Difference between revisions of "Hepatic failure"

Jump to: navigation, search
(Epidemiology and Demographics)
(Epidemiology and Demographics)
(One intermediate revision by the same user not shown)
(No difference)

Revision as of 18:11, 2 August 2020

Hepatic failure
ICD-10 K72.9
DiseasesDB 5728
MeSH D017093

WikiDoc Resources for Hepatic failure

Articles

Most recent articles on Hepatic failure

Most cited articles on Hepatic failure

Review articles on Hepatic failure

Articles on Hepatic failure in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Hepatic failure

Images of Hepatic failure

Photos of Hepatic failure

Podcasts & MP3s on Hepatic failure

Videos on Hepatic failure

Evidence Based Medicine

Cochrane Collaboration on Hepatic failure

Bandolier on Hepatic failure

TRIP on Hepatic failure

Clinical Trials

Ongoing Trials on Hepatic failure at Clinical Trials.gov

Trial results on Hepatic failure

Clinical Trials on Hepatic failure at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Hepatic failure

NICE Guidance on Hepatic failure

NHS PRODIGY Guidance

FDA on Hepatic failure

CDC on Hepatic failure

Books

Books on Hepatic failure

News

Hepatic failure in the news

Be alerted to news on Hepatic failure

News trends on Hepatic failure

Commentary

Blogs on Hepatic failure

Definitions

Definitions of Hepatic failure

Patient Resources / Community

Patient resources on Hepatic failure

Discussion groups on Hepatic failure

Patient Handouts on Hepatic failure

Directions to Hospitals Treating Hepatic failure

Risk calculators and risk factors for Hepatic failure

Healthcare Provider Resources

Symptoms of Hepatic failure

Causes & Risk Factors for Hepatic failure

Diagnostic studies for Hepatic failure

Treatment of Hepatic failure

Continuing Medical Education (CME)

CME Programs on Hepatic failure

International

Hepatic failure en Espanol

Hepatic failure en Francais

Business

Hepatic failure in the Marketplace

Patents on Hepatic failure

Experimental / Informatics

List of terms related to Hepatic failure

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Liver failure; fulminating hepatic failure

Overview

Liver failure is the inability of the liver to perform its normal synthetic and metabolic function as part of normal physiology.

Historical Perspective

Classification

Three forms are recognized:

  • Chronic liver failure - When liver failure occurs as a result of cirrhosis. It usually means that the liver has been failing gradually for some time (more than 6 months), possibly for years. This is called chronic liver failure or End-stage Liver Disease (ESLD).

Pathophysiology

  • The pathophysiology of cerebral edema and hepatic encephalopathy is seen in Acute Liver Failure is multi-factorial and includes altered blood-brain barrier secondary to inflammatory mediators leading to microglial activation, accumulation of glutamine secondary to ammonia crossing the BBB and subsequent oxidative stress leading to depletion of adenosine triphosphate (ATP) and guanosine triphosphate (GTP). This ultimately leads to astrocyte swelling and cerebral edema.
  • The pathogenesis of Acute-on-chronic liver failure is unclear but many theories are proposed in such as Neutrophilic dysfunction that increases the risk of infections, Circulating changes, oxidative stress, and Toxin Hypothesis.

Causes

Causes for Acute liver failure[5][10]:

Category Etiology of Acute liver failure
Viruses
Drugs
Metabolic diseases
Toxins
Vascular diseases
Malignant Infiltration
Autoimmune disease
Indeterminate
  • Unknown

Causes for chronic liver failure:

Differential Diagnosis

Epidemiology and Demographics

  • Acute liver failure affects approximately 2,000–3,000 Americans each year. Drug-induced hepatotoxicity occurs for more than 50% of acute liver failure cases including Acetaminophen toxicity (42%) and idiosyncratic drug reactions. Nearly 15% of cases remain of indeterminate etiology.[5][13][14]

Natural History, Complications and Prognosis

Natural History

Clinical features in Hepatic failure

  • Encephalopathy, classically graded on a scale of 1 to 4
  • Intracranial hypertension and cerebral edema
  • Hemodynamic changes and circulating failure such as Hypotension, Cardiac arrhythmia due to electrolyte abnormalities
  • Infection
  • Renal failure
  • Hematologic abnormalities

Complications

  • Neurological complications, increased intercranial pressure, cerebral edema, Abnormal hemostasis, and bleeding complications, hepatorenal syndrome, multiorgan failure,infection.[16][17]

Prognosis

prognosis of Acute liver failure

  • The prognosis in patients with acute liver failure is highly variable and depends on the etiology, subtypes (hyperacute, acute,...), age, and the degree of coagulopathy. Determining the prognosis for these patients is vital. Liver transplantation has dramatically improved short-term survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment.[18]
  • Identification of patients who will eventually require liver transplantation should be addressed through continuous medical assessment.The King's College Criteria (KCC) may be used.This scoring system is generally quite accurate in predicting poor prognosis and, along with clinical judgment, is useful for ensuring timely transfer to a liver transplant center.[14][19][18]

Prognosis of chronic liver failure

  • Patients with compensated cirrhosis have a median survival of 6–12 years. Decompensation and end stage liver disease occurs in 5%–7% annually; median survival then declines to 2 years.[20]
  • Several retrospectives studies have reported in patients with end-stage liver disease, the MELD score to have similar predictive value to the king's college criteria for mortality associated with ALF.

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies | Clinical prediction rules

History and symptoms

Social history

  • History of alcohol use:
    • Amount
    • Duration
  • History of illicit drug use
  • History of unprotected sexual intercourse
  • History of recent travel

Past Medical history

Menstrual history

Family history

Medication history

  • History of use of all medications used over the last 6 months, including prescription medications, over-the-counter agents, herbal supplements, wild mushrooms, or other alternatives/complementary therapies;

Symptoms

Physical Examination

  • Complete physical examination should be performed.
  • Assessment of mental status, the neurologic examination, and the fundoscopic examination in patients with Hepatic Encephalopathy of stage 2 or greater.

Neuromuscular

Laboratory Findings


laboratory tests are recommended for establishing an etiology and determining the prognosis of Acute liver failure:

Imaging

  • Abdominal ultrasound with Doppler to confirm portal and hepatic vein patency
  • Non-contrast computed tomography (CT) scan of the head for patients with Hepatic encephalopathy

Treatment

Effective medical Therapies for specific causes of liver failure and hepatic encephalopathy. Medical therapy includes antidotes to reverse the effect of Acute liver failure and various medications to Reduce ICP[14]

  • Acetaminophen intoxication Oral NAC: 140 mg/kg loading dose, then 70 mg/kg every 4 hours until discontinued by hepatology or transplantation surgery attending physician

IV NAC: 150 mg/kg loading dose, then 50 mg/kg IV over 4 hours, then 100 mg/kg IV over 16 hours as a continuous infusion until discontinued by hepatology or transplantation surgery attending physician

  • Amanita phalloides(mushroom intoxication) Charcoal: via NGT every 4 hours alternating with silymarin, Penicillin G: 1 g/kg/day IV and NAC (Dosing as for acetaminophen

overdose.),Silymarin: 300 mg PO/NGT every 12 hours,Legalon-SIL: 5 mg/kg/day IV (given in 4 divided doses) or 5 mg/kg IV loading dose followed by 20 mg/kg/day via continuous infusion

Treatment of complications:

Management of Hepatic Encephalopathy

Even minimal hepatic encephalopathy may benefit from treatment.[23]

Traditionally it has been presumed that excessive protein intake leads to increased generation of ammonia, which, in the setting of severe liver impairment, will accumulate and worsen the hepatic encephalopathy. While very large protein loads (such as gastrointestinal hemorrhage, because blood is rich in protein) are known to precipitate encephalopathy, the need for patients with chronic liver disease patients to be protein restricted has been disproven.[24] Indeed, because chronic liver disease is a catabolic state, a protein restricted diet would lead to protein malnutrition and a negative nitrogen balance.

Concomitant hypokalemia should be corrected as hypokalemia increases renal ammonia production and may promote conversion of ammonium into ammonia which can cross the blood-brain barrier.[25]

Lactulose is a compound that will cause osmotic diarrhea, thus lessening the time available for intestinal bacteria to metabolize protein into ammonia within the bowel. Further, it acidifies the environment in the lumen of the bowel. This promotes the conversion of lumenal ammonia (NH3) to ammonium (NH4+) which, by which virtue of its net charge, should be less readily absorbed into the bloodstream from the bowel lumen. Despite this theoretical and appealing mechanism, a meta-analysis of randomized controlled trials by the international Cochrane Collaboration found benefit, but suggests there is little evidence for its preferred use to treat hepatic encephalopathy.[26] Indeed, any drug (laxative) which speeds up transit through the bowel thereby lessening the time available for bacteria to metabolize protein into ammonia, works just as well.

Lactulose can be given rectally for patients who cannot take oral medications.[27][28][29] One regimen is 300 mL (200 gm) of lactulose syrup (10 gm/15 ml) in 1 L of water which is retained for 1 hour, with the patient in the Trendelenburg position.[30]

Antibiotics may be given to kill bacteria present in the bowel thereby decreasing bacterial conversion of protein to ammonia (and other toxic substances) there. Although effective, neomycin, a non-absorbable aminoglycoside antibiotic, is essentially contraindicated; it has been found that a proportion of the ingested dose is indeed absorbed due to increased gut permeability, thus increasing the risk of renal failure and hearing loss (i.e. two of the potential side effects of neomycin). The former side-effect, in particular, is especially worrisome given the already increased likelihood of renal failure in cirrhosis and portal hypertension (i.e. hepatorenal syndrome). Metronidazole has also been studied.[31]

Rifaximin , receieved orphan drug status in 2005 for the treatment of hepatic encephalopathy. In contrast to neomycin, its tolerability profile is comparable to placebo.[32] Multiple clinical trials have demonstrated that rifaximin at a dose of 400 mg taken orally 3 times a day was as effective as lactulose or lactilol at improving hepatic encephalopathy symptoms.[33] Similarly, rifaximin was as effective as neomycin and paromomycin.[34] Rifaximin was better tolerated than both the cathartics and the other nonabsorbable antibiotics. A number of concerns remain regarding rifaximin's role in the treatment of hepatic encephalopathy. It remains to be determined if rifaximin can improve severe encephalopathy symptoms as rapidly as lactulose. There are also concerns regarding the cost-effectiveness of the medication.

A meta-analysis of randomized controlled trials by the international cochrane collaboration found benefit from flumazenil.[35] The doses of flumazenil varied around a median of 2 milligrams over 10 minutes: flumazenil was given as a continuous infusion (12 trials), preceded by bolus injections in two trials. One trial used only bolus injections. Patients received flumazenil at a total dose ranging from 0.2 to 19.5 milligram (median 2 milligram). The median duration of treatment was 10 minutes (range one minute to 72 hours)'. However, the benefit was short.

L-ornithine-L-aspartate stimulates the urea cycle, and has shown encouraging results in randomized controlled trials.[36][37][38]

Contraindicated medications

Hepatic coma is considered an absolute contraindication to the use of the following medications:

Recommendations for the Treatment of Hepatic Encephalopathy (DO NOT EDIT)

  1. In early stages of encephalopathy, lactulose may be used either orally or rectally to effect a bowel purge, but should not be administered to the point of diarrhea, and may interfere with the surgical field by increasing bowel distention during liver transplantation.
  2. Patients who progress to high-grade hepatic encephalopathy (grade III or IV) should undergo endotracheal intubation.
  3. Seizure activity should be treated with phenytoin and benzodiazepines with short half-lives. Prophylactic phenytoin is not recommended.
  4. Intracranial pressure (ICP) monitoring is recommended in ALF patients with high-grade hepatic encephalopathy, in centers with expertise in ICP monitoring, in patients awaiting and undergoing liver transplantation.
  5. In the absence of ICP monitoring, frequent (hourly) neurological evaluation is recommended to identify early evidence of intracranial hypertension.
  6. In the event of intracranial hypertension, a mannitol bolus (0.5-1.0 gm/kg body weight) is recommended as first-line therapy; however, the prophylactic administration of mannitol is not recommended.
  7. In ALF patients at highest risk for cerebral edema (serum ammonia >150 µM, grade 3/4 hepatic encephalopathy, acute renal failure, requiring vasopressors to maintain mean arterial pressure [MAP]), the prophylactic induction of hypernatremia with hypertonic saline to a sodium level of 145-155 mEq/L is recommended.
  8. Short-acting barbiturates and the induction of hypothermia to a core body temperature of 34-35ºC may be considered for intracranial hypertension refractory to osmotic agents as a bridge to liver transplantation.
  9. Corticosteroids should not be used to control elevated ICP in patients with ALF.

Management of cerebral edema

  • Manitol
  • Hypertonic saline(%3)
  • Hyperventilation
  • Hypothermia
  • phenobarbital and IV Indomethacin
  • Hepatectomy

Treatment of hemodynamic instabilty

  • Invasive hemodynamic monitoring
  • Colloid, crystalloid fluids, and blood products
  • Vassopressors

Monitoring of renal function

  • Early fluid challenge
  • Hemodialysis if needed

Correcting of coagulopathy

Correcting of metabolic disorders

Consider liver transplantation

  • Liver transplantation: One of the most important, yet difficult, aspects of care for patients with Acute Liver failure is the determination of the need for urgent liver transplantation. We recommend early and rapid evaluation for transplantation candidacy. More than half of cases with Acute liver disease need liver transplantation with improved outcomes.[6]
  • For patients with chronic liver failure,the only existing cure is liver transplantation , an option that only a minority of patients will receive it.[20]


Contraindicated medications

Severe hepatic failure is considered an absolute contraindication to the use of the following medications:

The ALFSG index is a newer option that may be more accurate.[39]

References

  1. Riordan SM, Williams R (May 2008). "Perspectives on liver failure: past and future". Semin. Liver Dis. 28 (2): 137–41. doi:10.1055/s-2008-1073113. PMID 18452113.
  2. Bernuau J, Rueff B, Benhamou JP (May 1986). "Fulminant and subfulminant liver failure: definitions and causes". Semin. Liver Dis. 6 (2): 97–106. doi:10.1055/s-2008-1040593. PMID 3529410.
  3. 3.0 3.1 O'Grady JG, Schalm SW, Williams R (July 1993). "Acute liver failure: redefining the syndromes". Lancet. 342 (8866): 273–5. doi:10.1016/0140-6736(93)91818-7. PMID 8101303.
  4. Jalan R, Williams R (2002). "Acute-on-chronic liver failure: pathophysiological basis of therapeutic options". Blood Purif. 20 (3): 252–61. doi:10.1159/000047017. PMID 11867872.
  5. 5.0 5.1 5.2 Lee WM, Squires RH, Nyberg SL, Doo E, Hoofnagle JH (April 2008). "Acute liver failure: Summary of a workshop". Hepatology. 47 (4): 1401–15. doi:10.1002/hep.22177. PMC 3381946. PMID 18318440.
  6. 6.0 6.1 Rajaram P, Subramanian R (October 2018). "Acute Liver Failure". Semin Respir Crit Care Med. 39 (5): 513–522. doi:10.1055/s-0038-1673372. PMID 30485882.
  7. Gimson AE, O'Grady J, Ede RJ, Portmann B, Williams R (1986). "Late onset hepatic failure: clinical, serological and histological features". Hepatology. 6 (2): 288–94. doi:10.1002/hep.1840060222. PMID 3082735.
  8. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, Gustot T, Saliba F, Domenicali M, Gerbes A, Wendon J, Alessandria C, Laleman W, Zeuzem S, Trebicka J, Bernardi M, Arroyo V (June 2013). "Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis". Gastroenterology. 144 (7): 1426–37, 1437.e1–9. doi:10.1053/j.gastro.2013.02.042. PMID 23474284.
  9. Schuppan D, Afdhal NH (March 2008). "Liver cirrhosis". Lancet. 371 (9615): 838–51. doi:10.1016/S0140-6736(08)60383-9. PMC 2271178. PMID 18328931.
  10. Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, Harris SC (July 2006). "Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial". JAMA. 296 (1): 87–93. doi:10.1001/jama.296.1.87. PMID 16820551.
  11. Chayanupatkul M, Schiano TD (February 2020). "Acute Liver Failure Secondary to Drug-Induced Liver Injury". Clin Liver Dis. 24 (1): 75–87. doi:10.1016/j.cld.2019.09.005. PMID 31753252.
  12. Murray KF, Hadzic N, Wirth S, Bassett M, Kelly D (October 2008). "Drug-related hepatotoxicity and acute liver failure". J. Pediatr. Gastroenterol. Nutr. 47 (4): 395–405. doi:10.1097/MPG.0b013e3181709464. PMID 18852631.
  13. Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, Reisch JS, Schiødt FV, Ostapowicz G, Shakil AO, Lee WM (December 2005). "Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study". Hepatology. 42 (6): 1364–72. doi:10.1002/hep.20948. PMID 16317692.
  14. 14.0 14.1 14.2 Patton H, Misel M, Gish RG (March 2012). "Acute liver failure in adults: an evidence-based management protocol for clinicians". Gastroenterol Hepatol (N Y). 8 (3): 161–212. PMC 3365519. PMID 22675278.
  15. Asrani SK, Larson JJ, Yawn B, Therneau TM, Kim WR (August 2013). "Underestimation of liver-related mortality in the United States". Gastroenterology. 145 (2): 375–82.e1–2. doi:10.1053/j.gastro.2013.04.005. PMC 3890240. PMID 23583430.
  16. Munoz SJ (October 2014). "Complications of Acute Liver Failure". Gastroenterol Hepatol (N Y). 10 (10): 665–8. PMC 4988224. PMID 27540338.
  17. Davern TJ (December 2007). "Predicting prognosis in acute liver failure: Ammonia and the risk of cerebral edema". Hepatology. 46 (6): 1679–81. doi:10.1002/hep.22038. PMID 18046715.
  18. 18.0 18.1 Mendizabal M, Silva MO (January 2016). "Liver transplantation in acute liver failure: A challenging scenario". World J. Gastroenterol. 22 (4): 1523–31. doi:10.3748/wjg.v22.i4.1523. PMC 4721985. PMID 26819519.
  19. McDowell Torres D, Stevens RD, Gurakar A (July 2010). "Acute liver failure: a management challenge for the practicing gastroenterologist". Gastroenterol Hepatol (N Y). 6 (7): 444–50. PMC 2933761. PMID 20827368.
  20. 20.0 20.1 Potosek J, Curry M, Buss M, Chittenden E (November 2014). "Integration of palliative care in end-stage liver disease and liver transplantation". J Palliat Med. 17 (11): 1271–7. doi:10.1089/jpm.2013.0167. PMC 4229716. PMID 25390468.
  21. Flores YN, Lang CM, Salmerón J, Bastani R (2012). "Risk factors for liver disease and associated knowledge and practices among Mexican adults in the US and Mexico". J Community Health. 37 (2): 403–11. doi:10.1007/s10900-011-9457-4. PMID 21877109.
  22. Bloom S, Kemp W, Lubel J (2015). "Portal hypertension: pathophysiology, diagnosis and management". Intern Med J. 45 (1): 16–26. doi:10.1111/imj.12590. PMID 25230084.
  23. Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R (2007). "Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy". Hepatology. 45 (3): 549–59. doi:10.1002/hep.21533. PMID 17326150.
  24. Córdoba J, López-Hellín J, Planas M; et al. (2004). "Normal protein diet for episodic hepatic encephalopathy: results of a randomized study". J. Hepatol. 41 (1): 38–43. doi:10.1016/j.jhep.2004.03.023. PMID 15246205.
  25. Artz SA, Paes IC, Faloon WW (1966). "Hypokalemia-induced hepatic coma in cirrhosis. Occurrence despite neomycin therapy". Gastroenterology. 51 (6): 1046–53. PMID 5958605.
  26. Als-Nielsen B, Gluud L, Gluud C. "Nonabsorbable disaccharides for hepatic encephalopathy". Cochrane Database Syst Rev: CD003044. PMID 15106187.
  27. Kersh ES, Rifkin H (1973). "Lactulose enemas". Ann. Intern. Med. 78 (1): 81–4. PMID 4682313.
  28. Ratnaike RN, Hicks EP, Hislop IG (1975). "The rectal administration of lactulose". Australian and New Zealand journal of medicine. 5 (2): 137–40. PMID 240347.
  29. Uribe M, Campollo O, Vargas F; et al. (1987). "Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind, randomized clinical trial". Hepatology. 7 (4): 639–43. PMID 3301614.
  30. Blei AT, Córdoba J (2001). "Hepatic Encephalopathy". Am. J. Gastroenterol. 96 (7): 1968–76. doi:10.1111/j.1572-0241.2001.03964.x. PMID 11467622.
  31. Morgan MH, Read AE, Speller DC (1982). "Treatment of hepatic encephalopathy with metronidazole". Gut. 23 (1): 1–7. PMID 7035298.
  32. Williams R, James OF, Warnes TW, Morgan MY (2000). "Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study". European journal of gastroenterology & hepatology. 12 (2): 203–8. PMID 10741936.
  33. Bucci L, Palmieri GC (1993). "Double-blind, double-dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy". Current medical research and opinion. 13 (2): 109–18. PMID 8325041.
  34. Pedretti G, Calzetti C, Missale G, Fiaccadori F (1991). "Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial". The Italian journal of gastroenterology. 23 (4): 175–8. PMID 1751811.
  35. Als-Nielsen B, Gluud LL, Gluud C (2004). "Benzodiazepine receptor antagonists for hepatic encephalopathy". Cochrane database of systematic reviews (Online) (2): CD002798. doi:10.1002/14651858.CD002798.pub2. PMID 15106178.
  36. Poo J, Góngora J, Sánchez-Avila F, Aguilar-Castillo S, García-Ramos G, Fernández-Zertuche M, Rodríguez-Fragoso L, Uribe M (2006). "Efficacy of oral L-ornithine-L-aspartate in cirrhotic patients with hyperammonemic hepatic encephalopathy. Results of a randomized, lactulose-controlled study". Ann Hepatol. 5 (4): 281–8. PMID 17151582.
  37. Poo JL, Góngora J, Sánchez-Avila F; et al. (2006). "Efficacy of oral L-ornithine-L-aspartate in cirrhotic patients with hyperammonemic hepatic encephalopathy. Results of a randomized, lactulose-controlled study". Annals of hepatology : official journal of the Mexican Association of Hepatology. 5 (4): 281–8. PMID 17151582.
  38. Stauch S, Kircheis G, Adler G; et al. (1998). "Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study". J. Hepatol. 28 (5): 856–64. PMID 9625322.
  39. Rutherford A, King LY, Hynan LS, Vedvyas C, Lin W, Lee WM; et al. (2012). "Development of an accurate index for predicting outcomes of patients with acute liver failure". Gastroenterology. 143 (5): 1237–43. doi:10.1053/j.gastro.2012.07.113. PMC 3480539. PMID 22885329.

See Also

cs:Jaterní selhání sv:Leversvikt ur:فشل جگری