• There is currently no cure for cirrhosis of the liver and the disease can increase the risk for complications.
  • A new study reports around 10% of older U.S. veterans diagnosed with dementia have misdiagnosed hepatic encephalopathy, a complication of liver disease.
  • Cognitive decline due to hepatic encephalopathy is treatable and potentially reversible.
  • Scientists believe their findings highlight the importance of screening patients with cognitive impairment for liver disease.

As of 2017, about 112 million people around the world have the progressive liver disease cirrhosis.

Researchers estimate that liver diseases including cirrhosis account for 4% of all deaths globally.

There is currently no cure for cirrhosis. As the disease progresses, it can increase a person’s risk for certain complications including:

  • blood clotting issues
  • ascites — build-up of fluid in the abdomen
  • edema — swelling in the legs
  • high blood pressure in veins that carry blood to and from the liver
  • hepatic encephalopathy — a build-up of toxins in the brain that can cause a decline in brain function

Now researchers from Virginia Commonwealth University report that as many as 10% of older U.S. veterans diagnosed with dementia instead have misdiagnosed hepatic encephalopathy, which is treatable and potentially reversible.

Scientists believe their findings — recently published in the journal JAMA Network Open — highlight the importance of screening patients with cognitive impairment for liver disease.

According to Dr. Jasmohan S. Bajaj, professor in the Division of Gastroenterology, Hepatology, and Nutrition in the Department of Medicine at Virginia Commonwealth University and Richmond VA Medical Center, and lead author of this study, people with cirrhosis often have a condition called hepatic encephalopathy which can impact almost 60% of those tested.

“This can cause subclinical and overt symptoms such as mental slowing, tremors, confusion, and even coma,” Dr. Bajaj explained to Medical News Today. “This is partly because of the liver’s inability to clear the gut-derived toxins and also through inflammation that ultimately results in brain dysfunction.”

Dr. Bajaj said they decided to focus specifically on the veteran population because there can be confusion between hepatic encephalopathy, dementia, or both in this population.

“To support this hypothesis, we have several lines of evidence that prompted this study,” Dr. Bajaj continued.

“One, older patients with already diagnosed cirrhosis are more likely to develop a ‘dementia-like’ state. Two, brain dysfunction due to dementia and that related to cirrhosis often overlap and synergize to worsen (the) quality of life in affected patients. Three, gut-brain axis changes in people over 65 years old point towards a role of microbial changes regardless of cirrhosis. And four, we have found that a couple of patients that were deemed to be dementia actually had hepatic encephalopathy. Treatment of hepatic encephalopathy improved their mental function.”

— Dr. Jasmohan S. Bajaj, lead study author

For this study, Dr. Bajaj and his team analyzed medical records data of more than 177,000 U.S. veterans diagnosed with dementia but not cirrhosis between 2009 and 2019.

Researchers focused on the Fibrosis-4 (FIB-4) score of the study participants. FIB-4 is a tool used by doctors to assess a person’s liver disease risk using a person’s age and three specific biomarkers:

Depending on a person’s score they may be considered at a low, intermediate, or high risk for advanced liver fibrosis, which can lead to cirrhosis.

Researchers found that 10.3% of the veterans with dementia had high FIB-4 scores, meaning they were very likely to have cirrhosis.

“This unexpected link between dementia and liver health emphasizes the importance of screening patients for potentially treatable contributors to cognitive decline,” Dr. Bajaj says.

Dr. Bajaj said these findings highlight the importance of screening people for reversible cognitive decline caused by cirrhosis.

“If 10% have cirrhosis and even 50% of those have a component of treatable hepatic encephalopathy, this is still a large group of patients that could gain some of their mental acuities with easy therapy,” Dr. Bajaj explained.

“In addition, patients with cirrhosis are also at higher risk for other complications such as liver cancer, which can be screened for and treated but only if cirrhosis is suspected,” he continued.

The study also reported on a disparity in the amount of potentially undiagnosed cirrhosis in veterans with dementia living in urban areas, who were of Hispanic descent, and who were not white.

“This underlines another focus of where we should all be doing better to improve disparities and also educate patients, family members, and clinicians about the risk of cirrhosis and dementia sooner,” Dr. Bajaj said.

“We plan to try and replicate this in a non-veteran population as well as determining biomarkers for diagnosis of whether the subject with mental dysfunction has dementia, cirrhosis-related problems, or both,” he added.

After reviewing this study, Dr. David Frank, a neurologist at Hackensack Meridian Neuroscience Institute at Jersey Shore University Medical Center in New Jersey, told MNT that this study brings to attention a potentially clinically useful screening tool for a subset of these patients.

“Although we are beginning to see more useful medications for the treatment of Alzheimer’s dementia, the primary focus in initial evaluation remains the identification of potentially reversible/treatable underlying causes, and an algorithm that may identify more of such patients is certainly welcome,” Dr. Frank said.

MNT also spoke with Dr. Anurag Maheshwari, gastroenterologist and hepatologist at The Center for Liver and Hepatobiliary Diseases, part of The Melissa L. Posner Institute for Digestive Health & Liver Disease, at Mercy Medical Center in Baltimore, MD, about this study.

Dr. Maheshwari commented that the study highlights an important concept, which is that providers who are diagnosing patients with dementia need to be aware that hepatic encephalopathy can mimic dementia.

“It’s a matter of having better tools and awareness and education … to alert providers about the fact that if patients look like they’re having possible dementia, it may not be dementia — it may be hepatic encephalopathy and that’s something you have to be on the lookout for. The main purpose of the study is to provide better provider education amongst the folks who treat patients with neurocognitive decline but are not dealing with liver disease on a daily basis.”

— Dr. Anurag Maheshwari, gastroenterologist and hepatologist

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