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In patients with acute liver failure (ALF), elevated prothrombin time and thrombocytopenia can fuel a perception of a bleeding tendency. However, the incidence, site, risk factors, and clinical significance of bleeding complications have not been quantified in a large cohort of patients with ALF. We studied 1,770 adult patients enrolled in the ALF Study Group Registry between 1998 and 2016. Bleeding complications and blood component transfusions were collected for 7 days after admission. The relationship of bleeding complications to 21-day mortality was assessed. Despite a median international normalized ratio of 2.7 and platelet count of 96 × 109 /L on admission, bleeding complications were observed in only 187 patients (11%), including 173 spontaneous and 22 postprocedural bleeding episodes. Eighty-four percent of spontaneous bleeding episodes were from an upper gastrointestinal source and rarely resulted in red blood cell transfusion. Twenty patients experienced an intracranial bleed; half of these occurred spontaneously and half after intracranial pressure monitor placement, and this was the proximate cause of death in 20% and 50%, respectively. Bleeders and patients who received red blood cell transfusions were more acutely ill from extrahepatic organ system failure but not from hepatocellular failure. Consistent with this observation, bleeding complications were associated with lower platelet counts but not higher international normalized ratio. Transfusion of any blood component was associated with nearly 2-fold increased death or need for liver transplantation at day 21, but bleeding complications were the proximate cause of death in only 5% of cases. Conclusions 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).

Stroke is the second leading cause of death and the third leading cause of disability-adjusted life years worldwide. Although numerous therapies have been developed over the past 10 years to treat acute ischemic stroke, the stark reality remains that only 5% of these patients are so treated in the United States,1 in part, because of treatment window times 7 million stroke survivors …

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 the 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 to 7 days after admission, compared with 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 laboratory values (all P ≤ .001). The decrease in platelets during days 1 to 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 to 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 the 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.

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. 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. We classified 617 patients (36% of overall ALF group) by 3-week outcome after study admission: 117 were spontaneous survivors (SSs; survival without LT), 108 died without LT, and 392 underwent LT. Only 22% of N-acetyl-p-aminophenol (APAP) ALF patients were listed; however, this group of 173 patients demonstrated greater illness severity: higher coma grades and more patients requiring 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-related ALF, and 71% for hepatitis B-related ALF. APAP patients were more likely to die than non-APAP patients (24% versus 17%), and the median time to death was sooner (2 versus 4.5 days). Despite greater severity of illness, the listed APAP group still had a SS rate of 40% versus 11% for non-APAP causes (P

Functional outcomes for long-term survivors of acute liver failure (ALF) are not well characterized. The aim of this prospective study was to determine health-related quality of life in long-term adult ALF survivors. Acute Liver Failure Study Group registry participants completed the Centers for Disease Control and Prevention Health-Related Quality of Life 14 and Short Form 36 (SF-36) questionnaires at 1- and/or 2-year follow-up study visits. Responses were compared among ALF subgroups and to those for available general US population controls. Among the 282 adult ALF patients, 125 had undergone liver transplantation (LT), whereas 157, including 95 acetaminophen overdose (APAP) patients and 62 non-APAP patients, were spontaneous survivors (SSs). APAP SS patients reported significantly lower general health scores and more days of impaired mental and physical health, activity limitations due to poor health, pain, depression, and anxiety in comparison with the other groups (P ≤ 0.001). There were no significant differences in coma grade or in the use of mechanical ventilation or intracranial pressure monitoring among the patient groups during their ALF hospitalization, but APAP SSs had significantly higher rates of psychiatric disease and substance abuse (P

To determine the impact of maternal diabetes during pregnancy on racial disparities in fetal growth.Using linked birth certificate, inpatient hospital and prenatal claims data we examined live singleton births of mothers resident in South Carolina who self-reported their race as non-Hispanic white (NHW; n = 140,128) or non-Hispanic black (NHB; n = 82,492) and delivered at 28-42 weeks' gestation between 2004 and 2008.Prepregnancy diabetes prevalence was higher in NHB (3.0%) than in NHW (1.7%), while the prevalence of gestational diabetes mellitus (GDM) was similar in NHB (6.1%) and NHW (6.3%). At a delivery BMI of 35 kg/m(2), GDM exposure was associated with an average birthweight only 17 g (95% CI 4, 30) higher in NHW, but 78 g (95% CI 61, 95) higher in NHB (controlling for gestational age, maternal age, infant sex and availability of information on prenatal care). Figures for prepregnancy diabetes were 58 g (95% CI 34, 81) in NHW and 60 g (95% CI 37, 84) in NHB. GDM had a greater impact on birthweight in NHB than in NHW (60 g racial difference [95% CI 39, 82]), while prepregnancy diabetes had a large but similar impact. Similarly, the RR for GDM of having a large- relative to a normal-weight-for-gestational-age infant was lower in NHW (RR 1.41 [95% CI 1.34, 1.49]) than in NHB (RR 2.24 [95% CI 2.05, 2.46]).These data suggest that the negative effects of GDM combined with obesity during pregnancy may be greater in NHB than in NHW individuals.

Background & Aims The long-term clinical outcomes in initial survivors with acute liver failure (ALF) are not well known. The aim of this study was to provide an overview of the 2-year clinical outcomes among initial survivors and liver transplant (LT) recipients that were alive 3 weeks after enrolment in the Acute Liver Failure Study Group (ALFSG). Methods Outcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed. Results Two-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

Background Quantile regression, a robust semi-parametric approach, was used to examine the impact of gestational diabetes mellitus (GDM) across birthweight quantiles with a focus on maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG). Methods Using linked birth certificate, inpatient hospital and prenatal claims data we examined live singleton births to non-Hispanic white (NHW, 135,119) and non-Hispanic black (NHB, 76,675) women in South Carolina who delivered 28–44 weeks gestation in 2004–2008. Results At a maternal BMI of 30 kg/m2 at the 90th quantile of birthweight, exposure to GDM was associated with birthweights 84 grams (95% CI 57, 112) higher in NHW and 132 grams (95% CI: 104, 161) higher in NHB. Results at the 50th quantile were 34 grams (95% CI: 17, 51) and 78 grams (95% CI: 56, 100), respectively. At a maternal GWG of 13.5 kg at the 90th quantile of birthweight, exposure to GDM was associated with birthweights 83 grams (95% CI: 57, 109) higher in NHW and 135 grams (95% CI: 103, 167) higher in NHB. Results at the 50th quantile were 55 grams (95% CI: 40, 71) and 69 grams (95% CI: 46, 92), respectively. Summary Our findings indicate that GDM, maternal prepregnancy BMI and GWG increase birthweight more in NHW and NHB infants who are already at the greatest risk of macrosomia or being large for gestational age (LGA), that is those at the 90th rather than the median of the birthweight distribution.