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Seminars in Liver Disease Aug 2022Abbreviated pathogenesis and clinical course of the acute liver failure syndrome. The pathogenesis and clinical course of the syndrome of acute liver failure (ALF)...
Abbreviated pathogenesis and clinical course of the acute liver failure syndrome. The pathogenesis and clinical course of the syndrome of acute liver failure (ALF) differs depending upon the etiology of the primary liver injury. In turn, the severity of the liver injury and resulting synthetic failure is often the primary determinant of whether a patient is referred for emergency liver transplantation. Injuries by viral etiologies trigger the innate immune system via pathogen-associated molecular patterns (PAMPs), while toxin-induced (and presumably ischemia-induced) injuries do so via damage-associated molecular patterns (DAMPs). The course of the clinical syndrome further depends upon the relative intensity and composition of cytokine release, resulting in an early proinflammatory phenotype (SIRS) and later compensatory anti-inflammatory response phenotype (CARS). The outcomes of overwhelming immune activation are the systemic (extrahepatic) features of ALF (cardiovascular collapse, cerebral edema, acute kidney injury, respiratory failure, sepsis) which ultimately determine the likelihood of death.Acute liver failure (ALF) continues to carry a high risk of mortality or the need for transplantation despite recent improvements in overall outcomes over the past two decades. Optimal management begins with identifying that liver failure is indeed present and its etiology, since outcomes and the need for transplantation vary widely across the different etiologies. Most causes of ALF can be divided into hyperacute (ischemia and acetaminophen) and subacute types (other etiologies), based on time of evolution of signs and symptoms of liver failure; the former evolve in 3 to 4 days and the latter typically in 2 to 4 weeks. Both involve intense release of cytokines and hepatocellular contents into the circulation with multiorgan effects/consequences.Management involves optimizing fluid balance and cardiovascular support, including the use of continuous renal replacement therapy, vasopressors, and pulmonary ventilation. Early evaluation for liver transplantation is advised particularly for acetaminophen toxicity, which evolves so rapidly that delay is likely to lead to death.Vasopressor support, high-grade hepatic encephalopathy, and unfavorable (subacute) etiologies heighten the need for urgent listing for liver transplantation. Prognostic scores such as Kings Criteria, Model for End-Stage Liver Disease, and the Acute Liver Failure Group prognostic index take these features into account and provide reasonable but imperfect predictive accuracy. Future treatments may include liver support devices and/or agents that improve hepatocyte regeneration.
Topics: Acetaminophen; End Stage Liver Disease; Humans; Liver Failure, Acute; Liver Transplantation; Severity of Illness Index
PubMed: 36001996
DOI: 10.1055/s-0042-1755274 -
Advances in Clinical and Experimental... Apr 2018Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a... (Review)
Review
Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a significant impact on mortality in this group of patients. The pathophysiology of sepsis-associated liver dysfunction is very complicated and still not well understood. According to the Surviving Sepsis Campaign (SSC) Guidelines, the diagnosis of liver dysfunction during sepsis is based on the increase in bilirubin concentration >2 mg/dL and the occurrence of coagulation disorders with INR > 1.5. The lack of specificity and ability to distinguish acute liver failure from previous liver dysfunction disqualifies bilirubin as a single parameter reflecting the complex liver function. Clinical manifestations of sepsis-associated liver dysfunction include hypoxic hepatitis, sepsis-induced cholestasis and dysfunction of protein synthesis manifesting with, e.g., coagulopathies. Detoxifying liver dysfunction, which is associated with an increase in serum ammonia concentration, manifesting with e.g., confusion, loss of consciousness and hepatic encephalopathy, may be disguised by analgosedation used in the intensive care unit. To determine a liver dysfunction in a critically ill patient, the concept of shock liver may be used. It is a complex syndrome of hemodynamic, cellular, molecular and immunologic changes leading to severe liver hypoxia. In clinical practice, there is no standardized diagnostic panel that would allow for an early, clear diagnosis of acute liver dysfunction, and there is no therapeutic panel enabling the full restoration of damaged liver function. The aim of the article is to present the pathophysiology and clinical manifestations of sepsis-associated liver dysfunction.
Topics: Critical Illness; Humans; Intensive Care Units; Liver; Liver Failure; Sepsis; Shock, Septic
PubMed: 29558045
DOI: 10.17219/acem/68363 -
Liver Transplantation : Official... May 2016Neonatal acute liver failure (NALF) is a rare disease about which there is little published data; however, NALF is an extremely important condition as it is distinct... (Review)
Review
Neonatal acute liver failure (NALF) is a rare disease about which there is little published data; however, NALF is an extremely important condition as it is distinct from acute liver failure seen in older children and adults. First, unlike acute liver failure in older patients, NALF can be diagnosed in an infant with cirrhosis. This is due to the fetal-neonatal continuum of liver disease, or the principle that neonatal liver failure may be the result of a liver disease that began in utero. Further differences exist in the mechanism of disease, diagnostic principles, and the common etiologies of NALF when compared with pediatric and adult acute liver failure. This review will address many of the distinguishing features of NALF and focus on the most common etiologies of NALF, including gestational alloimmune liver disease (GALD), the most common cause of NALF. Additionally, this review will provide insight into the pathogenesis, diagnosis, and treatment of this rare condition. Liver Transplantation 22 677-685 2016 AASLD.
Topics: Diagnosis, Differential; Graft Survival; Humans; Infant, Newborn; Liver Cirrhosis; Liver Failure, Acute; Liver Transplantation
PubMed: 26946058
DOI: 10.1002/lt.24433 -
The New England Journal of Medicine Dec 2013
Review
Topics: Cardiovascular Diseases; Humans; Liver Failure, Acute; Liver Transplantation; Nutrition Therapy; Respiratory Insufficiency
PubMed: 24369077
DOI: 10.1056/NEJMra1208937 -
Clinical and Molecular Hepatology Jul 2023Acute-on-chronic liver failure is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high... (Review)
Review
Acute-on-chronic liver failure is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. The pathogenesis involves extensive hepatic necrosis, which is associated with severe systemic inflammation and subsequently causes the cytokine storm, leading to portal hypertension, organ dysfunction, and organ failure. These patients have increased gut permeability, releasing lipopolysaccharide (LPS) and damage-associated molecular patterns (DAMPS) in the blood, leading to hyper-immune activation and the secretion of cytokines, followed by immune paralysis, causing the development of infections and organ failure in a proportion of patients. Early detection and the institution of treatment, especially in the "Golden Window" period of 7 days, gives an opportunity for reversal of the syndrome. Scores like the Asian Pacific Association for the Study of the Liver (APASL) ACLF research consortium (AARC) score, a model for end stage liver disease (MELD), and the CLIF Consortium acute-on-chronic liver failure (CLIF-C ACLF) score can help in the prediction of mortality. Treatment strategy includes treatment of acute insult. Patients should be considered for early transplant with MELD score >28, AARC score >10, high-grade hepatic encephalopathy, and in the absence of >2 organ failure or overt sepsis to improve survival of up to 80% at five years. Patients, with no option of transplant, can be treated with emerging therapies like faecal microbial transplant, plasma exchange, etc., which need further evaluation.
Topics: Humans; Severity of Illness Index; Acute-On-Chronic Liver Failure; End Stage Liver Disease; Prognosis; Hepatic Encephalopathy
PubMed: 36938601
DOI: 10.3350/cmh.2022.0103 -
Clinical Medicine (London, England) Apr 2018Decompensated cirrhosis is a common reason for admission to the acute medical unit, and such patients typically have complex medical needs and are at high risk of... (Review)
Review
Decompensated cirrhosis is a common reason for admission to the acute medical unit, and such patients typically have complex medical needs and are at high risk of in-hospital death. It is therefore vital that these patients receive appropriate investigations and management as early as possible in their patient journey. Typical presenting clinical features include jaundice, ascites, hepatic encephalopathy, hepato-renal syndrome or variceal haemorrhage. A careful history, examination and investigations can help identify the precipitating cause (infections, gastrointestinal bleeding, high alcohol intake / alcohol-related hepatitis or drug-induced liver injury), so appropriate treatment can be given. A 'care bundle' that has been endorsed by the British Society of Gastroenterology is available to help guide the management of patients with decompensated cirrhosis for the first 24 hours and ensure all aspects are addressed. Specific management of complications, such as infections, gastrointestinal bleeding, hepatic encephalopathy and hepatorenal syndrome, are discussed.
Topics: Acute Disease; Ascites; Humans; Liver Cirrhosis; Liver Diseases, Alcoholic; Liver Failure
PubMed: 29700095
DOI: 10.7861/clinmedicine.18-2-s60 -
Hepatology (Baltimore, Md.) Oct 2023Acute liver failure (ALF) describes a clinical syndrome of rapid hepatocyte injury leading to liver failure manifested by coagulopathy and encephalopathy in the absence... (Review)
Review
Acute liver failure (ALF) describes a clinical syndrome of rapid hepatocyte injury leading to liver failure manifested by coagulopathy and encephalopathy in the absence of pre-existing cirrhosis. The hallmark diagnostic features are a prolonged prothrombin time (ie, an international normalized ratio of prothrombin time of ≥1.5) and any degree of mental status alteration (HE). As a rare, orphan disease, it seemed an obvious target for a multicenter network. The Acute Liver Failure Study Group (ALFSG) began in 1997 to more thoroughly study and understand the causes, natural history, and management of ALF. Over the course of 22 years, 3364 adult patients were enrolled in the study registry (2614 ALF and 857 acute liver injury-international normalized ratio 2.0 but no encephalopathy-ALI) and >150,000 biosamples collected, including serum, plasma, urine, DNA, and liver tissue. Within the Registry study sites, 4 prospective substudies were conducted and published, 2 interventional ( N -acetylcysteine and ornithine phenylacetate), 1 prognostic [ 13 C-methacetin breath test (MBT)], and 1 mechanistic (rotational thromboelastometry). To review ALFSG's accomplishments and consider next steps, a 2-day in-person conference was held at UT Southwestern Medical Center, Dallas, TX, entitled "Acute Liver Failure: Science and Practice," in May 2022. To summarize the important findings in the field, this review highlights the current state of understanding of ALF and, more importantly, asks what further studies are needed to improve our understanding of the pathogenesis, natural history, and management of this unique and dramatic condition.
Topics: Adult; Humans; Prospective Studies; Liver Failure, Acute; Prognosis; Liver Transplantation; Multicenter Studies as Topic
PubMed: 37183883
DOI: 10.1097/HEP.0000000000000458 -
Indian Pediatrics Apr 2022Guidelines for management of pediatric acute liver failure (PALF) were recently published by the North American Society for Pediatric Gastroenterology, Hepatology, and...
Guidelines for management of pediatric acute liver failure (PALF) were recently published by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). We, herein, update the readers about the diagnosis and management of PALF with emphasis on the changes in assessment and staging of hepatic encephalopathy, administration and goals of supportive therapy, frequency of monitoring, and management of complications.
Topics: Child; Child Nutritional Physiological Phenomena; Gastroenterology; Humans; Liver Failure, Acute; Nutritional Status
PubMed: 35410966
DOI: No ID Found -
World Journal of Gastroenterology Jan 2020Acute liver failure (ALF) and acute-on-chronic liver (ACLF) carry high short-term mortality rate, and may result from a wide variety of causes. Plasma exchange has been...
BACKGROUND
Acute liver failure (ALF) and acute-on-chronic liver (ACLF) carry high short-term mortality rate, and may result from a wide variety of causes. Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant. Other cohort studies demonstrated potential improvement in survival in patients with ACLF.
AIM
To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.
METHODS
Databases MEDLINE PubMed, and EMBASE were searched and relevant publications up to 30 March, 2019 were assessed. Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange, with or without another alternative non-bioartificial liver assist device.
RESULTS
Three hundred twenty four records were reviewed, of which 62 studies were found to be duplicates. Of the 262 records screened, 211 studies were excluded. Fifty-one articles were assessed for eligibility, for which 7 were excluded. Twenty-nine studies were included for ALF only, and 9 studies for ACLF only. Six studies included both ALF and ACLF patients. A total of 44 publications were included. Of the included publications, 2 were randomized controlled trials, 14 cohort studies, 12 case series, 16 case reports. All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment (SMT) for ACLF, a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60 (95%CI 0.46-0.77, < 0.01).
CONCLUSION
The level of evidence for use of high volume plasma exchange in selected ALF cases is high. Plasma exchange in ACLF improves survival at 30-and 90-d in non-transplanted patients. Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.
Topics: Acute-On-Chronic Liver Failure; Hospital Mortality; Humans; Liver Failure, Acute; Plasma Exchange; Randomized Controlled Trials as Topic; Survival Rate; Time Factors; Treatment Outcome
PubMed: 31988586
DOI: 10.3748/wjg.v26.i2.219 -
Clinics in Liver Disease Aug 2014The Model for End-Stage Liver Disease (MELD) has been the single best predictor of outcome of the progression of cirrhosis. Acute-on-chronic liver failure (ACLF) has... (Review)
Review
The Model for End-Stage Liver Disease (MELD) has been the single best predictor of outcome of the progression of cirrhosis. Acute-on-chronic liver failure (ACLF) has been proposed as an alternative path in the natural history of cirrhosis. ACLF occurs in patients with chronic liver disease and is characterized by a precipitating event, resulting in acute deterioration in liver function, multiorgan system failure, and high short-term mortality. In this review, the natural course of patients with ACLF, especially as it relates to management of cirrhotic patients on the transplant waiting list, and its impact on liver transplantation outcomes are defined.
Topics: End Stage Liver Disease; Humans; Liver Cirrhosis; Liver Failure, Acute; Liver Transplantation; Models, Biological; Multiple Organ Failure; Prognosis; Risk Factors
PubMed: 25017076
DOI: 10.1016/j.cld.2014.05.004