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ACUTE LIVER FAILURE
PRESENTATION
BY
DR SAQIB PERVEZ
MEDICAL `C`
LRH PESHAWAR
ACUTE LIVER FAILURE (AASLD 2011)
INTRODUCTION
ALF is a rare condition in which rapid
deterioration of liver function results in altered
mentation and coag...
DEFINITION
Evidence of coagulation abnormality , usually an
INR ≥ 1.5, & any degree of mental alteration
(encephalopathy)...
ACUTE LIVER FAILURE
A number of other terms have been used for
this condition , including fulminant hepatic
failure & ful...
CLASSIFICATION
ALF is classified in to three subcategories ,
depending upon the time lapsed b/w the
appearance of jaundic...
PATHOPHYSIOLOGY
 Loss of normal function of hepatic tissue which
occurs over a short period of time.
It results in the l...
CAUSES OF ALF
Viral hepatitis Hep A, B, E, D, HSV, VZV, CMV
Drugs Dose-related : Acetaminophen
Idiosyncratic : antibiotics...
VIRAL HEPATITIS
Viral hepatitis may lead to ALF.
Hepatitis A & B account for most of these cases.
Hepatitis C rarely ca...
VIRAL HEPATITIS
Atypical causes of viral hepatitis & ALF include:
HSV
CMV
EBV
Hemorrhagic fever viruses
Paramyxoviruses
A...
ACETAMINOPHEN
HEPATOTOXICITY
Acetaminophen is a dose related toxin, most
ingestion leading to ALF exceed 10gm/day
(150mg/...
ACETAMINOPHEN
HPATOTOXICITY
Because acetaminophen is the leading cause of
ALF (at least in the US & Europe) & there is an...
MUSHROOM POISONING
There is no available blood test to confirm the
presence of these toxins, but this diagnosis
should be...
DRUG INDUCED LIVER INJURY
Drugs other than acetaminophen rarely cause
dose-related toxicity.
Most examples of idiosyncra...
DRUG INDUCED LIVER INJURY
Certain herbal preparations, weight loss agents
& other nutritional supplements have been
found...
Uncommon cause of ALF.
Typically occurs in young patients,
accompanied by the abrupt onset of Coombs
negative hemolytic ...
WILSON DISEASE
Serum ceruloplasmin is typically low, but may
be normal in upto 15 % of cases & is reduced in
῀ 50% of oth...
Acute hepatic vein thrombosis
Abdominal pain, ascites and striking
hepatomegaly are often present.
Diagnosis confirmed ...
ACUTE ISCHEMIC INJURY
Shock liver: cardiac arrest; significant
hypotension/hypovolemia; severe CHF
Drug induced hypotens...
AIH patients that develop ALF represent the
most severe form of the disease.
Auto-antibodies absent (up to 30% of cases)...
 Acute Fatty Liver of Pregnancy/HELLP (Hemolysis,
Elevated Liver Enzymes, Low Platelets) Syndrome.
 A small no. of women...
MALIGNANT INFILTRATION
Malignant infiltration of the liver may cause ALF.
Acute severe hepatic infiltration occurs with
...
INDETERMINATE ETIOLOGY
If the etiological diagnosis remains elusive after
extensive initial evaluation , liver biopsy may...
CLINICAL MANIFESTATIONS
Many of the initial symptoms in patients with
ALF are non-specific : (fatigue, malaise,
anorexia,...
CLINICAL MANIFESTATIONS
The presence of hepatic encephalopathy is one
of the defining characteristics of ALF.
ACUTE LIVER...
CNS disturbances
– Hepatic encephalopathy
– Cerebral edema
– Seizures
Infections
Coagulopathy and bleeding
Renal failu...
DIFFERENTIAL DIGNOSES
Acute decompensation of cirrhosis
Alcoholic hepatitis with underlying cirrhosis
Sepsis with MOF
...
DIAGNOSIS
History
Physical examination
Investigations
ACUTE LIVER FAILURE (AASLD 2011)
HISTORY
Date of onset of jaundice & encephalopathy.
Alcohol abuse
Medication use (prescription & recreational)
Herbal ...
HISTORY
Exposure to risk factors for viral hepatitis (travel,
transfusion, sexual contacts, occupation, body
piercing)
E...
PHYSICAL EXAMINATION
Mental status examination & grading of HE.
Search for stigmata of CLD (usually absent)
Jaundice
R...
PHYSICAL EXAMINATION
Rapid development of ascitis in ALF patient,
accompanied by abdominal pain suggest the
possibility o...
INITIAL INVESTIGATIONS
Coagulation studies PT / INR
CBC Thrombocytopenia
LFTs Elevated levels of ALT, AST, ALP, Bilirubin
...
ETIOLOGY SPECIFIC
Viral hepatitis Anti-HAV IgM
HBsAg, anti-HBc IgM
Anti-HCV, HCV RNA
Hepatitis D virus IgM
Anti-HEV
HSV1 I...
MANAGEMENT
Therapy of ALF consist of general supportive
measures (complications), specific therapies for
some of the etio...
Tx OF COMPLICATIONS
Tx OF COMPLICATIONS
SPECIFIC TREATMENT
SPECIFIC TREATMENT
SPECIFIC TREATMENT
LIVER TRANSPLANTATION
It remains the only effective therapy for ALF
patients who fail to recover spontaneously.
king`s C...
KING`S COLLEGE CRITERIA
ACUTE LIVER FAILURE (AASLD 2011)
LIVER SUPPORT SYSTEMS
Are support devices which help in resting the
liver to provide it sometime to recover.
There are t...
PROGNOSIS
Cause of ALF: most significant predictor of
outcome
Acetaminophen, Hepatitis A, shock liver,
pregnancy related...
SUMMARY
Patients with ALF should be hospitalized &
monitored frequently, preferably in an ICU.
The precise etiology of A...
SUMMARY
The development of cerebral edema is the
major cause of morbidity & mortality in patients
with ALF.
ACUTE LIVER F...
ACUTE LIVER FAILURE (AASLD 2011)
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Acute liver failure

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Acute liver failure

  1. 1. ACUTE LIVER FAILURE PRESENTATION BY DR SAQIB PERVEZ MEDICAL `C` LRH PESHAWAR ACUTE LIVER FAILURE (AASLD 2011)
  2. 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. 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. 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. 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. 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. 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. 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. 9. VIRAL HEPATITIS Atypical causes of viral hepatitis & ALF include: HSV CMV EBV Hemorrhagic fever viruses Paramyxoviruses ACUTE LIVER FAILURE (AASLD 2011)
  10. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 24. CLINICAL MANIFESTATIONS The presence of hepatic encephalopathy is one of the defining characteristics of ALF. ACUTE LIVER FAILURE (AASLD 2011)
  25. 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. 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. 27. DIAGNOSIS History Physical examination Investigations ACUTE LIVER FAILURE (AASLD 2011)
  28. 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. 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. 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. 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. 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. 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. 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. 35. Tx OF COMPLICATIONS
  36. 36. Tx OF COMPLICATIONS
  37. 37. SPECIFIC TREATMENT
  38. 38. SPECIFIC TREATMENT
  39. 39. SPECIFIC TREATMENT
  40. 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. 41. KING`S COLLEGE CRITERIA ACUTE LIVER FAILURE (AASLD 2011)
  42. 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. 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. 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. 45. SUMMARY The development of cerebral edema is the major cause of morbidity & mortality in patients with ALF. ACUTE LIVER FAILURE (AASLD 2011)
  46. 46. ACUTE LIVER FAILURE (AASLD 2011)

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