2 diabetes seems to be caused by about a half a gram of fat within the cells of the pancreas.”

To investigate if a very low–calorie diet could be used as a routine treatment for type 2 diabetes, Dr. Taylor collaborated with his colleague, Mike Lean, MD, in launching the randomized controlled Diabetes Remission Clinical Trial (DiRECT) at 49 primary care practices in the United Kingdom (Diabetologia. 2018;61[3]:589-98). In all, 298 patients were randomized to either best-practice diabetes care alone (control arm) or with an additional evidence-based weight-management program (intervention arm). Remission was defined as having a hemoglobin A_1c level of less than 6.5% for at least 2 months without receiving glucose-lowering therapy.

At 1 year, 46% of patients in the intervention arm achieved remission, compared with 4% in the control arm (Lancet Diabetes Endocrinol. 2019;7[5]:344-55). At 2 years, 36% of patients in the intervention arm achieved remission, compared with 2% in the control arm. “The most common comment from study participants was, ‘I feel 10 years younger,’ ” Dr. Taylor said. “That’s important.”

The percentage of patients who achieved remission was 5% in those who lost less than 11 lb (5 kg), 29% in those who lost between 11 lb and 22 lb (5-10 kg), 60% in those who lost between 22 lb and 33 lb (10-15 kg), and 70% in those who lost 33 lb (15 kg) or more.

The researchers found that 62 patients achieved no remission at 12 or 24 months, 15 achieved remission at 12 but not at 24 months, and 48 achieved remission at 12 and 24 months. “We haven’t got this perfectly right yet,” Dr. Taylor said. “There is more work to do in understanding how to achieve prevention of weight gain, maybe with behavioral interventions and/or other agents such as [glucagonlike peptide–1] agonists. This is the start of a story, not the end of it.”

He and his associates also observed that delivery of fat from the liver to the rest of the body was increased in study participants who relapsed. “What effect did that have on the pancreas fat? The people who continued to be free of diabetes showed a slight fall in pancreatic fat between 5 and 24 months,” Dr. Taylor said. “In sharp contrast, the relapsers had a complete increase. Over the whole period of the study, the relapsers had not changed from baseline. It appears beyond reasonable doubt that excess pancreas fat seems to be driving the beta-cell problem underlying type 2 diabetes.”

Dr. Taylor reported that he has received lecture fees from Novartis, Lilly, and Janssen. He has also been an advisory board member for Wilmington Healthcare.

[email protected]

LOS ANGELES – More than 20 years ago, Roy Taylor, MD, began working to further understand the pathogenesis of hepatic insulin resistance in people with type 2 diabetes. It became clear that the main determinant was the amount of fat in the liver.

Vidyard Video

“If you reduced the amount of fat, the resistance went down,” Dr. Taylor, professor of medicine and metabolism at Newcastle University (England), said at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “We had a very clear picture of what might be controlling this awful matter of fasting glucose being too high.”

Then, Dr. Taylor read a study from Caterina Guidone, MD, and colleagues in Italy, which found that 1 week after patients with type 2 diabetes underwent gastric bypass surgery, their fasting plasma glucose levels became normal (Diabetes. 2006;55[7]:2025-31). “I was sitting at my desk and I thought, ‘This really changes type 2 diabetes,’ ” Dr. Taylor said. “It set in process a series of thoughts as to what was controlling what.”

This inspired ongoing work that Dr. Taylor termed the “twin-cycle hypothesis,” which postulates that chronic calorie excess leads to accumulation of liver fat, which spills over into the pancreas (Diabetologia. 2008;51[10]:1781-9).

“People with type 2 diabetes have been in positive calorie balance for a number of years,” he said. “That’s going to lead to an excess of fat in the body, and liver fat levels tend to rise with increasing body weight. If a person has normal insulin sensitivity in muscle tissue, then dealing with a meal is quite easy. Some 30 years ago, we showed using MR spectroscopy that you will have stored the carbohydrate from your breakfast in muscle, to the extent of about one-third of your breakfast, and the peak will be about 5 hours after breakfast. If you had your corn flakes at seven in the morning, by noon there will be peak in muscle, nicely stored away. However, if you happen to be insulin resistant in muscle, that doesn’t happen. There’s only one other pathway that the body can use, and that’s lipogenesis. The body can turn this very toxic substance [glucose] into safe storage [fat]. A lot of that happens in the liver. This means that people with insulin resistance tend to build up liver fat more rapidly than others.”

To test the twin-cycle hypothesis, Dr. Taylor and colleagues launched an 8-week study known as Counterpoint, which set out to induce negative calorie balance using a very low–calorie diet – about one-quarter of an average person’s daily food intake – in 11 people with diabetes (Diabetologia. 2011;54[10]:2506-14). The diet included consuming three packets of liquid formula food each day (46.4% carbohydrate, 32.5% protein, and 20.1% fat; plus vitamins, minerals, and trace elements), supplemented with portions of nonstarchy vegetables such that total energy intake was about 700 calories a day.

“On a liquid-formula diet, hunger is not a problem after the first 36 hours,” Dr. Taylor said. “This is one of the best-kept secrets of the obesity field. Our low-calorie diet was designed as something that people would be able to do in real life. We included nonstarchy vegetables to keep the bowels happy. That was important. It also fulfilled another point. People didn’t want just a liquid diet. They missed the sensation of chewing.”

The researchers also developed three-point Dixon MRI to measure pancreas and liver triacylglycerol content. “The pancreas was particularly challenging, and the full resources of the magnetic resonance physics team were needed to crack the technical problems,” he said.

After just 1 week of restricted energy intake, the fasting plasma glucose level normalized in the diabetic group, going from 9.2 to 5.9 mmol/L (P = .003), while insulin suppression of hepatic glucose output improved from 43% to 74 % (P = .003). By week 8, pancreatic triacylglycerol decreased from 8.0% to 1.1% (P = .03), and hepatic triacylglycerol content fell from 12.8% to 2.9% (P = .003).

“Within 7 days, there was a 30% drop in liver fat, and hepatic insulin resistance had disappeared,” Dr. Taylor said. “This is not a significant change – it’s a disappearance. For one individual, the amount of fat in the liver decreased from 36% to 2%. In fact, 2% [fat in the liver] was the average in the whole group. But what was simply amazing was the change in first-phase insulin response. It gradually increased throughout the 8 weeks of the study to become similar to the normal control group. We knew right away that a low-calorie diet would start correcting this central abnormality of type 2 diabetes.”

After the results from Counterpoint were published, Dr. Taylor received a “tsunami” of emails from researchers and from members of the public. “Some of the medical experts said it was a flash in the pan – interesting, but not relevant,” he said. “People with diabetes learned of it by the media, and it was talked about as a crash diet, which is unfortunate. First, it wasn’t a crash diet. This diet has to be very carefully planned, and people need to think about it in advance. They need to talk about it with their nearest and dearest, because it’s the spouse, the partner, the friends who will be supporting the individual through this journey. That’s critically important. People don’t eat as isolated individuals, they often eat as a family. We’re not talking about cure. We’re talking about reversal of the processes underpinning diabetes, with the aim of achieving remission.”

Dr. Taylor created a website devoted to providing information for clinicians and patients about the low-calorie diet and other tips on how to reverse type 2 diabetes. Soon afterward, he started to receive emails from people telling him about their experiences with the diet. “In the comfort of their own kitchens these people had lost the same amount of weight as in our trial subjects – about 33 pounds,” Dr. Taylor said. “Most of them had gotten rid of their type 2 diabetes. This was not something artificial as part of a research project. This was something that real people would do if the motivation was strong enough.”

To find out if the results from the Counterpoint study were sustainable, Dr. Taylor and his associates launched the Counterbalance study in 30 patients with type 2 diabetes who had a positive calorie imbalance and whom the researchers followed for 6 months. The 8-week diet consisted of consuming three packets of liquid formula a day comprising 43.0% carbohydrates, 34.0% protein, and 19.5% fat, as well as up to 240 g of nonstarchy vegetables (Diabetes Care. 2016;39[5]:808-15). “This was followed for a 6-month period of normal eating: Eating whatever foods they liked but in quantities to keep their weight steady,” Dr. Taylor explained. “These people gained no weight over the 6-month follow-up period. They achieved normalization of liver fat, and it remained normal.”

The patients’ hemoglobin A_1c levels fell from an average of 7.1% at baseline to less than 6.0%, and stayed at less than 6.0%. Patients who didn’t respond tended to have a longer duration of diabetes. Their beta cells had fallen to a level beyond that capable of recovery. “So the durability of the return to normal metabolic function was not in question, at least up to 6 months,” he said. “This study also gave us the opportunity to look at changes in pancreas fat. Was it likely that the liver fat was driving the pancreas fat? Yes.”

During the weight-loss period, the researchers found that there was the same degree of reduction of pancreas fat in the Counterbalance study as there’d been in the Counterpoint study. “Remarkably, it decreased slightly during the 6 months of follow-up,” Dr. Taylor said. “Those changes were significant. Type 2 diabetes seems to be caused by about a half a gram of fat within the cells of the pancreas.”

To investigate if a very low–calorie diet could be used as a routine treatment for type 2 diabetes, Dr. Taylor collaborated with his colleague, Mike Lean, MD, in launching the randomized controlled Diabetes Remission Clinical Trial (DiRECT) at 49 primary care practices in the United Kingdom (Diabetologia. 2018;61[3]:589-98). In all, 298 patients were randomized to either best-practice diabetes care alone (control arm) or with an additional evidence-based weight-management program (intervention arm). Remission was defined as having a hemoglobin A_1c level of less than 6.5% for at least 2 months without receiving glucose-lowering therapy.

At 1 year, 46% of patients in the intervention arm achieved remission, compared with 4% in the control arm (Lancet Diabetes Endocrinol. 2019;7[5]:344-55). At 2 years, 36% of patients in the intervention arm achieved remission, compared with 2% in the control arm. “The most common comment from study participants was, ‘I feel 10 years younger,’ ” Dr. Taylor said. “That’s important.”

The percentage of patients who achieved remission was 5% in those who lost less than 11 lb (5 kg), 29% in those who lost between 11 lb and 22 lb (5-10 kg), 60% in those who lost between 22 lb and 33 lb (10-15 kg), and 70% in those who lost 33 lb (15 kg) or more.

The researchers found that 62 patients achieved no remission at 12 or 24 months, 15 achieved remission at 12 but not at 24 months, and 48 achieved remission at 12 and 24 months. “We haven’t got this perfectly right yet,” Dr. Taylor said. “There is more work to do in understanding how to achieve prevention of weight gain, maybe with behavioral interventions and/or other agents such as [glucagonlike peptide–1] agonists. This is the start of a story, not the end of it.”

He and his associates also observed that delivery of fat from the liver to the rest of the body was increased in study participants who relapsed. “What effect did that have on the pancreas fat? The people who continued to be free of diabetes showed a slight fall in pancreatic fat between 5 and 24 months,” Dr. Taylor said. “In sharp contrast, the relapsers had a complete increase. Over the whole period of the study, the relapsers had not changed from baseline. It appears beyond reasonable doubt that excess pancreas fat seems to be driving the beta-cell problem underlying type 2 diabetes.”

Dr. Taylor reported that he has received lecture fees from Novartis, Lilly, and Janssen. He has also been an advisory board member for Wilmington Healthcare.

[email protected]

LOS ANGELES – More than 20 years ago, Roy Taylor, MD, began working to further understand the pathogenesis of hepatic insulin resistance in people with type 2 diabetes. It became clear that the main determinant was the amount of fat in the liver.

Vidyard Video

“If you reduced the amount of fat, the resistance went down,” Dr. Taylor, professor of medicine and metabolism at Newcastle University (England), said at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “We had a very clear picture of what might be controlling this awful matter of fasting glucose being too high.”

Then, Dr. Taylor read a study from Caterina Guidone, MD, and colleagues in Italy, which found that 1 week after patients with type 2 diabetes underwent gastric bypass surgery, their fasting plasma glucose levels became normal (Diabetes. 2006;55[7]:2025-31). “I was sitting at my desk and I thought, ‘This really changes type 2 diabetes,’ ” Dr. Taylor said. “It set in process a series of thoughts as to what was controlling what.”

This inspired ongoing work that Dr. Taylor termed the “twin-cycle hypothesis,” which postulates that chronic calorie excess leads to accumulation of liver fat, which spills over into the pancreas (Diabetologia. 2008;51[10]:1781-9).

“People with type 2 diabetes have been in positive calorie balance for a number of years,” he said. “That’s going to lead to an excess of fat in the body, and liver fat levels tend to rise with increasing body weight. If a person has normal insulin sensitivity in muscle tissue, then dealing with a meal is quite easy. Some 30 years ago, we showed using MR spectroscopy that you will have stored the carbohydrate from your breakfast in muscle, to the extent of about one-third of your breakfast, and the peak will be about 5 hours after breakfast. If you had your corn flakes at seven in the morning, by noon there will be peak in muscle, nicely stored away. However, if you happen to be insulin resistant in muscle, that doesn’t happen. There’s only one other pathway that the body can use, and that’s lipogenesis. The body can turn this very toxic substance [glucose] into safe storage [fat]. A lot of that happens in the liver. This means that people with insulin resistance tend to build up liver fat more rapidly than others.”

To test the twin-cycle hypothesis, Dr. Taylor and colleagues launched an 8-week study known as Counterpoint, which set out to induce negative calorie balance using a very low–calorie diet – about one-quarter of an average person’s daily food intake – in 11 people with diabetes (Diabetologia. 2011;54[10]:2506-14). The diet included consuming three packets of liquid formula food each day (46.4% carbohydrate, 32.5% protein, and 20.1% fat; plus vitamins, minerals, and trace elements), supplemented with portions of nonstarchy vegetables such that total energy intake was about 700 calories a day.

“On a liquid-formula diet, hunger is not a problem after the first 36 hours,” Dr. Taylor said. “This is one of the best-kept secrets of the obesity field. Our low-calorie diet was designed as something that people would be able to do in real life. We included nonstarchy vegetables to keep the bowels happy. That was important. It also fulfilled another point. People didn’t want just a liquid diet. They missed the sensation of chewing.”

The researchers also developed three-point Dixon MRI to measure pancreas and liver triacylglycerol content. “The pancreas was particularly challenging, and the full resources of the magnetic resonance physics team were needed to crack the technical problems,” he said.

After just 1 week of restricted energy intake, the fasting plasma glucose level normalized in the diabetic group, going from 9.2 to 5.9 mmol/L (P = .003), while insulin suppression of hepatic glucose output improved from 43% to 74 % (P = .003). By week 8, pancreatic triacylglycerol decreased from 8.0% to 1.1% (P = .03), and hepatic triacylglycerol content fell from 12.8% to 2.9% (P = .003).

“Within 7 days, there was a 30% drop in liver fat, and hepatic insulin resistance had disappeared,” Dr. Taylor said. “This is not a significant change – it’s a disappearance. For one individual, the amount of fat in the liver decreased from 36% to 2%. In fact, 2% [fat in the liver] was the average in the whole group. But what was simply amazing was the change in first-phase insulin response. It gradually increased throughout the 8 weeks of the study to become similar to the normal control group. We knew right away that a low-calorie diet would start correcting this central abnormality of type 2 diabetes.”

After the results from Counterpoint were published, Dr. Taylor received a “tsunami” of emails from researchers and from members of the public. “Some of the medical experts said it was a flash in the pan – interesting, but not relevant,” he said. “People with diabetes learned of it by the media, and it was talked about as a crash diet, which is unfortunate. First, it wasn’t a crash diet. This diet has to be very carefully planned, and people need to think about it in advance. They need to talk about it with their nearest and dearest, because it’s the spouse, the partner, the friends who will be supporting the individual through this journey. That’s critically important. People don’t eat as isolated individuals, they often eat as a family. We’re not talking about cure. We’re talking about reversal of the processes underpinning diabetes, with the aim of achieving remission.”

Dr. Taylor created a website devoted to providing information for clinicians and patients about the low-calorie diet and other tips on how to reverse type 2 diabetes. Soon afterward, he started to receive emails from people telling him about their experiences with the diet. “In the comfort of their own kitchens these people had lost the same amount of weight as in our trial subjects – about 33 pounds,” Dr. Taylor said. “Most of them had gotten rid of their type 2 diabetes. This was not something artificial as part of a research project. This was something that real people would do if the motivation was strong enough.”

To find out if the results from the Counterpoint study were sustainable, Dr. Taylor and his associates launched the Counterbalance study in 30 patients with type 2 diabetes who had a positive calorie imbalance and whom the researchers followed for 6 months. The 8-week diet consisted of consuming three packets of liquid formula a day comprising 43.0% carbohydrates, 34.0% protein, and 19.5% fat, as well as up to 240 g of nonstarchy vegetables (Diabetes Care. 2016;39[5]:808-15). “This was followed for a 6-month period of normal eating: Eating whatever foods they liked but in quantities to keep their weight steady,” Dr. Taylor explained. “These people gained no weight over the 6-month follow-up period. They achieved normalization of liver fat, and it remained normal.”

The patients’ hemoglobin A_1c levels fell from an average of 7.1% at baseline to less than 6.0%, and stayed at less than 6.0%. Patients who didn’t respond tended to have a longer duration of diabetes. Their beta cells had fallen to a level beyond that capable of recovery. “So the durability of the return to normal metabolic function was not in question, at least up to 6 months,” he said. “This study also gave us the opportunity to look at changes in pancreas fat. Was it likely that the liver fat was driving the pancreas fat? Yes.”

During the weight-loss period, the researchers found that there was the same degree of reduction of pancreas fat in the Counterbalance study as there’d been in the Counterpoint study. “Remarkably, it decreased slightly during the 6 months of follow-up,” Dr. Taylor said. “Those changes were significant. Type 2 diabetes seems to be caused by about a half a gram of fat within the cells of the pancreas.”

To investigate if a very low–calorie diet could be used as a routine treatment for type 2 diabetes, Dr. Taylor collaborated with his colleague, Mike Lean, MD, in launching the randomized controlled Diabetes Remission Clinical Trial (DiRECT) at 49 primary care practices in the United Kingdom (Diabetologia. 2018;61[3]:589-98). In all, 298 patients were randomized to either best-practice diabetes care alone (control arm) or with an additional evidence-based weight-management program (intervention arm). Remission was defined as having a hemoglobin A_1c level of less than 6.5% for at least 2 months without receiving glucose-lowering therapy.

At 1 year, 46% of patients in the intervention arm achieved remission, compared with 4% in the control arm (Lancet Diabetes Endocrinol. 2019;7[5]:344-55). At 2 years, 36% of patients in the intervention arm achieved remission, compared with 2% in the control arm. “The most common comment from study participants was, ‘I feel 10 years younger,’ ” Dr. Taylor said. “That’s important.”

The percentage of patients who achieved remission was 5% in those who lost less than 11 lb (5 kg), 29% in those who lost between 11 lb and 22 lb (5-10 kg), 60% in those who lost between 22 lb and 33 lb (10-15 kg), and 70% in those who lost 33 lb (15 kg) or more.

The researchers found that 62 patients achieved no remission at 12 or 24 months, 15 achieved remission at 12 but not at 24 months, and 48 achieved remission at 12 and 24 months. “We haven’t got this perfectly right yet,” Dr. Taylor said. “There is more work to do in understanding how to achieve prevention of weight gain, maybe with behavioral interventions and/or other agents such as [glucagonlike peptide–1] agonists. This is the start of a story, not the end of it.”

He and his associates also observed that delivery of fat from the liver to the rest of the body was increased in study participants who relapsed. “What effect did that have on the pancreas fat? The people who continued to be free of diabetes showed a slight fall in pancreatic fat between 5 and 24 months,” Dr. Taylor said. “In sharp contrast, the relapsers had a complete increase. Over the whole period of the study, the relapsers had not changed from baseline. It appears beyond reasonable doubt that excess pancreas fat seems to be driving the beta-cell problem underlying type 2 diabetes.”

Dr. Taylor reported that he has received lecture fees from Novartis, Lilly, and Janssen. He has also been an advisory board member for Wilmington Healthcare.

[email protected]

Hepatologists and gastroenterologists see multiple and substantial barriers to the use of palliative care in patients with end-stage liver disease, results of a recent survey show.

©Lighthaunter/Thinkstock

Cultural factors, unrealistic expectations of the patient, lack of reimbursement, and competing demands for physicians’ time were some of the barriers to palliative care cited most frequently in the survey, said the researchers, in their report on the survey results that appears in Clinical Gastroenterology and Hepatology.

Moreover, most responding physicians said they felt end-of-life advance care planning discussions take place too late in the course of illness, according to Nneka N. Ufere, MD, of the Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, and co-authors of the report.

“Multiple interventions targeted at patients, caregivers, institutions, and clinicians are needed to overcome barriers to improve the delivery of high-quality palliative and end-of-life care for patients with end-stage liver disease,” the researchers said.

Specialty palliative care can improve quality of life for patients with life-limiting conditions such as end-stage liver disease, which is associated with poor quality of life and a median survival of just two years without liver transplant, the authors said.

Advance care planning, in which patients discuss goals and care preferences in light of the expected course of illness, was a “critical component” of palliative care that can improve the quality of end-of-life care, Dr. Ufere and co-authors said.

Unfortunately, palliative care planning services are underutilized in end-stage liver disease, studies show, while rates of timely advance care planning discussions are low.

To find out why, Dr. Ufere and colleagues asked 1,238 physicians to fill out a web-based questionnaire designed to assess their perceptions of barriers to use of palliative care and barriers to timely advance care planning discussions. A total of 396 physicians (32%) completed the survey between February and April 2018.

Sixty percent were transplant hepatologists, and 79% of the survey participants said they worked in a teaching hospital, according to Dr. Ufere and co-authors, who added that no respondents had formal palliative care training.

Almost all respondents (95%) agreed that centers providing care for end-stage liver disease patients should have palliative care services, and most (86%) said they thought such patients would benefit from palliative care earlier in the course of disease.

While most (84%) agreed that a hepatologist was the best provider to discuss advance care planning with the patient, only about one-quarter (27%) said the hepatologist was best suited to provide palliative care, while most (88%) said the palliative care specialist was best for that role.

When asked about patient and caregiver barriers, nearly all respondents (95%) agreed that cultural factors that influenced palliative care perception was an issue, while 93% said patients’ unrealistic expectations was an issue.

Clinician barriers that respondents perceived included competing demands for clinicians’ time, cited by 91%, fear that palliative care might destroy the patient’s hope, cited by 82%, and the misperception that palliative care starts when active treatment ends, cited by 81%.

One potential solution to the competing demands on clinicians’ time would be development of “collaborative care models” between palliative care and hepatology services, according to Dr. Ufere and co-authors.

“Outpatient specialty palliative care visits, ideally temporally coordinated with the hepatology visits, can play a role not only in attending to symptom assessment and ACP, but also in addressing important psychosocial aspects of care, such as patient coping and well-being,” they said in their report on the survey.

Institutional barriers of note included limited reimbursement for time spent providing palliative care, cited by 76% and lack of a palliative care service, cited by nearly half (46%).

Some of the most commonly affirmed barriers to timely advance care planning discussions included insufficient training in end-of-life communication issues, and insufficient training in cultural competency issues related to the discussions.

In terms of timeliness, only 17% said advance care planning discussions happen at the right time, while 81% said they happen too late, investigators found.

Funding for the research came from the National Institutes of Health. The authors had no disclosures or conflicts of interest related to the report.

SOURCE: Ufere NN, et al. Clin Gastroenterol Hepatol. 2019 Mar 15. doi: 10.1016/j.cgh.2019.03.022.

Hepatologists and gastroenterologists see multiple and substantial barriers to the use of palliative care in patients with end-stage liver disease, results of a recent survey show.

©Lighthaunter/Thinkstock

Cultural factors, unrealistic expectations of the patient, lack of reimbursement, and competing demands for physicians’ time were some of the barriers to palliative care cited most frequently in the survey, said the researchers, in their report on the survey results that appears in Clinical Gastroenterology and Hepatology.

Moreover, most responding physicians said they felt end-of-life advance care planning discussions take place too late in the course of illness, according to Nneka N. Ufere, MD, of the Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, and co-authors of the report.

“Multiple interventions targeted at patients, caregivers, institutions, and clinicians are needed to overcome barriers to improve the delivery of high-quality palliative and end-of-life care for patients with end-stage liver disease,” the researchers said.

Specialty palliative care can improve quality of life for patients with life-limiting conditions such as end-stage liver disease, which is associated with poor quality of life and a median survival of just two years without liver transplant, the authors said.

Advance care planning, in which patients discuss goals and care preferences in light of the expected course of illness, was a “critical component” of palliative care that can improve the quality of end-of-life care, Dr. Ufere and co-authors said.

Unfortunately, palliative care planning services are underutilized in end-stage liver disease, studies show, while rates of timely advance care planning discussions are low.

To find out why, Dr. Ufere and colleagues asked 1,238 physicians to fill out a web-based questionnaire designed to assess their perceptions of barriers to use of palliative care and barriers to timely advance care planning discussions. A total of 396 physicians (32%) completed the survey between February and April 2018.

Sixty percent were transplant hepatologists, and 79% of the survey participants said they worked in a teaching hospital, according to Dr. Ufere and co-authors, who added that no respondents had formal palliative care training.

Almost all respondents (95%) agreed that centers providing care for end-stage liver disease patients should have palliative care services, and most (86%) said they thought such patients would benefit from palliative care earlier in the course of disease.

While most (84%) agreed that a hepatologist was the best provider to discuss advance care planning with the patient, only about one-quarter (27%) said the hepatologist was best suited to provide palliative care, while most (88%) said the palliative care specialist was best for that role.

When asked about patient and caregiver barriers, nearly all respondents (95%) agreed that cultural factors that influenced palliative care perception was an issue, while 93% said patients’ unrealistic expectations was an issue.

Clinician barriers that respondents perceived included competing demands for clinicians’ time, cited by 91%, fear that palliative care might destroy the patient’s hope, cited by 82%, and the misperception that palliative care starts when active treatment ends, cited by 81%.

One potential solution to the competing demands on clinicians’ time would be development of “collaborative care models” between palliative care and hepatology services, according to Dr. Ufere and co-authors.

“Outpatient specialty palliative care visits, ideally temporally coordinated with the hepatology visits, can play a role not only in attending to symptom assessment and ACP, but also in addressing important psychosocial aspects of care, such as patient coping and well-being,” they said in their report on the survey.

Institutional barriers of note included limited reimbursement for time spent providing palliative care, cited by 76% and lack of a palliative care service, cited by nearly half (46%).

Some of the most commonly affirmed barriers to timely advance care planning discussions included insufficient training in end-of-life communication issues, and insufficient training in cultural competency issues related to the discussions.

In terms of timeliness, only 17% said advance care planning discussions happen at the right time, while 81% said they happen too late, investigators found.

Funding for the research came from the National Institutes of Health. The authors had no disclosures or conflicts of interest related to the report.

SOURCE: Ufere NN, et al. Clin Gastroenterol Hepatol. 2019 Mar 15. doi: 10.1016/j.cgh.2019.03.022.

Hepatologists and gastroenterologists see multiple and substantial barriers to the use of palliative care in patients with end-stage liver disease, results of a recent survey show.

©Lighthaunter/Thinkstock

Cultural factors, unrealistic expectations of the patient, lack of reimbursement, and competing demands for physicians’ time were some of the barriers to palliative care cited most frequently in the survey, said the researchers, in their report on the survey results that appears in Clinical Gastroenterology and Hepatology.

Moreover, most responding physicians said they felt end-of-life advance care planning discussions take place too late in the course of illness, according to Nneka N. Ufere, MD, of the Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, and co-authors of the report.

“Multiple interventions targeted at patients, caregivers, institutions, and clinicians are needed to overcome barriers to improve the delivery of high-quality palliative and end-of-life care for patients with end-stage liver disease,” the researchers said.

Specialty palliative care can improve quality of life for patients with life-limiting conditions such as end-stage liver disease, which is associated with poor quality of life and a median survival of just two years without liver transplant, the authors said.

Advance care planning, in which patients discuss goals and care preferences in light of the expected course of illness, was a “critical component” of palliative care that can improve the quality of end-of-life care, Dr. Ufere and co-authors said.

Unfortunately, palliative care planning services are underutilized in end-stage liver disease, studies show, while rates of timely advance care planning discussions are low.

To find out why, Dr. Ufere and colleagues asked 1,238 physicians to fill out a web-based questionnaire designed to assess their perceptions of barriers to use of palliative care and barriers to timely advance care planning discussions. A total of 396 physicians (32%) completed the survey between February and April 2018.

Sixty percent were transplant hepatologists, and 79% of the survey participants said they worked in a teaching hospital, according to Dr. Ufere and co-authors, who added that no respondents had formal palliative care training.

Almost all respondents (95%) agreed that centers providing care for end-stage liver disease patients should have palliative care services, and most (86%) said they thought such patients would benefit from palliative care earlier in the course of disease.

While most (84%) agreed that a hepatologist was the best provider to discuss advance care planning with the patient, only about one-quarter (27%) said the hepatologist was best suited to provide palliative care, while most (88%) said the palliative care specialist was best for that role.

When asked about patient and caregiver barriers, nearly all respondents (95%) agreed that cultural factors that influenced palliative care perception was an issue, while 93% said patients’ unrealistic expectations was an issue.

Clinician barriers that respondents perceived included competing demands for clinicians’ time, cited by 91%, fear that palliative care might destroy the patient’s hope, cited by 82%, and the misperception that palliative care starts when active treatment ends, cited by 81%.

One potential solution to the competing demands on clinicians’ time would be development of “collaborative care models” between palliative care and hepatology services, according to Dr. Ufere and co-authors.

“Outpatient specialty palliative care visits, ideally temporally coordinated with the hepatology visits, can play a role not only in attending to symptom assessment and ACP, but also in addressing important psychosocial aspects of care, such as patient coping and well-being,” they said in their report on the survey.

Institutional barriers of note included limited reimbursement for time spent providing palliative care, cited by 76% and lack of a palliative care service, cited by nearly half (46%).

Some of the most commonly affirmed barriers to timely advance care planning discussions included insufficient training in end-of-life communication issues, and insufficient training in cultural competency issues related to the discussions.

In terms of timeliness, only 17% said advance care planning discussions happen at the right time, while 81% said they happen too late, investigators found.

Funding for the research came from the National Institutes of Health. The authors had no disclosures or conflicts of interest related to the report.

SOURCE: Ufere NN, et al. Clin Gastroenterol Hepatol. 2019 Mar 15. doi: 10.1016/j.cgh.2019.03.022.