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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 -
Research and Practice in Thrombosis and... Aug 2023Well-designed studies with sufficient sample size comparing andexanet alfa vs 4-factor prothrombin complex concentrate (4F-PCC) in routine clinical practice to evaluate...
Lower mortality with andexanet alfa vs 4-factor prothrombin complex concentrate for factor Xa inhibitor-related major bleeding in a U.S. hospital-based observational study.
BACKGROUND
Well-designed studies with sufficient sample size comparing andexanet alfa vs 4-factor prothrombin complex concentrate (4F-PCC) in routine clinical practice to evaluate clinical outcomes are limited.
OBJECTIVES
To compare in-hospital mortality in patients hospitalized with rivaroxaban- or apixaban-related major bleeding who were treated with andexanet alfa or 4F-PCC.
METHODS
An observational cohort study (ClinicalTrials.gov identifier: NCT05548777) was conducted using electronic health records between May 2018 and September 2022 from 354 U.S. hospitals. Inclusion criteria were age ≥18 years, inpatient admission with diagnosis code D68.32 (bleeding due to extrinsic anticoagulation), a record of use of the factor Xa inhibitors rivaroxaban or apixaban, andexanet alfa or 4F-PCC treatment during index hospitalization, and a documented discharge disposition. Multivariable logistic regression on in-hospital mortality with andexanet alfa vs 4F-PCC was performed. The robustness of the results was assessed via a supportive propensity score-weighted logistic regression.
RESULTS
The analysis included 4395 patients (andexanet alfa, = 2122; 4F-PCC, = 2273). There were 1328 patients with intracranial hemorrhage (ICH), 2567 with gastrointestinal (GI) bleeds, and 500 with critical compartment or other bleed types. In the multivariable analysis, odds of in-hospital mortality were 50% lower for andexanet alfa vs 4F-PCC (odds ratio [OR], 0.50; 95% CI, 0.39-0.65; < .01) and were consistent for both ICH (OR, 0.55; [0.39-0.76]; < .01) and GI bleeds (OR, 0.49 [0.29-0.81]; = .01). Similar results were obtained from the supporting propensity score-weighted logistic regression analyses.
CONCLUSION
In this large observational study, treatment with andexanet alfa in patients hospitalized with rivaroxaban- or apixaban-related major bleeds was associated with 50% lower odds of in-hospital mortality than 4F-PCC. The magnitude of the risk reduction was similar in ICH and GI bleeds.
PubMed: 37753225
DOI: 10.1016/j.rpth.2023.102192