The Role of Predictive Models in the Assessment of the Poor Outcomes in Pediatric Acute Liver Failure

Objectives: In children, acute liver failure (ALF) is a severe condition with high mortality. As some patients need liver transplantation (LT), it is essential to predict the fatal evolution and to refer them early for LT if needed. Our study aimed to evaluate the prognostic criteria and scores for assessing the outcome in children with ALF. Methods: Data of 161 children with ALF (54.66% female, mean age 7.66 ± 6.18 years) were analyzed based on final evolution (32.91% with fatal evolution or LT) and etiology. We calculated on the first day of hospitalization the PELD score (109 children), MELD, and MELD-Na score (52 children), and King’s College Criteria (KCC) for all patients. The Nazer prognostic index and Wilson index for predicting mortality were calculated for nine patients with ALF in Wilson’s disease (WD). Results: PELD, MELD, and MELD-Na scores were significantly higher in patients with fatal evolution (21.04 ± 13.28 vs. 13.99 ± 10.07, p = 0.0023; 36.20 ± 19.51 vs. 20.08 ± 8.57, p < 0.0001; and 33.07 ± 8.29 vs. 20.08 ± 8.47, p < 0.0001, respectively). Moreover, age, bilirubin, albumin, INR, and hemoglobin significantly differed in children with fatal evolution. Function to etiology, PELD, MELD, MELD-Na, and KCC accurately predicted fatal evolution in toxic ALF (25.33 vs. 9.90, p = 0.0032; 37.29 vs. 18.79, p < 0.0001; 34.29 vs. 19.24, p = 0.0002, respectively; with positive predicting value 100%, negative predicting value 88.52%, and accuracy 89.23% for King’s College criteria). The Wilson index for predicting mortality had an excellent predictive strength (100% sensibility and specificity), better than the Nazer prognostic index. Conclusions: Prognostic scores may be used to predict the fatal evolution of ALF in children in correlation with other parameters or criteria. Early estimation of the outcome of ALF is essential, mainly in countries where emergency LT is problematic, as the transfer to a specialized center could be delayed, affecting survival chances.

Acute Liver Failure Requiring Liver Transplantation due to Acute Hepatitis A Virus Infection

Introduction. Hepatitis A infection (HAV) is generally characterized by an acute icteric illness or may have a subclinical self-limited course, although rarely, can result in fulminant hepatitis and death. In 2019, the City of Philadelphia declared a public health emergency due to an HAV outbreak. We are reporting a series of four cases of acute liver failure (ALF) requiring liver transplantation (LT) due to acute HAV. Methods. Chart review and case descriptions of four patients with acute HAV-related ALF who were expeditiously evaluated, listed as Status 1A, and who underwent LT between August 2019 and October 2019 at Thomas Jefferson University Hospital. Results. All four patients presented with acute hepatocellular jaundice and had a positive HAV IgM, and all other causes of ALF were excluded. All four cases met the American Association for the Study of Liver Diseases (AASLD) criteria for ALF. Three of the four cases met King’s College Criteria of poor prognosis for nonacetaminophen-induced ALF. All four patients underwent successful LT and were discharged six to twelve days postoperatively. One patient died of disseminated Aspergillus infection five months after LT, while the others have had excellent clinical outcomes shown by one-year follow-ups. All four explants had remarkably similar histological changes, revealing acute hepatitis with massive necrosis accompanied by a prominent lymphoplasmacytic inflammatory infiltrate and bile ductular proliferation. Conclusion. Although rare, patients presenting with acute HAV need close monitoring as they may rapidly progress to ALF. Early referral to a transplant center afforded timely access to LT and yielded overall good one-year survival. Widespread HAV vaccination for high-risk individuals is an essential strategy for preventing disease and curbing such future outbreaks.

Mannitol is comparable to hypertonic saline for raised intracranial pressure in Acute Liver Failure (MAHAL Study): A RCT

Background: Raised intracranial pressure due to cerebral edema (CE) is central to development of hepatic encephalopathy in ALF. Mannitol (MT) & Hypertonic saline (HS) has been shown to improve CE. We compared the efficacy & safety of the two modalities Methods: ALF with CE were prospectively randomized in an open study to receive either 5 ml/kg of either 3% HS, as continuous infusion; titrated every 6 hourly to achieve serum sodium of <160(Group A; n=26) or 1 g/kg of 20% MN as a IV bolus, repeated every six hourly (Group B; n=25) in addition to standard ALF care. Primary end-point was reduction of intracranial pressure defined as optic nerve sheath diameter <5mm and middle cerebral arterial pulsatility index (PI) <1.2 at 12 hours. Results: Fifty-one patients with ALF, hepatitis E being commonest (33.3%), median jaundice to HE interval of 8(1-16) days, were randomized to HS (n=26) or MN (n=25). Baseline characteristics were comparable including King’s college criteria [>2: 38.4% vs.40%]. Overall, 61.5% patients in HS and 56% in MN group showed reduction in ICP at 12 hr. (p=0.25). Rebound increase in ICP indices was noted in 5(20%) patients in MT and none in HS (p<0.05) group. New onset acute kidney injury was commoner in MT than HS group. The ICU stay, and 28-day transplant free survival were not different between the groups. Conclusions: While both agents had comparable efficacy in reducing ICP and mortality in ALF patients was comparable, HS was significantly better in preventing reducing rebound CE with lower renal dysfunction.

Creatinine-lactate score predicts mortality in non-acetaminophen-induced acute liver failure in patients listed for liver transplantation

Background The aim of this study was to analyze prognostic indicators of in-hospital mortality among patients listed for urgent liver transplantation (LT) for non-acetaminophen (APAP)-induced acute liver failure (ALF). Methods ALF patients listed for LT according to the King’s College Criteria were retrospectively reviewed. Variables were recorded from medical records and electronic databases (HCMED and RedCap). Results The study included 100 patients, of which 69 were subject to LT and 31 died while waiting for LT. Patients were 35.5 ± 14.73 years old, and 78% were females. The main etiologies were virus (17%), drug-induced (32%), autoimmune (15%), and indeterminate hepatitis (31%). The prioritization-to-LT time interval was 1.5 days (0–9). The non-LT patients showed higher lactate (8.71 ± 5.36 vs. 4.48 ± 3.33 mmol/L), creatinine (229 ± 207 vs. 137 ± 136 µm/L), MELD (44 ± 8 vs. 38 ± 8), and BiLE scores (15.8 ± 5.5 vs. 10.3 ± 4.1) compared to LT patients (p < 0.05). Multiple logistic regression analysis identified creatinine and lactate as independent prognostic factors, and a creatinine-lactate (CL) score was developed. ROC analysis showed that creatinine, lactate, MELD, BiLE, and CL scores had considerable specificity (71–88%), but only BiLE, lactate, and CL presented high sensitivities (70%, 80%, and 87% respectively). AUCs were 0.696 for creatinine, 0.763 for lactate, 0.697 for MELD, 0.814 for BiLE, and 0.835 for CL. Conclusions CL and BiLE scores predict mortality with more accuracy than MELD in patients with ALF during prioritization time. Creatinine and lactate are independent prognostic factors for mortality.

Five-day outcome of hepatitis E-induced acute liver failure in the ICU

Background Hepatitis E virus (HEV) is an important cause of acute liver failure (ALF) in Bangladesh with pregnant mothers being more vulnerable. As HEV occurs in epidemics, it limits medical capabilities in this resource-poor country. Cerebral oedema, resulting in raised intracranial pressure (ICP), is an important cause of morbidity and mortality. Practical treatments are currently few. To study the baseline characteristics and clinical outcome of HEV-induced ALF in a recent HEV epidemic To detect raised ICP clinically and observe response to mannitol infusion. This was a prospective cohort study from June until August 2018 of 20 patients admitted to the intensive care unit (ICU) of a major Bangladeshi Referral Hospital with HEV-induced ALF. We diagnosed HEV infection by detecting serum anti-HEV IgM antibody. All were negative for hepatitis B surface antigen and hepatitis A IgM antibody. Data were collected on 5-day outcome after admission to ICU, monitoring all patients for signs of raised ICP. An intravenous bolus of 20% mannitol was administered at a single time point to patients with raised ICP. Results Twenty patients were included in the study. Ten (50%) patients, seven (70%) females, received mannitol infusion. HE worsened in eight (40%): seven female and three pregnant. Glasgow Coma scores deteriorated in six (30%): all (100%) females and three pregnant. Consciousness status was not significantly different between pregnant and non-pregnant subjects, nor between those who received mannitol and those who did not. Six patients met King’s College Criteria for liver transplantation. Conclusions Female patients had a worse outcome, but pregnancy status was not an additional risk factor in our cohort. Mannitol infusion was also not associated with a significant difference in outcome.