in this topic we are discussing about liver failure and its management

1. LIVER FAILURE
DR VISHAL JAINTH
SENIOR RESIDENT

2. LIVER STRUCTURE AND BLOOD SUPPLY
• LARGEST ORGAN OF BODY.
• WEIGHT 1-1.5 KG. RECIEVES 25% OF CARDIAC OUTPUT.
• CONTAINS SINUSOIDS WHICH ARE COMPOSED OF FENESTRATED
ENDOTHELIAL CELLS ,KUPFFER CELL,STELLATE CELL AND NATURAL KILLER
CELL.
• ENDOTHELIAL CELLS : 50% OF SINUSOIDAL CELLS.FUNCTIONS INCLUDES
ENDOCYTOSIS,SECRETION(INTERLEUKIN,INTERFERON,ENDOTHELIN,AND
NITRIC OXIDE)
• KUPFFER CELLS :PHAGOCYTIC.
• STELLATE CELLS: LIPOCYTE ,FAT STORING CELL OR ITO CELLS.
• NATURAL KILLER CELLS: LIVER ASSOCIATED LYMPHOCYTES.

3. BLOOD SUPPLY OF LIVER

5. BILIRUBIN METABOLISM

7. TYPES OF LIVER FAILURE
1. ACUTE LIVER FAILURE
2. ACUTE ON CHRONIC LIVER FAILURE

8. ACUTE LIVER FAILURE
• ABRUPT AND RAPID DETERIORATION IN LIVER FUNCTION WITHOUT
PRIOR LIVER DISEASE.
• INCLUDES 3 PARAMETER:
1.DEVELOPMENT OF JAUNDICE.
2.COAGULOPATHY,INR>1.5.
3.ALTERED MENTATION OF ANY GRADE.

9. CLASSIFICATION OF ACUTE LIVER FAILURE
• O GRADY CLASSIFIED INTO 3 CATEGORIES.
• DEPENDS UPON DURATION BETWEEN THE ONSET OF JAUNDICE AND
ENCEPHALOPATHY WITHOUT PREEXISTING CIRRHOSIS AND WITH AN
ILLNESS OF <26 WEEKS.
1.HYPERACUTE LIVER FAILURE: <7 DAYS (G00D SURVIVAL RATE)
2.ACUTE LIVER FAILURE : 7-28 DAYS.
3.SUB ACUTE LIVER FAILURE : 5-12 WEEKS (WORST PROGNOSIS).

10. ETIOLOGY OF ACUTE LIVER FAILURE
1. INFECTIOUS
HEPATITIS VIRUS A,B,C,D,E.
HERPES SIMPLEX.
2. ISCHAEMIC CONGESTIVE HEPATOPATHY.
3.SEPSIS INDUCED LIVER DYSFUNCTION.
4.DRUG INDUCED LIVER DYSFUNCTION.
5.AUTO IMMUNE HEPATITIS.
6.PREGNANCY
ACUTE FATTY LIVER OF PREGNANCY.
HELLP.
7.TOTAL PARENTERAL NUTRITION.
8.METABOLIC
WILSON DISEASE

11. 1.INFECTIONS
SYSTEMIC INFECTION AFFECTING THE LIVER BY HEP A,C,D,E (RNA VIRUS)ONLY
HEP B (DNA VIRUS)
IN THIS FEVER WITH JAUNDICE.
FROM ASYPTOMATIC TO INAPPARENT TO FULMINANT FATAL INFECTIONS.
2.ISCHAEMIC CONGESTIVE HEPATOPATHY
COMMONEST CAUSES OF DERRANGED LFT IN ICU.
PREDISPOSING FACTOR ARE SHOCK,HAEMORRHAGE,DEHYDRATION,HEAT
STROKE,AORTIC DISSECTION,PULMONARY EMBOLUS,CARDIOGENIC SHOCK.
PREDISPOSING FACTOR FOR CONGESTIVE HEPATOPATHY
ISCHAEMIC CARDIOMYOPATHY,HEART FAILURE,MITRAL VALVE
STENOSIS,TRICUSPID REGURGITATION.
PEAK ELEVATION IN FIRST 72 HR.
FACTOR RESOLVES NORMALISES LFT IN 7-10 DAYS.
TREATMENT BY IMPROVE CARDIAC STATUS AND ORGAN PERFUSION.

12. 3.SEPSIS INDUCED LIVER DYSFUNCTION
• BY RELEASE OF BACTERIAL AND INFLAMMATORY MEDIATOR.
• IN SEPSIS
1.BACTERIAL AND LIPOPOLYSACCHARIDES INHIBIT TRANSPORTER WHICH
TRANSPORT BILE SALT AND BILIBURIN IN BILE CANALICULI CAUSES
CHOLESTASIS.
2.ENDOTHELIAL CELL PRODUCE CYTOKINES (TNF,IL-1,IL-6 )AND NITRIC
OXIDE PRODUCTION.
3.RELEASE OF OXYGEN FREE RADICAL PROTEASE AND ELASTASE.
. ABNORMAL JAUNDICE ,LFT AFTER 2,3 DAYS.LIVER ENZYMES>3
TIMES,BILURUBIN >5 TIMES.
TREATMENT WITH SUPPORTIVE AND ANTI BIOTICS THEARAPY

13. DRUG INDUCED LIVER DYSFUNCTION

15. ACETAMINOPHEN
• MOST COMMON CAUSE OF DRUG INDUCED HEPATIC DYSFUNCTION.
• UPTO 4GM/DAY IS SAFE IN HEALTHY INDIVIDUAL.
• 95 PERCENT ELIMINATED BY HEPATIC CONJUGATION.
• 5 PERCENT IS CONVERTED TO N- ACETYL- P- BENZOQUINONE-
IMINE(NAPQI).IT INACTIVATES WITH GLUTAHIONE AND EXCRETES.
• GLUTATHIONE STORES DEPLETED AND NAPQI IS HIGHLY TOXIC AND
CAUSES LIVER NECROSIS.

16. TOXICITY PRESENT IN THREE PHASES:
FIRST PHASES :GI SYMPTOMS OF NAUSEA,VOMITING AND
ABDOMINAL PAIN IN FIRST FEW HOUR AFTER INGESTION.
SECOND PHASE(24-72 HR):MARKED ELEVATION OF LIVER
ENZYMES.
THIRD PHASES(72-96 HR):JAUNDICE AND ENCEPHALOPATHY.
ANTIDOTE:
NAC 150 MG/KG OVER 1 HOUR FOLLOWED BY 12.5 MG/KG/HR
FOR 4 HR THEN 6.25 MG/KG/HR FOR 67 HRS

17. ACUTE FATTY LIVER OF PREGNANCY
• PRESENT BETWEEN 30-38 WEEKS OF GESTATION.
• SYMPTOMS INCLUDE MALAISE HEADACHE,NAUSEA,VOMITTING.
• HELLP SYNDROME
• HAEMOLYSIS ,ELEVATED LIVER ENZYMES LOW PLATELET COUNT.

18. TOTAL PARENTERAL NUTRITION
• ON PROLONGED PARENTERAL NUTRITION (BEYOND 2 WEEKS).
• MORE COMMON IN INFANT THAN ADULT.
• LIPID EMULSIONS > 1GM/KG/DAY DEVELOP ACUTE LIVER DISEASE.
• SOYABEAN OIL DERIVATIVE LIPIDS EMULSION CONTAINS OMEGA 6
POLYUNSATURATED FATTY ACIDS STIMULATE PROINFLAMMATORY
RESPONSE AND INHIBIT BILIARY SECRETION.

19. CLINICAL FEATURES OF ACUTE LIVER FAILURE

20. HEPATIC ENCEPHALOPATHY
• SPECTRUM OF NEUROLOGIC OR PSYCHIATRIC ABNORMALITY
RESULTING FROM LIVER INSUFFICIENCY OR PORTOSYSTEMIC
SHUNTING.
• SUBTYPES DUE TO UNDERLYING DISEASES:
1.ACUTE LIVER FAILURE.
2.PORTOSYSTEMIC SHUNTING.
3.CIRRHOSIS.
IN ACUTE LIVER FAILURE RISK OF CEREBRAL OEDEMA WITH INCREASE
ICP AND CEREBRAL HERNIATION.

21. STAGING OF HEPATIC ENCEPHALOPATHY

22. IN HIGH GRADE HEPATIC ENCEPHALOPATHY ARTERIAL
AMMONIA LEVEL USEFUL.
1.LEVEL>100 MICROMOL/L PREDICT SEVERE
ENCEPHALOPATHY.
2.LEVEL >200 MICROMOL/L IS ASSOCIATED WITH
INTRACRANIAL HYPERTENSION IN HALF CASES.
3.LEVEL> 122 MICROMOL/LITRE FOR 3 DAYS (POOR
PROGNOSIS)

23. PATHOPHYSIOLOGY OF HEPATIC
ENCEPHALOPATHY

24. DUE TO INCREASED AMMONIA CAUSES
PRODUCTION OF GLUTAMINE IN ASTROCYTES
WHICH CAUSES INCREASE OSMOTIC ACTION AND
CAUSES BRAIN OEDEMA CAUSES LOSS OF
CEREBRAL AUTOREGULATION AND ITS
COMPLICATIONS
INTRACRANIAL HYPERTENSION AND BRAIN
HERNIATION.

25. MEDICAL THERAPY TO CONTROL
ENCEPHALOPATHY AND CEREBRAL OEDEMA
• NEUROLOGICAL SUPPORT.
• INTRACRANIAL PRESSURE MONITORING.
• JUGULAR BULB VENOUS SATURATION MONITORING.
• OSMOTHERAPY.
• THIOPENTONE.
• HYPOTHERMIA.
• PROPHYLACTIC PHENYTION.
• HYPERVENTILATION.
• AMMONIA LOWERING STRATEGIES.
• LOLA (L ORNITHINE L ASPARTATE).
• L ORNITHINE PHENYLACETATE.
• SODIUM BENZOATE.
• RIFAXIMIN.

26. 1.INTRACRANIAL PRESSURE MONITOR:
BY EPIDURAL TRANSDUCER.
GOAL IS TO MAINTAIN AN ICP <20 MM HG.
ICP>40 MM HG FOR 2 HR (CONTRAINDICATION FOR LIVER
TRANSPLANT)
2.JUGULAR BULB VENOUS STAURATION MONITORING:
CATHETER IN JUGULAR BULB.
SJVO2<55 % ISCHAEMIC BRAIN.
SJVO2>85 % HYPEREMIC BRAIN
3.OSMOTHERAPY:
INTRAVENOUS BOLUS OF MANNITOL (0.5-1 MG/KG 20%SOLUTION
OVER 5 MINS.
HIGH DOSES CAUSES ACUTE RENAL FAILURE AND DAMAGE BBB.

27. 4.THIOPENTONE:
LOADING DOSE 3-5 MG/KG OVER 15 MINS
CONTINUOUS INFUSION AT 0.5-2.0 MG/HR.
5.HYPOTHERMIA:
REDUCES CBF CEREBRAL METABOLISM
AMMONIA UPTAKE BY BRAIN GLUTAMINE
SYNTHESIS REDUCES ICP.

28. 6.LACTULOSE(NON ABSORBABLE DISACCHARIDES)
1.THEY DECREASE COLONIC TRANSIST TIME
REDUCES OPPORTUNITY FOR ABSORPTION OF
GUT DERIVED AMMONIA
2.NON ABSORBABLE DISACCHARIDES LOWERS
COLONIC PH CONVERT AMMONIA TO NON
ABSORBABLE AMMONIUM IONS.

29. 7.L ORNITHINE L ASPARTATE:
CONVERT TO GLUTAMATE.
AMMONIA+GLUTAMATE=GLUTAMINE
IN MUSCLE CELL DETOXIFICATION OF
AMMONIA TO GLUTAMINE.
8.L ORNITHINE PHENYLACETATE:
PHENYL ACETATE COMBINE WITH GLUTAMINE
FORM PHEMYL ACETYL GLUTAMINE WHICH IS
WATER SOLUBLE AND EXCRETES IN URINE

30. 9.RIFAXIMIN:
ANTIBIOTICS WITH BROAD SPECTRUM ACTIVITY
AGAINST ENTERIC BACTERIA
REGIMEN:1200MG DAILY (400MG EVERY 8 HRS
FOR 10-21 DAYS.
10.SODIUM BENZOATE:
FOOD PRESERVATIVE COMBINE WITH
AMMONIA AND GLYCINE TO FORM HIPPURATE
WHICH IS WATER SOLUBLE.

31. THERAPIES DIRECTED TOWARD
MANAGEMENT OF COMPLICATIONS
• PREVENTION AND TREATMENT OF INFECTIONS .
• HAEMODYNAMIC SUPPORT.
• COAGULOPATHY.
• MECHANICAL VENTILATION.
• RENAL SUPPORT.
• NUTRITIONAL AND METABOLIC SUPPORT

32. ACUTE ON CHRONIC LIVER FAILURE
• INVOLVES PATIENT WITH CHRONIC LIVER DISEASE DEVELOP DUE TO
DETERIORATION IN LIVER FUNCTION DUE TO ANY PRECIPITATING
EVENTS ASSOCIATED WITH INCREASE 3 MONTH MORTALITY CAUSED
BY MULTI SYSTEM ORGAN FAILURE.
• PRECIPITATING FACTOR:VIRAL HEPATITIS,DRUG,ALCOHAL
ASSOCIATED.
• CHIEF SYMPTOMS :
HYPERBILIRIBINAEMIA.
COAGULOPATHY.

33. CHRONIC LIVER DISEASE
• PERSISTENT LIVER INFLAMMATION ,LIVER CHEMISTRY ABNORMALITY
AND POSITIVE SEROLOGICAL AND MOLECULAR MARKER FOR 6
MONTHS.
• CHRONIC HEPATITIS C,ALCOHALIC LIVER DISEASE,NON ALCOHALIC
STEATOHEPATITIS.

34. FINDINGS IN CIRRHOSIS(CHRONIC LIVER
DISEASE)

35. COMPLICATIONS AND MANAGEMENT
• ASCITES.
• HEPATIC ENCEPHALOPATHY.
• VARICEAL BLEEDING.
• COAGULOPATHY.
• SPONTANEOUS BACTERIAL PEROTINITIS.
• HEPATORENALSYNDROME.
• HEPATOPULMONARY SYNDROME.

36. ASCITES

38. TREATMENT

39. REFRACTORY ASCITES

40. TREATMENT OF REFRACTORY ASCITES

41. VARICEAL BLEEDING

44. TREATMENT

45. CONTROL OF ACUTE BLEEDING

46. TRANSJUGULAR INTRAHEPATIC
PORTOSYSTEMIC SHUNT

47. SPONTANEOUS BACTERIAL PERITONITIS

49. TREATMENT

50. PROPHYLAXIS FOR RECURRENT SBP

51. HEPATORENAL SYNDROME

52. CRITERIA FOR HRS

54. MANAGEMENT OF HEPATORENAL SYNDROME

56. VASOPRESSOR THERAPY

57. COAGULOPATHY

58. HEPATOPULMONARY SYNDROME

60. LIVER TRANSPLANTATION
• SCORING SYSTEM:
1.MODEL FOR END STAGE LIVER DISEASE(MELD)SCORE.
2.KING COLLEGE HOSPITAL CRITERIA.
3.CLINCY CRITERIA.
• MELD IS USE MORE OFTEN.
• KCH HAS HIGHER ACCURACY IN PRDICTING OUTCOMES COMPARED
WITH CLINCHY CRITERIA.

61. MELD SCORE AND CLINCHY CRITERIA

62. KINGS COLLEGE CRITERIA

63. EXTRA CORPOREAL LIVER SUPPORT IN ACUTE
LIVER FAILURE

64. EFFECT OF LIVER ASSIST DEVICES
• ON HAEMODYNAMICS :INCREASES SVR,REMOVAL OF NO.
• ON METABOLISM: REMOVE LACTATE,BILE ACID
,BILIRUBIN,AMMONIA.
• ON HEPATIC FUNCTION: INCREASE FACTOR 7 ANTITHROMBIN 3
ALBUMIN ,PT
• ON CEREBRAL: IMPROVE ENCEPHALOPATHY,DECREASES ICP.
• ON RENAL FUNCTION: DECREASES BUN AND CREATININE.