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AGA Clinical Practice Update: Surgical risk assessment and perioperative management in cirrhosis
Patients with cirrhosis should be risk stratified and counseled accordingly before all but the most urgent surgeries, cautions a clinical practice update from the American Gastroenterological Association.
These risks, which include mortality and reflect “the profound effects of hepatic synthetic dysfunction and portal hypertension,” require presurgical evaluation based on CTP score (Child-Pugh class), Model for End-Stage Liver Disease (MELD) score, Mayo Postoperative Mortality Risk Score, or another proven risk-stratification system, writes Patrick G. Northup, MD, of the University of Virginia, Charlottesville, together with his associates. “There is no single definitive risk-stratification system to determine operative risk in all patients with cirrhosis, and we recommend using multiple methods,” they elaborated in Clinical Gastroenterology and Hepatology.
The prevalence of cirrhosis is rising, affected patients are living longer, and liver disease is more advanced and may involve comorbidities that merit consideration of surgery, noted Dr. Northup and his associates. However, cirrhosis increases the risk for serious postoperative complications, including hepatic decompensation, worsening of liver synthetic function, exacerbated portal hypertension, wound dehiscence, pleural effusions, pneumonia, bacterial peritonitis, bleeding, and multiple organ failure. Because clinical trials of surgery in cirrhotic patients are lacking, the experts stress the need for case-by-case management.
There is no definite threshold that precludes all surgeries in cases of cirrhosis, but a Child-Pugh class C (CTP score over 10) or MELD score over 20 greatly increases the risk of postoperative decompensation and death. For these patients, “all but the most urgent and life-saving procedures” should be canceled or postponed until after liver transplantation, the experts wrote. For less severe cirrhosis, it is key to consider the type and anatomic site of the proposed surgery. Hepatobiliary surgeries, other intra-abdominal surgeries, cardiovascular surgeries, and thoracic procedures are most likely to lead to serious complications.
Preoperative care should emphasize control of ascites, variceal bleeding risk, and hepatic encephalopathy. Bleeding and clotting safety thresholds in cirrhosis are unknown, and individualized management, ideally with viscoelastic testing–directed therapy, is warranted instead of protocol transfusions to a target international normalized ratio (INR). Bleeding events are more common in critically ill patients with plasma fibrinogen ratios under 100 mg/dL.
Segmental hepatic resection (usually for malignancy), the most studied procedure in cirrhosis, is generally safe in the absence of clinically significant portal hypertension. For patients who do have portal hypertension, transjugular intrahepatic portosystemic shunt (TIPS) has not clearly been shown to outperform conservative management, although small case series have found that TIPS during deep pelvic or colonic resection decompresses abdominal collaterals.
Because of the risk of poor outcomes, patients with cirrhosis and incompletely controlled ascites should not undergo abdominal hernia repair unless they have an incarceration that is not manually reducible or suspected strangulation. Bariatric surgery is contraindicated in cases of clinically significant portal hypertension but otherwise can be performed at a center with cirrhosis expertise. Sleeve gastrectomy at the same time as liver transplantation is also an option for select patients with obesity.
Elective cholecystectomy should be avoided, and required cases should be performed in experienced centers. “The gallbladder wall may appear thickened on imaging, which may lead to the erroneous diagnosis of acute cholecystitis,” the experts noted. Hence, the diagnosis “should be made only in the appropriate clinical setting, usually in the presence of biliary pain.”
Hepatic decompensation after surgery can be severe enough to merit liver transplantation. There is no agreed-on MELD score that mandates liver transplant evaluation before elective surgery, but the experts recommend doing so if the MELD score is 15 or greater or if risk of mortality within 3 months after surgery exceeds 15%.
Postoperative management of patients with cirrhosis should include aggressive measures to prevent portal hypertension. Monitor renal function closely and avoid volume depletion or overload, the experts advised. Patients should receive only short-acting benzodiazepines and lower opiate doses, administered less often, than in the general population. Avoiding constipation is vital to minimize hepatic encephalopathy, which makes oral rifaximin a better choice than lactulose. Patients should not receive NSAIDs, which can impair renal blood flow. To prevent liver toxicity, they should not be discharged on opiate/acetaminophen combinations, which they might unknowingly take along with another drug that contains acetaminophen.
The experts disclosed no external funding sources and reported having no conflicts of interest.
SOURCE: Northup PG et al. Clin Gastroenterol Hepatol. 2018 Sep 28. doi: 10.1016/j.cgh.2018.09.043.
Patients with cirrhosis should be risk stratified and counseled accordingly before all but the most urgent surgeries, cautions a clinical practice update from the American Gastroenterological Association.
These risks, which include mortality and reflect “the profound effects of hepatic synthetic dysfunction and portal hypertension,” require presurgical evaluation based on CTP score (Child-Pugh class), Model for End-Stage Liver Disease (MELD) score, Mayo Postoperative Mortality Risk Score, or another proven risk-stratification system, writes Patrick G. Northup, MD, of the University of Virginia, Charlottesville, together with his associates. “There is no single definitive risk-stratification system to determine operative risk in all patients with cirrhosis, and we recommend using multiple methods,” they elaborated in Clinical Gastroenterology and Hepatology.
The prevalence of cirrhosis is rising, affected patients are living longer, and liver disease is more advanced and may involve comorbidities that merit consideration of surgery, noted Dr. Northup and his associates. However, cirrhosis increases the risk for serious postoperative complications, including hepatic decompensation, worsening of liver synthetic function, exacerbated portal hypertension, wound dehiscence, pleural effusions, pneumonia, bacterial peritonitis, bleeding, and multiple organ failure. Because clinical trials of surgery in cirrhotic patients are lacking, the experts stress the need for case-by-case management.
There is no definite threshold that precludes all surgeries in cases of cirrhosis, but a Child-Pugh class C (CTP score over 10) or MELD score over 20 greatly increases the risk of postoperative decompensation and death. For these patients, “all but the most urgent and life-saving procedures” should be canceled or postponed until after liver transplantation, the experts wrote. For less severe cirrhosis, it is key to consider the type and anatomic site of the proposed surgery. Hepatobiliary surgeries, other intra-abdominal surgeries, cardiovascular surgeries, and thoracic procedures are most likely to lead to serious complications.
Preoperative care should emphasize control of ascites, variceal bleeding risk, and hepatic encephalopathy. Bleeding and clotting safety thresholds in cirrhosis are unknown, and individualized management, ideally with viscoelastic testing–directed therapy, is warranted instead of protocol transfusions to a target international normalized ratio (INR). Bleeding events are more common in critically ill patients with plasma fibrinogen ratios under 100 mg/dL.
Segmental hepatic resection (usually for malignancy), the most studied procedure in cirrhosis, is generally safe in the absence of clinically significant portal hypertension. For patients who do have portal hypertension, transjugular intrahepatic portosystemic shunt (TIPS) has not clearly been shown to outperform conservative management, although small case series have found that TIPS during deep pelvic or colonic resection decompresses abdominal collaterals.
Because of the risk of poor outcomes, patients with cirrhosis and incompletely controlled ascites should not undergo abdominal hernia repair unless they have an incarceration that is not manually reducible or suspected strangulation. Bariatric surgery is contraindicated in cases of clinically significant portal hypertension but otherwise can be performed at a center with cirrhosis expertise. Sleeve gastrectomy at the same time as liver transplantation is also an option for select patients with obesity.
Elective cholecystectomy should be avoided, and required cases should be performed in experienced centers. “The gallbladder wall may appear thickened on imaging, which may lead to the erroneous diagnosis of acute cholecystitis,” the experts noted. Hence, the diagnosis “should be made only in the appropriate clinical setting, usually in the presence of biliary pain.”
Hepatic decompensation after surgery can be severe enough to merit liver transplantation. There is no agreed-on MELD score that mandates liver transplant evaluation before elective surgery, but the experts recommend doing so if the MELD score is 15 or greater or if risk of mortality within 3 months after surgery exceeds 15%.
Postoperative management of patients with cirrhosis should include aggressive measures to prevent portal hypertension. Monitor renal function closely and avoid volume depletion or overload, the experts advised. Patients should receive only short-acting benzodiazepines and lower opiate doses, administered less often, than in the general population. Avoiding constipation is vital to minimize hepatic encephalopathy, which makes oral rifaximin a better choice than lactulose. Patients should not receive NSAIDs, which can impair renal blood flow. To prevent liver toxicity, they should not be discharged on opiate/acetaminophen combinations, which they might unknowingly take along with another drug that contains acetaminophen.
The experts disclosed no external funding sources and reported having no conflicts of interest.
SOURCE: Northup PG et al. Clin Gastroenterol Hepatol. 2018 Sep 28. doi: 10.1016/j.cgh.2018.09.043.
Patients with cirrhosis should be risk stratified and counseled accordingly before all but the most urgent surgeries, cautions a clinical practice update from the American Gastroenterological Association.
These risks, which include mortality and reflect “the profound effects of hepatic synthetic dysfunction and portal hypertension,” require presurgical evaluation based on CTP score (Child-Pugh class), Model for End-Stage Liver Disease (MELD) score, Mayo Postoperative Mortality Risk Score, or another proven risk-stratification system, writes Patrick G. Northup, MD, of the University of Virginia, Charlottesville, together with his associates. “There is no single definitive risk-stratification system to determine operative risk in all patients with cirrhosis, and we recommend using multiple methods,” they elaborated in Clinical Gastroenterology and Hepatology.
The prevalence of cirrhosis is rising, affected patients are living longer, and liver disease is more advanced and may involve comorbidities that merit consideration of surgery, noted Dr. Northup and his associates. However, cirrhosis increases the risk for serious postoperative complications, including hepatic decompensation, worsening of liver synthetic function, exacerbated portal hypertension, wound dehiscence, pleural effusions, pneumonia, bacterial peritonitis, bleeding, and multiple organ failure. Because clinical trials of surgery in cirrhotic patients are lacking, the experts stress the need for case-by-case management.
There is no definite threshold that precludes all surgeries in cases of cirrhosis, but a Child-Pugh class C (CTP score over 10) or MELD score over 20 greatly increases the risk of postoperative decompensation and death. For these patients, “all but the most urgent and life-saving procedures” should be canceled or postponed until after liver transplantation, the experts wrote. For less severe cirrhosis, it is key to consider the type and anatomic site of the proposed surgery. Hepatobiliary surgeries, other intra-abdominal surgeries, cardiovascular surgeries, and thoracic procedures are most likely to lead to serious complications.
Preoperative care should emphasize control of ascites, variceal bleeding risk, and hepatic encephalopathy. Bleeding and clotting safety thresholds in cirrhosis are unknown, and individualized management, ideally with viscoelastic testing–directed therapy, is warranted instead of protocol transfusions to a target international normalized ratio (INR). Bleeding events are more common in critically ill patients with plasma fibrinogen ratios under 100 mg/dL.
Segmental hepatic resection (usually for malignancy), the most studied procedure in cirrhosis, is generally safe in the absence of clinically significant portal hypertension. For patients who do have portal hypertension, transjugular intrahepatic portosystemic shunt (TIPS) has not clearly been shown to outperform conservative management, although small case series have found that TIPS during deep pelvic or colonic resection decompresses abdominal collaterals.
Because of the risk of poor outcomes, patients with cirrhosis and incompletely controlled ascites should not undergo abdominal hernia repair unless they have an incarceration that is not manually reducible or suspected strangulation. Bariatric surgery is contraindicated in cases of clinically significant portal hypertension but otherwise can be performed at a center with cirrhosis expertise. Sleeve gastrectomy at the same time as liver transplantation is also an option for select patients with obesity.
Elective cholecystectomy should be avoided, and required cases should be performed in experienced centers. “The gallbladder wall may appear thickened on imaging, which may lead to the erroneous diagnosis of acute cholecystitis,” the experts noted. Hence, the diagnosis “should be made only in the appropriate clinical setting, usually in the presence of biliary pain.”
Hepatic decompensation after surgery can be severe enough to merit liver transplantation. There is no agreed-on MELD score that mandates liver transplant evaluation before elective surgery, but the experts recommend doing so if the MELD score is 15 or greater or if risk of mortality within 3 months after surgery exceeds 15%.
Postoperative management of patients with cirrhosis should include aggressive measures to prevent portal hypertension. Monitor renal function closely and avoid volume depletion or overload, the experts advised. Patients should receive only short-acting benzodiazepines and lower opiate doses, administered less often, than in the general population. Avoiding constipation is vital to minimize hepatic encephalopathy, which makes oral rifaximin a better choice than lactulose. Patients should not receive NSAIDs, which can impair renal blood flow. To prevent liver toxicity, they should not be discharged on opiate/acetaminophen combinations, which they might unknowingly take along with another drug that contains acetaminophen.
The experts disclosed no external funding sources and reported having no conflicts of interest.
SOURCE: Northup PG et al. Clin Gastroenterol Hepatol. 2018 Sep 28. doi: 10.1016/j.cgh.2018.09.043.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Caring for aging HIV-infected patients requires close attention to unrelated diseases
A substantial proportion of non–AIDS-defining cancers, and other noninfectious comorbid diseases, could be prevented with interventions on traditional risk factors in HIV-infected patients, according to the results of large database analysis published online in The Lancet HIV.
The researchers analyzed traditional and HIV-related risk factors for four validated noncommunicable disease outcomes (non–AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease) among participants of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), according to Keri N. Althoff, PhD, of Johns Hopkins University, Baltimore, and her colleagues on behalf of the NA-ACCORD.
The study comprised individuals with the assessed disease conditions from among more than 180,000 adults (aged 18 years or older) with HIV from more than 200 sites who had at least two care visits within 12 months. The researchers used a population attributable fraction (PAF) approach to quantify the proportion of noncommunicable diseases that could be eliminated if particular risk factors were not present. According to the researchers, PAF can be used to inform prioritization of interventions.
Dr. Althoff and her colleagues found that, for non–AIDS-defining cancer, the significant preventable or modifiable risk factors were smoking, low CD4 cell count, detectable HIV RNA, a history of clinical AIDS diagnosis, and hepatitis B infection.
For myocardial infarction, the significant factors were smoking, elevated total cholesterol, hypertension, stage 4 chronic kidney disease, a low CD4 cell count, detectable HIV RNA, and hepatitis C infection.
For end-stage liver disease, the significant factors were low CD4 cell count, detectable HIV RNA, a history of a clinical AIDS diagnosis, and hepatitis B or C infection.
For end-stage renal disease, the significantly associated risk factors were elevated total cholesterol, hypertension, diabetes, low CD4 cell count, detectable HIV RNA, and a history of clinical AIDS diagnosis.
The most substantial PAF for each of the respective diseases was as follows: smoking for non–AIDS-related cancers (24%; 95% confidence interval, 13%-35%), elevated total cholesterol for myocardial infarction (44%; 95% CI, 30%-58%), and hepatitis C infection for end-stage liver disease (30%; 95% CI, 21%-39%). In addition, hypertension had the highest PAF for end-stage renal disease (39%; 95% CI, 26%-51%).
“Modifications to individual-level interventions and models of HIV care, and the implementation of structural and policy-level interventions that focus on prevention and modification of traditional risk factors are necessary to avoid noncommunicable diseases and preserve health among successfully antiretroviral-treated adults aging with HIV,” the researchers concluded.
The study was funded by the National Institutes of Health and the NA-ACCORD. Dr. Althoff reported having no relevant disclosures.
SOURCE: Althoff KN et al. The Lancet HIV. 2019 Jan 22. doi: 10.1016/S2352-3018(18)30295-9.
A substantial proportion of non–AIDS-defining cancers, and other noninfectious comorbid diseases, could be prevented with interventions on traditional risk factors in HIV-infected patients, according to the results of large database analysis published online in The Lancet HIV.
The researchers analyzed traditional and HIV-related risk factors for four validated noncommunicable disease outcomes (non–AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease) among participants of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), according to Keri N. Althoff, PhD, of Johns Hopkins University, Baltimore, and her colleagues on behalf of the NA-ACCORD.
The study comprised individuals with the assessed disease conditions from among more than 180,000 adults (aged 18 years or older) with HIV from more than 200 sites who had at least two care visits within 12 months. The researchers used a population attributable fraction (PAF) approach to quantify the proportion of noncommunicable diseases that could be eliminated if particular risk factors were not present. According to the researchers, PAF can be used to inform prioritization of interventions.
Dr. Althoff and her colleagues found that, for non–AIDS-defining cancer, the significant preventable or modifiable risk factors were smoking, low CD4 cell count, detectable HIV RNA, a history of clinical AIDS diagnosis, and hepatitis B infection.
For myocardial infarction, the significant factors were smoking, elevated total cholesterol, hypertension, stage 4 chronic kidney disease, a low CD4 cell count, detectable HIV RNA, and hepatitis C infection.
For end-stage liver disease, the significant factors were low CD4 cell count, detectable HIV RNA, a history of a clinical AIDS diagnosis, and hepatitis B or C infection.
For end-stage renal disease, the significantly associated risk factors were elevated total cholesterol, hypertension, diabetes, low CD4 cell count, detectable HIV RNA, and a history of clinical AIDS diagnosis.
The most substantial PAF for each of the respective diseases was as follows: smoking for non–AIDS-related cancers (24%; 95% confidence interval, 13%-35%), elevated total cholesterol for myocardial infarction (44%; 95% CI, 30%-58%), and hepatitis C infection for end-stage liver disease (30%; 95% CI, 21%-39%). In addition, hypertension had the highest PAF for end-stage renal disease (39%; 95% CI, 26%-51%).
“Modifications to individual-level interventions and models of HIV care, and the implementation of structural and policy-level interventions that focus on prevention and modification of traditional risk factors are necessary to avoid noncommunicable diseases and preserve health among successfully antiretroviral-treated adults aging with HIV,” the researchers concluded.
The study was funded by the National Institutes of Health and the NA-ACCORD. Dr. Althoff reported having no relevant disclosures.
SOURCE: Althoff KN et al. The Lancet HIV. 2019 Jan 22. doi: 10.1016/S2352-3018(18)30295-9.
A substantial proportion of non–AIDS-defining cancers, and other noninfectious comorbid diseases, could be prevented with interventions on traditional risk factors in HIV-infected patients, according to the results of large database analysis published online in The Lancet HIV.
The researchers analyzed traditional and HIV-related risk factors for four validated noncommunicable disease outcomes (non–AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease) among participants of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), according to Keri N. Althoff, PhD, of Johns Hopkins University, Baltimore, and her colleagues on behalf of the NA-ACCORD.
The study comprised individuals with the assessed disease conditions from among more than 180,000 adults (aged 18 years or older) with HIV from more than 200 sites who had at least two care visits within 12 months. The researchers used a population attributable fraction (PAF) approach to quantify the proportion of noncommunicable diseases that could be eliminated if particular risk factors were not present. According to the researchers, PAF can be used to inform prioritization of interventions.
Dr. Althoff and her colleagues found that, for non–AIDS-defining cancer, the significant preventable or modifiable risk factors were smoking, low CD4 cell count, detectable HIV RNA, a history of clinical AIDS diagnosis, and hepatitis B infection.
For myocardial infarction, the significant factors were smoking, elevated total cholesterol, hypertension, stage 4 chronic kidney disease, a low CD4 cell count, detectable HIV RNA, and hepatitis C infection.
For end-stage liver disease, the significant factors were low CD4 cell count, detectable HIV RNA, a history of a clinical AIDS diagnosis, and hepatitis B or C infection.
For end-stage renal disease, the significantly associated risk factors were elevated total cholesterol, hypertension, diabetes, low CD4 cell count, detectable HIV RNA, and a history of clinical AIDS diagnosis.
The most substantial PAF for each of the respective diseases was as follows: smoking for non–AIDS-related cancers (24%; 95% confidence interval, 13%-35%), elevated total cholesterol for myocardial infarction (44%; 95% CI, 30%-58%), and hepatitis C infection for end-stage liver disease (30%; 95% CI, 21%-39%). In addition, hypertension had the highest PAF for end-stage renal disease (39%; 95% CI, 26%-51%).
“Modifications to individual-level interventions and models of HIV care, and the implementation of structural and policy-level interventions that focus on prevention and modification of traditional risk factors are necessary to avoid noncommunicable diseases and preserve health among successfully antiretroviral-treated adults aging with HIV,” the researchers concluded.
The study was funded by the National Institutes of Health and the NA-ACCORD. Dr. Althoff reported having no relevant disclosures.
SOURCE: Althoff KN et al. The Lancet HIV. 2019 Jan 22. doi: 10.1016/S2352-3018(18)30295-9.
FROM THE LANCET HIV
Perceptions of liver transplantation for ALD are evolving
“The findings suggest that early liver transplant for alcoholic hepatitis may be leading to broader acceptance of ALD for liver transplant,” Brian P. Lee, MD, of the University of California, San Francisco, and his colleagues wrote in JAMA Internal Medicine.
The researchers conducted a prospective cohort study of 9,438 patients with ALD who received a liver transplant from 2002 to 2016. Data were obtained from the United Network for Organ Sharing national database.
Study participants were evaluated for patterns, both nationally and regionally, related to liver transplant for the treatment of ALD. In addition, Dr. Lee and his colleagues completed a sensitivity analysis, which evaluated specific clinical parameters, including patient and graft survival, hepatocellular carcinoma (HCC), and hepatitis C viral (HCV) infection.
“Because there is no national policy regarding early liver transplant, we hypothesized that changes may vary regionally as liver transplant programs shifted their attitudes toward increased acceptance of early liver transplant for alcoholic hepatitis and ALD,” the researchers wrote.
After analysis, the researchers found that liver transplantation for patients with ALD increased proportionally from 24.2% to 36.7% from 2002 to 2016, respectively. With HCV-infected recipients included, the proportion of liver transplants rose from 15.3% to 30.6% over the same period, representing a twofold increase of transplants received for this indication.
The degree of increase was reported to vary based on geographic region and was linked with differences in patient-specific factors.
“There may be regional disparities in access to liver transplant for ALD; whether this is related to different attitudes toward ALD and requirements for sobriety is unknown,” they added.
The researchers acknowledged that a key limitation of the study was the use of registry data. As a result, Dr. Lee and his colleagues reported that all conclusions are not causal, but rather only by association.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases UCSF Liver Center. The authors reported no conflicts of interests.
SOURCE: Lee BP et al. JAMA Intern Med. 2019 Jan 22. doi: 10.1001/jamainternmed.2018.6536.
One of the most significant findings of the study by Brian P. Lee, MD, and his colleagues is the major shift in attitudes surrounding the eligibility criteria for patients with ALD to undergo liver transplantation.
More than 3 decades ago, a group of surgical experts gathered together to discuss evaluation criteria for candidacy of individuals to undergo liver transplantation. They recommended that patients with ALD be required to restrict alcohol consumption for 6 months prior to being listed eligible for surgery. The group presumed that a period of complete avoidance may induce some degree of disease remission, circumventing the need for transplant altogether.
However, these suggestions were given without the use of evidence, formed largely on the basis of opinion, and recent data dispute these recommendations. On the contrary, relapse rates for alcohol use disorder has been shown to be due to factors other than length of abstinence. While these findings have lessened bias surrounding ALD and liver transplantation, the assumption still remains prevalent in clinical practice today.
These results highlight the unanswered question of how to best approach treatment of individuals with ALD, and whether the recent rise of patients undergoing liver transplantation for ALD, without a continued duration of abstinence, should be a concern of clinicians.
Mack C. Mitchell, MD, is affiliated with the department of internal medicine at the University of Texas in Dallas. Dr. Mitchell reported having financial affiliations with the National Institute of Alcohol and Alcohol Abuse. These comments are adapted from his accompanying editorial (JAMA Intern Med. 2019 Jan 22. doi: 10.1001/jamainternmed.2018.6532 ).
One of the most significant findings of the study by Brian P. Lee, MD, and his colleagues is the major shift in attitudes surrounding the eligibility criteria for patients with ALD to undergo liver transplantation.
More than 3 decades ago, a group of surgical experts gathered together to discuss evaluation criteria for candidacy of individuals to undergo liver transplantation. They recommended that patients with ALD be required to restrict alcohol consumption for 6 months prior to being listed eligible for surgery. The group presumed that a period of complete avoidance may induce some degree of disease remission, circumventing the need for transplant altogether.
However, these suggestions were given without the use of evidence, formed largely on the basis of opinion, and recent data dispute these recommendations. On the contrary, relapse rates for alcohol use disorder has been shown to be due to factors other than length of abstinence. While these findings have lessened bias surrounding ALD and liver transplantation, the assumption still remains prevalent in clinical practice today.
These results highlight the unanswered question of how to best approach treatment of individuals with ALD, and whether the recent rise of patients undergoing liver transplantation for ALD, without a continued duration of abstinence, should be a concern of clinicians.
Mack C. Mitchell, MD, is affiliated with the department of internal medicine at the University of Texas in Dallas. Dr. Mitchell reported having financial affiliations with the National Institute of Alcohol and Alcohol Abuse. These comments are adapted from his accompanying editorial (JAMA Intern Med. 2019 Jan 22. doi: 10.1001/jamainternmed.2018.6532 ).
One of the most significant findings of the study by Brian P. Lee, MD, and his colleagues is the major shift in attitudes surrounding the eligibility criteria for patients with ALD to undergo liver transplantation.
More than 3 decades ago, a group of surgical experts gathered together to discuss evaluation criteria for candidacy of individuals to undergo liver transplantation. They recommended that patients with ALD be required to restrict alcohol consumption for 6 months prior to being listed eligible for surgery. The group presumed that a period of complete avoidance may induce some degree of disease remission, circumventing the need for transplant altogether.
However, these suggestions were given without the use of evidence, formed largely on the basis of opinion, and recent data dispute these recommendations. On the contrary, relapse rates for alcohol use disorder has been shown to be due to factors other than length of abstinence. While these findings have lessened bias surrounding ALD and liver transplantation, the assumption still remains prevalent in clinical practice today.
These results highlight the unanswered question of how to best approach treatment of individuals with ALD, and whether the recent rise of patients undergoing liver transplantation for ALD, without a continued duration of abstinence, should be a concern of clinicians.
Mack C. Mitchell, MD, is affiliated with the department of internal medicine at the University of Texas in Dallas. Dr. Mitchell reported having financial affiliations with the National Institute of Alcohol and Alcohol Abuse. These comments are adapted from his accompanying editorial (JAMA Intern Med. 2019 Jan 22. doi: 10.1001/jamainternmed.2018.6532 ).
“The findings suggest that early liver transplant for alcoholic hepatitis may be leading to broader acceptance of ALD for liver transplant,” Brian P. Lee, MD, of the University of California, San Francisco, and his colleagues wrote in JAMA Internal Medicine.
The researchers conducted a prospective cohort study of 9,438 patients with ALD who received a liver transplant from 2002 to 2016. Data were obtained from the United Network for Organ Sharing national database.
Study participants were evaluated for patterns, both nationally and regionally, related to liver transplant for the treatment of ALD. In addition, Dr. Lee and his colleagues completed a sensitivity analysis, which evaluated specific clinical parameters, including patient and graft survival, hepatocellular carcinoma (HCC), and hepatitis C viral (HCV) infection.
“Because there is no national policy regarding early liver transplant, we hypothesized that changes may vary regionally as liver transplant programs shifted their attitudes toward increased acceptance of early liver transplant for alcoholic hepatitis and ALD,” the researchers wrote.
After analysis, the researchers found that liver transplantation for patients with ALD increased proportionally from 24.2% to 36.7% from 2002 to 2016, respectively. With HCV-infected recipients included, the proportion of liver transplants rose from 15.3% to 30.6% over the same period, representing a twofold increase of transplants received for this indication.
The degree of increase was reported to vary based on geographic region and was linked with differences in patient-specific factors.
“There may be regional disparities in access to liver transplant for ALD; whether this is related to different attitudes toward ALD and requirements for sobriety is unknown,” they added.
The researchers acknowledged that a key limitation of the study was the use of registry data. As a result, Dr. Lee and his colleagues reported that all conclusions are not causal, but rather only by association.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases UCSF Liver Center. The authors reported no conflicts of interests.
SOURCE: Lee BP et al. JAMA Intern Med. 2019 Jan 22. doi: 10.1001/jamainternmed.2018.6536.
“The findings suggest that early liver transplant for alcoholic hepatitis may be leading to broader acceptance of ALD for liver transplant,” Brian P. Lee, MD, of the University of California, San Francisco, and his colleagues wrote in JAMA Internal Medicine.
The researchers conducted a prospective cohort study of 9,438 patients with ALD who received a liver transplant from 2002 to 2016. Data were obtained from the United Network for Organ Sharing national database.
Study participants were evaluated for patterns, both nationally and regionally, related to liver transplant for the treatment of ALD. In addition, Dr. Lee and his colleagues completed a sensitivity analysis, which evaluated specific clinical parameters, including patient and graft survival, hepatocellular carcinoma (HCC), and hepatitis C viral (HCV) infection.
“Because there is no national policy regarding early liver transplant, we hypothesized that changes may vary regionally as liver transplant programs shifted their attitudes toward increased acceptance of early liver transplant for alcoholic hepatitis and ALD,” the researchers wrote.
After analysis, the researchers found that liver transplantation for patients with ALD increased proportionally from 24.2% to 36.7% from 2002 to 2016, respectively. With HCV-infected recipients included, the proportion of liver transplants rose from 15.3% to 30.6% over the same period, representing a twofold increase of transplants received for this indication.
The degree of increase was reported to vary based on geographic region and was linked with differences in patient-specific factors.
“There may be regional disparities in access to liver transplant for ALD; whether this is related to different attitudes toward ALD and requirements for sobriety is unknown,” they added.
The researchers acknowledged that a key limitation of the study was the use of registry data. As a result, Dr. Lee and his colleagues reported that all conclusions are not causal, but rather only by association.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases UCSF Liver Center. The authors reported no conflicts of interests.
SOURCE: Lee BP et al. JAMA Intern Med. 2019 Jan 22. doi: 10.1001/jamainternmed.2018.6536.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Liver transplantation for alcohol-associated liver disease (ALD) is occurring earlier and more frequently than before.
Major finding: The proportion of patients undergoing liver transplantation for ALD has nearly doubled from 2002 to 2016.
Study details: A prospective cohort study of 9,438 patients who underwent liver transplant for ALD in the United States from 2002 to 2016.
Disclosures: The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases UCSF Liver Center. The authors reported no conflicts of interest.
Source: Lee BP et al. JAMA Intern Med. 2019 Jan 22. doi: 10.1001/jamainternmed.2018.6536.
Host stress response may be a factor in early-stage HCV clearance
The cellular stress response in hepatocytes may play a major role in controlling hepatitis C virus (HCV). This response may be an important host factor for virus clearance during the early stages of HCV infection, according to a review of acute and chronic HCV infection by W. Alfredo Ríos-Ocampo, MD, and his colleagues (Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The reviewers examined the mechanisms of induction and modulation of oxidative stress and endoplasmic-reticular stress with regard to viral persistence and cell survival. The accumulated research indicates that the activation of the eIF2-alpha/ATF4 pathway and selective autophagy induction are involved in the elimination of harmful viral proteins after oxidative stress induction. This all suggests a negative role of autophagy upon HCV infection or a negative regulation of viral replication.
“We conclude from published studies and our own research that viral protein synthesis activates adaptive responses, including autophagy pathways, that act to limit viral protein load and thereby reduce oxidative stress and cell death. Exploitation of these pathways to reduce viral replication will be the next goal and might be a valuable addition to antiviral therapy,” the reviewers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Ríos-Ocampo, WA, et al. Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The cellular stress response in hepatocytes may play a major role in controlling hepatitis C virus (HCV). This response may be an important host factor for virus clearance during the early stages of HCV infection, according to a review of acute and chronic HCV infection by W. Alfredo Ríos-Ocampo, MD, and his colleagues (Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The reviewers examined the mechanisms of induction and modulation of oxidative stress and endoplasmic-reticular stress with regard to viral persistence and cell survival. The accumulated research indicates that the activation of the eIF2-alpha/ATF4 pathway and selective autophagy induction are involved in the elimination of harmful viral proteins after oxidative stress induction. This all suggests a negative role of autophagy upon HCV infection or a negative regulation of viral replication.
“We conclude from published studies and our own research that viral protein synthesis activates adaptive responses, including autophagy pathways, that act to limit viral protein load and thereby reduce oxidative stress and cell death. Exploitation of these pathways to reduce viral replication will be the next goal and might be a valuable addition to antiviral therapy,” the reviewers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Ríos-Ocampo, WA, et al. Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The cellular stress response in hepatocytes may play a major role in controlling hepatitis C virus (HCV). This response may be an important host factor for virus clearance during the early stages of HCV infection, according to a review of acute and chronic HCV infection by W. Alfredo Ríos-Ocampo, MD, and his colleagues (Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The reviewers examined the mechanisms of induction and modulation of oxidative stress and endoplasmic-reticular stress with regard to viral persistence and cell survival. The accumulated research indicates that the activation of the eIF2-alpha/ATF4 pathway and selective autophagy induction are involved in the elimination of harmful viral proteins after oxidative stress induction. This all suggests a negative role of autophagy upon HCV infection or a negative regulation of viral replication.
“We conclude from published studies and our own research that viral protein synthesis activates adaptive responses, including autophagy pathways, that act to limit viral protein load and thereby reduce oxidative stress and cell death. Exploitation of these pathways to reduce viral replication will be the next goal and might be a valuable addition to antiviral therapy,” the reviewers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Ríos-Ocampo, WA, et al. Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
FROM VIRUS RESEARCH
FDA approves cabozantinib for previously treated HCC
The Food and Drug Administration has approved cabozantinib tablets (Cabometyx) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
Approval was based on an improvement in overall survival over placebo seen in the phase 3 CELESTIAL trial for patients with advanced HCC who received prior sorafenib.
Median overall survival was 10.2 months with cabozantinib versus 8.0 months with placebo (hazard ratio, 0.76; 95% confidence interval, 0.63-0.92; P = .0049). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (HR, 0.44; 95% CI, 0.36-0.52; P less than .0001). Objective response rates were 4% with cabozantinib and 0.4% with placebo (P = .0086), Exelixis, makers of the drug, said in a press release.
The most common grade 3 or 4 adverse events in the patients who received cabozantinib, compared with those who received placebo, were palmar-plantar erythrodysesthesia (17% vs. 0%), hypertension (16% vs. 2%), increased aspartate aminotransferase (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism, and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure).
Cabozantinib is also approved to treat renal cell carcinoma and medullary thyroid cancer.
Checkpoint inhibitor pembrolizumab was granted accelerated approval for the same HCC indication – to treat patients who have been previously treated with sorafenib – in late 2018.
Exelixis and its partner Ipsen have launched a phase 3 trial of cabozantinib in combination with the checkpoint inhibitor atezolizumab versus sorafenib in previously untreated advanced HCC. The trial will also explore single-agent activity of cabozantinib in the first-line setting, the company said in the press release.
The Food and Drug Administration has approved cabozantinib tablets (Cabometyx) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
Approval was based on an improvement in overall survival over placebo seen in the phase 3 CELESTIAL trial for patients with advanced HCC who received prior sorafenib.
Median overall survival was 10.2 months with cabozantinib versus 8.0 months with placebo (hazard ratio, 0.76; 95% confidence interval, 0.63-0.92; P = .0049). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (HR, 0.44; 95% CI, 0.36-0.52; P less than .0001). Objective response rates were 4% with cabozantinib and 0.4% with placebo (P = .0086), Exelixis, makers of the drug, said in a press release.
The most common grade 3 or 4 adverse events in the patients who received cabozantinib, compared with those who received placebo, were palmar-plantar erythrodysesthesia (17% vs. 0%), hypertension (16% vs. 2%), increased aspartate aminotransferase (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism, and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure).
Cabozantinib is also approved to treat renal cell carcinoma and medullary thyroid cancer.
Checkpoint inhibitor pembrolizumab was granted accelerated approval for the same HCC indication – to treat patients who have been previously treated with sorafenib – in late 2018.
Exelixis and its partner Ipsen have launched a phase 3 trial of cabozantinib in combination with the checkpoint inhibitor atezolizumab versus sorafenib in previously untreated advanced HCC. The trial will also explore single-agent activity of cabozantinib in the first-line setting, the company said in the press release.
The Food and Drug Administration has approved cabozantinib tablets (Cabometyx) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
Approval was based on an improvement in overall survival over placebo seen in the phase 3 CELESTIAL trial for patients with advanced HCC who received prior sorafenib.
Median overall survival was 10.2 months with cabozantinib versus 8.0 months with placebo (hazard ratio, 0.76; 95% confidence interval, 0.63-0.92; P = .0049). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (HR, 0.44; 95% CI, 0.36-0.52; P less than .0001). Objective response rates were 4% with cabozantinib and 0.4% with placebo (P = .0086), Exelixis, makers of the drug, said in a press release.
The most common grade 3 or 4 adverse events in the patients who received cabozantinib, compared with those who received placebo, were palmar-plantar erythrodysesthesia (17% vs. 0%), hypertension (16% vs. 2%), increased aspartate aminotransferase (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism, and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure).
Cabozantinib is also approved to treat renal cell carcinoma and medullary thyroid cancer.
Checkpoint inhibitor pembrolizumab was granted accelerated approval for the same HCC indication – to treat patients who have been previously treated with sorafenib – in late 2018.
Exelixis and its partner Ipsen have launched a phase 3 trial of cabozantinib in combination with the checkpoint inhibitor atezolizumab versus sorafenib in previously untreated advanced HCC. The trial will also explore single-agent activity of cabozantinib in the first-line setting, the company said in the press release.
Postdiagnosis statin use lowers mortality rate for patients with HCC
Statin use after a diagnosis of hepatocellular carcinoma (HCC) was associated with a reduced risk of all-cause and cancer-specific mortality, according to recent research published in Clinical Gastroenterology and Hepatology.
“Our current findings are biologically plausible since statins inhibit not only cholesterol synthesis but also reduce other important downstream products, including membrane integrity maintenance, cell signaling, protein synthesis, and cell-cycle progression,” wrote Aaron P. Thrift, PhD, of the section of epidemiology and population sciences and department of medicine at Baylor College of Medicine in Houston, and his colleagues. “Not only can statins have a direct impact on cancer cells through inhibition of the mevalonate pathway within the cancer cells, but the reduction of circulating cholesterol levels through hepatic pathways is indeed considered important.”
Dr. Thrift and his colleagues performed a retrospective cohort analysis of data from 15,422 patients with HCC in the VA Central Cancer Registry who were diagnosed between 2002 and 2016 and filled a prescription for statins. The researchers looked at statin prescriptions filled prior to and after diagnosis, following patients from diagnosis up to a 3-month lag period. The statins analyzed included atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin.
Overall, 78.8% of patients died during 26,680 person-years of follow-up and the median survival time was 17.24 months. The researchers found 14.9% of patients (2,293 patients) with HCC filled prescriptions for statins after their cancer diagnosis. The median time to begin statins after diagnosis was 2.37 months, and patients who used statins after diagnosis had a median survival time of 26.38 months compared with 15.67 months for patients who did not use statins after diagnosis. For HCC patients who used statins, there was a decreased risk of all-cause mortality (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95) and cancer-specific mortality (adjusted HR, 0.85; 95% CI, 0.77-0.93), which was consistent for both high-dose and low-dose statins and for lag periods between 0 months and 12 months after diagnosis.
Limitations in the study were the exclusion of any statins filled at non-VA pharmacies, baseline differences in statin users and nonstatin users that could have affected results, potential misclassification of cirrhosis in the registry, and the lack of generalization to other populations due to a veteran-specific patient cohort.
This study was funded by the National Institutes of Health and VA Health Services Research and Development Service Center for Innovations in Quality, Effectiveness, and Safety. The authors report having no conflicts of interest.
SOURCE: Thrift AP et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2018.12.046.
Statin use after a diagnosis of hepatocellular carcinoma (HCC) was associated with a reduced risk of all-cause and cancer-specific mortality, according to recent research published in Clinical Gastroenterology and Hepatology.
“Our current findings are biologically plausible since statins inhibit not only cholesterol synthesis but also reduce other important downstream products, including membrane integrity maintenance, cell signaling, protein synthesis, and cell-cycle progression,” wrote Aaron P. Thrift, PhD, of the section of epidemiology and population sciences and department of medicine at Baylor College of Medicine in Houston, and his colleagues. “Not only can statins have a direct impact on cancer cells through inhibition of the mevalonate pathway within the cancer cells, but the reduction of circulating cholesterol levels through hepatic pathways is indeed considered important.”
Dr. Thrift and his colleagues performed a retrospective cohort analysis of data from 15,422 patients with HCC in the VA Central Cancer Registry who were diagnosed between 2002 and 2016 and filled a prescription for statins. The researchers looked at statin prescriptions filled prior to and after diagnosis, following patients from diagnosis up to a 3-month lag period. The statins analyzed included atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin.
Overall, 78.8% of patients died during 26,680 person-years of follow-up and the median survival time was 17.24 months. The researchers found 14.9% of patients (2,293 patients) with HCC filled prescriptions for statins after their cancer diagnosis. The median time to begin statins after diagnosis was 2.37 months, and patients who used statins after diagnosis had a median survival time of 26.38 months compared with 15.67 months for patients who did not use statins after diagnosis. For HCC patients who used statins, there was a decreased risk of all-cause mortality (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95) and cancer-specific mortality (adjusted HR, 0.85; 95% CI, 0.77-0.93), which was consistent for both high-dose and low-dose statins and for lag periods between 0 months and 12 months after diagnosis.
Limitations in the study were the exclusion of any statins filled at non-VA pharmacies, baseline differences in statin users and nonstatin users that could have affected results, potential misclassification of cirrhosis in the registry, and the lack of generalization to other populations due to a veteran-specific patient cohort.
This study was funded by the National Institutes of Health and VA Health Services Research and Development Service Center for Innovations in Quality, Effectiveness, and Safety. The authors report having no conflicts of interest.
SOURCE: Thrift AP et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2018.12.046.
Statin use after a diagnosis of hepatocellular carcinoma (HCC) was associated with a reduced risk of all-cause and cancer-specific mortality, according to recent research published in Clinical Gastroenterology and Hepatology.
“Our current findings are biologically plausible since statins inhibit not only cholesterol synthesis but also reduce other important downstream products, including membrane integrity maintenance, cell signaling, protein synthesis, and cell-cycle progression,” wrote Aaron P. Thrift, PhD, of the section of epidemiology and population sciences and department of medicine at Baylor College of Medicine in Houston, and his colleagues. “Not only can statins have a direct impact on cancer cells through inhibition of the mevalonate pathway within the cancer cells, but the reduction of circulating cholesterol levels through hepatic pathways is indeed considered important.”
Dr. Thrift and his colleagues performed a retrospective cohort analysis of data from 15,422 patients with HCC in the VA Central Cancer Registry who were diagnosed between 2002 and 2016 and filled a prescription for statins. The researchers looked at statin prescriptions filled prior to and after diagnosis, following patients from diagnosis up to a 3-month lag period. The statins analyzed included atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin.
Overall, 78.8% of patients died during 26,680 person-years of follow-up and the median survival time was 17.24 months. The researchers found 14.9% of patients (2,293 patients) with HCC filled prescriptions for statins after their cancer diagnosis. The median time to begin statins after diagnosis was 2.37 months, and patients who used statins after diagnosis had a median survival time of 26.38 months compared with 15.67 months for patients who did not use statins after diagnosis. For HCC patients who used statins, there was a decreased risk of all-cause mortality (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95) and cancer-specific mortality (adjusted HR, 0.85; 95% CI, 0.77-0.93), which was consistent for both high-dose and low-dose statins and for lag periods between 0 months and 12 months after diagnosis.
Limitations in the study were the exclusion of any statins filled at non-VA pharmacies, baseline differences in statin users and nonstatin users that could have affected results, potential misclassification of cirrhosis in the registry, and the lack of generalization to other populations due to a veteran-specific patient cohort.
This study was funded by the National Institutes of Health and VA Health Services Research and Development Service Center for Innovations in Quality, Effectiveness, and Safety. The authors report having no conflicts of interest.
SOURCE: Thrift AP et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2018.12.046.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The use of statins after diagnosis of hepatocellular carcinoma was associated with a lower risk of death.
Major finding: In 14.9% of patients who used statins after diagnosis, the rate of all-cause mortality (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95) and cancer-specific mortality (adjusted HR, 0.85; 95% CI, 0.77-0.93) was lower, and was consistent for both high-dose and low-dose statins.
Study details: A retrospective analysis of 15,422 patients with hepatocellular carcinoma in the VA Central Cancer Registry between 2002 and 2016.
Disclosures: This study was funded by the National Institutes of Health and VA Health Services Research and Development Service Center for Innovations in Quality, Effectiveness, and Safety. The authors report having no conflicts of interest.
Source: Thrift AP et al. Clin Gastroenterol Hepatol. 2018. doi: 10.1016/j.cgh.2018.12.046.
Risk-based testing missed 35% of HCV-positive prison inmates
Routine testing for hepatitis C virus at inmate entry should be considered by U.S. state prisons, according to Sabrina A. Assoumou, MD, of the Boston Medical Center and her colleagues.
The researchers performed a retrospective analysis of individuals entering the Washington state prison system, which routinely offers hepatitis C virus (HCV) testing, in order to compare routine opt-out testing with current risk-based and one-time testing for individuals born between 1945 and 1965. Additionally, liver fibrosis stage was characterized in blood samples from HCV-positive individuals, the investigators wrote in the American Journal of Preventative Medicine.
Between 2012 and 2016, 24,567 (83%) individuals were tested for HCV antibody, and of these, 4,921 (20%) tested positive. A total of 2,403 (49%) of those testing positive had subsequent hepatitis HCV RNA testing, with 1,727 (72%) of these showing chronic infection.
As expected, Dr. Assoumou and her colleagues found that reactive antibodies was more prevalent in individuals born between 1945 and 1965, compared with other years (44% vs. 17%). However, in actual case numbers, most (72%) were outside of this age bracket. Overall, they calculated that up to 35% of positive HCV tests would be missed using testing targeted by birth cohort and risk behavior alone. Among the chronically infected individuals, 23% had showed at least moderate liver fibrosis.
“Routine opt-out testing identified a substantial number of HCV cases that would have been missed by targeted testing. Almost one-quarter of individuals with chronic HCV had significant liver fibrosis and thus a more urgent need for treatment to prevent complications,” Dr Assoumou and her colleagues concluded.
The researchers reported that they had no conflicts of interest.
SOURCE: Assoumou SA et al, Am J Prev Med. 2019;56:8-16.
Routine testing for hepatitis C virus at inmate entry should be considered by U.S. state prisons, according to Sabrina A. Assoumou, MD, of the Boston Medical Center and her colleagues.
The researchers performed a retrospective analysis of individuals entering the Washington state prison system, which routinely offers hepatitis C virus (HCV) testing, in order to compare routine opt-out testing with current risk-based and one-time testing for individuals born between 1945 and 1965. Additionally, liver fibrosis stage was characterized in blood samples from HCV-positive individuals, the investigators wrote in the American Journal of Preventative Medicine.
Between 2012 and 2016, 24,567 (83%) individuals were tested for HCV antibody, and of these, 4,921 (20%) tested positive. A total of 2,403 (49%) of those testing positive had subsequent hepatitis HCV RNA testing, with 1,727 (72%) of these showing chronic infection.
As expected, Dr. Assoumou and her colleagues found that reactive antibodies was more prevalent in individuals born between 1945 and 1965, compared with other years (44% vs. 17%). However, in actual case numbers, most (72%) were outside of this age bracket. Overall, they calculated that up to 35% of positive HCV tests would be missed using testing targeted by birth cohort and risk behavior alone. Among the chronically infected individuals, 23% had showed at least moderate liver fibrosis.
“Routine opt-out testing identified a substantial number of HCV cases that would have been missed by targeted testing. Almost one-quarter of individuals with chronic HCV had significant liver fibrosis and thus a more urgent need for treatment to prevent complications,” Dr Assoumou and her colleagues concluded.
The researchers reported that they had no conflicts of interest.
SOURCE: Assoumou SA et al, Am J Prev Med. 2019;56:8-16.
Routine testing for hepatitis C virus at inmate entry should be considered by U.S. state prisons, according to Sabrina A. Assoumou, MD, of the Boston Medical Center and her colleagues.
The researchers performed a retrospective analysis of individuals entering the Washington state prison system, which routinely offers hepatitis C virus (HCV) testing, in order to compare routine opt-out testing with current risk-based and one-time testing for individuals born between 1945 and 1965. Additionally, liver fibrosis stage was characterized in blood samples from HCV-positive individuals, the investigators wrote in the American Journal of Preventative Medicine.
Between 2012 and 2016, 24,567 (83%) individuals were tested for HCV antibody, and of these, 4,921 (20%) tested positive. A total of 2,403 (49%) of those testing positive had subsequent hepatitis HCV RNA testing, with 1,727 (72%) of these showing chronic infection.
As expected, Dr. Assoumou and her colleagues found that reactive antibodies was more prevalent in individuals born between 1945 and 1965, compared with other years (44% vs. 17%). However, in actual case numbers, most (72%) were outside of this age bracket. Overall, they calculated that up to 35% of positive HCV tests would be missed using testing targeted by birth cohort and risk behavior alone. Among the chronically infected individuals, 23% had showed at least moderate liver fibrosis.
“Routine opt-out testing identified a substantial number of HCV cases that would have been missed by targeted testing. Almost one-quarter of individuals with chronic HCV had significant liver fibrosis and thus a more urgent need for treatment to prevent complications,” Dr Assoumou and her colleagues concluded.
The researchers reported that they had no conflicts of interest.
SOURCE: Assoumou SA et al, Am J Prev Med. 2019;56:8-16.
FROM THE AMERICAN JOURNAL OF PREVENTIVE MEDICINE
Biomarker algorithm may offer noninvasive look at liver fibrosis
Serum biomarkers may enable a noninvasive method of detecting advanced hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), according to results from a recent study.
An algorithm created by the investigators distinguished NAFLD patients with advanced liver fibrosis from those with mild to moderate fibrosis, reported lead author Rohit Loomba, MD, of the University of California at San Diego and his colleagues.
“Liver biopsy is currently the gold standard for diagnosing NASH [nonalcoholic steatohepatitis] and staging liver fibrosis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, it is a costly and invasive procedure with an all-cause mortality risk of approximately 0.2%. Liver biopsy typically samples only 1/50,000th of the organ, and it is liable to sampling error with an error rate of 25% for diagnosis of hepatic fibrosis.”
Existing serum-based tests are reliable for diagnosing nonfibrotic NAFLD, but they may misdiagnosis patients with advanced fibrosis. Although imaging-based techniques may provide better diagnostic accuracy, some are available only for subgroups of patients, while others come with a high financial burden. Diagnostic shortcomings may have a major effect on patient outcomes, particularly when risk groups are considered.
“Fibrosis stages F3 and F4 (advanced fibrosis) are primary predictors of liver-related morbidity and mortality, with 11%-22% of NASH patients reported to have advanced fibrosis,” the investigators noted.
The investigators therefore aimed to distinguish such high-risk NAFLD patients from those with mild or moderate liver fibrosis. Three biomarkers were included: hyaluronic acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP-1), and alpha2-macroglobulin (A2M). Each biomarker has documented associations with liver fibrosis. For instance, higher A2M concentrations inhibit fibrinolysis, HA is associated with excessive extracellular matrix and fibrotic tissue, and TIMP-1 is a known liver fibrosis marker and inhibitor of extracellular matrix degradation. The relative strengths of each in detecting advanced liver fibrosis was determined through an algorithm.
The investigators relied on archived serum samples from Duke University, Durham, N.C., (n = 792) and University of California at San Diego (n = 244) that were collected within 11 days of liver biopsy. Biopsies were performed with 15- to 16-gauge needles using at least eight portal tracts, and these samples were used to diagnose NAFLD. Patients with alcoholic liver disease or hepatitis C virus were excluded.
Algorithm training was based on serum measurements from 396 patients treated at Duke University. Samples were divided into mild to moderate (F0-F2) or advanced (F3-F4) fibrosis and split into 10 subsets. The logical regression model was trained on nine subsets and tested on the 10th, with iterations 10 times through this sequence until all 10 samples were tested. This process was repeated 10,000 times. Using the median coefficients from 100,000 logistical regression models, the samples were scored using the algorithm from 0 to 100, with higher numbers representing more advanced fibrosis, and the relative weights of each biomarker measurement were determined.
A noninferiority protocol was used to validate the algorithm, through which the area under the receiver operating characteristic (AUROC) curve was calculated. The AUROC curve of the validation samples was 0.856, with 0.5 being the score for a random algorithm. The algorithm correctly classified 90.0% of F0 cases, 75.0% of F1 cases, 53.8% of F2 cases, 77.4% of F3 cases, and 94.4% of F4 cases. The sensitivity was 79.7% and the specificity was 75.7%.
The algorithm was superior to Fibrosis-4 (FIB-4) and NAFLD Fibrosis Score (NFS) in two validation cohorts. In a combination of validation cohorts, the algorithm correctly identified 79.5% of F3-F4 patients, compared with rates of 25.8% and 28.0% from FIB-4 and NFS, respectively. The investigators noted that the algorithm was unaffected by sex or age. In contrast, FIB-4 is biased toward females, and both FIB-4 and NFS are less accurate with patients aged 35 years or younger.
“Performance of the training and validation sets was robust and well matched, enabling the reliable differentiation of NAFLD patients with and without advanced fibrosis,” the investigators concluded.
The study was supported by Prometheus Laboratories. Authors not employed by Prometheus Laboratories were employed by Duke University or the University of California, San Diego; each institution received funding from Prometheus Laboratories.
SOURCE: Loomba R et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.004.
Serum biomarkers may enable a noninvasive method of detecting advanced hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), according to results from a recent study.
An algorithm created by the investigators distinguished NAFLD patients with advanced liver fibrosis from those with mild to moderate fibrosis, reported lead author Rohit Loomba, MD, of the University of California at San Diego and his colleagues.
“Liver biopsy is currently the gold standard for diagnosing NASH [nonalcoholic steatohepatitis] and staging liver fibrosis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, it is a costly and invasive procedure with an all-cause mortality risk of approximately 0.2%. Liver biopsy typically samples only 1/50,000th of the organ, and it is liable to sampling error with an error rate of 25% for diagnosis of hepatic fibrosis.”
Existing serum-based tests are reliable for diagnosing nonfibrotic NAFLD, but they may misdiagnosis patients with advanced fibrosis. Although imaging-based techniques may provide better diagnostic accuracy, some are available only for subgroups of patients, while others come with a high financial burden. Diagnostic shortcomings may have a major effect on patient outcomes, particularly when risk groups are considered.
“Fibrosis stages F3 and F4 (advanced fibrosis) are primary predictors of liver-related morbidity and mortality, with 11%-22% of NASH patients reported to have advanced fibrosis,” the investigators noted.
The investigators therefore aimed to distinguish such high-risk NAFLD patients from those with mild or moderate liver fibrosis. Three biomarkers were included: hyaluronic acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP-1), and alpha2-macroglobulin (A2M). Each biomarker has documented associations with liver fibrosis. For instance, higher A2M concentrations inhibit fibrinolysis, HA is associated with excessive extracellular matrix and fibrotic tissue, and TIMP-1 is a known liver fibrosis marker and inhibitor of extracellular matrix degradation. The relative strengths of each in detecting advanced liver fibrosis was determined through an algorithm.
The investigators relied on archived serum samples from Duke University, Durham, N.C., (n = 792) and University of California at San Diego (n = 244) that were collected within 11 days of liver biopsy. Biopsies were performed with 15- to 16-gauge needles using at least eight portal tracts, and these samples were used to diagnose NAFLD. Patients with alcoholic liver disease or hepatitis C virus were excluded.
Algorithm training was based on serum measurements from 396 patients treated at Duke University. Samples were divided into mild to moderate (F0-F2) or advanced (F3-F4) fibrosis and split into 10 subsets. The logical regression model was trained on nine subsets and tested on the 10th, with iterations 10 times through this sequence until all 10 samples were tested. This process was repeated 10,000 times. Using the median coefficients from 100,000 logistical regression models, the samples were scored using the algorithm from 0 to 100, with higher numbers representing more advanced fibrosis, and the relative weights of each biomarker measurement were determined.
A noninferiority protocol was used to validate the algorithm, through which the area under the receiver operating characteristic (AUROC) curve was calculated. The AUROC curve of the validation samples was 0.856, with 0.5 being the score for a random algorithm. The algorithm correctly classified 90.0% of F0 cases, 75.0% of F1 cases, 53.8% of F2 cases, 77.4% of F3 cases, and 94.4% of F4 cases. The sensitivity was 79.7% and the specificity was 75.7%.
The algorithm was superior to Fibrosis-4 (FIB-4) and NAFLD Fibrosis Score (NFS) in two validation cohorts. In a combination of validation cohorts, the algorithm correctly identified 79.5% of F3-F4 patients, compared with rates of 25.8% and 28.0% from FIB-4 and NFS, respectively. The investigators noted that the algorithm was unaffected by sex or age. In contrast, FIB-4 is biased toward females, and both FIB-4 and NFS are less accurate with patients aged 35 years or younger.
“Performance of the training and validation sets was robust and well matched, enabling the reliable differentiation of NAFLD patients with and without advanced fibrosis,” the investigators concluded.
The study was supported by Prometheus Laboratories. Authors not employed by Prometheus Laboratories were employed by Duke University or the University of California, San Diego; each institution received funding from Prometheus Laboratories.
SOURCE: Loomba R et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.004.
Serum biomarkers may enable a noninvasive method of detecting advanced hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), according to results from a recent study.
An algorithm created by the investigators distinguished NAFLD patients with advanced liver fibrosis from those with mild to moderate fibrosis, reported lead author Rohit Loomba, MD, of the University of California at San Diego and his colleagues.
“Liver biopsy is currently the gold standard for diagnosing NASH [nonalcoholic steatohepatitis] and staging liver fibrosis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, it is a costly and invasive procedure with an all-cause mortality risk of approximately 0.2%. Liver biopsy typically samples only 1/50,000th of the organ, and it is liable to sampling error with an error rate of 25% for diagnosis of hepatic fibrosis.”
Existing serum-based tests are reliable for diagnosing nonfibrotic NAFLD, but they may misdiagnosis patients with advanced fibrosis. Although imaging-based techniques may provide better diagnostic accuracy, some are available only for subgroups of patients, while others come with a high financial burden. Diagnostic shortcomings may have a major effect on patient outcomes, particularly when risk groups are considered.
“Fibrosis stages F3 and F4 (advanced fibrosis) are primary predictors of liver-related morbidity and mortality, with 11%-22% of NASH patients reported to have advanced fibrosis,” the investigators noted.
The investigators therefore aimed to distinguish such high-risk NAFLD patients from those with mild or moderate liver fibrosis. Three biomarkers were included: hyaluronic acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP-1), and alpha2-macroglobulin (A2M). Each biomarker has documented associations with liver fibrosis. For instance, higher A2M concentrations inhibit fibrinolysis, HA is associated with excessive extracellular matrix and fibrotic tissue, and TIMP-1 is a known liver fibrosis marker and inhibitor of extracellular matrix degradation. The relative strengths of each in detecting advanced liver fibrosis was determined through an algorithm.
The investigators relied on archived serum samples from Duke University, Durham, N.C., (n = 792) and University of California at San Diego (n = 244) that were collected within 11 days of liver biopsy. Biopsies were performed with 15- to 16-gauge needles using at least eight portal tracts, and these samples were used to diagnose NAFLD. Patients with alcoholic liver disease or hepatitis C virus were excluded.
Algorithm training was based on serum measurements from 396 patients treated at Duke University. Samples were divided into mild to moderate (F0-F2) or advanced (F3-F4) fibrosis and split into 10 subsets. The logical regression model was trained on nine subsets and tested on the 10th, with iterations 10 times through this sequence until all 10 samples were tested. This process was repeated 10,000 times. Using the median coefficients from 100,000 logistical regression models, the samples were scored using the algorithm from 0 to 100, with higher numbers representing more advanced fibrosis, and the relative weights of each biomarker measurement were determined.
A noninferiority protocol was used to validate the algorithm, through which the area under the receiver operating characteristic (AUROC) curve was calculated. The AUROC curve of the validation samples was 0.856, with 0.5 being the score for a random algorithm. The algorithm correctly classified 90.0% of F0 cases, 75.0% of F1 cases, 53.8% of F2 cases, 77.4% of F3 cases, and 94.4% of F4 cases. The sensitivity was 79.7% and the specificity was 75.7%.
The algorithm was superior to Fibrosis-4 (FIB-4) and NAFLD Fibrosis Score (NFS) in two validation cohorts. In a combination of validation cohorts, the algorithm correctly identified 79.5% of F3-F4 patients, compared with rates of 25.8% and 28.0% from FIB-4 and NFS, respectively. The investigators noted that the algorithm was unaffected by sex or age. In contrast, FIB-4 is biased toward females, and both FIB-4 and NFS are less accurate with patients aged 35 years or younger.
“Performance of the training and validation sets was robust and well matched, enabling the reliable differentiation of NAFLD patients with and without advanced fibrosis,” the investigators concluded.
The study was supported by Prometheus Laboratories. Authors not employed by Prometheus Laboratories were employed by Duke University or the University of California, San Diego; each institution received funding from Prometheus Laboratories.
SOURCE: Loomba R et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.004.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: A serum biomarker–based algorithm may provide a noninvasive method of detecting advanced hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).
Major finding: The area under the receiver operator characteristic (AUROC) curve for a combination of validation samples was 0.856.
Study details: A retrospective study of liver fibrosis serum markers and clinical data from 396 patients with NAFLD and various stages of fibrosis.
Disclosures: The study was supported by Prometheus Laboratories. Authors not employed by Prometheus Laboratories were employed by Duke University or the University of California, San Diego; each institution received funding from Prometheus Laboratories.
Source: Loomba R et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.004.
HCC screening linked with improved tumor detection
“Our study’s aim was to characterize utilization of HCC screening receipt and its association with early tumor detection and improved survival in a nationally representative cohort of patients in the United States,” wrote Debra T. Choi, PhD, MPH, of Baylor College of Medicine, Houston, and her colleagues.
The researchers retrospectively studied a cohort of 13,174 patients with HCC from 2003 to 2013 included in the Surveillance, Epidemiology, and End Results Program–Medicare database. They examined the acquisition of HCC in the 3 years leading up to HCC diagnosis using three separate categories: consistent, inconsistent, or no screening. Dr. Choi and her colleagues studied the associations between receiving HCC screening and subsequent effects on overall survival.
“HCC prognosis depends on tumor stage at the time of diagnosis, with curative treatment options only available for patients diagnosed at an early stage,” the researchers wrote. “Patients with early-stage HCC can achieve 5-year survival rates of 70% if they undergo surgical resection or liver transplantation, compared to a median survival of 1 year for patients with advanced HCC,” they added.
After multivariable analysis, the investigators found that 51.1% of patients with cirrhosis did not receive screening in the 3 years leading up to HCC diagnosis. In addition, they went on to report that only 6.8% of patients were consistently screened on an annual basis.
“HCC screening receipt was associated with early tumor detection and potentially improved overall survival, with attenuated benefits in those with inconsistent screening compared to those who had received consistent screening,” they explained.
In terms of efficacy, consistent screening was associated with an increased rate of early-stage tumor detection (odds ratio, 1.98, 95% confidence interval, 1.68-2.33) and decreased risk of death (hazard ratio, 0.76, 95% CI, 0.70-0.83) after adjustment for lead time bias. Given these results, Dr. Choi and her colleagues said that early HCC screening may help with hepatic tumor detection at later disease stages.
“Given the demonstrated benefits of HCC screening, [it] is an important step to reverse the high rates of late stage diagnosis and poor survival,” they added.
The investigators noted that several patient-specific factors may be driving these associations. In particular, they found a link between female sex and receiving HCC screening. Dr. Choi and her colleagues suggested this association is not related to the perceived benefits from screening.
“Studies have suggested females may be more likely to adhere to screening recommendations; however, patient adherence is not a common barrier to HCC screening completion and therefore it is unclear if this is the sole driver of this association,” they acknowledged.
Moving forward, the researchers highlighted the importance of educating primary care providers about the benefits of screening. Moreover, they said that screening receipt is currently on the rise, which has shown positive effects on overall survival.
The Center for Innovations in Quality, Effectiveness, and Safety funded the study. Additional support was provided by the Texas A&M Health Science Center Engineering Experiment Station big data seed grant program. The authors reported no conflicts of interest.
SOURCE: Choi DT et al. Clin Gastroenterol Hepatol. 2018 Oct 25. doi: 10.1016/j.cgh.2018.10.031.
“Our study’s aim was to characterize utilization of HCC screening receipt and its association with early tumor detection and improved survival in a nationally representative cohort of patients in the United States,” wrote Debra T. Choi, PhD, MPH, of Baylor College of Medicine, Houston, and her colleagues.
The researchers retrospectively studied a cohort of 13,174 patients with HCC from 2003 to 2013 included in the Surveillance, Epidemiology, and End Results Program–Medicare database. They examined the acquisition of HCC in the 3 years leading up to HCC diagnosis using three separate categories: consistent, inconsistent, or no screening. Dr. Choi and her colleagues studied the associations between receiving HCC screening and subsequent effects on overall survival.
“HCC prognosis depends on tumor stage at the time of diagnosis, with curative treatment options only available for patients diagnosed at an early stage,” the researchers wrote. “Patients with early-stage HCC can achieve 5-year survival rates of 70% if they undergo surgical resection or liver transplantation, compared to a median survival of 1 year for patients with advanced HCC,” they added.
After multivariable analysis, the investigators found that 51.1% of patients with cirrhosis did not receive screening in the 3 years leading up to HCC diagnosis. In addition, they went on to report that only 6.8% of patients were consistently screened on an annual basis.
“HCC screening receipt was associated with early tumor detection and potentially improved overall survival, with attenuated benefits in those with inconsistent screening compared to those who had received consistent screening,” they explained.
In terms of efficacy, consistent screening was associated with an increased rate of early-stage tumor detection (odds ratio, 1.98, 95% confidence interval, 1.68-2.33) and decreased risk of death (hazard ratio, 0.76, 95% CI, 0.70-0.83) after adjustment for lead time bias. Given these results, Dr. Choi and her colleagues said that early HCC screening may help with hepatic tumor detection at later disease stages.
“Given the demonstrated benefits of HCC screening, [it] is an important step to reverse the high rates of late stage diagnosis and poor survival,” they added.
The investigators noted that several patient-specific factors may be driving these associations. In particular, they found a link between female sex and receiving HCC screening. Dr. Choi and her colleagues suggested this association is not related to the perceived benefits from screening.
“Studies have suggested females may be more likely to adhere to screening recommendations; however, patient adherence is not a common barrier to HCC screening completion and therefore it is unclear if this is the sole driver of this association,” they acknowledged.
Moving forward, the researchers highlighted the importance of educating primary care providers about the benefits of screening. Moreover, they said that screening receipt is currently on the rise, which has shown positive effects on overall survival.
The Center for Innovations in Quality, Effectiveness, and Safety funded the study. Additional support was provided by the Texas A&M Health Science Center Engineering Experiment Station big data seed grant program. The authors reported no conflicts of interest.
SOURCE: Choi DT et al. Clin Gastroenterol Hepatol. 2018 Oct 25. doi: 10.1016/j.cgh.2018.10.031.
“Our study’s aim was to characterize utilization of HCC screening receipt and its association with early tumor detection and improved survival in a nationally representative cohort of patients in the United States,” wrote Debra T. Choi, PhD, MPH, of Baylor College of Medicine, Houston, and her colleagues.
The researchers retrospectively studied a cohort of 13,174 patients with HCC from 2003 to 2013 included in the Surveillance, Epidemiology, and End Results Program–Medicare database. They examined the acquisition of HCC in the 3 years leading up to HCC diagnosis using three separate categories: consistent, inconsistent, or no screening. Dr. Choi and her colleagues studied the associations between receiving HCC screening and subsequent effects on overall survival.
“HCC prognosis depends on tumor stage at the time of diagnosis, with curative treatment options only available for patients diagnosed at an early stage,” the researchers wrote. “Patients with early-stage HCC can achieve 5-year survival rates of 70% if they undergo surgical resection or liver transplantation, compared to a median survival of 1 year for patients with advanced HCC,” they added.
After multivariable analysis, the investigators found that 51.1% of patients with cirrhosis did not receive screening in the 3 years leading up to HCC diagnosis. In addition, they went on to report that only 6.8% of patients were consistently screened on an annual basis.
“HCC screening receipt was associated with early tumor detection and potentially improved overall survival, with attenuated benefits in those with inconsistent screening compared to those who had received consistent screening,” they explained.
In terms of efficacy, consistent screening was associated with an increased rate of early-stage tumor detection (odds ratio, 1.98, 95% confidence interval, 1.68-2.33) and decreased risk of death (hazard ratio, 0.76, 95% CI, 0.70-0.83) after adjustment for lead time bias. Given these results, Dr. Choi and her colleagues said that early HCC screening may help with hepatic tumor detection at later disease stages.
“Given the demonstrated benefits of HCC screening, [it] is an important step to reverse the high rates of late stage diagnosis and poor survival,” they added.
The investigators noted that several patient-specific factors may be driving these associations. In particular, they found a link between female sex and receiving HCC screening. Dr. Choi and her colleagues suggested this association is not related to the perceived benefits from screening.
“Studies have suggested females may be more likely to adhere to screening recommendations; however, patient adherence is not a common barrier to HCC screening completion and therefore it is unclear if this is the sole driver of this association,” they acknowledged.
Moving forward, the researchers highlighted the importance of educating primary care providers about the benefits of screening. Moreover, they said that screening receipt is currently on the rise, which has shown positive effects on overall survival.
The Center for Innovations in Quality, Effectiveness, and Safety funded the study. Additional support was provided by the Texas A&M Health Science Center Engineering Experiment Station big data seed grant program. The authors reported no conflicts of interest.
SOURCE: Choi DT et al. Clin Gastroenterol Hepatol. 2018 Oct 25. doi: 10.1016/j.cgh.2018.10.031.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Hepatocellular carcinoma (HCC) screening for patients with cirrhosis remains an underutilized technique to detect early-stage malignancy.
Major finding: Regular HCC screening was associated with an increased rate of early-stage tumor detection (odds ratio, 1.98).
Study details: Retrospective analysis of 13,174 patients with HCC who were screened 3 years prior to cancer diagnosis.
Disclosures: The Center for Innovations in Quality, Effectiveness, and Safety funded the study. Additional support was provided by the Texas A&M Health Science Center Engineering Experiment Station big data seed grant program. The authors reported no conflicts of interest.
Source: Choi DT et al. Clin Gastroenterol Hepatol. 2018 Oct 25. doi: 10.1016/j.cgh.2018.10.031.
It’s time for universal HCV screening in the ED
SAN FRANCISCO – Emergency departments are the ideal place to screen for hepatitis C infection, according to investigators from Vanderbilt University, Nashville, Tenn.
Current recommendations call for screening baby boomers born from 1945 to 1965 and patients with risk factors, especially injection drug use. The problem is that the guidelines don’t say, exactly, how and where that should be done, so uptake has been spotty. Also, people aren’t exactly forthcoming when it comes to admitting IV drug use.
Enter universal screening in the ED. Vanderbilt is one of several academic centers that have adopted the approach, and others are following suit. Across the board, they’ve found that HCV infection is more common than projections based on baby boomer and risk factor demographics suggest, and, even more importantly, the boomer/risk factor strategy misses a large number of active cases, said Cody A. Chastain, MD, assistant professor of infectious diseases at Vanderbilt, who led the ED screening initiative.
In short, universal screening in the ED would keep people from falling through the cracks.
From April 2017 to March 2018, every adult who had blood drawn at Vanderbilt’s tertiary care ED was asked by a nurse if they’d also like to be checked for HCV, so long as they were alert enough for the conversation. If they agreed, an additional phlebotomy tube was added to the draw, and sent off for testing. Fewer than 5% of patients opted out.
Antibody positive samples were automatically screened for active disease by HCV RNA. Results were entered into the medical record and shared with patients at discharge. Active cases were counseled and offered linkage to care, regardless of insurance status.
The initiative screened 11,637 patients; 1,008 (8.7%) were antibody positive, of whom 488 (48%) were RNA positive. Thirty-seven percent of the active cases were in non–baby boomers – most born after 1965 – with no known injection drug use. The baby boomer/risk factor model would have missed most of them.
Also, spontaneous clearance – antibody positive, RNA negative without HCV treatment – “is dramatically higher” than what’s thought. “The historic estimate of 20% clearly is not reflected” in the Vanderbilt results, nor in similar universal screening studies; “spontaneous clearance is about 50% or so,” Dr. Chastain said.
Even so, “virtually every study published in this space finds more cases of infection than traditional screening would find. [Our work] is just one more piece of data” to indicate the usefulness of the approach. “Emergency departments [are] ideal for hepatitis C screening,” he said at IDWeek, an annual scientific meeting on infectious diseases, where he presented the findings.
“This is well trodden territory; we’ve already addressed it with HIV. We recognized that HIV screening had a stigma and was a challenge, [so we] moved to universal screening” of all adults, at least once. It “drastically improved screening rates. I don’t see a rational reason” not to do this for hepatitis C. “There are very well-meaning people who engage in the cost effectiveness side of this discussion, but I don’t think it helps us in our efforts to control this epidemic from a public health standpoint,” Dr. Chastain said.
Vanderbilt continues to screen for HCV in the ED; the next step is to see how well efforts to link active cases with care are working. Many times during the study, Dr. Chastain said positive patients eventually revealed that they already knew they had HCV, but had been told there was nothing they could do about it, so they didn’t get care. Maybe they were told that because they didn’t have insurance.
Vanderbilt has dropped screening ED patients born before 1945 because the odds of picking up an unknown HCV infection proved to be tiny, and, in any case, patients are generally too comorbid for treatment. It’s made screening more efficient.
Dr. Chastain reported that he had no personal disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.
SOURCE: Chastain C et al. 2018 ID Week, Abstract 932.
SAN FRANCISCO – Emergency departments are the ideal place to screen for hepatitis C infection, according to investigators from Vanderbilt University, Nashville, Tenn.
Current recommendations call for screening baby boomers born from 1945 to 1965 and patients with risk factors, especially injection drug use. The problem is that the guidelines don’t say, exactly, how and where that should be done, so uptake has been spotty. Also, people aren’t exactly forthcoming when it comes to admitting IV drug use.
Enter universal screening in the ED. Vanderbilt is one of several academic centers that have adopted the approach, and others are following suit. Across the board, they’ve found that HCV infection is more common than projections based on baby boomer and risk factor demographics suggest, and, even more importantly, the boomer/risk factor strategy misses a large number of active cases, said Cody A. Chastain, MD, assistant professor of infectious diseases at Vanderbilt, who led the ED screening initiative.
In short, universal screening in the ED would keep people from falling through the cracks.
From April 2017 to March 2018, every adult who had blood drawn at Vanderbilt’s tertiary care ED was asked by a nurse if they’d also like to be checked for HCV, so long as they were alert enough for the conversation. If they agreed, an additional phlebotomy tube was added to the draw, and sent off for testing. Fewer than 5% of patients opted out.
Antibody positive samples were automatically screened for active disease by HCV RNA. Results were entered into the medical record and shared with patients at discharge. Active cases were counseled and offered linkage to care, regardless of insurance status.
The initiative screened 11,637 patients; 1,008 (8.7%) were antibody positive, of whom 488 (48%) were RNA positive. Thirty-seven percent of the active cases were in non–baby boomers – most born after 1965 – with no known injection drug use. The baby boomer/risk factor model would have missed most of them.
Also, spontaneous clearance – antibody positive, RNA negative without HCV treatment – “is dramatically higher” than what’s thought. “The historic estimate of 20% clearly is not reflected” in the Vanderbilt results, nor in similar universal screening studies; “spontaneous clearance is about 50% or so,” Dr. Chastain said.
Even so, “virtually every study published in this space finds more cases of infection than traditional screening would find. [Our work] is just one more piece of data” to indicate the usefulness of the approach. “Emergency departments [are] ideal for hepatitis C screening,” he said at IDWeek, an annual scientific meeting on infectious diseases, where he presented the findings.
“This is well trodden territory; we’ve already addressed it with HIV. We recognized that HIV screening had a stigma and was a challenge, [so we] moved to universal screening” of all adults, at least once. It “drastically improved screening rates. I don’t see a rational reason” not to do this for hepatitis C. “There are very well-meaning people who engage in the cost effectiveness side of this discussion, but I don’t think it helps us in our efforts to control this epidemic from a public health standpoint,” Dr. Chastain said.
Vanderbilt continues to screen for HCV in the ED; the next step is to see how well efforts to link active cases with care are working. Many times during the study, Dr. Chastain said positive patients eventually revealed that they already knew they had HCV, but had been told there was nothing they could do about it, so they didn’t get care. Maybe they were told that because they didn’t have insurance.
Vanderbilt has dropped screening ED patients born before 1945 because the odds of picking up an unknown HCV infection proved to be tiny, and, in any case, patients are generally too comorbid for treatment. It’s made screening more efficient.
Dr. Chastain reported that he had no personal disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.
SOURCE: Chastain C et al. 2018 ID Week, Abstract 932.
SAN FRANCISCO – Emergency departments are the ideal place to screen for hepatitis C infection, according to investigators from Vanderbilt University, Nashville, Tenn.
Current recommendations call for screening baby boomers born from 1945 to 1965 and patients with risk factors, especially injection drug use. The problem is that the guidelines don’t say, exactly, how and where that should be done, so uptake has been spotty. Also, people aren’t exactly forthcoming when it comes to admitting IV drug use.
Enter universal screening in the ED. Vanderbilt is one of several academic centers that have adopted the approach, and others are following suit. Across the board, they’ve found that HCV infection is more common than projections based on baby boomer and risk factor demographics suggest, and, even more importantly, the boomer/risk factor strategy misses a large number of active cases, said Cody A. Chastain, MD, assistant professor of infectious diseases at Vanderbilt, who led the ED screening initiative.
In short, universal screening in the ED would keep people from falling through the cracks.
From April 2017 to March 2018, every adult who had blood drawn at Vanderbilt’s tertiary care ED was asked by a nurse if they’d also like to be checked for HCV, so long as they were alert enough for the conversation. If they agreed, an additional phlebotomy tube was added to the draw, and sent off for testing. Fewer than 5% of patients opted out.
Antibody positive samples were automatically screened for active disease by HCV RNA. Results were entered into the medical record and shared with patients at discharge. Active cases were counseled and offered linkage to care, regardless of insurance status.
The initiative screened 11,637 patients; 1,008 (8.7%) were antibody positive, of whom 488 (48%) were RNA positive. Thirty-seven percent of the active cases were in non–baby boomers – most born after 1965 – with no known injection drug use. The baby boomer/risk factor model would have missed most of them.
Also, spontaneous clearance – antibody positive, RNA negative without HCV treatment – “is dramatically higher” than what’s thought. “The historic estimate of 20% clearly is not reflected” in the Vanderbilt results, nor in similar universal screening studies; “spontaneous clearance is about 50% or so,” Dr. Chastain said.
Even so, “virtually every study published in this space finds more cases of infection than traditional screening would find. [Our work] is just one more piece of data” to indicate the usefulness of the approach. “Emergency departments [are] ideal for hepatitis C screening,” he said at IDWeek, an annual scientific meeting on infectious diseases, where he presented the findings.
“This is well trodden territory; we’ve already addressed it with HIV. We recognized that HIV screening had a stigma and was a challenge, [so we] moved to universal screening” of all adults, at least once. It “drastically improved screening rates. I don’t see a rational reason” not to do this for hepatitis C. “There are very well-meaning people who engage in the cost effectiveness side of this discussion, but I don’t think it helps us in our efforts to control this epidemic from a public health standpoint,” Dr. Chastain said.
Vanderbilt continues to screen for HCV in the ED; the next step is to see how well efforts to link active cases with care are working. Many times during the study, Dr. Chastain said positive patients eventually revealed that they already knew they had HCV, but had been told there was nothing they could do about it, so they didn’t get care. Maybe they were told that because they didn’t have insurance.
Vanderbilt has dropped screening ED patients born before 1945 because the odds of picking up an unknown HCV infection proved to be tiny, and, in any case, patients are generally too comorbid for treatment. It’s made screening more efficient.
Dr. Chastain reported that he had no personal disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.
SOURCE: Chastain C et al. 2018 ID Week, Abstract 932.
REPORTING FROM IDWEEK 2018
Key clinical point: HCV infection is more common than traditionally thought; screening in the ED will keep people from falling through the cracks.
Major finding: Of patients screened; 8.7% were antibody positive, with 48% of these RNA positive; 37% of active cases were in non–baby boomers with no known injection drug use. Spontaneous remission appeared to top 50%.
Study details: Quality improvement initiative in Vanderbilt University’s tertiary care ED.
Disclosures: Dr. Chastain reported that he had no disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.
Source: Chastain C et al. 2018 ID Week, Abstract 932.