High Lactic Acid Does Not Trigger Hepatic Encephalopathy—It Is a Consequence, Not a Cause
Elevated lactic acid levels do not trigger hepatic encephalopathy (HE); rather, increased brain lactate is a consequence of the metabolic derangements occurring in HE, reflecting the severity of neuronal dysfunction rather than causing it. 1, 2
Understanding the Relationship Between Lactate and Hepatic Encephalopathy
Brain Lactate as a Marker of Severity, Not a Precipitant
Cerebrospinal fluid (CSF) lactate levels are elevated in patients with HE (1.92 mmol/L vs. 1.40 mmol/L in controls) and correlate directly with the severity of encephalopathy. 1
In patients with moderate (stage 2) HE, 9 of 11 had CSF lactate levels below 2 mmol/L, while in severe (stage 3-4) HE, 4 of 5 patients had levels exceeding 2 mmol/L. 1
CSF lactate decreases as neurological symptoms improve with treatment, indicating it reflects metabolic impairment rather than driving the encephalopathy. 1
Mechanisms of Lactate Accumulation in HE
The increase in brain lactate during liver failure occurs through three potential pathways 2:
- Blood-borne lactate crossing the blood-brain barrier (systemic hyperlactatemia)
- Increased glycolysis secondary to cerebral energy failure or metabolic impairment
- Altered lactate production/release or decreased utilization/uptake by brain cells
These mechanisms represent consequences of the underlying hepatic dysfunction and associated metabolic derangements, not precipitating factors for HE. 2
Recognized Precipitating Factors for Hepatic Encephalopathy
The established precipitating factors that actually trigger HE episodes are well-defined and do not include elevated lactic acid 3:
- Gastrointestinal bleeding (requiring endoscopy, transfusion, vasoactive drugs)
- Infection/sepsis (requiring antibiotics after appropriate cultures)
- Constipation (treated with enemas or laxatives)
- Dehydration (from excessive diuretics or paracentesis)
- Renal dysfunction and electrolyte abnormalities (hyponatremia, hypokalemia)
- Sedating medications (benzodiazepines, opioids)
- Acute liver dysfunction
Approximately 80-90% of HE episodes can be attributed to identifiable precipitating factors, and many cases improve simply by eliminating these triggers. 3
Clinical Implications and Therapeutic Considerations
The Role of Lactic Acid in HE Treatment
Lactulose therapy works by producing lactic acid and acetic acid in the colon through bacterial degradation, which lowers intestinal pH and traps ammonia as non-absorbable ammonium. 3, 4
This therapeutic production of lactic acid in the gut is beneficial and leads to recovery in 70-90% of HE patients. 3
The intestinal production of lactic acid by lactulose is mechanistically distinct from systemic or brain lactate accumulation and represents a treatment strategy, not a disease trigger. 3, 4
Important Caveats
Systemic hyperlactatemia from other causes (sepsis, shock, tissue hypoperfusion) may coexist with HE but represents a separate pathophysiological process requiring its own management. 3
When sepsis is present in cirrhotic patients, neurological symptoms occur in 21-33% of cases (60-68% in septic shock), with systemic inflammation and hyperammonemia acting synergistically. 3
In such cases, treat the underlying sepsis and metabolic derangement while simultaneously managing HE with standard therapies (lactulose as first-line, rifaximin as add-on). 3
Bottom Line for Clinical Practice
Do not attribute HE episodes to elevated lactic acid levels. Instead, focus on identifying and correcting the established precipitating factors listed above. 3 If systemic lactate is elevated, investigate for sepsis, shock, or tissue hypoperfusion as separate but potentially coexisting conditions that require their own targeted interventions. 3 The presence of elevated brain lactate in HE patients reflects the severity of metabolic brain dysfunction and can serve as a prognostic marker, but it is not a therapeutic target for preventing or treating HE. 1, 2