Neurofilament Light Chain in Cerebrospinal Fluid and Blood Identifies Patients With Minimal and Overt Hepatic Encephalopathy.

In adults with cirrhosis, diagnose hepatic encephalopathy (HE) clinically: an alteration in mental status graded by the West Haven criteria (minimal + grade 1 = covert; grades 2-4 = overt, e.g. disorientation, asterixis, somnolence to coma) in a patient with liver disease/portosystemic shunting, made only after excluding other causes of altered mentation (structural, infectious, metabolic, toxic). Use the operational classification (type, time course [episodic/recurrent/persistent], and precipitated vs spontaneous). Measure blood ammonia primarily as a RULE-OUT test: a NORMAL ammonia level questions the diagnosis of HE (high negative predictive value), but ammonia does NOT add diagnostic, staging or prognostic value in a patient with known HE and should not be used to grade HE or to titrate therapy; sample and handle it correctly (prompt, on ice). In every patient with overt HE, actively search for and treat a precipitating factor, infection, GI bleeding, dehydration/diuretic overuse, electrolyte disturbance, constipation, sedatives/psychoactive drugs. Treat an episode of overt HE with a non-absorbable disaccharide (lactulose) titrated to 2-3 soft bowel movements per day (oral, or by enema in grade 3-4 to avoid aspiration); polyethylene glycol may be substituted for a lactulose enema in patients with persistent constipation, sub-ileus, or intolerance to lactulose, and although small single-centre trials suggest more rapid resolution of HE, the evidence is limited and whether it should replace or be combined with lactulose is unclear, so it is not an established faster-acting alternative or adjunct. After a first episode of overt HE, give lactulose as secondary prophylaxis (titrated to 2-3 BM/day); add rifaximin 550 mg twice daily as an ADJUNCT to lactulose only after >=1 further episode of overt HE occurs within 6 months of the first (or continue rifaximin already in use). Do not restrict dietary protein: target the general cirrhosis nutrition goals (protein 1.2-1.5 g/kg/day, energy ~35 kcal/kg/day) with meals distributed across the day and a late-evening snack; in recurrent/persistent HE, substitution of animal protein with vegetable and dairy protein can be considered provided total protein intake is not compromised. For HE refractory to lactulose + rifaximin, reconsider the diagnosis and re-search for a missed precipitant or a large spontaneous portosystemic shunt; obliteration of an accessible portosystemic shunt can be considered in stable patients with preserved liver function (MELD <11), and post-TIPS HE refractory to medical therapy may warrant TIPS reduction/occlusion. Evaluate for liver transplantation in eligible patients, refer for transplant assessment in patients with recurrent/persistent HE (and hepatic myelopathy as soon as possible), recognizing that a first episode of overt HE already carries a poor prognosis.