Joan CordobaUniversitat Autònoma de Barcelona

TRACTAMENT DE L’ENCEFALOPATIA HEPATICA

58 a varon confusion

Antecedentes

- Cirrosis VHCAscitis 2 años antes, control con espironolactoneVarices tt propranolol

- Infeccion orina 2 semanas antes. Cipro x 7 d.

CASO CLINICO

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

Bajaj APT 2010

ACUTE CHRONICSUBCLINICAL

OR LATENT

Severity and duration of neurological manifestations in cirrhosis

Bajaj APT 2010

MANAGEMENT OF THE EPISODE OF HEDiagnosisExclusion of other neurological diseases

Search of precipitating factorsGI bleeding, constipation, high protein loadinfection uremia, dehydration, hyponatremia sedatives

Assessment of liver function

Hb 13 g/dL, Leukocytes 5100, Platelets 68000creatinine 1 mg/dL Na 126 K 5.3 AST 105 ALT 73 NH3 129INR 1.6 bilirubin 2.4 mg/dL albumin 2.4 mg/dLUrine: 3 wc/f, 6 rc/f Chest x-ray: normalBlood 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 HETherapy: iv saline, stop diuretics, lactuloseImprovement in sodium (to 133 in 4 days)

Terminal liver failure: without jaundice? Additional anti-encephalopathy therapies: diet? drugs?Undiagnosed precipitating factor: additional tests?

Non-response at 1 week

2- Treatment HE: enema + neomycine + precipitating fact

0 g 12 g 24 g48 g 1,2 g.kg

1.2 g.kg.d1- DietNG tube30 Kcal.kg.d14 days

NORMAL PROTEIN

LOW PROTEIN

Cordoba, J Hepatology 2004

Oral intake of proteins during episodic HE

DAY0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

HE

PAT

IC E

NC

EPH

ALO

PAT

HY

STA

GE

0

1

2

3

4HYPOPROTEIC DIETNORMOPROTEIC DIET 30 patients randomized

10 patients finished before day 14 (died, GI bleeding, withdraw consent..)

No differences in the outcome

CT-scanPersistent HE = large porto-systemic shunts

Riggio O, Hepatology 2005

Cava

Left renal vein

Coils

Spleno-renal shunt

Occlusion of shunts improves HE for MELD<11

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 HEAmmonia 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 DRUGSPlacebo-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

Sharma BJ, Gastroenterology 2009

Lactulose prevents recurrence

Bass NM, NEJM 2010

2 episodes of HE in the previous 6 months90% on lactulose

Rifaximin improves lactulose

N=299

Canditato a trasplante

Alta con medicación preventiva: lactulosa

Tratamiento tras el alta

Author Agent Duration  Improved MHE?

Testing of clinicallyrelevant 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

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

Tratamiento tras el alta

Tratamiento multifactorial EH

Cordoba J, Sem Liv Dis 2008

SNC

MUSCULO

INTESTINO

RIÑON

HIGADO

Fuentes amoniacoInfeccionesFunción renalExpansión volemia

Despres d’un primer episodi d’encefalopatia es recomana

¿Que no es recomana?1. Avaluar el risc d’accidents2. Indicar tractament amb lactulosa o lactitol3. Fer una dieta normoproteica4. Emplear dosis baixes de diurètics, o

evitarlos5. Fer tractament amb yogurt