FULMINANT HEPATITIS

Ulfa Kholili
Gastroentero Hepatology
Internal Medicine Department
Airlangga University dr Soetomo Hospital
Outline :
Definitions & Classifications of HF
Etiology
Pathogenesis
Clinical Manifestations
Diagnosis
Currrent principal management in ALF
Basic Aspect of Nutrition in ALF
Treatment and Management of Organ Complications
Prognosis
 FULMINANT HEPATITIS
Rare syndrome
massive necrosis of liver parenchyma deterioration in liver function
Decrease in liver size (acute yellow atrophy)
Usually occurs after infections with certain hepatitis viruses, exposure
to toxic agents, or drug-induced injury
High mortality rate
Complexity in managing the treatment

(Ichai & Samuel, 2008; Arroyo et al., 2012)

 Common Definitions of ALF

Loss of liver function in patients with no pre-existing chronic

liver diseas

Characterized by:
Coagulation disorders (INR 1.5 or prolonged prothrombin time
(>20 seconds)
Any degree of mental alteration caused by hepatic encephalopathy

< 26 weeks after onset of symptoms

(Koch & Trautwein, 2010, Morabito & Adebayo, 2014)

Classifications

(Morabito & Adebayo, 2014)

Times, Presentations & Prognosis

(Patton et al., 2012; EASL, 2017)

Fulminant Hepatitis

Acute Liver Failure

 Etiology
Causa

Viral Hepatitis A, B, C, D, E,
HSV, CMV, EBV

Toxic dependent Acetaminophen (Paracetamol), Isoniazid,

Tetracyclin, Metotrexat, Carbon tertrachoride,
Amphetamine, Amanita phalloides - Toxin

Metabolic Wilson Disesae, A-1 AT Defficiency, Galactosemia,

Tyrosinemia, Reye Syndrome

Vascular Budd Chiari syndrome, Veno occlussive disease,

Shock, Heart Failure

Miscellenous Autoimmune Hepatitis

Associated Pregnancy HELLP Syndrome

(OGrady et al., 2016)
https://doi.org/10.5124/jkma.2013.56.12.1
067
 (Yoon et al,&2016)
(Bunchorntavakul Reddy, 2013)
 Pathogenesis

Extra Hepatic
Liver Injury
Injury
Dysfunctions
Direct injury Innate immune
Cardiovasc

PAMPs DAMPs Pulmonary

Viral hepatitis Toxic mediated Brain

Renal Direct
Hepatocytes
Immune cell Paracetamol
Necrosis toxicity
Cytokines released SIRS

(Morabito & Adebayo, 2014; Privitera et al., 2014)

 Depends on the etiology

Clinical Non-specific manifestations

Anorexia
Manifestation

Fatigue
Abdominal pain
Fever
Diarrhea (caused by Amanita
phalloides)

Specific manifestations
Jaundice
Altered mental status (hepatic
encephalopathy)
Bleeding (uncommon)
Hypertension (with ICH)
Hypovolemia

(Koch & Trautwein, 2010; Paneckel et al., 2015; EASL, 2017)

Differential Diagnosis of ALF Based on
Clinical Feature

(EASL, 2017)
 Diagnosis
TRIAD signs & symptoms Anamnesis
Jaundice
Altered mental status
Physical
Coagulopathy
Examination
Find the etiology
IMPORTANT for determining Laboratorium
early/specific
management and Other
prognosis diagnostic
(Koch & Trautein, 2010; Patton et al., 2012; EASL, 2017)
The severity of liver injury and direct management,
Assessment of prognosis
Liver biopsy is not helpful and limited indication
 To date, no single therapy has been
shown to improve outcome in all ALF
Principles patients
of Management Need for multi specialities (the care
team)
Acute loss of
The main aim of management:
hepatocellular
functions Supportive

Complications management that present

Systemic
ALF inflammatory The most frequent causes of death:
response
Multiple Organ Failure
Multi-organ Infection (severe sepsis)
system failure

(Morabito & Adebayo, 2014; EASL, 2017)

 Current Management

: PPI (stop when enteral nutritions have been started

(maximum 5 days)

(HE grade 2 or more ICU)

(EASL, 2017)
Etiology-Specific Therapy

(Patton et al., 2012)


Basic Aspect of
Nutrition in ALF
NOTE:
Oral intake should be
avoided if HE progresses
(patients may require
urgent intubation)
Main goal :
Minimize catabolism
Support liver regeneration & glucose
homeostasis
In the catabolic stage an energy input of 30 kcal/
kgbw (maintained blood glucose 140 mg/dl)
Protein and amino acids is 11.2 g/kgbw
(calculated independent of ammonia levels)
Lipids administration during longterm (>3 days)
parenteral nutrition
Vitamins and micronutrients
(Koch & Trautwein, 2010; Patton et al., 2012; EASL, 2017
Suggested Criteria for Referral a Cases of
ALF to Specialist Units

(EASL, 2017)
 Treatment and Management of Organ
Complications
FFP and coagulation factors Asses HE at 2-hourly intervals HE grade 2 or
administration: more ICU
Maintain
- Limited to invasive procedur (insertion of CPP >55 mmHg & ICP <25 mmHg
ICP monitors) or active bleeding treat if ICP >25 mmHg with
- Prophylactic is not advised Mannitol (150 ml, 20%), hypertonic saline (200 ml,
Hb target is 7 g/dl 2.7%; 20 ml, 30%)
Correct electrolyte abnormalities
If resistant: short period of hyperventilation ( arterial
Aggressive investigation for infection
PaO2 if: 25-30 mmHg) Avoid hypoglycemia (monitor hourly)
- Abnormalities of blood/urine lab Avoidance of fever IV glucose infusion (target 140 mg/dL)
- Unexplaine fever or pyrexia unresponsive
Avoidance of hypo/hyperglycemia Consider the possibility of functional
to antibiotics Steroid are not recommended adrenal insufficiency (IV hydrocortison
- Leucocytosis Maintain serum osmolarity <320 mOsmol200-300 mg/day)
- Deterioration in hepatic coma
Assess volume status Mechanically ventilate (when Institute early CRRT, indicated to
- Established renal failure
Avoid fluid overload grade 3 HE develops) correct:
Start empiric antibiotic therapy (broad
Maintain SBP >90mmHg, MAP >65, Use standard sedation and lung Acidosis
spectrum) if infection is suspected
CPP 50-80 mmHg protective ventilator technique Metabolic disturbance (
Fluid replacement (crystalloid over Avoid of excessive hyper or ammonia &/or progressive HE)
colloid) hypocarbia
Vasopressors (NE at a starting
dose of 0.05 g/kg/min) (Patton et al., 2012; Yarema et al., 2012; EASL, 2017)
 Liver Support System

Artificial (noncell-based systems)

The molecular absorbent and recirculating system (MARS) Both using
The Prometheus-system albumin

Bioartificial (cell-based systems)

Human
Extracorporeal liver assist device (ELAD)
hepatocytes
Bioartificial extracorporeal liver support system (BELS) Porcine
HepatAssist liver support system hepatocytes

(Yerema et al., 2012; EASL, 2017)

 Criteria for Emergency Liver Transplantation

Liver
Transplantation
(> 3.4 mg/dL) or anuria
or prothrombin time >100 sec

prothrombin time >100 sec

Two criteria most
widely used :
(>17.5 mg/dL)
The Kings College or prothrombin time >50 sec

The Clichy

(Koch & Trautwein, 2010; EASL, 2017)

 Prognosis
Varies greatly with the underlying aetiology, the grade of HE, the
patients age, and the progression in clinical course
Spontaneous recovery of liver function depends on the grade of HE
(HE grade I-II 65-70%; HE grade III 40-50%; HE grade IV <20%)
PT or INR is the best indicator of survival
Survival
Less than 15% (prior to transplantation)
65% (including those undergoing transplantation)

(Koch & Trautwein, 2010; EASL, 2017)

Take care of your liver
You only have ONE!

Thank You