Acute liver failure

acute liver failure by Dr Saqib Pervez

1. ACUTE LIVER FAILURE
PRESENTATION
BY
DR SAQIB PERVEZ
MEDICAL `C`
LRH PESHAWAR
ACUTE LIVER FAILURE (AASLD 2011)

2. INTRODUCTION
ALF is a rare condition in which rapid
deterioration of liver function results in altered
mentation and coagulopathy in individuals
without known pre-existing liver disease.
ALF often affects young persons & carries a
high morbidity & mortality
ACUTE LIVER FAILURE (AASLD 2011)

3. DEFINITION
Evidence of coagulation abnormality , usually an
INR ≥ 1.5, & any degree of mental alteration
(encephalopathy) in a patient without pre-
existing cirrhosis & with an illness of < 26 weeks
duration.
Patients with wilson disease , vertically acquired
HBV, or AIH may be included in spite of the
possibility of cirrhosis if their disease has only
been recognized for < 26 weeks.
ACUTE LIVER FAILURE (AASLD 2011)

4. ACUTE LIVER FAILURE
A number of other terms have been used for
this condition , including fulminant hepatic
failure & fulminant hepatitis or necrosis.
“Acute liver failure” is a better overall term that
should encompass all durations upto 26 weeks.
ACUTE LIVER FAILURE (AASLD 2011)

5. CLASSIFICATION
ALF is classified in to three subcategories ,
depending upon the time lapsed b/w the
appearance of jaundice , to the development of
encephalopathy.
 1) Hyper acute : < 7 days
 2) Acute : 7 – 21days
 3) Sub acute : > 21 days & < 26 weeks
ACUTE LIVER FAILURE (AASLD 2011)

6. PATHOPHYSIOLOGY
 Loss of normal function of hepatic tissue which
occurs over a short period of time.
It results in the loss of the metabolic , secretory ,
& regulatory effects of the liver cells.
This results in the rapid accumulation of toxic
substances , which then manifests in the patient
as an altered sensorium , cerebral edema ,
hemodynamic abnormalities & even multiorgan
failure.
ACUTE LIVER FAILURE (AASLD 2011)

7. CAUSES OF ALF
Viral hepatitis Hep A, B, E, D, HSV, VZV, CMV
Drugs Dose-related : Acetaminophen
Idiosyncratic : antibiotics, anti TB, .
. anticonvulsants, NSAIDs
Toxin Mushroom poisoning, CCl4
Vascular Ischemic hepatitis, Budd-Chiari syndrome,
veno-occlusive disease
Metabolic Wilson disease
Pregnancy Acute fatty liver, Eclampsia, HELLP
syndrome
Misc Malignant infiltration, sepsis, AIH
Indeterminate
ACUTE LIVER FAILURE (AASLD 2011)

8. VIRAL HEPATITIS
Viral hepatitis may lead to ALF.
Hepatitis A & B account for most of these cases.
Hepatitis C rarely causes ALF.
Hepatitis D, as a co-infection or super infection
with HBV can lead to ALF.
Hepatitis E (often observed in pregnant women)
in an endemic area is an imp cause of ALF.
ACUTE LIVER FAILURE (AASLD 2011)

9. VIRAL HEPATITIS
Atypical causes of viral hepatitis & ALF include:
HSV
CMV
EBV
Hemorrhagic fever viruses
Paramyxoviruses
ACUTE LIVER FAILURE (AASLD 2011)

10. ACETAMINOPHEN
HEPATOTOXICITY
Acetaminophen is a dose related toxin, most
ingestion leading to ALF exceed 10gm/day
(150mg/kg).
However severe liver injury can occur rarely
when doses as low as 3-4 gm/day are taken.
Very high ALT levels are typically seen , serum
levels exceeding 3500 IU/L are highly correlated
with acetaminophen poisoning.
ACUTE LIVER FAILURE (AASLD 2011)

11. ACETAMINOPHEN
HPATOTOXICITY
Because acetaminophen is the leading cause of
ALF (at least in the US & Europe) & there is an
available antidote, acetaminophen levels should
be drawn in all patients presenting with ALF.
Specific indication that acetaminophen may be
the culprit include very high ALT & low bilirubin
levels, in the absence of apparent hypotension
& cardiovascular collapse.
ACUTE LIVER FAILURE (AASLD 2011)

12. MUSHROOM POISONING
There is no available blood test to confirm the
presence of these toxins, but this diagnosis
should be suspected in patients with a history of
severe GI symptoms (nausea, vomiting,
diarrhea, abdominal cramping), which occurs
within hours to a day of ingestion.
ACUTE LIVER FAILURE (AASLD 2011)

13. DRUG INDUCED LIVER INJURY
Drugs other than acetaminophen rarely cause
dose-related toxicity.
Most examples of idiosyncratic drug
hepatotoxicity occurs within the first 6 months
after drug initiation.
Classes of drugs commonly implicated include
antibiotics, NSAIDs & anticonvulsants.
ACUTE LIVER FAILURE (AASLD 2011)

14. DRUG INDUCED LIVER INJURY
Certain herbal preparations, weight loss agents
& other nutritional supplements have been
found to cause liver injury, so inquiry about such
substances should be included in a complete
medication history.
ACUTE LIVER FAILURE (AASLD 2011)

15. Uncommon cause of ALF.
Typically occurs in young patients,
accompanied by the abrupt onset of Coombs
negative hemolytic anemia with serum bilirubin
levels >20 mg/dl.
Kayser-Fleischer rings are present in about 50%
of patients
WILSON DISEASE
ACUTE LIVER FAILURE (AASLD 2011)

16. WILSON DISEASE
Serum ceruloplasmin is typically low, but may
be normal in upto 15 % of cases & is reduced in
῀ 50% of other forms of ALF.
High urinary & plasma copper levels as well as
hepatic copper measurement will confirm the
diagnosis.
Very low serum ALP & uric acid levels.
A high bilirubin (mg/dl) to ALP (IU/L) ratio ( >
2.0) is a rapid (indirect) indicator.
ACUTE LIVER FAILURE (AASLD 2011)

17. Acute hepatic vein thrombosis
Abdominal pain, ascites and striking
hepatomegaly are often present.
Diagnosis confirmed with hepatic imaging
studies (computed tomography, Doppler
ultrasonography, venography, magnetic
resonance venography) & testing to identify
hypercoagulable conditions (polycythemia,
malignancies).
BUDD CHIARI SYNDROME
ACUTE LIVER FAILURE (AASLD 2011)

18. ACUTE ISCHEMIC INJURY
Shock liver: cardiac arrest; significant
hypotension/hypovolemia; severe CHF
Drug induced hypotension/hypoperfusion: long
acting niacin; cocaine; methamphetamines
Documented hypotension not always found
Transaminases often > 1000-2000 mg/dL;
Simultaneous renal insufficiency and/or muscle
necrosis often found
ACUTE LIVER FAILURE (AASLD 2011)

19. AIH patients that develop ALF represent the
most severe form of the disease.
Auto-antibodies absent (up to 30% of cases)
Liver biopsy should be considered if
autoimmune hepatitis is suspected and
autoantibodies are negative.
AUTOIMMUNE HEPATITIS
ACUTE LIVER FAILURE (AASLD 2011)

20. Acute Fatty Liver of Pregnancy/HELLP (Hemolysis,
Elevated Liver Enzymes, Low Platelets) Syndrome.
A small no. of women near the end of pregnancy will
develop rapidly progressive hepatocyte failure associated
with increased fetal or maternal mortality.
A variety of presentation may be seen generally confined
to the last trimester.
Triad of jaundice, coagulopathy, and low platelets
Hypoglycemia and features of pre-eclampsia are
common.
ALF IN PREGNANCY
ACUTE LIVER FAILURE (AASLD 2011)

21. MALIGNANT INFILTRATION
Malignant infiltration of the liver may cause ALF.
Acute severe hepatic infiltration occurs with
breast Ca, small cell lung Ca, lymphoma,
melanoma & myeloma.
In patients with ALF who have a previous
cancer history or massive hepatomegaly,
consider underlying malignancy & obtain
imaging & liver biopsy to confirm or exclude the
diagnosis.
ACUTE LIVER FAILURE (AASLD 2011)

22. INDETERMINATE ETIOLOGY
If the etiological diagnosis remains elusive after
extensive initial evaluation , liver biopsy may be
appropiate to attempt to identify a specific
etiology that might influence treatment strategy.
Causes of cases believed to represent
indeterminate ALF , & subsequently recognized
include acetaminophen, AIH , & malignancies.
ACUTE LIVER FAILURE (AASLD 2011)

23. CLINICAL MANIFESTATIONS
Many of the initial symptoms in patients with
ALF are non-specific : (fatigue, malaise,
anorexia, nausea, vomiting, abdominal pain,
lethargy).
As the liver failure progress, patients who were
initially anicteric may develop jaundice, & those
with subtle mental status changes (e.g lethargy,
difficulty sleeping) may become confused or
eventually comatose.
ACUTE LIVER FAILURE (AASLD 2011)

24. CLINICAL MANIFESTATIONS
The presence of hepatic encephalopathy is one
of the defining characteristics of ALF.
ACUTE LIVER FAILURE (AASLD 2011)

25. CNS disturbances
–Hepatic encephalopathy
–Cerebral edema
–Seizures
Infections
Coagulopathy and bleeding
Renal failure & hemodynamic collapse
Metabolic derangements
COMPLICATIONS
ACUTE LIVER FAILURE (AASLD 2011)

26. DIFFERENTIAL DIGNOSES
Acute decompensation of cirrhosis
Alcoholic hepatitis with underlying cirrhosis
Sepsis with MOF
Eclampsia & pre-eclampsia
Severe liver involvement of systemic infections
(malaria, typhoid, leptospirosis, riketsial
infection etc)
ACUTE LIVER FAILURE (AASLD 2011)

27. DIAGNOSIS
History
Physical examination
Investigations
ACUTE LIVER FAILURE (AASLD 2011)

28. HISTORY
Date of onset of jaundice & encephalopathy.
Alcohol abuse
Medication use (prescription & recreational)
Herbal or traditional medicine use
Family hx of liver disease (wilson disease)
Exposure to hepatic toxins (mushroom, organic
solvents)
ACUTE LIVER FAILURE (AASLD 2011)

29. HISTORY
Exposure to risk factors for viral hepatitis (travel,
transfusion, sexual contacts, occupation, body
piercing)
Evidence of complications (e.g renal failure,
seizures, bleeding, infections)
ACUTE LIVER FAILURE (AASLD 2011)

30. PHYSICAL EXAMINATION
Mental status examination & grading of HE.
Search for stigmata of CLD (usually absent)
Jaundice
RUQ tenderness
Hepatomegaly (viral hepatitis, malignant
infiltration, CHF, Budd Chiari syndrome)
ACUTE LIVER FAILURE (AASLD 2011)

31. PHYSICAL EXAMINATION
Rapid development of ascitis in ALF patient,
accompanied by abdominal pain suggest the
possibility of BC syndrome.
Clinical signs of elevated ICP (systemic
hypertension, bradycardia & irregular respiration
_cushing triad & other neurologic changes such
as pupillary dilatation or decerebrate posture)
ACUTE LIVER FAILURE (AASLD 2011)

32. INITIAL INVESTIGATIONS
Coagulation studies PT / INR
CBC Thrombocytopenia
LFTs Elevated levels of ALT, AST, ALP, Bilirubin
RBS May be low
Serum electrolytes Including HCO3, Ca, Mg, Phosphorus
RFTs Creatinine may be elevated
Blood group & screen
Pregnancy test
ABGs May reveal hypoxemia
Ammonia Elevated
Arterial lactate Often elevated
ACUTE LIVER FAILURE (AASLD 2011)

33. ETIOLOGY SPECIFIC
Viral hepatitis Anti-HAV IgM
HBsAg, anti-HBc IgM
Anti-HCV, HCV RNA
Hepatitis D virus IgM
Anti-HEV
HSV1 IgM, VZV
Wilson disease Ceruloplasmin, serum & urinary copper
Autoimmune hepatitis ANA, ASMA, Immunoglobulin levels
Budd Chiari syndrome Hepatic doppler USG, Abd CT or MRI
Drugs and toxins Acetaminophen level
Toxicology screen
Indeterminate Liver biopsy
ACUTE LIVER FAILURE (AASLD 2011)

34. MANAGEMENT
Therapy of ALF consist of general supportive
measures (complications), specific therapies for
some of the etiologies, liver transplantation &
other methods of temporary liver support.
ACUTE LIVER FAILURE (AASLD 2011)

35. Tx OF COMPLICATIONS

36. Tx OF COMPLICATIONS

37. SPECIFIC TREATMENT

38. SPECIFIC TREATMENT

39. SPECIFIC TREATMENT

40. LIVER TRANSPLANTATION
It remains the only effective therapy for ALF
patients who fail to recover spontaneously.
king`s College criteria is used to select the
patient that should be referred to a transplant
center for transplantation.
ACUTE LIVER FAILURE (AASLD 2011)

41. KING`S COLLEGE CRITERIA
ACUTE LIVER FAILURE (AASLD 2011)

42. LIVER SUPPORT SYSTEMS
Are support devices which help in resting the
liver to provide it sometime to recover.
There are two kinds of devices, sorbent based
artificial systems & cell based bio-artificial
systems.
There is no good evidence showing a decrease
in mortality with their use in ALF.
They are not currently recommended outside of
clinical trials.
ACUTE LIVER FAILURE (AASLD 2011)

43. PROGNOSIS
Cause of ALF: most significant predictor of
outcome
Acetaminophen, Hepatitis A, shock liver,
pregnancy related with > 50% OLT free
survival
All others < 20% OLT free survival
Degree of encephalopathy: Grade I-II with 65-
70% spontaneous recovery; Grade III-IV < 20%
Age: > 40 yr or < 10 yr have worse outcome
ACUTE LIVER FAILURE (AASLD 2011)

44. SUMMARY
Patients with ALF should be hospitalized &
monitored frequently, preferably in an ICU.
The precise etiology of ALF should be sought to
guide further management decisions.
NAC may be used in the setting of non-
acetaminophen ALF including, e.g DILI &
hepatitis B.
ACUTE LIVER FAILURE (AASLD 2011)

45. SUMMARY
The development of cerebral edema is the
major cause of morbidity & mortality in patients
with ALF.
ACUTE LIVER FAILURE (AASLD 2011)

46. ACUTE LIVER FAILURE (AASLD 2011)