====== Hepatic encephalopathy ======

===== Diagnosis =====

The diagnosis of hepatic [[encephalopathy]] is a clinical one, once other causes for confusion or coma have been excluded; no test fully diagnoses or excludes it. 

Serum [[ammonia]] levels are elevated in 90% of people, but not all hyperammonaemia (high ammonia levels in the blood) is associated with encephalopathy.

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The efficacy of the [[blood-brain barrier]] is compromised in certain pathological states (e.g. [[tumor]], [[infection]], [[trauma]], [[stroke]], [[hepatic encephalopathy]]...), and can also be manipulated pharmacologically (e.g. hypertonic [[mannitol]] increases the permeability, whereas [[steroid]]s reduce the penetration of small hydrophilic molecules).

It is important to rule it out for [[brain death criteria]].

===== Complications =====

[[Osmotic demyelination syndrome]]

[[Central pontine myelinolysis]] (CPM) over-correcting serum sodium in patients with hepatic [[encephalopathy]].

[[Coma]]..

===== Systematic reviews =====
Krishnan et al. reviewed 2,824 unique publications; 15 met the criteria for inclusion. Categories of biomarkers reported were inflammatory cytokines, products of amino acid metabolism, trace elements and vitamins, and hepatic and neuro biomarkers. Of 19 individual biomarkers, only five were measured in more than one study. Elevations in interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were most commonly reported as associated with HE. Notably, we observed lower average IL-6 and TNF-alpha levels in pediatric-only studies compared to mixed-age studies. Overall, high bias and poor applicability to our review question were observed. We encountered low numbers of studies with a pediatric focus, and few conducted with low-bias study designs.

Investigated biomarkers span a large range of categories and suggest potentially useful correlations with HE. Further well-designed prospective biomarker research is necessary to better elucidate the pathogenesis of HE in children and improve early detection and clinical care
((Krishnan K, Rao M, Chang N, Casazza M, Rasmussen LK. Novel serum biomarkers associated with pediatric hepatic encephalopathy: A systematic review. J Pediatr Gastroenterol Nutr. 2023 Apr 24. doi: 10.1097/MPG.0000000000003801. Epub ahead of print. PMID: 37084331.)).