Can hepatic encephalopathy cause nausea in patients with a history of liver disease, particularly those with cirrhosis?

Hepatic Encephalopathy and Nausea

Nausea is documented as a common adverse effect in patients being treated for hepatic encephalopathy, but it is not listed as a primary clinical manifestation of hepatic encephalopathy itself in the major international guidelines.

Clinical Manifestations of Hepatic Encephalopathy

The 2014 AASLD/EASL guidelines provide comprehensive descriptions of hepatic encephalopathy presentations, focusing on neuropsychiatric and motor symptoms rather than gastrointestinal symptoms 1:

Primary Neuropsychiatric Features

• Cognitive changes: Altered attention, working memory impairment, psychomotor slowing, and visuospatial deficits occur in minimal/covert HE 1
• Personality changes: Apathy, irritability, and disinhibition are commonly reported by relatives 1
• Consciousness alterations: Progressive disorientation to time and space, inappropriate behavior, confusion, somnolence, stupor, and ultimately coma 1
• Sleep disturbances: Excessive daytime sleepiness is frequent, though complete sleep-wake reversal is less consistent 1

Motor System Abnormalities

• Extrapyramidal signs: Hypomimia, muscular rigidity, bradykinesia, parkinsonian-like tremor, and dyskinesia are common findings 1
• Pyramidal signs: Hypertonia, hyperreflexia, and positive Babinski sign can be observed 1
• Asterixis: The characteristic "flapping tremor" (actually a negative myoclonus) appears in early to middle stages preceding stupor 1

Nausea in the Context of Hepatic Encephalopathy

Treatment-Related Nausea

Nausea appears primarily as an adverse effect of hepatic encephalopathy treatments rather than as a symptom of the condition itself:

• Rifaximin trials: Nausea occurred in 14% of patients receiving rifaximin 550 mg twice daily for hepatic encephalopathy prevention, compared to 13% in placebo 2
• Treatment discontinuation: In travelers' diarrhea trials, nausea was among the adverse reactions leading to rifaximin discontinuation 2

Alternative Explanations for Nausea in Cirrhotic Patients

When nausea occurs in patients with liver disease, consider these alternative causes rather than attributing it directly to hepatic encephalopathy 1:

• Concomitant disorders: Renal dysfunction, hyponatremia, diabetes mellitus, sepsis, and thiamine deficiency commonly coexist with cirrhosis and can cause altered mental status and gastrointestinal symptoms 1
• Medication effects: Lactulose and rifaximin, the mainstays of HE treatment, can cause gastrointestinal side effects including nausea 3, 2
• Advanced liver disease complications: Ascites, portal hypertension, and other decompensation features may contribute to nausea independently 1

Clinical Pitfalls to Avoid

• Do not assume nausea indicates hepatic encephalopathy: The major guidelines do not list nausea among the clinical presentations of HE 1
• Systematically evaluate for precipitating factors: Infections, gastrointestinal bleeding, electrolyte disturbances, and medications cause 90% of overt HE episodes and may independently cause nausea 3
• Consider alternative diagnoses: The neurological manifestations of HE are nonspecific; concomitant disorders must be considered as additional sources of symptoms 1
• Distinguish HE from other causes of altered mental status: Renal dysfunction, hyponatremia, sepsis, and thiamine deficiency (Wernicke's encephalopathy) can present with overlapping symptoms 1

Bottom Line

While nausea may occur in patients with cirrhosis and hepatic encephalopathy, it is not a recognized primary manifestation of HE according to AASLD/EASL guidelines 1. When present, nausea more likely represents treatment side effects 2, concomitant complications of advanced liver disease 1, or alternative diagnoses requiring systematic evaluation 3.