TRACTAMENT DE L ENCEFALOPATIA HEPATICA Joan Cordoba Universitat Autònoma de Barcelona
CASO CLINICO 58 a varon confusion Antecedentes - Cirrosis VHC Ascitis 2 años antes, control con espironolactone Varices tt propranolol - Infeccion orina 2 semanas antes. Cipro x 7 d. Enf actual Progresivamente 4 dias somnolencia, temblor, incapacidad funcional (comer, beber, control estínteres.) Temp 36ºC, TA 98/60, FC 60, pulsi: 99% No ascitis, no edemas, no deshidratacion, no melenas (examen rectal) Estuporoso, responde estimulos verbales, emitiendo un habla no comprensible Flapping tremor, no deficit motor, reflejos simétricos Diagnostico: Episodio Encefalopatia Hepática
Severity and duration ACUTE CHRONIC SUBCLINICAL OR LATENT Bajaj APT 2010
Severity and duration of neurological manifestations in cirrhosis Bajaj APT 2010
MANAGEMENT OF THE EPISODE OF HE Diagnosis Exclusion of other neurological diseases Search of precipitating factors GI bleeding, constipation, high protein load infection uremia, dehydration, hyponatremia sedatives Assessment of liver function Hb 13 g/dl, Leukocytes 5100, Platelets 68000 creatinine 1 mg/dl Na 126 K 5.3 AST 105 ALT 73 NH 3 129 INR 1.6 bilirubin 2.4 mg/dl albumin 2.4 mg/dl Urine: 3 wc/f, 6 rc/f Chest x-ray: normal Blood and urinary cultures: negative HE precipitated by hyponatremia/diuretics
Hyponatremia: risk factor for HE Guevara M et al, AJG 2009;104:1382-9
Treatment of HE Therapy: iv saline, stop diuretics, lactulose Improvement in sodium (to 133 in 4 days) Non-response at 1 week Terminal liver failure: without jaundice? Additional anti-encephalopathy therapies: diet? drugs? Undiagnosed precipitating factor: additional tests?
Oral intake of proteins during episodic HE 1- Diet NG tube 30 Kcal.kg.d 14 days NORMAL PROTEIN LOW PROTEIN 0 g 12 g 24 g 1.2 g.kg.d 48 g 1,2 g.kg 2- Treatment HE: enema + neomycine + precipitating fact HEPATIC ENCEPHALOPATHY STAGE 4 3 2 1 0 HYPOPROTEIC DIET NORMOPROTEIC DIET 30 patients randomized 10 patients finished before day 14 (died, GI bleeding, withdraw consent..) No differences in the outcome 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 DAY Cordoba, J Hepatology 2004
CT-scan Persistent HE = large porto-systemic shunts Riggio O, Hepatology 2005
Occlusion of shunts improves HE for MELD<11 Cava Coils Spleno-renal shunt Left renal vein Laleman W 2012 Hepatology 2013
CT of the patient Esophageal and paraesophageal varices Lack of large portosytemic shunts
Additional information given by the CT Hidden prostatic abscess Drainage + culture: E Coli resistant to quinolones & sensitive to cotrimoxazol Disappearance of HE
MANAGEMENT OF OVERT HE Ammonia and inflammation key factors in precipitating HE Unresolved episode of HE without severe liver failure and without comorbidities: keep on searching (shunts? hidden infections? benzodiacepines?) ANTI-ENCEPHALOPATHY DRUGS Placebo-controlled studies in overt HE are old (management of cirrhosis has changed, standard of care not established) - Non-absorbable disaccharides (lactulose, lactitol) some evidences suggest that are better than cathartics - Non-absorbable antibiotics (neomycin, rifaximin) several studies suggest that are better than disaccharides - Benefits of combination for overt HE not demonstrated - Alternative pathways for ammonia disposal: L-Ornithine L-Aspartate iv. improves mental status in persistent HE
Lactulose prevents recurrence Sharma BJ, Gastroenterology 2009
Rifaximin improves lactulose 2 episodes of HE in the previous 6 months 90% on lactulose N=299 Bass NM, NEJM 2010
Canditato a trasplante Tratamiento tras el alta Alta con medicación preventiva: lactulosa
Author Agent Duration Improved MHE? Testing of clinically relevant outcomes Watanabe Lactulose 8 weeks Yes _ Li Probiotic 24 weeks Yes _ Horsmans Lactulose 2 weeks Yes _ Prasad Lactulose 90 days Yes Improved quality of life Morgan Rifaximin 8 weeks Yes _ Bajaj Yogurt 60 days Yes Trend: reduced OHE Liu Synbiotic 60 days Yes CTP improvement Malguanera Probiotic 90 days Yes _ Sidhu Rifaximin 90 days Yes Improved quality of life Bajaj Rifaximin 60 days Yes Improved driving
Tratamiento tras el alta Objetivo: evitar descompensaciones y evitar riesgos, mejorar calidad devida, llegar al trasplante Trabajo: carpintero en baja hasta trasplante Conducción 2-3 veces por semana Conyugue: nota empeoramiento conducción (varios golpes carroceria), se le pide no conduzca Solicitamos pruebas psicométricas para convencerle
SNC Tratamiento multifactorial EH MUSCULO HIGADO INTESTINO RIÑON Fuentes amoniaco Infecciones Función renal Expansión volemia Cordoba J, Sem Liv Dis 2008
Despres d un primer episodi d encefalopatia es recomana Que no es recomana? 1. Avaluar el risc d accidents 2. Indicar tractament amb lactulosa o lactitol 3. Fer una dieta normoproteica 4. Emplear dosis baixes de diurètics, o evitarlos 5. Fer tractament amb yogurt