Liver Failure Research Articles

Clinical presentation and outcomes of patients with rhabdomyolysis: A tertiary care center experience.

To evaluate the clinical and laboratory features, complications, and outcomes of patients with rhabdomyolysis in the Saudi population. Retrospectives descriptive study of adult patients who presented to King Abdulaziz Medical City (KAMC) withrhabdomyolysis between January 2016 and December 2022. Most of the participants (84.5%) were male, with a median age of 41 years and a body mass index of 26.5kg/m2. Medications, mainly statins (22.4%) and illicit drugs (15.5%), constituted the root causes of rhabdomyolysis in the cohort (44.8%). The most common presenting complaints were myalgia (63.8%) and fatigue (37.9%). More than one-third of the participants (32.8%) developed AKI, with 3 patients requiring temporary hemodialysis, and only 8.6% developed acute liver failure (ALF). Intensive care unit (ICU) admission was required for 10 patients (17.2%), and the overall mortality rate was 8.6%. Patients who developed complications (composite outcomes of AKI, ALF, multiorgan failure, or death) had significantly reduced kidney function and higher levels of blood urea nitrogen, anion gap, and uric acid upon admission than those who did not. This study offers a thorough understanding of clinical and laboratory features, causes, complications, and outcomes of rhabdomyolysis among Saudi patients. The insights gained enhance our understanding of rhabdomyolysis within this population, providing a foundation for future research and improvements in clinical management.

Acute liver failure in pregnancy.

Liver function abnormalities are noted in a minority of pregnancies with multiple causes for the same. A small proportion of these develop severe liver injury and progress to acute liver failure (ALF). There is a discrete set of etiology for ALF in pregnancy and comprehensive understanding will help in urgent evaluation. Certain diseasessuch as acute fatty liver of pregnancy, hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome and pre-eclampsia are secondary to pregnant state and can present as ALF. Quick and targeted evaluation with urgent institution of etiology-specific management, especially urgent delivery in patients with pregnancy-associated liver diseases, is the key to avoiding maternal deaths. Pregnancy, as also the fetal life, imparts a further layer of complication in assessment, prognosis and management of these sick patients with ALF. Optimal management often requires a multidisciplinary approach in a well-equipped centre. In this review, we discuss evaluation, assessment and management of pregnant patients with ALF, focussing on approach to pregnancy-associated liver diseases.

3D Printing of a Vascularized Mini‐Liver Based on the Size‐Dependent Functional Enhancements of Cell Spheroids for Rescue of Liver Failure (Adv. Sci. 17/2024)

3D Printing of a Vascularized Mini‐Liver Based on the Size‐Dependent Functional Enhancements of Cell Spheroids for Rescue of Liver Failure (Adv. Sci. 17/2024)

Quantitative Myocardial Perfusion in Liver Transplantation Candidates: Poorly metabolized caffeine inhibition of vasodilatory stress

BackgroundData on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine reducing stress perfusion. MethodConsecutive LT candidates (n=114) undergoing cardiac rest/stress PET were instructed to abstain from caffeine for 2 days extended to 5 and 7 days. Due to persistently high prevalence of measurable blood caffeine after 5-day caffeine abstinence, dipyridamole (n=41) initially used was changed to dobutamine (n=73). Associations of absolute flow, coronary flow reserve (CFR), detectable blood caffeine, and Modified End-Stage Liver Disease (MELD) score for liver failure severity were evaluated. Coronary flow data of LT candidates were compared to non-LT control group (n=102 for dipyridamole, n=29 for dobutamine) ResultsPrevalence of patients with detectable blood caffeine was 63.3%, 36.7% and 33.3% after 2-, 5- and 7-day of caffeine abstinence, respectively. MELD score was associated with detectable caffeine (odd ratio 1.18,p<0.001). CFR was higher during dipyridamole stress without-caffeine vs. with-caffeine (2.22±0.80 vs. 1.55±0.37,p=0.048) but lower than dobutamine stress (2.22±0.80 vs. 2.82±1.02,p=0.026). Mediation analysis suggested that the dominant association between CFR and MELD score in dipyridamole group derived from caffeine-impaired CFR and liver failure/caffeine interaction. CFR in LT candidates was lower than non-LT control population in both dipyridamole and dobutamine group. ConclusionsWe demonstrate exceptionally high prevalence of detectable blood caffeine in LT candidates undergoing stress PET myocardial perfusion imaging resulting in reduced CFR with dipyridamole compared to dobutamine. The delayed caffeine clearance in LT candidates makes dobutamine a preferred stress agent in this population.

Multimodal decoding of human liver regeneration.

The liver has a unique ability to regenerate1,2; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option3-5. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut-liver barrier may advance new areas of therapeutic discovery in regenerative medicine.

Transplanting Livers in Young Children – Looking Back at 100 Cases

ABSTRACT Introduction: Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease (ESLD). However, its acceptance in India has been discouraging more due to financial and logistic reasons than the availability of expertise. This report outlines our journey and highlights issues pertinent to circumstances in an emerging economy like India. Aim: The aim is to review a single center’s 100 case experience with liver transplantation (LT). Materials and Methods: A prospective analysis of all children who underwent LT since 2005 at our institute was done. The data were collated from a maintained structured database. Results: Hundred children underwent LT. Sixty-four were boys. Age ranged from 5 to 144 months, with a median of 17 months. The mean weight of the cohort was 7.5 kg (ranging from 3.7 to 31.5 kg), with 60% of our children weighing between 5 and 10 kg. Biliary atresia is the most common indication (57%); others include metabolic disorders, progressive familial intrahepatic cholestasis, and hepatoblastoma. Two patients were for acute liver failure. Ninety-one children underwent live donor LT (mothers being the majority of the donors). None of the donors had any major postoperative complications. Major intraoperative complications include sepsis (39%), vascular complications (17%), biliary leak (11%), and intestinal complications (11%). Early postoperative deaths occurred in 18% of patients with sepsis being most common cause. The mean follow-up was 8.5 years and the overall survival is 70%. The mean survival is time (months) = 176.1. All surviving patients were followed up and had achieved good catch up growth by 3rd and 5th years posttransplant. The long-term sequalae include recurrent intercurrent infections, graft rejection (9%), posttransplant lymphoproliferative disease (5%), and portal vein stenosis (5%). Conclusion: Our experience demonstrates the feasibility of LT in children with ESLD in India. With longer-living grafts, patients often struggle with other issues such as compliance with follow-up, financial issues, recurrent infections, and neurological problems. Close monitoring with regular follow-up of patients helps in early recognition and treatment of late-onset complications, thus helping the overall long-term outcomes.

Outcomes and risk factors for mortality in clostridioides difficile infection in patients with NAFLD and NASH

Introduction and ObjectivesNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH. MethodsWe conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017. Patients with a diagnosis of CDI, NAFLD, and NASH were identified using International Classification of Diseases (Tenth Revision) codes. The outcomes of our study include length of stay, hospitalization cost, mortality, and predictors of mortality. ResultsThe CDI and NASH cohort had a higher degree of comorbidity burden and prevalence of peptic ulcer disease, congestive heart failure, diabetes mellitus, and cirrhosis. Patients with NASH and CDI had a significantly higher mortality rate compared to the CDI only cohort (mortality, 7.11 % vs 6.36 %; P = 0.042). Patients with CDI and NASH were at increased risk for liver-related complications, acute kidney injury, and septic shock (P < 0.001) compared to patients with CDI only. Older age, intestinal complications, pneumonia, sepsis and septic shock, and liver failure conferred an increased risk of mortality among the CDI and NASH cohort. ConclusionsPatients with NASH had a higher rate of liver-related complications, progression to septic shock, and mortality rate following CDI infection compared to the CDI only cohort.

Comments on “Clinically relevant therapeutic approaches against acetaminophen (APAP) hepatotoxicity and acute liver failure”

Comments on “Clinically relevant therapeutic approaches against acetaminophen (APAP) hepatotoxicity and acute liver failure”

Safety and Effectiveness of Portal Vein Embolization after Hepatic Arterial Infusion Therapy

Portal vein embolization (PVE) is a potential tool useful for inducing future liver remnant (FLR) hypertrophy in patients with advanced hepatic malignancies who are at high risk of hepatic insufficiency if treated with surgical resection. However, the safety and effectiveness of PVE in the context of patients who have undergone hepatic arterial infusion (HAI) are unknown. This retrospective, single-center study identified 9 patients who underwent PVE after HAI between January 2015 and December 2022. There were no major adverse events, including biliary, or high-grade liver failure. Analysis showed an increase in standardized FLR from 21.1% (SEM ± 2.4) to 34.8% (SEM ± 2.1) over 9.8 weeks (SEM ± 1.2), with a mean kinetic growth rate of 1.9% (interquartile range, 0.9%–2.4%). This study suggested compatibility of PVE after HAI. Patients who have undergone HAI therapy should not be excluded from consideration of PVE as part of their operative clearance strategy.

Plasma exchange improves survival in acute liver failure- An updated systematic review and meta-analysis focussed on comparing within single etiology.

Therapeutic plasma exchange (PLEX) is increasingly used in patients with acute liver failure (ALF) as either stand-alone therapy or bridge to liver transplantation. Etiology plays a major role in prognosis of these patients and benefit of PLEX may consequently differ across etiologies. This systematic review and meta-analysis aims to evaluate the efficacy of PLEX in treating ALF, focussing on studies with single etiology. We conducted a systematic literature search and identified studies comparing PLEX vs. standard medical therapy (SMT) for patients with ALF across all age groups. The protocol was registered in theInternational Prospective Register of Systematic Reviews (PROSPERO) (CRD42023442383). Pooled risk-ratios were determined by Mantel-Haenszel method within a random effect model. Primary outcome was mortality at ≤ 60-days and 90days. Secondary outcome was adverse events attributable to PLEX. Eight studies (pooled sample size in PLEX arm:284; randomized trials:2; Comparative cohorts:6) with retrievable data on ALF were included in this systematic review. Analysis showed that PLEX was associated with significant reduction in mortality at ≤ 60-days (RR 0.64; CI, 0.51-0.80; P < 0.001) and at 90-days (RR 0.67; CI, 0.50-0.90; P = 0.008) as compared to SMT. On sub-group analysis, the survival benefit was noted irrespective of the volume of plasma exchanged during PLEX. Three studies (pooled sample size in PLEX arm: 110; all comparative cohorts) were identified, which included patients with a single etiology for ALF. These studies included patients with Wilson's disease, rodenticidal hepatotoxicity and acute fatty liver of pregnancy. Pooled analysis of studies with single etiology ALF showed better reduction in ≤ 90-day mortality with PLEX (RR 0.53; CI, 0.37-0.74; P < 0.001). Studies reported no major side-effects attributable to PLEX. PLEX is safe and improves survival, independent of the volumes utilized, in patients with ALF as compared to standard medical treatment. The survival benefit is especially pronounced in studies restricted to single etiology.

Transplantace jater pro chronickou hepatitidu C – význam protivirové léčby v roce 2024

Summary: Liver failure due to cirrhosis and hepatocellular carcinoma (HCC) in hepatitis C (HCV) infection is still one of the main indications for liver transplantation (LTx) in Western countries. In patients with compensated liver cirrhosis C, antiviral therapy should be initiated promptly, as complications, i.e. decompensation of the disease and HCC, can occur in a short time frame. Successful antiviral treatment of HCV in patients with cirrhosis reduces the risk of decompensation, HCC, and death from liver failure, thus reducing the need for LTx in these patients. Treatment in a patient with decompensated liver cirrhosis before LTx aims not only to prevent HCV recurrence in the liver graft but also to improve liver function. In patients on the waiting list, improvement of liver function may lead to removal from the waiting list. LTx should be considered in all patients with chronic liver failure due to HCV in whom we expect prolongation of life expectancy after LTx compared to the natural course of their liver disease or for whom LTx will significantly improve the quality of life. LTx should be considered when life expectancy due to liver disease is one year or less. Before LTx, the patient should be thoroughly examined to exclude comorbidities that substantially complicate or preclude LTx. The advent of direct-acting antivirals into HCV treatment regimens represents a revolutionary step to prevent HCV recurrence in the graft, is either by eradicating HCV before LTx or by early treatment after LTx. Currently, HCV recurrence in the liver graft either by eradicating HCV before LTx or by early treatment after LTx. Currently, HCV recurrence in the liver graft no longer leads to worse survival in patients transplanted for HCV, and outcomes are fully comparable to those of LTx for other diagnoses. Key words: HCV – cirrhosis C – liver failure – hepatocellular carcinoma – liver transplantation – HCV recurrence

Biallelic Deletion of PEX26 Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease

Introduction: Peroxisome biogenesis disorders (PBDs) encompass a group of diseases marked by clinical and genetic heterogeneity. Phenotypes linked to PBDs include Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease (IRD), rhizomelic chondrodysplasia punctata type 1, and Heimler syndrome. PBD phenotypes manifest through hypotonia, developmental delay, facial dysmorphism, seizures, liver dysfunction, sensorineural hearing loss, and retinal dystrophy. Methods: The proband underwent comprehensive clinical evaluation, followed by whole-exome sequencing (WES) coupled with copy number analysis (CNV), aimed at identifying potential disease-causing variants aligning with the observed phenotype. Results: Our findings detail an individual exhibiting developmental delay, hearing loss, visual impairment, hepatomegaly, and splenomegaly, attributed to a biallelic deletion of exon 4 in the PEX26 gene. The WES analysis of the index case did not uncover any pathogenic/likely pathogenic single-nucleotide variations that could account for the observed clinical findings. However, the CNV data derived from WES revealed a homozygous deletion in exon 4 of the PEX26 gene (NM_001127649.3), providing a plausible explanation for the patient’s clinical features. The exon 4 region of PEX26 encodes the transmembrane domain of the protein. The transmembrane domain plays a crucial role in anchoring the protein within lipid bilayers, and its absence can disrupt proper localization and functioning. As a result, this structural alteration may impact the protein’s ability to facilitate essential cellular processes related to peroxisome biogenesis and function. Conclusion: The index patient, which presented with hearing loss, retinal involvement and hepatic dysfunction in adolescence age, has atypical clinical course that can be considered unusual for Zellweger syndrome (ZS) and IRD phenotypes, and its rare genotypic data (in-frame single exon deletion) expands the PBD disease spectrum. This study revealed for the first time that PEX26 protein transmembrane domain loss exhibits an unusual course with clinical findings of IRD and ZS phenotypes. WES studies, incorporating CNV analyses, empower the identification of novel genetic alterations in genes seldom associated with gross deletion/duplication variations, such as those in the PEX26 gene. This not only enhances diagnostic rates in rare diseases but also contributes to broadening the spectrum of causal mutations.

Metabolic dysfunction-associated steatotic liver disease in people with HIV is associated with lower BMI and more liver fibrosis compared to the uninfected population

Aim: People with HIV (PWH) are at high risk of metabolic dysfunction-associated steatotic liver disease (MASLD), defined by the presence of hepatic steatosis plus any among overweight, diabetes, hypertension, or dyslipidemia. There are limited data whether MASLD in PWH differs in clinical presentation from MASLD in the uninfected population. Aim: to compare the severity of metabolic and hepatic dysfunction between MASLD patients with and without HIV. Methods: 212 consecutive HIV mono-infected patients with MASLD at McGill University in Montreal were compared to a sex and age matched MASLD HIV negative control group at Policlinico Hospital in Milan. Fibroscan with controlled attenuation parameter (CAP) was used to define MASLD (CAP≥248 dB/m), severe MASLD (CAP&gt;280 dB/m), and significant liver fibrosis (liver stiffness measurement&gt;7.0 kPa). Results: PWH with MASLD presented lower median BMI (28[25-31] vs 29[27-32] Kg/m2, p=0.002) and lower prevalence of obesity (26% vs 44%, p&lt;0.001) compared to MASLD uninfected patients, along with a lower prevalence of hypertension (21% vs 38%, p&lt;0.001). The prevalence of dyslipidemia (41% vs 26%, p&lt;0.001), hypertriglyceridemia (26% vs 9%, p&lt;0.001) and low HDL cholesterol (34% vs 15%, p&lt;0.001) was higher in MASLD patients with vs without HIV. No difference in cardiovascular events and diabetes prevalence was observed between the two groups. Regarding liver disease, PWH with MASLD had lower prevalence of severe MASLD (54% vs 74% p&lt;0.001) but higher prevalence of significant liver fibrosis (15 vs 7%, p=0.03) compared to MASLD uninfected patients. After adjustment, HIV positivity was an independent factor associated with significant liver fibrosis (figure). Conclusions: Despite having lower BMI, PWH with MASLD have a more severe hepatic presentation and atherogenic lipid profile than MASLD uninfected patients. HIV positivity seems to be independently associated with significant liver fibrosis. Screening and follow-up for MASLD and liver fibrosis is recommended in PWH, even if they are lean.

Kupffer cell diversity maintains liver function in alcohol-associated liver disease.

Liver macrophages are heterogeneous and play an important role in alcohol-associated liver disease (ALD) but there is limited understanding of the functions of specific macrophage subsets in the disease. We used a Western Diet Alcohol (WDA) mouse model of ALD to examine the hepatic myeloid cell compartment by scRNA seq and targeted Kupffer cell (KC) ablation to understand the diversity and function of liver macrophages in ALD. In the WDA liver, KCs and infiltrating monocytes/macrophages (IMs) each represented about 50% of the myeloid pool. Five major KC clusters all expressed genes associated with receptor mediated endocytosis and lipid metabolism, but most were predicted to be non-inflammatory and antifibrotic with one minor KC cluster having a pro-inflammatory and extracellular matrix degradation gene signature. IM clusters, in contrast, were predicted to be pro-inflammatory and pro-fibrotic. In vivo diphtheria toxin based selective KC ablation during alcohol exposure resulted in a liver failure phenotype with increases in PT/INR and bilirubin, loss of differentiated hepatocyte gene expression, and an increase in expression of hepatocyte progenitor markers such as EpCAM, CK-7 and Igf2bp3. Gene set enrichment analysis of whole liver RNAseq from the KC ablated WDA mice showed a similar pattern as seen in human alcoholic hepatitis. In this ALD model, KCs are anti-inflammatory and are critical for maintenance of hepatocyte differentiation. IMs are largely pro-inflammatory and contribute more to liver fibrosis. Future targeting of specific macrophage subsets may provide new approaches to treatment of liver failure and fibrosis in ALD.

Biallelic Variants of MRPS36 Cause a New Form of Leigh Syndrome.

The MRPS36 gene encodes a recently identified component of the 2-oxoglutarate dehydrogenase complex (OGDHC), a key enzyme of the Krebs cycle catalyzing the oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA. Defective OGDHC activity causes a clinically variable metabolic disorder characterized by global developmental delay, severe neurological impairment, liver failure, and early-onset lactic acidosis. We investigated the molecular cause underlying Leigh syndrome with bilateral striatal necrosis in two siblings through exome sequencing. Functional studies included measurement of the OGDHC enzymatic activity and MRPS36 mRNA levels in fibroblasts, assessment of protein stability in transfected cells, and structural analysis. A literature review was performed to define the etiological and phenotypic spectrum of OGDHC deficiency. In the two affected brothers, exome sequencing identified a homozygous nonsense variant (c.283G>T, p.Glu95*) of MRPS36. The variant did not affect transcript processing and stability, nor protein levels, but resulted in a shorter protein lacking nine residues that contribute to the structural and functional organization of the OGDHC complex. OGDHC enzymatic activity was significantly reduced. The review of previously reported cases of OGDHC deficiency supports the association of this enzymatic defect with Leigh phenotypic spectrum and early-onset movement disorder. Slightly elevated plasma levels of glutamate and glutamine were observed in our and literature patients with OGDHC defect. Our findings point to MRPS36 as a new disease gene implicated in Leigh syndrome. The slight elevation of plasma levels of glutamate and glutamine observed in patients with OGDHC deficiency represents a candidate metabolic signature of this neurometabolic disorder. © 2024 International Parkinson and Movement Disorder Society.

Transplantace jater pro ACLF

Summary: Acute-on-chronic liver failure (ACLF) occurs in about one third of patients hospitalized for decmopensation of liver cirrhosis. It is defined as a failure of at least one organ, mostly the kidneys and/or liver, and very high short-term mortality. The most common trigger, precipitating event, is an infection or alcohol abuse. ACLF is caused by an excessive inflammatory reaction to the presence od microbial or sterile molecular structures in the blood circulation, and a disturbed immune response. ACLF is a very dynamic process and the condition must be reevaluated continuously according to the available scoring systems, early contact the transplant center and consider the possibility of this only curative treatment. We should be aware of renal function, nutrition, antimicrobial treatment and in patients with alcoholic hepatitis, it is necessary to consider the administration of corticosteroids. Liver transplantation for ACLF has somewhat worse one-year survival compared to other transplant groups, but long-term survival is comparable. Key words: ACLF – precipitating event – alcohol hepatitis – infection – liver transplantation

Toxicological effects of two major types of potash used as food additives in Nigeria: Biochemical, hematological, and histopathological analysis of major organs in Wistar rats

Trona or natron, often called potash, are evaporites, which are natural salts used unregulated in Nigeria as food additives, particularly to soften hard beans or tenderize tough cow meat, and for medical purposes. A 90-day sub-chronic toxicological study was conducted on Wistar rats weighing 120-140g to investigate the effects of consumption of these natural salts on hematological, histological and biochemical parameters. The experimental design involved 30 rats (n=10), considering attrition of two rats per group. The animals were divided into 3 groups. Group 1 was administered potash type A, group 2 administered potash type B while group 3(control) received only food and water. Standard methods were used to analyze all parameters. All results were presented as mean ± SD, with p-values &lt; 0.05 considered significant. Each potash type has LD50s exceeding 5000mg/kg. Potash types significantly increased AST and ALT levels (p&lt;0.05) in liver function measures compared to the control group. In both potash types, creatinine levels were considerably higher (p&lt;0.05) than the control, but Urea levels were not statistically different (p&gt;0.05). Sample A (Trona) reduced RBCs, Hb, and PCV more than sample B (natron) in rats. Both types had WBCs and Platelets that were similar to controls (p&gt;0.05). Effects of potash on four electrolytes :Na+, K+, Cl- and HCO3- shows that potash type B contained elevated (p&lt;0.05) levels of sodium than type A. Our results indicate that chronic consumption of each potash type or even both types, might expose users to hypernatremia, electrolyte imbalance, hematological problems, liver and kidney failures.

Dengue-related acute liver failure-A scoping review.

Infection by dengue virus is common in tropical countries. Hepatic involvement in dengue can range from asymptomatic elevation of transaminases to life-threatening acute liver failure (ALF). Dengue-related ALF (DALF) is responsible for significant morbidity and mortality, especially in Southeast Asia. However, there is a scarcity of literature on DALF, necessitating a thorough examination of its clinical determinants and management strategies. All relevant studies related to DALF were reviewed until December 2023. Case reports, case series and studies reporting ALF in dengue infection were included. Demographics, clinical profiles, management and outcomes of DALF cases were analyzed, which revealed a predominance of DALF incidence in pediatric patients (1.1% to 15.8%) and an upward trend over the years, particularly in India. The proportion of ALF cases attributable to dengue was also higher among pediatric ALF patients (6.7% to 34.3%). Age ≤ 40years, persistent nausea, vomiting and elevated serum bilirubin and alkaline phosphatase (ALP) with aspartate aminotransferase (AST) > 1000IU/mL within the first five days of illness, more than 10% of atypical lymphocytes in peripheral blood, platelet count of < 50,000/cu·mm, severe hepatitis at presentation and baseline model for end-stage liver disease (MELD) > 15 were the risk factors for the development of DALF. Histopathological features of DALF included multi-lobular hepatic necrosis, steatosis and occasional cholestasis. Mortality in DALF ranged from 0% to 80%; admission pH and lactate strongly predicted mortality, while mortality was found to be significantly higher in patients with cirrhosis. N-Acetyl cysteine (NAC) has been used as a treatment modality with varying results. There is limited evidence regarding the use of extra-corporeal support systems, while candidate selection for liver transplantation (LT) in DALF remains poorly defined.

Clinical characteristics and outcomes of acute liver failure in neonates: a retrospective cohort in China.

Neonatal acute liver failure (NALF), as a rare disease with high mortality, has limited relevant literature reports in China. We attempted to analyze a NALF cohort to improve the prognosis of this disease. We included all patients diagnosed with NALF at our institution between 2016 and 2021 and retrospectively reviewed their electronic records. NALF was defined as an INR ≥ 2.0 due to liver disease 28days after birth. Comparisons were made according to etiology and outcome. The Kaplan-Meier method was used to estimate survival. Fifty-eight patients were included in this study. Etiologies included hypoxic/ischemic injury (29.3%), infection (27.6%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (10.3%), inherited metabolic diseases (5.2%), hemophagocytic lymphohistiocytosis (1.7%), other etiologies (12.1%), and unidentified causes (13.8%). Enteroviruses constituted 87.5% of the viral infections, whereas herpes simplex virus accounted for no infections. The median INR was significantly lower in the infection group than in the GALD-NH group (P < 0.05 for multiple comparisons). At the last follow-up, none of the patients had undergone liver transplantation, and the overall mortality rate was 50%. Liver function completely recovered in 31% of the patients, all of whom survived. The overall median survival time was 48days; 26days for hypoxic/ischemic injury and 43days for GALD-NH. The incidence of cholestasis was significantly greater among surviving patients (P = 0.018). Conclusion: Hypoxic/ischemic injury and infection are the predominant etiologies of NALF in China. The overall prognosis of NALF is poor, but its short-term prognosis is determined by the etiology. What is Known: • Neonatal acute liver failure (NALF) is a rare disorder with limited cohort studies, especially in China. • Gestational alloimmune liver disease, viral infections (especially herpes simplex virus), metabolic diseases and ischemic insults are common etiologies of NALF, which are significantly different from other populations. • There are no reliable biochemical markers to predict the outcome of NALF. What is New: • In this first report on a Chinese NALF cohort, we demonstrate that hypoxic/ischemic injury and infection (excluding herpes simplex virus) are the predominant etiologies of NALF. • The overall prognosis of NALF is poor, and its etiology determines the short-term outcome.

Dual Tragedy of Fetal and Maternal Loss: A Case of Acute Liver Failure in the Third Trimester

Dual Tragedy of Fetal and Maternal Loss: A Case of Acute Liver Failure in the Third Trimester