Despite a perceived bleeding diathesis, clinically significant bleeding is uncommon in patients with ALF; bleeding complications in patients with ALF are markers of severe systemic inflammation rather than of coagulopathy and so portend a poor prognosis. (Hepatology 2018;67:1931-1942).

BACKGROUND & AIMS Analyses of outcomes after acute liver failure (ALF) have typically included all ALF patients regardless of whether they were listed for liver transplantation (LT). We hypothesized that limiting analysis to listed patients might provide novel insights into factors associated with outcome, focusing attention on disease evolution after listing. METHODS Listed adult ALF patients enrolled in the US Acute Liver Failure Study Group registry between 2000 and 2013 were analyzed to determine baseline factors associated with 21-day outcomes after listing. RESULTS We classified 617 patients (36% of overall ALF group) by 3-week outcome after study admission: 117 survived spontaneously (without LT, SS), 108 died without LT, and 392 underwent LT. Only 22% of acetaminophen (APAP) ALF patients were listed; however, this group of 173 patients demonstrated greater illness severity: higher coma grades, and more patients required ventilator, vasopressor or renal replacement therapy support. Only 62/173 (36%) of APAP patients received a graft, versus 66% for drug-induced liver injury patients, 86% for autoimmune and 71% for hepatitis B-related ALF. APAP patients were more likely to die than non-APAP patients (24% vs 17%), and the median time to death was sooner (2 vs 4.5 days). Despite greater severity of illness, the listed APAP group still had a SS rate of 40% vs. 11% for non-APAP causes (p < 0.001). CONCLUSIONS APAP outcomes evolve rapidly, mainly to SS or death. Patients with APAP ALF listed for LT had the highest death rate of any etiology, while more slowly evolving etiologies yielded higher LT rates, and consequently, fewer deaths. Decisions to list and transplant must be made early in all ALF patients, particularly in those with APAP ALF.

Background & Aims Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We investigated whether patients with ALF develop thrombocytopenia in proportion to the SIRS, MOSF, and poor outcome. Methods In a retrospective study, we collected data on post-admission platelet counts of 1598 patients included in the ALF Study Group Registry from 1998 through October, 2012. We investigated correlations between platelet counts and clinical features of ALF, laboratory test results, and outcomes. Of the patients studied, 752 (47%) survived without liver transplantation, 390 (24%) received liver transplants, and 517 (32%) died. Results In patients with SIRS, platelet counts decreased 2–7 days after admission, compared to patients without SIRS (P≤.001). Patients with abnormal levels of creatinine, phosphate, lactate, or bicarbonate had significantly lower platelet counts than patients with normal levels of these laboratories (all P≤.001). The decrease in platelets during days 1–7 after admission was proportional to the grade of hepatic encephalopathy and requirement for vasopressor and renal replacement therapy. Although platelet numbers decreased after admission in the overall population, platelets were significantly lower 2–7 days after admission in patients with outcomes of death or liver transplantation than in patients who made spontaneous recoveries and survived. In contrast, international normalized ratios over time were not associated with SIRS, laboratory test results associated with poor outcomes, grade of hepatic encephalopathy, or requirement for renal replacement therapy. Conclusions The development of thrombocytopenia in patients with ALF is associated with development of MOSF and poor outcome. We speculate that SIRS-induced activation of platelets, yielding microparticles, results in clearance of platelet remnants and subsequent thrombocytopenia.

BACKGROUND The long-term clinical outcomes in initial survivors with acute liver failure (ALF) are not well known. AIMS The aim of the current study is to provide an overview of the 2 year clinical outcomes amongst initial survivors and liver transplant (LT) recipients that were alive 3 weeks after enrollment in the Acute Liver Failure Study Group (ALFSG). METHODS Outcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed. RESULTS 2-year patient survival was significantly higher in the 262 LT recipients (92.4%) compared to the 306 acetaminophen (APAP) spontaneous survivors (SS) (89.5%) and 200 non-APAP SS (75.5%) (p < 0.0001). The causes of death were similar in the 3 groups but the time to death was significantly longer in the LT recipients (p< 0.0001). Independent predictors of 2-year mortality in the APAP group were a high serum phosphate level and patient age (c-statistic = 0.65 (0.54, 0.76)), patient age and days from jaundice to ALF onset in the non-APAP group (c-statistic =0.69 (0.60, 0.78)), and patient age, days from jaundice, and higher coma grade in the LT recipients (c-statistic=0.74 (0.61, 0.87)). The LT recipients were significantly more likely to be employed and have a higher educational level (p < 0.05). CONCLUSIONS Two-year outcomes in initial survivors of ALF are generally good but non-APAP patients have a significantly lower survival which may relate to pre-existing medical co-morbidities. Spontaneous survivors with APAP overdose experience substantial morbidity during follow-up from ongoing psychiatric and substance abuse issues.

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