Liver Failure Research Articles

Clinical significance of transjugular liver biopsy in acute liver failure – a real-world analysis

BackgroundHistopathological characterization obtained by transjugular liver biopsy (TJLB) may theoretically contribute to clarification of the exact aetiology of acute liver failure (ALF). It's unclear whether the histopathological information from TJLB, due to the small specimen size, significantly contributes to diagnosing ALF causes, guiding therapy decisions, or predicting overall prognosis. This retrospective study aimed to analyse safety and clinical significance of TJLB in patients with ALF.MethodsThis retrospective, monocentric study investigated safety and efficacy of TJLB in patients with ALF over a ten-year period at a tertiary care transplant-center. The predictive value of various clinical and laboratory characteristics as well as histopathological findings obtained by TJLB on 28-day liver-transplant-free survival were evaluated by calculating uni- and multivariate Cox-proportional hazard regression models. Additional univariate logistic regression analyses were performed to explore the influence of degree of intrahepatic necrosis on the secondary endpoints intensive-care-unit (ICU) admission, need for endotracheal intubation, renal replacement therapy and high-urgency listing for LTX.ResultsA total of 43 patients with ALF receiving TJLB were included into the study. In most cases (n = 39/43 cases) TJLB confirmed the initially already clinically presumed ALF aetiology and the therapeutic approach was unchanged by additional histological examination in the majority of patients (36/43 cases). However, in patients with a high suspicion for aetiologies potentially treatable by medical immunosuppression (e.g. AIH, GvHD), TJLB significantly influenced further treatment planning and/or adjustment. While the degree of intrahepatic necrosis showed significance in the univariate analysis (p = 0.04), it did not demonstrate a significant predictive effect on liver transplant-free survival in the multivariate analysis (p = 0.1). Only consecutive ICU admission was more likely with higher extent of intrahepatic necrosis (Odds ratio (OR) 1.04 (95% CI 1–1.08), p = 0.046).ConclusionsPerformance of TJLB in ALF led to a change in suspected diagnosis and to a significant change in therapeutic measures only in those patients with a presumed high risk for aetiologies potentially responsive to immunosuppressive therapy. Clinical assessment alone was accurate enough, with additional histopathological examination adding no significant value, to predict overall prognosis of patients with ALF.

Comparison of serum alkaline phosphatase levels between two measurement methods in chronic hemodialysis patients in Japan: involvement of ABO blood group system and relationship with mortality risk.

Elevated serum alkaline phosphatase (ALP) levels are a risk factor for all-cause mortality in hemodialysis patients. Traditionally in Japan, ALP measurements were conducted using the JSCC method, which yields higher ALP measurement values than the IFCC method, mainly due to its increased sensitivity to intestinal ALP. Serum total ALP levels before and after switching the assay method from JSCC to IFCC were compared among different blood types in 521 hemodialysis patients (Study 1). The association between ALP levels measured by the JSCC method and 7-year mortality was analyzed, including blood types and liver function parameters as covariates, in 510 hemodialysis patients (Study 2). ALP levels measured by the JSCC method were approximately three times higher than those measured by the IFCC method, with significant elevation in patients with blood types B and O compared to those with blood types A and AB. Similarly, ALP levels measured by the IFCC method were significantly higher in patients with blood types B and O compared to those with blood types A and AB (Study 1). The highest tertile of ALP levels showed a significantly increased risk of all-cause mortality, even after adjusting for patient background. However, this significance disappeared when serum liver function-related or inflammatory markers were included as covariates (Study 2). ALP levels measured by the JSCC method are associated with life prognosis, but caution should be exercised due to their elevation in patients with blood types B and O and in those with hepatic dysfunction or inflammation.

Prognostic factors for pediatric patients with severe intestinal motility disorders: a single institution's experience.

To identify the prognostic factors for pediatric severe intestinal motility disorder (IMD). We reviewed the medical records of patients with severe IMD, who required total parenteral nutrition (TPN) for ≥ 60days at our institution between April, 1984 and March, 2023, examining their characteristics to identify prognostic factors. The types of IMD in the 14 patients enrolled in this study were as follows: isolated hypoganglionosis (IHG, n = 6), extensive aganglionosis (EAG: n = 6), and chronic idiopathic intestinal pseudo-obstruction (CIIP, n = 2). There was no significant difference in mortality among the three types of severe IMD. Weaning-off TPN and the use of the colon were not significant prognostic factors, but cholestasis was a significant prognostic factor (p = 0.005). There was a high mortality rate (50%), with the major causes of death being intestinal failure-associated liver disease (IFALD) following hepatic failure, and catheter-related blood stream infection (CRBSI). One IHG patient underwent small bowel transplantation but died of acute rejection. Severe IMD is still associated with a high mortality rate and cholestasis predicts the prognosis. Thus, preventing or improving IFALD and CRBSI caused by long-term TPN is important for reducing the mortality rate.

Current status of etiology and outcomes of acute liver failure in India-A multicentre study from tertiary centres.

Acute liver failure (ALF) is a medical emergency and liver transplantation (LT) may be required as definitive therapy. The etiology varies across geographical locations and is mostly viral dominant in India. We aimed at evaluating the spectrum, impact of interventions (plasma exchange [PLEx], continuous renal replacement therapy [CRRT]) and outcomes of ALF in India in recent times. A multicentre retrospective study across four major tertiary care centres. As many as 183ALF patients (median age, 23years; females, 43.1%; model for end-stage liver disease [MELD], 32.7) from January 2021 to December 2023 were included. Nineteen percent had infection and 40.4% of patients satisfied King's College criteria (KCC) at admission. Most common cause for ALF was hepatitis A virus (HAV) (44.2%) followed by rodenticide poisoning (10.3%). Approximately 35% of patients each received either PLEx or CRRT. The 7, 14 and 21-day transplant-free survival probability was 65.5%, 60.1%, and 57.3%, respectively. Only 3.8% of patients underwent liver transplantation. On multivariable Cox regression analysis, hemoglobin (HR, 0.74 [0.63-0.87]), lactate (HR, 1.14 [1.03-1.26]), advanced hepatic encephalopathy (HE) (HR, 4.87 [1.89-12.5]) and fulfilling KCC [HR, 10.04 [4.57-22.06]) at admission were the independent predictors of mortality. A model including KCC + lactate + HE ≥ 3 with or without hemoglobin had an AUROC of 0.81-0.84 to predict mortality. In those who underwent PLEx, advanced HE (HR, 4.13 [1.75-9.7]), procalcitonin (HR, 1.18 [1.07-1.30]) and KCC (HR, 4.6 [1.6-13.1), while for those who received CRRT, lactate (HR, 1.37 [1.22-1.54]) and KCC (HR, 6.4 [2.5-15.8]) independently predicted mortality. Hepatitis A virus is currently the most common cause for ALF in India, emphasizing the need for universal vaccination programmes. Spontaneous survival in tertiary care centres is 57%. LT rates were low.

Risk factors for secondary infection after liver failure and effect of comprehensive nursing intervention.

In patients with liver failure (LF), the high rate of secondary infections, which are associated with poor prognosis, highlights the clinical significance of understanding the underlying risk factors and implementing targeted intervention programs. To investigate risk factors for secondary infections in patients with LF and evaluate the effectiveness of comprehensive nursing interventions. This retrospective study included 64 patients with LF, including 32 with and 32 without secondary infections. A questionnaire was used to collect data on age; laboratory parameters, including total and direct bilirubin, prothrombin time, blood ammonia, and other biochemical parameters; invasive procedures; and complications. Patients with secondary infections received comprehensive nursing intervention in addition to routine nursing care, whereas those without secondary infections received only routine nursing care to compare the effect of nursing intervention on outcomes. The infection rate, which was not associated with age or complications, was significantly associated with biochemical parameters and invasive procedures (P < 0.05). The infection rate was 61.6% in patients who had undergone invasive procedures and 32.1% in those who had not undergone invasive procedures during the hospital stay. The infection rate was also significantly associated with the type of LF (P < 0.05), with the lowest rate observed in patients with acute LF and the highest rate observed in those with subacute LF. The nursing satisfaction rate was 58.3% in the uninfected group and 91.7% in the infected group, indicating significantly higher satisfaction in the infected group (P < 0.05). In patients with LF, the rate of secondary infections was high and associated with biochemical parameters and type of LF. Comprehensive nursing intervention can improve patient satisfaction.

Acute-on-chronic liver failure in metabolic dysfunction-associated fatty liver disease patients: a disease multiplier.

Acute-on-chronic liver failure (ACLF) is a syndrome of liver failure due to an acute hepatic insult leading to liver failure with or without extra-hepatic organ failure in a patient of chronic liver disease (CLD) with or without cirrhosis presenting for the first time. The definition is still with controversy; hence, homogeneity and clarity of the case is an unmet need. There is a paradigm shift noted as far as the etiology of CLD is concerned with rise in metabolic dysfunction-associated fatty liver disease (MAFLD) and ethanol as the dominant cause even in developing countries. MAFLD is the change in nomenclature from NAFLD to justify the metabolic derangement in these group of patients. The shift from an exclusion-based criteria to one that has evolved to a diagnosis that requires positive criteria has profound significance. Clearly there is a difference in terms of its prevalence, disease progression, and liver-related events, as well as management of metabolic risk factors and MAFLD itself which requires further understanding. In tandem with the global rise in MAFLD, the incidence of MAFLD-ACLF is increasing. Excessive alcohol consumption causes metabolic and toxic injury to the liver resulting in nearly similar pathway of fatty liver, hepatitis, and cirrhosis. The interaction of MAFLD as an additional underlying chronic liver injury in ACLF patients is complex due to the presence of metabolic risk factors that are unique to MAFLD. There is lack of clarity on how MAFLD affects the clinical course of ACLF due to scarcity of this specific data. This narrative review aims to understand the unique effects, consequences, and management of MAFLD as the chronic liver injury component in ACLF.

Rescue liver transplantation for post-hepatectomy liver failure- single center retrospective analysis

IntroductionLiver transplantation (LT) is a well-established method applied for the treatment of various liver diseases, including primary and secondary malignancies, as well as acute liver failure triggered by different mechanisms. In turn, liver failure (PHLF) is the most severe complication observed after liver resection (LR). PHLF is an extremely rare indication for LT. The aim of the present study was to assess the results of LT in patients with PHLF.MethodsRelevant cases were extracted from the prospectively collected database of all LTs performed in our center. All clinical variables, details of the perioperative course of each patient and long-term follow-up data were thoroughly assessed.ResultsBetween January 2000 and August 2023, 2703 LTs were carried out. Among them, six patients underwent LT for PHLF, which accounted for 0.2% of all patients. The median age of the patients was 38 years (range 24–66 years). All patients underwent major liver resection before listing for LT. The 90-day mortality after LT was 66.7% (4 out of 6 patients), and all patients experienced complications in the posttransplant course. One patient required early retransplantation due to primary non-function (PNF). The last two transplanted patients are alive at 7 years and 12 months after LT, respectively.ConclusionsIn an unselected population of patients with PHLF, LT is a very morbid procedure associated with high mortality but should be considered the only life-saving option in this group.

Serum Vitamin D level in sepsis patients and its correlation with clinical outcome

Background: Serum Vitamin D plays an important role in sepsis; lack of Vitamin D has been linked to a higher risk for the progression of infections, as it signifies an immune system mediator. Aims and Objectives: In this study, our aim is to evaluate the correlation between serum levels of Vitamin D and clinical outcome in sepsis patients. Materials and Methods: The present prospective cohort study was performed on patients over 18 years of age suspected of sepsis presenting to an emergency department during 1 year. For all eligible patients, the blood sample was drawn for the measurement of serum level of Vitamin D3, and its correlation with outcomes such as mortality, renal failure, and liver failure was assessed. Results: One hundred and sixty patients with a mean age of 48.5±20.587 years were studied (60.0% males). The mean serum level of Vitamin D3 in the studied patients was 32.0±12.54 ng/mL. By considering 30–100 ng/mL as the normal range of Vitamin D, 70% of the patients had Vitamin D deficiency. Only age (r=−0.261, P=0.037) and mortality (r=−0.426, P=0.025) showed a significant correlation with mean Vitamin D. Conclusion: Based on the result of this study, out of 160 patients, 61.25% of patients with sepsis are Vitamin D deficient. There is a significant and inverse relationship between mortality and advanced age which were associated with serum Vitamin D3 levels. Hence, supplementing with Vitamin D appears to have potential benefits in reducing infection rates, sepsis-related deaths, and infection prevalence, particularly in the elderly.

Intravenous delivery of furosemide using lipid-based versus polymer-based nanocapsules: in vitro and in vivo studies

: Furosemide (FSM), a potent loop diuretic, is used to treat edema due to hypertension, congestive heart failure, and liver and renal failures. FSM applications are limited by its low bioavailability. Our aim is to use different nanoencapsulation strategies to control the release of FSM and enhance its pharmacokinetic properties. Subsequently, two types of FSM-loaded nanocapsules, namely FSM-loaded lipid nanocapsules (LNCs) and polymeric nanocapsules (PNCs), were developed, physicochemically characterized, and subjected to pharmacokinetic and pharmacodynamic studies. Lipid nanocapsules were prepared by the simple phase inversion method using LabrafacTM lipid, while the polymeric nanocapsules were prepared by nanoprecipitation method using polycaprolactone polymer. Transmission electron microscopy ascertains spherical structures, corroborating the nanometric diameter of both types of nanocapsules. The particle size of the optimized FSM-loaded LNCs and FSM-loaded PNCs was 32.19 ± 0.72 nm and 230.7 ± 5.13 nm, respectively. The percent entrapment efficiency was 63.56 ± 1.40% for the optimized PNCs. The in vitro release study indicated prolonged drug release compared to drug solutions. The two loaded nanocapsules systems succeeded in enhancing the pharmacokinetic parameters in comparison to the marketed FSM solution with superior diuretic activity (p < 0.05). The results of the stability study and the terminal sterilization by autoclave indicated the superiority of LNCs over PNCs in maintaining the physical parameters under storage conditions and the drastic conditions of sterilization.

Enhancing Outcomes in Chronic Fibrotic Interstitial Lung Disease Through Aggressive Management of Nintedanib-Induced Adverse Drug Reactions: A Retrospective Analysis.

Nintedanib, a tyrosine kinase inhibitor, is integral in slowing pulmonary fibrosis progression in chronic fibrotic interstitial lung disease (ILD). However, the occurrence of adverse drug reactions (ADRs) often limits its use, leading to treatment discontinuation, typically within 3-12 months. Discontinuation adversely affects patient outcomes. The study investigated whether aggressive ADR management can prolong nintedanib therapy and improve patient outcomes. This retrospective, single-center study enrolled Taiwanese patients with chronic fibrotic ILD who were treated with nintedanib from January 2016 to December 2022 in Kaohsiung Chang Gung Memorial Hospital. Patients were categorized into those who discontinued treatment within 180 days and those continuing beyond. Management of ADRs was identified through concurrent prescriptions for symptoms such as nausea, vomiting, diarrhea, or hepatic dysfunction. Baseline demographics, comorbidities, pulmonary function tests, and instances of acute exacerbation were analyzed. The study enrolled 94 patients, with 71 (75.5%) experiencing ADRs. Among these, 41 (43.6%) discontinued nintedanib within 180 days. The administration of medications for managing nausea/vomiting [17 (41.5%) versus 36 (67.9%), p = 0.0103] and diarrhea [12 (29.3%) versus 33 (62.3%), p = 0.0015] was less frequent in the discontinued group compared with the continued group. Additionally, a higher incidence of acute exacerbation was observed in the discontinued group (34.1% versus 20.8%, p = 0.016). Aggressive management of ADRs may enhance patient tolerance to nintedanib, potentially prolonging treatment duration and improving outcomes in chronic fibrotic ILD.

Systematic review and meta-analysis of the effect of N-acetylcysteine on outcomes after liver resection.

N-Acetylcysteine (NAC) is a recognized antioxidative agent that facilitates the conjugation of toxic metabolites. In recent years, NAC has been routinely used to limit ischaemia-reperfusion injury in liver transplantation. There remains, however, contradictory evidence on its effectiveness in liver resection. This meta-analysis examines the effectiveness of NAC in improving outcomes following hepatectomy. A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases was performed to identify relevant randomized controlled trials (RCTs) published since database inception until November 2023. The outcomes of Day 1 biochemical markers (lactate, ALT, bilirubin, and INR), length of stay, transfusion rates, and morbidity were extracted. Quantitative pooling of data was based on a random-effects model. The study protocol was registered on PROSPERO (Registration no: CRD42023442429). Five RCTs reporting on 388 patients undergoing hepatectomy were included in the analysis. There were no significant differences in patient demographics between groups. Post-operative lactate was lower in patients receiving NAC (WMD -0.61, 95% CI -1.19 to -0.04, I2 = 67%). There were, however, no differences in the post-operative INR (WMD -0.04, 95% CI -0.19 to 0.12, I2 = 96%) and ALT (WMD -94.94, 95% CI -228.46 to 40.38; I2 = 67%). More importantly, there were no statistically significant differences in length of stay, transfusion rates, and morbidity between the two groups. The administration of NAC in liver resection did not alter important biochemical parameters suggesting any real effectiveness in reducing hepatic dysfunction. There were no improvements in the clinical outcomes of length of stay, transfusion rates, and overall morbidity.

VHDvDB 2.0: Database and Group Comparison Server for Hepatitis Delta Virus

The hepatitis delta virus (HDV) is a unique pathogen with significant global health implications, affecting individuals who are coinfected with the hepatitis B virus (HBV). HDV infection has profound clinical consequences, manifesting either as coinfection with HBV, resulting in acute hepatitis and potential liver failure, or as superinfection in chronic HBV cases, substantially increasing the risk of cirrhosis and hepatocellular carcinoma. Given the complex dynamics of HDV infection and the urgent need for advanced research tools, this article introduces vHDvDB 2.0, a comprehensive HDV full-length sequence database. This innovative platform integrates data preprocessing, secondary structure prediction, and epidemiological research tools. The primary goal of vHDvDB 2.0 is to consolidate HDV sequence data into a user-friendly repository, thereby facilitating access for researchers and enhancing the broader scientific understanding of HDV. The significance of this database lies in its potential to streamline HDV research by providing a centralized resource for analyzing viral sequences and exploring genotype-specific characteristics. It will also enable more in-depth research within the HDV sequence domains.

Realizing Textbook Outcomes Following Liver Resection for Hepatic Neoplasms with Development and Validation of a Predictive Nomogram.

'Textbook Outcome' (TO) represents an effort to define a standardized, composite quality benchmark based on intraoperative and postoperative endpoints. This study aimed to assess the applicability of TO as an outcome measure following liver resection for hepatic neoplasms from a low- to middle-income economy and determine its impact on long-term survival. Based on identified perioperative predictors, we developed and validated a nomogram-based scoring and risk stratification system. We retrospectively analyzed patients undergoing curative resections for hepatic neoplasms between 2012 and 2023. Rates of TO were assessed over time and factors associated with achieving a TO were evaluated. Using stepwise regression, a prediction nomogram for achieving TO was established based on perioperative risk factors. Of the 1018 consecutive patients who underwent liver resections, a TO was achieved in 64.9% (661/1018). The factor most responsible for not achieving TO was significant post-hepatectomy liver failure (22%). Realization of TO was independently associated with improved overall and disease-free survival. On logistic regression, American Society of Anesthesiologists score of 2 (p=0.0002), perihilar cholangiocarcinoma (p=0.011), major hepatectomy (p=0.0006), blood loss >1500mL (p=0.007), and presence of lymphovascular emboli on pathology (p=0.026) were associated with the non-realization of TO. These independent risk factors were integrated into a nomogram prediction model with the predictive efficiency for TO (area under the curve 75.21%, 95% confidence interval 70.69-79.72%). TO is a realizable outcome measure and should be adopted. We recommend the use of the nomogram proposed as a convenient tool for patient selection and prognosticating outcomes following hepatectomy.

Acute liver failure following fatal zinc phosphide poisoning in a dog

AbstractZinc phosphide is a highly toxic rodenticide that leads to organ dysfunction by disruption of oxidative phosphorylation via inhibition of the final enzyme of the mitochondrial transport chain (cytochrome C oxidase). A 5‐year‐old, female, spayed Shiba Inu presented in status epilepticus secondary to ingestion of this poison. The dog developed rapid progressive neurological decline, severe cardiotoxicity and acute liver failure, the latter manifested by hepatic encephalopathy and clinicopathological abnormalities, including coagulopathy, progressive liver enzyme elevations and hyperbilirubinemia, hypoglycaemia, hypoalbuminaemia, hypocholesterolaemia and low blood urea nitrogen. The dog ultimately died after 22 hours of hospitalisation. While this toxicosis is reported in several other species, this is the first case report documenting clinical acute liver failure secondary to zinc phosphide poisoning in a dog. Previous canine reports of zinc phosphide exposure suggest a generally favourable prognosis, whereas this case of toxicity was rapidly fatal, suggesting that reassessment of prognosis secondary to this toxicity is prudent.

Usefulness of Picture Archiving and Communication System-Based Quantitative Ultrasound Measurements in Evaluation of Allograft Dysfunction in Patients With Liver Transplantation.

The aim of this study was to assess the usefulness of picture archiving and communication system (PACS)-based quantitative grayscale ultrasonography (US) measurements in detecting allograft dysfunction in posttransplant patients. In this retrospective study, 116 patients with liver transplantation who underwent biopsy for allograft evaluation were recruited from the database. All participants had US images prior to procedure. Normal, acute cellular rejection (ACR), recurrent hepatitis (Hep), or combined (ACR/Hep) groups were generated based on pathology results. Region of interests were drawn for liver and rectus abdominus muscle to perform quantitative US analysis. The liver/muscle mean ratio (L/M) and heterogeneity index (HI; liver standard deviation/liver mean) were obtained. The ratios of groups were compared, and receiver-operating-characteristic analysis was performed. There was a significant difference between normal (n = 16) and each of other groups (ACR, 39; Hep, 36; combined, 25) for L/M and HI (P < 0.05). No significant difference was detected between ACR, Hep, and combined groups. The areas under the curve for L/M and HI were 0.755 (moderate) and 0.817 (good), respectively. To differentiate abnormal (ACR, Hep, and combined) from normal allografts sensitivity, specificity, PPV, and NPV were 50.0%, 87.5%, 96.2%, and 21.9% for cut point of L/M ≥1 and 84.0%, 68.8%, 94.4%, and 40.7% for cut point of HI ≥0.2 with odds ratios of 7.52 (for L/M ≥1) and 13.10 (for HI ≥0.2), respectively (P < 0.01). L/M has moderate and HI has good discrimination of normal from abnormal allograft in liver transplant patients. PACS-based quantitative US measurements is an objective, easy to use, noninvasive auxiliary tool to discriminate hepatic allograft dysfunction.

Elevated maternal serum bile acids Level, hypertensive disorders of pregnancy and adverse fetal Outcomes: A cohort study of 117,789 pregnant women in China

BackgroundElevated maternal serum total bile acids (sTBA) level during pregnancy was associated with adverse fetal outcomes. Women with elevated sTBA could complicate with hepatic dysfunction or vascular disorders (hypertensive disorders of pregnancy, HDP), which aggravated adverse fetal outcomes. However, the relationships among sTBA level, hepatic dysfunction, HDP and adverse fetal outcomes were still illusive. ObjectiveWe aimed to explore whether hepatic dysfunction or vascular disorders (HDP) mediated the associations between elevated sTBA level and adverse fetal outcomes. MethodsA large retrospective cohort study encompassing 117,789 Chinese pregnant women with singleton delivery between Jan 2014 and Dec 2022 was conducted. Causal mediation analysis was applied to assess the mediating role of hepatic dysfunction (alanine transaminase > 40 U/L) or HDP in explaining the relationship between high maternal sTBA level (≥10 μmol/L) and adverse fetal outcomes, including low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB). ResultssTBA level were positively associated with LBW (adjusted odds ratio (aOR) = 1.40; [95 % confidence interval (CI): 1.24–1.59]), SGA (aOR=1.31; [95 % CI: 1.18–1.46]), and PTB (aOR=1.27; [95 % CI: 1.15–1.41]), respectively. The estimated proportions of the total associations mediated by HDP were 47 % [95 % CI: 31 %–63 %] for LBW, 24 % [95 % CI: 13 %–35 %] for SGA, and 34 % [95 % CI: 19 %–49 %] for PTB, excepting the direct effects of high sTBA level. The contribution of hepatic dysfunction as a mediator was weaker on the association between high sTBA level on fetal outcomes, as the proportions mediated and 95 % CI were 16 % [4 %–29 %], 4 % [-6%–14 %], 32 % [15 %–50 %] for LBW, SGA, and PTB, respectively. Moreover, the mediating effect of hepatic dysfunction was nearly eliminated after excluding cases of HDP in the sensitivity analysis. ConclusionsThe substantial mediating effects through HDP highlighted its significant role in adverse fetal outcomes associated with elevated sTBA level. The findings also provoked new insights into understanding the mechanism and developing clinical management strategies (i.e. vascular protection) for adverse fetal outcomes associated with elevated sTBA level.

Sarcopenia is associated with short- and long-term mortality in patients with acute-on-chronic liver failure.

While sarcopenia is recognized as a predictor of mortality in cirrhosis, its influence on acute-on-chronic liver failure (ACLF) remains uncertain. Despite multiple studies examining the impact of sarcopenia on short-term mortality in patients with ACLF, the sample size of these studies was limited, and their outcomes were inconsistent. Therefore, this study aimed to explore the impact of sarcopenia on both short- and long-term mortality in patients with ACLF. This retrospective cohort study included 414 patients with ACLF that were treated between January 2016 and September 2022. Sarcopenia was diagnosed based on the measurement of the skeletal muscle index at the third lumbar vertebra (L3-SMI). Subsequently, the patients were divided into sarcopenia and non-sarcopenia groups. We analysed the basic clinical data of the two groups. Multivariate Cox proportional analysis was used to analyse short-term (28days) and long-term (1year and overall) mortality rates. A total of 414 patients were included, with a mean age of 52.88±13.41years. Among them, 318 (76.8%) were male, and 239 (57.7%) had sarcopenia. A total of 280 (67.6%) patients died during the study period. Among them, 153 patients died within 28days (37%) and 209 patients died within 1year (50.5%). We found that the 28-day, 1-year and overall mortality rates in the sarcopenia group were significantly higher than those in the non-sarcopenia group (37% vs. 22.3%, P<0.01; 50.5% vs. 34.9%, P<0.01; and 67.6% vs. 53.1%, P<0.01, respectively). Multivariate Cox regression analysis revealed that sarcopenia was significantly associated with increased mortality. The hazard ratios for sarcopenia were 2.05 (95% confidence interval [CI] 1.41-3.00, P<0.01) for 28-day mortality, 1.81 (95% CI 1.29-2.54, P<0.01) for 1-year mortality and 1.82 (95% CI 1.30-2.55, P<0.01) for overall mortality. In addition, muscle density and international normalized ratio were associated with short- and long-term mortality. Sarcopenia is associated with both short- and long-term mortality in patients with ACLF. Therefore, regular monitoring for sarcopenia is important for these patients.

Identification and genomic analyses of a Streptococcus suis ST25 strain associated with the first human septicemia in mainland China

Streptococcus suis (S. suis) is a Gram-positive bacterium and the main culprit behind zoonotic outbreaks, posing a serious threat to public health. The prevalent strains in China are mainly of sequence types (ST) 1 and 7, with few cases of human infections caused by other sequence type being reported. This study presents the first isolation of a ST25 strain from the blood of a septicemic patient. A 57-year-old febrile patient was admitted to a hospital in Hainan of China, diagnosed as septicemia and hepatic dysfunction. A strain of S. suis was isolated from blood culture and confirmed to be serotype 2 and ST25 through 16S rRNA sequencing and whole-genome sequencing, and its genome was further analyzed for gene functions and presence of drug resistance genes. The full-length genome of strain HN28 spans 2,280,124 bp and encodes a total of 2291 proteins. Genes annotated in COG, GO, KEGG, CAZy, and PHl databases accounted for 75.38 %, 69.14 %, 55.35 %, 4.58 %, and 11.87 % of the total predicted proteins, respectively. Virulence factor analysis revealed the presence of seven putative virulence genes in strain HN28. Analysis using the CARD database identified 51 resistance genes in HN28, alongside abundant exocytosis systems. These findings underscore the occurrence of S. suis infections in humans caused by less common ST, emphasizing the need for enhanced epidemiological investigations and monitoring of S. suis infections in the human population.

Distinct Clinical Courses and Shortened Lifespans in Childhood-Onset DNA Polymerase Gamma Deficiency.

DNA polymerase subunit gamma (POLG) deficiency is likely the most frequent cause of nuclear-encoded mitochondrial disorders. POLG-related disorders reportedly constitute a spectrum of overlapping phenotypes from infancy to late adulthood. We retrospectively reviewed natural histories for 40 children carrying biallelic pathogenic POLG variants. The patients were identified by the French coordinating center for mitochondrial disorders (CARAMMEL), making this a large monocentric series on childhood-onset POLG deficiency. Three patterns of clinical course and survival were observed, distinguished by main category of symptoms: neurologic, hepatic, and gastrointestinal. A total of 24 patients needed urgent neurointensive care for tonic-clonic seizures, myoclonic epilepsy, and status epilepticus, occasionally precipitated by valproate administration. Other neurologic symptoms included dystonia, cerebellar ataxia, and peripheral neuropathy. We report 6 POLG-deficient patients with polyradiculoneuropathy mimicking subacute Guillain-Barré syndrome and provide postgadolinium MRI evidence of diffuse cranial nerve root and cauda equina enhancement, suggesting these disorders have an inflammatory component. Children presenting with enteral nervous system involvement had vomiting, gastroparesis, and chronic intestinal pseudo-obstruction. They had later ages of onset and lived much longer. Primarily, hepatic presentations had the earliest onset and shortest survivals. Secondary hepatic failure was frequently precipitated by valproate administration given before diagnosis to patients with focal impaired awareness seizures or absence of seizures. These POLG deficiencies were often fatal, with age at death ranging from 3 months to 10 years, with a significant difference in survival between the 3 clinical forms; 6 of the 40 children did survive. No genotype-phenotype correlations were found for the 3 clinical course types. The study demonstrates the prevalence of neurologic presentation and the extent of central, peripheral, and autonomous nervous system involvement in 60% of patients. Most of the patients with early onset and rapidly fatal hepatic failure did not live long enough to develop neurologic symptoms. The study revealed a new clinical form of POLG deficiency presenting with neurodigestive symptoms with longer lifespan. We also propose that POLG deficiency should be considered in children presenting with unexplained polyradiculoneuropathy, demyelinating neuropathy, and elevated CSF protein. Finally, valproate administration remains a notable cause of avoidable death in POLG-deficient patients.

Understanding acute kidney injury (AKI) in liver cirrhosis from the acute-on-chronic liver failure (ACLF) perspective

Understanding acute kidney injury (AKI) in liver cirrhosis from the acute-on-chronic liver failure (ACLF) perspective