Acetaminophen-Linked Liver Failure Risk Heightened in Bariatric Surgery Patients

BOSTON – Prior bariatric surgery appears to be an independent risk factor for acetaminophen-related acute liver failure or injury, investigators reported at the annual meeting of the American Association for the Study of Liver Diseases.

A retrospective study of patients with acute liver failure (ALF) showed that 9 of 54 (17%) patients with ALF attributed to acetaminophen (APAP-ALF) had previously had bariatric surgery, compared with none of 47 patients with ALF from other causes, said Dr. Edward W. Holt, a researcher at the California Pacific Medical Center in San Francisco.

Although previous studies have shown associations between bariatric surgery and between alcohol abuse and APAP-ALF, they found that there were no significant differences in rates of suicidal ideation, depression, or alcohol abuse between patients who underwent bariatric surgery and those who had not, suggesting that bariatric surgery itself was a risk factor, Dr. Holt said.

"We feel that the implications of these findings are important," he said. "If validated in a larger cohort, our novel finding may identify a new group of patients at higher risk for APAP-ALF. If validated, additional warnings for patients with prior bariatric surgery may be warranted, similar to those currently in place for patients who consume three or more alcoholic drinks daily."

Possible explanations for the association include higher peak serum concentrations of ethanol after a challenge in patients who have undergone bariatric surgery, as well as higher rates of suicidal behaviors among these patients, compared with controls.

The investigators retrospectively reviewed data from their center on a prospectively identified cohort of 101 patients with acute liver failure from acetaminophen and other causes, including drug-induced, infections, lymphoma, ischemia, and heatstroke. Of the 54 patients with APAP-ALF, 8 had undergone roux-en-Y gastric bypass, and one had a duodenal switch procedure, at a mean of nearly 6 years before diagnosis of ALF.

Among the patients in the APAP-ALF group, the prevalence of bariatric surgery was 25.3-fold higher than the estimated prevalence in the general population (16.7% vs. 0.5%; estimate based on published literature and national hospital discharge data).

The patients with APAP-ALF and ALF from other causes were similar in age, but there were more women (P = .02) and whites (P less than .0001) in the APAP-ALF group, and patients in this group had significantly fewer deaths (P less than .0006) and transplants (P less than .0001).

When the researchers looked at possible risk factors for ALF, they found that patients in the ALF/other group had significantly lower frequencies of depression (P less than .001), alcohol abuse (P = .01), and acetaminophen-containing combination analgesics (P less than .0001). But when they compared patients with or without bariatric surgery, there were no significant differences in any of the variables mentioned above.

Dr. Holt noted that the study was limited by its single-center design, inability to test proposed mechanisms for the increased risk seen in patients who had undergone bariatric surgery (such as changes in glutathione levels), and the inability to perform a logistic regression analysis, as none of the patients with non-APAP ALF had undergone surgery.

In the question-and-response portion following his presentation, Dr. Holt was asked whether liver biopsies had been performed to see if patients had background steatohepatitis or fibrosis that might account for the results, and whether body mass index data were available.

He noted that the patients came primarily from his institution’s wide referral base, and they therefore did not have all the demographic or clinical information about each patient that they would have liked.

The study was internally funded. Dr. Holt reported no relevant financial disclosures.

BOSTON – Prior bariatric surgery appears to be an independent risk factor for acetaminophen-related acute liver failure or injury, investigators reported at the annual meeting of the American Association for the Study of Liver Diseases.

A retrospective study of patients with acute liver failure (ALF) showed that 9 of 54 (17%) patients with ALF attributed to acetaminophen (APAP-ALF) had previously had bariatric surgery, compared with none of 47 patients with ALF from other causes, said Dr. Edward W. Holt, a researcher at the California Pacific Medical Center in San Francisco.

Although previous studies have shown associations between bariatric surgery and between alcohol abuse and APAP-ALF, they found that there were no significant differences in rates of suicidal ideation, depression, or alcohol abuse between patients who underwent bariatric surgery and those who had not, suggesting that bariatric surgery itself was a risk factor, Dr. Holt said.

"We feel that the implications of these findings are important," he said. "If validated in a larger cohort, our novel finding may identify a new group of patients at higher risk for APAP-ALF. If validated, additional warnings for patients with prior bariatric surgery may be warranted, similar to those currently in place for patients who consume three or more alcoholic drinks daily."

Possible explanations for the association include higher peak serum concentrations of ethanol after a challenge in patients who have undergone bariatric surgery, as well as higher rates of suicidal behaviors among these patients, compared with controls.

The investigators retrospectively reviewed data from their center on a prospectively identified cohort of 101 patients with acute liver failure from acetaminophen and other causes, including drug-induced, infections, lymphoma, ischemia, and heatstroke. Of the 54 patients with APAP-ALF, 8 had undergone roux-en-Y gastric bypass, and one had a duodenal switch procedure, at a mean of nearly 6 years before diagnosis of ALF.

Among the patients in the APAP-ALF group, the prevalence of bariatric surgery was 25.3-fold higher than the estimated prevalence in the general population (16.7% vs. 0.5%; estimate based on published literature and national hospital discharge data).

The patients with APAP-ALF and ALF from other causes were similar in age, but there were more women (P = .02) and whites (P less than .0001) in the APAP-ALF group, and patients in this group had significantly fewer deaths (P less than .0006) and transplants (P less than .0001).

When the researchers looked at possible risk factors for ALF, they found that patients in the ALF/other group had significantly lower frequencies of depression (P less than .001), alcohol abuse (P = .01), and acetaminophen-containing combination analgesics (P less than .0001). But when they compared patients with or without bariatric surgery, there were no significant differences in any of the variables mentioned above.

Dr. Holt noted that the study was limited by its single-center design, inability to test proposed mechanisms for the increased risk seen in patients who had undergone bariatric surgery (such as changes in glutathione levels), and the inability to perform a logistic regression analysis, as none of the patients with non-APAP ALF had undergone surgery.

In the question-and-response portion following his presentation, Dr. Holt was asked whether liver biopsies had been performed to see if patients had background steatohepatitis or fibrosis that might account for the results, and whether body mass index data were available.

He noted that the patients came primarily from his institution’s wide referral base, and they therefore did not have all the demographic or clinical information about each patient that they would have liked.

The study was internally funded. Dr. Holt reported no relevant financial disclosures.

BOSTON – Prior bariatric surgery appears to be an independent risk factor for acetaminophen-related acute liver failure or injury, investigators reported at the annual meeting of the American Association for the Study of Liver Diseases.

A retrospective study of patients with acute liver failure (ALF) showed that 9 of 54 (17%) patients with ALF attributed to acetaminophen (APAP-ALF) had previously had bariatric surgery, compared with none of 47 patients with ALF from other causes, said Dr. Edward W. Holt, a researcher at the California Pacific Medical Center in San Francisco.

Although previous studies have shown associations between bariatric surgery and between alcohol abuse and APAP-ALF, they found that there were no significant differences in rates of suicidal ideation, depression, or alcohol abuse between patients who underwent bariatric surgery and those who had not, suggesting that bariatric surgery itself was a risk factor, Dr. Holt said.

"We feel that the implications of these findings are important," he said. "If validated in a larger cohort, our novel finding may identify a new group of patients at higher risk for APAP-ALF. If validated, additional warnings for patients with prior bariatric surgery may be warranted, similar to those currently in place for patients who consume three or more alcoholic drinks daily."

Possible explanations for the association include higher peak serum concentrations of ethanol after a challenge in patients who have undergone bariatric surgery, as well as higher rates of suicidal behaviors among these patients, compared with controls.

The investigators retrospectively reviewed data from their center on a prospectively identified cohort of 101 patients with acute liver failure from acetaminophen and other causes, including drug-induced, infections, lymphoma, ischemia, and heatstroke. Of the 54 patients with APAP-ALF, 8 had undergone roux-en-Y gastric bypass, and one had a duodenal switch procedure, at a mean of nearly 6 years before diagnosis of ALF.

Among the patients in the APAP-ALF group, the prevalence of bariatric surgery was 25.3-fold higher than the estimated prevalence in the general population (16.7% vs. 0.5%; estimate based on published literature and national hospital discharge data).

The patients with APAP-ALF and ALF from other causes were similar in age, but there were more women (P = .02) and whites (P less than .0001) in the APAP-ALF group, and patients in this group had significantly fewer deaths (P less than .0006) and transplants (P less than .0001).

When the researchers looked at possible risk factors for ALF, they found that patients in the ALF/other group had significantly lower frequencies of depression (P less than .001), alcohol abuse (P = .01), and acetaminophen-containing combination analgesics (P less than .0001). But when they compared patients with or without bariatric surgery, there were no significant differences in any of the variables mentioned above.

Dr. Holt noted that the study was limited by its single-center design, inability to test proposed mechanisms for the increased risk seen in patients who had undergone bariatric surgery (such as changes in glutathione levels), and the inability to perform a logistic regression analysis, as none of the patients with non-APAP ALF had undergone surgery.

In the question-and-response portion following his presentation, Dr. Holt was asked whether liver biopsies had been performed to see if patients had background steatohepatitis or fibrosis that might account for the results, and whether body mass index data were available.

He noted that the patients came primarily from his institution’s wide referral base, and they therefore did not have all the demographic or clinical information about each patient that they would have liked.

The study was internally funded. Dr. Holt reported no relevant financial disclosures.