The Natural History of Severe Acute Liver Injury

Abstract

OBJECTIVES Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10× elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR≥2.0, ALT≥10× elevated, and bilirubin≥3.0 mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure. RESULTS Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death. CONCLUSIONS A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center.

Analysis of weekend effect in severe acute liver injury: A nationwide database study

“…The Acute Liver Failure Study Group reported a full recovery as the clinical outcome in 93.0% of patients with severe ALI . The observed survival in our sample was considerably lower, at 57.5%, which may be due to selection of patients with greater illness severity based on the diagnosis codes we used to define severe ALI, as well as inclusion of patients who progress to acute liver failure.…”

“…Severe acute liver injury (ALI) and acute liver failure result in high morbidity and mortality in the absence of prompt diagnosis and cause‐specific management . Acute liver failure causes diffuse cerebral dysfunction due to cerebral edema and elevated intracranial pressure, causing high neurological morbidity and mortality in otherwise healthy adults despite potential reversibility with prompt treatment .…”

Outcomes of Acute Liver Injury in Adults Due to Wilson’s Disease: Is Survival Without Transplant Possible?

“…However, there is a deficit of knowledge of the course of the disease in the patient with WD with acute liver injury (ALI), the precursor to ALF in the natural history of untreated WD. The distinction is critical because the prognosis of ALF due to WD is poor without LT. Our study is unique in capturing a particularly rare cohort of patients presenting with WD‐ALI, different from those categorized with ALF due to WD in lacking hepatic encephalopathy. Out of 822 patients with ALI enrolled in the Acute Liver Failure Study Group (ALFSG) registry over a 10‐year period, only 1% were found to have confirmed WD‐ALI.…”

“…Prognostic scoring systems have been developed separately for WD and for all patients presenting with ALI to help identify which patients will have a poor nontransplant survival and who may be rescued with medical therapy . A prognostic score for WD previously developed by Nazer et al was modified by Dhawan et al in 2005 in a study that included exclusively pediatric WD patients.…”

“…This modified score (the revised Wilson index) has proven both sensitive and specific at predicting mortality of ALF and chronic liver failure due to WD without transplantation, and it can therefore help with prognostication and organ allocation in liver failure due to WD. A prognostic score was also developed by the ALFSG, examining all etiologies of ALI, that was based on nearly 400 patients to predict which patients were likely to progress to ALF, LT, or death . However, none of these prognostic scores were specifically developed for WD patients with ALI, and therefore, they require validation for this patient group.…”