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66. Methods of Complex Resuscitation Measures and Intensive Therapy for Liver Dysfunction - Acute Liver Failure
Authors:
1. Khalbaev Kahraman Galatovich
2. Abhay Raj Chauhan, Group 9
3. Md Nadeem, Group 12
(1, Surgeon, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
2, Student, Group : 9 , International Medical Faculty, Osh State University, Osh, Kyrgyz Republic)
3, Student Group : 12 , International Medical Faculty, Osh State University, Osh , Kyrgyz Republic)
Abstract
Acute liver failure (ALF) is a rare, life-threatening syndrome characterized by rapid loss of hepatic function in a patient without preexisting cirrhosis, usually with development of coagulopathy and hepatic encephalopathy. Management requires immediate critical-care resuscitation, organ-support strategies, disease-specific therapies, early recognition of complications (cerebral edema, sepsis, coagulopathy, renal failure), and timely consideration for liver transplantation. This article reviews the definitions and types of ALF, pathogenesis, drugs of choice and their mechanisms, and detailed intensive care resuscitation and management strategies used in contemporary practice. (pmc.ncbi.nlm.nih.gov)
Definition and types
Definition. Acute liver failure is defined as the rapid development (usually within days to 26 weeks) of severe hepatic injury with impaired synthetic function (INR ≥1.5) and any degree of hepatic encephalopathy in a patient without chronic liver disease. (bspghan.org.uk)
Types / common etiologies.
• Acetaminophen (paracetamol) toxicity — the commonest identifiable cause in many regions.
• Viral hepatitis (A, B, E; less commonly other viruses).
• Drug-induced liver injury (antibiotics, antituberculars, herbal supplements).
• Autoimmune hepatitis.
• Wilson disease, Budd–Chiari syndrome, ischemic hepatitis (shock liver).
• Indeterminate/cryptogenic.
Etiology influences prognosis and specific therapy (e.g., NAC for acetaminophen; chelation/urgent transplant for Wilson disease). (pmc.ncbi.nlm.nih.gov)
Pathogenesis (brief)
ALF results from massive or sub-massive hepatocellular necrosis and/or apoptosis leading to loss of synthetic (coagulation factors, albumin), metabolic (ammonia clearance, drug metabolism), detoxification, and immunologic functions. Downstream consequences include hyperammonemia and cerebral edema, systemic inflammatory response with vasodilatation/hypotension, renal failure (hepatorenal physiology and acute tubular injury), coagulopathy, and high susceptibility to infections. Cellular mechanisms vary by cause (e.g., oxidative metabolite formation and glutathione depletion in acetaminophen toxicity; immune-mediated injury in autoimmune hepatitis; copper-induced oxidative injury in Wilson disease). (pmc.ncbi.nlm.nih.gov)
Prognostication / criteria for transplant referral
Early identification of patients unlikely to recover is essential. Widely used tools include the King’s College Criteria (separate for acetaminophen and non-acetaminophen etiologies) and other clinical risk scores; however, no score is perfect and transplant assessment should be individualized and done early with a transplant center. (pmc.ncbi.nlm.nih.gov)
Overall approach in the ICU — initial resuscitation (ABCs) and principles
1. Immediate stabilization and ICU admission. Any patient with suspected ALF + encephalopathy or coagulopathy requires ICU-level care and early contact with a liver transplant service. (bspghan.org.uk)
2. Airway and breathing. Protect the airway in patients with decreased consciousness (GCS ≤8, rising ammonia, agitation/combative) — early endotracheal intubation with lung-protective ventilation is recommended because aspiration and uncontrolled intracranial pressure (ICP) can be catastrophic. Avoid hypercapnia; normocapnia or slight hypocapnia may reduce ICP transiently but be cautious as prolonged hyperventilation has harms. (pmc.ncbi.nlm.nih.gov)
3. Circulation and hemodynamics. Treat hypotension aggressively with fluid resuscitation guided by dynamic assessments; use vasopressors (norepinephrine first-line) for persistent vasodilatory shock. Avoid excessive fluid that worsens cerebral edema. Monitor for lactic acidosis and tissue hypoperfusion. (pmc.ncbi.nlm.nih.gov)
4. Monitoring. Hourly neuro checks, invasive arterial pressure monitoring, central venous access for vasoactive drugs, frequent labs (INR, ammonia, lactate, electrolytes, glucose), and continuous temperature monitoring. Consider invasive ICP monitoring only at specialized centers and selected patients because of bleeding risk; clinical surveillance and imaging are commonly used. (Ovid)
Disease-specific therapies — drugs of choice and mechanisms
1. N-acetylcysteine (NAC)
• Indications: Antidote for acetaminophen overdose; also used in early non-acetaminophen ALF because of potential antioxidant, vasodilatory and microcirculatory benefits and improved transplant-free survival described in several studies. Start as early as possible when acetaminophen toxicity suspected; many guidelines also recommend NAC for non-acetaminophen ALF.
• Mechanism: Replenishes glutathione, enhances hepatic detoxification of N-acetyl-p-benzoquinone imine (NAPQI) in acetaminophen toxicity, and exerts antioxidant and hemodynamic effects.
• Drug of choice / regimen: Intravenous NAC regimens vary (e.g., loading dose followed by infusion over 20–72 h depending on protocol). Local protocol and toxicology guidance should be followed. (cdn.who.int)
2. Antivirals / Immunosuppression / Chelation / Disease-targeted therapy
• Acute hepatitis B: Antiviral therapy (entecavir/tenofovir) may be indicated in hepatitis B–related ALF.
• Autoimmune hepatitis: High-dose corticosteroids may be attempted when autoimmune hepatitis is strongly suspected, but response is variable and transplant assessment should proceed in parallel.
• Wilson disease: Chelation (e.g., penicillamine) is not adequate in fulminant Wilson disease — urgent transplant is often required; plasmapheresis may be temporizing by removing copper and toxins. (AASLD)
3. Antimicrobials
• Empirical broad-spectrum antibiotics should be considered early if infection is suspected; ALF patients are at high risk of bacterial and fungal infections and culture-directed therapy should follow. Prophylactic routine antibiotics are not universally recommended but a low threshold for starting therapy is appropriate in unstable patients. (pmc.ncbi.nlm.nih.gov)
Management of major complications
A. Cerebral edema & intracranial hypertension (ICH)
• Risk: Most common in younger ALF patients and with hyperacute presentations, high arterial ammonia and severe encephalopathy (grade III–IV). ICH is the leading immediate cause of death in ALF. (Ovid)
• Monitoring: Frequent neuro assessment; consider ICP monitoring in specialized centers (weigh bleeding risk). Serial CT/MRI if indicated. (Ovid)
• Medical measures (first line):
o Head-of-bed elevation (30°), neutral neck position.
o Osmotherapy: IV mannitol (0.5–1 g/kg bolus) or hypertonic saline (bolus or infusion) to reduce ICP; randomized trials and observational data support both approaches — selection individualized. Avoid repeated mannitol if serum osmolality too high or renal impairment. (PubMed)
o Control of hyperammonemia: Lactulose, rifaximin (enteric ammonia reduction), and extracorporeal removal (CRRT or hemoperfusion) for severe hyperammonemia. (Frontiers)
o Temperature control (target normothermia to mild hypothermia in select cases) and sedation to reduce metabolic demand. (Ovid)
• Rescue measures: Escalation to surgical decompression is rarely feasible; consider extracorporeal liver support and urgent transplant where possible. (Ovid)
B. Coagulopathy and bleeding risk
• Principle: ALF causes reduced synthesis of clotting factors causing prolonged INR, but routine correction of INR is not indicated unless there is active bleeding or an invasive procedure planned. Use targeted blood component therapy guided by clinical bleeding, point-of-care coagulation testing (TEG/ROTEM) where available. Vitamin K should be given if deficiency possible. Platelets, FFP, cryoprecipitate as clinically indicated. Antifibrinolytics (tranexamic acid) may be used selectively when hyperfibrinolysis suspected. (pmc.ncbi.nlm.nih.gov)
C. Renal failure and renal support
• Acute kidney injury is common (hepatorenal physiology, ATN). Continuous renal replacement therapy (CRRT) is frequently preferred over intermittent hemodialysis in hemodynamically unstable ALF patients and when cerebral edema is a concern (slower solute/volume shifts). CRRT may also help remove ammonia and inflammatory mediators though evidence for survival benefit is evolving. (pmc.ncbi.nlm.nih.gov)
D. Hemodynamic support
• Vasopressors: Norepinephrine as first-line for vasodilatory shock; vasopressin analogues may be added. Avoid excessive volume that can worsen cerebral edema. Correct underlying metabolic derangements. (pmc.ncbi.nlm.nih.gov)
E. Metabolic derangements and nutrition
• Glucose control: Hypoglycemia is common—maintain euglycemia with IV dextrose as indicated.
• Electrolytes: Rapid correction of hyponatremia/hypernatremia and potassium abnormalities. Avoid abrupt sodium changes if cerebral edema is present.
• Nutrition: Early enteral nutrition (unless contraindicated) with protein not absolutely restricted in ALF — adequate calories and protein to limit catabolism; specialist nutrition consult recommended. (pmc.ncbi.nlm.nih.gov)
F. Immunity and infection control
• Prophylactic antifungals/antibiotics are not standard; but ALF patients are immunocompromised and have high nosocomial infection rates — low threshold for cultures and targeted treatment. Maintain strict infection control and line care. (pmc.ncbi.nlm.nih.gov)
Extracorporeal liver support and plasma therapies
• Therapeutic plasma exchange (TPE): May provide temporary improvement by removing toxins, cytokines, and replacing coagulation factors; data suggest some benefit as bridge to transplant or spontaneous recovery in selected patients. (pmc.ncbi.nlm.nih.gov)
• Molecular adsorbent recirculating system (MARS) and other liver support devices: Offer detoxification but randomized data for survival benefit are mixed; these modalities are considered bridges to transplant or recovery in specialized centers. (pmc.ncbi.nlm.nih.gov)
When to list for liver transplantation
• Urgent transplant referral should be made early when criteria for poor prognosis are met (e.g., King’s College Criteria and clinical deterioration). Rapid coordination with a transplant center is critical because many candidates deteriorate rapidly. Bridging measures (CRRT, TPE, extracorporeal support) are used while arranging transplant. (pmc.ncbi.nlm.nih.gov)
Practical algorithm (summary steps)
1. Admit to ICU, immediate contact with transplant center. (bspghan.org.uk)
2. Secure airway if decreased consciousness; protect against aspiration and manage ventilation to minimize ICP elevation. (Ovid)
3. Hemodynamic support: guided fluids, norepinephrine if needed. (pmc.ncbi.nlm.nih.gov)
4. Start disease-specific therapy (NAC if acetaminophen or suspected; antivirals/corticosteroids as appropriate). (cdn.who.int)
5. Monitor and treat complications — cerebral edema (osmotherapy/CRRT), renal failure (CRRT), coagulopathy (targeted transfusion/TEG guidance), infections (early cultures/antibiotics). (europepmc.org)
6. Early prognostication and decision for transplant listing. (pmc.ncbi.nlm.nih.gov)
Key practical points and pearls
• Start NAC early when acetaminophen ingestion is suspected — it is inexpensive and low risk and may improve outcomes even in non-acetaminophen ALF. (cdn.who.int)
• ICP/crania care is central in severe encephalopathy — small changes in management may determine survival or catastrophic herniation. (Ovid)
• Do not correct INR routinely for laboratory abnormality alone; correct for bleeding or procedures and use point-of-care coagulation when available. (pmc.ncbi.nlm.nih.gov)
• Engage transplant services early—timing is everything in ALF. (pmc.ncbi.nlm.nih.gov)
Conclusion
Acute liver failure remains a high-mortality condition requiring rapid diagnosis, immediate ICU resuscitation, organ-support measures, targeted disease therapy (e.g., NAC, antivirals, steroids when indicated), and early transplant assessment. Multidisciplinary care in a liver-capable ICU, frequent reassessment, and use of extracorporeal support when available are core components of contemporary management.
References
1. American Association for the Study of Liver Diseases (AASLD). The Management of Acute Liver Failure. AASLD practice guideline. (AASLD)
2. European Association for the Study of the Liver (EASL). Clinical Practice Guidelines — Management of Acute Liver Failure. 2017/2022 updates. (EASL-The Home of Hepatology.)
3. Tujios S, et al. Management of Acute Liver Failure: Update 2022. Hepatology review. (pmc.ncbi.nlm.nih.gov)
4. World Health Organization (WHO) review — N-acetylcysteine for acute liver failure. (cdn.who.int)
5. Amjad W, et al. N-acetylcysteine in non-acetaminophen-induced acute liver failure. 2021 review (PMC). (pmc.ncbi.nlm.nih.gov)
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20. Fernández J, et al. Acute liver failure: A practical update. 2024 review. (sciencedirect.com)
21. European PMC / PubMed entry for MAHAL trial and related cerebral edema studies. (europepmc.org)
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26. PMC: Beyond KCH selection and options in acute liver failure (Bernal/Wendon commentary on prognostication). (pmc.ncbi.nlm.nih.gov)
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29. Cochrane CENTRAL: Hypertonic saline vs mannitol and related meta-analyses for raised ICP in brain injury — evidence relevant to ALF cerebral edema management. (Cochrane Library)
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