Acute (fulminant) hepatic failure It is a rare syndrome in which hepatic encephalopathy results from a sudden severe impairment of hepatic function. It must occur within 8 weeks of onset of the precipitating illness In the absence of evidence of pre-existing liver disease

Clinical grading of hepatic encephalopathy Hepatic encephalopathy is the cardinal manifestation of acute hepatic failure. Clinical grading of hepatic encephalopathy Clinical grade Clinical signs Grade 1 Poor concentration, slurred speech, slow mentation, disordered sleep rhythm Grade 2 Drowsy but easily rousable, occasional aggressive behavior, lethargic Grade 3 Marked confusion, drowsy, sleepy but responds to pain & voice, gross disorientation Grade 4 Unresponsive to voice, may or may not respond to painful stimuli, unconscious

Fulminant hepatic failure Hepatic encephalopathy include the following: Reduced alertness & poor concentration Behavioral abnormalities e.g. restlessness, aggressive outbursts & mania Confusion Disorientation Inversion of sleep rhythm Slurred speech Yawning Hiccup Convulsions

Fulminant hepatic failure Flapping tremor (asterixis) is characteristic for cases of acute hepatic failure but may be absent. Cerebral edema: Produce increased intracranial pressure This results in: Unequal or abnormally reacting pupils Fixed pupils Hypertensive episodes Bradycardia Hyperventilation Profuse sweating Local or general myoclonus Focal fits Decerebrate posturing Papiledema Right hypochondrial pain (occasionally)

Fulminant hepatic failure Examination can reveal: Jaundice Fetor hepaticus Initially the liver is enlarged (later may become impalpable) Splenomegaly (uncommon) Ascites & edema (late features)

Fulminant hepatic failure Investigations to determine the cause of acute hepatic failure: Toxicology screen of blood & urine IgM anti-HBc IgM anti-HAV. Anti-HEV, HCV, CMV, herpes simplex, EBV Ceruloplasmin, serum copper, urinary copper Autoantibodies: ANF, AMA, ASMA, LKM. Ultrasound of liver & Doppler of hepatic veins

Adverse prognostic criteria in acute hepatic failure Paracetamol overdose: pH < 7.3 at or beyond 24 hours following the overdose OR Serum creatinine >300 μmol/l, prothrombin time >100 seconds and encephalopathy grade 3 or 4 Non-paracetamol cases: Prothrombin time >100 seconds Any THREE of the following: Jaundice to encephalopathy time > 7 days Age < 10 yrs or > 40 yrs Indeterminate or drug-induced causes Bilirubin > 300 μmol/l Prothrombin time > 50 seconds These adverse prognosis criteria predict a mortality rate of ≥ 90%

Observations in fulminant hepatic failure Neurological: Conscious level Pupils Size Equality Reactivity Fundi: Papiledema Plantar responses Cardiorespiratory: Pulse Blood pressure Central venous pressure Respiratory rate Fluid balance: Input: Oral Intravenous Output: Hourly urine output 24 hours sodium output Vomiting Diarrhea

Observations in fulminant hepatic failure Blood analysis: Arterial blood gases Peripheral blood count (including platelets) Creatinine, urea Na, K, HCO3, Ca, Mg Glucose (2-hourly in acute phase). Prothrombin time Infection surveillance: Cultures: Blood Urine Throat Sputum Canula sites Chest radiograph Temperature

Complications of acute hepatic failure Encephalopathy Cerebral edema Respiratory failure Hypotension Hypothermia Infection Bleeding Pancreatitis Renal failure Metabolic: Hypoglycemia Hypokalemia Hypocalcemia Hypomagnesemia Acid-base disturbance

Management Conservative treatment Intensive care unit Role of N-acetylecystein therapy Liver transplantation

Chronic liver failure Chronic liver failure is a syndrome complex that can occur as a consequence of insidious destruction of the hepatocytes. It is more commonly precipitated by a number of events such as variceal hemorrhage or infection. Liver cirrhosis results from progressive and widespread death of liver cells associated with inflammation and fibrosis.

Causes of cirrhosis Any cause of chronic hepatitis Alcohol Primary biliary cirrhosis Primary sclerosing cholangitis Secondary biliary cirrhosis (stones, strictures) Hemochromatosis Wilson’s disease α-1 antitrypsin deficiency Cystic fibrosis

Pathophysiology Recurrent or persistent hepatocyte death: Viral hepatitis Alcohol Prolonged biliary damage or obstruction: Primary biliary cirrhosis Sclerosing cholangitis Post-surgical biliary stricture Stone Persistent blockage to the venous return: Veno-occlusive disease Budd Chiari syndrome

World wide the most common causes of cirrhosis are: Viral hepatitis Prolonged, excessive alcohol consumption

Clinical features of hepatic cirrhosis Hepatomegaly (although the liver may be small) Jaundice Ascites Circulatory changes: Spider telangiectasia Palmar erythema Cyanosis Endocrine changes: Loss of libido Loss of hair Men: gynecomastia, testicular atrophy, impotence Women: breast atrophy, irregular menses, amenorrhea Hemorhagic tendency: Bruises, purpura, epistaxis, menprrhagia Portal hypertension: Splenomegaly Collateral vessels Variceal bleeding Fetor hepaticus Hepatic (portasystemic) encephalopathy Other features: Pigmentation Digital clubbing Low grade fever

Stigmata of chronic liver disease

Gynecomastia in male patient with liver cirrhosis

Ascites with dilated blood vessels

Ascites with everted umbilicus

Spontaneous bruises in patient with cirrohsis

Hepato-splenomegaly

Spider naevi (telangeicatasia) in patient with alcoholic cirrhosis

Spider nevi Spider nevi Notice fading of peripheral capillaries after pressing the central arteriole Spider nevi

Palmar erythema

Duputyrine contracture

Management This includes: Treatment of any cause The maintenance of nutrition Treatment of the complications of liver cirrhosis. Chronic liver failure due to liver cirrhosis can also be treated by orthotopic liver transplantation.

Indications for orthoptopic liver transplantation Cholestatic form of cirrhosis especially that is due to primary biliary cirrhosis Alcoholic cirrhosis (the patient must has capacity for abstinence) Cirrhosis due to hepatitis C virus Rarer indications include: α -1 antitrypsin deficiency Hemachromatosis

Signs of liver failure pointing to transplantation Sustained or increased jaundice Bilirubin > 100 mmol/l in cholestatic diseases like primary biliary cirrhosis Ascites or hepatic encephalopathy not responding readily to medical therapy Hypoalbuminemia Albumin < 30g/l Additional indications: Fatigue & lethargy affecting the quality of life. Intractable itching in cholestatic disease Recurrent variceal bleeding

Main contraindications for liver transplantation Sepsis AIDS Extrahepatic malignancy Active alcohol or other substance misuse Marked cardiorespiratory dysfunction Survival at 1 year after transplantation is about 80% and the prognosis thereafter is good