Indian J Pediatr (2010) 77:1288–1295
DOI 10.1007/s12098-010-0167-1
SYMPOSIUM ON PICU PROTOCOLS OF AIIMS
Intensive Care Management of Children with Acute
Liver Failure
Vidyut Bhatia & Rakesh Lodha
Received: 15 July 2010 / Accepted: 30 July 2010 / Published online: 27 August 2010
# Dr. K C Chaudhuri Foundation 2010
Abstract Acute liver failure is an uncommon condition
associated with multi organ involvement, high morbidity and
mortality. Etiology of acute liver failure varies with age and
geographical location. Most cases of acute liver failure in India
are due to infectious causes predominantly viral hepatitis. A
significant group with indeterminate causation remains, despite
careful investigation. The etiology of acute liver failure in
infants is largely metabolic. The mainstay of management is
supportive care in an intensive care unit. Monitoring of clinical
and biochemical parameters is done frequently until the patient
becomes stable. Mortality is predominantly due to raised
intracranial pressure, infections and multi-organ failure. Liver
transplant is an important life saving procedure for children
with acute liver failure.
Keywords Acute liver failure . Viral hepatitis . Intensive
care management
Introduction
Acute liver failure is a rare but devastating illness with a very
high mortality. Bucuvalas has defined liver failure as “....results
when loss of liver function, caused by rapid death or injury to
a large proportion of hepatocytes, leaves insufficient paren-
chymal mass to sustain life.”[1]. Liver failure can develop in
absence of pre-existing liver disease when it is known simply
as acute liver failure (ALF) or as acute decompensation of a
diseased liver secondary to a identified or unidentified liver
disorder known as acute on chronic liver failure (ACLF) [2].
V. Bhatia : R. Lodha (*)
Department of Pediatrics, All India Institute of Medical Sciences,
New Delhi 110029, India
e-mail: rakesh_lodha@hotmail.com
The definition in adults of ALF as “evidence of coagulation
abnormality, usually an INR ≥1.5, and any degree of mental
alteration (encephalopathy) in a patient without pre-existing
cirrhosis and with an illness of ≤26 weeks duration” [3] does
not satisfactorily encompass the complexity of the condition
in the pediatric population. In the largest study of ALF in
children, the following definition of ALF was taken [4]:
(1) Children with no known evidence of chronic liver
disease,
(2) Biochemical evidence of acute liver injury, and
(3) hepatic-based coagulopathy defined as a prothrombin
time (PT) ≥15 s or INR ≥1.5 not corrected by vitamin
K in the presence of clinical hepatic encephalopathy
(HE) or a PT ≥20 s or INR ≥2.0 regardless of the
presence or absence of clinical HE.
Initial Assessment
The history should include details about the onset of jaundice,
mental status changes, evidences of coagulation disturbances,
vomiting, fever, contact with an infectious agent, blood
transfusions and any relation to drug intake (acetaminophen,
antituberculous treatment). Consanguinity in the family or
history suggestive of Wilson’s disease, early infantile death,
viral hepatitis, autoimmune conditions should prompt a search
for the above conditions. The history should also be focused on
ruling out any underlying chronic liver condition. Develop-
mental delay or seizures suggest a metabolic condition.
Physical examination should include the assessment of
growth, development and nutrition of the child. Signs of
chronic liver disease like clubbing, telangiectasia, xanthomas,
palmar erythema, and prominent abdominal veins should be
looked for. Fetor hepaticus, testicular atrophy and gynecomas-
Indian J Pediatr (2010) 77:1288–1295
tia are rarely seen in children. The physical examination should
also include the liver span and its extent below the costal
margin, splenic enlargement, ascites and a complete neurolog-
ical examination for staging of the encephalopathy.
After initial assessment of the child, the management
progresses in multiple parallel paths (Fig. 1). The first path
consists of the immediate management of the patient. The
second concurrent path follows the etiological work-up of the
patient. The third path moves towards the management of
complications.
Management
ALF is a multisystem disease with a dynamic and often
unpredictable course. Mortality in ALF is predominantly due to
raised intracranial pressure, infections and multi-organ failure;
therefore, efforts are directed toward management of these
conditions while awaiting recovery of liver function or liver
transplantation. Formulation of set protocols is restricted in
view of scarcity of controlled clinical trials in pediatric
populations. Most recommendations have been based on
observations from single-centre, uncontrolled trials or from
case series or extrapolated from adult studies.
Immediate Measures
The child should be nursed in a quiet environment
preferably in an intensive care setting. A central venous
line should be placed in order to measure central venous
pressure, administer fluids, medications, and blood prod-
ucts, and collect blood samples. Volume resuscitation
should be carried out aggressively if required. Intravenous
fluids should be started at 3/4th maintenance requirement.
The fluids should be glucose based with a glucose infusion
rate of at least 6–8 mg/kg/min. The composition of
maintenance fluids can be tailored to the electrolyte, sugar
and renal status of the patient. Vasoactive drugs like
dopamine, dobutamine, etc. should be used if clinically
indicated. Strict intake and output charting should be done.
Nasogastric tube should be inserted for feeding/ drainage
and a urinary catheter for output measurement. Care of
bowel, back, bladder, skin, eyes should be done.
Monitoring of clinical and biochemical parameters
should be done frequently until the patient becomes stable.
The following parameters should be monitored.
1. Continuous oxygen saturation monitoring
2. 4 hourly vital signs (including blood pressure); more
frequently in an unstable child
3. 12 hourly neurological observations/coma grading
4. 12 hourly electrolyte, sugar and arterial blood gases
1289
5. Daily coagulation studies and full blood counts
6. Daily measurements of liver span and weight
7. Daily prescription review
8. LFT, Urea, creatinine, calcium and phosphate twice-
weekly
9. Surveillance blood and urine cultures
Consider mechanical ventilation of patients in grade-3 or
4 encephalopathy or with hypoxia [5]. If required, sedate
the child with midazolam. For painful or invasive proce-
dures, a short-acting sedative (like midazolam) along with
morphine/ fentanyl may be given. Otherwise, medications
that affect level of consciousness should be avoided in
order not to complicate assessment of or worsen the
encephalopathy (Table 1).
Etiology
The etiology of acute liver failure varies with the age and
the geographical location. Studies from India show that
infectious hepatitis is the most important cause of ALF in
majority of the cases [6–11]. In the largest study on acute
liver failure in children, which included patients from
United States, England or Canada, the etiology in the 348
children included acute acetaminophen toxicity (14%),
metabolic disease (10%), autoimmune liver disease (6%),
non-acetaminophen drug-related hepatotoxicity (5%), infec-
tions (6%), and other diagnosed conditions (10%); 49%
were indeterminate[4]. In infants, the main causes of ALF
are inherited metabolic disorders and infections [12]
(Table 2).
The initial investigations are directed towards establishing
the etiology and performing a baseline evaluation of the
patient’s clinical status.
Management of Complications
Metabolic, Electrolyte and Acid Base Disturbances
(Table 3)
Metabolic, electrolyte and acid-base disturbances frequently
occur in acute liver failure. Most commonly seen are
hyponatremia, hypokalemia, hypocalcemia, hypophosphate-
mia and hypomagnesemia.
Hyponatremia occurs commonly and is usually secondary
to decreased water excretion by the kidney, excess
antidiuretic hormone or excess administration of hypotonic
saline [13].
Hypernatremia can also occur secondary to vigorous use
of lactulose [14].
1290 Indian J Pediatr (2010) 77:1288–1295

Fig. 1 Initial assessment and management of patients with deranged liver functions and mental status changes
Indian J Pediatr (2010) 77:1288–1295 1291

Table 1 Indian studies on children with acute liver failure following initial presentation [4]. Close monitoring in an
Year of Study Location n Contribution by Reference intensive care setting is recommended because the grade of
Infectious encephalopathy may change rapidly. With any sudden change
hepatitis
in mental status, the patient should be evaluated for
1996 AIIMS, New Delhi n=40 75% [6] hypoglycemia, infection, and intracranial hemorrhage. In
1999 Pune n=36 61.1% [7] patients who have grade 1–2 encephalopathy, sedatives should
2002 Chandigarh n=67 94% [8]
be avoided, and the patient should be observed closely in a
2004 SGRH, New Delhi n=32 62.5% [9]
2005 CMC, Vellore n=22 not clear [10]
quiet intensive care setting.
2007 Kolkata n=45 66.6% [11]

Management of Intracranial Hypertension (ICH)

Hypokalemia Children with ALF usually have hypokalemia
but can present with hyperkalemia or normokalemia as well
[15]. Serum levels of potassium can be normal even though
total body potassium stores are reduced [16, 17]. The severity
of potassium depletion is related to the severity of liver
dysfunction. The postulated mechanisms are decreased dietary
intake, effects of chronic illness, increased losses in the urine
due to diuretic therapy or secondary hyperaldosteronism and
frequent gastrointestinal losses [15].
Hypophosphatemia Severe hypophosphatemia is a common
occurrence in ALF patients. The severity of hypophosphatemia
is postulated to be due to amount of regenerative liver mass.
Phosphate levels return to normal as liver synthetic function
improves [18–20]. This is presumably because phosphate may
be a substrate for various kinase enzymes that phosphorylate
proteins that play critical role during rapid liver regeneration.
Acid base disturbances The origin of acid-base disorders in
patients with liver disease is complex [15]. As the liver’s
metabolic function worsens, particularly in the setting of renal
dysfunction, hemodynamic compromise, and hepatic enceph-
alopathy, acid-base disorders ensue. The most common acid-
base disorder is respiratory alkalosis. Metabolic acidosis alone
or in combination with respiratory alkalosis also is common.
All ALF patients should be started on maintenance I.V. fluids
at admission with 3 mEq K+ (as 15% KCl) in every 100 ml of
fluid administered. After the serum K+ reports are available,
they should be given potassium supplements as per the
guidelines given in Table 3.
Hypoglycemia Patients with acute liver failure are at increased
risk for hypoglycemia as a result of failure of hepatic
gluconeogenesis, hypoinsulinemia and secondary bacterial
infections. Frequent monitoring of blood sugar, initially every
1 to 2 h is recommended.
Management of Hepatic Encephalopathy (Table 4)
Two thirds of infants and children presenting with acute liver
failure develop hepatic encephalopathy during their first week
(Table 5)
In patients who have grade 3–4 encephalopathy, 70–80%
patients develop intracranial hypertension. It is also the most
common cause of death in them. The head should be elevated
to 30° and endotracheal intubation should be performed (ensure
adequate sedation during the procedure). During the elevation
of the head of the bed, mean arterial pressure should be
maintained to avoid decreasing the cerebral perfusion pressure.
High levels of positive end-expiratory pressure (PEEP) should
be avoided because they may increase hepatic venous pressure
and intracranial pressure (ICP). Mannitol bolus of 0.5 g/kg as a
20% solution over 15 min may be given in the event of acute
rise of ICP. The boluses may be repeated provided that the
serum osmolality is less than 320 mOsm/L. Other methods that
are used include infusion of 3% hypertonic saline to keep serum
sodium between 145–155 mEq/L [22]. Steroids are not
indicated for treatment of intracranial hypertension in ALF.
Management of Coagulopathy and Hemorrhage
Intravenous vitamin K is given to correct any reversible
coagulopathy (2–10 mg). Correction of coagulopathy with
Table 2 Investigations in infants and children with acute liver failure
First Line investigations
Complete hemogram; Serum electrolytes; Blood Sugar; arterial blood gas
Liver function tests; Kidney function tests; Cholesterol; Prothrombin time
Blood ammonia, lactate
Viral Markers: HBsAg; Anti HCV; HAV IgM; HEV IgM; HBc IgM
Autoimmune markers: ANA/SMA/LKM
Ultrasound Abdomen
Serum Ceruloplasmin; Eye examination (KF ring); 24 hrs urinary copper
excretion
Special investigations for neonates and infants
Urinary succinylacetone
GALT assay
Alfa-fetoprotein
Serum ferritin
Fructose challenge
1292 Indian J Pediatr (2010) 77:1288–1295

Table 3 Fluid and metabolic complications and their management [21] Table 5 Management of intracranial hypertension

Abnormality Management Position Head end elevated and head in neutral position
Ventilation Elective; maintain pCO2 Between 25 to 28 mm Hg;
Hypotension • Resuscitate with normal saline, Ringer’s lactate, plasma this however, should be used only as a short term
or blood measure in view of the potential deleterious effect of
• Avoid fluid overload vasoconstriction on cerebral oxygen utilization.
• If shock does not improve with fluid administration, start Mannitol 0.5 g/kg as a 20% solution over 15 min. Monitor with
vasopressors; dopamine is the preferred initial drug serum osmolality
Metabolic • Suspect fluid deficit and correct Hypertonic 3% solution infusion (to maintain serum sodium between
acidosis • Look for sepsis saline 145–155 mEq/L)

Hypokalemia Give potassium chloride infusion (per 100 mL IV fluids) Corticosteroids Not indicated

• 3 mEq (1.5 mL KCl) if K+ >3 mEq/L

• 4 mEq (2 mL KCl) if K+ between 2.5 and 3 mEq/L and vasoconstrictors. The trigger for systemic vasoconstriction
• 5 mEq (2.5 mL KCl) if K between two and 2.5 mEq/L
+ is probably splanchnic vasodilatation that occurs following
• 6 mEq (3 mL KCl) if K+ below 2 mEq/L portal hypertension [24]. The International Ascites Club has
Metabolic • Increase potassium chloride to the next step classified HRS into two clinical types according to the rate of
Alkalosis progression of renal failure [25]. Type I HRS is characterized
Hyponatremia • Restrict fluids to 2/3 to 3/4 maintenance by rapidly progressive reduction of renal function as defined
• Restrict sodium infusion to less than 2 mEq/kg/day by a doubling of the initial serum creatinine to a level greater
Hypoglycemia • Increase the glucose infusion rate than 2.5 mg/dL or a 50% reduction of the initial 24-hour
• Maintain blood sugar between 100 to 200 mg/dL creatinine clearance to a level lower than 20 mL/min in less
than 2 weeks. The remaining types in which the renal failure
fresh frozen plasma is done only with hemorrhage or in does not have a rapidly progressive course are classified as
preparation for invasive procedures or if coagulopathy is type II HRS. This classification essentially meant for adults is
severe (PT >60 s). Usually 10 to 15 mL/kg of fresh frozen also being used in children as a separate classification system
plasma every six hours or an infusion of 3 to 5 mL/kg/hr is for children does not exist.
required. Platelet count and function are depressed in liver Therapy for HRS is primarily focussed on decreasing
failure and contribute to increased bleeding time. Throm- splanchnic circulation either with drugs (vasoconstrictors) or
bocytopenia should be corrected if the platelet count falls through TIPS procedure and maintaining circulating volume
below 50×109/L. with colloid or fresh frozen plasma. Studies in the adults have
used vasoconstrictor agents like vasopressin analogues (terli-
Prophylaxis for GI bleed The most common site of pressin) [26] and alpha agonists (norepinephrine and medo-
bleeding is the GI tract, hence prophylactic administration drine) and have shown them to be very effective in reversal of
of proton pump inhibitors (Pantoprazole- 20–40 mg/day in
children older than 5 years; Omeprazole 1 mg/kg/day) or Table 6 Recommended dietary intakes for children with acute and
acute on chronic liver failure
Ranitidine (3–5 mg/kg/day) is routinely done [23].
Component Recommended intake Comments Reference
Renal failure Functional renal failure or hepatorenal syndrome
Energy 150% of Children with long [30]
(HRS) is the most common cause of renal insufficiency in ALF. recommended standing liver disease
HRS is secondary to intense renal vasoconstriction which is in allowance already suffer from
turn due to activation of a number of systemic vasoconstrictor varying degrees of
malnutrition therefore
mechanisms and an imbalance between intra-renal vasodilators need extra calories
Carbohydrates 15–20 g/kg/day [31]
Table 4 Mangement of hepatic encephalopathy Fat 8 g/kg/day with 50% [31]
as medium chain
Bowel washes With acidic fluid (1 teaspoon vinegar in half liter triglycerides
of clean water), 6 to 8 hourly Protein (Non- 2–3 g/kg/day For promoting growth and [30]
Lactulose By oral or nasogastric route. 0.5 mL/kg/dose. Up encephalo- to maintain positive
to 4 times a day maximum 30 mL/dose. It pathic state) nitrogen balance.
should produce 2 to 4 loose acid stools per day Vegetable and dairy
product based.
Enteral feeding No restrictions in grade 1–2 encephalopathy; Protein Low grade (I-II) 1-2 Further protein restriction [30, 32]
vegetable proteins preferred (encepha- g/kg/day High grade can exacerbate HE by
Anticonvulsants (if Phenytoin or phenobarbitone lopathic (III-IV) 0.5–1 g/kg/ causing breakdown of
seizures present) state) day endogenous protein
Indian J Pediatr (2010) 77:1288–1295 1293

Table 7 Etiology specific management of underlying ALF Specific Management

Etiology Management Ref
Specific therapy should be administered if the underlying cause
Infections of ALF has been determined (Table 7).
Hepatitis B Lamivudine 4 mg/kg/day once daily orally [33]
HSV Acyclovir 10 mg/kg 8 hourly [34]
Drugs and Toxins
Liver Transplant
Acetaminophen NAC oral: 140 mg/kg loading dose followed by 17 [35]
Poisoning doses of 70 mg/kg every 4 hrs for a total of
1330 mg/kg over 72 hrs Liver transplant is an important life saving procedure for
NAC IV intermittent: 140 mg/kg loading dose followed
by 12 maintenance doses of 70 mg/kg every 4 hrs ALF in children [5]. It should be offered to those patients
NAC IV infusion: loading dose 150 mg/kg infused over whose condition is likely to be benefitted with transplan-
15 minutes, followed by 50 mg/kg infused over 4 hrs tation. Children should be listed for liver transplantation
and then 100 mg/kg infused over 16 hrs
Amanita Penicillin G 1 g/kg iv, silibinin 15–30 mg/kg/day and [36]
Table 8 Indications for liver transplant in children
Poisoning NAC as for acetaminophen poisoning
Immune Dysregulation
Chronic cholestatic liver disease
Autoimmune Methyl prednisolone 60 mg/kg IV [28,
hepatitis 37] Extrahepatic biliary atresia (most common indication)
Metabolic disorders Arteriohepatic dysplasia (Alagille syndrome)
Galactosemia Galactose and lactose free diets e.g. Nusobee, [38] Neonatal hepatitis
ProSoyal
Primary sclerosing cholangitis
HFI Fructose free diets, avoiding fructose and sorbitol [38]
infusions Caroli’s disease
Tyrosinemia Nitisinone, a diet low in phenylalanine and tyrosine [38– Langerhan’s cell histiocytosis (histiocytosis X)
41]
Inborn errors of metabolism
Bile acid synthesis Primary bile acid therapy [38]
defects Alpha-1-antitrypsin deficiency
Neonatal Anti-oxidant cocktail [42] Tyrosinemia
hemochro-
matosis Wilson’s disease
Miscellaneous metabolic or genetic liver disease
NAC N-acetyl cysteine Glycogen storage disease, type 1
Glycogen storage disease, type 4
Type 1 hyperoxaluria
functional renal insufficiency [24]. A suggested dosage Crigler-Najjar syndrome
regimen for drugs to be used in children with type 1 HRS is Ornithine transcarbamylase deficiency
as follows: Terlipressin: 5–20 μg/kg/dose every 4 h as IV Familial hypercholesterolemia
bolus and norepinephrine starting at 0.2 μg/kg/min, then Protein C deficiency

increased progressively so that blood pressure is maintained Niemann-Pick and other lipidosis
Gaucher’s disease
within normal for age [27].
Erythropoietic protoporphyria
Hemophilia A
Hemophilia B
Urea cycle enzyme deficiency
Feeding
Hepatocellular injury
Viral hepatitis
ALF is a catabolic state characterized by a negative nitrogen
Autoimmune hepatitis
balance and thus, with immunodeficiency [28]. Oral or
Drug-induced liver failure
nasogastric feeding is usually well tolerated and should be
Amanita mushroom poisoning
started as early as possible [29]. Enteral route of feeding is
Hepatic venous outflow tract obstruction
preferred because it is more physiologic and associated with
Mass occupying lesions
less risk of severe systemic infections. Initial scepticism
Hepatoblastoma
regarding increased risk of the variceal bleeding due to tube
Hepatocellular carcinoma
feeding has not been found to be supported by appropriate
Hemangioendothelioma
clinical trials. On the contrary, tube feeding yields superior
Miscellaneous
results over ad lib oral feeding. There is no role for dietary Cystic fibrosis
restrictions. Vegetable source of protein is preferred. The Congenital hepatic fibrosis
recommended nutritional intake in children with liver failure is TPN induced cirrhosis
given in Table 6.
1294
when there is evidence that hepatic decompensation is (i)
unavoidable (based on knowledge of the history of the disease
itself), (ii) imminent, or (iii) has already occurred. The diseases
for which liver transplant is indicated are given in Table 8.
Recent Advances
In acute liver failure, since most of the toxins are albumin
bound and are not filterable using the conventional dialysis,
three different albumin dialysis systems have been devel-
oped using albumin as the scavenging molecule [43].These
are the MARS (Molecular adsorbent recirculation system),
SPAD (Single pass albumin dialysis) and the Prometheus
systems. These were mainly research tools that are now
beginning to be used in the clinical management of
pediatric ALF patients [44].
Role of N-acetylcysteine (NAC) and L-ornithine
L-aspartate (LOLA)
The evidence for use of NAC in causes other than
acetaminophen poisoning is limited but a recent study has
demonstrated its benefits in adults with early stage of
encephalopathy [45]. On the other hand, a randomised
controlled trial on the benefits of LOLA failed to
demonstrate any benefit in terms of mortality or lowering
of ammonia in patients with acute liver failure [46].
Prognosis
A multivariate analysis in 97 children identified time to
onset of hepatic encephalopathy >7 days, PT >55 sec, and
ALT ≤2384 IU/L at admission as significant independent
predictors for death or liver transplant [47]. A recent study
evaluating a pediatric Liver Injury Unit score based upon
total bilirubin, INR, and ammonia at presentation and with
“peak” values, appears to effectively predict survival
without liver transplant; further prospective analyses will
be necessary to confirm these findings [48].
References
1. Bucuvalas J, Yazigi N, Squires Jr RH. Acute liver failure in
children. Clin Liver Dis. 2006;10:149–68.
2. Sarin SK, Kumar A, Almeida JA, et al. Acute-on-chronic liver
failure: consensus recommendations of the Asian Pacific
Association for the study of the liver (APASL). Hepatol Int.
2009;3:269–82.
3. Polson J, Lee WM. AASLD position paper: the management of
acute liver failure. Hepatology. 2005;41:1179–97.
Indian J Pediatr (2010) 77:1288–1295
4. Squires Jr RH, Shneider BL, Bucuvalas J, et al. Acute liver failure
in children: the first 348 patients in the pediatric acute liver failure
study group. J Pediatr. 2006;148:652–8.
5. Dhawan A, Cheeseman P, Mieli-Vergani G. Approaches to acute
liver failure in children. Pediatr Transplant. 2004;8:584–8.
6. Arora NK, Nanda SK, Gulati S, et al. Acute viral hepatitis types
E, A, and B singly and in combination in acute liver failure in
children in north India. J Med Virol. 1996;48:215–21.
7. Bendre SV, Bavdekar AR, Bhave SA, Pandit AN, Chitambar SD,
Arankalle VA. Fulminant hepatic failure: etiology, viral markers
and outcome. Indian Pediatr. 1999;36:1107–12.
8. Poddar U, Thapa BR, Prasad A, Sharma AK, Singh K. Natural
history and risk factors in fulminant hepatic failure. Arch Dis
Child. 2002;87:54–6.
9. Mohan N. Hepatic failure and encephalopathy. In: Sachdev HPS,
Choudhury P, Bagga A, Chugh K, Ramji S, Puri RK, editors.
Principles of pediatric & neonatal emergencies. 2nd ed. New
Delhi: Jaypee Brothers Medical Publishers Ltd; 2004. p. 236–44.
10. Bhowmick K, Mammen A, Moses PD, Agarwal I, Mathew L,
Kang G. Hepatitis A in pediatric acute liver failure in southern
India. Indian J Gastroenterol. 2005;24:34.
11. Samanta T, Ganguly S. Aetiology, clinical profile and prognostic
indicators for children with acute liver failure admitted in a
teaching hospital in Kolkata. Trop Gastroenterol. 2007;28:135–9.
12. Durand P, Debray D, Mandel R, et al. Acute liver failure in
infancy: a 14-year experience of a pediatric liver transplantation
center. J Pediatr. 2001;139:871–6.
13. Record CO, Iles RA, Cohen RD, Williams R. Acid-base and
metabolic disturbances in fulminant hepatic failure. Gut.
1975;16:144–9.
14. Nelson DC, McGrew Jr WR, Hoyumpa Jr AM. Hypernatremia
and lactulose therapy. JAMA. 1983;249:1295–8.
15. Ahya SN, Jose Soler M, Levitsky J, Batlle D. Acid-base and
potassium disorders in liver disease. Semin Nephrol. 2006;26:466–
70.
16. Heinemann HO, Emirgil C. Hypokalemia in liver disease.
Metabolism. 1960;9:869–79.
17. Trocki O, Wotton MJ, Cleghorn GJ, Shepherd RW. Value of total
body potassium in assessing the nutritional status of children with
end-stage liver disease. Ann NY Acad Sci. 2000;904:400–5.
18. Quiros-Tejeira RE, Molina RA, et al. Resolution of hypophosphatemia
is associated with recovery of hepatic function in children with
fulminant hepatic failure. Transpl Int. 2005;18:1061–6.
19. Baquerizo A, Anselmo D, Shackleton C, et al. Phosphorus as an
early predictive factor in patients with acute liver failure.
Transplantation. 2003;75:2007–14.
20. Chung PY, Sitrin MD, Te HS. Serum phosphorus levels predict clinical
outcome in fulminant hepatic failure. Liver Transpl. 2003;9:248–53.
21. Arora NK, Mathur P, Ahuja A, Oberoi A. Acute liver failure.
Indian J Pediatr. 2003;70:73–9.
22. Murphy N, Auzinger G, Bernel W, Wendon J. The effect of
hypertonic sodium chloride on intracranial pressure in patients
with acute liver failure. Hepatology. 2004;39:464–70.
23. Macdougall BR, Bailey RJ, Williams R. H2-receptor antagonists and
antacids in the prevention of acute gastrointestinal haemorrhage in
fulminant hepatic failure. Two controlled trials. Lancet. 1977;1:617–9.
24. O’Beirne JP, Heneghan MA. Current management of the
hepatorenal syndrome. Hepatol Res. 2005;32:243–9.
25. Arroyo V, Gines P, Gerbes AL, et al. Definition and diagnostic criteria
of refractory ascites and hepatorenal syndrome in cirrhosis. Interna-
tional Ascites Club. Hepatology. 1996;23:164–76.
26. Gerbes AL, Gulberg V. Progress in treatment of massive ascites and
hepatorenal syndrome. World J Gastroenterol. 2006;12:516–9.
27. Debray D, Yousef N, Durand P. New management options for
end-stage chronic liver disease and acute liver failure: potential for
pediatric patients. Paediatr Drugs. 2006;8:1–13.
Indian J Pediatr (2010) 77:1288–1295
28. Stravitz RT, Kramer AH, Davern T, et al. Intensive care of patients
with acute liver failure: recommendations of the U.S. Acute Liver
Failure Study Group. Crit Care Med. 2007;35:2498–508.
29. Sekido H, Matsuo K, Takeda K, et al. Impact of early enteral
nutrition after liver transplantation for acute hepatic failure: report
of four cases. Transplant Proc. 2003;35:369–71.
30. Shetty AK, Schmidt-Sommerfeld E, Udall Jr JN. Nutritional
aspects of liver disease in children. Nutrition. 1999;15:727–9.
31. Hartley JL, Kelly DA. End stage liver failure. Paediatr Child Health.
2010;20:30–5.
32. Cordoba J, Lopez-Hellin J, Planas M, et al. Normal protein diet
for episodic hepatic encephalopathy: results of a randomized
study. J Hepatol. 2004;41:38–43.
33. Tillmann HL, Hadem J, Leifeld L, et al. Safety and efficacy of
lamivudine in patients with severe acute or fulminant hepatitis B,
a multicenter experience. J Viral Hepat. 2006;13:256–63.
34. Riediger C, Sauer P, Matevossian E, Muller MW, Buchler P,
Friess H. Herpes simplex virus sepsis and acute liver failure. Clin
Transplant. 2009;23 Suppl 21:37–41.
35. Marzullo L. An update of N-acetylcysteine treatment for acute
acetaminophen toxicity in children. Curr Opin Pediatr. 2005;17:239–
45.
36. Broussard CN, Aggarwal A, Lacey SR, et al. Mushroom
poisoning–from diarrhea to liver transplantation. Am J Gastro-
enterol. 2001;96:3195–8.
37. Sogo T, Fujisawa T, Inui A, et al. Intravenous methylprednisolone
pulse therapy for children with autoimmune hepatitis. Hepatol Res.
2006;34:187–92.
38. Clayton PT. Inborn errors presenting with liver dysfunction.
Semin Neonatol. 2002;7:49–63.
1295
39. Masurel-Paulet A, Poggi-Bach J, Rolland MO, Bernard O, Guffon N,
Dobbelaere D, et al. NTBC treatment in tyrosinaemia type I: long-term
outcome in French patients. J Inherit Metab Dis. 2008;31:81–7.
40. Joshi SN, Venugopalan P. Experience with NTBC therapy in
hereditary tyrosinaemia type I: an alternative to liver transplanta-
tion. Ann Trop Paediatr. 2004;24:259–65.
41. Crone J, Moslinger D, Bodamer OA, et al. Reversibility of
cirrhotic regenerative liver nodules upon NTBC treatment in a
child with tyrosinaemia type I. Acta Paediatr. 2003;92:625–8.
42. Knisely AS, Mieli-Vergani G, Whitington PF. Neonatal hemo-
chromatosis. Gastroenterol Clin North Am. 2003;32:877–89.
43. Karvellas CJ, Gibney N, Kutsogiannis D, Wendon J, Bain VG.
Bench-to-bedside review: current evidence for extracorporeal
albumin dialysis systems in liver failure. Crit Care. 2007;11:215.
44. Novelli G, Rossi M, Morabito V, et al. Pediatric acute liver failure
with molecular adsorbent recirculating system treatment. Trans-
plant Proc. 2008;40:1921–4.
45. Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine
improves transplant-free survival in early stage non-acetaminophen
acute liver failure. Gastroenterology. 2009;137:856–64. 64 e1.
46. Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK. Efficacy
of L-ornithine L-aspartate in acute liver failure: a double-blind,
randomized, placebo-controlled study. Gastroenterology.
2009;136:2159–68.
47. Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic
indicators of childhood fulminant hepatic failure in the United
kingdom. J Pediatr Gastroenterol Nutr. 2005;40:575–81.
48. Lu BR, Gralla J, Liu E, Dobyns EL, Narkewicz MR, Sokol RJ.
Evaluation of a scoring system for assessing prognosis in pediatric
acute liver failure. Clin Gastroenterol Hepatol. 2008;6:1140–5.