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Hepatic encephalopathy

Hepatic encephalopathy is a decline in brain function that appears when a damaged liver can no longer clean the blood properly and toxins build up, above all ammonia, which reaches the brain. It is not a disease of the head but a consequence of liver disease, almost always cirrhosis. That is why, when the liver improves or the trigger is corrected, the encephalopathy usually reverses.

If you are caring for someone with cirrhosis, this is the most important thing to know: encephalopathy shows up as confusion, changes in behavior or drowsiness, it is treatable, and it is often set off by something concrete (an infection, constipation, bleeding) that can be corrected. Recognizing it early keeps it from progressing toward coma.

Why does it happen?

A healthy liver processes ammonia and other toxic substances produced in the gut and removes them. In cirrhosis, two things fail at once: the liver has fewer cells able to do that work, and part of the blood coming from the gut bypasses the liver through collateral veins (so-called portosystemic shunting). As a result, ammonia and other toxins reach the brain and disturb how it works.

How is it recognized? Symptoms

Encephalopathy can be mild and hard to spot, or obvious. Family members should learn to recognize these signs:

  • Changes in behavior and personality: irritability, apathy, or conduct that is unusual for the person.
  • Confusion and disorientation: not knowing the day or where they are, trouble following a conversation.
  • Sleep disturbance: excessive daytime drowsiness and nighttime insomnia (the sleep-wake cycle reverses).
  • Slowness, poor concentration, and memory loss.
  • Hand tremor when the arms are held out, a flapping motion (asterixis).
  • In the most severe cases, stupor and coma.

A useful early sign for families is that the person starts sleeping during the day and stays awake and confused at night. Whenever the mental state of someone with cirrhosis changes suddenly, seek care promptly.

What triggers it?

Most episodes have a precipitating factor worth looking for and treating, because correcting it is a central part of the treatment:

  • Infections, especially infection of the ascites fluid (spontaneous bacterial peritonitis) and urinary infections.
  • Constipation, which increases the production and absorption of ammonia in the gut.
  • Gastrointestinal bleeding, for example from esophageal varices; blood in the gut is a major source of ammonia.
  • Dehydration and electrolyte imbalances, often from overuse of diuretics, vomiting, or diarrhea.
  • Sedatives or sleeping pills (benzodiazepines, opioids), which further depress the nervous system.
  • Alcohol use and, sometimes, a sudden excess of protein.

Treatment

Treatment works on two fronts that go together: correcting the factor that triggered the episode (treating the infection, controlling the bleeding, stopping the sedative, rehydrating) and reducing the production and absorption of ammonia in the gut.

  • Lactulose (first line). This is a non-absorbable sugar that acidifies the gut, traps ammonia, and speeds up transit to remove it. The dose is adjusted to achieve two or three soft stools a day. Avoiding constipation is key, and lactulose also helps prevent episodes from recurring.
  • Rifaximin. This is a barely absorbed antibiotic that acts on the gut bacteria that produce ammonia. It is added to lactulose, mainly to prevent recurrence in people who have already had episodes, and it reduces hospitalizations.
  • Nutrition. Restricting protein is no longer recommended. On the contrary, a person with cirrhosis needs a good protein intake to avoid losing muscle mass, since muscle helps remove ammonia. Plant-based and dairy proteins are preferred, spread through the day, with a bedtime snack. Your physician or dietitian should guide this.
  • Avoid sedatives and review all medications.

Prognosis

Hepatic encephalopathy is a sign that liver disease is advanced. Although each episode usually reverses with treatment, its appearance marks a change in prognosis and calls for evaluating the person for a liver transplant, the treatment that resolves liver failure at its root. In the meantime, keeping up the lactulose, preventing constipation and infections, and seeking care early at any change in behavior are the best tools to avoid relapses.

See also

References

  1. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the AASLD and the EASL. Hepatology. 2014;60(2):715-735.
  2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol. 2022;77(3):807-824.
  3. Bass NM, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081.
  4. Sharma BC, et al. Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo. Gastroenterology. 2009;137(3):885-891.
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