ACUTE LIVER FAILURE.pptxxxxxxxxxxxxxxxxx

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1. LIVER FAILURE SCHOOL OF CLINICAL SCIENCES MAKENI INTERNAL MEDICINE LECTURER: DR MARTIN PREPARED BY GROUP SIX 2022 COHORT

2. PREPARED AND PRESENTED BY MOSETTA A.B. KOROMA 22059 ISATA KATTIE KOROMA 22058 MOSES JOHN KOROMA 22057 MARIAN MUYO KANU 22051 ISHA MEDISHER KARGBO 22054 SENNATU F. KOROMA 22060 FREDA KAWIE 22055 FORAY KONDEH 22056

3. Presentation outline Brief overview of the liver Definition Epidemiology Classification Etiology/Risk factors Pathophysiology Clinical presentation Differential diagnosis Diagnosis Management Complication Prognosis

4. Abbreviations INR - International normalized ratio ALF - Acute Liver Failure HF - Hepatic Failure HDV - Hepatitis D virus HEV - Hepatitis E virus HAV - Hepatitis A virus CMV - Cytomegalovirus HSV - Herpes Simplex Virus

5. BASIC LIVER ANATOMY The liver is the largest gland in the body weighing 1400-1600 gm in the males and 1200-1400 gm in the females. There are 2 main anatomical lobes—right and left , the right being about six times the size of the left lobe.

6. Continuation of the anatomy The right lobe has quadrate lobe on its inferior surface and a caudate lobe on the posterior surface. The right and left lobes are separated anteriorly by a fold of peritoneum called the falciform ligament, inferiorly by the fissure for the ligamentum teres , and posteriorly by the fissure for the ligamentum venosum

7. BLOOD SUPPLY The liver receives a blood supply from two sources . The first is the hepatic artery which delivers oxygenated blood from the general circulation. The second is the hepatic portal vein delivering deoxygenated blood from the small intestine containing nutrients.

8. BLOOD SUPPLY Cont … The blood flows through the liver tissue to the hepatic cells where many metabolic functions take place. 􀀀 The blood drains out of the liver via the hepatic vein. The liver tissue is not vascularised with a capillary network as with most other organs, but consists of blood filled sinusoids surrounding the hepatic cells.

9. DEFINITION A clinical syndrome that results from massive necrosis of liver cells leading to hepatic encephalopathy and impaired synthetic function causing coagulopathy (INR>1.5) in a person with previous normal liver or compensated liver disease.

10. ALF includes; Biochemical evidence of acute liver (usually <8 wks duration) N o evidence of a known chronic liver disease ; H epatic-based coagulopathy that is not corrected by parenteral administration of vitamin K; Hepatic encephalopathy must be present if the uncorrected prothrombin time (PT) is ≥ 15 seconds or international normalized ratio (INR) is 1.5 to 1.9, respectively; and Hepatic encephalopathy is not required if the PT is ≥ 20 seconds or INR ≥2.0, respectively

11. Interval:jaundice to encephalopathy Cerebral oedema prognosis Leading causes Hyper-acute <7days common moderate Virus A,B;acetaminophen Acute 8-28days common poor Non-A/B/ C;drugs Sub-acute 29days to 12weeks poor poor Non-A/B/ C;drugs

12. EPIDEMIOLOGY A pproximately 2000 cases annually occurring in the United States. Acetaminophen or paracetamol overdoses are prominent causes of f uminant h epatic failure in Europe and, in particular , Great Britain. In the developing world, acute HBV infection dominates as a cause of fulminant hepatic failure because of the high prevalence of HBV. More often in women (73 %) than in men Patients younger than 10 years and older than 40 years tend to fare relatively poorly women with acute liver failure- older (39 y) than men (32.5 y

13. ETIOLOGY/RISK FACTORS Idiopathic – 15% It Can be subdivided into two based on etiology , these are: 1 . Direct liver parenchymal injury 2. Indirect liver parenchymal injury (vascular) Generally, when you have a massive liver cell death. The liver has enough time to compensate and regenerate, but when it happens abruptly, acutely without having time time compensate and regenerate, that is why the liver fails

14. Direct liver parenchymal injury Drug induced liver injury - I diosyncratic hypersensitivity ( Herbal Drugs) - Paracetamol Toxicity ( people that takes more than 4g of paracetamol a day) Viral induced liver injury - Hepatitis A,B,C and E viruses - Herpes Simplex virus (mostly seen in immuno -compromise patients)

15. Direct liver parenchymal injury cont … Antibody mediated - Autoimmune hepatitis ( ANA, Antismooth muscles antibody etc ) Acute fatty infiltration of the liver during pregnancy

16. Indirect liver parenchymal injury Vascular: Portal Vein thrombosis, Budd Chiari Syndrome, ischaemic hepatitis ( shock) Metabolic : wilsons disease Malignancy : Primary and metastatic Miscellaneous: Right sided heart failure

17. Etiology of ALF In different age group Neonates Infants Infection HSV, Adeno virus HBV HAV, HBV, HSV Infection Inborn errors of metabolism Galatosemia , tyrosinaemia , Hereditary fructose Intolerance hereditary fructose Intolerance Immune mediated Neonatal Autoimmune hepatitis Ischemia & abnormal Perfusion Hemochromatosis, Hemophagocytic syndrome Congestive heart failure, severe aspyxia Congestive heart Failure, Drugs & toxins other Acetaminophen,INH , valproate malignancy

18. Etiology Cont 2-10 year old 10-18 yrs old Infection HAV, HBV, HSV HAV, HBV, HSV, HCV Drugs & toxins Acetaminophen, INH, valproate Acetaminophen, INH, valproate Immune mediated Autoimmune hepatitis, hemophagocytic syndrome Autoimmune hepatitis, hemophagocytic syndrome Ischemia & abnormal Perfusion Budd- Chiari syndrome, Heart failure, cardiac Surgery, myocarditis Budd- Chiari syndrome, Heart failure, cardiac Surgery, myocarditis Metabolic Wilson’s disease, Reye’s syndrome, Wilson’s disease, Reye’s syndrome, other Hemophagocytic syndrome, septicemia , heat stroke Hemophagocytic syndrome, septicemia , heat stroke

19. PATHOPHYSIOLOGY

20. Mechanisms of hepatic injury Immune mediated hepatocellular injury Viral infections - Drug hepatotoxicity ( dihydralazine , halothane) Direct hepatocellular injury Hepatotrophic virus family-HAV , HBV, HCV Toxic or reactive metabolites- acetaminophen Toxic metabolites of compounds-metabolic diseases Ischemic hepatocellular Injury Shock states, SIRS

21. Effects are:

22. Pathophysiology cont … CEREBRAL EDEMA - development of cerebral edema /intracranial hypertension is the major cause of morbidity and mortality of patients suffering from acute liver failure- ? Etiology - multifactorial Increase of intracranial blood volume and cerebral blood flow - because of disruption of cerebral autoregulation - elevated systemic concentrations of nitric oxide, bacterial endotoxin, tumor necrotic factor-alpha (TNF-a), and interleukin-1 (IL-1) and -6 ( IL-6 )

23. Pathophysiology cont … Accumulation of glutamine in astrocytes leads to swelling and edema MULTISYSTEM ORGAN FAILURE Hyperdynamic circula tion state leads to low systemic vascular resistance (mimics sepsis) circulatory insufficiency and poor organ perfusion may initiate FHF or lead to complications

24. Pathophysiology cont … ENCEPHALOPATHY Wide variety of agents, including ammonia, free fatty acids, phenols , bile acids and aromatic amino acids combine to produce hepatic encephalopathy by several different mechanisms : D irect cellular effect Indirect: cause metabolic derangement 􀀀 conversion to false neurotransmitters A lteration of permeability of BBB: allows entry of toxic metabolites into the brain and thus contributes to cerebral oedema - major cause of death: present in 32% of patients at PM.

25. CLINICAL PRESENTATION HISTORY Duration of illness . Onset of jaundice and encephalopathy . Risk factors for hepatitis: eg - street food, sanitation, BT, surgery. Drug & immunization history H/O any bleeding episode.

26. CLINICAL PRESENTATION cont … Features of hepatic encephalopathy-Initially reduced alertness and poor concentration, progressing through behavioural abnormalities such as restlessness and aggressive outbursts, to drowsiness and coma Weakness , nausea and vomiting Right hypochondrial discomfort Family history Systemic enquiry

27. Physical examination Jaundice Anaemia Vital signs: Hypotension, tachycardia, tachypnoea . Mental status. Hepatomegaly –uncommon, liver usually N size - smaller 􀀀 Splenomegaly

28. Physical examination cont … Stigmata of chronic liver disease- ALF 2’ to compensated diseases(caput medusa, spider nevi, spider angiomata , ascites, contractures, palmar erythema) Ascites Features of raised ICP- unequal and fixed pupils Flapping 'hepatic' tremor Profuse sweating, local or general myoclonus, focal fits or decerebrate posturing Papilloedema occurs rarely and is a late sign Fetor hepaticus

29. Physical examination cont … Cardiovascular - hypotension with low SVR Pulmonary- respiratory alkalosis, impaired peripheral O 2 uptake, pulmonary edema , ARDS GIT- GI bleeding ( decreased clotting factors & platelets, DIC ), pancreatitis due to ischaemia Renal - ATN , hepatorenal syndrome, hyponatremia , hypokalemia , hypophosphatemia Hematology - coagulopathy, infection Endocrine - hypoglycemia , adrenal insufficiency

30. Investigation Complete blood count : Leucocytosis , thrombocytopenia Liver function test(LFT): Serum bilirubin ALT: raised AST :raised especially in paracetamol Alkaline phospatase : may be normal Albumin : usually normal unless in prolonged course

31. Investigation cont … Biochemical test : U/E/Cs Serum Electrolytes- Hypokalaemia and others. Serum Glucose- Hypoglycaemia. Serum Creatinine Serum Ammonia- Serum Calcium , Phosphate, Magnesium Serum lactate: At 4 hours(>3.5) or at 12 hours(>3) are early predictors of outcome in acetamenophan induced ALF.

32. Investigation cont … Blood cultures Blood grouping and cross matching Blood sugar levels Blood gas analysis : To detect cause Serological marker Anti HAV IgM HBsAg , AntiHBcore IgM antibody 􀀀 Anti HEV IgM Screening for other viruses- HSV, CMV etc.

33. Investigation cont … Immunological test S. immunoglobulin, ANA, anti SMA, antiLKM1 Serum acetamenophen level USG of HBS Screening for metabolic disease EEG-encephalopathy has xteristic pattern Liver biopsy : in auto-immune, metabolic causes of liver failure

34. Management of ALF Medical: To maintain physiological functions of liver Supportive care Specific treatment Surgical: Extracorporeal systems Liver transplantation

35. Supportive care Quiet environment. ICU- hemodynamic and ventilatory support Avoid sedation and stimulation Fluid restriction - 60-80% of daily requirement Choice of fluid: 0.225% nacl in 10% dextrose Prevention of hypoglycemia (maintain glucose level >4 mmol /l)

36. Supportive care IV H2 blocker or PPI Antibiotics : Cefuroxime, amoxicillin, fluconazole or Cefotaxime + flucoxacillin Anaemia should be corrected to ensure maximum oxygen supply to tissue. 􀀀 Lactulose-metabolized to organic acids by colonic bacteria . Reduces ammonia produced by bacteria & traps ammonia in acidic intestinal contents. Avoid diarrhea ! IV N- acetylcysteine benefits pts after paracetamol overdose even with encephalopathy and coagulopathy- same dose as PCM

37. Close Monitoring Continuous O2 saturation Clinical status: Pulse & BP hourly, liver size 12hrly Strict input-output chart : Avoid fluid overload CVP , Foley’s and arterial line : MAP > 60mmHg Frequent evaluation of blood glucose and neurological status. 1 2 hourly electrolyte and coagulation studies

38. Plasmapharesis Blood purification procedure High volume plasmaphoresis associated with rise in conscious level, haemodynamics and reduction in arterial ammonia concentrations Disadvantage is that possible hepatic growth factors are removed along with hepatotoxic mediators

39. Liver transplantation Patients with anticipated survival of < 80% and no contraindication to transplantation should be placed on waiting list as soon as possible. Multi-organ failure is major C/I to transplantation. Cerebral perfusion pressure <40 mmHg is a relative contraindication .

40. ALF: common complications E ncephalopathy Cerebral oedema Raised ICP Infection Coagulapathy H ypoglycemia Dyselectrolytemia Acid base disturbance. Multi-organ failure

41. REFERENCES Macleods clinical examination 14 th edition 121055 Hutchisons clinical methods Harrisons internal medicine Mayo clini Pubmed ncbi