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Address for correspondence: Shalimar, Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences New Delhi, India.
Acute liver failure (ALF) is a major success story in gastroenterology, with improvements in critical care and liver transplant resulting in significant improvements in patient outcomes in the current era compared to the dismal survival rates in the pretransplant era. However, the ever-increasing list of transplant candidates and limited organ pool makes judicious patient selection and organ use mandatory to achieve good patient outcomes and prevent organ wastage. Several scoring systems exist to facilitate the identification of patients who need a liver transplant and would therefore need an early referral to a specialized liver unit. The timing of the liver transplant is also crucial as transplanting a patient too early would lead to those who would recover spontaneously receiving an organ (wastage), and a late decision might result in the patient becoming unfit for transplant (delisted) or have an advanced disease which would result in poor post-transplant outcomes. The current article reviews the indications and contraindications of liver transplant in ALF patients, the various prognostic scoring systems, etiology-specific outcomes, prioritization and timing of referral.
Acute liver failure (ALF) is a potentially fatal complication of severe hepatic illness. Most definitions define liver failure by the presence of encephalopathy and coagulopathy—International normalized ratio (INR) > 1.5 or prothrombin time >15 s) in patients without pre-existing liver disease. ALF may also be classified based on differences in the time interval between the onset of symptoms and encephalopathy, which has prognostic significance (Table 1).
It can be precipitated by a multitude of factors with regional and global differences (Table 2). Thus, while viral hepatitis is the leading cause of ALF in India, acetaminophen (APAP) overdose, autoimmune hepatitis (AIH) and other metabolic diseases contribute to the burden of ALF in Europe and the America.
In the pre-transplant era, the short-term mortality of ALF was very high (approximately 80–85%) as the treatment was limited to supportive care, and therapy was directed toward the inciting agent, when identifiable.
The earliest theoretical possibility of liver transplantation (LT) for the management of ALF was considered in an National Institutes of Health consensus in 1983.
All these studies concluded that patients who received urgent liver transplants had better outcomes than those who did not receive transplants. However, the overall outcomes in such patients were worse than patients receiving elective liver transplants for end-stage liver disease.
Current guidelines advocate that a transplant center should be contacted at an early stage in the management of all patients having ALF, and plans should be in place to transfer these patients to the expert center should the need arise.
The United Network for Organ Sharing (United States of America) recognizes the unique position of ALF in terms of poor short-term mortality. It designates patients having ALF as “Status 1”, the highest priority on the transplant list.
Patients who are “Status 1” are usually those who are admitted to the intensive care unit with either renal failure (on hemodialysis) or respiratory failure (on mechanical ventilation) or have an INR>2 in a patient with onset of hepatic encephalopathy within 8 weeks of initial symptoms of liver disease. These patients are usually not likely to survive for a period >7 days.
Evaluation for liver transplantation in adults: 2013 practice guideline by the American association for the study of liver diseases and the American society of transplantation.
By virtue of their priority listing, these patients can bypass all other patients with chronic illnesses (who have usually been on the transplant list for longer duration). Although listing as “Status 1” does not guarantee a liver transplant, waiting times are as low as 48–72 h for those who receive the organ.
ALF accounted for approximately 8% of all LT in Europe (1988–2009) and 3.9% of listing for orthotopic liver transplant in the United States (1995–2005).
However, over the past 3 decades, there has been significant improvement in critical care medicine which has translated into higher transplant-free survival (TFS) of almost 50% in patients having ALF.
The overall 1- and 5-year survival after LT is 79% and 72%, respectively; this continues to be higher than the TFS rates. However, TFS rates in recent studies indicate that all patients having ALF may not need LT, and some may improve with good supportive care only.
These unnecessary LT not only deny the organs to other patients but also add to the pressure of using marginal and ABO-incompatible grafts to meet the ever-increasing need for organs for patients on the transplant list.
This current review focuses on the indication, prioritization, timing, and referral of patients with ALF for a liver transplant.
INDICATION
As discussed previously, LT in patients with ALF should ideally be reserved for those who are not likely to improve with supportive care alone. This underscores the need for robust prognostic models and identification of factors which portend a poor outcome in such patients, who should be referred for early LT.
The most common etiologies of ALF are viral hepatitis and drugs. Among viral etiologies, hepatitis A, B, and E are predominant, while cytomegalovirus, varicella zoster virus, herpes simplex virus, and Dengue virus are less common. Although effective vaccination against hepatitis B has led to an overall reduction in incidence, it continues to be an important cause of ALF in south Asia.
The availability of oral nucleos(t)ide analogs provides the opportunity for early intervention at the stage of acute liver injury, preventing disease progression to ALF. However, mortality rates are still higher in HBV-ALF compared to Hepatitis A or E-related ALF.
Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are enteric hepatotropic viruses responsible for causing ALF. Factors which portend a poor prognosis in patients of HAV-ALF include male sex, age over 40 years, low or undetectable HAV viral load, high serum bilirubin levels, underlying cirrhosis, and long hospital stay.
HEV infections are predominantly caused by genotypes 1 and 2 in the developing world (which is waterborne) while autochthonous infections with genotype 3 and 4 are more common in the Western world.
The clinical course is largely benign in most patients, presenting as transaminitis that requires only supportive care. In a retrospective analysis of 1462 cases over a 29 year period at a tertiary care center in India, HEV was found to account for 28.7% cases of ALF compared to the Western world, where it is considered an emerging infection (prevalence rates being 10–15% in Germany and <1% in the USA).
Advanced age, female sex, elevated bilirubin, presence of cerebral edema, prolonged prothrombin time, and infection is associated with poor in-hospital outcomes in HEV-related ALF.
Several drugs have been implicated in causing drug-induced liver injury (DILI). The most common agents are APAP, anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide), antibiotics (nitrofurantoin, ketoconazole), anti-epileptics (phenytoin, valproate), recreational agents, herbal and complementary medications, and so on. APAP overdose is one of the leading causes of DILI in the West and accounts for close to 50% of cases of ALF and 13.8% of LT for ALF in the United States.
One of the largest prospective studies involving 22 centers in the United States over 6 years reported that 42% of cases of ALF were APAP-related. The TFS was 65%, and of the remaining patients, 8% of patients received LT. The use of N-acetylcysteine in the early stages of APAP-induced ALF has further improved the TFS, and LT is now reserved for advanced stages of ALF with cerebral dysfunction.
A prospective multicentric study of 1198 patients enrolled over 10.5 years in the United States revealed that 11.1% of patients were likely to have drug-related ALF (of which the diagnosis was highly likely in 81% of cases). The most commonly implicated drugs were antimicrobials (46% cases), and the overall TFS was low (27.1%). Of these, 56 patients received LT, of whom 52 (92.8%) patients survived the acute episode.
The significantly better outcomes with APAP than other drugs are attributed to the known dose-related injury, short latency, and rapid presentation (hyperacute ALF), while the other agents present with a slow, subacute, and protracted course, which is known to be associated with poorer outcomes.
Anti-tubercular drugs are a leading cause of ALF in India accounting for 29.5% of patients having ALF at a tertiary care center in India. Three distinct factors were found to portend a poor prognosis in these patients: serum bilirubin (≥10.8 mg/dl), prolonged prothrombin time (>26 s), and grade 3/4 encephalopathy on presentation.
There is very limited data on outcomes of LT in patients with AIH-ALF, although data from the European Liver Transplant Registry showed survival of 60.3% after 15 years of transplant in AIH patients, with infections being the leading cause of post-transplant mortality.
De Martin et al., in their retrospective multicentric analysis, defined the Survival and prognostic factors for acute severe autoimmune hepatitis (SURFASA) score to identify patients with poor response to corticosteroids who would benefit from an early transplant listing.
However, Lin et al. identified that the predictive ability of the SURFASA score was similar to model for end stage liver disease (MELD) and MELD-Na and needs further validation.
Indeterminate-ALF is also known as cryptogenic, seronegative, non-A non-B, non-A non-B non-C, and non-A non-E ALF. It is well known that in the absence of any identified etiology, outcomes in the absence of LT are dismal, with TFS being 20%.
Several other diseases may present with ALF—such as Wilson's Disease (WD), toxins and infiltrative malignancies. Mushroom poisoning (amatoxin from Amanita phalloides) is a unique cause of liver injury limited to high consumption of wild mushrooms. A recent study identified that patients with acute liver injury due to mushroom toxicity have favorable survival comparable to other etiologies of ALF, but among those who progress to ALF, up to 50% may require a transplant. This same study also identified that extrahepatic organ failures (contributing to a poor outcome) were limited to patients progressing to ALF and not those with hepatitis alone. Thus, early intervention (prior to the onset of encephalopathy) with medical and supportive care along with early LT may be crucial in patients with mushroom poisoning.
India, an agrarian country, sees many cases of rodenticide-mediated liver failure due to accidental or intentional overdose. Mohanka et al. described a case series of 19 patients with rodenticide ingestion where the active toxin was yellow phosphorus. Seven patients survived with supportive care only, while 5 patients required LT. The mortality rate was 36.8%. The survivors were noted to have lower lactate levels, lower dose ingestion, and less than grade 3 encephalopathy. Patients with higher King's college criteria (KCC) and sequential organ failure assessment (SOFA) scores had worse outcomes. The presence of cardiomyopathy portended a universally poor outcome.
Acute liver failure secondary to yellow phosphorus rodenticide poisoning: outcomes at a center with dedicated liver intensive care and transplant unit.
Varghese et al., in a separate cohort of patients with rodenticide-mediated ALF, have also demonstrated the efficacy of therapeutic plasma exchange in improving TFS.
The role of plasmapheresis as a bridge to transplant was described by Pham et al. in their multicentre registry study where 10 patients underwent plasmapheresis (median 3.5 procedures per patient). Subsequently, 9 out of 10 patients received an LT, while one did not. The study reported 100% survival at 6 months providing evidence that plasmapheresis may have a role as a bridge to a liver transplant.
A recent study from India demonstrated higher median survival (38 days) and TFS (47.3%) among children undergoing high volume plasma exchange for WD-ALF compared to those who received standard medical care (14 days, 16.6%, respectively), thus substantiating the role of plasmapheresis as a bridge to transplant and also in improving TFS in this group of patients.
Parekh et al. reviewed the Budd Chiari syndrome (BCS) data of 20 patients in the acute liver failure study group (ALFSG) registry and 19 cases reported in the literature. Up to one-third of patients may need an LT, with the ALFSG group reporting a median survival of 3.5 months (1–8 months).
In a retrospective analysis, Thuluvath et al. identified that approximately 6% of patients in their cohort of 5306 patients of BCS presented with ALF and 5% received LT. Mortality rates were high (35%) in this group. They proposed a model involving 5 factors-acute respiratory failure, sepsis, SBP, age, and primary or malignancy (whether metastatic or with primary or secondary involvement of the liver) to predict outcomes in patients of BCS-ALF.
Casey et al. reported their experience of 35 patients with pregnancy-related liver disease progressing to ALF, where the TFS was 71.4% for AFLP and 62.5% for hemolysis, elevated liver enzymes, low platelets (HELLP), respectively. Ten patients did not improve post-termination of pregnancy. Of these patients, 6 (1 AFLP, 4 HELLP, 1 overlap) patients received LT with 1 post-transplant mortality. All 4 patients who did not receive transplants died. They also reported that all patients having ALF in this group met the Swansea criteria, indicating that it is not very helpful to distinguish ALF from AFLP.
Similar results were reported by Westbrook et al. in their group of 54 patients. In this group, the TFS was 86% (43/50), while 75% (3/4) of patients receiving LT survived. Overall, serum lactate >2.8 mg/dl had the best discriminatory value with 73% sensitivity and 75% specificity to predict death or LT. The addition of hepatic encephalopathy increased the sensitivity to 90% and 86%, respectively. KCC was not a good predictor of outcome in this cohort.
The available data on TFS and post LT survival in various etiologies discussed are summarized in Table 3.
PRIORITIZATION
The above discussion highlights the importance of LT in changing the outcomes of patients having ALF. However, the donor pool of organs is small, and not all patients requiring LT can receive one in time. Thus, with the ever-increasing advancements in critical care and ever-expanding criteria for utilization of marginal grafts, it becomes imperative to judiciously identify the following:
: (i) those patients who will improve without a transplant, (ii) those who would require a transplant, (iii) patients who require a transplant but are too sick to undergo surgery or unlikely to recover (futile care) Thus, patients in group (ii) should be prioritized for LT while transplant should be discouraged in groups (i) and (iii). In order to standardize the process of prioritization (and subsequent referral), several scoring systems have been developed over time.
Some of these scoring systems relate to the severity of liver dysfunction in general (Child score, MELD score, Clichy score, Bilirubin-Lactate-Etiology, the ALF early dynamic, ALFSG score, while some are related to specific etiologies (KCC, Ganzert, Escudie criteria, Wilson's Index). Finally, the use of some scoring systems has been extrapolated from their validation in patients with multiorgan failure syndrome (acute physiology and chronic health evaluation, sequential organ failure assessment). Dynamic assessment of prognostic scores (day 1 and day 3) performs better than one-time assessment for predicting outcomes.
Ability of King's college criteria and model for end-stage liver disease scores to predict mortality of patients with acute liver failure: a meta-analysis.
APAP-ALF: Pooled Sen and Spec 80% and 53%, as compared to 76% and 73% in non-APAP-ALF, with DOR of 6.55 compared to 8.42 for Non-APAP-ALF. In APAP-ALF, MELD>33 on Day 1 after the onset of HE had a Sen and Spec: 60% and 69%: predicting mortality.
Ability of King's college criteria and model for end-stage liver disease scores to predict mortality of patients with acute liver failure: a meta-analysis.
listed 18 patients: 8 (44.4%) received an LT and survived while 5 recovered spontaneously. The remaining 5 patients died while waiting for an LT. Zaman et al.
For APAP-ALF: Sen and Spec: 75% and 56% for mortality; PPV: 50%. For non-APAP-ALF: Sen and Spec: 69% and 50%, PPV 64%. Major drawback: included HBV patients only
reported 808 cases of ALF of which 587 received LT while 112 had spontaneous recovery. The 1-year survival rate and survival after LT was 66.3% and 74.2%, respectively.
Arterial Ammonia, bilirubin, HE greater than Grade II, INR
Scores ≥4: Higher mortality (Sen: 73%, Spec: 93%). Performs better than KCC and MELD in predicting outcomes, even when serial values of three days are taken. The higher PPV and NPV of the ALFED score as compared to KCC and MELD may be useful in choosing candidates for LT and limiting wastage of organs
Coma grade, INR, bilirubin, phosphorus, M30 levels
Sen and Spec: 85.6% and 64.7% for poor outcomes. AUROC was higher (0.82) compared to MELD (0.70) and KCC (0.65). Major limiting factor: cytokeratin-18 cleavage fragments not routinely available.
listed 75 patients for LT of whom 45 (60%) received a transplant. 35/45 (77.7%) patients survived while 12 patients on the list recovered spontaneously.
Ability of King's college criteria and model for end-stage liver disease scores to predict mortality of patients with acute liver failure: a meta-analysis.
Ability of King's college criteria and model for end-stage liver disease scores to predict mortality of patients with acute liver failure: a meta-analysis.
Ability of King's college criteria and model for end-stage liver disease scores to predict mortality of patients with acute liver failure: a meta-analysis.
Early indicators of prognosis in fulminant hepatic failure: an assessment of the model for end-stage liver disease (MELD) and King's college hospital criteria.
Sen 100% and Spec 98% The authors reported a better predictive value of this criteria compared to KCC. Limitations: retrospective, heterogeneity in baseline cohort
6 patients were listed for LT of whom 4 (66.6%) received an organ. Of the transplanted patients, only 2 survived, while the other 2 patients expired within 24 h of LT
Age, bilirubin, INR, ammonia, creatinine and hemoglobin
Performs better (c statistic 0.84) than the KCC (0.64), MELD (0.74) and MELD-Na (0.72).
74 patients (25.2%) in the derivation set received LT, while only 3 patients (5.4%) in the validation cohort underwent LT. TFS was 59.2% and 58.9% in each group, respectively.
The sequential organ failure assessment (SOFA) score is prognostically superior to the model for end-stage liver disease (MELD) and MELD variants following paracetamol (acetaminophen) overdose.
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 liver failure.
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 liver failure.
≥124 μmol/L: Sen, Spec 78.6% and 76.3%, DA: 77.5%. >122 μmol/L for first three days: higher risk of mortality (OR 10.7), cerebral edema and infections. Limitations: needs validation at LT centers.
The major scoring systems being used at present include KCC, MELD, and the Clichy score. Several other scoring systems have been touted from time to time, but no single score can accurately predict outcomes in patients having ALF. The initial scores were static prognostic models, which did not reflect the dynamic nature of the disease process. With time and advancements in laboratory medicine, the availability of serial lactate values and ammonia help to assess the changing clinical situations in these patients more rapidly, which translates to earlier decision-making. However, these tests have limitations (e.g. renal dysfunction, sepsis affecting ammonia values). Thus an ideal scoring system would be dynamic, performs well across etiologies with high positive predictive value (indicating that a deserving patient gets a transplant) with a high negative predictive value (indicating that those who would survive without transplant are not listed). It should also allow sufficiently early identification of patients who need LT so that they may be referred to a transplant center in time.
TIMING
The timing of LT is paramount in patients having ALF.
This becomes even more pertinent, with several centers reporting high rates of TFS and a dearth of available organs in the face of an ever-burgeoning demand (Figure 1). Recent data suggest a reduction in incidence of cerebral edema and intracranial hypertension in patients with ALF.
Transplanting a patient too early in the course of illness increases the likelihood of giving an organ to a patient with a high probability of spontaneous recovery with supportive care (Figure 2). Similarly, a late decision would rob a potential candidate of a life-saving intervention.
Although the above-mentioned prognostic scores help stratify patients and identify those who would have a poor outcome, as of now no test can be treated as a gold standard, and at the time of writing, no single test is used by any recognized transplant organization as a criterion for organ allocation.
Figure 2Timepoints in management of ALF—Point A: Consideration for liver transplant, Point B: Transplant unlikely to be of further benefit. Points A and B are determined by dynamic application of prognostic scores. ALF, acute liver failure.
Poor prognostic markers in patients with ALF are provided in Figure 3. These markers may be pointers for early transfer to a specialized transplant center and early institution of care by multidisciplinary teams.
Hepatic encephalopathy is often associated with a poor prognosis, but outcomes seem to be associated with the time of onset rather than the grade of coma. Thus a patient with a hyperacute presentation with high grade HE may fare better than one with a subacute ALF with low grade HE.
Similarly, as highlighted before, in some etiologies such as mushroom poisoning, mortality rates may be high even in the absence of HE due to early onset of extrahepatic organ failures.
INR also holds a unique position in the assessment of prognosis as the interpretation of a high INR should be done in the context of the etiology. Thus while an INR of 4 would not indicate a poor prognosis in a patient with APAP-ALF, the same value would be considered alarming in a patient with non-APAP-ALF.
Overall, there is only a single absolute contraindication to LT in an ALF patient-irreversible brain injury (Table 5). Multiple relative contraindications exist, and the final decision would be dependent on the judgment of the treating team with regard to the chances of survival of the patient post-transplant (Figure 4).
In general, the onset of hepatic encephalopathy is clinically regarded as a parameter to identify a patient with a potentially poor prognosis, and these patients are considered for transfer.
An early transfer to an SLU provides the opportunity for better monitoring and management of these patients, which includes intensive care, intracranial pressure monitoring (ICP), and a multidisciplinary approach.
The Scottish look back study reviewing the management of ALF patients over 22 years in Scotland reported better outcomes with early referral to an SLU.
Another study by Reddy et al. supports these results and reports better outcomes in patients having SLU due to better critical care services and higher LT rates, particularly in patients with APAP-ALF who may have a rapidly downhill progression.
However, while SLUs have shown better outcomes in patients over time, some aspects of critical care have also come under criticism, such as the role of ICP management, which has shown to have no impact on survival or neurological recovery in APAP-ALF patients, and is associated with worse 21-day outcomes in patients of non-APAP-ALF.
Due to the general dearth of donor livers for transplant, several clinical devices and newer treatment methods have been tried in ALF such as (i) extracorporeal liver support (ECLS) and (ii) plasma-exchange.
ECLS include two types of devices—artificial (A-ECLS) and bioartificial (B-ECLS). At present, only 3 A-ECLS (molecular adsorbent recirculating system (MARS), prometheus, and single pass albumin dialysis) and 2 B-ECLS devices have been evaluated in humans (HepatAssist and extracorporeal liver assist device). Despite a lot of enthusiasm over its theoretical benefits in ALF, none of these devices have shown a mortality benefit in randomized trials.
The role of plasmapheresis in WD and rodenticide poisoning has been discussed previously. A recent meta-analysis reviewed the use of plasmapheresis in ALF and demonstrated significantly better encephalopathy, biochemical, and hemodynamic parameters than standard medical care. The 30- and 90-day TFS was also better in those receiving plasmapheresis. The main limitation of the data is the lack of randomized trials with majority of the data being retrospective- or case-based.
A recent RCT from India compared standard volume plasma exchange with standard medical therapy and reported significantly lower lactate and serum ammonia levels along with higher TFS at 21 days (75%) in the plasma exchange arm.
Further standardization of volume of plasma exchanged, duration, and so on needs to be optimized but in view of the encouraging results with the procedure, it is currently recognized as a level 1 indication by European Association for Study of the Liver.
Live donor liver transplant (LDLT) has changed the landscape of LT by offering a donor liver from close relatives of the patient. This has led to significant decrease in the wait time for a liver as well as improved outcomes and lower cold ischemia times (CIT).
Campsen et al. reviewed the LDLT data available from 9 US centers over a 9 year period (1998–2007) and reported survival rates of 70% and a median waiting time of 1 day for a transplant.
A study of 40 adults with ALF undergoing LDLT from India in 2019 also reported similar lower median wait times and benefits, although noting that a strict protocol should be followed to avoid any morbidity and mortality that may arise from rapid screening of the donor.
However, despite the many benefits, LDLT involves major surgery on a live individual, thus making it imperative to assess the need for transplant in the patient. If the prognostic scores are not well applied, the end result may be risking the life of both the donor and patient for an unnecessary transplant.
Another limitation to LDLT is that the rates of biopsy-proven rejection and graft loss were similar to deceased donor liver transplant (DDLT) in a large cohort reviewed by Shaked et al., demonstrating that the lower CIT does not provide an immunological benefit.
Several ethical concerns such as issues with autonomy, beneficence, non-maleficence, and equity have also limited the popularity of LDLT, and it continues to lag behind DDLT.
In contrast to the Western world, LDLT rates are higher in India, due to the stigma associated with organ harvesting after death and the lack of a strong, centralized organ procurement, and distribution agency (and national policies supporting the same), which leads to most private institutions imbibing available organs and no common pool for those awaiting transplants.
The reversibility of ALF with LT has spurred research worldwide on how best to identify those who would benefit from early transplantation as well as in methods to address the dearth of organ availability. Future avenues of research and advancements would largely relate to better prognostic systems, better critical care medicine practices to improve the TFS and alternatives to organ transplants such as liver organoids or hepatocyte transplantation. However, several issues pertinent to India exist, which also need to be addressed. This involves the establishment of a system of transplant registries and centralized regulations such as in the US to ensure that the most deserving patients receive organs. Patient education and de-stigmatizing organ donation would help reduce the acute shortage of organs in our country. Making organ donation an opt-out option is another area which may be explored.
ALF is a rare condition associated with risks of extrahepatic organ failure and high mortality. Improvements in critical care medicine have improved patients' TFS rates and not all patients require LT. Current guidelines support informing SLUs when encountering a patient with ALF. Several scoring systems are available to dynamically assess and identify patients with poor prognostic features. These patients merit early referral to a higher center and consideration for a liver transplant. Patients with ALF are accorded highest priority with short waiting times for LT, hence accurate prognostication is required to prevent organ wastage as well as correct timing to prevent transplantation to patients who cannot be salvaged. The timing and referral are finely balanced and need careful consideration in each case. No prognostic system is foolproof or can be considered a gold standard in clinical practice. DDLT and LDLT are the definitive treatment options, while plasmapheresis may be used as a bridge to transplantation.
Credit authorship statement
Sagnik Biswas: review of literature and drafting manuscript.
Dr Shalimar: conceptualization, review of literature, drafting manuscript, critical review.
CONFLICTS OF INTEREST
All authors have none to declare.
FUNDING INFORMATION
None.
References
Shalimar
Acharya Subrat K.
Lee William M.
Worldwide differences in acute liver failure.
in: Critical Care in Acute Liver Failure. Future Medicine Ltd,
2013: 32-46
Evaluation for liver transplantation in adults: 2013 practice guideline by the American association for the study of liver diseases and the American society of transplantation.
Acute liver failure secondary to yellow phosphorus rodenticide poisoning: outcomes at a center with dedicated liver intensive care and transplant unit.
Ability of King's college criteria and model for end-stage liver disease scores to predict mortality of patients with acute liver failure: a meta-analysis.
Early indicators of prognosis in fulminant hepatic failure: an assessment of the model for end-stage liver disease (MELD) and King's college hospital criteria.
The sequential organ failure assessment (SOFA) score is prognostically superior to the model for end-stage liver disease (MELD) and MELD variants following paracetamol (acetaminophen) overdose.
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 liver failure.
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