Undiagnosed cases of cirrhosis, common in veterans with dementia, can lead to cognitive impairment

Newly announced national cohort study JAMA network open found that 5% to 10% of veterans with dementia have advanced liver fibrosis and high Fibrosis 4 scores suggestive of cirrhosis, even though they have never received a formal diagnosis of cirrhosis. showed that. These findings suggest that clinicians should screen for cirrhosis in patients with dementia to uncover reversible factors associated with cognitive impairment, such as hepatic encephalopathy (HE), and improve outcomes. There is.^{1, 2}

Of the 177,422 veterans diagnosed with dementia (97.1% male, 80.7% Caucasian, mean age 78.35 years, standard deviation 10.97 years), 5.3% of the cohort not previously diagnosed with cirrhosis had fibrosis-4. (FIB-4). 4) The score exceeds 3.25 (n = 9373), suggesting cirrhosis. Of note, the researchers found that 10.3% of the entire cohort had a FIB-4 score greater than 2.67, suggestive of advanced fibrosis (n = 18,390), and had a previous diagnosis of cirrhosis. I observed that there was no.

Important clinical points

• Veterans with dementia and undiagnosed cirrhosis present a significant risk for liver disease, highlighting the importance of screening for reversible factors that affect cognitive function.
• This study found that a significant proportion of veterans with dementia without diagnosed cirrhosis had progressive fibrosis as indicated by FIB-4 scores.
• The association of increased FIB-4 scores with older age, male gender, congestive heart failure, viral hepatitis, and alcohol use disorder highlights the multifactorial nature of liver disease risk in this population.

“We focused on this because the population of patients with cirrhosis is aging and more people are newly diagnosed with cirrhosis at older ages. Additionally, patients with HE (occult and overt) are more likely to have cirrhosis. It affects nearly 50% of patients, and several risk factors such as alcohol, obesity, and diabetes predispose to both cirrhosis and dementia,” said lead author Jasmohan Bajaj, MD, associate professor of medicine. Ta. said a gastroenterologist in the Division of Gastroenterology, Hepatology and Nutrition at Virginia Commonwealth University and the Richmond VA Medical Center. neurology live®.

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Researchers conducted a retrospective cohort study between 2009 and 2019 using data from the Veterans Health Administration and two separate validation cohorts from the Richmond Veterans Affairs Medical Center. Participants included in the analysis had a diagnosis of dementia at two or more visits, had no prior diagnosis of cirrhosis, and had sufficient laboratory test results to calculate a FIB-4 score. The researchers entered 65 years of age (rather than his actual age) as an input variable to calculate his FIB-4 score, since older age can cause his FIB-4 score to be incorrect.

In a multivariate logistic regression model, researchers found that FIB-4 greater than 3.25 was associated with older age (OR, 1.07; 95% CI, 1.06-1.09), male gender (OR, 1.43; 95% CI, 1.26- 1.61). ), congestive heart failure (OR, 1.48; 95% CI, 1.43-1.54), viral hepatitis (OR, 1.79; 95% CI, 1.66-1.91), alcohol use disorder identification test score (OR, 1.56; 95% CI , 1.44-1.68) and chronic kidney disease (OR, 1.11; 95% CI, 1.04-1.17). The authors found that patients with FIB-4 >3.25 were more likely to be white (OR, 0.79; 95% CI, 0.73-0.85), have diabetes (OR, 0.78; 95% CI, 0.73-0.84), and hyperlipidemia. He pointed out that there is an inverse correlation with the disease. (OR, 0.84; 95% CI, 0.79-0.89), stroke (OR, 0.85; 95% CI, 0.79-0.91), smoking disorder (OR, 0.78; 95% CI, 0.70-0.87), and public setting. Similar results were found using FIB-4 scores above 2.67 for overall residence in .

In a local validation cohort of patients with dementia, researchers observed similar high rates of FIB-4 scores (4.4% to 11.2%). Of these 9 patients, 4 had diabetes, 3 had previous AUD, and none were obese. Five patients were tested for hepatitis C virus antibodies (one was positive), and one had already been diagnosed with liver cirrhosis and was being followed up at a hepatology department. Upon further evaluation, potential cirrhosis was likely present in 7 patients (8.7) in the validation cohort.

“In a previous study of veterans with cirrhosis, the only decompensation event that overlapped with dementia was HE. As you know, this study wanted to examine the rate of undiagnosed cirrhosis in dementia. On the contrary, it did not diagnose HE or decompensation, but only focused on diagnosing cirrhosis,” Bajaj added. “We found a diagnosis of cirrhosis, but hypothesized that some or most of them may have hidden or pre-existing overt HE as a contributor. and viral hepatitis, but other factors such as diabetes and hyperlipidemia were not actually associated with undiagnosed cirrhosis because the population had dementia. This is most likely because it consisted only of patients.”

A previous study conducted by Baja et al. American Journal of Gastroenterology We showed that dementia in US veterans is associated with HE.³ Investigators used the VA Corporate Data Warehouse to identify veterans with cirrhosis through International Classification of Diseases-10 codes between October 1, 2019 and September 30, 2021. Baseline characteristics were compared between cohorts based on the presence or absence of cirrhosis. dementia. Factors associated with a diagnosis of dementia were assessed using a multivariate logistic regression model in which the authors adjusted for demographics, comorbidities, etiology of cirrhosis, and complications of cirrhosis.

Of the 71,552 veterans with cirrhosis, 5,647 (7.89%) were diagnosed with dementia. The authors observed that patients with dementia were older, more often Caucasian, lived in urban areas, and had a diagnosis of alcohol-related cirrhosis. Of note, these patients also more frequently suffered from metabolic syndrome, brain trauma, and cerebrovascular disease. Multivariate analysis showed that the presence of decompensated events was associated with dementia, and that individual decompensated events were associated with dementia, independent of other risk factors, HE was associated with dementia, but ascites was not. clarified that it is not.

“These raise awareness among health care providers and families of people with dementia to ascertain whether undiagnosed cirrhosis exists and therefore whether there is a possibility of HE contributing to mental impairment. These may include the use of FIB-4, taking a deeper history for risk factors for cirrhosis, and referral to gastroenterology/hepatology if necessary,” said Baja. Ta. “Strategies need to be discussed within health systems to validate this in other populations and define strategies such as using FIB-4 and other test-related assessments to exclude patients with cirrhosis. ”

References
1. Bajaj JS, Silvey SG, Rogal S, et al. Undiagnosed liver cirrhosis and hepatic encephalopathy in a national cohort of veterans with dementia. JAMA Net Open. 2024;7(1):e2353965. Published January 2, 2024. doi:10.1001/jamanetworkopen.2023.53965
2. Hostetler AJ. One in 10 veterans diagnosed with dementia may actually be suffering from cognitive decline due to cirrhosis. news release. Virginia Commonwealth University. Published on January 31, 2023. Accessed February 8, 2024. https://www.vcuhealth.org/news/1-of-10-veterans-diagnosed-with-dementia-may-instead-have-cognitive-decline-from-cirrhosis
3. Adejumo A, Nord A, Rogal SS, et al. In U.S. veterans, dementia often occurs with hepatic encephalopathy but not with other complications of cirrhosis. Am J Gastroenterol. 2023;118(3):475-480. doi:10.14309/ajg.0000000000002189