This protocol addresses patients with covert hepatic encephalopathy (CHE) or minimal hepatic encephalopathy (MHE) — the subclinical, grade 1 or below form of HE identified only through specialized neuropsychological or neurophysiological testing, with no overt HE (grade 2 or higher).
Because CHE has low clinical reproducibility, its diagnosis depends on excluding overt HE in the appropriate clinical context rather than on bedside assessment alone.
The patient has already received a theragnostic trial of lactulose (orally) or, as an alternative, rifaximin, for a limited duration (typically 4–8 weeks) with a pre-specified symptom-based response criterion.
Escalation to this protocol is triggered when the first line fails to achieve improvement in neuropsychological test results and reversal of minimal hepatic encephalopathy, or when adherence and symptom assessment at 4–8 weeks do not demonstrate adequate response.
For patients whose CHE or MHE has not responded to first-line therapy, the structured protocol considers second-line agents tailored to individual patient characteristics — the selection depends on specific comorbid features present at the time of assessment. The full algorithm and criteria for choosing among these agents are detailed in the complete protocol.
MHE is the subclinical form of HE that can only be identified through specialized neuropsychological or neurophysiological testing.
Given the low reproducibility of clinical diagnosis of CHE (minimal or grade 1 HE), CHE should be defined by excluding OHE (grade 2 or higher) in the appropriate clinical context.
A second-line agent could be considered for treating MHE/CHE in certain patients (e.g., branch-chained amino acid [BCAA]/ l-ornithine-l-aspartate [LOLA] if sarcopenia/frailty; zinc if low serum levels, and l-carnitine if concomitant skeletal muscle cramps).
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