Carolyn Crist

A reduction in portal hepatic pressure gradient (PPG) soon after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) greater than 60% was associated with improved ascites control at 6 weeks in a study published in Hepatology.

“The probability of ascites resolution is much higher if PPG reduction exceeded 60% of PPG before TIPS,” wrote the researchers, led by co–first authors Alexander Queck, MD, a postdoctoral researcher in the department of internal medicine at University Hospital Frankfurt (Germany) and Goethe University Frankfurt, and Louise Schwierz, MD, of the department of internal medicine in the University Hospital Bonn (Germany). “This study suggests that, even in patients with uncomplicated TIPS insertion, a short-term follow-up 6 weeks after TIPS should be scheduled to be able to predict their course of disease.”

Alexander Raths/Fotolia

The authors investigated the decrease of PPG in a single-center, retrospective analysis of 341 patients with liver cirrhosis undergoing TIPS insertion for recurrent or refractory ascites between March 1994 and July 2015. During each procedure, portal and inferior vena cava pressures were invasively measured and correlated with patients’ outcomes and ascites progression over time. In 241 patients, or 71%, chronic alcohol consumption was the reason for cirrhosis development, followed by 13% with chronic viral hepatitis (n = 43). Median survival after TIPS insertion was 102 weeks, and 19 patients received liver transplants over time.

Median portal pressure before TIPS placement was 28 mm Hg, which decreased to a median of 21 mm Hg after TIPS. Median PPG levels were 19 mm Hg before TIPS and 8 mm Hg immediately after TIPS placement.

At the time of TIPS placement, 65 patients, or 19%, had hepatic encephalopathy, and nine had severe hepatic encephalopathy. Six weeks after TIPS, two had episodes of hepatic encephalopathy.

After 6 weeks, ascites significantly improved through TIPS insertion. About 47% had a complete resolution of ascites at 6 weeks, whereas 29% had ascites detectable only by ultrasound and 24% of patients still needed large-volume paracentesis. There was an association between extent of PPG reduction and ascites resolution: Median PPG reduction was 55% of initial PPG in patients with persistence of severe ascites, 58% in patients with ascites detected by ultrasound, and 65% in patients with complete resolution of ascites at 6 weeks after TIPS.

Ascites resolved in 54% of patients with higher PPG reduction (60% or above), compared with 39% of patients with lower PPG reduction (below 60%). Ascites that was detected by ultrasound in another 27% of patients with higher PPG reduction, compared with 31% of patients with lower PPG reduction. In addition, persistent severe ascites was seen in 19% of patients with higher PPG reduction, compared with 30% of patients with lower PPG reduction.

The authors also noted the importance of timing follow-up evaluation: They noted that post-TIPS follow-up is a frequent question and not yet standardized; in this study, they found that, with follow-up at 6 weeks, they could “clearly stratify the course post TIPS” and this could “detect patients at high risk of unstable course of disease.”

PPG reduction of more than 60% after TIPS correlated with resolution of severe ascites 6 weeks after TIPS, the study authors concluded.

A reduction in portal hepatic pressure gradient (PPG) soon after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) greater than 60% was associated with improved ascites control at 6 weeks in a study published in Hepatology.

“The probability of ascites resolution is much higher if PPG reduction exceeded 60% of PPG before TIPS,” wrote the researchers, led by co–first authors Alexander Queck, MD, a postdoctoral researcher in the department of internal medicine at University Hospital Frankfurt (Germany) and Goethe University Frankfurt, and Louise Schwierz, MD, of the department of internal medicine in the University Hospital Bonn (Germany). “This study suggests that, even in patients with uncomplicated TIPS insertion, a short-term follow-up 6 weeks after TIPS should be scheduled to be able to predict their course of disease.”

Alexander Raths/Fotolia

The authors investigated the decrease of PPG in a single-center, retrospective analysis of 341 patients with liver cirrhosis undergoing TIPS insertion for recurrent or refractory ascites between March 1994 and July 2015. During each procedure, portal and inferior vena cava pressures were invasively measured and correlated with patients’ outcomes and ascites progression over time. In 241 patients, or 71%, chronic alcohol consumption was the reason for cirrhosis development, followed by 13% with chronic viral hepatitis (n = 43). Median survival after TIPS insertion was 102 weeks, and 19 patients received liver transplants over time.

Median portal pressure before TIPS placement was 28 mm Hg, which decreased to a median of 21 mm Hg after TIPS. Median PPG levels were 19 mm Hg before TIPS and 8 mm Hg immediately after TIPS placement.

At the time of TIPS placement, 65 patients, or 19%, had hepatic encephalopathy, and nine had severe hepatic encephalopathy. Six weeks after TIPS, two had episodes of hepatic encephalopathy.

After 6 weeks, ascites significantly improved through TIPS insertion. About 47% had a complete resolution of ascites at 6 weeks, whereas 29% had ascites detectable only by ultrasound and 24% of patients still needed large-volume paracentesis. There was an association between extent of PPG reduction and ascites resolution: Median PPG reduction was 55% of initial PPG in patients with persistence of severe ascites, 58% in patients with ascites detected by ultrasound, and 65% in patients with complete resolution of ascites at 6 weeks after TIPS.

Ascites resolved in 54% of patients with higher PPG reduction (60% or above), compared with 39% of patients with lower PPG reduction (below 60%). Ascites that was detected by ultrasound in another 27% of patients with higher PPG reduction, compared with 31% of patients with lower PPG reduction. In addition, persistent severe ascites was seen in 19% of patients with higher PPG reduction, compared with 30% of patients with lower PPG reduction.

The authors also noted the importance of timing follow-up evaluation: They noted that post-TIPS follow-up is a frequent question and not yet standardized; in this study, they found that, with follow-up at 6 weeks, they could “clearly stratify the course post TIPS” and this could “detect patients at high risk of unstable course of disease.”

PPG reduction of more than 60% after TIPS correlated with resolution of severe ascites 6 weeks after TIPS, the study authors concluded.

A reduction in portal hepatic pressure gradient (PPG) soon after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) greater than 60% was associated with improved ascites control at 6 weeks in a study published in Hepatology.

“The probability of ascites resolution is much higher if PPG reduction exceeded 60% of PPG before TIPS,” wrote the researchers, led by co–first authors Alexander Queck, MD, a postdoctoral researcher in the department of internal medicine at University Hospital Frankfurt (Germany) and Goethe University Frankfurt, and Louise Schwierz, MD, of the department of internal medicine in the University Hospital Bonn (Germany). “This study suggests that, even in patients with uncomplicated TIPS insertion, a short-term follow-up 6 weeks after TIPS should be scheduled to be able to predict their course of disease.”

Alexander Raths/Fotolia

The authors investigated the decrease of PPG in a single-center, retrospective analysis of 341 patients with liver cirrhosis undergoing TIPS insertion for recurrent or refractory ascites between March 1994 and July 2015. During each procedure, portal and inferior vena cava pressures were invasively measured and correlated with patients’ outcomes and ascites progression over time. In 241 patients, or 71%, chronic alcohol consumption was the reason for cirrhosis development, followed by 13% with chronic viral hepatitis (n = 43). Median survival after TIPS insertion was 102 weeks, and 19 patients received liver transplants over time.

Median portal pressure before TIPS placement was 28 mm Hg, which decreased to a median of 21 mm Hg after TIPS. Median PPG levels were 19 mm Hg before TIPS and 8 mm Hg immediately after TIPS placement.

At the time of TIPS placement, 65 patients, or 19%, had hepatic encephalopathy, and nine had severe hepatic encephalopathy. Six weeks after TIPS, two had episodes of hepatic encephalopathy.

After 6 weeks, ascites significantly improved through TIPS insertion. About 47% had a complete resolution of ascites at 6 weeks, whereas 29% had ascites detectable only by ultrasound and 24% of patients still needed large-volume paracentesis. There was an association between extent of PPG reduction and ascites resolution: Median PPG reduction was 55% of initial PPG in patients with persistence of severe ascites, 58% in patients with ascites detected by ultrasound, and 65% in patients with complete resolution of ascites at 6 weeks after TIPS.

Ascites resolved in 54% of patients with higher PPG reduction (60% or above), compared with 39% of patients with lower PPG reduction (below 60%). Ascites that was detected by ultrasound in another 27% of patients with higher PPG reduction, compared with 31% of patients with lower PPG reduction. In addition, persistent severe ascites was seen in 19% of patients with higher PPG reduction, compared with 30% of patients with lower PPG reduction.

The authors also noted the importance of timing follow-up evaluation: They noted that post-TIPS follow-up is a frequent question and not yet standardized; in this study, they found that, with follow-up at 6 weeks, they could “clearly stratify the course post TIPS” and this could “detect patients at high risk of unstable course of disease.”

PPG reduction of more than 60% after TIPS correlated with resolution of severe ascites 6 weeks after TIPS, the study authors concluded.

Hepatic protein PP2A-C-alpha may serve as a protective factor against parenteral nutrition–associated hepatic steatosis by improving liver function, according to a recent study published in Cellular and Molecular Gastroenterology and Hepatology.

Parenteral nutrition–associated hepatic steatosis likely involves the down-regulation of hepatic PP2A-C-alpha and consequent increased phosphorylation of Akt2; this in turn alters hepatic lipid metabolism, promotes triglyceride accumulation, and leads to liver injury, wrote the researchers, led by Gulisudumu Maitiabula and Feng Tian of the Research Institute of General Surgery at Jinling Hospital, Nanjing, China, and the Medical School of Nanjing University.

“Our study provides a strong rationale that PP2A-C-alpha may be involved in the pathogenesis of [parenteral nutrition–associated hepatic steatosis],” they wrote. “Further research is merited to establish whether interventions to enhance PP2A function might suppress the development of hepatic steatosis in patients receiving long-term [parenteral nutrition].”

Parenteral nutrition can be a lifesaving therapy for patients with intestinal failure caused by insufficient bowel length or function, the authors noted However, long-term use can lead to potentially fatal complications such as liver disease, but an understanding of the pathological mechanisms behind parenteral nutrition–associated hepatic steatosis limited.

The research team performed comparative proteomic/phosphoproteomic analyses of liver samples from 10 patients with parenteral nutrition–associated hepatic steatosis, as well as 8 cholelithiasis patients as controls, who were admitted to Jinling Hospital between June 2018 and June 2019. The researchers also assessed the effect of PP2A-C-alpha on liver injury from total parenteral nutrition in mice.

The research team found that PP2A-C-alpha was down-regulated in patients and mice with parenteral nutrition–associated hepatic steatosis. In addition, in patients with parenteral nutrition–associated hepatic steatosis, they found enhanced activation of serine/threonine kinase Akt2 and decreased activation of AMPK.

Mice that were given total parenteral nutrition infusion for 14 days developed hepatic steatosis, down-regulation of PP2A-C-alpha, activation of Akt2, and inhibition of AMPK. Hepatocyte-specific deletion of PP2A-C-alpha in mice given parenteral nutrition exacerbated the Akt2 activation, AMPK inhibition, and hepatic steatosis through an effect on fatty acid degradation.

On the other hand, forced expression of PP2A-C-alpha led to reductions in hepatocyte fat deposition and the pathological score for liver steatosis. Overexpression also significantly improved hepatic steatosis, suppressed Akt2, and activated AMPK. In addition, pharmacological activation of Akt2 in mice overexpressing PP2A-C-alpha led to the aggravation of hepatic steatosis.

“Collectively, these observations suggest that [parenteral nutrition] for [more than] 14 days leads to a down-regulation in PP2A-C-alpha expression that activates Akt2-dependent signaling, which would likely lead to hepatic steatosis,” the study authors wrote.

Intervention trials of PP2A-C-alpha in humans have not been performed because PP2A-C-alpha activators or effector analogs were unavailable for clinical use, they wrote. Additional clinical studies are needed to investigate the effects of PP2A-C-alpha intervention on the development of hepatic steatosis in patients receiving long-term parenteral nutrition.

The study was supported by the National Natural Science Foundation of China, the Science Foundation of Outstanding Youth in Jiangsu Province, the National Science and Technology Research Funding for Public Welfare Medical Projects, “The 13th Five-Year Plan” Foundation of Jiangsu Province for Medical Key Talents, and the Natural Science Foundation of Jiangsu Province. The study authors disclosed no conflicts of interest.

Hepatic protein PP2A-C-alpha may serve as a protective factor against parenteral nutrition–associated hepatic steatosis by improving liver function, according to a recent study published in Cellular and Molecular Gastroenterology and Hepatology.

Parenteral nutrition–associated hepatic steatosis likely involves the down-regulation of hepatic PP2A-C-alpha and consequent increased phosphorylation of Akt2; this in turn alters hepatic lipid metabolism, promotes triglyceride accumulation, and leads to liver injury, wrote the researchers, led by Gulisudumu Maitiabula and Feng Tian of the Research Institute of General Surgery at Jinling Hospital, Nanjing, China, and the Medical School of Nanjing University.

“Our study provides a strong rationale that PP2A-C-alpha may be involved in the pathogenesis of [parenteral nutrition–associated hepatic steatosis],” they wrote. “Further research is merited to establish whether interventions to enhance PP2A function might suppress the development of hepatic steatosis in patients receiving long-term [parenteral nutrition].”

Parenteral nutrition can be a lifesaving therapy for patients with intestinal failure caused by insufficient bowel length or function, the authors noted However, long-term use can lead to potentially fatal complications such as liver disease, but an understanding of the pathological mechanisms behind parenteral nutrition–associated hepatic steatosis limited.

The research team performed comparative proteomic/phosphoproteomic analyses of liver samples from 10 patients with parenteral nutrition–associated hepatic steatosis, as well as 8 cholelithiasis patients as controls, who were admitted to Jinling Hospital between June 2018 and June 2019. The researchers also assessed the effect of PP2A-C-alpha on liver injury from total parenteral nutrition in mice.

The research team found that PP2A-C-alpha was down-regulated in patients and mice with parenteral nutrition–associated hepatic steatosis. In addition, in patients with parenteral nutrition–associated hepatic steatosis, they found enhanced activation of serine/threonine kinase Akt2 and decreased activation of AMPK.

Mice that were given total parenteral nutrition infusion for 14 days developed hepatic steatosis, down-regulation of PP2A-C-alpha, activation of Akt2, and inhibition of AMPK. Hepatocyte-specific deletion of PP2A-C-alpha in mice given parenteral nutrition exacerbated the Akt2 activation, AMPK inhibition, and hepatic steatosis through an effect on fatty acid degradation.

On the other hand, forced expression of PP2A-C-alpha led to reductions in hepatocyte fat deposition and the pathological score for liver steatosis. Overexpression also significantly improved hepatic steatosis, suppressed Akt2, and activated AMPK. In addition, pharmacological activation of Akt2 in mice overexpressing PP2A-C-alpha led to the aggravation of hepatic steatosis.

“Collectively, these observations suggest that [parenteral nutrition] for [more than] 14 days leads to a down-regulation in PP2A-C-alpha expression that activates Akt2-dependent signaling, which would likely lead to hepatic steatosis,” the study authors wrote.

Intervention trials of PP2A-C-alpha in humans have not been performed because PP2A-C-alpha activators or effector analogs were unavailable for clinical use, they wrote. Additional clinical studies are needed to investigate the effects of PP2A-C-alpha intervention on the development of hepatic steatosis in patients receiving long-term parenteral nutrition.

The study was supported by the National Natural Science Foundation of China, the Science Foundation of Outstanding Youth in Jiangsu Province, the National Science and Technology Research Funding for Public Welfare Medical Projects, “The 13th Five-Year Plan” Foundation of Jiangsu Province for Medical Key Talents, and the Natural Science Foundation of Jiangsu Province. The study authors disclosed no conflicts of interest.

Hepatic protein PP2A-C-alpha may serve as a protective factor against parenteral nutrition–associated hepatic steatosis by improving liver function, according to a recent study published in Cellular and Molecular Gastroenterology and Hepatology.

Parenteral nutrition–associated hepatic steatosis likely involves the down-regulation of hepatic PP2A-C-alpha and consequent increased phosphorylation of Akt2; this in turn alters hepatic lipid metabolism, promotes triglyceride accumulation, and leads to liver injury, wrote the researchers, led by Gulisudumu Maitiabula and Feng Tian of the Research Institute of General Surgery at Jinling Hospital, Nanjing, China, and the Medical School of Nanjing University.

“Our study provides a strong rationale that PP2A-C-alpha may be involved in the pathogenesis of [parenteral nutrition–associated hepatic steatosis],” they wrote. “Further research is merited to establish whether interventions to enhance PP2A function might suppress the development of hepatic steatosis in patients receiving long-term [parenteral nutrition].”

Parenteral nutrition can be a lifesaving therapy for patients with intestinal failure caused by insufficient bowel length or function, the authors noted However, long-term use can lead to potentially fatal complications such as liver disease, but an understanding of the pathological mechanisms behind parenteral nutrition–associated hepatic steatosis limited.

The research team performed comparative proteomic/phosphoproteomic analyses of liver samples from 10 patients with parenteral nutrition–associated hepatic steatosis, as well as 8 cholelithiasis patients as controls, who were admitted to Jinling Hospital between June 2018 and June 2019. The researchers also assessed the effect of PP2A-C-alpha on liver injury from total parenteral nutrition in mice.

The research team found that PP2A-C-alpha was down-regulated in patients and mice with parenteral nutrition–associated hepatic steatosis. In addition, in patients with parenteral nutrition–associated hepatic steatosis, they found enhanced activation of serine/threonine kinase Akt2 and decreased activation of AMPK.

Mice that were given total parenteral nutrition infusion for 14 days developed hepatic steatosis, down-regulation of PP2A-C-alpha, activation of Akt2, and inhibition of AMPK. Hepatocyte-specific deletion of PP2A-C-alpha in mice given parenteral nutrition exacerbated the Akt2 activation, AMPK inhibition, and hepatic steatosis through an effect on fatty acid degradation.

On the other hand, forced expression of PP2A-C-alpha led to reductions in hepatocyte fat deposition and the pathological score for liver steatosis. Overexpression also significantly improved hepatic steatosis, suppressed Akt2, and activated AMPK. In addition, pharmacological activation of Akt2 in mice overexpressing PP2A-C-alpha led to the aggravation of hepatic steatosis.

“Collectively, these observations suggest that [parenteral nutrition] for [more than] 14 days leads to a down-regulation in PP2A-C-alpha expression that activates Akt2-dependent signaling, which would likely lead to hepatic steatosis,” the study authors wrote.

Intervention trials of PP2A-C-alpha in humans have not been performed because PP2A-C-alpha activators or effector analogs were unavailable for clinical use, they wrote. Additional clinical studies are needed to investigate the effects of PP2A-C-alpha intervention on the development of hepatic steatosis in patients receiving long-term parenteral nutrition.

The study was supported by the National Natural Science Foundation of China, the Science Foundation of Outstanding Youth in Jiangsu Province, the National Science and Technology Research Funding for Public Welfare Medical Projects, “The 13th Five-Year Plan” Foundation of Jiangsu Province for Medical Key Talents, and the Natural Science Foundation of Jiangsu Province. The study authors disclosed no conflicts of interest.

Mortality after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is increased for patients aged 70 and older with cirrhosis, but creatinine and sodium levels can help with decision-making, according to a study published in Hepatology.

TIPS can improve survival in cirrhotic patients with refractory ascites or portal hypertensive bleeding, and age alone shouldn’t preclude older patients from receiving TIPS, wrote the researchers led by Francesco Vizzutti, MD, of the department of experimental and clinical medicine at the University of Florence in Italy.

“However, the indication for TIPS in older adult patients (70 years and over) is debated, and a specific prediction model developed in this particular setting is lacking,” they wrote.

JFalcetti / iStock / Getty Images

Dr. Vizzutti and colleagues aimed to develop and validate a multivariable model to accurately predict mortality in older adults. They prospectively enrolled 411 patients at four Italian referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of variceal bleeding between October 2020 and March 2021.

All patients underwent TIPS placement using Viatorr-covered stent grafts. All patients had follow-up outpatient appointments every 6 months until the end of the study or when clinically indicated, such as recurrence of portal hypertension complications or TIPS dysfunction.

The research team created a competing risks model to predict liver-related mortality attributable to liver failure, portal hypertensive bleeding, hepatorenal syndrome, or hepatocellular carcinoma, with orthotopic liver transplant and death from extrahepatic causes considered as competing events. In older adults, the only competing event was death from extrahepatic causes because this age group could not receive orthotopic liver transplant.

Alcohol use disorder was the most common etiology at 37%, followed by viral infection at 30%. At the time of TIPS placement, alcohol use disorder was present as a main or concomitant etiology of liver disease in 181 patients, including 36 with active alcohol consumption.

Compared with younger patients, older adults had significantly higher prevalence of viral etiology (at 41%) and lower prevalence of alcohol use disorder (at 18%). In terms of liver function, older adults had significantly less advanced liver disease based on international normalized ratio levels, likely “reflecting a more careful selection by physicians when managing older adults,” the study authors wrote. However, older adults had significantly higher creatinine levels than younger patients, “underlining the importance of the assessment of kidney function when selecting patients for TIPS placement,” the authors wrote.

During a median follow-up time of about 20 months after TIPS placement, 99 of 411 (or 24%) of patients died of liver-related causes, 49 underwent a transplant, and 17 died of extrahepatic causes. Among the 99 older adults, 44 (or 44%) died of liver-related causes, and 7 patients died of extrahepatic causes.

In the overall cohort, the probabilities of liver-related death were 13% after 1 year, 17% after 2 years, and 24% after 3 years. The probabilities were higher in older adults, at 19% after 1 year, 30% after 2 years, and 41% after 3 years.

According to the model, age, alcoholic etiology, creatinine levels, and international normalized ratio levels were independently associated with a higher risk of liver-related death. In older adults, creatinine and sodium levels were the only independent risk factors for death.

Notably, older adult patients with favorable creatinine and sodium levels (1.2 mg/dL and 140 mEq/L, respectively) had survival probabilities of liver-related death at 1, 2, and 3 years from TIPS placement of 14%, 26%, and 34%, respectively, the authors wrote. In contrast, older adults with creatinine levels of 2.5 mg/dL and sodium levels of 130 mEq/L had worse outcomes, with risks of liver-related death of 71%, 92%, and 96%, respectively.

“These results suggest that older adult patients with preserved renal function and normal sodium levels could obtain a survival outcome after TIPS placement similar to younger patients,” they wrote. “Moreover, the occurrence of [hepatic encephalopathy] and/or recurrence of ascites or bleeding was not significantly different comparing the two groups of patients according to age.”

Future research should update the prediction model with larger sample sizes, the study authors wrote.

“The decision for or against TIPS should be made only after carefully weighing the risks and benefits, taking into consideration the available literature,” said Bubu Banini, MD, PhD, an assistant professor of digestive diseases and translational research director of the Metabolic Health and Weight Loss Program at Yale University, New Haven, Conn.

Dr. Banini, who wasn’t involved with the study, said the prediction model could be a useful tool to guide the decision-making process.

“As is usually the case with management of portal hypertension–related complications, a multidisciplinary discussion with evaluation of a multitude of factors, including quality of life, comorbidities, risks, and benefits, should guide decision-making,” she said.

Dr. Banini highlighted the finding that alcohol etiology for cirrhosis was associated with higher mortality compared with viral etiology.

“This is important in the context of unfortunately increasing trends in alcohol consumption in the pre- and peri-COVID era and the increased prevalence of alcohol-associated liver disease, especially in women,” she said.

The study was supported by grants from the University of Florence and the University of Modena and Reggio Emilia. The study authors have received lecture fees from Gore Medical, which creates stent grafts. Dr. Banini reported no relevant disclosures.

Mortality after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is increased for patients aged 70 and older with cirrhosis, but creatinine and sodium levels can help with decision-making, according to a study published in Hepatology.

TIPS can improve survival in cirrhotic patients with refractory ascites or portal hypertensive bleeding, and age alone shouldn’t preclude older patients from receiving TIPS, wrote the researchers led by Francesco Vizzutti, MD, of the department of experimental and clinical medicine at the University of Florence in Italy.

“However, the indication for TIPS in older adult patients (70 years and over) is debated, and a specific prediction model developed in this particular setting is lacking,” they wrote.

JFalcetti / iStock / Getty Images

Dr. Vizzutti and colleagues aimed to develop and validate a multivariable model to accurately predict mortality in older adults. They prospectively enrolled 411 patients at four Italian referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of variceal bleeding between October 2020 and March 2021.

All patients underwent TIPS placement using Viatorr-covered stent grafts. All patients had follow-up outpatient appointments every 6 months until the end of the study or when clinically indicated, such as recurrence of portal hypertension complications or TIPS dysfunction.

The research team created a competing risks model to predict liver-related mortality attributable to liver failure, portal hypertensive bleeding, hepatorenal syndrome, or hepatocellular carcinoma, with orthotopic liver transplant and death from extrahepatic causes considered as competing events. In older adults, the only competing event was death from extrahepatic causes because this age group could not receive orthotopic liver transplant.

Alcohol use disorder was the most common etiology at 37%, followed by viral infection at 30%. At the time of TIPS placement, alcohol use disorder was present as a main or concomitant etiology of liver disease in 181 patients, including 36 with active alcohol consumption.

Compared with younger patients, older adults had significantly higher prevalence of viral etiology (at 41%) and lower prevalence of alcohol use disorder (at 18%). In terms of liver function, older adults had significantly less advanced liver disease based on international normalized ratio levels, likely “reflecting a more careful selection by physicians when managing older adults,” the study authors wrote. However, older adults had significantly higher creatinine levels than younger patients, “underlining the importance of the assessment of kidney function when selecting patients for TIPS placement,” the authors wrote.

During a median follow-up time of about 20 months after TIPS placement, 99 of 411 (or 24%) of patients died of liver-related causes, 49 underwent a transplant, and 17 died of extrahepatic causes. Among the 99 older adults, 44 (or 44%) died of liver-related causes, and 7 patients died of extrahepatic causes.

In the overall cohort, the probabilities of liver-related death were 13% after 1 year, 17% after 2 years, and 24% after 3 years. The probabilities were higher in older adults, at 19% after 1 year, 30% after 2 years, and 41% after 3 years.

According to the model, age, alcoholic etiology, creatinine levels, and international normalized ratio levels were independently associated with a higher risk of liver-related death. In older adults, creatinine and sodium levels were the only independent risk factors for death.

Notably, older adult patients with favorable creatinine and sodium levels (1.2 mg/dL and 140 mEq/L, respectively) had survival probabilities of liver-related death at 1, 2, and 3 years from TIPS placement of 14%, 26%, and 34%, respectively, the authors wrote. In contrast, older adults with creatinine levels of 2.5 mg/dL and sodium levels of 130 mEq/L had worse outcomes, with risks of liver-related death of 71%, 92%, and 96%, respectively.

“These results suggest that older adult patients with preserved renal function and normal sodium levels could obtain a survival outcome after TIPS placement similar to younger patients,” they wrote. “Moreover, the occurrence of [hepatic encephalopathy] and/or recurrence of ascites or bleeding was not significantly different comparing the two groups of patients according to age.”

Future research should update the prediction model with larger sample sizes, the study authors wrote.

“The decision for or against TIPS should be made only after carefully weighing the risks and benefits, taking into consideration the available literature,” said Bubu Banini, MD, PhD, an assistant professor of digestive diseases and translational research director of the Metabolic Health and Weight Loss Program at Yale University, New Haven, Conn.

Dr. Banini, who wasn’t involved with the study, said the prediction model could be a useful tool to guide the decision-making process.

“As is usually the case with management of portal hypertension–related complications, a multidisciplinary discussion with evaluation of a multitude of factors, including quality of life, comorbidities, risks, and benefits, should guide decision-making,” she said.

Dr. Banini highlighted the finding that alcohol etiology for cirrhosis was associated with higher mortality compared with viral etiology.

“This is important in the context of unfortunately increasing trends in alcohol consumption in the pre- and peri-COVID era and the increased prevalence of alcohol-associated liver disease, especially in women,” she said.

The study was supported by grants from the University of Florence and the University of Modena and Reggio Emilia. The study authors have received lecture fees from Gore Medical, which creates stent grafts. Dr. Banini reported no relevant disclosures.

Mortality after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is increased for patients aged 70 and older with cirrhosis, but creatinine and sodium levels can help with decision-making, according to a study published in Hepatology.

TIPS can improve survival in cirrhotic patients with refractory ascites or portal hypertensive bleeding, and age alone shouldn’t preclude older patients from receiving TIPS, wrote the researchers led by Francesco Vizzutti, MD, of the department of experimental and clinical medicine at the University of Florence in Italy.

“However, the indication for TIPS in older adult patients (70 years and over) is debated, and a specific prediction model developed in this particular setting is lacking,” they wrote.

JFalcetti / iStock / Getty Images

Dr. Vizzutti and colleagues aimed to develop and validate a multivariable model to accurately predict mortality in older adults. They prospectively enrolled 411 patients at four Italian referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of variceal bleeding between October 2020 and March 2021.

All patients underwent TIPS placement using Viatorr-covered stent grafts. All patients had follow-up outpatient appointments every 6 months until the end of the study or when clinically indicated, such as recurrence of portal hypertension complications or TIPS dysfunction.

The research team created a competing risks model to predict liver-related mortality attributable to liver failure, portal hypertensive bleeding, hepatorenal syndrome, or hepatocellular carcinoma, with orthotopic liver transplant and death from extrahepatic causes considered as competing events. In older adults, the only competing event was death from extrahepatic causes because this age group could not receive orthotopic liver transplant.

Alcohol use disorder was the most common etiology at 37%, followed by viral infection at 30%. At the time of TIPS placement, alcohol use disorder was present as a main or concomitant etiology of liver disease in 181 patients, including 36 with active alcohol consumption.

Compared with younger patients, older adults had significantly higher prevalence of viral etiology (at 41%) and lower prevalence of alcohol use disorder (at 18%). In terms of liver function, older adults had significantly less advanced liver disease based on international normalized ratio levels, likely “reflecting a more careful selection by physicians when managing older adults,” the study authors wrote. However, older adults had significantly higher creatinine levels than younger patients, “underlining the importance of the assessment of kidney function when selecting patients for TIPS placement,” the authors wrote.

During a median follow-up time of about 20 months after TIPS placement, 99 of 411 (or 24%) of patients died of liver-related causes, 49 underwent a transplant, and 17 died of extrahepatic causes. Among the 99 older adults, 44 (or 44%) died of liver-related causes, and 7 patients died of extrahepatic causes.

In the overall cohort, the probabilities of liver-related death were 13% after 1 year, 17% after 2 years, and 24% after 3 years. The probabilities were higher in older adults, at 19% after 1 year, 30% after 2 years, and 41% after 3 years.

According to the model, age, alcoholic etiology, creatinine levels, and international normalized ratio levels were independently associated with a higher risk of liver-related death. In older adults, creatinine and sodium levels were the only independent risk factors for death.

Notably, older adult patients with favorable creatinine and sodium levels (1.2 mg/dL and 140 mEq/L, respectively) had survival probabilities of liver-related death at 1, 2, and 3 years from TIPS placement of 14%, 26%, and 34%, respectively, the authors wrote. In contrast, older adults with creatinine levels of 2.5 mg/dL and sodium levels of 130 mEq/L had worse outcomes, with risks of liver-related death of 71%, 92%, and 96%, respectively.

“These results suggest that older adult patients with preserved renal function and normal sodium levels could obtain a survival outcome after TIPS placement similar to younger patients,” they wrote. “Moreover, the occurrence of [hepatic encephalopathy] and/or recurrence of ascites or bleeding was not significantly different comparing the two groups of patients according to age.”

Future research should update the prediction model with larger sample sizes, the study authors wrote.

“The decision for or against TIPS should be made only after carefully weighing the risks and benefits, taking into consideration the available literature,” said Bubu Banini, MD, PhD, an assistant professor of digestive diseases and translational research director of the Metabolic Health and Weight Loss Program at Yale University, New Haven, Conn.

Dr. Banini, who wasn’t involved with the study, said the prediction model could be a useful tool to guide the decision-making process.

“As is usually the case with management of portal hypertension–related complications, a multidisciplinary discussion with evaluation of a multitude of factors, including quality of life, comorbidities, risks, and benefits, should guide decision-making,” she said.

Dr. Banini highlighted the finding that alcohol etiology for cirrhosis was associated with higher mortality compared with viral etiology.

“This is important in the context of unfortunately increasing trends in alcohol consumption in the pre- and peri-COVID era and the increased prevalence of alcohol-associated liver disease, especially in women,” she said.

The study was supported by grants from the University of Florence and the University of Modena and Reggio Emilia. The study authors have received lecture fees from Gore Medical, which creates stent grafts. Dr. Banini reported no relevant disclosures.

Taking a brief walk after eating can help lower the risk of type 2 diabetes, according to a recent study published in Sports Medicine (2022 Aug;52:1765-87).

Light walking after a meal – even for 2-5 minutes – can reduce blood sugar and insulin levels, the researchers found.

Blood sugar levels spike after eating, and the insulin produced to control them can lead to diabetes and cardiovascular issues, the researchers explained.

“With standing and walking, there are contractions of your muscles” that use glucose and lower blood sugar levels, Aidan Buffey, the lead study author and a PhD student in physical education and sport sciences at the University of Limerick (Ireland), told The Times.

“If you can do physical activity before the glucose peak, typically 60-90 minutes [after eating], that is when you’re going to have the benefit of not having the glucose spike,” he said.

Mr. Buffey and colleagues looked at seven studies to understand what would happen if you used standing or easy walking to interrupt prolonged sitting.

In five of the studies, none of the participants had prediabetes or type 2 diabetes. The other two studies included people with and without diabetes. The people in the studies were asked to either stand or walk for 2-5 minutes every 20-30 minutes over the course of a full day.

All seven studies showed that standing after a meal is better than sitting, and taking a short walk offered even better health benefits. Those who stood up for a short period of time after a meal had improved blood sugar levels but not insulin, while those who took a brief walk after a meal had lower blood sugar and insulin levels. Those who walked also had blood sugar levels that rose and fell more gradually, which is critical for managing diabetes.

Going for a walk, doing housework, or finding other ways to move your body within 60-90 minutes after eating could offer the best results, the study authors concluded.

These “mini-walks” could also be useful during the workday to break up prolonged periods of sitting at a desk.

“People are not going to get up and run on a treadmill or run around the office,” Mr. Buffey told The New York Times.

But making mini-walks a normal thing during the workday could be easy and acceptable at the office, he said. Even if people can’t take walks, standing up will help somewhat.

“Each small thing you do will have benefits, even if it is a small step,” Kershaw Patel, MD, a preventive cardiologist at Houston Methodist Hospital, told the newspaper. Dr. Patel wasn’t involved with the study.

“It’s a gradual effect of more activity, better health,” he said. “Each incremental step, each incremental stand or brisk walk appears to have a benefit.”

A version of this article first appeared on WebMD.com.

Taking a brief walk after eating can help lower the risk of type 2 diabetes, according to a recent study published in Sports Medicine (2022 Aug;52:1765-87).

Light walking after a meal – even for 2-5 minutes – can reduce blood sugar and insulin levels, the researchers found.

Blood sugar levels spike after eating, and the insulin produced to control them can lead to diabetes and cardiovascular issues, the researchers explained.

“With standing and walking, there are contractions of your muscles” that use glucose and lower blood sugar levels, Aidan Buffey, the lead study author and a PhD student in physical education and sport sciences at the University of Limerick (Ireland), told The Times.

“If you can do physical activity before the glucose peak, typically 60-90 minutes [after eating], that is when you’re going to have the benefit of not having the glucose spike,” he said.

Mr. Buffey and colleagues looked at seven studies to understand what would happen if you used standing or easy walking to interrupt prolonged sitting.

In five of the studies, none of the participants had prediabetes or type 2 diabetes. The other two studies included people with and without diabetes. The people in the studies were asked to either stand or walk for 2-5 minutes every 20-30 minutes over the course of a full day.

All seven studies showed that standing after a meal is better than sitting, and taking a short walk offered even better health benefits. Those who stood up for a short period of time after a meal had improved blood sugar levels but not insulin, while those who took a brief walk after a meal had lower blood sugar and insulin levels. Those who walked also had blood sugar levels that rose and fell more gradually, which is critical for managing diabetes.

Going for a walk, doing housework, or finding other ways to move your body within 60-90 minutes after eating could offer the best results, the study authors concluded.

These “mini-walks” could also be useful during the workday to break up prolonged periods of sitting at a desk.

“People are not going to get up and run on a treadmill or run around the office,” Mr. Buffey told The New York Times.

But making mini-walks a normal thing during the workday could be easy and acceptable at the office, he said. Even if people can’t take walks, standing up will help somewhat.

“Each small thing you do will have benefits, even if it is a small step,” Kershaw Patel, MD, a preventive cardiologist at Houston Methodist Hospital, told the newspaper. Dr. Patel wasn’t involved with the study.

“It’s a gradual effect of more activity, better health,” he said. “Each incremental step, each incremental stand or brisk walk appears to have a benefit.”

A version of this article first appeared on WebMD.com.

Taking a brief walk after eating can help lower the risk of type 2 diabetes, according to a recent study published in Sports Medicine (2022 Aug;52:1765-87).

Light walking after a meal – even for 2-5 minutes – can reduce blood sugar and insulin levels, the researchers found.

Blood sugar levels spike after eating, and the insulin produced to control them can lead to diabetes and cardiovascular issues, the researchers explained.

“With standing and walking, there are contractions of your muscles” that use glucose and lower blood sugar levels, Aidan Buffey, the lead study author and a PhD student in physical education and sport sciences at the University of Limerick (Ireland), told The Times.

“If you can do physical activity before the glucose peak, typically 60-90 minutes [after eating], that is when you’re going to have the benefit of not having the glucose spike,” he said.

Mr. Buffey and colleagues looked at seven studies to understand what would happen if you used standing or easy walking to interrupt prolonged sitting.

In five of the studies, none of the participants had prediabetes or type 2 diabetes. The other two studies included people with and without diabetes. The people in the studies were asked to either stand or walk for 2-5 minutes every 20-30 minutes over the course of a full day.

All seven studies showed that standing after a meal is better than sitting, and taking a short walk offered even better health benefits. Those who stood up for a short period of time after a meal had improved blood sugar levels but not insulin, while those who took a brief walk after a meal had lower blood sugar and insulin levels. Those who walked also had blood sugar levels that rose and fell more gradually, which is critical for managing diabetes.

Going for a walk, doing housework, or finding other ways to move your body within 60-90 minutes after eating could offer the best results, the study authors concluded.

These “mini-walks” could also be useful during the workday to break up prolonged periods of sitting at a desk.

“People are not going to get up and run on a treadmill or run around the office,” Mr. Buffey told The New York Times.

But making mini-walks a normal thing during the workday could be easy and acceptable at the office, he said. Even if people can’t take walks, standing up will help somewhat.

“Each small thing you do will have benefits, even if it is a small step,” Kershaw Patel, MD, a preventive cardiologist at Houston Methodist Hospital, told the newspaper. Dr. Patel wasn’t involved with the study.

“It’s a gradual effect of more activity, better health,” he said. “Each incremental step, each incremental stand or brisk walk appears to have a benefit.”

A version of this article first appeared on WebMD.com.

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vonoprazan, a potassium-competitive acid blocker, appears to be superior to standard proton pump inhibitor–based therapy in clarithromycin-resistant Helicobacter pylori strains, as well as noninferior to standard care in nonresistant infections, according to a recent study that supported a Food and Drug Administration approval of vonoprazan dual and triple therapies in May 2022.

For decades, H. pylori has been mostly treated by proton pump inhibitor–based triple therapy, which includes a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. However, eradication rates have dropped below 80% in the United States and Europe, according to the authors, mainly because of rising rates of clarithromycin resistance.

Since H. pylori is a leading cause of peptic ulcer, gastric adenocarcinoma, and gastric mucosa–associated lymphoid tissue lymphoma, better eradication methods should be highlighted, researchers led by William Chey, MD, professor of medicine and director of the GI Physiology Laboratory at Michigan Medicine in Ann Arbor, wrote in Gastroenterology.

In a multicenter, randomized, controlled, phase 3 trial, the research team studied 1,046 treatment-naive adults with H. pylori infection at 103 sites in the U.S., the U.K., Bulgaria, the Czech Republic, Hungary, and Poland between December 2019 and January 2021.

The patients were randomized to receive open-label vonoprazan dual therapy or a double-blind triple therapy twice a day for 14 days. The vonoprazan dual therapy consisted of 20 mg of vonoprazan twice daily and 1 gram of amoxicillin three times per day. The triple therapy consisted of 20 mg of vonoprazan or 30 mg of lansoprazole (standard care), each given with 1 gram of amoxicillin and 500 mg of clarithromycin.

The primary outcome assessed noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains, with a noninferiority margin of 10%. Secondary outcomes assessed the superiority in eradication rates in clarithromycin-resistant infections, as well as in all patients.

Eradication rates for nonresistant strains were 84.7% for vonoprazan triple therapy and 78.5% for vonoprazan dual therapy, compared with 78.8% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered noninferior to standard therapy.

The eradication rates in clarithromycin-resistant infections were 65.8% for vonoprazan triple therapy and 69.6% in vonoprazan dual therapy, compared with 31.9% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior to standard therapy, with a difference of 33.9 percentage points for triple therapy and 37.7 percentage points for dual therapy.

In all patients, the eradication rates were 80.8% for vonoprazan triple therapy and 77.2% for vonoprazan dual therapy, compared with 68.5% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior, with a difference of 12.3 percentage points for triple therapy and 8.7 percentage points for dual therapy.

Treatment-emergent adverse events were reported in 34.1% of patients in the vonoprazan triple therapy group and 29.9% of patients in the vonoprazan dual therapy group, compared with 34.5% in the lansoprazole triple-therapy group. Most adverse events were mild to moderate.

Serious adverse events occurred in 1.3% of the overall study population, including 1.7% of the vonoprazan triple therapy group, 1.4% of the vonoprazan dual therapy group, and 0.9% of the lansoprazole triple therapy group. None were considered related to the study drugs.

Vonoprazan was approved for the treatment of H. pylori infections by the FDA in May 2022, and had already been approved for treatment of H. pylori infections and other acid-related diseases in several other countries. It decreases intragastric pH and maintains it to a greater degree than that of proton pump inhibitors, which has been associated with higher eradication rates, the authors wrote.

“Optimizing current regimens offers the potential to increase eradication rates and reduce additional antibiotic usage, thereby promoting and improving antimicrobial stewardship,” the study authors wrote.

The study was funded by Phathom Pharmaceuticals, which contributed to the design and conduct of the trial, collection and interpretation of the data, preparation and review of the manuscript, and the decision to submit the manuscript for publication. The study authors declared various conflicts of interest, including some who have received compensation as a consultant, advisory committee member, or employee for Phathom Pharmaceuticals.

Vonoprazan, a potassium-competitive acid blocker, appears to be superior to standard proton pump inhibitor–based therapy in clarithromycin-resistant Helicobacter pylori strains, as well as noninferior to standard care in nonresistant infections, according to a recent study that supported a Food and Drug Administration approval of vonoprazan dual and triple therapies in May 2022.

For decades, H. pylori has been mostly treated by proton pump inhibitor–based triple therapy, which includes a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. However, eradication rates have dropped below 80% in the United States and Europe, according to the authors, mainly because of rising rates of clarithromycin resistance.

Since H. pylori is a leading cause of peptic ulcer, gastric adenocarcinoma, and gastric mucosa–associated lymphoid tissue lymphoma, better eradication methods should be highlighted, researchers led by William Chey, MD, professor of medicine and director of the GI Physiology Laboratory at Michigan Medicine in Ann Arbor, wrote in Gastroenterology.

In a multicenter, randomized, controlled, phase 3 trial, the research team studied 1,046 treatment-naive adults with H. pylori infection at 103 sites in the U.S., the U.K., Bulgaria, the Czech Republic, Hungary, and Poland between December 2019 and January 2021.

The patients were randomized to receive open-label vonoprazan dual therapy or a double-blind triple therapy twice a day for 14 days. The vonoprazan dual therapy consisted of 20 mg of vonoprazan twice daily and 1 gram of amoxicillin three times per day. The triple therapy consisted of 20 mg of vonoprazan or 30 mg of lansoprazole (standard care), each given with 1 gram of amoxicillin and 500 mg of clarithromycin.

The primary outcome assessed noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains, with a noninferiority margin of 10%. Secondary outcomes assessed the superiority in eradication rates in clarithromycin-resistant infections, as well as in all patients.

Eradication rates for nonresistant strains were 84.7% for vonoprazan triple therapy and 78.5% for vonoprazan dual therapy, compared with 78.8% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered noninferior to standard therapy.

The eradication rates in clarithromycin-resistant infections were 65.8% for vonoprazan triple therapy and 69.6% in vonoprazan dual therapy, compared with 31.9% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior to standard therapy, with a difference of 33.9 percentage points for triple therapy and 37.7 percentage points for dual therapy.

In all patients, the eradication rates were 80.8% for vonoprazan triple therapy and 77.2% for vonoprazan dual therapy, compared with 68.5% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior, with a difference of 12.3 percentage points for triple therapy and 8.7 percentage points for dual therapy.

Treatment-emergent adverse events were reported in 34.1% of patients in the vonoprazan triple therapy group and 29.9% of patients in the vonoprazan dual therapy group, compared with 34.5% in the lansoprazole triple-therapy group. Most adverse events were mild to moderate.

Serious adverse events occurred in 1.3% of the overall study population, including 1.7% of the vonoprazan triple therapy group, 1.4% of the vonoprazan dual therapy group, and 0.9% of the lansoprazole triple therapy group. None were considered related to the study drugs.

Vonoprazan was approved for the treatment of H. pylori infections by the FDA in May 2022, and had already been approved for treatment of H. pylori infections and other acid-related diseases in several other countries. It decreases intragastric pH and maintains it to a greater degree than that of proton pump inhibitors, which has been associated with higher eradication rates, the authors wrote.

“Optimizing current regimens offers the potential to increase eradication rates and reduce additional antibiotic usage, thereby promoting and improving antimicrobial stewardship,” the study authors wrote.

The study was funded by Phathom Pharmaceuticals, which contributed to the design and conduct of the trial, collection and interpretation of the data, preparation and review of the manuscript, and the decision to submit the manuscript for publication. The study authors declared various conflicts of interest, including some who have received compensation as a consultant, advisory committee member, or employee for Phathom Pharmaceuticals.

Vonoprazan, a potassium-competitive acid blocker, appears to be superior to standard proton pump inhibitor–based therapy in clarithromycin-resistant Helicobacter pylori strains, as well as noninferior to standard care in nonresistant infections, according to a recent study that supported a Food and Drug Administration approval of vonoprazan dual and triple therapies in May 2022.

For decades, H. pylori has been mostly treated by proton pump inhibitor–based triple therapy, which includes a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. However, eradication rates have dropped below 80% in the United States and Europe, according to the authors, mainly because of rising rates of clarithromycin resistance.

Since H. pylori is a leading cause of peptic ulcer, gastric adenocarcinoma, and gastric mucosa–associated lymphoid tissue lymphoma, better eradication methods should be highlighted, researchers led by William Chey, MD, professor of medicine and director of the GI Physiology Laboratory at Michigan Medicine in Ann Arbor, wrote in Gastroenterology.

In a multicenter, randomized, controlled, phase 3 trial, the research team studied 1,046 treatment-naive adults with H. pylori infection at 103 sites in the U.S., the U.K., Bulgaria, the Czech Republic, Hungary, and Poland between December 2019 and January 2021.

The patients were randomized to receive open-label vonoprazan dual therapy or a double-blind triple therapy twice a day for 14 days. The vonoprazan dual therapy consisted of 20 mg of vonoprazan twice daily and 1 gram of amoxicillin three times per day. The triple therapy consisted of 20 mg of vonoprazan or 30 mg of lansoprazole (standard care), each given with 1 gram of amoxicillin and 500 mg of clarithromycin.

The primary outcome assessed noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains, with a noninferiority margin of 10%. Secondary outcomes assessed the superiority in eradication rates in clarithromycin-resistant infections, as well as in all patients.

Eradication rates for nonresistant strains were 84.7% for vonoprazan triple therapy and 78.5% for vonoprazan dual therapy, compared with 78.8% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered noninferior to standard therapy.

The eradication rates in clarithromycin-resistant infections were 65.8% for vonoprazan triple therapy and 69.6% in vonoprazan dual therapy, compared with 31.9% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior to standard therapy, with a difference of 33.9 percentage points for triple therapy and 37.7 percentage points for dual therapy.

In all patients, the eradication rates were 80.8% for vonoprazan triple therapy and 77.2% for vonoprazan dual therapy, compared with 68.5% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior, with a difference of 12.3 percentage points for triple therapy and 8.7 percentage points for dual therapy.

Treatment-emergent adverse events were reported in 34.1% of patients in the vonoprazan triple therapy group and 29.9% of patients in the vonoprazan dual therapy group, compared with 34.5% in the lansoprazole triple-therapy group. Most adverse events were mild to moderate.

Serious adverse events occurred in 1.3% of the overall study population, including 1.7% of the vonoprazan triple therapy group, 1.4% of the vonoprazan dual therapy group, and 0.9% of the lansoprazole triple therapy group. None were considered related to the study drugs.

Vonoprazan was approved for the treatment of H. pylori infections by the FDA in May 2022, and had already been approved for treatment of H. pylori infections and other acid-related diseases in several other countries. It decreases intragastric pH and maintains it to a greater degree than that of proton pump inhibitors, which has been associated with higher eradication rates, the authors wrote.

“Optimizing current regimens offers the potential to increase eradication rates and reduce additional antibiotic usage, thereby promoting and improving antimicrobial stewardship,” the study authors wrote.

The study was funded by Phathom Pharmaceuticals, which contributed to the design and conduct of the trial, collection and interpretation of the data, preparation and review of the manuscript, and the decision to submit the manuscript for publication. The study authors declared various conflicts of interest, including some who have received compensation as a consultant, advisory committee member, or employee for Phathom Pharmaceuticals.

A risk-tailored early-detection strategy for pancreatic cancer that targets patients with new-onset diabetes could be cost effective, according to a recent study.

Screening for pancreatic ductal adenocarcinoma in asymptomatic adults is not recommended, but patients with new-onset diabetes have a risk that’s eight times higher than expected. Screening these patients could improve diagnosis and survival rates if the cancer can be identified at earlier stages, researchers led by Louise Wang, MD, a gastroenterology fellow at the University of Pennsylvania, Philadelphia, wrote in Clinical Gastroenterology and Hepatology.

“As we continue to improve therapies for early-stage pancreatic cancers, especially among the local/resectable stage, the case for the targeted early-detection strategy will be stronger,” they wrote. “Policy makers should take into consideration these novel findings when formulating [pancreatic ductal adenocarcinoma] screening policy and making coverage determinations.”

The research team compared early detection strategies for pancreatic ductal adenocarcinoma that target new-onset diabetes patients at age 50 years and older with standard of care, defined as no early detection strategy. They looked at various minimal predicted cancer risk thresholds versus current standard of care in a Markov state-transition decision model. The analysis assumed a health care sector perspective and a lifetime horizon, with two willingness-to-pay thresholds ($100,000 and $150,000) per quality-adjusted life-year gained.

The researchers used data from one of their previously published studies, which included 89,881 patients with new-onset diabetes diagnosed at age 50 or older. The cumulative incidence of pancreatic cancer was 0.42% during the 3 years after diagnosis.

In the early detection strategy, all patients 50 years and older who were newly diagnosed with diabetes mellitus were placed into low-risk and high-risk cohorts based on their predicted 3-year risk of pancreatic ductal adenocarcinoma under a range of assumed minimum-risk thresholds – 0.5%, 1%, 2%, 3%, 4%, and 5%; these thresholds were based on a previously established prediction model.

The research team found that the early detection strategy that targeted patients with a minimum predicted 3-year pancreatic ductal adenocarcinoma risk of 1% was cost effective, based on a willingness-to-pay threshold of $150,000 per quality-adjusted life-year. The incremental cost-effectiveness ratio was $116,911 per quality-adjusted life-year.

At a willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the early detection strategy at the 2% risk threshold was cost effective. The incremental cost-effectiveness ratio was $63,045 per quality-adjusted life-year.

The most influential factors included the proportion of pancreatic ductal adenocarcinomas detected at the local stage, costs of treatment for metastatic cancer, utilities of local and regional cancers, and sensitivity of screening.

A probabilistic sensitivity analysis confirmed that, at a willingness-to-pay threshold of $150,000, early detection at the 1% risk threshold was favored at 30.6%, followed by the 0.5% risk threshold at 20.4%, compared with the standard of care at 1.7%. In addition, at a willingness-to-pay threshold of $100,000, early detection at the 1% risk threshold was favored at 27.3%, followed by the 2% risk threshold at 22.8%, as compared with the standard of care at 2%.

The two early detection strategies were cost effective, capturing 26%-45% of the pancreatic ductal adenocarcinoma cases in patients with new-onset diabetes.

The study authors noted several limitations, including the inability to incorporate out-of-pocket costs for patients, as well as focusing the analysis on the health care perspective.

“We acknowledge that, by incorporating the full consequences of decisions for all stakeholders, a societal perspective would have offered a more complete view on which to base public policy,” they wrote.

At the same time, “given the substantial prevalence of [new-onset diabetes] among [pancreatic ductal adenocarcinoma] cases, this strategy could improve the survival of a substantial proportion of sporadic PDAC cases in the general population,” they concluded.

The study authors reported various disclosures, including grants and research support from Takeda Pharmaceuticals USA, Janssen Pharmaceuticals, the National Institutes of Health, the Crohn’s and Colitis Foundation, Lilly Oncology, GSK, and Clovis Oncology.

A risk-tailored early-detection strategy for pancreatic cancer that targets patients with new-onset diabetes could be cost effective, according to a recent study.

Screening for pancreatic ductal adenocarcinoma in asymptomatic adults is not recommended, but patients with new-onset diabetes have a risk that’s eight times higher than expected. Screening these patients could improve diagnosis and survival rates if the cancer can be identified at earlier stages, researchers led by Louise Wang, MD, a gastroenterology fellow at the University of Pennsylvania, Philadelphia, wrote in Clinical Gastroenterology and Hepatology.

“As we continue to improve therapies for early-stage pancreatic cancers, especially among the local/resectable stage, the case for the targeted early-detection strategy will be stronger,” they wrote. “Policy makers should take into consideration these novel findings when formulating [pancreatic ductal adenocarcinoma] screening policy and making coverage determinations.”

The research team compared early detection strategies for pancreatic ductal adenocarcinoma that target new-onset diabetes patients at age 50 years and older with standard of care, defined as no early detection strategy. They looked at various minimal predicted cancer risk thresholds versus current standard of care in a Markov state-transition decision model. The analysis assumed a health care sector perspective and a lifetime horizon, with two willingness-to-pay thresholds ($100,000 and $150,000) per quality-adjusted life-year gained.

The researchers used data from one of their previously published studies, which included 89,881 patients with new-onset diabetes diagnosed at age 50 or older. The cumulative incidence of pancreatic cancer was 0.42% during the 3 years after diagnosis.

In the early detection strategy, all patients 50 years and older who were newly diagnosed with diabetes mellitus were placed into low-risk and high-risk cohorts based on their predicted 3-year risk of pancreatic ductal adenocarcinoma under a range of assumed minimum-risk thresholds – 0.5%, 1%, 2%, 3%, 4%, and 5%; these thresholds were based on a previously established prediction model.

The research team found that the early detection strategy that targeted patients with a minimum predicted 3-year pancreatic ductal adenocarcinoma risk of 1% was cost effective, based on a willingness-to-pay threshold of $150,000 per quality-adjusted life-year. The incremental cost-effectiveness ratio was $116,911 per quality-adjusted life-year.

At a willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the early detection strategy at the 2% risk threshold was cost effective. The incremental cost-effectiveness ratio was $63,045 per quality-adjusted life-year.

The most influential factors included the proportion of pancreatic ductal adenocarcinomas detected at the local stage, costs of treatment for metastatic cancer, utilities of local and regional cancers, and sensitivity of screening.

A probabilistic sensitivity analysis confirmed that, at a willingness-to-pay threshold of $150,000, early detection at the 1% risk threshold was favored at 30.6%, followed by the 0.5% risk threshold at 20.4%, compared with the standard of care at 1.7%. In addition, at a willingness-to-pay threshold of $100,000, early detection at the 1% risk threshold was favored at 27.3%, followed by the 2% risk threshold at 22.8%, as compared with the standard of care at 2%.

The two early detection strategies were cost effective, capturing 26%-45% of the pancreatic ductal adenocarcinoma cases in patients with new-onset diabetes.

The study authors noted several limitations, including the inability to incorporate out-of-pocket costs for patients, as well as focusing the analysis on the health care perspective.

“We acknowledge that, by incorporating the full consequences of decisions for all stakeholders, a societal perspective would have offered a more complete view on which to base public policy,” they wrote.

At the same time, “given the substantial prevalence of [new-onset diabetes] among [pancreatic ductal adenocarcinoma] cases, this strategy could improve the survival of a substantial proportion of sporadic PDAC cases in the general population,” they concluded.

The study authors reported various disclosures, including grants and research support from Takeda Pharmaceuticals USA, Janssen Pharmaceuticals, the National Institutes of Health, the Crohn’s and Colitis Foundation, Lilly Oncology, GSK, and Clovis Oncology.

A risk-tailored early-detection strategy for pancreatic cancer that targets patients with new-onset diabetes could be cost effective, according to a recent study.

Screening for pancreatic ductal adenocarcinoma in asymptomatic adults is not recommended, but patients with new-onset diabetes have a risk that’s eight times higher than expected. Screening these patients could improve diagnosis and survival rates if the cancer can be identified at earlier stages, researchers led by Louise Wang, MD, a gastroenterology fellow at the University of Pennsylvania, Philadelphia, wrote in Clinical Gastroenterology and Hepatology.

“As we continue to improve therapies for early-stage pancreatic cancers, especially among the local/resectable stage, the case for the targeted early-detection strategy will be stronger,” they wrote. “Policy makers should take into consideration these novel findings when formulating [pancreatic ductal adenocarcinoma] screening policy and making coverage determinations.”

The research team compared early detection strategies for pancreatic ductal adenocarcinoma that target new-onset diabetes patients at age 50 years and older with standard of care, defined as no early detection strategy. They looked at various minimal predicted cancer risk thresholds versus current standard of care in a Markov state-transition decision model. The analysis assumed a health care sector perspective and a lifetime horizon, with two willingness-to-pay thresholds ($100,000 and $150,000) per quality-adjusted life-year gained.

The researchers used data from one of their previously published studies, which included 89,881 patients with new-onset diabetes diagnosed at age 50 or older. The cumulative incidence of pancreatic cancer was 0.42% during the 3 years after diagnosis.

In the early detection strategy, all patients 50 years and older who were newly diagnosed with diabetes mellitus were placed into low-risk and high-risk cohorts based on their predicted 3-year risk of pancreatic ductal adenocarcinoma under a range of assumed minimum-risk thresholds – 0.5%, 1%, 2%, 3%, 4%, and 5%; these thresholds were based on a previously established prediction model.

The research team found that the early detection strategy that targeted patients with a minimum predicted 3-year pancreatic ductal adenocarcinoma risk of 1% was cost effective, based on a willingness-to-pay threshold of $150,000 per quality-adjusted life-year. The incremental cost-effectiveness ratio was $116,911 per quality-adjusted life-year.

At a willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the early detection strategy at the 2% risk threshold was cost effective. The incremental cost-effectiveness ratio was $63,045 per quality-adjusted life-year.

The most influential factors included the proportion of pancreatic ductal adenocarcinomas detected at the local stage, costs of treatment for metastatic cancer, utilities of local and regional cancers, and sensitivity of screening.

A probabilistic sensitivity analysis confirmed that, at a willingness-to-pay threshold of $150,000, early detection at the 1% risk threshold was favored at 30.6%, followed by the 0.5% risk threshold at 20.4%, compared with the standard of care at 1.7%. In addition, at a willingness-to-pay threshold of $100,000, early detection at the 1% risk threshold was favored at 27.3%, followed by the 2% risk threshold at 22.8%, as compared with the standard of care at 2%.

The two early detection strategies were cost effective, capturing 26%-45% of the pancreatic ductal adenocarcinoma cases in patients with new-onset diabetes.

The study authors noted several limitations, including the inability to incorporate out-of-pocket costs for patients, as well as focusing the analysis on the health care perspective.

“We acknowledge that, by incorporating the full consequences of decisions for all stakeholders, a societal perspective would have offered a more complete view on which to base public policy,” they wrote.

At the same time, “given the substantial prevalence of [new-onset diabetes] among [pancreatic ductal adenocarcinoma] cases, this strategy could improve the survival of a substantial proportion of sporadic PDAC cases in the general population,” they concluded.

The study authors reported various disclosures, including grants and research support from Takeda Pharmaceuticals USA, Janssen Pharmaceuticals, the National Institutes of Health, the Crohn’s and Colitis Foundation, Lilly Oncology, GSK, and Clovis Oncology.

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

A version of this article first appeared on WebMD.com.

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

A version of this article first appeared on WebMD.com.

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

A version of this article first appeared on WebMD.com.

A new blood test that analyzes DNA shed by metastatic cancers could reveal characteristics unique to each patient’s tumor and allow physicians to develop more personalized treatment plans, according to a new report.

The blood test focuses on circulating tumor DNA (ctDNA). By sequencing the complete genome of ctDNA, researchers can learn about the different metastases spread throughout the body.

“A key goal in cancer research is to better understand metastatic cancer in each affected person so we can select the best treatments and avoid giving toxic therapies to people who will not derive benefit,” senior author Alexander Wyatt, MD, DPhil, assistant professor of genitourinary cancer genomics at the University of British Columbia, Vancouver, and senior research scientist at the Vancouver Prostate Center, told this news organization.

“However, biopsies of metastatic cancer are rarely performed since they are invasive and have risks of complications,” he said. “In the past, this major barrier has prevented the widespread study of metastatic cancer and progress to better treatment of this lethal disease.”

The study was published in Nature.
 

Test methods

Blood-based biopsy technology, also known as “liquid biopsy,” has emerged as a tool for clinical cancer genotyping and longitudinal disease monitoring. Tests that use ctDNA have begun to influence the clinical management of people with cancer, the study authors wrote, though the full potential for understanding metastatic cancer biology hasn’t yet been unlocked.

Dr. Wyatt and colleagues analyzed serial plasma and synchronous metastases in patients with aggressive, treatment-resistant prostate cancer through deep whole-genome sequencing, which allows for a comprehensive assessment of every part of the genetic code within the cancer cells.

The researchers assessed all classes of genomic alterations and found that ctDNA contains multiple dominant populations, indicating that most people with metastatic cancer have different metastases spread around the body. They found that the whole-genome sequencing process provides a host of information about these different metastases.

The research team used newly developed computer programs to provide information about the genetic makeup of each cancer population, which can tell researchers about a person’s overall disease rather than about one metastatic tumor. In the future, this information could allow clinicians to make better decisions about managing a patient’s cancer.

The researchers studied multiple ctDNA samples collected over time to understand how a patient’s cancer evolved in response to treatment. They focused on inhibitors of the androgen receptor pathway. They found that current therapies for metastatic prostate cancer actively change the composition of cancer populations in the body and that treatment often selects for biologically aggressive cancer populations that underlie clinical resistance. This allowed them to pinpoint new genetic resistance mechanisms to the most common treatments for metastatic prostate cancer. The technique could be applied to other cancers as well.

The research team used nucleosome footprints in ctDNA to infer mRNA expression in metastases upon which biopsies were synchronously performed. They identified treatment-induced changes in androgen receptor transcription factor signaling activity. This means whole-genome sequencing of ctDNA can reveal the active processes occurring within cells, allowing clinicians to predict which treatments will be effective or ineffective in each patient.

“Our research significantly expands the breadth of cancer information that can be obtained from only a few drops of blood,” said Dr. Wyatt. “From a clinical perspective, this extra information can be used in new clinical trials that are testing strategies to direct cancer treatments only to those whose quality or whose length of life will be improved.”
 

Clinical trials

The study authors wrote that whole-genome ctDNA sequencing technology, which is minimally invasive, inexpensive, and scalable, is now being deployed in large clinical trials to help discover new treatment resistance mechanisms. These include precision oncology clinical trials that are being conducted with Canadian cancer patients at the Vancouver Prostate Centre and BC Cancer.

The technology can also be implemented in existing commercial ctDNA testing platforms, which means that patients could soon directly benefit from more comprehensive liquid biopsy testing. The research team has made the methods and computer code publicly and freely available so that the technology can be applied to other cancer types and clinical settings.

“Understanding how clonal evolution occurs and what drives it is one of the key questions that need to be addressed in almost all cancers, and this study provides that level of insight for advanced prostate cancer, as well as a model and tools for how to carry out this work,” Christopher Mueller, MD, PhD, a cancer biologist and geneticist at Queen’s Cancer Research Institute and a professor of biomedical and molecular sciences at Queen’s University, both in Kingston, Ont., said in an interview.

Dr. Mueller, who wasn’t involved with this study, has researched biomarkers and ctDNA as avenues for more precise management of advanced prostate cancer. He and his colleagues have developed blood tests for detecting and monitoring metastatic breast cancer, uveal melanoma, and prostate, pancreatic, and lung cancer.

“The expansion of treatment-resistant clones is how we lose almost all cancer patients, and they clearly demonstrate that in castrate-resistant prostate cancer, changes in the androgen receptor locus almost always drive this process,” Dr. Mueller said. “Understanding clonal evolution will allow us to design treatment strategies that overcome or limit their expansion, hopefully extending the lives of these patients.”

The study was funded by the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Prostate Cancer Foundation, Prostate Cancer Canada, the Movember Foundation, the Jane and Aatos Erkko Foundation, the Academy of Finland Center of Excellence program, the Terry Fox New Frontiers Program, and the BC Cancer Foundation. Dr. Wyatt has served on advisory boards or has received honoraria from AstraZeneca, Astellas, Janssen, and Merck, and his research lab has a contract research agreement with ESSA Pharma. Dr. Mueller disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new blood test that analyzes DNA shed by metastatic cancers could reveal characteristics unique to each patient’s tumor and allow physicians to develop more personalized treatment plans, according to a new report.

The blood test focuses on circulating tumor DNA (ctDNA). By sequencing the complete genome of ctDNA, researchers can learn about the different metastases spread throughout the body.

“A key goal in cancer research is to better understand metastatic cancer in each affected person so we can select the best treatments and avoid giving toxic therapies to people who will not derive benefit,” senior author Alexander Wyatt, MD, DPhil, assistant professor of genitourinary cancer genomics at the University of British Columbia, Vancouver, and senior research scientist at the Vancouver Prostate Center, told this news organization.

“However, biopsies of metastatic cancer are rarely performed since they are invasive and have risks of complications,” he said. “In the past, this major barrier has prevented the widespread study of metastatic cancer and progress to better treatment of this lethal disease.”

The study was published in Nature.
 

Test methods

Blood-based biopsy technology, also known as “liquid biopsy,” has emerged as a tool for clinical cancer genotyping and longitudinal disease monitoring. Tests that use ctDNA have begun to influence the clinical management of people with cancer, the study authors wrote, though the full potential for understanding metastatic cancer biology hasn’t yet been unlocked.

Dr. Wyatt and colleagues analyzed serial plasma and synchronous metastases in patients with aggressive, treatment-resistant prostate cancer through deep whole-genome sequencing, which allows for a comprehensive assessment of every part of the genetic code within the cancer cells.

The researchers assessed all classes of genomic alterations and found that ctDNA contains multiple dominant populations, indicating that most people with metastatic cancer have different metastases spread around the body. They found that the whole-genome sequencing process provides a host of information about these different metastases.

The research team used newly developed computer programs to provide information about the genetic makeup of each cancer population, which can tell researchers about a person’s overall disease rather than about one metastatic tumor. In the future, this information could allow clinicians to make better decisions about managing a patient’s cancer.

The researchers studied multiple ctDNA samples collected over time to understand how a patient’s cancer evolved in response to treatment. They focused on inhibitors of the androgen receptor pathway. They found that current therapies for metastatic prostate cancer actively change the composition of cancer populations in the body and that treatment often selects for biologically aggressive cancer populations that underlie clinical resistance. This allowed them to pinpoint new genetic resistance mechanisms to the most common treatments for metastatic prostate cancer. The technique could be applied to other cancers as well.

The research team used nucleosome footprints in ctDNA to infer mRNA expression in metastases upon which biopsies were synchronously performed. They identified treatment-induced changes in androgen receptor transcription factor signaling activity. This means whole-genome sequencing of ctDNA can reveal the active processes occurring within cells, allowing clinicians to predict which treatments will be effective or ineffective in each patient.

“Our research significantly expands the breadth of cancer information that can be obtained from only a few drops of blood,” said Dr. Wyatt. “From a clinical perspective, this extra information can be used in new clinical trials that are testing strategies to direct cancer treatments only to those whose quality or whose length of life will be improved.”
 

Clinical trials

The study authors wrote that whole-genome ctDNA sequencing technology, which is minimally invasive, inexpensive, and scalable, is now being deployed in large clinical trials to help discover new treatment resistance mechanisms. These include precision oncology clinical trials that are being conducted with Canadian cancer patients at the Vancouver Prostate Centre and BC Cancer.

The technology can also be implemented in existing commercial ctDNA testing platforms, which means that patients could soon directly benefit from more comprehensive liquid biopsy testing. The research team has made the methods and computer code publicly and freely available so that the technology can be applied to other cancer types and clinical settings.

“Understanding how clonal evolution occurs and what drives it is one of the key questions that need to be addressed in almost all cancers, and this study provides that level of insight for advanced prostate cancer, as well as a model and tools for how to carry out this work,” Christopher Mueller, MD, PhD, a cancer biologist and geneticist at Queen’s Cancer Research Institute and a professor of biomedical and molecular sciences at Queen’s University, both in Kingston, Ont., said in an interview.

Dr. Mueller, who wasn’t involved with this study, has researched biomarkers and ctDNA as avenues for more precise management of advanced prostate cancer. He and his colleagues have developed blood tests for detecting and monitoring metastatic breast cancer, uveal melanoma, and prostate, pancreatic, and lung cancer.

“The expansion of treatment-resistant clones is how we lose almost all cancer patients, and they clearly demonstrate that in castrate-resistant prostate cancer, changes in the androgen receptor locus almost always drive this process,” Dr. Mueller said. “Understanding clonal evolution will allow us to design treatment strategies that overcome or limit their expansion, hopefully extending the lives of these patients.”

The study was funded by the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Prostate Cancer Foundation, Prostate Cancer Canada, the Movember Foundation, the Jane and Aatos Erkko Foundation, the Academy of Finland Center of Excellence program, the Terry Fox New Frontiers Program, and the BC Cancer Foundation. Dr. Wyatt has served on advisory boards or has received honoraria from AstraZeneca, Astellas, Janssen, and Merck, and his research lab has a contract research agreement with ESSA Pharma. Dr. Mueller disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new blood test that analyzes DNA shed by metastatic cancers could reveal characteristics unique to each patient’s tumor and allow physicians to develop more personalized treatment plans, according to a new report.

The blood test focuses on circulating tumor DNA (ctDNA). By sequencing the complete genome of ctDNA, researchers can learn about the different metastases spread throughout the body.

“A key goal in cancer research is to better understand metastatic cancer in each affected person so we can select the best treatments and avoid giving toxic therapies to people who will not derive benefit,” senior author Alexander Wyatt, MD, DPhil, assistant professor of genitourinary cancer genomics at the University of British Columbia, Vancouver, and senior research scientist at the Vancouver Prostate Center, told this news organization.

“However, biopsies of metastatic cancer are rarely performed since they are invasive and have risks of complications,” he said. “In the past, this major barrier has prevented the widespread study of metastatic cancer and progress to better treatment of this lethal disease.”

The study was published in Nature.
 

Test methods

Blood-based biopsy technology, also known as “liquid biopsy,” has emerged as a tool for clinical cancer genotyping and longitudinal disease monitoring. Tests that use ctDNA have begun to influence the clinical management of people with cancer, the study authors wrote, though the full potential for understanding metastatic cancer biology hasn’t yet been unlocked.

Dr. Wyatt and colleagues analyzed serial plasma and synchronous metastases in patients with aggressive, treatment-resistant prostate cancer through deep whole-genome sequencing, which allows for a comprehensive assessment of every part of the genetic code within the cancer cells.

The researchers assessed all classes of genomic alterations and found that ctDNA contains multiple dominant populations, indicating that most people with metastatic cancer have different metastases spread around the body. They found that the whole-genome sequencing process provides a host of information about these different metastases.

The research team used newly developed computer programs to provide information about the genetic makeup of each cancer population, which can tell researchers about a person’s overall disease rather than about one metastatic tumor. In the future, this information could allow clinicians to make better decisions about managing a patient’s cancer.

The researchers studied multiple ctDNA samples collected over time to understand how a patient’s cancer evolved in response to treatment. They focused on inhibitors of the androgen receptor pathway. They found that current therapies for metastatic prostate cancer actively change the composition of cancer populations in the body and that treatment often selects for biologically aggressive cancer populations that underlie clinical resistance. This allowed them to pinpoint new genetic resistance mechanisms to the most common treatments for metastatic prostate cancer. The technique could be applied to other cancers as well.

The research team used nucleosome footprints in ctDNA to infer mRNA expression in metastases upon which biopsies were synchronously performed. They identified treatment-induced changes in androgen receptor transcription factor signaling activity. This means whole-genome sequencing of ctDNA can reveal the active processes occurring within cells, allowing clinicians to predict which treatments will be effective or ineffective in each patient.

“Our research significantly expands the breadth of cancer information that can be obtained from only a few drops of blood,” said Dr. Wyatt. “From a clinical perspective, this extra information can be used in new clinical trials that are testing strategies to direct cancer treatments only to those whose quality or whose length of life will be improved.”
 

Clinical trials

The study authors wrote that whole-genome ctDNA sequencing technology, which is minimally invasive, inexpensive, and scalable, is now being deployed in large clinical trials to help discover new treatment resistance mechanisms. These include precision oncology clinical trials that are being conducted with Canadian cancer patients at the Vancouver Prostate Centre and BC Cancer.

The technology can also be implemented in existing commercial ctDNA testing platforms, which means that patients could soon directly benefit from more comprehensive liquid biopsy testing. The research team has made the methods and computer code publicly and freely available so that the technology can be applied to other cancer types and clinical settings.

“Understanding how clonal evolution occurs and what drives it is one of the key questions that need to be addressed in almost all cancers, and this study provides that level of insight for advanced prostate cancer, as well as a model and tools for how to carry out this work,” Christopher Mueller, MD, PhD, a cancer biologist and geneticist at Queen’s Cancer Research Institute and a professor of biomedical and molecular sciences at Queen’s University, both in Kingston, Ont., said in an interview.

Dr. Mueller, who wasn’t involved with this study, has researched biomarkers and ctDNA as avenues for more precise management of advanced prostate cancer. He and his colleagues have developed blood tests for detecting and monitoring metastatic breast cancer, uveal melanoma, and prostate, pancreatic, and lung cancer.

“The expansion of treatment-resistant clones is how we lose almost all cancer patients, and they clearly demonstrate that in castrate-resistant prostate cancer, changes in the androgen receptor locus almost always drive this process,” Dr. Mueller said. “Understanding clonal evolution will allow us to design treatment strategies that overcome or limit their expansion, hopefully extending the lives of these patients.”

The study was funded by the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Prostate Cancer Foundation, Prostate Cancer Canada, the Movember Foundation, the Jane and Aatos Erkko Foundation, the Academy of Finland Center of Excellence program, the Terry Fox New Frontiers Program, and the BC Cancer Foundation. Dr. Wyatt has served on advisory boards or has received honoraria from AstraZeneca, Astellas, Janssen, and Merck, and his research lab has a contract research agreement with ESSA Pharma. Dr. Mueller disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Edgewell Personal Care Co., the maker of Banana Boat sunscreen, is recalling a scalp spray because it contains trace levels of benzene, a chemical that can cause cancer at high levels.

The company announced a voluntary recall for three batches of the Banana Boat Hair & Scalp Spray SPF 30, which came in 6-ounce bottles and was sold across the U.S. through various retailers and online, according to a recall alert by the Food and Drug Administration.

The three batches have a UPC label of 0-79656-04041-8 and fall under the lot codes 20016AF, 20084BF, and 21139AF, with the expiration dates of December 2022, February 2023, and April 2024, respectively.

“An internal review found that some samples of the product contained trace levels of benzene. While benzene is not an ingredient in any Banana Boat products, the review showed the unexpected levels of benzene came from the propellant that sprays the product out of the can,” according to the recall notice.

“Importantly, no other batches of Hair & Scalp (either before or after these batch codes) and no other Banana Boat products are in the scope of this recall and may continue to be used by consumers safely and as intended,” the company wrote.

Benzene is classified as a human carcinogen, the FDA wrote. Exposure to benzene can occur through the nose, mouth, and skin, and it can result in serious conditions such as leukemia, bone marrow cancer, and blood disorders.

“Benzene is ubiquitous in the environment. Humans around the world have daily exposures to it indoors and outdoors from multiple sources,” the company said. “Daily exposure to benzene in the recalled products would not be expected to cause adverse health consequences according to an independent health assessment using established exposure modeling guidelines.”

Edgewell said it hasn’t received any reports of bad events related to the recall. The company has told retailers to remove the affected batches from shelves.

Banana Boat will reimburse consumers who purchased a product with one of the affected lot codes, which are on the bottom of the can. In the meantime, consumers should stop using the affected product right away and discard it.

The recall comes a little over a year after Johnson & Johnson recalled five sunscreens due to low levels of benzene, according to The Associated Press. That recall included Aveeno and Neutrogena products in spray cans.

Consumers with questions about the recall can contact Edgewell Personal Care at 888-686-3988 Monday through Friday, 9 a.m. to 6 p.m. ET. People can also read more at the Banana Boat FAQ page or file for a refund directly on the Banana Boat Recall page.

A version of this article first appeared on WebMD.com.

Edgewell Personal Care Co., the maker of Banana Boat sunscreen, is recalling a scalp spray because it contains trace levels of benzene, a chemical that can cause cancer at high levels.

The company announced a voluntary recall for three batches of the Banana Boat Hair & Scalp Spray SPF 30, which came in 6-ounce bottles and was sold across the U.S. through various retailers and online, according to a recall alert by the Food and Drug Administration.

The three batches have a UPC label of 0-79656-04041-8 and fall under the lot codes 20016AF, 20084BF, and 21139AF, with the expiration dates of December 2022, February 2023, and April 2024, respectively.

“An internal review found that some samples of the product contained trace levels of benzene. While benzene is not an ingredient in any Banana Boat products, the review showed the unexpected levels of benzene came from the propellant that sprays the product out of the can,” according to the recall notice.

“Importantly, no other batches of Hair & Scalp (either before or after these batch codes) and no other Banana Boat products are in the scope of this recall and may continue to be used by consumers safely and as intended,” the company wrote.

Benzene is classified as a human carcinogen, the FDA wrote. Exposure to benzene can occur through the nose, mouth, and skin, and it can result in serious conditions such as leukemia, bone marrow cancer, and blood disorders.

“Benzene is ubiquitous in the environment. Humans around the world have daily exposures to it indoors and outdoors from multiple sources,” the company said. “Daily exposure to benzene in the recalled products would not be expected to cause adverse health consequences according to an independent health assessment using established exposure modeling guidelines.”

Edgewell said it hasn’t received any reports of bad events related to the recall. The company has told retailers to remove the affected batches from shelves.

Banana Boat will reimburse consumers who purchased a product with one of the affected lot codes, which are on the bottom of the can. In the meantime, consumers should stop using the affected product right away and discard it.

The recall comes a little over a year after Johnson & Johnson recalled five sunscreens due to low levels of benzene, according to The Associated Press. That recall included Aveeno and Neutrogena products in spray cans.

Consumers with questions about the recall can contact Edgewell Personal Care at 888-686-3988 Monday through Friday, 9 a.m. to 6 p.m. ET. People can also read more at the Banana Boat FAQ page or file for a refund directly on the Banana Boat Recall page.

A version of this article first appeared on WebMD.com.

Edgewell Personal Care Co., the maker of Banana Boat sunscreen, is recalling a scalp spray because it contains trace levels of benzene, a chemical that can cause cancer at high levels.

The company announced a voluntary recall for three batches of the Banana Boat Hair & Scalp Spray SPF 30, which came in 6-ounce bottles and was sold across the U.S. through various retailers and online, according to a recall alert by the Food and Drug Administration.

The three batches have a UPC label of 0-79656-04041-8 and fall under the lot codes 20016AF, 20084BF, and 21139AF, with the expiration dates of December 2022, February 2023, and April 2024, respectively.

“An internal review found that some samples of the product contained trace levels of benzene. While benzene is not an ingredient in any Banana Boat products, the review showed the unexpected levels of benzene came from the propellant that sprays the product out of the can,” according to the recall notice.

“Importantly, no other batches of Hair & Scalp (either before or after these batch codes) and no other Banana Boat products are in the scope of this recall and may continue to be used by consumers safely and as intended,” the company wrote.

Benzene is classified as a human carcinogen, the FDA wrote. Exposure to benzene can occur through the nose, mouth, and skin, and it can result in serious conditions such as leukemia, bone marrow cancer, and blood disorders.

“Benzene is ubiquitous in the environment. Humans around the world have daily exposures to it indoors and outdoors from multiple sources,” the company said. “Daily exposure to benzene in the recalled products would not be expected to cause adverse health consequences according to an independent health assessment using established exposure modeling guidelines.”

Edgewell said it hasn’t received any reports of bad events related to the recall. The company has told retailers to remove the affected batches from shelves.

Banana Boat will reimburse consumers who purchased a product with one of the affected lot codes, which are on the bottom of the can. In the meantime, consumers should stop using the affected product right away and discard it.

The recall comes a little over a year after Johnson & Johnson recalled five sunscreens due to low levels of benzene, according to The Associated Press. That recall included Aveeno and Neutrogena products in spray cans.

Consumers with questions about the recall can contact Edgewell Personal Care at 888-686-3988 Monday through Friday, 9 a.m. to 6 p.m. ET. People can also read more at the Banana Boat FAQ page or file for a refund directly on the Banana Boat Recall page.

A version of this article first appeared on WebMD.com.