In a large cohort of ALF patients, hyperammonemia was associated with high-grade HE and worse 21-day TFS. CRRT was associated with a reduction in serum ammonia level and improvement of 21-day TFS. (Hepatology 2017).
Wilson’s disease (WD) is a rare cause of acute liver failure (ALF) that is thought to have a uniformly fatal outcome without liver transplantation (LT). Previous studies proposed diagnostic and prognostic criteria for WD‐ALF. It is not known whether these apply to WD patients presenting as severe acute liver injury (ALI) without encephalopathy. From 2008 to 2018, 822 patients with ALI in the US Acute Liver Failure Study Group (ALFSG) registry were enrolled and prospectively followed. The diagnosis of WD‐ALI was confirmed in 8 patients. Serum biochemical diagnostic ratios predicting WD‐ALF (alkaline phosphatase [ALP]:total bilirubin(TB) and aspartate aminotransferase [AST]:alanine aminotransferase [ALT]) were determined in these patients, and predictors of prognosis for WD‐ALI were evaluated. Of these 8 ALI‐WD patients, 5 received an LT. Ratios of both ALP:TB of <4 and AST:ALT of >2.2 on study admission were met in 4 LT patients. All LT patients were female. The Model for End‐Stage Liver Disease scores on admission were generally higher in LT patients. All transplanted patients had an initial revised WD score of >11 (>10 predicting poor outcome without LT in WD‐ALF), whereas in non‐LT patients, 2 had scores of 9, and 1 a score of 13. Also, 3 LT patients were started on chelation therapy, 2 were started on plasmapheresis, and 1 was started on Molecular Adsorbent Recirculating System therapy. All non‐LT patients were treated with chelation. At 21 days, all patients were alive and discharged from the hospital. In conclusion, some patients with ALI due to WD may survive without LT. Revised Wilson index scores >10 predict poor outcome in most patients with WD‐ALI, as they do for WD‐ALF, and they correlate positively with the ALI model in this cohort. Biochemical ratios for WD diagnosis appear more applicable to ALF compared with WD‐ALI.
OBJECTIVES
The increasing use of complementary and alternative medicines (CAMs) has been associated with a rising incidence of CAM-induced drug-induced liver injury (DILI). The aim of this study was to examine the clinical features and outcomes among patients with acute liver failure (ALF) and acute liver injury (ALI) enrolled in the Acute Liver Failure Study Group database, comparing CAM-induced with prescription medicine (PM)-induced DILI.
METHODS
A total of 2,626 hospitalized patients with ALF/ALI of any etiology were prospectively enrolled between 1998 and 2015 from 32 academic transplant centers. Only those with CAM or PM-induced ALI/ALF were selected for analysis.
RESULTS
A total of 253 (9.6%) subjects were found to have idiosyncratic DILI, of which 41 (16.3%) were from CAM and 210 (83.7%) were due to PM. The fraction of DILI-ALF/ALI cases due to CAM increased from 1998–2007 to 2007–2015 (12.4 vs. 21.1%, P=0.047). There was no difference in the type of liver injury—hepatocellular, cholestatic, or mixed—between groups as determined by R score (P=0.26). PM-induced DILI showed higher serum alkaline phosphatase levels compared with the CAM group (median IU/L, 171 vs. 125, P=0.003). The CAM population had fewer comorbid conditions (1.0 vs. 2.0, P<0.005), higher transplantation rates (56 vs. 32%, P<0.005), and a lower ALF-specific 21-day transplant-free survival (17 vs. 34%, P=0.044).
CONCLUSIONS
CAM-induced DILI is at least as severe in presentation as that observed due to PM with higher rates of transplantation and lower transplant-free survival in those who progress to ALF. This study highlights the increasing incidence of CAM-induced liver injury and emphasizes the importance of early referral and evaluation for liver transplantation when CAM-induced liver injury is suspected.
In an analysis of the Acute Liver Failure Study Group cohort, we found acetaminophen-induced ALI and ALF to be more common among women. Women have greater critical care needs than men, and increased risk for severe HE, which could be due in part to increased use of sedatives. Future studies should investigate sex differences in acetaminophen metabolism and hepatotoxicity, particularly among users of opioids.
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