Can Hepatic Encephalopathy Be a Cause of Death?
Yes, hepatic encephalopathy is definitively associated with mortality and can contribute to death in patients with liver disease, though it typically reflects underlying severe liver failure rather than being the sole direct cause of death.
Mortality Risk and Prognostic Impact
Hepatic encephalopathy is strongly associated with poor survival and represents a marker of advanced, decompensated liver disease. 1 The evidence clearly demonstrates:
- Unless the underlying liver disease is successfully treated, HE is associated with poor survival and a high risk of recurrence. 1
- Approximately 30% of patients with cirrhosis die in hepatic coma. 2
- HE is a clinical event that defines the decompensated phase of cirrhosis, similar to variceal bleeding or ascites, and marks a transition to significantly worse prognosis. 1
Mechanisms of Death Related to HE
The mortality associated with HE occurs through several pathways:
Direct Complications of Severe HE
- Patients with overt HE grade 3-4 are at high risk of aspiration due to inability to protect their airways when Glasgow coma score falls below 7. 1 This aspiration risk can lead to respiratory failure and death.
- In acute liver failure, HE is associated with increased intracranial pressure and brain edema with a deleterious clinical course and poor prognosis unless liver transplantation is available. 2
HE as a Marker of Underlying Fatal Disease
- Several studies demonstrate that the occurrence of HE in patients with equivalent MELD scores significantly increases short- and medium-term risk of death with a 2-4 times increased relative risk compared to patients without HE. 1
- The prognostic effect of HE is even greater when it occurs in the context of acute-on-chronic liver failure (ACLF). 1
- HE in hospitalized cirrhotic patients is associated with a high mortality rate, and its presence adds further to the mortality of patients with ACLF. 3
Precipitating Factors That Increase Mortality
- Several HE-precipitating factors (e.g., infection and bleeding) are themselves associated with increased mortality, and effective management of such factors may improve prognosis. 1
- In a recent ICU study, in-hospital mortality was 50% with median transplant-free survival of only 0.8 months in cirrhotic patients admitted with overt HE. 4
- Multiple concomitant precipitating factors (present in 82% of ICU patients with HE) were independently associated with death or need for liver transplantation. 4
Clinical Context and Reversibility
An important caveat is that overt HE in cirrhotic patients is potentially fully reversible and is not an absolute contraindication for ICU admission. 1 This distinguishes it from irreversible terminal conditions:
- Up to 90% of patients can be expected to recover from episodic overt HE by correction of precipitating factors. 1
- Emergency liver transplantation in patients with severe HE in acute liver failure results in rapid resolution of HE together with marked survival improvement. 1
- Cognitive sequelae of HE persist in less than 5% of patients post-transplant, predominantly those with grade 3-4 HE before transplantation. 1
Prognostic Scoring
The addition of an encephalopathy score to the MELD score significantly improves the short- and medium-term predictive value of mortality. 1 This underscores that HE provides independent prognostic information beyond standard liver function measures and should be considered in transplant allocation decisions. 1
Quality of Life Impact
Even minimal HE significantly compromises quality of life and is predictive of the onset of overt HE, which further worsens prognosis. 1, 5, 6 The burden extends beyond mortality to include substantial morbidity and reduced functional capacity. 5