Falla heptica aguda

Adaptado de: American Association for the Study of Liver Diseases, 2011

1) Cmo se define la falla heptica aguda?

Cuadro clnico de injuria heptica aguda, encefalopata y tiempo de protrombina elevado (o INR
como equivalente) en un paciente sin cirrosis o enfermedad heptica pre-existente.
La falla heptica aguda se diferencia de la falla heptica crnica, en que la primera tiene una
duracin menor a 26 semanas.

2) Cmo se clasifica?
- Hiperaguda: evolucin menor a 7 das
- Aguda: evolucin entre 7 a 21 das
- Subaguda: entre 21 das y menos de 26 semanas
3) Complicacin ms comn de la falla heptica hiperaguda o aguda: edema cerebral
4) Complicacin ms comn de la falla heptica subaguda: falla renal e hipertensin portal
5) Cul clase de falla heptica aguda tiene mejor pronstico? la hiperaguda
6) Cules son las causas mayores de falla heptica aguda?
Se pueden recordar con la pnemotecnia:
A = acetaminofn, hepatitis "A", hepatitis "autoinmune", Amanita phalloides (toxicidad por
hongo), Adenovirus
B = hepatitis "B", sndrome de "Budd Chiari"
C = criptognica, hepatitis "C", citomegalovirus
D = hepatitis D, "drogas y toxinas"
E = hepatitis E, Epstein Barr virus
F = "Fatty; infiltracin grasa"; "fatty liver of pregnancy" (hgado graso agudo del embarazo)
G = gentico- enf Wilson

H = hipoperfusin (hepatitis isqumica/ enfermedad veno-oclusiva/ sepsis); sndrome Hellp,

Herpes-virus - Hemofagoctico, sndrome
I = infiltracin tumoral
Se estima que entre un 60-80% de casos se puede establecer la causa.
7) Cules de las anteriores, son las causas ms frecuentes de falla heptica aguda
(FHA)?
Las virales y la inducida por acetaminofn
8) Qu etiologa sospechar de acuerdo a la magnitud de elevacin de las
transaminasas?
- Elevacin masiva (>3500): intoxicacin por acetaminofn (tambin puede asociarse a baja
hiperbilirrubinemia)
- Elevacin entre 25-250 veces + DHL elevada: injuria heptica isqumica
- Elevacin entre 1000-2000 U/L:
- ALT ms elevada que AST = hepatitis B
- Proporcin AST:ALT 2:1 + FA baja + FA/bilirrubina total menor de 4/ anemia hemoltica
coombs negativo = enfermedad de Wilson
- Elevacin menor de 1000 + hiperbilirrubinemia + trombocitopenia = hgado graso agudo del
embarazo/ HELLP

9) Mencione las manifestaciones clnicas de la FHA.

- Sntomas: fatiga, malestar general, letargia, anorexia, nauseas o vmito, dolor en cuadrante
superior derecho, prurito, ictericia, distensin abdominal por asctis
- Hallazgos fsicos: por definicin la falla heptica aguda se acompaa de encefalopata.
- Otros: ictericia, lesiones en piel (herpes), dolor en hipocondrio derecho y hepatomegalia.

10) Cmo se clasifica la encefalopata heptica?

Grado I. Cambios en el comportamiento, con leve confusin, lenguaje "enrredado" y trastornos
del sueo.
Grado II. Letargia y confusin moderada. Asterixis pronunciada.

Grado III. Confusin marcada (estupor), lenguaje incoherente, el paciente despierta con
estmulos. Asterixis pronunciada. Edema cerebral (25-35%)
Grado IV. Coma, sin respuesta al dolor. Edema cerebral (75%)
11) Qu signos clnicos se buscan en el paciente con edema cerebral? Hipertensin,
bradicardia, depresin respiratoria (trada de cushing), convulsiones, poca reactividad pupilar.
12) Qu trastornos metablicos deben anticiparse y tratarse en el paciente con FHA?
La disfuncin renal
La hipoglucemia
Hipofosfatemia, hipomagnesemia
Trastornos cido-base
13) Dnde debe ser tratado el paciente? en una unidad que cuente con trasplante heptico,
pues slo el 40% de pacientes con FHA se recuperan espontneamente; si el paciente tiene
encefalopata grado II en adelante, debe ser vigilado en la UCI
14) Cmo usar N-acetilcistena?
Se usa en intoxicacin por acetaminofn (puede considerarse su uso en pacientes no candidatos
a trasplante heptico o con causa de FHA indeterminada). Gastroenterology. 2009;137(3):856.
Dosificacin: 150 mg/kg durante una hora; luego: 12,5 mg/kg/h por 4 horas; luego: 6,25 mg/kg
por las siguientes 67 horas restantes.
Es ms eficaz, cuando se usa en pacientes con encefalopata grado I
15) Qu otros aspectos deben vigilarse en el paciente con FHA?estos pacientes presentan
altas tasas de infeccin. Las guas sugieren obtener cultivos de rutina (sangre, orina, esputo) y
estudios de imagen (Rx de torax).
No est indicado el uso de antibiticos profilcticos en ste grupo de pacientes.
Otro aspecto fundamental, que ha de proveerse es la nutricin.
Evitar medicaciones hepatotxicas (evitar sedacin) y opioides (disminuyen umbral convulsivo)

Encefalopata heptica: no est demostrado que el uso de lactulosa o rifaximina, afecte el

pronstico de los pacientes.

16) Criterios de trasplante heptico:

se define por los distintos modelos pronsticos disponibles (MELD, SOFA, Clichy y ALFSG)
Uno de los ms simples, con los criterios "King College":
. En toxicidad por acetaminofn:
- Ph menor de 7,3 independiente de grado de encefalopata
- Encefalopata grado III o IV con Tp mayor de 100 segundos y creatinina mayor de 3,4 mg/dl
. En otras causas de FHA:
- Tp mayor de 100 segundos, independiente del grado de encefalopata
- Cualquiera de 3 de los siguientes: edad menor de 10 aos o mayor de 40 aos; etiologa de
la enfermedad desfavorable (hepatitis viral no A, no B; reaccin medicamentosa idiosincrtica;
enfermedad de Wilson); duracin de la ictericia antes de la encefalopata mayor de 7 das; Tp
mayor de 50 segundos; bilirrubina srica mayor de 18 mg/dl

Enfoque diagnstico del paciente con cirrosis

Cundo sospechar cirrosis? En los siguientes escenarios:
1. Examen fsico compatible con enfermedad heptica crnica: esplenomegalia, telangiectasias en
araa, eritema palmar, osteoartropata hipertrfica, contractura de Dupuytren, uas de Terry, uas
de Muehrcke, ginecomastia, prdida del vello axilar, atrofia testicular, caput medusae, ictericia,
ascitis, asterixis, fetor heptico, acropaquia.

Cuando hay hepatomegalia en un paciente con cirrosis, sospeche: hepatitis alcholica,

hepatocarcinoma, enfermedad metastsica, enfermedad infiltrativa.
2. Enfermedad cirrtica descompensada, caracterizada por la presencia de complicaciones como
varices hemorrgicas, ascitis, peritonitis bacteriana espontnea o encefalopata heptica.
- Un metaanlisis mostr que los mejores factores predictivos para cirrosis en adultos son:
presencia de ascitis (LR 7.2), plaquetas < 160.000/mm3 (LR 6.3), angiomas aracniformes (LR
4.3), puntuacin en la escala de Bonacini >7 (LR 9.4).

- Los factores asociados a un valor predictivo bajo para cirrosis son: conteo de
plaquetas 160.000 mm3 (LR 0.29), ausencia de hepatomegalia (LR 0.37), ndice de Lok <20%
(LR 0.09).
- El ndice de Lok se calcula usando el conteo de plaquetas, ALT, AST y el INR, sin embargo, se
debe tener en cuenta que este solo ha sido validado para la infeccin por hepatitis C.

Laboratorio:
Pruebas de funcin heptica:
- Aminotransferasas: aspartato aminotransferasa (AST) y alanino aminotransferasa (ALT),
usualmente estn moderadamente elevadas en los pacientes con cirrosis, casi siempre AST est
ms elevada que ALT. S las aminotransferasas estn normales NO se excluye el diagnstico de
cirrosis.
- Relacin AST/ALT > 2:1 es sugestiva de cirrosis (en cuadros agudos: hepatitis alcohlica).
- Fosfatasa alcalina: se encuentra elevada en el contexto de la cirrosis, su elevacin puede ser el
doble o el triple del lmite superior normal, ya que aumentos mayores sugieren enfermedad
heptica colestsica (colangitis esclerosante primaria o cirrosis biliar primaria).
- Gamma glutamil transpeptidasa (GGT): sus niveles son proporcionales a los de fosfatasa
alcalina, elevaciones superiores se correlacionan con enfermedad heptica alcohlica.

- Bilirrubinas: en cirrosis compensada estn normales, pero aumentan a medida que la cirrosis
progresa.
- Albmina: dado que es un medidor de la funcin heptica, ayuda a conocer la gravedad de la
cirrosis. Se debe tener en cuenta que la hipoalbuminemia no es especfica de la enfermedad
heptica, tambin puede estar en falla cardaca, sndrome nefrtico, enteropata perdedora de
protenas o malnutricin.
- Tiempo de protrombina: al igual que la albmina, da cuenta de la gravedad de la cirrosis pero no
es especfico para enfermedad heptica.

Pruebas hematolgicas:
- La anormalidad hematolgica ms comn es la trombocitopenia, causada por el secuestro
esplnico de plaquetas.
- Tambin se puede presentar anemia cuyo origen es multifactorial: sangrados gastrointestinales,
deficiencia de folatos, toxicidad por alcohol, hiperesplenismo, anemia aplstica asociada con
hepatitis y anemia de enfermedad crnica.
- Adems pueden aparecer leucopenia y neutropenia debido al hiperesplenismo.

Imagenologa:
- Ecografa: es la imagen rutinaria para la evaluacin de cirrosis. Los hallazgos caractersticos de
cirrosis son la superficie nodular y aparicin de reas de ecogenicidad irregulares en regin
heptica. Estas caractersticas tambin se pueden ver en la esteatosis heptica. Usualmente hay
atrofia del lbulo derecho e hipertrofia del caudado o el izquierdo. La ecografa tambin es til
para detectar esplenomegalia, ascitis, hipertensin portal y trombosis de las venas portales.
- Tomografa computarizada: NO es de uso rutinario en cirrosis, ya que provee informacin similar
a la de la ecografa, pero a expensas de la exposicin a radiacin y un medio de contraste.
Cuando se buscan focos de hepatocarcinoma, debe hacerse con la modalidad trifsica.

- Resonancia Magntica: no est clara su utilidad en el diagnstico de cirrosis; se sabe que la

angiografa por resonancia magntica es ms sensible que la ecografa para el diagnstico de las
complicaciones de la cirrosis, como la trombosis de venas portales. La resonancia est indicada
en la bsqueda de hepatocarcinoma.
Biopsia: es el estndar de oro para el diagnstico de cirrosis, con una sensibilidad que vara del
80 al 100%.
- Si la clnica, los exmenes de laboratorio y las imgenes sugieren la presencia de cirrosis, y si la
biopsia heptica no modifica el manejo del paciente, NO es necesario realizarla.
- La biopsia puede ser til para encontrar las causas metablicas de cirrosis, como:
hemocromatosis hereditaria, esteatohepatitis no alcohlica, enfermedad de Wilson y deficiencia
de 1 antitripsina.

Cundo referir al paciente a un especialista?

- Despus de test no invasivos (laboratorio e imgenes) si el diagnstico de cirrosis no est claro.
- Si se requiere una biopsia heptica.
- Se desconoce la etiologa de la enfermedad, y ya se descartaron las etiologas principales
(cirrosis alcohlica, hepatitis B y C, hemocromatosis y enfermedad heptica no alcohlica).

Orig in alAlp habet ic al

How is acute hepatic encephalopathy tx?

lactulose (a nonabsorbable disaccharide) and a reduced-protein
diet
Abx (neomycin and rifaximin) and laxative can also help
If sphincter oddi is found to be dysfunctional, what is the tx?
causes post cholecystectomy pain
Tx: ERCP w/ sphincterotomy
What are the causes of post cholecystectomy pain?
functional etiology
sphincter of Oddi dysfunction
common bile duct stones
What is the central process that causes non-alcoholic fatty liver
disease?
insulin resistance
also see increasing rate of lipolysis and elevating circulating insulin
levels
What is Reye syndrome?
fatty liver w/ encephalopathy
seen in children <15yo
preceded by URI with influenza or varicella in 60-80% of all cases
If tx w/ salicylates, increases likelihood of developing Reye
syndrome
ASA is contraindicated in children except in tx of Kawasaki's
Reye: diffuse mitochondral injury that leads to nausea, vomiting,
headache, excitability, delirium, combativeness, hypoglycemia, liver
failure, and progressive CNS damage.
Histo: extensive fatty vacuolizationo f the liver w/o inflammation is
present

Enlarged liver, but no icterus

Elevated serum aminotransferases, elevated ammonia levels, PT
prolongation, hypoglycemia and metabolic acidosis
TX: glu with FFP and mannitol to decrease cerebral edema
How is possible Hep B exposure tx?
Give Hep B vaccine and Hep B immunoglobulin ASAP!
How is gallbladder carcinoma tx?
rare malignancy that arises in Hispanic and SW Native American
females who have a history of gallstones.
Risk Factors: procelain gallbladder, salmonella typhi carriage,
anatomic variations, carcinogen exposure
Tx: radical surgical intervention: cholecystectomy, removal of
gallbladder bed, pancreatic head, LN, portions of the liver or biliary
tree. Sufficient tx
What is a hyatid cyst?
infxn with Echinococcus granulosus
DOGS are host
unilocular cystic lesion in liver, lung, muscle, bones
Usually ASx and generally dx on screening for some other problem.
May cause sx. Compression on surrounding tissues. Imaging can be
used for dx along with serological test. "eggshell" calcification of a
hepatic cyst on CT is highly suggestive
Tx: surgical resection under the cover of albendazole. DO NOT
aspirate because of risk of anaphylactic shock secondary to spilling
of cyst contents
What is the appropriate tx for acute cholecysitis?

laparoscopic cholecystectomy w/in 72hours during the same

hospitalization
What are the sx of chronic liver disease?
weight loss
gynecomastia
testicular atrophy
impotence
hyperestrogenism due to increased portosystemic shunting and
decreased synthesis of sex hormone binding globulin.
telangiectasias
palmar erythema
decreases in TSH, T4, T3 due to hypothalamic-pituitary dysfxn
What conditions is acalculous cholecystitis commonly seen?
hospitalized pts with:
1. extensive burns
2. severe trauma
3. prolonged TPN
4. prolonged fasting
5. mechanical ventilation
Complications
- gangrene
- perforation
- emphysematous cholecystitis
What is a choledochal cyst?
congenital abnormality of the biliary ducts characterized by
dilatation of intra or extra-hepatic biliary ducts or both.
multifactorial origin: related to anamalous pancreaticobiliary
junction that leads to weakness and dilatation of biliary wall due to
the reflux of alkaline pancreatic secretions into the biliary tree.
Many types.
remember: dilatation of the intra and/or extra hepatic biliary ducts

What is Charcot's triad of ascending cholangitis?

Fever
Severe jaundice
RUQ pain
can also see confusion and hypotension-->suppurative cholangitis
= Reynold's pentad
How is ascending cholangitis Tx?
ERCP if don't respond to supportive care and Abx
What is prophylactic tx for esophageal varices?
propranolol (b-blockers)
What is SAAG?
Serum ascites albumin gradient: distinguishes transudative from
exudative fluid accumulation
- calculated by subtracting ascites albumin concentration from the
serum albumin concentration.
- difference > 1.1g/dl or greater is 95% accurate in diagnosing a
transudative process consistent with portal hypertension (increased
hydrostatic pressure w/in liver's capillary beds)
What are extrahepatic sequelae of chronic hep C?
chronic arthralgias (often with a false-positive rheumatoid factor or
antinuclear antibody), cryoglobulinemia, porphyria cutanea tarda,
and glomerulonephritis
What is intrahepatic cholestasis of pregnancy?
functional disorder of bile formation that develops in the second
and third trimesters of pregnancy
- intense pruritis (see skin excoriations)
- increased serum bile acid concentrations
- jaundice
- increased alk phos

- increased total and direct bilirubin

- increased serum aminotransferases
Tx: sx relief and prevent complications to mom and baby.
- Ursodeoxycholic acid: increases bile flow to relieve pruritus
- hydroxyzine and cholestyramine
- may need early delivery
Resolves after pregnancy
Complications: (bad for baby)
- fetal prematurity
- meconium-stained amniotic fluid
- intrauterine demise
If a patient presents with chronic liver disease, what vaccines
should they receive?
Hep A and B
If an individual has a history of blood transfusion, what should
they be screened for?
Hep B and C
Why do cirrhotic patients present with pleural effusions?
hepatic hydrothorax
transudative pleural effusion more common on the right
occurs secondary to small defects in the diaphragm which permits
abdominal ascites fluid to pass into pleural space
How is hepatic hydrothorax tx?
liver transplantation
therapeutic thoracentesis followed by salt restricted diet and
diuretics
If diet fails, TIPS

If a patient comes in with acute pancreatitis, what is the first

imaging modality to be used?
US: search for gallstones!
Then Abd CT to confirm dx of acute pancreatitis and identify
complications
What are the risk factors for pancreatic cancer?
family hx
chronic pancreatitis
smoking
diabetes mellitus
obesity
diet high in fat
NOT alcohol
What are the antibodies seen in pts with PBC?
anti-mitochondrial antibodies
**What vaccines should pregnant pts with Hep C receive?
Hep A and B, if not already immune
What conditions should be considered in pts with liver bx results
that show Mallory bodies?
alcohol liver injury and Wilson's disease
What is Dubin-Johnson syndrome?
conjugated chronic hyperbilirubinemia NOT assoc w/ hemolysis
benign condition and common in Sephardic Jews
- icterus (may only be present if ill, pregnant or using OCPs)
- otherwise ASx
- may complain of fatigue, abd pain, weakness)
Liver Bx: dense pigment, black
No Tx necessary

What is Rotor Syndrome?

benign condition
defect of hepatic storage of conjugated bilirubin, resulting in
leakage into the plasma
chronic and mild hyperbilirubinemia of both the unconjugated and
conjugated forms then develops, w/o any suggestion of hemolysis
LFTs normal
NO pigmented granules in hepatocytes on Bx
What is Gilbert's syndrome?
mild unconjugated hyperbilirubinemia thought to be provoked by
one of the classic triggers (fasting, stress, illness)
What is Crigler-Najjar syndrome?
rare, autosomal recessive disease characterized by significant
unconjugated hyperbilirubinemia
phototherapy or plasmapheresis helpful in short term
Liver transplant only curative option
How is chronic Hep B tx?
interferon or lamivudine
What is pancreatic necrosis?
most severe form of acute pancreatitis that can lead to systemic
hypotension and eventual shock.
Locally released and activated pancreatic enzymes can increase
vascular permeability w/in and around the pancreas-->loss of large
volume of plasma into the retroperitoneum. Pancreatic enzymes
also cause widespread vasodilation, capillary leak, that results in
hypotension because of the systemic inflammation
Tx: aggressive fluid resuscitation and abx to prevent
superinfection.
What is the most common drug used to treat PBC?

ursodeoxycholic acid
- relieves sx and lengthens transplant-free survival time
How is acute pancreatitis tx?
analgesics, IV fluids, NPO
What are the sx of cirrhosis that are a result of hyperestrogenism?
gynecomastia
testicular atrophy
decreased body hair
spider angiomas
palmar erythema
What additional hx is needed if lab results reveals an elevation of
aminotransferases?
Hepatitis risk factors:
- alcohol or drug use
- travel outside of the country
- blood transfusions
- high- risk sexual practices
What are the familial disorders that cause an unconjugated
hyperbilirubinemia?
Gilbert's syndrome
Crigler-Najjer type 1
Crigler-Najjer type 2
What are the dx criteria for SBP?
cirrhosis/ascites
low grade fever
abd discomfort
altered mental status
paracentesis with a PMN count > 250
positive ascites culture confirms dx

What is the tumor marker that is elevated in hepatocellular

carcinoma?
AFP
What is the first step in evaluating patients with suspected
hepatocellular carcinoma?
AFP measurement
What are the risk factors for HCC?
chronic viral hepatitis
cirrhosis
many ASx and some present with weight loss, abd pain, palpable
mass
How do you treat coagulopathy in patients with liver failure?
FFP
What are the liver tests used to evaluate liver functionality?
prothrombin time
bilirubin
albumin
cholestrol
What are the liver tests to evaluate liver structural integrity and
cellular intactness?
transaminases
GGT
alk phos
What does progressive decrease in transaminase levels signal?
recovery from liver injury OR
few hepatocytes are functional
What are the risk factors for pancreatic cancer?

1. male sex
2. increasing age (50yo)
3. black race
4. cigarette smoking: most consistent risk factor (2-3x more likely
in heavy smokers)
5. chronic pancreatitis
6. long-standing diabetes
7. obesity
8. familial pancreatitis
9. pancreatic cancer in a close relative
NOT Risk Factors:
- alcohol consumption
- gall stones
- coffee intake
What causes acute cholecystitis?
gallstone obstructing cystic duct with subsequent inflammation and
infection
What are the indications to initiate treatment in hep C pts?
elevated ALT, detectable HCV RNA, histo evidence of chronic hep of
at least moderate grade-->antiviral tx: interferon and ribavirin
How should newborns to mothers with active hep B be treated?
hep B immune globulin (passive immunization)+
active immunization w/ recomb HBV vaccine
How should pts with a liver mass suspected to be an amebic
abscess be treated?
empiric tx with oral flagyl
DO NOT ASPIRATE
How does anaphylactic reaction to transfusion products manifest?
common in pts with IgA deficiency

rapid onset of sx with associated bronchospasm and hypotension,

plus absence of fever
How does ABO mismatching present?
rapid hemolysis
fever, flank pain, dark urine, and manifestations of DIC
What is another name for Wilson's disease?
hepatolenticular degeneration
If AST and ALT are markedly elevated, think hepatocellular injury
caused by...?
alcohol and meds (acetaminophen)
alcohol will have AST: ALT 2:1 ratio
If a pt with liver disease complains of abd pain and has a LEFT
pleural effusion, what should you consider?
MALIGNANCY: metastatic disease
If a pt presents with panacinar emphysema and cirrhosis, what
condition should be considered?
alpha-1 antitrypsin deficiency
What imaging test should be used to dx pancreatic cancer?
abd CT
What is the mechanism for the pain caused by biliary colic?
gallbladder becomes distended as it contracts against an
obstructed cystic duct. The distenion is what causes pain
What is the best screening test for acute hep B infection?
HBsAg and anti-HBc
What are the less common causes for acute pancreatitis?

hypertriglyceridemia (triglyceride levels over 1000mg/dL) will see

eruptive xanthomas on physical exam
Dx: fasting lipid profile
What liver condition is similar to vanishing bile duct syndrome?
progressive ductopenia, loss of intrahepatic bile ducts. Most
common cause of ductopenia in adults is PBC
Which neuromuscular blocking agent is safe to use in pts with
renal and liver dysfunction?
atracurium
metabolized in plasma and hydrolyzed by serum esterases
Which liver conditions are reversible?
fatty liver (steatosis)
alcoholic hepatitis
early fibrosis of the liver
reversible with cessation of alcohol intake
True cirrhosis is irreversible
When should you suspect ischemic hepatic injury?
setting of hypotension and acute, massive increases in AST and ALT
with milder increases in total bili and alkphos
if pt survives, liver enzymes will normalize in a few weeks
What is emphysematous cholecystitis?
acute cholecystitis in elderly diabetic males
arises due to infection of the gallbladder wall with gas-forming
bacteria
How is liver damage assessed in pts with chronic hepatitis?
liver bx
What condition can falsley elevate alk phos?

Paget's disease: bone remodeling and abnormal osteoid formation.

Alk phos elevated, but serum calcium, phosphorus and other LFTs
normal
What is an indication that hyperbilirubinemia is conjugated form?
presence of bilirubin in urine
What are the extra-hepatic complications of Chronic Hep C?
membranoproliferative glomerulonephritis-->proteinuria
1. cryoglobulinemia
2. b-cell lymphomas
3. plasmacytomas
4. autoimmune diseases like Sjogren's syndrome and thyroiditis
5. Lichen planus
6. porphyria cutanea tarda
7. idiopathic thrombocytopenic purpura