Fulminant Hepatic Faliure

• BY Dr Mohd. Moaaz Kidwai

• Moderator- Dr. Sunil Mehendiratta

Overview

• In 1970, ALF was classically defined as FHF in patients with no prior liver disease in which rapidly deteriorating hepatocellular function ensued within 8 weeks

• It was redefined by O'Gradey et al. in 1993, who used the term ALF to describe a clinical syndrome in which encephalopathy occurs between 8 and 28 days after the onset of jaundice

Further subclassification depending on the jaundice-to-encephalopathy time-• hyperacute -onset within 1 week• acute – between 8 days and 4 weeks• subacute -between 29 days and 12 weeks

defintionThe currently accepted definition in children includes-• biochemical evidence of acute liver injury (usually

<8 wk duration)• no evidence of chronic liver disease• and hepatic-based coagulopathy defined as (PT)

>15 sec or INR >1.5 not corrected by vitamin K in the presence of clinical hepatic encephalopathy or

• PT >20 sec or INR >2 regardless of the presence of clinical hepatic encephalopathy.

Etiology• ALF is rare and represents a syndrome, rather

than a specific disease.• the results of a recent multicenter study of

ALF identified acetaminophen overdose as the most frequent cause in the United States (46% of cases) (3) as well as in European countries (7).

• On the other hand, in Africa and Asia, viral hepatitis remains the leading cause of ALF

Pathophysiology• The mechanisms that lead to FHF are poorly

understood • Massive destruction represent both a direct

cytotoxic effect and hyperimmune responseWhatever the initial cause of hepatocyte injury, various factors can contribute to the pathogenesis of liver failure, including -• Impaired hepatocyte regeneration,• Altered parenchymal perfusion • Endotoxemia • Decreased hepatic reticuloendothelial function

Clinical features• Presentation is mostly like septic shock• Progressive jaundice, fetor hepaticus, fever,

anorexia, vomiting, and abdominal pain are common

• These symptoms finally lead to the development of encephalopathy

• Eventulally MODS and death due to herniation

Management

• Initial Assessment• Investigations and monitoring • Immediate management• Specific treatment• Treatment of complications• Liver transplantation

Initial Assesment

• History- onset, mentl status, bleeding - Drug, GDD, seizures - F/HExamination-Assesment of growth and nutrition - Signs of CLD - CNS exam, Liver span.

Investigations

• CBC, SE, RBS, ABG• LFT, RFT, PTINR• Blood Amonia, Lactate• Viral markers , Autoimmune markers• USG abdomen• Screen for wilson disease• In neonates and infants-

Monitoring

• Vitals • 12 hrly CNS exam and coma grading• 12hrly SE, ABG, RBS• Daily coagulation studies and CBC• Daily liverspan and weight • LFT, Urea, S.Cr, Ca and phos. twice weekly• Input and output chating• Blood and urine cultures• Daily prescription review

Immidiate management• Need for mech. Vent. if grade 3-4 enceph.• Avoid sedatives• Central venous line-• Volume resuscitation and vasoactive drugs• Once euloumic – gvie 3/4th IVF with GIR=6-

8mg/kg/min• Prophylactic use of PPI• Care of comatose

Specific treatmentHBV Lamivudine

HSV Acycloir

Acetaminophen NAC

Autoimmune hepatitis Methyl prednisolone 60mg/kg iv

Galactosemia Galcatose and lactose free diet

HFI Fructose free diet

Tyrosinemia Nitisone, Diet low in tyrosine and phenyalanine

Neonatal hemochromatosis Antioxidant cocktail

Treatment of complications

• Metabolic• Encephloathy• Cerebral edema• Coagulopathy• Renal failure• Infections• Dietary support

Metabolic Abnormality• Hyponatremia- dilutional• Hypokalemia- reduced intake and urine losses - add KCL to IVF• Hypophoshatemia- liver regeneration Early phosphorus administration is associated with better prognosis. • Hypoglycemia-frequent monitoring needed• Acid Base status- metabolic acidosis and

respiratory alkalosis

Encephalopathy• Close CNS monitoring frequently• Identify and correct precipitating factors• Restrict protein intake• Bowe wash with several enemas.• Lactulose every 2-4 hr orally or by NGT in

doses (10-50 mL) sufficient to cause diarrhea• Oral or rectal administration of rifaximin or

neomycin.(nonabsorbable A/B)

Cerebral edema

• 70-80% of stage 3-4 Encephalopathy pts.• Most common cause of deathMgmt-• Mechanical vent. with low PEEP• Monitor the ICP• Head end elevation • Can use mannitol or 3% NS

Coagulopathy• Due to decreased synthesis of clotting factors,

increase in peripheral consumption and at least some degree of DIC and TCP.

• prophylactic treatment with FFP in the absence of bleeding is unadvised.

• FFP infusion and platelet transfusion are advised before invasive procedures and also in presence of clinically significant bleeding.

• Plasmapheresis and Factor VIIa.

Renal Failure• Causes- Hypovoloumia, sepsis, HRS Hepatorenal Syndrome• Due to renal vasoconstriction• Two types based on rate of progression• Type 1- rapidly prog. with doubling of S.Cr in

less than 2 weeks • Type 2- gradually prog. type• TIPS procedure or vasoconstrictor drugs• Continuous hemodiaysis

Infections

• Monitor closely for infection- sepsis, pneumonia, peritonitis, and UTI.

• Mostly gram +ve but –ve and fungal also. • Serial blood cultures for bacteria and fungi. • Both antibacterial and antifungal is

recommended for patients with significant isolates on surveillance cultures, refractory hypotension, or clinical evidence of SIRS.

Dietary supportComponent Recommended intake

Energy 150% of recommended allowance

Carbohydrate 15-20g/kg/day

Fat 8g/kg/day and 50% as MCT

Protein in non encephalopathic state 2-3g/kg/d

Protein in encephalopathic state Grade 1-2=1-2g/kg/dGrade 3-4=0.5-1g/kg/day

Temporary Liver support• bridge for the patient with liver failure to liver

transplantation or regeneration.• Nonbiologic systems-albumin containing

dialysate (MARS, SPAD, Promethius)• Biologic liver support devices - liver cell lines

or porcine hepatocytes.• Infusions of hepatic stem cells

Liver TransplantationTYPES- • Orthotopic liver transplantation• Reduced-size allografts and living donor

transplantation- in infants

Indication- when hepatic decompensation is imminent or has occurred

New Therapies Undergoing Current Trial

• To date, the NAC trial is one of the very few controlled trials in ALF and its results remain controversial

• A blinded, controlled trial performed in India using L-ornithine L-acetate infusions in 203 patients with ALF- no benefit

• Ornithine phenyl acetate, is currently under consideration

Prognosis• Varies with the cause of liver failure and stage

of hepatic encephalopathy.• Brainstem herniation is the most common

cause of death• Various prognostication scores developed

Poor prognosis markers • Liver necrosis and multiorgan failure• Age <1 yr, stage 4, an INR >4, and the need for

dialysis before transplantation• Ammonia >200 μmol/L is associated with a 5-

fold increased risk of death• Sepsis, severe hemorrhage, renal failure,

apastic anemia

Take Home Message• ALF often is missed and the clinical scenario

resembles septic shock.• Drug intake should be considered when the

history is obscure or pt is in coma• Determining etiology of ALF is essential to

management and understanding prognosis• Do not replace clotting factors unless bleeding is

actually occurring—use INR as a prognostic tool.• Ammonia-lowering agents may prolong short-

term survival.• Listing for transplantation should be done timely

THANK YOU