Hepatic encephalopathy: Clinical sciences

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Introduction 0:00–0:41

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.

Unstable Patient 0:41–1:14

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.

Stable Patient 1:14–2:30

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.

Labs2:30–3:51

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.

Covert HE - Grade I 3:51–5:06

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.

Overt HE - Grades II, III, and IV 5:06–6:10

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.
Now here’s another clinical pearl to keep in mind! Patients with grades III or IV encephalopathy are at increased risk of developing cerebral edema.
These patients should be monitored closely for the development of seizures and signs of elevated intracranial pressure! Once you admit your patient to the hospital, your next step is to assess for a precipitating factor.

Overt HE - Precipitating Factor 6:10–7:11

Some of the most important precipitating factors include infections, such as spontaneous bacterial peritonitis and urinary tract infections.
There could also be gastrointestinal bleeding, like esophageal varices and peptic ulcers, or renal failure. Other causes may include dehydration, electrolyte imbalance, and medications associated with central nervous system depression.
And here’s one last clinical pearl! If a patient with hepatic encephalopathy presents with ascites, you must perform a paracentesis and order ascitic fluid analysis, including cultures, to rule out spontaneous bacterial peritonitis.
This is because hepatic encephalopathy can be the primary manifestation of spontaneous bacterial peritonitis! Once you’ve identified the precipitating factor, initiate treatment for the underlying cause, and start lactulose.

Overt HE - Treatment 7:11–8:27

Titrate the dose of lactulose until your patient has 2 to 4 bowel movements per day, and assess their response to treatment after 48 hours.
If there's an adequate response, meaning your patient's mental status is improving, continue lactulose indefinitely as prophylaxis against future episodes of hepatic encephalopathy.
On the other hand, if there’s an inadequate response, meaning your patient’s mental status is not improving, add rifaximin to the treatment regimen.
Rifaximin is an antibiotic that’s poorly absorbed and concentrates in the gastrointestinal tract. It works by eliminating ammonia-producing bacteria and subsequently reducing the amount of ammonia absorbed into circulation.
Once you add rifaximin, wait 48 hours and assess your patient’s response to treatment. If they improve, continue lactulose indefinitely and rifaximin for at least three months.
However, if there’s inadequate improvement, obtain a surgical consultation for liver transplantation. Alright, as a quick recap…Hepatic encephalopathy refers to a potentially reversible neuropsychiatric complication of advanced liver disease, most commonly cirrhosis.

Review 8:27–9:36

If suspected, first obtain a focused history, physical exam, and labs. Impaired mental status, physical findings, and lab results consistent with liver dysfunction confirm the diagnosis.
Next, assess the level of mental impairment and grade the severity from grade I to IV. Grade I is covert hepatic encephalopathy, which usually requires periodic follow-ups and possibly lactulose.
On the flip side, grades II to IV are referred to as overt hepatic encephalopathy and require immediate hospitalization.
Management primarily relies on treating the underlying cause and lactulose. If your patient’s mental status does not improve with lactulose, add rifaximin to the current treatment regimen.
Finally, in severe cases, consult your surgery team for liver