RCSI Liver Failure 2023 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Liver Failure Class Year 2 Course Pathology Lecturer Dr Eman Aljufairi Date October 2023  LEARNING OUTCOMES Describe acute liver failure and explain the common causes Describe hepatic...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Liver Failure Class Year 2 Course Pathology Lecturer Dr Eman Aljufairi Date October 2023  LEARNING OUTCOMES Describe acute liver failure and explain the common causes Describe hepatic encephalopathy Describe how cirrhosis presents and define decompensated/complicated cirrhosis Summarise the causes and significance of portal hypertension, ascites & varices Classify jaundice Describe the causes and effects of cholestasis  ACUTE LIVER FAILURE Acute liver failure: Acute liver injury with encephalopathy and deranged coagulation (INR >1.5) in a patient with a previously normal liver Acute liver failure is a rare but life threatening syndrome that is due to hepatitis from many causes The causes vary throughout the world. Most involve viral hepatitis but paracetamol overdose is common in UK Histologically there is necrosis of acini involving a substantial part of the liver Severe fatty change may be seen in some cases e.g. in pregnancy, Reye syndrome or after intravenous tetracycline INR: international normalised ratio  CAUSES OF ACUTE HEPATIC FAILURE Virus - hepatitis A, hepatitis B, cytomegalovirus, haemorrhage fever virus Drugs – many e.g. paracetamol, antibiotics, antidepressants, salicylate (Reye syndrome), NSAID, herbal medicines Toxins, organic solvents, mushroom toxin Hepatic failure in pregnancy - acute fatty liver of pregnancy, HELLP syndrome Vascular causes – Budd-Chiari syndrome, portal vein thrombosis Alpha-1 antitrypsin deficiency Wilson disease Malignancy, extensive metastases Heatstroke Viral hemorrhagic fevers (VHF) are a group of viral diseases that affect multiple organ systems in the body and may be accompanied by hemorrhage, or bleeding.  CLINICAL FEATURES OF ACUTE LIVER FAILURE Jaundice Hepatic encephalopathy Fever, vomiting, low blood pressure, low blood glucose Cerebral oedema in 80% of patients Impaired gluconeogenesis Kidney injury – hepatorenal syndrome Acute tubular necrosis  HEPATORENAL SYNDROME Renal impairment secondary to liver disease Haemodynamic effects of portal hypertension reduce renal perfusion, typically a/w ascites Diagnosis of exclusion – no other kidney pathology: ▪ Hypovolaemia/shock (e.g. infection, bleeding) ▪ Acute tubular necrosis (shock or nephrotoxic drugs) Poor prognosis  HEPATIC ENCEPHALOPATHY Spectrum of neuro-psychiatric abnormalities seen in liver dysfunction and/or porto-systemic shunting Functional disturbance of brain, potentially reversible If severe associated with cerebral oedema and cerebral hypoperfusion Classification: Type A: acute liver failure Type B: porto-systemic shunting with normal liver Type C: cirrhosis (= decompensation) Episodic (may be recurrent) HE +/- persistent HE STAGES OF HEPATIC ENCEPHALOPATHY Stages of Hepatic Encephalopathy Confusion Drowsiness Somnolence Coma 1 2 3 4 Stage  STAGES OF HEPATIC ENCEPHALOPATHY Minimal HE may be revealed by psychometric testing Minimal HE can affect social function/work life/behaviour, fitness to drive Minimal HE + stage 1 HE = covert HE, stages 2 to 4 = overt HE PSYCHOMETRIC TESTING FOR COVERT HE B  HEPATIC ENCEPHALOPATHY: PATHOGENESIS Reduced detoxification in liver Portosystemic shunting allows more ammonia to enter the systemic circulation bypassing liver ▪ Detoxification of ammonia occurs more in skeletal muscle/kidney and converted to glutamate (NOT UREA as in liver) ▪ Astrocytes in brain also detoxify ammonia via glutamine synthetase ▪ Increase glutamine in brain brings more water into astrocytes → swelling of astrocytes → cerebral edema & intracranial hypertension  HEPATIC ENCEPHALOPATHY Treatment: Identify and correct precipitating factors ▪ Infection ▪ Bleeding, other causes of hypoperfusion ▪ Dehydration (diuretics) ▪ Drugs (sedatives e.g. opiates, alcohol Reduce ammonia production & absorption ▪ Lactulose (oral or enema) - gut acidification ▪ Non-absorbable antibiotic (e.g. rifaximin) - reduce urease-producing bacteria ▪ Fluids - Dehydration decrease toxins clearence ▪ Stop diuretic therapy  PORTAL HYPERTENSION Classified by level/site of origin of portal hypertension Commonest cause is cirrhosis Pathogenesis in cirrhosis: ▪ Initiated: increased resistance to portal blood flow ▪ Augmented: increased portal blood flow Classification of causes of portal hypertension: Pre-hepatic: portal vein thrombosis Hepatic: ▪ Cirrhosis ▪ Non-cirrhotic e.g. portal tract fibrosis due to schistosomiasis Post-hepatic: obstruction venous outflow from liver (rare)  CONSEQUENCES OF PORTAL HYPERTENSION Porto-systemic collaterals: ▪ Extrahepatic - portal venous and systemic venous circulations anastomose: - Varices (oesophageal and gastric, risk of bleed) - Rectal, periumbilical (‘caput medusae’) Caput medusae Shunting of portal venous blood (reduced Dilated abdominal wall veins liver function) due to collateral drainage through portosystemic Haemodynamic alterations: anastomoses in periumbilical ▪ Ascites and hepatorenal syndrome area Splenomegaly (congestive) ▪ secondary hypersplenism  OESOPHAGEAL AND GASTRIC VARICES OESOPHAGEAL VARICES…LEFT NORMAL, MIDDLE MILD, RIGHT SEVERE 30% of patients with oesophageal varices will have a bleed ▪ Mortality high die, high rate of recurrence Heavy alcohol users ▪ Remember: not all upper GI bleeds are varices OESOPHAGEAL AND GASTRIC VARICES Primary prevention Screen to identify and treat moderate to severe varices before first bleed Endoscopic band ligation and/or non-selective beta blockers Secondary prevention Treat to prevent recurrent bleeding Endoscopic band ligation and/or non-selective beta blockers Variceal bleed: ▪Resuscitate, drugs to reduce portal blood flow ▪Prevent/treat complications (aspiration, infection, HE) ▪Endoscopic treatment of varices by band ligation ▪Endoscopic sclerotherapy not favoured (complications) ▪If above fail: placement of TIPS or surgery  ASCITES IN LIVER DISEASE Sodium retention by the kidneys → increases the volume of extracellular fluid → ascites and edema Increased hydrostatic pressure due to portal hypertension Lower oncotic pressure (to keep fluid in) due to low albumin Abdominal distension Shifting/flank dullness- on percussion, the region of dullness shifts when the patient is turned from supine position to side-lying  ASCITES Cirrhosis commonest cause (>80%) Other causes ▪ Malignancy (ovarian cancer classic, but also GI cancers) ▪ Rare: non-cirrhotic portal hypertension ▪ Rare: heart failure, pancreatitis, TB  ASCITES: MANAGEMENT Paracentesis = tap of ascites fluid ▪ Diagnostic tap – do cell count, microbiology (blood culture bottles), albumin, cytology ▪ Therapeutic tap - diuretic-resistant ascites in cirrhosis ▪ Na+ restriction, diuretics (spironolactone) ▪ Avoid NSAID (risk of acute renal failure and hyponatremia, lowers effect of diuretics) ▪ High index of suspicion for infection (low threshold for paracentesis) ▪ Diuretic-resistant = refractory ascites SPONTANEOUS BACTERIAL PERITONITIS Infection of ascites fluid without evidence of surgically-treatable intra-abdominal cause Infection associated with cirrhosis (E. coli, Klebsiella) Early diagnosis, prompt treatment gives better outcome Subtle/silent presentation Low threshold for paracentesis of ascites fluid Suspect: ▪ Fever, abdominal pain/tenderness, altered mental state ▪ Treat if ascites fluid cell count >250 polys/mm3 ▪ Antibiotic prophylaxis if high risk (e.g., previous SBP or bleed)  LIVER BLOOD TESTS Related to liver cell (hepatocellular) damage: ▪ Transaminases (ALT, AST) Related to obstruction to bile flow (cholestasis): ▪ Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) ▪ Bilirubin Related to liver function ▪ Bilirubin – abnormality not liver or biliary tract specific ▪ Albumin (long half life, indicator of chronic damage) ▪ Coagulation function (PT/INR) (clotting factors have short half life– better indicator of acute damage)  HEPATOCELLULAR DAMAGE: LIVER ENZYMES Alanine transaminase sensitive/specific marker for hepatocellular damage Aspartate transaminase less specific, also in muscle, myocardium, kidney Both leak from damaged hepatocytes ▪ Level of rise is poor correlation with severity/prognosis ▪ Very high in acute hepatocellular damage ▪ May be only mildly elevated or normal despite chronic liver disease ▪ AST/ALT ratio can be informative - Usually 2 suggests alcohol-related damage  AST/ALT RATIO Ratio of AST to ALT made by hepatocytes is approximately 2.5:1. AST is removed from serum by the liver sinusoidal cells twice as quickly, so resulting serum levels are about equal in healthy individuals BUT in conditions with chronic, constant hepatocyte damage (e.g., alcoholic hepatitis, hepatocellular carcinoma) and during early- stage acute liver damage (e.g. viral hepatitis) the serum levels of AST and ALT reflect levels closer to background in hepatocytes An AST/ALT ratio >5 indicates extrahepatic source of AST  OBSTRUCTIVE (CHOLESTATIC) LIVER ENZYMES Alkaline phosphatase (ALP Situated on hepatocyte border of bile canaliculi Hepatocytes react to obstruction to bile flow by leaking alkaline phosphatase Other sources: bone, placenta Gamma-glutamyl transferase (GGT) Very sensitive but not specific Good for correlating with elevated alkaline phosphatase to demonstrate that ALP is of liver origin Also induced by alcohol, drugs. Isolated rise not usually investigated ADDITIONAL TESTS TO ESTABLISH CAUSE Viral serology –Hepatitis viruses, sometimes EBV, CMV Iron storage status - Transferrin saturation /% sat. of total iron binding capacity and Ferritin Autoimmune (ANA, SMA, anti-LKM, AMA, pANCA) and immunoglobulin G and M levels Copper metabolism (Wilson disease, very rare) – Caeruloplasmin Impaired transport of copper in Wilson disease decreases copper secretion into the bile, thus causing the copper overload in the liver. Impaired transport also interferes with incorporation of copper into caeruloplasmin, thus decreasing serum levels of caeruloplasmin. Alpha-1-antitrypsin levels (A1AT deficiency, very rare) BILIRUBIN, JAUNDICE AND CHOLESTASIS Bilirubin normal 50umol/l “Biochemical jaundice” >18