Hepatic encephalopathy: Clinical sciences

Hepatic encephalopathy refers to a potentially reversible neuropsychiatric complication of advanced liver disease, most commonly cirrhosis. In cirrhosis, impaired liver function results in the accumulation of toxic substances, like ammonia, which can eventually reach the brain and cause neurological dysfunction. Symptoms can vary from mild confusion to severe brain dysfunction with features like stupor or coma. Mild cases are referred to as covert hepatic encephalopathy, while severe cases are called overt hepatic encephalopathy.

If your patient presents with a chief concern suggesting hepatic encephalopathy, first perform an ABCDE assessment to determine if they are unstable or stable.

If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. Finally, if needed, provide supplemental oxygen to maintain oxygen saturation above 90 percent.

Okay, now let’s go back to the ABCDE assessment and focus on stable patients.

If your patient is stable, your first step is to obtain a focused history and physical examination. History will typically reveal impaired mental status, which can range from mild confusion, changes in behavior, to coma. Family or caregivers may report deficits in memory, attention, and behavioral changes, as well as disturbances in the sleep-wake cycle.

Additionally, the physical exam will usually reveal signs of underlying liver disease, like jaundice, ascites, palmar erythema, and telangiectasias. You might also notice hypertonia, hyperreflexia, and asterixis, which is characterized by a flapping tremor of the wrists that occurs when the arms are extended. With these findings, you should suspect hepatic encephalopathy!

Now, here’s a clinical pearl to keep in mind! Hepatic encephalopathy typically doesn't cause focal neurological deficits, such as unilateral body weakness or aphasia. If you see these findings, you should consider other conditions, such as a stroke.

Now, once you suspect hepatic encephalopathy, order labs, including a CBC, CMP, and coagulation studies, like prothrombin time, or PT; partial thromboplastin time, or PTT, and international normalized ratio, or INR.

Lab results usually show thrombocytopenia in combination with elevated AST, ALT, ALP, and bilirubin. Additionally, your patient will typically have low albumin levels. Finally, impaired synthetic liver function will result in elevated PT, PTT, and INR. At this point, you can make a clinical diagnosis of hepatic encephalopathy!

Now here’s another clinical pearl to keep in mind! In hepatic encephalopathy, the ammonia level has a poor positive predictive value. This is because other conditions can cause an elevated ammonia level, such as renal dysfunction or urea cycle disorders. On the flip side, the ammonia test has an excellent negative predictive value, meaning that if your patient has normal ammonia levels, it is unlikely that liver dysfunction is the cause of encephalopathy.

Now that you’ve diagnosed hepatic encephalopathy, your next step is to assess the level of mental impairment and grade the severity.

Let’s start with grade I. If your patient’s signs and symptoms are limited to behavioral change, mild confusion, slurred speech, and disordered sleep, diagnose grade I hepatic encephalopathy, also known as covert hepatic encephalopathy. As the name implies, the changes are frequently subtle and may not significantly impact your patient’s ability to function. Management of covert hepatic encephalopathy focuses on periodic follow-up to monitor for signs of progression. If your patient’s symptoms are negatively impacting their quality of life, such as their ability to drive or their work performance, then initiate treatment with lactulose. Lactulose is a nonabsorbable disaccharide that acidifies ammonia in the gastrointestinal tract, preventing its absorption into circulation. Lactulose is typically titrated to achieve two to four bowel movements per day, but in covert hepatic encephalopathy, a lower maintenance dose might be enough.

Now, switching gears and moving on to grades II, III, and IV. If your patient presents with lethargy and moderate confusion, that’s grade II hepatic encephalopathy. On the flip side, if your patient presents with marked confusion, stupor, incoherent speech, and is sleepy but still arousable, categorize it as grade III hepatic encephalopathy. Finally, if your patient is comatose and unresponsive to pain, that’s grade IV hepatic encephalopathy. Grades II, III, and IV are defined as overt hepatic encephalopathy, so admit your patient to the hospital for treatment.