see also: [[Hepatitis]], [[Pre-eclampsia#HELLP|HELLP]] see: [Hayes' Acute liver failure](x-devonthink-item://38D3B113-38CB-47F4-8461-F5491C6A5047) > acute hepatic dysfunction that leads to encephalopathy AND coagulopathy > > hepatic dysfunction / jaundice / ↓ albumin, encephalopathy, coagulopathy ## Causes **Infectious** - [[Hepatitis]] (eg A-E) - CMV - EBV - toxoplasmosis **Non-infectious** - cirrhosis ([[Alcohol-related disease|EtOH]] or NASH) - autoimmune hepatitis - toxin ingestion - [[Paracetamol overdose]] - mushrooms - allopurinol - amanita phalloides mushroom - isoniazid - halothane / volatile anaesthetics (inhaled) - sulfa - MDMA - [[Solvents]] - pregnancy -- a/w [[Pre-eclampsia|Eclampsia]] and HELLP - *Budd chiari syndrome* (acute hepatic vein occlusion) - Wilson's disease - Reye's syndrome in children - haemochromatosis - severe [[Heat-related illness|hyperthermia]] of any cause - severe hypotension of any cause **insults which may precipitate acute deterioration in pt with chronic liver disease:** - [[Spontaneous Bacterial Peritonitis]] - hepatotoxins (alcohol, paracetmaol, nSAIDS, abx (fluclox and augmentin), gent, IV contrast - dehydration - UGI B - uraemia ### Causes in children - \<1 year - tyrosinemia - mitochondrial defects - urea cycle disorder - fructose intolerance - galactosemia - viral hepatitis - neonatal haemochromatosis - \>1 year - idiopathic (45%) - viral - drug-related ## Hepatic encephalopathy grading - Gr 1 - sleepy, confusions, nightmares - Gr 2 - drowsiness, inappropriate behaviour - Gr 3 - stupor, confusion, agitation - Gr 4 - coma, increased reflexes, up-going plantars ## Prognostic factors - age <10 or > 40 - bilirubin > 200 mmol/L - PT >100 s - longer duration of jaundice # Investigations - FBC - check eosinophil count (can be ↑ in autoimmune hepatitis or drug allergy hepatitis) - [[Paracetamol overdose|Paracetamol level]] - LDH -- often ↑ in malignancy - CK and urinary myoglobin -- ↑ in hyperthermic injuries - Hep A Ix -- Anti-HAV, Hep A IgM - Hep B Ix -- Hep B C Ab, Surface antigen, Hep B DNA - LFTs -- AST may only be mod elevated at tiem fo symptoms - Ammonia -- ==does not correlate well with level of coma== - coags > Hep C rarely causes *acute* liver failure ## Special Cases ### Pregnancy - neutrophilia can happen in acute fatty liver of pregnancy - [[thrombocytopaenia]] (part of [[Pre-eclampsia#HELLP|HELLP]] syndrome) ### Rare causes of heptatitis - Wilson's disease → ↑ urinary copper, ↓ ceruloplasmin, haemolysis - returned traveller → Dengue, Malaria, yellow fever - autoimmune hepatitis → anti smooth muscle antibodies ### Immunocompromised patient - EBV - CMV - HSV - Varicella ### Thrombophilia patient - consider Budd-Chiari syndrome (acute hepatic vein occlusion) - noted in pts with [[thrombophilia|hypercoaguability]] disorders eg antiphospholipid, paroxysmal nocturnal haemoglobinuria, Factor V Leiden. - rarer causes are protein C and S def, antithrombin III def - Secondary Budd Chiari is rare; can be fro tumor or polycistic kidney disease # management - Cerebral oedema - mannitol 0.3 - 0.4 g/kg - elevate head of bed - lactulose - +/- flumazanil - +/- ICP monitoring - clotting abnormalities - correct w/ Vitamin K, FFP if bleeding - renal failure - albumin replacement - terlipressin - haemofiltration if required | Complication | Assessment | Management | | ------------------------------------------------------------------------------------------------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | [[#Hepatic encephalopathy grading\|Hepatic Encephalopathy]] | - grade<br>- ↑ ammonia | - support airway if needed<br>- *lactulose* 30mL for 2 hours then QID (1mL/kg up to 30 mL in child)<br>- ↓ protein diet<br>- +/- NAC | | [[Spontaneous Bacterial Peritonitis\|SBP]] | [[Spontaneous Bacterial Peritonitis#ascites tap\|Ascitic tap]]:<br>- WCC > 250<br>- ascites: serum LDH ≥ 0.5 <br>- glucose < 2.8<br>- protein > 10<br>- +ve leucocyte esterase<br>- ph < 7.35 | Ceftriaxone 2g od | | coagulopathy | - INR reflects hepatic synthetic failure (if pt hasn't had warfarin)<br>- many pts with cirrhosis have a "rebalanced" coagulation (i.e. ↓ anticoagulants like protein C and protein S), so hard to evaluate overall bleeding risk based on INR alone<br>- consider [[TEG, ROTEM, coagulation studies\|TEG/ROTEM]]<br>- look for sources of bleeding | - +/- [[Warfarin, DOAC, heparin reversal#vitamin K\|vitamin K]] 10mg daily<br>- [[FFP]], platelets, and/or recombinant factor VIIa if bleeding or prior to procedures | | [[Upper GI Bleed#Variceal bleeding treatment\|Bleeding Oesophageal varicies]] | look for [[Upper GI Bleed\|UGIB]] and melena | - [[Massive blood transfusion\|MTP]]<br>- [[FFP]]<br>- +/- terlipressin 2mg IV Q4H then 1mg IV Q4H OR [[octreotide]] 50mcg bolus then 50mcg/h infusion<br>- ceftriaxone 1g<br>- IV PPI 80mg | | [[Alcohol Withdrawal Syndrome]] | see AWS score | - thiammine and oxazepam 15-30mg q2H max 210 mg<br>- diazepam not recomended in liver failure | | [[Acute Renal Failure]] | creatinine | - supportive/dialysis<br>- replace albumin<br>- avod nephrotoxins (NSAIDs, gentamicin, IV contrast) | | [[hypoglycaemia]] | 10 or 50% dextrose | | | [[hypokalemia\|hypo-k]] / [[hyponatremia\|hypo-na]] / [[hypophosphataemia\|hypo-PO4]] / [[Hypomagnesemia\|hypo-mg]] | - review for [[Anorexia#Refeeding syndrome\|Refeeding syndrome]] | - replace electrolytes and optimise volume state | | resp failure | from pleural effusions, intrapulmonary shunting, ascites causing atelectasis, aspiration, or ARDS | O2, NIV, intubation, etc<br>- minimise PEEP to maximise splanchnic blood flow | ## Bleeding risk vs thrombosis > Thank you Dr. Drey for below explanation: Patients with end-stage liver disease are paradoxically at an *increased* risk of thrombosis despite presenting with thrombocytopenia and elevated INR, both of which typically suggest a bleeding tendency. This counterintuitive phenomenon arises from a complex interplay of factors that collectively create a hypercoagulable state: 1. Endothelial Dysfunction: Liver disease often leads to damage of the endothelial cells lining blood vessels, resulting in an imbalance between procoagulant and anticoagulant factors. This dysfunction promotes clot formation. 2. Impaired Synthesis of Coagulation Regulators: While the liver's diminished capacity reduces production of clotting factors (leading to elevated INR), it also decreases synthesis of natural anticoagulants such as protein C, protein S, and antithrombin III. This reduction skews the hemostatic balance toward thrombosis. 3. Elevated von Willebrand Factor (VWF) Levels: ESLD is associated with increased levels of VWF, a protein that facilitates platelet adhesion. Concurrently, levels of ADAMTS13, the enzyme responsible for cleaving VWF, are reduced. This imbalance enhances platelet aggregation and thrombus formation. 4. Platelet Function Alterations: Although platelet counts are reduced in ESLD, the remaining platelets may exhibit heightened reactivity. This compensatory mechanism can inadvertently increase the risk of clot formation. 5. Portal Hypertension and Collateral Circulation: Chronic liver disease often leads to portal hypertension, which stimulates the development of collateral blood vessels. These vessels are prone to thrombosis due to altered blood flow dynamics. Collectively, these factors contribute to a rebalanced yet fragile hemostatic system in ESLD patients, where the risk of thrombosis is heightened despite laboratory indicators that traditionally suggest bleeding risks. > [!references]- > Ton Lisman, Robert J. Porte, > Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases, > Research and Practice in Thrombosis and Haemostasis, > Volume 1, Issue 2, > 2017, > Pages 150-161, > ISSN 2475-0379, > https://doi.org/10.1002/rth2.12028. > (https://www.sciencedirect.com/science/article/pii/S2475037922021677) > > Bente P. van den Boom, Ton Lisman > Pathophysiology and management of bleeding and thrombosis in patients with liver disease > International Journal of Laboratory Hematology: Volume 44, Issue S1 > 21 April 2022 > Pages 79-88 > https://doi.org/10.1111/ijlh.13856 > (https://onlinelibrary.wiley.com/doi/full/10.1111/ijlh.13856) > > Flores B, Trivedi HD, Robson SC, Bonder A. > Hemostasis, bleeding and thrombosis in liver disease. > J Transl Sci. 2017 May;3(3):10.15761/JTS.1000182. > doi: 10.15761/JTS.1000182. > Epub 2017 Mar 4. > (https://pmc.ncbi.nlm.nih.gov/articles/PMC6136435/) >