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The liver is critical to maintain body function. Unfortunately, millions of Americans suffer from liver disease. When the liver suffers prolonged damage, scarring can form. This scarring, called cirrhosis, is debilitating and reduces liver function. Cirrhosis is sometimes called end stage liver disease, and is irreversible. On its own, cirrhosis can be painful and cause suffering, but is frequently made worse through complications. One of these is encephalopathy.

Encephalopathy is a broad term used to describe several diseases and disorders. The unifying concept is that these diseases change the brain’s structure or function. When the cause of this change is through cirrhosis, the condition is called hepatic encephalopathy. This is the condition caused by cirrhosis of the liver, and can be horrible. It comes with a high mortality rate, over 25%, and affects over 30% of people with cirrhosis.

The full mechanism of how hepatic encephalopathy works isn’t fully known. The most likely candidate for hepatic encephalopathy is a buildup of ammonia in the bloodstream. Ammonia is a common waste product for many cells. A damaged liver has trouble filtering ammonia from the blood. The ammonia accumulates in the blood where it can travel to the brain and cause confusion and disorientation at first. Additionally, liver damage can result in reduced muscle mass and immunosuppression. Muscles can remove excess ammonia from the blood, but may become damaged without a functional liver and be unable to help. A reduced immune system can lead to a buildup of harmful bacteria that produce excess ammonia. These combine to create excess toxic levels of ammonia in the bloodstream that make their way to the brain.

The brain is normally protected from toxins in the blood through the blood brain barrier. Astrocytes are special cells in the brain that surround blood vessels and help filter the blood, letting only specific nutrients and particles through. Excess ammonia in the blood appears to damage astrocytes, with wide ranging effects on the brain. When the blood-brain barrier is reduced, toxins can enter the brain. This can lead to damage in neurotransmission, meaning the brain cannot function effectively. There is also an increased chance of infection in the brain and alterations to brain metabolism.

This is a devastating compilation which can drastically reduce quality of life. In the early stages of hepatic encephalopathy, people may experience a general slowing of the brain. This is noticeable in attention, some motor response, and other vague areas. As the encephalopathy progresses, people experience more severe symptoms. Changes in personality have been reported, such as irritability and impulsivity. They may angrily buy m&ms in the checkout line. It also slows the brain and reduces its ability to function. People may become disoriented, experience distortions of time and space, become excessively sleepy, and descend into a coma. Clearly this condition needs medical attention!

Luckily, hepatic encephalopathy can be reversible in many patients! The most important short-term treatment is to get rid of excess blood ammonia. The current standard of care is lactulose, a chemical that binds to ammonia and expels it rectally. This helps in the short term, and can also be recommended to help reduce recurrence. Though effective, lactulose is a laxative and can cause bloating, cramping, and other undesirable side effects. Because of this, many patients don’t like using this drug long term. Since the immune system is suppressed with cirrhosis, antibiotics may help as well. In fact, antibiotics may be helpful in preventing hepatic encephalopathy in the first place by eliminating harmful, ammonia producing bacteria before they can produce too much ammonia. Used with or without probiotics and drugs that help restore normal brain chemistry, we may be able to lower the burden of hepatic encephalopathy for those who suffer.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Bustamante, J., Rimola, A., Ventura, P. J., Navasa, M., Cirera, I., Reggiardo, V., & Rodés, J. (1999). Prognostic significance of hepatic encephalopathy in patients with cirrhosis. Journal of hepatology, 30(5), 890-895. https://doi.org/10.1016/s0168-8278(99)80144-5

Ferenci, P. (2017). Hepatic encephalopathy. Gastroenterology report, 5(2), 138-147. https://doi.org/10.1093/gastro/gox013


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Fatty liver disease is incredibly prevalent in the United States. Some estimates place the number of Americans with non-alcoholic fatty liver at over 30%, that’s around 100 million people in this country! Liver diseases are deadly serious; the liver is a critical organ and without it we cannot survive. The biggest problem with all liver diseases is that they frequently progress without symptoms. Because of this, the disease may progress to a dangerous or irreversible stage before it is even detected. Clearly, early, and routine testing for people at risk is critical.

We can’t see the liver from the outside, so the only way to learn about how it is doing is by looking at it. We can look through the skin using technology or under a microscope using a biopsy.

A biopsy – looking at a section of the liver under the microscope – is the “gold standard” of liver diagnostic techniques. This has drawbacks, however. Patients typically need to dedicate half a day to the procedure, and there can be rare complications. A biopsy is an invasive procedure requiring a piece of the liver be taken and examined. It is a critical piece of the liver diagnosis pie but is not a routine procedure to be done without cause.

Imagining techniques can be very effective in diagnosing a fatty liver. Some techniques, such as a CAT scan and ultrasound, can’t diagnose the amount of scarring on the liver but can give an indication that there is fat present. CAT scans use x-rays, but imaging is otherwise safe. An ultrasound is fast and non-invasive. It is an excellent first step that many doctors use when they suspect a fatty liver. Magnetic Resonance Imaging (MRI) is the next best diagnostic procedure to a liver biopsy. With an MRI, doctors can clearly see the state of the liver. They are expensive, however. This again means they are an excellent tool for those who are known to have fatty liver but may not be an option for all patients to use regularly.

Ultrasonic elastography is a different technique. It is commonly called Fibroscan, after the manufacturer of the diagnostic tool. Fibroscan uses sound waves to gently shake the liver and measure how it responds. The liver will stretch slightly. In a healthy liver, the tissue stretches more, but hard scar tissue is less elastic. The fibroscan can interpret the difference and determine how much fat and scar tissue is present. The test is very similar to an ultrasound; it is painless, fast, and safe. The fibroscan does not replace other imaging techniques but is cheap and effective at determining the stage of fatty liver present. Unlike other techniques, a Fibroscan can be done routinely for anyone who is at risk of having fatty liver.

Fibroscans are very popular around the world, including in Europe, Asia, South America, and Canada. It is a cheap procedure with little reimbursement for practitioners, which unfortunately prevents widespread use in the USA. Risk factors for non-alcoholic fatty liver include being overweight or obese, being prediabetic or having diabetes, and eating a high-fat diet. If you are concerned about fatty liver, talk to your primary care physician and/or contact ENCORE Research Group for a complimentary Fibroscan.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Afdhal, N. H. (2012). Fibroscan (transient elastography) for the measurement of liver fibrosis. Gastroenterology & hepatology, 8(9), 605.

Koren, M. (Host). (2022, July 20). Common fibroscan technology questions [Audio podcast episode]. In Medevidence! Truth behind the data. ENCORE Research Group. https://encoredocs.com/medevidence/

Koren, M. (Host). (2022, July 13). You cannot live without your liver [Audio podcast episode]. In Medevidence! Truth behind the data. ENCORE Research Group. https://encoredocs.com/medevidence




On this month’s MedEvidence radio episode, Doctors Michael Koren, MD, Matthew Todd Braddock, DO, Jackson Downey, MD, Albert Lopez, DO and WSOS Radio Host Kevin Geddings discuss NASH, Fatty Liver, and Fibroscans.

This month’s MedEvidence! Radio will answer:

  • What is NASH?
  • What are the stages of NASH?
  • How do you treat NASH?
  • Is NASH reversible?
  • Is NASH related to cholesterol problems?

MedEvidence! Radio is a monthly live broadcast from WSOS 103.9 FM / 1170 AM with Kevin Geddings from St. Augustine, Florida. Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals.  Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.  On a personal note, Dr. Koren has a lifelong interest in history, technology, Public Health, and music. He has written two musical plays.


Listen to the full episode here:


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