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Spleen/liver stiffness ratio differentiates HCV, ALD
The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.
Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.
The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.
They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).
“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.
The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.
SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.
The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.
Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.
The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.
They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).
“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.
The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.
SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.
The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.
Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.
The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.
They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).
“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.
The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.
SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.
FROM JHEP REPORTS
USPSTF updates, reaffirms recommendation for HBV screening in pregnant women
The according to task force member Douglas K. Owens, MD, of the Veterans Affairs Palo Alto (Calif.) Health Care System and other members of the task force.
The recommendation statement, published in JAMA, was based on an evidence report and systematic review also published in JAMA. In that review, two studies of fair quality were identified; one included 155,081 infants born to HBV-positive women identified for case management through the national Perinatal Hepatitis B Prevention Program from 1994 to 2008, and the other included 4,446 infants born in a large, regional health care organization in the United States between 1997 and 2010. In both, low rates of perinatal transmission were reported for those periods – between 0.5% and 1.9% – with the rate falling over time.
In the 2009 recommendation, the USPSTF found adequate evidence that serologic testing for hepatitis B surface antigen accurately identifies HBV infection, and that interventions were effective in preventing perinatal transmission. That recommendation has been reaffirmed in the current update, with HBV screening receiving a grade of A, which is the strongest the USPSTF offers.
In a related editorial, Neil S. Silverman, MD, of the Center for Fetal Medicine and Women’s Ultrasound in Los Angeles noted several improvements in maternal HBV therapy since the publication of the original 2009 recommendation, including maternal HBV-targeted antiviral therapy during pregnancy as an adjunct to neonatal immunoprophylaxis and the ability to refer women for chronic treatment of their HBV disease to prevent long-term infection complications. The task forces also noted that HBV screening of all pregnant women is mandated by law in 26 states.
One member of the task force reported receiving grants and/or personal fees from Healthwise, another member reported receiving personal fees from UpToDate; a third reported participating in the American Association for the Study of Liver Diseases’ Hepatitis B Guidance and Hepatitis B Systematic Review Group. The evidence and review study was funded by the Agency for Healthcare Research and Quality. Dr. Silverman reported no disclosures.
SOURCes: Owens DK et al. JAMA. 2019 Jul 23. doi: 10.1001/jama.2019.9365; Henderson JT et al. JAMA. 2019 Jul 23;32(4):360-2; Silverman NS. JAMA. 2019 Jul 23;32(4):312-14.
The according to task force member Douglas K. Owens, MD, of the Veterans Affairs Palo Alto (Calif.) Health Care System and other members of the task force.
The recommendation statement, published in JAMA, was based on an evidence report and systematic review also published in JAMA. In that review, two studies of fair quality were identified; one included 155,081 infants born to HBV-positive women identified for case management through the national Perinatal Hepatitis B Prevention Program from 1994 to 2008, and the other included 4,446 infants born in a large, regional health care organization in the United States between 1997 and 2010. In both, low rates of perinatal transmission were reported for those periods – between 0.5% and 1.9% – with the rate falling over time.
In the 2009 recommendation, the USPSTF found adequate evidence that serologic testing for hepatitis B surface antigen accurately identifies HBV infection, and that interventions were effective in preventing perinatal transmission. That recommendation has been reaffirmed in the current update, with HBV screening receiving a grade of A, which is the strongest the USPSTF offers.
In a related editorial, Neil S. Silverman, MD, of the Center for Fetal Medicine and Women’s Ultrasound in Los Angeles noted several improvements in maternal HBV therapy since the publication of the original 2009 recommendation, including maternal HBV-targeted antiviral therapy during pregnancy as an adjunct to neonatal immunoprophylaxis and the ability to refer women for chronic treatment of their HBV disease to prevent long-term infection complications. The task forces also noted that HBV screening of all pregnant women is mandated by law in 26 states.
One member of the task force reported receiving grants and/or personal fees from Healthwise, another member reported receiving personal fees from UpToDate; a third reported participating in the American Association for the Study of Liver Diseases’ Hepatitis B Guidance and Hepatitis B Systematic Review Group. The evidence and review study was funded by the Agency for Healthcare Research and Quality. Dr. Silverman reported no disclosures.
SOURCes: Owens DK et al. JAMA. 2019 Jul 23. doi: 10.1001/jama.2019.9365; Henderson JT et al. JAMA. 2019 Jul 23;32(4):360-2; Silverman NS. JAMA. 2019 Jul 23;32(4):312-14.
The according to task force member Douglas K. Owens, MD, of the Veterans Affairs Palo Alto (Calif.) Health Care System and other members of the task force.
The recommendation statement, published in JAMA, was based on an evidence report and systematic review also published in JAMA. In that review, two studies of fair quality were identified; one included 155,081 infants born to HBV-positive women identified for case management through the national Perinatal Hepatitis B Prevention Program from 1994 to 2008, and the other included 4,446 infants born in a large, regional health care organization in the United States between 1997 and 2010. In both, low rates of perinatal transmission were reported for those periods – between 0.5% and 1.9% – with the rate falling over time.
In the 2009 recommendation, the USPSTF found adequate evidence that serologic testing for hepatitis B surface antigen accurately identifies HBV infection, and that interventions were effective in preventing perinatal transmission. That recommendation has been reaffirmed in the current update, with HBV screening receiving a grade of A, which is the strongest the USPSTF offers.
In a related editorial, Neil S. Silverman, MD, of the Center for Fetal Medicine and Women’s Ultrasound in Los Angeles noted several improvements in maternal HBV therapy since the publication of the original 2009 recommendation, including maternal HBV-targeted antiviral therapy during pregnancy as an adjunct to neonatal immunoprophylaxis and the ability to refer women for chronic treatment of their HBV disease to prevent long-term infection complications. The task forces also noted that HBV screening of all pregnant women is mandated by law in 26 states.
One member of the task force reported receiving grants and/or personal fees from Healthwise, another member reported receiving personal fees from UpToDate; a third reported participating in the American Association for the Study of Liver Diseases’ Hepatitis B Guidance and Hepatitis B Systematic Review Group. The evidence and review study was funded by the Agency for Healthcare Research and Quality. Dr. Silverman reported no disclosures.
SOURCes: Owens DK et al. JAMA. 2019 Jul 23. doi: 10.1001/jama.2019.9365; Henderson JT et al. JAMA. 2019 Jul 23;32(4):360-2; Silverman NS. JAMA. 2019 Jul 23;32(4):312-14.
FROM JAMA
Microbiome – Impact on health and disease
The gut microbiota influences our biology through our mucosal immune system as well as by leading to the production of bioactive small molecules. I’ll describe how gut microbiota influences colon cancer, liver disease, the production of bioactive compounds, as well as the current status and future prospects of microbiota therapeutics.
The gut microbiota may be a factor in colon cancer. Studies have shown that bacterial biofilms are associated with right-sided colon cancers in humans. More recently, a study has shown that mucosal biofilm formation is carcinogenic in an animal model, suggesting that such biofilms may play a role in the disease pathogenesis. From the standpoint of the liver, the microbiome may be a biomarker for diseases such as cirrhosis and fibrosis in patients with nonalcoholic steatohepatitis. Therapeutically, a recent study suggests that the function of gut microbiota can be altered by introducing an engineered Escherichia coli bacterial strain to treat hyperammonemia by modifying its metabolism to overproduce arginine, thereby sequestering ammonia produced by gut bacteria into the amino acids (Sci Transl Med. 2019 Jan 16;11[475]. doi: 10.1126/scitranslmed.aau7975). Drug metabolism also can be influenced by the gut microbiota and vice versa. For example, drugs such as metformin have effects on the composition of the gut microbiota in humans. In turn, the gut microbiota and its metabolites can have an influence on hepatic drug metabolism, thereby altering xenobiotic pharmacokinetics and pharmacodynamics.
The production of bioactive small molecules by bacterial metabolism is a topic of intense interest in the microbiome field. Such small molecules have been shown to act as antibiotics, neurotransmitters, immune modulators, and ligands for host receptors. Some of these small metabolites are generated through the dietary aromatic amino acids in which the bacterial enzymatic pathways are being elucidated. Such small molecules have a myriad of functions. For example, indole propionic acid, a bacterial metabolite of tryptophan, can activate the pregnane X receptor to fortify intestinal epithelial barrier function, a pathway that may have relevance to inflammatory bowel disease.
Probiotics that are found in dietary supplements represent our currently available strategy for the prevention and/or treatment of disease through the delivery of specific live microbes. However, there are limitations to their effectiveness since none have been approved for the prevention or treatment of any disease process. Via an intensive human subject study, (Cell. 2018 Sep 6;174[6]:1388-405) investigators have shown that the mucosally associated microbiota was a better biomarker for probiotic engraftment than stool was, where the response was very personalized. It’s possible that the personalized nature of probiotic engraftment may indicate that “one size may not fit all.” There will be a technical review and guideline document published by the American Gastroenterological Association early in 2020.
Currently, the only effective therapeutic modality for the treatment of a human disease by deeply altering the composition of the gut microbiota is the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). However, there is now early evidence that FMT might have efficacy in the treatment of a disease other than recurrent CDI, namely ulcerative colitis. Although the short-term risks for FMT are low and quantifiable and long-term risks are largely hypothetical, there is a need for caution and regulation in the practice of FMT. Indeed, long-term engraftment of bacterial strains from the donor into the recipient has been demonstrated. Ultimately, as the science in the microbiota field moves forward together with product development, more sophisticated microbiota-based therapeutics will be generated. During this interim period, the AGA and partner national societies have developed an FMT National Registry to gather information on FMT practice, assess effectiveness as well as short- and long-term safety, and promote scientific investigation.
In conclusion, the field of gut microbiome research is very dynamic and exciting with tremendous opportunities at the intersection between fabulous science and technology, clinical practice, and federal regulation involving the practice of FMT, concurrent in a significant interest in intellectual property and business.
Dr. Wu is the Ferdinand G. Weisbrod Professor in Gastroenterology at the University of Pennsylvania, Philadelphia. He has received research funding from Seres Therapeutics, Intercept Pharmaceuticals, and Takeda; is on the scientific advisory board for Danone and Biocodex; and does consulting for Hitachi High-Technologies. Dr. Wu made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.
The gut microbiota influences our biology through our mucosal immune system as well as by leading to the production of bioactive small molecules. I’ll describe how gut microbiota influences colon cancer, liver disease, the production of bioactive compounds, as well as the current status and future prospects of microbiota therapeutics.
The gut microbiota may be a factor in colon cancer. Studies have shown that bacterial biofilms are associated with right-sided colon cancers in humans. More recently, a study has shown that mucosal biofilm formation is carcinogenic in an animal model, suggesting that such biofilms may play a role in the disease pathogenesis. From the standpoint of the liver, the microbiome may be a biomarker for diseases such as cirrhosis and fibrosis in patients with nonalcoholic steatohepatitis. Therapeutically, a recent study suggests that the function of gut microbiota can be altered by introducing an engineered Escherichia coli bacterial strain to treat hyperammonemia by modifying its metabolism to overproduce arginine, thereby sequestering ammonia produced by gut bacteria into the amino acids (Sci Transl Med. 2019 Jan 16;11[475]. doi: 10.1126/scitranslmed.aau7975). Drug metabolism also can be influenced by the gut microbiota and vice versa. For example, drugs such as metformin have effects on the composition of the gut microbiota in humans. In turn, the gut microbiota and its metabolites can have an influence on hepatic drug metabolism, thereby altering xenobiotic pharmacokinetics and pharmacodynamics.
The production of bioactive small molecules by bacterial metabolism is a topic of intense interest in the microbiome field. Such small molecules have been shown to act as antibiotics, neurotransmitters, immune modulators, and ligands for host receptors. Some of these small metabolites are generated through the dietary aromatic amino acids in which the bacterial enzymatic pathways are being elucidated. Such small molecules have a myriad of functions. For example, indole propionic acid, a bacterial metabolite of tryptophan, can activate the pregnane X receptor to fortify intestinal epithelial barrier function, a pathway that may have relevance to inflammatory bowel disease.
Probiotics that are found in dietary supplements represent our currently available strategy for the prevention and/or treatment of disease through the delivery of specific live microbes. However, there are limitations to their effectiveness since none have been approved for the prevention or treatment of any disease process. Via an intensive human subject study, (Cell. 2018 Sep 6;174[6]:1388-405) investigators have shown that the mucosally associated microbiota was a better biomarker for probiotic engraftment than stool was, where the response was very personalized. It’s possible that the personalized nature of probiotic engraftment may indicate that “one size may not fit all.” There will be a technical review and guideline document published by the American Gastroenterological Association early in 2020.
Currently, the only effective therapeutic modality for the treatment of a human disease by deeply altering the composition of the gut microbiota is the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). However, there is now early evidence that FMT might have efficacy in the treatment of a disease other than recurrent CDI, namely ulcerative colitis. Although the short-term risks for FMT are low and quantifiable and long-term risks are largely hypothetical, there is a need for caution and regulation in the practice of FMT. Indeed, long-term engraftment of bacterial strains from the donor into the recipient has been demonstrated. Ultimately, as the science in the microbiota field moves forward together with product development, more sophisticated microbiota-based therapeutics will be generated. During this interim period, the AGA and partner national societies have developed an FMT National Registry to gather information on FMT practice, assess effectiveness as well as short- and long-term safety, and promote scientific investigation.
In conclusion, the field of gut microbiome research is very dynamic and exciting with tremendous opportunities at the intersection between fabulous science and technology, clinical practice, and federal regulation involving the practice of FMT, concurrent in a significant interest in intellectual property and business.
Dr. Wu is the Ferdinand G. Weisbrod Professor in Gastroenterology at the University of Pennsylvania, Philadelphia. He has received research funding from Seres Therapeutics, Intercept Pharmaceuticals, and Takeda; is on the scientific advisory board for Danone and Biocodex; and does consulting for Hitachi High-Technologies. Dr. Wu made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.
The gut microbiota influences our biology through our mucosal immune system as well as by leading to the production of bioactive small molecules. I’ll describe how gut microbiota influences colon cancer, liver disease, the production of bioactive compounds, as well as the current status and future prospects of microbiota therapeutics.
The gut microbiota may be a factor in colon cancer. Studies have shown that bacterial biofilms are associated with right-sided colon cancers in humans. More recently, a study has shown that mucosal biofilm formation is carcinogenic in an animal model, suggesting that such biofilms may play a role in the disease pathogenesis. From the standpoint of the liver, the microbiome may be a biomarker for diseases such as cirrhosis and fibrosis in patients with nonalcoholic steatohepatitis. Therapeutically, a recent study suggests that the function of gut microbiota can be altered by introducing an engineered Escherichia coli bacterial strain to treat hyperammonemia by modifying its metabolism to overproduce arginine, thereby sequestering ammonia produced by gut bacteria into the amino acids (Sci Transl Med. 2019 Jan 16;11[475]. doi: 10.1126/scitranslmed.aau7975). Drug metabolism also can be influenced by the gut microbiota and vice versa. For example, drugs such as metformin have effects on the composition of the gut microbiota in humans. In turn, the gut microbiota and its metabolites can have an influence on hepatic drug metabolism, thereby altering xenobiotic pharmacokinetics and pharmacodynamics.
The production of bioactive small molecules by bacterial metabolism is a topic of intense interest in the microbiome field. Such small molecules have been shown to act as antibiotics, neurotransmitters, immune modulators, and ligands for host receptors. Some of these small metabolites are generated through the dietary aromatic amino acids in which the bacterial enzymatic pathways are being elucidated. Such small molecules have a myriad of functions. For example, indole propionic acid, a bacterial metabolite of tryptophan, can activate the pregnane X receptor to fortify intestinal epithelial barrier function, a pathway that may have relevance to inflammatory bowel disease.
Probiotics that are found in dietary supplements represent our currently available strategy for the prevention and/or treatment of disease through the delivery of specific live microbes. However, there are limitations to their effectiveness since none have been approved for the prevention or treatment of any disease process. Via an intensive human subject study, (Cell. 2018 Sep 6;174[6]:1388-405) investigators have shown that the mucosally associated microbiota was a better biomarker for probiotic engraftment than stool was, where the response was very personalized. It’s possible that the personalized nature of probiotic engraftment may indicate that “one size may not fit all.” There will be a technical review and guideline document published by the American Gastroenterological Association early in 2020.
Currently, the only effective therapeutic modality for the treatment of a human disease by deeply altering the composition of the gut microbiota is the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). However, there is now early evidence that FMT might have efficacy in the treatment of a disease other than recurrent CDI, namely ulcerative colitis. Although the short-term risks for FMT are low and quantifiable and long-term risks are largely hypothetical, there is a need for caution and regulation in the practice of FMT. Indeed, long-term engraftment of bacterial strains from the donor into the recipient has been demonstrated. Ultimately, as the science in the microbiota field moves forward together with product development, more sophisticated microbiota-based therapeutics will be generated. During this interim period, the AGA and partner national societies have developed an FMT National Registry to gather information on FMT practice, assess effectiveness as well as short- and long-term safety, and promote scientific investigation.
In conclusion, the field of gut microbiome research is very dynamic and exciting with tremendous opportunities at the intersection between fabulous science and technology, clinical practice, and federal regulation involving the practice of FMT, concurrent in a significant interest in intellectual property and business.
Dr. Wu is the Ferdinand G. Weisbrod Professor in Gastroenterology at the University of Pennsylvania, Philadelphia. He has received research funding from Seres Therapeutics, Intercept Pharmaceuticals, and Takeda; is on the scientific advisory board for Danone and Biocodex; and does consulting for Hitachi High-Technologies. Dr. Wu made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.
The changing epidemiology of hepatocellular carcinoma
Three main changes characterize the secular trends in the incidence of hepatocellular carcinoma (HCC) in the United States. First, the overall incidence and mortality rates of HCC have been rising for the past 3 decades. Second, Hispanics are disproportionately affected by the HCC increase and have recently surpassed Asian Americans as the racial/ethnic group at highest HCC risk. Third, Southern and Western states have registered higher incidence rates of HCC than did the rest of the country, with Texas having the highest rates.
There are significant racial/ethnic differences in the population distribution of HCC risk factors, notably the disproportionately high prevalence of metabolic syndrome (e.g., obesity, abdominal obesity, and diabetes) and nonalcoholic fatty liver disease (NAFLD) in Hispanics. This observation may explain some of the findings in the secular trends of HCC described above. Most, but not all, studies have reported modest increases in relative risk of HCC in persons with obesity as measured by body mass index. However, studies investigating more specific obesity measures such as obesity in early adulthood or abdominal obesity reported higher and more consistent HCC risk than did those using body mass index. Hispanics have been shown to have a higher proportion of abdominal, especially visceral fat, than African Americans. The prevalence of NAFLD in the United States has doubled over the last 2 decades, and is estimated to affect 15%-20% of adults overall, but up to 30% in adult Texas Hispanics. Recently, a large cohort study including 296,707 patients with NAFLD and an equal number of matched controls without NAFLD from 130 facilities of the Department of Veterans Affairs found that patients with NAFLD had several-fold higher HCC risk than controls. The study also reported that HCC incidence rates for patients with NAFLD ranged from 1.6 to 23.7 per 1000 person-years, with the highest risk among older Hispanic patients with cirrhosis. Approximately 20% of patients with NAFLD and HCC had no evidence of cirrhosis. Lastly, type 2 diabetes, a condition that also is disproportionately higher in Hispanics than in other racial/ethnic groups in the United States has been consistently associated with an approximately twofold increase in the risk of HCC.
Risk factors for cirrhosis and HCC in contemporary clinical practice, and to a lesser extent, in the general population have shifted from active viral hepatitis to resolved hepatitis C infection or adequately suppressed hepatitis B infection as well as alcoholic liver disease and NAFLD. The shift from uncommon risk factors that carry a considerable increased risk of cirrhosis and HCC (active hepatitis C virus, hepatitis B virus) to more common but weaker risk factors (alcohol, NAFLD) is likely to result in a larger pool of chronic liver disease patients at risk for developing cirrhosis and HCC. However, given that the relative risk of HCC is lower with these emerging risk factors, it also will become increasingly difficult to define the highest-risk groups in need of interventions or monitoring. Therefore, there is a clear need for risk-stratification tools for cirrhosis and HCC in patients with HCV and a sustained virologic response, adequate HBV suppression, alcoholic liver disease, and NAFLD.
Dr. El-Serag is with the section of gastroenterology and hepatology, department of medicine, Baylor College of Medicine, Houston. Dr. El-Serag made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.
Three main changes characterize the secular trends in the incidence of hepatocellular carcinoma (HCC) in the United States. First, the overall incidence and mortality rates of HCC have been rising for the past 3 decades. Second, Hispanics are disproportionately affected by the HCC increase and have recently surpassed Asian Americans as the racial/ethnic group at highest HCC risk. Third, Southern and Western states have registered higher incidence rates of HCC than did the rest of the country, with Texas having the highest rates.
There are significant racial/ethnic differences in the population distribution of HCC risk factors, notably the disproportionately high prevalence of metabolic syndrome (e.g., obesity, abdominal obesity, and diabetes) and nonalcoholic fatty liver disease (NAFLD) in Hispanics. This observation may explain some of the findings in the secular trends of HCC described above. Most, but not all, studies have reported modest increases in relative risk of HCC in persons with obesity as measured by body mass index. However, studies investigating more specific obesity measures such as obesity in early adulthood or abdominal obesity reported higher and more consistent HCC risk than did those using body mass index. Hispanics have been shown to have a higher proportion of abdominal, especially visceral fat, than African Americans. The prevalence of NAFLD in the United States has doubled over the last 2 decades, and is estimated to affect 15%-20% of adults overall, but up to 30% in adult Texas Hispanics. Recently, a large cohort study including 296,707 patients with NAFLD and an equal number of matched controls without NAFLD from 130 facilities of the Department of Veterans Affairs found that patients with NAFLD had several-fold higher HCC risk than controls. The study also reported that HCC incidence rates for patients with NAFLD ranged from 1.6 to 23.7 per 1000 person-years, with the highest risk among older Hispanic patients with cirrhosis. Approximately 20% of patients with NAFLD and HCC had no evidence of cirrhosis. Lastly, type 2 diabetes, a condition that also is disproportionately higher in Hispanics than in other racial/ethnic groups in the United States has been consistently associated with an approximately twofold increase in the risk of HCC.
Risk factors for cirrhosis and HCC in contemporary clinical practice, and to a lesser extent, in the general population have shifted from active viral hepatitis to resolved hepatitis C infection or adequately suppressed hepatitis B infection as well as alcoholic liver disease and NAFLD. The shift from uncommon risk factors that carry a considerable increased risk of cirrhosis and HCC (active hepatitis C virus, hepatitis B virus) to more common but weaker risk factors (alcohol, NAFLD) is likely to result in a larger pool of chronic liver disease patients at risk for developing cirrhosis and HCC. However, given that the relative risk of HCC is lower with these emerging risk factors, it also will become increasingly difficult to define the highest-risk groups in need of interventions or monitoring. Therefore, there is a clear need for risk-stratification tools for cirrhosis and HCC in patients with HCV and a sustained virologic response, adequate HBV suppression, alcoholic liver disease, and NAFLD.
Dr. El-Serag is with the section of gastroenterology and hepatology, department of medicine, Baylor College of Medicine, Houston. Dr. El-Serag made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.
Three main changes characterize the secular trends in the incidence of hepatocellular carcinoma (HCC) in the United States. First, the overall incidence and mortality rates of HCC have been rising for the past 3 decades. Second, Hispanics are disproportionately affected by the HCC increase and have recently surpassed Asian Americans as the racial/ethnic group at highest HCC risk. Third, Southern and Western states have registered higher incidence rates of HCC than did the rest of the country, with Texas having the highest rates.
There are significant racial/ethnic differences in the population distribution of HCC risk factors, notably the disproportionately high prevalence of metabolic syndrome (e.g., obesity, abdominal obesity, and diabetes) and nonalcoholic fatty liver disease (NAFLD) in Hispanics. This observation may explain some of the findings in the secular trends of HCC described above. Most, but not all, studies have reported modest increases in relative risk of HCC in persons with obesity as measured by body mass index. However, studies investigating more specific obesity measures such as obesity in early adulthood or abdominal obesity reported higher and more consistent HCC risk than did those using body mass index. Hispanics have been shown to have a higher proportion of abdominal, especially visceral fat, than African Americans. The prevalence of NAFLD in the United States has doubled over the last 2 decades, and is estimated to affect 15%-20% of adults overall, but up to 30% in adult Texas Hispanics. Recently, a large cohort study including 296,707 patients with NAFLD and an equal number of matched controls without NAFLD from 130 facilities of the Department of Veterans Affairs found that patients with NAFLD had several-fold higher HCC risk than controls. The study also reported that HCC incidence rates for patients with NAFLD ranged from 1.6 to 23.7 per 1000 person-years, with the highest risk among older Hispanic patients with cirrhosis. Approximately 20% of patients with NAFLD and HCC had no evidence of cirrhosis. Lastly, type 2 diabetes, a condition that also is disproportionately higher in Hispanics than in other racial/ethnic groups in the United States has been consistently associated with an approximately twofold increase in the risk of HCC.
Risk factors for cirrhosis and HCC in contemporary clinical practice, and to a lesser extent, in the general population have shifted from active viral hepatitis to resolved hepatitis C infection or adequately suppressed hepatitis B infection as well as alcoholic liver disease and NAFLD. The shift from uncommon risk factors that carry a considerable increased risk of cirrhosis and HCC (active hepatitis C virus, hepatitis B virus) to more common but weaker risk factors (alcohol, NAFLD) is likely to result in a larger pool of chronic liver disease patients at risk for developing cirrhosis and HCC. However, given that the relative risk of HCC is lower with these emerging risk factors, it also will become increasingly difficult to define the highest-risk groups in need of interventions or monitoring. Therefore, there is a clear need for risk-stratification tools for cirrhosis and HCC in patients with HCV and a sustained virologic response, adequate HBV suppression, alcoholic liver disease, and NAFLD.
Dr. El-Serag is with the section of gastroenterology and hepatology, department of medicine, Baylor College of Medicine, Houston. Dr. El-Serag made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.
Louisiana HCV program cuts costs – and hassles
Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.
The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.
State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.
“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”
The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.
“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”
He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”
Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.
Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.
“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”
Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv
Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.
The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.
State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.
“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”
The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.
“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”
He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”
Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.
Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.
“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”
Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv
Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.
The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.
State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.
“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”
The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.
“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”
He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”
Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.
Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.
“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”
Visit the AGA GI Patient Center for information to share with your patients about hepatitis C at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv
HCC surveillance after anti-HCV therapy cost effective only for patients with cirrhosis
For patients with hepatitis C virus (HCV)–related cirrhosis (F4), but not those with advanced fibrosis (F3), hepatocellular carcinoma (HCC) surveillance after a sustained virologic response (SVR) is cost effective, according to investigators.
Current international guidelines call for HCC surveillance among all patients with advanced fibrosis (F3) or cirrhosis (F4) who have achieved SVR, but this is “very unlikely to be cost effective,” reported lead author Hooman Farhang Zangneh, MD, of Toronto General Hospital and colleagues. “HCV-related HCC rarely occurs in patients without cirrhosis,” the investigators explained in Clinical Gastroenterology and Hepatology. “With cirrhosis present, HCC incidence is 1.4% to 4.9% per year. If found early, options for curative therapy include radiofrequency ablation (RFA), surgical resection, and liver transplantation.”
The investigators developed a Markov model to determine which at-risk patients could undergo surveillance while remaining below willingness-to-pay thresholds. Specifically, cost-effectiveness was assessed for ultrasound screenings annually (every year) or biannually (twice a year) among patients with advanced fibrosis (F3) or compensated cirrhosis (F4) who were aged 50 years and had an SVR. Relevant data were drawn from expert opinions, medical literature, and Canada Life Tables. Various HCC incidence rates were tested, including a constant annual rate, rates based on type of antiviral treatment (direct-acting and interferon-based therapies), others based on stage of fibrosis, and another that increased with age. The model was validated by applying it to patients with F3 or F4 fibrosis who had not yet achieved an SVR. All monetary values were reported in 2015 Canadian dollars.
Representative of current guidelines, the investigators first tested costs when conducting surveillance among all patients with F3 or F4 fibrosis with an assumed constant HCC annual incidence rate of 0.5%. Biannual ultrasound surveillance after SVR caught more cases of HCC still in a curable stage (78%) than no surveillance (29%); however, false-positives were relatively common at 21.8% and 15.7% for biannual and annual surveillance, respectively. The investigators noted that in the real world, some of these false-positives are not detected by more advanced imaging, so patients go on to receive unnecessary RFA, which incurs additional costs. Partly for this reason, while biannual surveillance was more effective, it was also more expensive, with an incremental cost-effectiveness ratio (ICER) of $106,792 per quality-adjusted life-years (QALY), compared with $72,105 per QALY for annual surveillance.
Including only patients with F3 fibrosis after interferon-based therapy, using an HCC incidence of 0.23%, biannual and annual ICERs rose to $484,160 and $204,708 per QALY, respectively, both of which exceed standard willingness-to-pay thresholds. In comparison, annual and biannual ICERs were at most $55,850 and $42,305 per QALY, respectively, among patients with cirrhosis before interferon-induced SVR, using an HCC incidence rate of up to 1.39% per year.
“These results suggest that biannual (or annual) HCC surveillance is likely to be cost effective for patients with cirrhosis, but not for patients with F3 fibrosis before SVR,” the investigators wrote.
Costs for HCC surveillance among cirrhosis patients after direct-acting antiviral-induced SVR were still lower, at $43,229 and $34,307 per QALY, which were far lower than costs for patients with F3 fibrosis, which were $188,157 and $111,667 per QALY.
Focusing on the evident savings associated with surveillance of patients with cirrhosis, the investigators tested two diagnostic thresholds within this population with the aim of reducing costs further. They found that surveillance of patients with a pretreatment aspartate aminotransferase to platelet ratio index (APRI) greater than 2.0 (HCC incidence, 0.89%) was associated with biannual and annual ICERs of $48,729 and $37,806 per QALY, respectively, but when APRI was less than 2.0 (HCC incidence, 0.093%), surveillance was less effective and more expensive than no surveillance at all. A similar trend was found for an FIB-4 threshold of 3.25.
Employment of age-stratified risk of HCC also reduced costs of screening for patients with cirrhosis. With this strategy, ICER was $48,432 per QALY for biannual surveillance and $37,201 per QALY for annual surveillance.
“These data suggest that, if we assume HCC incidence increases with age, biannual or annual surveillance will be cost effective for the vast majority, if not all, patients with cirrhosis before SVR,” the investigators wrote.
“Our analysis suggests that HCC surveillance is very unlikely to be cost effective in patients with F3 fibrosis, whereas both annual and biannual modalities are likely to be cost effective at standard willingness-to-pay thresholds for patients with cirrhosis compared with no surveillance,” the investigators wrote.
“Additional long-term follow-up data are required to help identify patients at highest risk of HCC after SVR to tailor surveillance guidelines,” the investigators concluded.
The study was funded by the Toronto Centre for Liver Disease. The investigators declared no conflicts of interest.
This story was updated on 7/12/2019.
SOURCE: Zangneh et al. Clin Gastroenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.018.
For patients with hepatitis C virus (HCV)–related cirrhosis (F4), but not those with advanced fibrosis (F3), hepatocellular carcinoma (HCC) surveillance after a sustained virologic response (SVR) is cost effective, according to investigators.
Current international guidelines call for HCC surveillance among all patients with advanced fibrosis (F3) or cirrhosis (F4) who have achieved SVR, but this is “very unlikely to be cost effective,” reported lead author Hooman Farhang Zangneh, MD, of Toronto General Hospital and colleagues. “HCV-related HCC rarely occurs in patients without cirrhosis,” the investigators explained in Clinical Gastroenterology and Hepatology. “With cirrhosis present, HCC incidence is 1.4% to 4.9% per year. If found early, options for curative therapy include radiofrequency ablation (RFA), surgical resection, and liver transplantation.”
The investigators developed a Markov model to determine which at-risk patients could undergo surveillance while remaining below willingness-to-pay thresholds. Specifically, cost-effectiveness was assessed for ultrasound screenings annually (every year) or biannually (twice a year) among patients with advanced fibrosis (F3) or compensated cirrhosis (F4) who were aged 50 years and had an SVR. Relevant data were drawn from expert opinions, medical literature, and Canada Life Tables. Various HCC incidence rates were tested, including a constant annual rate, rates based on type of antiviral treatment (direct-acting and interferon-based therapies), others based on stage of fibrosis, and another that increased with age. The model was validated by applying it to patients with F3 or F4 fibrosis who had not yet achieved an SVR. All monetary values were reported in 2015 Canadian dollars.
Representative of current guidelines, the investigators first tested costs when conducting surveillance among all patients with F3 or F4 fibrosis with an assumed constant HCC annual incidence rate of 0.5%. Biannual ultrasound surveillance after SVR caught more cases of HCC still in a curable stage (78%) than no surveillance (29%); however, false-positives were relatively common at 21.8% and 15.7% for biannual and annual surveillance, respectively. The investigators noted that in the real world, some of these false-positives are not detected by more advanced imaging, so patients go on to receive unnecessary RFA, which incurs additional costs. Partly for this reason, while biannual surveillance was more effective, it was also more expensive, with an incremental cost-effectiveness ratio (ICER) of $106,792 per quality-adjusted life-years (QALY), compared with $72,105 per QALY for annual surveillance.
Including only patients with F3 fibrosis after interferon-based therapy, using an HCC incidence of 0.23%, biannual and annual ICERs rose to $484,160 and $204,708 per QALY, respectively, both of which exceed standard willingness-to-pay thresholds. In comparison, annual and biannual ICERs were at most $55,850 and $42,305 per QALY, respectively, among patients with cirrhosis before interferon-induced SVR, using an HCC incidence rate of up to 1.39% per year.
“These results suggest that biannual (or annual) HCC surveillance is likely to be cost effective for patients with cirrhosis, but not for patients with F3 fibrosis before SVR,” the investigators wrote.
Costs for HCC surveillance among cirrhosis patients after direct-acting antiviral-induced SVR were still lower, at $43,229 and $34,307 per QALY, which were far lower than costs for patients with F3 fibrosis, which were $188,157 and $111,667 per QALY.
Focusing on the evident savings associated with surveillance of patients with cirrhosis, the investigators tested two diagnostic thresholds within this population with the aim of reducing costs further. They found that surveillance of patients with a pretreatment aspartate aminotransferase to platelet ratio index (APRI) greater than 2.0 (HCC incidence, 0.89%) was associated with biannual and annual ICERs of $48,729 and $37,806 per QALY, respectively, but when APRI was less than 2.0 (HCC incidence, 0.093%), surveillance was less effective and more expensive than no surveillance at all. A similar trend was found for an FIB-4 threshold of 3.25.
Employment of age-stratified risk of HCC also reduced costs of screening for patients with cirrhosis. With this strategy, ICER was $48,432 per QALY for biannual surveillance and $37,201 per QALY for annual surveillance.
“These data suggest that, if we assume HCC incidence increases with age, biannual or annual surveillance will be cost effective for the vast majority, if not all, patients with cirrhosis before SVR,” the investigators wrote.
“Our analysis suggests that HCC surveillance is very unlikely to be cost effective in patients with F3 fibrosis, whereas both annual and biannual modalities are likely to be cost effective at standard willingness-to-pay thresholds for patients with cirrhosis compared with no surveillance,” the investigators wrote.
“Additional long-term follow-up data are required to help identify patients at highest risk of HCC after SVR to tailor surveillance guidelines,” the investigators concluded.
The study was funded by the Toronto Centre for Liver Disease. The investigators declared no conflicts of interest.
This story was updated on 7/12/2019.
SOURCE: Zangneh et al. Clin Gastroenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.018.
For patients with hepatitis C virus (HCV)–related cirrhosis (F4), but not those with advanced fibrosis (F3), hepatocellular carcinoma (HCC) surveillance after a sustained virologic response (SVR) is cost effective, according to investigators.
Current international guidelines call for HCC surveillance among all patients with advanced fibrosis (F3) or cirrhosis (F4) who have achieved SVR, but this is “very unlikely to be cost effective,” reported lead author Hooman Farhang Zangneh, MD, of Toronto General Hospital and colleagues. “HCV-related HCC rarely occurs in patients without cirrhosis,” the investigators explained in Clinical Gastroenterology and Hepatology. “With cirrhosis present, HCC incidence is 1.4% to 4.9% per year. If found early, options for curative therapy include radiofrequency ablation (RFA), surgical resection, and liver transplantation.”
The investigators developed a Markov model to determine which at-risk patients could undergo surveillance while remaining below willingness-to-pay thresholds. Specifically, cost-effectiveness was assessed for ultrasound screenings annually (every year) or biannually (twice a year) among patients with advanced fibrosis (F3) or compensated cirrhosis (F4) who were aged 50 years and had an SVR. Relevant data were drawn from expert opinions, medical literature, and Canada Life Tables. Various HCC incidence rates were tested, including a constant annual rate, rates based on type of antiviral treatment (direct-acting and interferon-based therapies), others based on stage of fibrosis, and another that increased with age. The model was validated by applying it to patients with F3 or F4 fibrosis who had not yet achieved an SVR. All monetary values were reported in 2015 Canadian dollars.
Representative of current guidelines, the investigators first tested costs when conducting surveillance among all patients with F3 or F4 fibrosis with an assumed constant HCC annual incidence rate of 0.5%. Biannual ultrasound surveillance after SVR caught more cases of HCC still in a curable stage (78%) than no surveillance (29%); however, false-positives were relatively common at 21.8% and 15.7% for biannual and annual surveillance, respectively. The investigators noted that in the real world, some of these false-positives are not detected by more advanced imaging, so patients go on to receive unnecessary RFA, which incurs additional costs. Partly for this reason, while biannual surveillance was more effective, it was also more expensive, with an incremental cost-effectiveness ratio (ICER) of $106,792 per quality-adjusted life-years (QALY), compared with $72,105 per QALY for annual surveillance.
Including only patients with F3 fibrosis after interferon-based therapy, using an HCC incidence of 0.23%, biannual and annual ICERs rose to $484,160 and $204,708 per QALY, respectively, both of which exceed standard willingness-to-pay thresholds. In comparison, annual and biannual ICERs were at most $55,850 and $42,305 per QALY, respectively, among patients with cirrhosis before interferon-induced SVR, using an HCC incidence rate of up to 1.39% per year.
“These results suggest that biannual (or annual) HCC surveillance is likely to be cost effective for patients with cirrhosis, but not for patients with F3 fibrosis before SVR,” the investigators wrote.
Costs for HCC surveillance among cirrhosis patients after direct-acting antiviral-induced SVR were still lower, at $43,229 and $34,307 per QALY, which were far lower than costs for patients with F3 fibrosis, which were $188,157 and $111,667 per QALY.
Focusing on the evident savings associated with surveillance of patients with cirrhosis, the investigators tested two diagnostic thresholds within this population with the aim of reducing costs further. They found that surveillance of patients with a pretreatment aspartate aminotransferase to platelet ratio index (APRI) greater than 2.0 (HCC incidence, 0.89%) was associated with biannual and annual ICERs of $48,729 and $37,806 per QALY, respectively, but when APRI was less than 2.0 (HCC incidence, 0.093%), surveillance was less effective and more expensive than no surveillance at all. A similar trend was found for an FIB-4 threshold of 3.25.
Employment of age-stratified risk of HCC also reduced costs of screening for patients with cirrhosis. With this strategy, ICER was $48,432 per QALY for biannual surveillance and $37,201 per QALY for annual surveillance.
“These data suggest that, if we assume HCC incidence increases with age, biannual or annual surveillance will be cost effective for the vast majority, if not all, patients with cirrhosis before SVR,” the investigators wrote.
“Our analysis suggests that HCC surveillance is very unlikely to be cost effective in patients with F3 fibrosis, whereas both annual and biannual modalities are likely to be cost effective at standard willingness-to-pay thresholds for patients with cirrhosis compared with no surveillance,” the investigators wrote.
“Additional long-term follow-up data are required to help identify patients at highest risk of HCC after SVR to tailor surveillance guidelines,” the investigators concluded.
The study was funded by the Toronto Centre for Liver Disease. The investigators declared no conflicts of interest.
This story was updated on 7/12/2019.
SOURCE: Zangneh et al. Clin Gastroenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.018.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Mortality caused by chronic liver disease in setting of diabetes continues to rise
results from a large database analysis showed.
“While diabetes-related mortality has been reported to be decreasing due to improved awareness and management, our results highlight the need to better address NAFLD [nonalcoholic fatty liver disease] and end-stage liver disease among individuals with diabetes,” researchers led by Donghee Kim, MD, PhD, wrote in an article published in Clinical Gastroenterology and Hepatology.
In an effort to estimate the trends in chronic liver disease–related mortality among individuals with diabetes from 2007 to 2017 in the United States, Dr. Kim, of the division of gastroenterology and hepatology at Stanford (Calif.) University, and colleagues analyzed mortality records from the National Vital Statistic System database. They calculated age-specific mortality by dividing the number of deaths by the total U.S. census population for each year and standardized them according to age distribution of 2010 U.S. standard population. The researchers used joinpoint regression analysis to determine trends.
Of 2,686,590 individuals with diabetes identified, 48,761 had chronic liver disease as the underlying cause of death listed on the death certificate. Among individuals who had diabetes listed on their death certificate, the age-standardized mortality for cirrhosis and hepatocellular carcinoma as an underlying cause of death increased with an annual rate of 1.2% and 1.9%, respectively. Based on etiology, age-standardized mortality for hepatitis C and hepatitis B viral infections decreased at an annual rate of 4.4% and 5.1%, respectively. On the other hand, mortality among individuals with NAFLD and alcoholic liver disease increased at annual rates of 11.6% and 1.4%, respectively.
“When we defined chronic liver disease as an underlying or contributing cause of death among individuals with diabetes listed on the death certificate, the overall results remained similar,” the researchers wrote. They acknowledged certain limitations of the analysis, including the fact that using death certificates and ICD-10 codes “has the potential for misclassification and underestimation for diabetes and chronic liver disease–related mortality. However, the coding method has been constant over time, so it is unlikely to account for present trends. Increasing obesity and associated insulin resistance likely explain the link between diabetes and NAFLD and end-stage liver disease through hepatic inflammation and various proinflammatory cytokines.”
One of the study authors was supported by the National Institutes of Health. None of the other authors reported having relevant disclosures.
SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.
results from a large database analysis showed.
“While diabetes-related mortality has been reported to be decreasing due to improved awareness and management, our results highlight the need to better address NAFLD [nonalcoholic fatty liver disease] and end-stage liver disease among individuals with diabetes,” researchers led by Donghee Kim, MD, PhD, wrote in an article published in Clinical Gastroenterology and Hepatology.
In an effort to estimate the trends in chronic liver disease–related mortality among individuals with diabetes from 2007 to 2017 in the United States, Dr. Kim, of the division of gastroenterology and hepatology at Stanford (Calif.) University, and colleagues analyzed mortality records from the National Vital Statistic System database. They calculated age-specific mortality by dividing the number of deaths by the total U.S. census population for each year and standardized them according to age distribution of 2010 U.S. standard population. The researchers used joinpoint regression analysis to determine trends.
Of 2,686,590 individuals with diabetes identified, 48,761 had chronic liver disease as the underlying cause of death listed on the death certificate. Among individuals who had diabetes listed on their death certificate, the age-standardized mortality for cirrhosis and hepatocellular carcinoma as an underlying cause of death increased with an annual rate of 1.2% and 1.9%, respectively. Based on etiology, age-standardized mortality for hepatitis C and hepatitis B viral infections decreased at an annual rate of 4.4% and 5.1%, respectively. On the other hand, mortality among individuals with NAFLD and alcoholic liver disease increased at annual rates of 11.6% and 1.4%, respectively.
“When we defined chronic liver disease as an underlying or contributing cause of death among individuals with diabetes listed on the death certificate, the overall results remained similar,” the researchers wrote. They acknowledged certain limitations of the analysis, including the fact that using death certificates and ICD-10 codes “has the potential for misclassification and underestimation for diabetes and chronic liver disease–related mortality. However, the coding method has been constant over time, so it is unlikely to account for present trends. Increasing obesity and associated insulin resistance likely explain the link between diabetes and NAFLD and end-stage liver disease through hepatic inflammation and various proinflammatory cytokines.”
One of the study authors was supported by the National Institutes of Health. None of the other authors reported having relevant disclosures.
SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.
results from a large database analysis showed.
“While diabetes-related mortality has been reported to be decreasing due to improved awareness and management, our results highlight the need to better address NAFLD [nonalcoholic fatty liver disease] and end-stage liver disease among individuals with diabetes,” researchers led by Donghee Kim, MD, PhD, wrote in an article published in Clinical Gastroenterology and Hepatology.
In an effort to estimate the trends in chronic liver disease–related mortality among individuals with diabetes from 2007 to 2017 in the United States, Dr. Kim, of the division of gastroenterology and hepatology at Stanford (Calif.) University, and colleagues analyzed mortality records from the National Vital Statistic System database. They calculated age-specific mortality by dividing the number of deaths by the total U.S. census population for each year and standardized them according to age distribution of 2010 U.S. standard population. The researchers used joinpoint regression analysis to determine trends.
Of 2,686,590 individuals with diabetes identified, 48,761 had chronic liver disease as the underlying cause of death listed on the death certificate. Among individuals who had diabetes listed on their death certificate, the age-standardized mortality for cirrhosis and hepatocellular carcinoma as an underlying cause of death increased with an annual rate of 1.2% and 1.9%, respectively. Based on etiology, age-standardized mortality for hepatitis C and hepatitis B viral infections decreased at an annual rate of 4.4% and 5.1%, respectively. On the other hand, mortality among individuals with NAFLD and alcoholic liver disease increased at annual rates of 11.6% and 1.4%, respectively.
“When we defined chronic liver disease as an underlying or contributing cause of death among individuals with diabetes listed on the death certificate, the overall results remained similar,” the researchers wrote. They acknowledged certain limitations of the analysis, including the fact that using death certificates and ICD-10 codes “has the potential for misclassification and underestimation for diabetes and chronic liver disease–related mortality. However, the coding method has been constant over time, so it is unlikely to account for present trends. Increasing obesity and associated insulin resistance likely explain the link between diabetes and NAFLD and end-stage liver disease through hepatic inflammation and various proinflammatory cytokines.”
One of the study authors was supported by the National Institutes of Health. None of the other authors reported having relevant disclosures.
SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Formal weight loss programs improve NAFLD
For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.
The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues.
“Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine.“However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.
To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease.
The literature search returned 22 eligible studies involving 2,588 patients. The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I2 = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I2 = 94%), histologic NAFLD activity score (-0.92; I2= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I2 =0%), alanine aminotransferase (-9.81 U/L; I2= 97%), aspartate transaminase (-4.84 U/L; I2 = 96%), alkaline phosphatase (-5.53 U/L; I2 = 96%), and gamma-glutamyl transferase (-4.35 U/L; I2 = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.
“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”
“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.
The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.
SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at https://www.gastro.org/practice-guidance/practice-updates/obesity-practice-guide
For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.
The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues.
“Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine.“However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.
To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease.
The literature search returned 22 eligible studies involving 2,588 patients. The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I2 = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I2 = 94%), histologic NAFLD activity score (-0.92; I2= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I2 =0%), alanine aminotransferase (-9.81 U/L; I2= 97%), aspartate transaminase (-4.84 U/L; I2 = 96%), alkaline phosphatase (-5.53 U/L; I2 = 96%), and gamma-glutamyl transferase (-4.35 U/L; I2 = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.
“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”
“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.
The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.
SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at https://www.gastro.org/practice-guidance/practice-updates/obesity-practice-guide
For patients with nonalcoholic fatty liver disease (NAFLD), formal weight loss programs lead to statistically and clinically significant improvements in biomarkers of liver disease, based on a recent meta-analysis.
The findings support changing NAFLD guidelines to recommend weight loss interventions, according to lead author Dimitrios A. Koutoukidis, PhD, of the University of Oxford, UK, and colleagues.
“Clinical guidelines around the world recommend physicians offer advice on lifestyle modification, which mostly includes weight loss through hypoenergetic diets and increased physical activity,” the investigators wrote in JAMA Internal Medicine.“However, whether clinicians provide advice and the type of advice they give vary greatly, and guidelines rarely specifically recommend treatment programs to support weight loss,” they added.
To investigate associations between methods of weight loss and improvements in NAFLD, the investigators screened for studies involving behavioral weight loss programs, pharmacotherapy, or bariatric surgery, alone or in combination. To limit confounding, studies combining weight loss with other potential treatments, such as medications, were excluded. Weight loss interventions were compared to liver disease outcomes associated with lower-intensity weight loss intervention or none or minimal weight loss support, using at least 1 reported biomarker of liver disease.
The literature search returned 22 eligible studies involving 2,588 patients. The investigators found that more intensive weight loss programs were associated with greater weight loss than lower intensity methods (-3.61 kg; I2 = 95%). Multiple biomarkers of liver disease showed significant improvements in association with formal weight loss programs, including histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; I2 = 94%), histologic NAFLD activity score (-0.92; I2= 95%), presence of nonalcoholic steatohepatitis (OR, 0.14; I2 =0%), alanine aminotransferase (-9.81 U/L; I2= 97%), aspartate transaminase (-4.84 U/L; I2 = 96%), alkaline phosphatase (-5.53 U/L; I2 = 96%), and gamma-glutamyl transferase (-4.35 U/L; I2 = 92%). Weight loss interventions were not significantly associated with histologic liver fibrosis or inflammation, the investigators noted.
“The advantages [of weight loss interventions] seem to be greater in people who are overweight and with NAFLD, but our exploratory results suggest that weight loss interventions might still be beneficial in the minority of people with healthy weight and NAFLD,” the investigators wrote. “Clinicians may use these findings to counsel people with NAFLD on the expected clinically significant improvements in liver biomarkers after weight loss and direct the patients toward valuable interventions.”
“The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD,” the investigators concluded.
The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.
SOURCE: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at https://www.gastro.org/practice-guidance/practice-updates/obesity-practice-guide
FROM JAMA INTERNAL MEDICINE
Key clinical point: Major finding: Weight loss interventions were associated with significantly decreased alanine aminotransferase (-9.81 U/L; I2 = 97%).
Study details: A meta-analysis of randomized clinicals involving weight loss interventions for patients with nonalcoholic fatty liver disease (NAFLD).
Disclosures: The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford NIHR Collaboration and Leadership in Applied Health Research. The investigators reported grants for other research from Cambridge Weight Plan.
Source: Koutoukidis et al. JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2248.
Past studies have attempted to investigate the relationship between weight loss and nonalcoholic fatty liver disease (NAFLD), but they did so with various interventions and outcomes measures. Fortunately, the study by Dr. Koutoukidis and colleagues helps clear up this variability with a well-conducted systematic review. The results offer a convincing case that formal weight loss programs should be a cornerstone of NALFD treatment, based on improvements in blood, histologic, and radiologic biomarkers of liver disease. Since pharmacologic options for NAFLD are limited, these findings are particularly important.
Although the study did not reveal improvements in fibrosis or inflammation with weight loss, this is likely due to the scarcity of trials with histologic measures or long-term follow-up. Where long-term follow-up was available, weight loss was not maintained, disallowing clear conclusions. Still, other studies have shown that sustained weight loss is associated with improvements in fibrosis and mortality, so clinicians should feel encouraged that formal weight loss programs for patients with NAFLD likely have life-saving consequences.
Elizabeth Adler, MD and Danielle Brandman, MD , are with the University of California, San Francisco. Dr. Brandman reported financial affiliations with Conatus, Gilead, and Allergan. Their remarks are adapted from an accompanying editorial (JAMA Int Med. 2019 Jul 1. doi: 10.1001/jamainternmed.2019.2244 ).
AGA Clinical Practice Update: Coagulation in cirrhosis
Cirrhosis can involve “precarious” changes in hemostatic pathways that tip the scales toward either bleeding or hypercoagulation, experts wrote in an American Gastroenterological Association Clinical Practice Update.
Based on current evidence, clinicians should not routinely correct thrombocytopenia and coagulopathy in patients with cirrhosis prior to low-risk procedures, such as therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation, Jacqueline G. O’Leary, MD, of Dallas VA Medical Center and her three coreviewers wrote in Gastroenterology.
To optimize clot formation prior to high-risk procedures, and in patients with active bleeding, a platelet count above 50,000 per mcL is still recommended. However, it may be more meaningful to couple that platelet target with a fibrinogen level above 120 mg/dL rather than rely on the international normalized ratio (INR), the experts wrote. Not only does INR vary significantly depending on which thromboplastin is used in the test, but “correcting” INR with a fresh frozen plasma infusion does not affect thrombin production and worsens portal hypertension. Using cryoprecipitate to replenish fibrinogen has less impact on portal hypertension. “Global tests of clot formation, such as rotational thromboelastometry (ROTEM), thromboelastography (TEG), sonorheometry, and thrombin generation may eventually have a role in the evaluation of clotting in patients with cirrhosis but currently lack validated target levels,” the experts wrote.
They advised clinicians to limit the use of blood products (such as fresh frozen plasma and pooled platelet transfusions) because of cost and the risk of exacerbated portal hypertension, infection, and immunologic complications. For severe anemia and uremia, red blood cell transfusion (250 mL) can be considered. Platelet-rich plasma from one donor is less immunologically risky than a pooled platelet transfusion. Thrombopoietin agonists are “a good alternative” to platelet transfusion but require about 10 days for response. Alternative prothrombotic therapies include oral thrombopoietin receptor agonists (avatrombopag and lusutrombopag) to boost platelet count before an invasive procedure, antifibrinolytic therapy (aminocaproic acid and tranexamic acid) for persistent bleeding from mucosal oozing or puncture wounds. Desmopressin should only be considered for patients with comorbid renal failure.
For anticoagulation, the practice update recommends considering systemic heparin infusion for cirrhotic patients with symptomatic deep venous thrombosis (DVT) or portal vein thrombosis (PVT). However, the anti–factor Xa assay will not reliably monitor response if patients have low liver-derived antithrombin III (heparin cofactor). “With newly diagnosed PVT, the decision to intervene with directed therapy rests on the extent of the thrombosis, presence or absence of attributable symptoms, and the risk of bleeding and falls,” the experts stated.
Six-month follow-up imaging is recommended to assess anticoagulation efficacy. More frequent imaging can be considered for PVT patients considered at high risk for therapeutic anticoagulation. If clots do not fully resolve after 6 months of treatment, options including extending therapy with the same agent, switching to a different anticoagulant class, or receiving transjugular intrahepatic portosystemic shunt (TIPS). “The role for TIPS in PVT is evolving and may address complications like portal hypertensive bleeding, medically refractory clot, and the need for repeated banding after variceal bleeding,” the experts noted.
Prophylaxis of DVT is recommended for all hospitalized patients with cirrhosis. Vitamin K antagonists and direct-acting oral anticoagulants (dabigatran, apixaban, rivaroxaban, and edoxaban) are alternatives to heparin for anticoagulation of cirrhotic patients with either PVT and DVT, the experts wrote. However, DOACs are not recommended for most Child-Pugh B patients or for any Child-Pugh C patients.
No funding sources or conflicts of interest were reported.
SOURCE: O’Leary JG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.070.
Cirrhosis can involve “precarious” changes in hemostatic pathways that tip the scales toward either bleeding or hypercoagulation, experts wrote in an American Gastroenterological Association Clinical Practice Update.
Based on current evidence, clinicians should not routinely correct thrombocytopenia and coagulopathy in patients with cirrhosis prior to low-risk procedures, such as therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation, Jacqueline G. O’Leary, MD, of Dallas VA Medical Center and her three coreviewers wrote in Gastroenterology.
To optimize clot formation prior to high-risk procedures, and in patients with active bleeding, a platelet count above 50,000 per mcL is still recommended. However, it may be more meaningful to couple that platelet target with a fibrinogen level above 120 mg/dL rather than rely on the international normalized ratio (INR), the experts wrote. Not only does INR vary significantly depending on which thromboplastin is used in the test, but “correcting” INR with a fresh frozen plasma infusion does not affect thrombin production and worsens portal hypertension. Using cryoprecipitate to replenish fibrinogen has less impact on portal hypertension. “Global tests of clot formation, such as rotational thromboelastometry (ROTEM), thromboelastography (TEG), sonorheometry, and thrombin generation may eventually have a role in the evaluation of clotting in patients with cirrhosis but currently lack validated target levels,” the experts wrote.
They advised clinicians to limit the use of blood products (such as fresh frozen plasma and pooled platelet transfusions) because of cost and the risk of exacerbated portal hypertension, infection, and immunologic complications. For severe anemia and uremia, red blood cell transfusion (250 mL) can be considered. Platelet-rich plasma from one donor is less immunologically risky than a pooled platelet transfusion. Thrombopoietin agonists are “a good alternative” to platelet transfusion but require about 10 days for response. Alternative prothrombotic therapies include oral thrombopoietin receptor agonists (avatrombopag and lusutrombopag) to boost platelet count before an invasive procedure, antifibrinolytic therapy (aminocaproic acid and tranexamic acid) for persistent bleeding from mucosal oozing or puncture wounds. Desmopressin should only be considered for patients with comorbid renal failure.
For anticoagulation, the practice update recommends considering systemic heparin infusion for cirrhotic patients with symptomatic deep venous thrombosis (DVT) or portal vein thrombosis (PVT). However, the anti–factor Xa assay will not reliably monitor response if patients have low liver-derived antithrombin III (heparin cofactor). “With newly diagnosed PVT, the decision to intervene with directed therapy rests on the extent of the thrombosis, presence or absence of attributable symptoms, and the risk of bleeding and falls,” the experts stated.
Six-month follow-up imaging is recommended to assess anticoagulation efficacy. More frequent imaging can be considered for PVT patients considered at high risk for therapeutic anticoagulation. If clots do not fully resolve after 6 months of treatment, options including extending therapy with the same agent, switching to a different anticoagulant class, or receiving transjugular intrahepatic portosystemic shunt (TIPS). “The role for TIPS in PVT is evolving and may address complications like portal hypertensive bleeding, medically refractory clot, and the need for repeated banding after variceal bleeding,” the experts noted.
Prophylaxis of DVT is recommended for all hospitalized patients with cirrhosis. Vitamin K antagonists and direct-acting oral anticoagulants (dabigatran, apixaban, rivaroxaban, and edoxaban) are alternatives to heparin for anticoagulation of cirrhotic patients with either PVT and DVT, the experts wrote. However, DOACs are not recommended for most Child-Pugh B patients or for any Child-Pugh C patients.
No funding sources or conflicts of interest were reported.
SOURCE: O’Leary JG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.070.
Cirrhosis can involve “precarious” changes in hemostatic pathways that tip the scales toward either bleeding or hypercoagulation, experts wrote in an American Gastroenterological Association Clinical Practice Update.
Based on current evidence, clinicians should not routinely correct thrombocytopenia and coagulopathy in patients with cirrhosis prior to low-risk procedures, such as therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation, Jacqueline G. O’Leary, MD, of Dallas VA Medical Center and her three coreviewers wrote in Gastroenterology.
To optimize clot formation prior to high-risk procedures, and in patients with active bleeding, a platelet count above 50,000 per mcL is still recommended. However, it may be more meaningful to couple that platelet target with a fibrinogen level above 120 mg/dL rather than rely on the international normalized ratio (INR), the experts wrote. Not only does INR vary significantly depending on which thromboplastin is used in the test, but “correcting” INR with a fresh frozen plasma infusion does not affect thrombin production and worsens portal hypertension. Using cryoprecipitate to replenish fibrinogen has less impact on portal hypertension. “Global tests of clot formation, such as rotational thromboelastometry (ROTEM), thromboelastography (TEG), sonorheometry, and thrombin generation may eventually have a role in the evaluation of clotting in patients with cirrhosis but currently lack validated target levels,” the experts wrote.
They advised clinicians to limit the use of blood products (such as fresh frozen plasma and pooled platelet transfusions) because of cost and the risk of exacerbated portal hypertension, infection, and immunologic complications. For severe anemia and uremia, red blood cell transfusion (250 mL) can be considered. Platelet-rich plasma from one donor is less immunologically risky than a pooled platelet transfusion. Thrombopoietin agonists are “a good alternative” to platelet transfusion but require about 10 days for response. Alternative prothrombotic therapies include oral thrombopoietin receptor agonists (avatrombopag and lusutrombopag) to boost platelet count before an invasive procedure, antifibrinolytic therapy (aminocaproic acid and tranexamic acid) for persistent bleeding from mucosal oozing or puncture wounds. Desmopressin should only be considered for patients with comorbid renal failure.
For anticoagulation, the practice update recommends considering systemic heparin infusion for cirrhotic patients with symptomatic deep venous thrombosis (DVT) or portal vein thrombosis (PVT). However, the anti–factor Xa assay will not reliably monitor response if patients have low liver-derived antithrombin III (heparin cofactor). “With newly diagnosed PVT, the decision to intervene with directed therapy rests on the extent of the thrombosis, presence or absence of attributable symptoms, and the risk of bleeding and falls,” the experts stated.
Six-month follow-up imaging is recommended to assess anticoagulation efficacy. More frequent imaging can be considered for PVT patients considered at high risk for therapeutic anticoagulation. If clots do not fully resolve after 6 months of treatment, options including extending therapy with the same agent, switching to a different anticoagulant class, or receiving transjugular intrahepatic portosystemic shunt (TIPS). “The role for TIPS in PVT is evolving and may address complications like portal hypertensive bleeding, medically refractory clot, and the need for repeated banding after variceal bleeding,” the experts noted.
Prophylaxis of DVT is recommended for all hospitalized patients with cirrhosis. Vitamin K antagonists and direct-acting oral anticoagulants (dabigatran, apixaban, rivaroxaban, and edoxaban) are alternatives to heparin for anticoagulation of cirrhotic patients with either PVT and DVT, the experts wrote. However, DOACs are not recommended for most Child-Pugh B patients or for any Child-Pugh C patients.
No funding sources or conflicts of interest were reported.
SOURCE: O’Leary JG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.070.
FROM GASTROENTEROLOGY
Study finds differences for HCC in women
SAN DIEGO – Hepatocellular carcinoma is the third leading cause of cancer-related death in the United States and its incidence is increasing worldwide. While it affects men much more frequently than women, approximately 4 to 1, the differences in risk factors between men and women have never been studied.
At the annual Digestive Disease Week, Meaghan Phipps, MD, of New York–Presbyterian Hospital, described in a video interview how she and her colleagues set up a retrospective study of these differences in 5,327 patients at five large academic centers around the country. She and her colleagues found that women tended to present later, and with less severe disease, which was more likely to be treated with resection than transplantation. Women had better overall survival. Women were significantly more likely to present without cirrhosis and with nonalcoholic fatty liver disease than were men. Dr. Phipps noted that they did not characterize the women in their study by menopausal status, and suggested that this would be an important thing to look at in a future prospective study because it has long been thought that estrogen confers some protection against hepatocellular carcinoma.
SAN DIEGO – Hepatocellular carcinoma is the third leading cause of cancer-related death in the United States and its incidence is increasing worldwide. While it affects men much more frequently than women, approximately 4 to 1, the differences in risk factors between men and women have never been studied.
At the annual Digestive Disease Week, Meaghan Phipps, MD, of New York–Presbyterian Hospital, described in a video interview how she and her colleagues set up a retrospective study of these differences in 5,327 patients at five large academic centers around the country. She and her colleagues found that women tended to present later, and with less severe disease, which was more likely to be treated with resection than transplantation. Women had better overall survival. Women were significantly more likely to present without cirrhosis and with nonalcoholic fatty liver disease than were men. Dr. Phipps noted that they did not characterize the women in their study by menopausal status, and suggested that this would be an important thing to look at in a future prospective study because it has long been thought that estrogen confers some protection against hepatocellular carcinoma.
SAN DIEGO – Hepatocellular carcinoma is the third leading cause of cancer-related death in the United States and its incidence is increasing worldwide. While it affects men much more frequently than women, approximately 4 to 1, the differences in risk factors between men and women have never been studied.
At the annual Digestive Disease Week, Meaghan Phipps, MD, of New York–Presbyterian Hospital, described in a video interview how she and her colleagues set up a retrospective study of these differences in 5,327 patients at five large academic centers around the country. She and her colleagues found that women tended to present later, and with less severe disease, which was more likely to be treated with resection than transplantation. Women had better overall survival. Women were significantly more likely to present without cirrhosis and with nonalcoholic fatty liver disease than were men. Dr. Phipps noted that they did not characterize the women in their study by menopausal status, and suggested that this would be an important thing to look at in a future prospective study because it has long been thought that estrogen confers some protection against hepatocellular carcinoma.
REPORTING FROM DDW 2019
