REVIEW URRENT C OPINION
Current management of acute liver failure Mark J.W. McPhail, Stephen Kriese, and Michael A. Heneghan
Purpose of review Acute liver failure (ALF) is a rare but life-threatening systemic disorder. Survival rates with or without emergency liver transplantation (ELT) are increasing. The benefit of ELT in some cases has been questioned and the potential for survival with medical management alone is changing our approach to the management of this disease. Recent findings Survival rates for all causes of ALF are increasing because of improvements in the care of the critically ill patient. A multifactorial approach involving support of respiratory, circulatory and renal function together with measures to avoid intracranial hypertension, metabolic disequilibrium and sepsis are required. For those who do not respond to these measures or specific antidotes, the selection methods for those likely to benefit from transplantation remain imperfect and novel methods based on the prediction of hepatic regeneration are required. For patients with ALF secondary to acetaminophen overdose, some experts believe a randomized controlled trial is required to find those most likely to benefit from ELT. Summary ALF remains a life-threatening condition with a high mortality rate requiring prompt support of multiorgan failure. Historical listing criteria for ELT are being questioned and improvement in medical management offers the option of continued improvements in transplant-free survival. Keywords acute liver failure, fulminant hepatic failure, liver transplantation
INTRODUCTION Acute liver failure (ALF) is a rare but life-threatening illness wherein sudden loss of liver function occurs in a patient with no previous liver abnormality [1 ]. The cardinal clinical manifestations are hepatocellular jaundice, coagulopathy and encephalopathy. Although the incidence is low (1.5) in a patient with no history of chronic liver disease. The time frame between the onset of jaundice and encephalopathy in this framework defines whether ALF is hyperacute (150 mmol/l) or clinical features suggestive of intracerebral haemorrhage, ICP monitoring is recommended [14]. This is particularly so in patients who are young and more likely to develop intracerebral haemorrhage in the presence of cerebral oedema. There is no consensus on the best method to perform ICP measurement nor the cerebral perfusion pressure to target and therefore those from the neurosurgical literature are used. Continuous veno-venous haemofiltration is associated with a quantifiable reduction in ammonia [15] and is recommended in patients with ALF even when renal dysfunction itself does not warrant renal replacement therapy. General intensive care measures to reduce ICP are common to other neurological or neurosurgical conditions such as head of bed elevation, intravenous sedation, neuromuscular blockade and control of serum sodium levels (aim >140 mmol/l). Bolus mannitol or hypertonic saline is reserved for flares of ICP, poorly controlled serum sodium or where clinical signs consistent with high ICP occur in the absence of real-time measurement. Therapeutic hypothermia that is commonly used in patients with severe traumatic brain injury was recently explored in a retrospective cohort analysis in patients with ALF and found not to be associated with a survival benefit [16 ] or increase in the incidence of septic or bleeding complications. Although randomized trial data are awaited, many practitioners will at least avoid hyperthermia in an attempt to minimize cerebral oxygen demand while &&
212
www.co-gastroenterology.com
avoiding the potential complications of therapeutic hypothermia.
NOVEL THERAPIES Some current expert opinion would argue that for some causes of ALF (in particular AALF), the success of medical management alone may one day result in further significant reductions in the use of ELT in that context. Several reports and case series have recently emerged on the potential role of high-volume plasma exchange in patients with ALF [17]. The therapeutic aim is to clear the plasma of harmful inflammatory mediators that can prolong or exacerbate inflammation and delay resolution of liver injury [18]. In one small study, 9/10 patients whilst undergoing plasma exchange improved their biochemical parameters and spontaneously survived [19]. Controlled studies are awaited but such techniques may be particularly useful for those patients in whom ELT is contraindicated. Although liver assist devices have shown some promise in acute-on-chronic liver failure in managing hyperbilirubinaemia and encephalopathy, there is no evidence to support their use in ALF [20 ]. Hepatocyte transplantation represents a novel method of augmenting liver function in ALF as either a bridge to ELT or to allow sufficient time for recovery of native liver function without resorting to auxiliary liver transplantation [21]. Hepatocyte transplantation is obtained from tissue for donor livers not used for transplantation and therefore preselects more marginal graft tissue. Cell &
Volume 31 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Current management of acute liver failure McPhail et al.
stability is enhanced by preservation in N-acetylcysteine. Cryopreservation is required for ‘off-the-shelf’ use in emergencies prior to intraportal injection of hepatocytes. Metabolic disorders are those best suited to these techniques although a clinical benefit in Wilson’s disease as a cause of ALF has not been demonstrated [22].
FULMINANT STANDARD OF CARE Improvement in the management of patients with ALF is therefore aimed at providing the best possible environment for hepatic regeneration whereas specific antidotes are targeted at the cause factor. The success of these protocols has been profound but there remains a need for therapies to augment spontaneous survival further, whereas for some patients, ELT remains the only viable option. These cases of ALF with or without poor prognostic signs are best managed in specialist transplant centres and timely decisions made regarding prognosis.
PROGNOSTICATION AND LISTING DECISIONS The most important clinical decision in the management of ALF is whether to wait list the patient for ELT. This is based on the prediction of death with medical management alone and several prognostic schemas are available. The most widely used are the King’s College criteria that are split into two subcriteria for ALF caused by acetaminophen overdose or other causes [23]. Although simple, easily applicable and highly specific, they lack sensitivity and therefore other prognostic methods have been developed. These alternative methods share many similarities in their use of coagulation parameters, bilirubin, severity of hepatic encephalopathy, serum lactate or extrahepatic (primarily renal) organ failure. Owing to a relatively low incidence of ALF secondary to viral hepatitis in the cohort used to develop King’s criteria, the so-called Clichy criteria [8], which were derived from a cohort of patients with acute HBV-induced ALF in France, remain in use. The primary difference between Clichy and King’s criteria is the presence of low age-adjusted factor V Leiden levels as an additional poor prognostic marker. The model for end-stage liver disease (MELD) score has proven highly successful in decision making and listing for orthotopic liver transplantation in patients with cirrhosis. Several studies have demonstrated that MELD score higher than 30 had high positive predictive values (>80%) to predict the need for ELT. Nevertheless, the overall accuracy is not higher than King’s criteria.
The sequential organ failure assessment score (SOFA) was developed following expert consensus and describes severity of organ failure of the respiratory, cardiovascular, renal, liver, cerebral and haematological systems. Recent application of SOFA and modifications in patients with cirrhosis and organ failure has been highly effective. Other investigators have demonstrated SOFA to have high discriminatory power to prognosticate in AALF over King’s College criteria or MELD [24]. As yet, SOFA has not been sufficiently validated in this population to allow it to influence decision making for ELT. Of the many new but poorly validated prognostic measures, a recent development from the Acute Liver Failure Study Group has promise [25]. This score combines coma grade, international normalized ratio, serum phosphate and bilirubin and a novel circulating measure of apoptosis (M30) which has been shown to be elevated in patients with ALF [26]. This outperformed both MELD and King’s criteria in predicting outcome. Nevertheless, it requires use of a novel measurement (M30 levels) that is not in widespread use.
TRANSPLANTATION IN ACUTE LIVER FAILURE ALF remains an uncommon indication for liver transplantation, accounting for 5–8% of liver transplants in the USA and Europe [4,27]. Although there has been an increase in the total numbers of individuals transplanted for ALF, the proportions of ELT undertaken for acetaminophen toxicity and viral liver disease has decreased over the past 20 years [3 ]. Whole cadaveric grafts from brainstem dead donors’ remains are used in the majority of transplants for ALF [4]. Although grafts from deceased donors remain rare for ALF in the USA and Europe, some small cohort studies suggest that equivalent outcomes may be obtained [28]. Posttransplantation survival rates continue to improve for ALF, although they remain poorer than those undergoing elective transplantation [4]. Registry data from the USA and Europe report patient survival rates of 78 and 74% at 1 year and 72 and 57% at 5 years, respectively [4,27]. Patients are at greatest risk of death in the first year following, with two thirds of deaths occurring within the first 3 months [4]. Early deaths occur predominantly because of infection, primary nonfunction, intraoperative and technical complications and rejection [4]. Analysis of European registry data suggests that patient death or graft loss is associated with increasing recipient and donor age, donor-recipient ABO
0267-1379 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
&&
www.co-gastroenterology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
213
Liver
mismatching, male gender, acetaminophen-related ALF and reduced graft sizes [4]. Long-term outcomes following transplantation are similar for the various causes of ALF. Disease recurrence is more commonly seen in patients with viral disease than other causes [4]. Psychological morbidity remains an important cause of posttransplant mortality; 7% of deaths in this group were due to suicide, trauma or nonadherence to medications [4]. Enhanced screening for prohibitive psychological morbidity now occurs in most centres prior to ELT [3 ]. &&
CONCLUSION ALF remains a rare but life-threatening condition requiring high-quality care in specialist centres. The role of ELT is changing as survival from medical management alone improves and the requirement for up-to-date prognostic systems emerges. Outcomes following ELT have also improved with a selection of graft and operative options available to transplant teams. Acknowledgements The authors are grateful to the NIHR Biomedical Research Centre at King’s College London for infrastructure support. M.J.W.M. is grateful to the NIHR Biomedical Research Centre at Imperial College London for infrastructure support. Financial support and sponsorship S.K. is funded by a Doctoral Research Fellowship Award from the National Institute of Health Research. Conflicts of interest The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Bernal W, Wendon J. Acute liver failure. N Engl J Med 2013; 369:2525– & 2534. High quality overview of ALF. 2. Bateman DN. Pack size and paracetamol overdose: 16 years later. Clin Toxicol 2014; 52:821–823.
214
www.co-gastroenterology.com
3. Bernal W, Hyyrylainen A, Gera A, et al. Lessons from look-back in acute liver failure? A single centre experience of 3300 patients. J Hepatol 2013; 59:74–80. Very large historical single centre cohort over prolonged time frame describing changes in outcome of patients with ALF. 4. Germani G, Theocharidou E, Adam R, et al. Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database. J Hepatol 2012; 57:288–296. 5. Bernal W, Cross TJ, Auzinger G, et al. Outcome after wait-listing for emergency liver transplantation in acute liver failure: a single centre experience. J Hepatol 2009; 50:306–313. 6. Trey C, Davidson CS. The management of fulminant hepatic failure. Prog Liver Dis 1970; 3:282–298. 7. O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993; 342:273–275. 8. Bernuau J, Rueff B, Benhamou JP. Fulminant and subfulminant liver failure: definitions and causes. Semin Liver Dis 1986; 6:97–106. 9. Mochida S, Nakayama N, Matsui A, et al. Re-evaluation of the guideline published by the acute liver failure study group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis. Hepatol Res 2008; 38:970–979. 10. Yeoman AD, Westbrook RH, Zen Y, et al. Prognosis of acute severe auto& immune hepatitis (AS-AIH): The role of corticosteroids in modifying outcome. J Hepatol 2014; 61:876–882. Timely description of ALF of autoimmune aetiology and role of corticosteroids and transplantation. 11. Karvellas CJ, Pink F, McPhail M, et al. Predictors of bacteraemia and mortality in patients with acute liver failure. Intensive Care Med 2009; 35:1390–1396. 12. Kumar R, Shalimar. Sharma H, et al. Persistent hyperammonemia is associated with complications and poor outcomes in patients with acute liver failure. Clin Gastroenterol Hepatol 2012; 10:925–931. 13. Acharya SK, Bhatia V, Sreenivas V, et al. Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology 2009; 136:2159–2168. 14. Bernal W, Hall C, Karvellas CJ, et al. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology 2007; 46:1844–1852. 15. Slack AJ, Auzinger G, Willars C, et al. Ammonia clearance with haemofiltration in adults with liver disease. Liver Int 2014; 34:42–48. 16. Karvellas CJ, Stravitz RT, Battenhouse H, et al., for the USALFSG. Ther&& apeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis. Liver Transplant 2015; 21:4–12. Largest series of patients studied for clinical benefit of therapeutic hypothermia in ALF. 17. Chen KJ, Chen TH, Sue YM, et al. High-volume plasma exchange in a patient with acute liver failure due to nonexertional heat stroke in a sauna. J Clin Apheresis 2014; 29:281–283. 18. Bernsmeier C, Antoniades CG, Wendon J. What’s new in acute liver failure? Intensive Care Med 2014; 40:1545–1548. 19. Komura T, Taniguchi T, Sakai Y, et al. Efficacy of continuous plasma diafiltration therapy in critical patients with acute liver failure. J Gastroenterol Hepatol 2014; 29:782–786. 20. Struecker B, Raschzok N, Sauer IM. Liver support strategies: cutting-edge & technologies. Nat Rev Gastroenterol Hepatol 2014; 11:166–176. Review of modern liver support technologies in high quality journal. 21. Hughes RD, Mitry RR, Dhawan A. Current status of hepatocyte transplantation. Transplantation 2012; 93:342–347. 22. Filippi C, Dhawan A. Current status of human hepatocyte transplantation and its potential for Wilson’s disease. Ann NY Acad Sci 2014; 1315:50–55. 23. O’Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97:439–445. 24. Cholongitas E, Theocharidou E, Vasianopoulou P, et al. Comparison of the sequential organ failure assessment score with the King’s College Hospital criteria and the model for end-stage liver disease score for the prognosis of acetaminophen-induced acute liverfailure. Liver Transplant 2012; 18:405–412. 25. Rutherford A, King LY, Hynan LS, et al., Group ALFS. Development of an accurate index for predicting outcomes of patients with acute liver failure. Gastroenterology 2012; 143:1237–1243. 26. Possamai LA, McPhail MJ, Quaglia A, et al. Character and temporal evolution of apoptosis in acetaminophen-induced acute liver failure. Crit Care Med 2013; 41:2543–2550. 27. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2012 annual data report. Rockville, MD: Department of Health and Human Services, HRaSA; 2014. 28. Jin YJ, Lim YS, Han S, et al. Predicting survival after living and deceased donor liver transplantation in adult patients with acute liver failure. J Gastroenterol 2012; 47:1115–1124.
&&
Volume 31 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Current management of acute liver failure Mark J.W. McPhail, Stephen Kriese, and Michael A. Heneghan
Purpose of review Acute liver failure (ALF) is a rare but life-threatening systemic disorder. Survival rates with or without emergency liver transplantation (ELT) are increasing. The benefit of ELT in some cases has been questioned and the potential for survival with medical management alone is changing our approach to the management of this disease. Recent findings Survival rates for all causes of ALF are increasing because of improvements in the care of the critically ill patient. A multifactorial approach involving support of respiratory, circulatory and renal function together with measures to avoid intracranial hypertension, metabolic disequilibrium and sepsis are required. For those who do not respond to these measures or specific antidotes, the selection methods for those likely to benefit from transplantation remain imperfect and novel methods based on the prediction of hepatic regeneration are required. For patients with ALF secondary to acetaminophen overdose, some experts believe a randomized controlled trial is required to find those most likely to benefit from ELT. Summary ALF remains a life-threatening condition with a high mortality rate requiring prompt support of multiorgan failure. Historical listing criteria for ELT are being questioned and improvement in medical management offers the option of continued improvements in transplant-free survival. Keywords acute liver failure, fulminant hepatic failure, liver transplantation
INTRODUCTION Acute liver failure (ALF) is a rare but life-threatening illness wherein sudden loss of liver function occurs in a patient with no previous liver abnormality [1 ]. The cardinal clinical manifestations are hepatocellular jaundice, coagulopathy and encephalopathy. Although the incidence is low (1.5) in a patient with no history of chronic liver disease. The time frame between the onset of jaundice and encephalopathy in this framework defines whether ALF is hyperacute (150 mmol/l) or clinical features suggestive of intracerebral haemorrhage, ICP monitoring is recommended [14]. This is particularly so in patients who are young and more likely to develop intracerebral haemorrhage in the presence of cerebral oedema. There is no consensus on the best method to perform ICP measurement nor the cerebral perfusion pressure to target and therefore those from the neurosurgical literature are used. Continuous veno-venous haemofiltration is associated with a quantifiable reduction in ammonia [15] and is recommended in patients with ALF even when renal dysfunction itself does not warrant renal replacement therapy. General intensive care measures to reduce ICP are common to other neurological or neurosurgical conditions such as head of bed elevation, intravenous sedation, neuromuscular blockade and control of serum sodium levels (aim >140 mmol/l). Bolus mannitol or hypertonic saline is reserved for flares of ICP, poorly controlled serum sodium or where clinical signs consistent with high ICP occur in the absence of real-time measurement. Therapeutic hypothermia that is commonly used in patients with severe traumatic brain injury was recently explored in a retrospective cohort analysis in patients with ALF and found not to be associated with a survival benefit [16 ] or increase in the incidence of septic or bleeding complications. Although randomized trial data are awaited, many practitioners will at least avoid hyperthermia in an attempt to minimize cerebral oxygen demand while &&
212
www.co-gastroenterology.com
avoiding the potential complications of therapeutic hypothermia.
NOVEL THERAPIES Some current expert opinion would argue that for some causes of ALF (in particular AALF), the success of medical management alone may one day result in further significant reductions in the use of ELT in that context. Several reports and case series have recently emerged on the potential role of high-volume plasma exchange in patients with ALF [17]. The therapeutic aim is to clear the plasma of harmful inflammatory mediators that can prolong or exacerbate inflammation and delay resolution of liver injury [18]. In one small study, 9/10 patients whilst undergoing plasma exchange improved their biochemical parameters and spontaneously survived [19]. Controlled studies are awaited but such techniques may be particularly useful for those patients in whom ELT is contraindicated. Although liver assist devices have shown some promise in acute-on-chronic liver failure in managing hyperbilirubinaemia and encephalopathy, there is no evidence to support their use in ALF [20 ]. Hepatocyte transplantation represents a novel method of augmenting liver function in ALF as either a bridge to ELT or to allow sufficient time for recovery of native liver function without resorting to auxiliary liver transplantation [21]. Hepatocyte transplantation is obtained from tissue for donor livers not used for transplantation and therefore preselects more marginal graft tissue. Cell &
Volume 31 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Current management of acute liver failure McPhail et al.
stability is enhanced by preservation in N-acetylcysteine. Cryopreservation is required for ‘off-the-shelf’ use in emergencies prior to intraportal injection of hepatocytes. Metabolic disorders are those best suited to these techniques although a clinical benefit in Wilson’s disease as a cause of ALF has not been demonstrated [22].
FULMINANT STANDARD OF CARE Improvement in the management of patients with ALF is therefore aimed at providing the best possible environment for hepatic regeneration whereas specific antidotes are targeted at the cause factor. The success of these protocols has been profound but there remains a need for therapies to augment spontaneous survival further, whereas for some patients, ELT remains the only viable option. These cases of ALF with or without poor prognostic signs are best managed in specialist transplant centres and timely decisions made regarding prognosis.
PROGNOSTICATION AND LISTING DECISIONS The most important clinical decision in the management of ALF is whether to wait list the patient for ELT. This is based on the prediction of death with medical management alone and several prognostic schemas are available. The most widely used are the King’s College criteria that are split into two subcriteria for ALF caused by acetaminophen overdose or other causes [23]. Although simple, easily applicable and highly specific, they lack sensitivity and therefore other prognostic methods have been developed. These alternative methods share many similarities in their use of coagulation parameters, bilirubin, severity of hepatic encephalopathy, serum lactate or extrahepatic (primarily renal) organ failure. Owing to a relatively low incidence of ALF secondary to viral hepatitis in the cohort used to develop King’s criteria, the so-called Clichy criteria [8], which were derived from a cohort of patients with acute HBV-induced ALF in France, remain in use. The primary difference between Clichy and King’s criteria is the presence of low age-adjusted factor V Leiden levels as an additional poor prognostic marker. The model for end-stage liver disease (MELD) score has proven highly successful in decision making and listing for orthotopic liver transplantation in patients with cirrhosis. Several studies have demonstrated that MELD score higher than 30 had high positive predictive values (>80%) to predict the need for ELT. Nevertheless, the overall accuracy is not higher than King’s criteria.
The sequential organ failure assessment score (SOFA) was developed following expert consensus and describes severity of organ failure of the respiratory, cardiovascular, renal, liver, cerebral and haematological systems. Recent application of SOFA and modifications in patients with cirrhosis and organ failure has been highly effective. Other investigators have demonstrated SOFA to have high discriminatory power to prognosticate in AALF over King’s College criteria or MELD [24]. As yet, SOFA has not been sufficiently validated in this population to allow it to influence decision making for ELT. Of the many new but poorly validated prognostic measures, a recent development from the Acute Liver Failure Study Group has promise [25]. This score combines coma grade, international normalized ratio, serum phosphate and bilirubin and a novel circulating measure of apoptosis (M30) which has been shown to be elevated in patients with ALF [26]. This outperformed both MELD and King’s criteria in predicting outcome. Nevertheless, it requires use of a novel measurement (M30 levels) that is not in widespread use.
TRANSPLANTATION IN ACUTE LIVER FAILURE ALF remains an uncommon indication for liver transplantation, accounting for 5–8% of liver transplants in the USA and Europe [4,27]. Although there has been an increase in the total numbers of individuals transplanted for ALF, the proportions of ELT undertaken for acetaminophen toxicity and viral liver disease has decreased over the past 20 years [3 ]. Whole cadaveric grafts from brainstem dead donors’ remains are used in the majority of transplants for ALF [4]. Although grafts from deceased donors remain rare for ALF in the USA and Europe, some small cohort studies suggest that equivalent outcomes may be obtained [28]. Posttransplantation survival rates continue to improve for ALF, although they remain poorer than those undergoing elective transplantation [4]. Registry data from the USA and Europe report patient survival rates of 78 and 74% at 1 year and 72 and 57% at 5 years, respectively [4,27]. Patients are at greatest risk of death in the first year following, with two thirds of deaths occurring within the first 3 months [4]. Early deaths occur predominantly because of infection, primary nonfunction, intraoperative and technical complications and rejection [4]. Analysis of European registry data suggests that patient death or graft loss is associated with increasing recipient and donor age, donor-recipient ABO
0267-1379 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
&&
www.co-gastroenterology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
213
Liver
mismatching, male gender, acetaminophen-related ALF and reduced graft sizes [4]. Long-term outcomes following transplantation are similar for the various causes of ALF. Disease recurrence is more commonly seen in patients with viral disease than other causes [4]. Psychological morbidity remains an important cause of posttransplant mortality; 7% of deaths in this group were due to suicide, trauma or nonadherence to medications [4]. Enhanced screening for prohibitive psychological morbidity now occurs in most centres prior to ELT [3 ]. &&
CONCLUSION ALF remains a rare but life-threatening condition requiring high-quality care in specialist centres. The role of ELT is changing as survival from medical management alone improves and the requirement for up-to-date prognostic systems emerges. Outcomes following ELT have also improved with a selection of graft and operative options available to transplant teams. Acknowledgements The authors are grateful to the NIHR Biomedical Research Centre at King’s College London for infrastructure support. M.J.W.M. is grateful to the NIHR Biomedical Research Centre at Imperial College London for infrastructure support. Financial support and sponsorship S.K. is funded by a Doctoral Research Fellowship Award from the National Institute of Health Research. Conflicts of interest The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Bernal W, Wendon J. Acute liver failure. N Engl J Med 2013; 369:2525– & 2534. High quality overview of ALF. 2. Bateman DN. Pack size and paracetamol overdose: 16 years later. Clin Toxicol 2014; 52:821–823.
214
www.co-gastroenterology.com
3. Bernal W, Hyyrylainen A, Gera A, et al. Lessons from look-back in acute liver failure? A single centre experience of 3300 patients. J Hepatol 2013; 59:74–80. Very large historical single centre cohort over prolonged time frame describing changes in outcome of patients with ALF. 4. Germani G, Theocharidou E, Adam R, et al. Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database. J Hepatol 2012; 57:288–296. 5. Bernal W, Cross TJ, Auzinger G, et al. Outcome after wait-listing for emergency liver transplantation in acute liver failure: a single centre experience. J Hepatol 2009; 50:306–313. 6. Trey C, Davidson CS. The management of fulminant hepatic failure. Prog Liver Dis 1970; 3:282–298. 7. O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993; 342:273–275. 8. Bernuau J, Rueff B, Benhamou JP. Fulminant and subfulminant liver failure: definitions and causes. Semin Liver Dis 1986; 6:97–106. 9. Mochida S, Nakayama N, Matsui A, et al. Re-evaluation of the guideline published by the acute liver failure study group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis. Hepatol Res 2008; 38:970–979. 10. Yeoman AD, Westbrook RH, Zen Y, et al. Prognosis of acute severe auto& immune hepatitis (AS-AIH): The role of corticosteroids in modifying outcome. J Hepatol 2014; 61:876–882. Timely description of ALF of autoimmune aetiology and role of corticosteroids and transplantation. 11. Karvellas CJ, Pink F, McPhail M, et al. Predictors of bacteraemia and mortality in patients with acute liver failure. Intensive Care Med 2009; 35:1390–1396. 12. Kumar R, Shalimar. Sharma H, et al. Persistent hyperammonemia is associated with complications and poor outcomes in patients with acute liver failure. Clin Gastroenterol Hepatol 2012; 10:925–931. 13. Acharya SK, Bhatia V, Sreenivas V, et al. Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology 2009; 136:2159–2168. 14. Bernal W, Hall C, Karvellas CJ, et al. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology 2007; 46:1844–1852. 15. Slack AJ, Auzinger G, Willars C, et al. Ammonia clearance with haemofiltration in adults with liver disease. Liver Int 2014; 34:42–48. 16. Karvellas CJ, Stravitz RT, Battenhouse H, et al., for the USALFSG. Ther&& apeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis. Liver Transplant 2015; 21:4–12. Largest series of patients studied for clinical benefit of therapeutic hypothermia in ALF. 17. Chen KJ, Chen TH, Sue YM, et al. High-volume plasma exchange in a patient with acute liver failure due to nonexertional heat stroke in a sauna. J Clin Apheresis 2014; 29:281–283. 18. Bernsmeier C, Antoniades CG, Wendon J. What’s new in acute liver failure? Intensive Care Med 2014; 40:1545–1548. 19. Komura T, Taniguchi T, Sakai Y, et al. Efficacy of continuous plasma diafiltration therapy in critical patients with acute liver failure. J Gastroenterol Hepatol 2014; 29:782–786. 20. Struecker B, Raschzok N, Sauer IM. Liver support strategies: cutting-edge & technologies. Nat Rev Gastroenterol Hepatol 2014; 11:166–176. Review of modern liver support technologies in high quality journal. 21. Hughes RD, Mitry RR, Dhawan A. Current status of hepatocyte transplantation. Transplantation 2012; 93:342–347. 22. Filippi C, Dhawan A. Current status of human hepatocyte transplantation and its potential for Wilson’s disease. Ann NY Acad Sci 2014; 1315:50–55. 23. O’Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97:439–445. 24. Cholongitas E, Theocharidou E, Vasianopoulou P, et al. Comparison of the sequential organ failure assessment score with the King’s College Hospital criteria and the model for end-stage liver disease score for the prognosis of acetaminophen-induced acute liverfailure. Liver Transplant 2012; 18:405–412. 25. Rutherford A, King LY, Hynan LS, et al., Group ALFS. Development of an accurate index for predicting outcomes of patients with acute liver failure. Gastroenterology 2012; 143:1237–1243. 26. Possamai LA, McPhail MJ, Quaglia A, et al. Character and temporal evolution of apoptosis in acetaminophen-induced acute liver failure. Crit Care Med 2013; 41:2543–2550. 27. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2012 annual data report. Rockville, MD: Department of Health and Human Services, HRaSA; 2014. 28. Jin YJ, Lim YS, Han S, et al. Predicting survival after living and deceased donor liver transplantation in adult patients with acute liver failure. J Gastroenterol 2012; 47:1115–1124.
&&
Volume 31 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
