1128 CLINICAL GUIDELINES
Acute Liver Failure Guidelines
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Alexandra Shingina, MD, MSc1, Nizar Mukhtar, MD2, Jamilé Wakim-Fleming, MD, FACG3, Saleh Alqahtani, MBChB, MS4,5,
Robert J. Wong, MD, MS, FACG6, Berkeley N. Limketkai, MD, PhD, FACG7, Anne M. Larson, MD8 and Lafaine Grant, MD9
YQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 06/28/2023
Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid
clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies
are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines
represent the suggested approach to the identification, treatment, and management of ALF and represent the official
practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the
Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When
no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of
clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios.
KEYWORDS: Acute liver failure; liver transplantation; fulminant liver failure; acute liver injury; jaundice; coagulopathy; hepatotoxicity;
multi-organ failure; hepatic encephalopathy
SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/C963
Am J Gastroenterol 2023;118:1128–1153. https://doi.org/10.14309/ajg.0000000000002340; published online March 20, 2023
INTRODUCTION based and population-based factors (3). Furthermore, a narrative
Acute liver failure (ALF) is a life-threatening condition that occurs in evidence summary for each section provides important definitions
patients with no preexisting liver disease and is characterized by liver and further details for the data supporting the statements.
injury (abnormal liver tests), coagulopathy (international normal- Under the auspices of the American College of Gastroen-
ized ratio [INR] .1.5), and hepatic encephalopathy (HE). It has a terology (ACG) Practice Parameters Committee, a group of
multitude of etiologies and a variety of clinical presentations that can experts in the area of ALF were identified for the writing group.
affect virtually every organ system. It is imperative for clinicians The proposed writing group was reviewed by the ACG Practice
to recognize ALF early in patient presentation because initiation Parameters Committee and the ACG leadership, and the final
of treatment and transplant considerations could be lifesaving. approved writing group consisted of the current authorship
The current guideline represents the summary of existing data on team, which includes hepatology experts across a broad range of
diagnosis and management of patients with ALF. practice settings and different stages of clinical and research
The guideline is structured in the format of statements that were career development. Regular meetings were conducted among
considered to be clinically important by the content authors. The this writing group throughout the guideline development pro-
Grading of Recommendations, Assessment, Development, and cess to formulate PICO questions that guided the subsequent
Evaluation (GRADE) process was used to assess the quality of literature search, development of recommendation statements
evidence for each statement (Table 1) (1). The quality of evidence is and key concepts, GRADE assessments, and the preparation of
expressed as high (we are confident in the effect estimate to support the full guideline document.
a particular recommendation), moderate, low, or very low (we have We conducted an electronic search using MEDLINE, EMBASE,
very little confidence in the effect estimate to support a particular and the Cochrane Library through January 2022. We limited
recommendation) based on the risk of bias of the studies, evidence the search to English language and fully published articles. For
of publication bias, heterogeneity among studies, directness of the each PICO question developed, we comprehensively reviewed
evidence, and precision of the estimate of effect (2). A strength of the existing literature, with a focus on studies of the highest quality
recommendation is given as either strong (recommendations) or of evidence (e.g., when available, systematic reviews and meta-
conditional (suggestions) based on the quality of evidence, risks vs analyses, followed by randomized controlled trials, followed by
benefits, feasibility, and costs taking into account perceived patient- observational studies).
1
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; 2Department of Gastroenterology, Kaiser Permanente, San Francisco,
California, USA; 3Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland Ohio, USA;
4
Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA; 5Liver Transplantation Unit, King Faisal Specialist Hospital &
Research Center, Riyadh, Saudi Arabia; 6Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, Gastroenterology
Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA; 7Division of Gastroenterology, UCLA, Los Angeles, California, USA; 8Division of
Gastroenterology and Hepatology, University of Washington, Seattle, Washington, USA; 9Division of Digestive and Liver Diseases, UT Southwestern Medical Center,
Dallas, Texas, USA. Correspondence: Alexandra Shingina. E-mail: .
Received October 14, 2022; accepted April 4, 2023
The American Journal of GASTROENTEROLOGY VOLUME 118 | JULY 2023 www.amjgastro.com
Copyright © 2023 by The American College of Gastroenterology. Unauthorized reproduction of this article is prohibited.
, Acute Liver Failure Guidelines 1129
Table 1. Grading of recommendations assessment, development, and evaluation quality criteria
Quality of evidence Study design Factors lowering the quality of evidence Factors increasing the quality of evidence
High Randomized trial Risk of bias: Strong Association:
21: serious risk of bias 11: strong, no plausible confounders
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22: very serious risk of bias 12: very strong, no major threats to validity
Consistency: 11: evidence of a dose response gradient
21: serious inconsistency 11: all plausible confounders would have
22: very serious inconsistency reduced the effect
Moderate Directness:
YQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 06/28/2023
Low Observational study 21: serious indirectness
Very low Any other evidence 22: very serious indirectness
Precision:
21: serious imprecision
22: very serious imprecision
Publication bias:
21: likely presence of reporting bias
22: very likely presence of reporting bias
In addition to guideline recommendations, the authors have DEFINITION AND PRESENTATION OF ACUTE
highlighted key concept statements that were not included in LIVER FAILURE
the GRADE assessment. Key concepts are statements that the ALF is a rare, acute, potentially reversible condition resulting in
GRADE process has not been applied to and can include both severe liver impairment and rapid clinical deterioration in pa-
expert opinion recommendations and definitions/epidemiological tients without preexisting liver disease (4,5). First described in
statements. Table 2 is a summary of recommendations, whereas 1970, its definition has been refined over the years (5). The def-
Table 3 summarizes the key concept statements. inition of what constitutes ALF varies globally. The most used
Table 2. Recommendations
Statement GRADE quality Strength of recommendation
System-specific management: CNS
1. In patients with ALF and grade 2 or higher encephalopathy, we suggest early CRRT for management of Conditional Very low
hyperammonemia even in the absence of conventional RRT indications
System-specific management: coagulopathy
2. In patients with ALF, in the absence of active bleeding or impending high-risk procedure, we Conditional Very low
recommend against routine correction of coagulopathy
System-specific management: infection
3. In patients with ALF, we recommend against the routine use of prophylactic antimicrobial agents, Conditional Low
given no improvement in either rate of bloodstream infection or 21-day mortality
System-specific management: hemodynamics and renal failure
4. In patients with ALF, we recommend norepinephrine as the first-line vasopressor for hypotension Strong Moderate
refractory to fluid resuscitation
5. In patients with ALF with hypotension not responsive to norepinephrine, we suggest adding Conditional Low
vasopressin as a secondary agent
Etiology-specific management
6. In patients with suspected APAP toxicity, we recommend early administration of N-acetylcysteine Strong Low
7. In patients with non-APAP ALF, we suggest the initiation of intravenous NAC Strong Moderate
8. In patients with ALF due to reactivation of HBV, we recommend starting antiviral therapy Strong Low
9. In patients with ALF due to mushroom poisoning, we recommend initiation of IV silibinin as soon as Conditional Very low
possible. IV penicillin G may be used if IV silibinin is unavailable
Liver transplantation: prognostic models
10. In patients with ALF, we recommend using either the KCC criteria or MELD score for prognostication. Conditional Low
Patients meeting the KCC criteria or presenting with MELD .25 are at high risk of poor outcomes.
ALF, acute liver failure; APAP, N-acetyl-p-aminophenol; CNS, central nervous system; CRRT, continuous renal replacement therapy; HBV, hepatitis B virus; IV, intravenous;
KCC, King’s College Criteria; MELD, Model for End-Stage Liver Disease; NAC, N-acetylcysteine; RRT, renal replacement therapy.
© 2023 by The American College of Gastroenterology The American Journal of GASTROENTEROLOGY
Copyright © 2023 by The American College of Gastroenterology. Unauthorized reproduction of this article is prohibited.
, 1130 Shingina et al
Table 3. Key concepts
General management
Comprehensive testing to elucidate a diagnosis and exclude underlying chronic liver disease is essential in the evaluation of ALF (Table 7).
Biomarkers (ETG or PETH) should be used in addition to psychosocial assessment when alcohol-induced liver disease is suspected.
Grade 2 encephalopathy should prompt transfer to intensive care unit (ICU) while intubation for airway protections should be considered for grade 3 and 4 HE.
Downloaded from http://journals.lww.com/ajg by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWn
Referral for consultation by hepatology or gastroenterology as soon as possible after identification of ALF. Early communication with the transplant center is crucial
to patient management.
When to biopsy
Liver biopsy may help exclude infiltrative disease and malignancy and to identify patients with contraindication to LT.
YQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 06/28/2023
Liver biopsy may help diagnose autoimmune hepatitis, which may respond to immunosuppressive therapy and potentially spare patients the long-term
complications of LT.
There is insufficient evidence to recommend the routine use of liver biopsy in other settings.
When considering liver biopsy in the evaluation of patients with ALF, we suggest using transjugular liver biopsy over other methods.
System-specific management: CNS
ALF patients with grade 2 or higher encephalopathy should be monitored in an ICU setting.
Patients with ALF with grade 3 and 4 encephalopathy should be intubated for airway protection.
There is no conclusive evidence to recommend for or against the use of lactulose or rifaximin for
the treatment of encephalopathy in patients with ALF.
There is no conclusive evidence to recommend routine ICP monitor placement in patients with ALF.
There is no conclusive evidence to recommend routine use of hypothermia to control intracranial pressure in patients with ALF.
System-specific management: coagulopathy
The INR does not accurately reflect bleeding risk in patients with ALF.
Viscoelastic tests may provide a more accurate assessment of coagulopathy in patients with ALF.
System-specific management: infection
In patients with ALF, early assessment for infection is prudent because clinical signs of infection are frequently absent.
There is insufficient evidence in patients with ALF to recommend the use of procalcitonin as a biomarker of infection.
Empiric antibiotic and antifungal therapy may be considered in the setting of clinical deterioration of the patient.
In patients with ALF, we suggest regular surveillance cultures; however, the optimal frequency is unknown.
In patients with ALF and hypotension, intravenous fluid resuscitation should be initiated.
Renal replacement therapy should be considered early in patients with acute kidney injury, electrolyte or metabolic abnormalities, and/or volume overload.
In patients with ALF requiring renal replacement therapy, we recommend CRRT over intermittent hemodialysis.
System-specific management: nutritional and metabolic support
In patients with ALF, monitoring and correction of glucose, fluid, and electrolyte imbalances should be performed.
In patients with ALF, enteral nutritional support should be started if the patient is unable to resume oral intake within 5–7 d.
System-specific management: other management considerations
There is insufficient evidence to recommend for or against the routine use of high-volume plasma exchange or artificial/bioartificial liver support devices in patients
with ALF
Etiology-specific management: acetaminophen hepatotoxicity
In patients with APAP-ALI or APAP-ALF, the duration of NAC treatment should be individualized based on
the patient’s clinical condition and laboratory values.
In patients with APAP overdose, we recommend single-dose activated charcoal administration if
ingestion is known to have occurred within 4 hr.
Etiology-specific management: viral hepatitis
In patients presenting with ALF, grade 2 encephalopathy and features suggestive of HSV infection, we suggest empiric treatment with IV acyclovir until
confirmatory testing with HSV PCR is obtained.
Etiology-specific management: mushroom poisoning
In patients presenting with mushroom poisoning and acute liver injury, Escudie criteria can be used to predict the need for liver transplantation even before the
development of encephalopathy.
Gastric lavage and activated charcoal should be administered within the first few hours after ingestion, provided no contraindications exist.
Etiology-specific management: Wilson disease
In patients presenting with ALF due to suspected or confirmed Wilson disease, liver transplantation evaluation should be initiated during diagnosis because of the
lack of effective medical therapy
Etiology-specific management: AIH
In patients presenting with AS-AIH, we suggest the use of IV corticosteroids.
In patients with AS-AIH, which has progressed to ALF, we recommend early evaluation for liver transplantation
The American Journal of GASTROENTEROLOGY VOLUME 118 | JULY 2023 www.amjgastro.com
Copyright © 2023 by The American College of Gastroenterology. Unauthorized reproduction of this article is prohibited.
Acute Liver Failure Guidelines
Downloaded from http://journals.lww.com/ajg by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWn
Alexandra Shingina, MD, MSc1, Nizar Mukhtar, MD2, Jamilé Wakim-Fleming, MD, FACG3, Saleh Alqahtani, MBChB, MS4,5,
Robert J. Wong, MD, MS, FACG6, Berkeley N. Limketkai, MD, PhD, FACG7, Anne M. Larson, MD8 and Lafaine Grant, MD9
YQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 06/28/2023
Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid
clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies
are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines
represent the suggested approach to the identification, treatment, and management of ALF and represent the official
practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the
Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When
no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of
clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios.
KEYWORDS: Acute liver failure; liver transplantation; fulminant liver failure; acute liver injury; jaundice; coagulopathy; hepatotoxicity;
multi-organ failure; hepatic encephalopathy
SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/C963
Am J Gastroenterol 2023;118:1128–1153. https://doi.org/10.14309/ajg.0000000000002340; published online March 20, 2023
INTRODUCTION based and population-based factors (3). Furthermore, a narrative
Acute liver failure (ALF) is a life-threatening condition that occurs in evidence summary for each section provides important definitions
patients with no preexisting liver disease and is characterized by liver and further details for the data supporting the statements.
injury (abnormal liver tests), coagulopathy (international normal- Under the auspices of the American College of Gastroen-
ized ratio [INR] .1.5), and hepatic encephalopathy (HE). It has a terology (ACG) Practice Parameters Committee, a group of
multitude of etiologies and a variety of clinical presentations that can experts in the area of ALF were identified for the writing group.
affect virtually every organ system. It is imperative for clinicians The proposed writing group was reviewed by the ACG Practice
to recognize ALF early in patient presentation because initiation Parameters Committee and the ACG leadership, and the final
of treatment and transplant considerations could be lifesaving. approved writing group consisted of the current authorship
The current guideline represents the summary of existing data on team, which includes hepatology experts across a broad range of
diagnosis and management of patients with ALF. practice settings and different stages of clinical and research
The guideline is structured in the format of statements that were career development. Regular meetings were conducted among
considered to be clinically important by the content authors. The this writing group throughout the guideline development pro-
Grading of Recommendations, Assessment, Development, and cess to formulate PICO questions that guided the subsequent
Evaluation (GRADE) process was used to assess the quality of literature search, development of recommendation statements
evidence for each statement (Table 1) (1). The quality of evidence is and key concepts, GRADE assessments, and the preparation of
expressed as high (we are confident in the effect estimate to support the full guideline document.
a particular recommendation), moderate, low, or very low (we have We conducted an electronic search using MEDLINE, EMBASE,
very little confidence in the effect estimate to support a particular and the Cochrane Library through January 2022. We limited
recommendation) based on the risk of bias of the studies, evidence the search to English language and fully published articles. For
of publication bias, heterogeneity among studies, directness of the each PICO question developed, we comprehensively reviewed
evidence, and precision of the estimate of effect (2). A strength of the existing literature, with a focus on studies of the highest quality
recommendation is given as either strong (recommendations) or of evidence (e.g., when available, systematic reviews and meta-
conditional (suggestions) based on the quality of evidence, risks vs analyses, followed by randomized controlled trials, followed by
benefits, feasibility, and costs taking into account perceived patient- observational studies).
1
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; 2Department of Gastroenterology, Kaiser Permanente, San Francisco,
California, USA; 3Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland Ohio, USA;
4
Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA; 5Liver Transplantation Unit, King Faisal Specialist Hospital &
Research Center, Riyadh, Saudi Arabia; 6Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, Gastroenterology
Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA; 7Division of Gastroenterology, UCLA, Los Angeles, California, USA; 8Division of
Gastroenterology and Hepatology, University of Washington, Seattle, Washington, USA; 9Division of Digestive and Liver Diseases, UT Southwestern Medical Center,
Dallas, Texas, USA. Correspondence: Alexandra Shingina. E-mail: .
Received October 14, 2022; accepted April 4, 2023
The American Journal of GASTROENTEROLOGY VOLUME 118 | JULY 2023 www.amjgastro.com
Copyright © 2023 by The American College of Gastroenterology. Unauthorized reproduction of this article is prohibited.
, Acute Liver Failure Guidelines 1129
Table 1. Grading of recommendations assessment, development, and evaluation quality criteria
Quality of evidence Study design Factors lowering the quality of evidence Factors increasing the quality of evidence
High Randomized trial Risk of bias: Strong Association:
21: serious risk of bias 11: strong, no plausible confounders
Downloaded from http://journals.lww.com/ajg by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWn
22: very serious risk of bias 12: very strong, no major threats to validity
Consistency: 11: evidence of a dose response gradient
21: serious inconsistency 11: all plausible confounders would have
22: very serious inconsistency reduced the effect
Moderate Directness:
YQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 06/28/2023
Low Observational study 21: serious indirectness
Very low Any other evidence 22: very serious indirectness
Precision:
21: serious imprecision
22: very serious imprecision
Publication bias:
21: likely presence of reporting bias
22: very likely presence of reporting bias
In addition to guideline recommendations, the authors have DEFINITION AND PRESENTATION OF ACUTE
highlighted key concept statements that were not included in LIVER FAILURE
the GRADE assessment. Key concepts are statements that the ALF is a rare, acute, potentially reversible condition resulting in
GRADE process has not been applied to and can include both severe liver impairment and rapid clinical deterioration in pa-
expert opinion recommendations and definitions/epidemiological tients without preexisting liver disease (4,5). First described in
statements. Table 2 is a summary of recommendations, whereas 1970, its definition has been refined over the years (5). The def-
Table 3 summarizes the key concept statements. inition of what constitutes ALF varies globally. The most used
Table 2. Recommendations
Statement GRADE quality Strength of recommendation
System-specific management: CNS
1. In patients with ALF and grade 2 or higher encephalopathy, we suggest early CRRT for management of Conditional Very low
hyperammonemia even in the absence of conventional RRT indications
System-specific management: coagulopathy
2. In patients with ALF, in the absence of active bleeding or impending high-risk procedure, we Conditional Very low
recommend against routine correction of coagulopathy
System-specific management: infection
3. In patients with ALF, we recommend against the routine use of prophylactic antimicrobial agents, Conditional Low
given no improvement in either rate of bloodstream infection or 21-day mortality
System-specific management: hemodynamics and renal failure
4. In patients with ALF, we recommend norepinephrine as the first-line vasopressor for hypotension Strong Moderate
refractory to fluid resuscitation
5. In patients with ALF with hypotension not responsive to norepinephrine, we suggest adding Conditional Low
vasopressin as a secondary agent
Etiology-specific management
6. In patients with suspected APAP toxicity, we recommend early administration of N-acetylcysteine Strong Low
7. In patients with non-APAP ALF, we suggest the initiation of intravenous NAC Strong Moderate
8. In patients with ALF due to reactivation of HBV, we recommend starting antiviral therapy Strong Low
9. In patients with ALF due to mushroom poisoning, we recommend initiation of IV silibinin as soon as Conditional Very low
possible. IV penicillin G may be used if IV silibinin is unavailable
Liver transplantation: prognostic models
10. In patients with ALF, we recommend using either the KCC criteria or MELD score for prognostication. Conditional Low
Patients meeting the KCC criteria or presenting with MELD .25 are at high risk of poor outcomes.
ALF, acute liver failure; APAP, N-acetyl-p-aminophenol; CNS, central nervous system; CRRT, continuous renal replacement therapy; HBV, hepatitis B virus; IV, intravenous;
KCC, King’s College Criteria; MELD, Model for End-Stage Liver Disease; NAC, N-acetylcysteine; RRT, renal replacement therapy.
© 2023 by The American College of Gastroenterology The American Journal of GASTROENTEROLOGY
Copyright © 2023 by The American College of Gastroenterology. Unauthorized reproduction of this article is prohibited.
, 1130 Shingina et al
Table 3. Key concepts
General management
Comprehensive testing to elucidate a diagnosis and exclude underlying chronic liver disease is essential in the evaluation of ALF (Table 7).
Biomarkers (ETG or PETH) should be used in addition to psychosocial assessment when alcohol-induced liver disease is suspected.
Grade 2 encephalopathy should prompt transfer to intensive care unit (ICU) while intubation for airway protections should be considered for grade 3 and 4 HE.
Downloaded from http://journals.lww.com/ajg by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWn
Referral for consultation by hepatology or gastroenterology as soon as possible after identification of ALF. Early communication with the transplant center is crucial
to patient management.
When to biopsy
Liver biopsy may help exclude infiltrative disease and malignancy and to identify patients with contraindication to LT.
YQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 06/28/2023
Liver biopsy may help diagnose autoimmune hepatitis, which may respond to immunosuppressive therapy and potentially spare patients the long-term
complications of LT.
There is insufficient evidence to recommend the routine use of liver biopsy in other settings.
When considering liver biopsy in the evaluation of patients with ALF, we suggest using transjugular liver biopsy over other methods.
System-specific management: CNS
ALF patients with grade 2 or higher encephalopathy should be monitored in an ICU setting.
Patients with ALF with grade 3 and 4 encephalopathy should be intubated for airway protection.
There is no conclusive evidence to recommend for or against the use of lactulose or rifaximin for
the treatment of encephalopathy in patients with ALF.
There is no conclusive evidence to recommend routine ICP monitor placement in patients with ALF.
There is no conclusive evidence to recommend routine use of hypothermia to control intracranial pressure in patients with ALF.
System-specific management: coagulopathy
The INR does not accurately reflect bleeding risk in patients with ALF.
Viscoelastic tests may provide a more accurate assessment of coagulopathy in patients with ALF.
System-specific management: infection
In patients with ALF, early assessment for infection is prudent because clinical signs of infection are frequently absent.
There is insufficient evidence in patients with ALF to recommend the use of procalcitonin as a biomarker of infection.
Empiric antibiotic and antifungal therapy may be considered in the setting of clinical deterioration of the patient.
In patients with ALF, we suggest regular surveillance cultures; however, the optimal frequency is unknown.
In patients with ALF and hypotension, intravenous fluid resuscitation should be initiated.
Renal replacement therapy should be considered early in patients with acute kidney injury, electrolyte or metabolic abnormalities, and/or volume overload.
In patients with ALF requiring renal replacement therapy, we recommend CRRT over intermittent hemodialysis.
System-specific management: nutritional and metabolic support
In patients with ALF, monitoring and correction of glucose, fluid, and electrolyte imbalances should be performed.
In patients with ALF, enteral nutritional support should be started if the patient is unable to resume oral intake within 5–7 d.
System-specific management: other management considerations
There is insufficient evidence to recommend for or against the routine use of high-volume plasma exchange or artificial/bioartificial liver support devices in patients
with ALF
Etiology-specific management: acetaminophen hepatotoxicity
In patients with APAP-ALI or APAP-ALF, the duration of NAC treatment should be individualized based on
the patient’s clinical condition and laboratory values.
In patients with APAP overdose, we recommend single-dose activated charcoal administration if
ingestion is known to have occurred within 4 hr.
Etiology-specific management: viral hepatitis
In patients presenting with ALF, grade 2 encephalopathy and features suggestive of HSV infection, we suggest empiric treatment with IV acyclovir until
confirmatory testing with HSV PCR is obtained.
Etiology-specific management: mushroom poisoning
In patients presenting with mushroom poisoning and acute liver injury, Escudie criteria can be used to predict the need for liver transplantation even before the
development of encephalopathy.
Gastric lavage and activated charcoal should be administered within the first few hours after ingestion, provided no contraindications exist.
Etiology-specific management: Wilson disease
In patients presenting with ALF due to suspected or confirmed Wilson disease, liver transplantation evaluation should be initiated during diagnosis because of the
lack of effective medical therapy
Etiology-specific management: AIH
In patients presenting with AS-AIH, we suggest the use of IV corticosteroids.
In patients with AS-AIH, which has progressed to ALF, we recommend early evaluation for liver transplantation
The American Journal of GASTROENTEROLOGY VOLUME 118 | JULY 2023 www.amjgastro.com
Copyright © 2023 by The American College of Gastroenterology. Unauthorized reproduction of this article is prohibited.
