OBJECTIVE: To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2). METHODS: Three children who were diagnosed with ILFS2 at the Children's Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). RESULTS: The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c.3596G>A and c.1181A>T in child 1, c.2617C>T and c.2T>C in child 2, and c.3596G>A and c.2817_2818insT in child 3. Among these, the c.1181A>T and c.2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+PM3+PP3) and pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION Combined with the patient's clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c.1181A>T and c.2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.
Humans ; Exome Sequencing ; Genetic Testing/methods* ; Liver Failure, Acute/etiology* ; Mutation ; Child ; Adult ; Neoplasm Proteins

OBJECTIVES: To explore the role of the cGAS-STING signaling pathway in the therapeutic mechanism of Liangxue Jiedu Huayu Formula (LXJDHYF) for acute-on-chronic liver failure (ACLF) in mice. METHODS: Thirty C57BL/6 mice were randomly divided into blank control group, model group, low- and high-dose LXJDHYF groups, and H151 (a specific cGAS-STING pathway inhibitor) group (n=6). In all but the control group, the mice were treated with CCl₄ to induce liver cirrhosis followed by intraperitoneal injections of lipopolysaccharide and D-amino galactose to establish mouse models of ACLF. After the treatments, the mouse livers were collected for HE and TUNEL staining, and serum levels of ALT, AST and TBil were determined. In bone marrow-derived macrophages (BMDMs) and liver tissues of ACLF mice, the expressions of cGAS-STING signaling pathway-related mRNAs including IFN‑β, ISG15, IL-6 and TNF-α were determined with RT-qPCR, and the phosphorylation levels of IRF3 and STING proteins were investigated using Western blotting. RESULTS: Compared with the mice in the model group, the LXJDHYF-treated mice exhibited milder hepatocyte necrosis and inflammatory cell infiltration in the liver with significantly reduced hepatocyte apoptosis. LXJDHYF treatment also significantly lowered serum levels of ALT, AST, TBil, IL-6 and TNF-α in ACLF mice and effectively suppressed the expressions of cGAS-STING signaling pathway-related mRNA in both the BMDMs and the liver tissues and the phosphorylation of IRF3 and STING proteins in the BMDMs. CONCLUSIONS LXJDHYF can significantly improve liver function and attenuate inflammation in ACLF mice possibly by inhibiting excessive activation of the cGAS-STING signaling pathway.
Animals ; Signal Transduction/drug effects* ; Mice ; Nucleotidyltransferases/metabolism* ; Mice, Inbred C57BL ; Acute-On-Chronic Liver Failure/etiology* ; Membrane Proteins/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Liver/metabolism* ; Disease Models, Animal ; Interferon Regulatory Factor-3/metabolism* ; Interleukin-6/metabolism* ; Male

The three-day-old female infant was admitted to the hospital due to respiratory distress after birth. She was born premature at 36⁺² weeks gestational age. Prenatal ultrasound suggested abnormal development of the fetal liver vessels, and she had dyspnea that required respiratory support after birth. Chest X-ray indicated an enlarged cardiac silhouette, and cardiac ultrasound revealed enlargement of the right atrium and right ventricle. Diagnosis of hepatic hemangioma with arteriovenous fistula was confirmed through liver ultrasound and abdominal enhanced CT. At 19 days old, she underwent ligation of the hepatic artery under general anesthesia, which led to an improvement in cardiac function and she was subsequently discharged. Genetic testing revealed a mutation in the ACVRL1 gene, which was inherited from the mother. The article primarily introduces a case of neonatal heart failure caused by hepatic hemangioma with arteriovenous fistula, and multi-disciplinary diagnosis and treatment of this disease.
Female ; Humans ; Infant, Newborn ; Pregnancy ; Activin Receptors, Type II ; Arteriovenous Fistula/complications* ; Dyspnea ; Heart Failure/etiology* ; Hemangioma/complications* ; Liver

Patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF) show high morbidity and mortality. Independent prognostic predictors of short-term HBV-ACLF mortality include the Child-Turcotte-Pugh (CTP) score, the model for end-stage liver disease (MELD) score, other MELD-based indices and the dynamic changes in these indices. The aims of this study were to evaluate the existing prognostic scores in a large cohort of HBV-ACLF patients and create a new predictive model. We retrospectively reviewed 392 HBV-ACLF patients from December 2008 to November 2011 and evaluated their 3-month survival. The predictive accuracy of CTP, MELD and MELD-based indices and the dynamic changes in the MELD-related scores (Δ scoring systems) upon admission and after two weeks of treatment were compared using the area under the receiver operating characteristic (ROC) curve method. Life-threatening factors and a series of bio-clinical parameters were studied by univariate and multivariate analyses. Among the existing scores, MELD had the best predictive ability. However, our new regression model provided an area under the curve of 0.930 ± 0.0161 (95% CI: 0.869 to 0.943), which was significantly larger than that obtained with the MELD score at admission and after two weeks of treatment as well as with the dynamic changes of the MELD score (0.819, 0.921, and 0.826, respectively) (Z=3.542, P=0.0004). In a large cohort of patients retrospectively reviewed for this study, our prognostic model was superior to the MELD score and is, therefore, a promising predictor of short-term survival in patients with HBV-ACLF.
Acute Disease ; Adult ; Chronic Disease ; Female ; Hepatitis B ; complications ; Humans ; Liver Failure ; etiology ; Male ; Middle Aged ; Prognosis

Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year-old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine.
Adult ; Alanine Transaminase/blood ; Anticonvulsants/*adverse effects/therapeutic use ; Aspartate Aminotransferases/blood ; Drug Hypersensitivity/complications/*diagnosis ; Humans ; Liver/enzymology/metabolism ; Liver Failure/*etiology ; Male ; Stevens-Johnson Syndrome/diagnosis/drug therapy ; Triazines/*adverse effects/therapeutic use

BACKGROUND/AIMS: Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. METHODS: Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. RESULTS: A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (> or =28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (> or =grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). CONCLUSIONS: Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.
Acute-On-Chronic Liver Failure/*diagnosis/drug therapy/etiology ; Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antiviral Agents/therapeutic use ; Cyclophosphamide/therapeutic use ; DNA, Viral/analysis ; Doxorubicin/therapeutic use ; Female ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/drug therapy ; Hospitalization ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Prednisone/therapeutic use ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Vincristine/therapeutic use ; Young Adult

OBJECTIVETo investigate the clinical application, indication, timing and prognosis of blood purification (artificial liver, BP) in treatment of acute liver failure in children.

METHODArtificial liver was used to treat 30 cases of pediatric acute liver failure (PALF), who were hospitalized in pediatric intensive care unit of Bayi Children's Hospital Affiliated to Beijing Military Command General Hospital, during March 2010 to July 2013. Simple plasma exchange (PE) mode was used for PALF without complications, while PE combined with continuous veno-venous hemodiafiltration (CVVHDF) mode was used for PALF with cerebral edema and/or hepatorenal syndrome and/or serious abnormality of electrolyte and acid-base balance.

RESULTSixteen cases survived and restored hepatic function, with a survival rate of 53.3%. Single PE therapy could significantly decrease total bilirubin (TBIL) from (293.96 ± 214.52) µmol/L to (155.64 ± 140.97) µmol/L (P = 0.033), increase prothrombin time activity (PTA) from (34.50 ± 18.34) % to (60.50 ± 33.97) % (P = 0.013), while it did not significantly influence ammonia from (156.43 ± 67.23) µmol/L to (124.03 ± 62.58) µmol/L (P = 0.156) and alanine transarninase (ALT) from (752.53 ± 1 291.84) U/L to (132.00 ± 98.57) U/L (P = 0.066). PE + CVVHDF therapy could significantly ameliorate TBIL from (326.90 ± 233.85) µmol/L to (157.53 ± 125.31) µmol/L (P = 0.033), ALT from (1 476.64 ± 1 728.18) U/L to (169.38 ± 207.18) U/L (P = 0.019), ammonia from (215.83 ± 83.92) µmol/L to (141.25 ± 63.09) µmol/L (P = 0.022) and PTA from (36.68 ± 23.13)% to (71.75 ± 50.50) % (P = 0.044). Prothrombin time (PT) from (29.71 ± 17.75)s to (16.27 ± 6.38)s (P = 0.008) , ALT from (1 574.11 ± 1 775.96) U/L to (145.81 ± 113.89 ) U/L (P = 0.003) , TBIL from (233.16 ± 219.70) µmol/L to (75.19 ± 86.07) µmol/L (P = 0.012) , ammonia from (182.75 ± 90.07) µmol/L to (101.81 ± 37.14) µmol/L (P = 0.002) and PTA from (38.38 ± 20.39)% to (83.13 ± 41.68)% (P = 0.001) in survived cases significantly ameliorated after BP therapy. TBIL from (394.04 ± 192.80) µmol/L to (249.34 ± 113.97) µmol/L (P = 0.023) in died cases declined significantly after BP therapy, while alteration of PT, ALT, ammonia , and PTA had no statistical significance (P > 0.10) after BP therapy.

CONCLUSIONPE + CVVHDF therapy could significantly ameliorate not only TBIL and PTA but also ammonia and ALT compared with single PE therapy. The decline of only an index like TBIL or ALT after BP therapy could not improve the prognosis. The inconsistency between serum bilirubin and ALT levels was an important factor that suggested poor prognosis of ALF, and it might increase survival rate to use BP therapy before that inconsistency emerged.

Adolescent ; Bilirubin ; blood ; Biomarkers ; blood ; Brain Edema ; etiology ; therapy ; Child ; Child, Preschool ; Female ; Hemodiafiltration ; methods ; Heparin ; pharmacology ; Hepatorenal Syndrome ; etiology ; therapy ; Humans ; Infant ; Liver Failure, Acute ; blood ; complications ; mortality ; therapy ; Liver Function Tests ; Male ; Plasma Exchange ; Prothrombin Time ; Survival Rate ; Treatment Outcome

OBJECTIVETo compare the clinical values of the model for end-stage liver disease (MELD)-Na scoring system and the Child-Turcotte-Pugh (CTP) scoring system for predicting the short-term prognosis of acute-on-chronic hepatitis B liver failure.

METHODSA total of 339 patients with acute-on-chronic hepatitis B liver failure and admitted to the Eighth People's Hospital of Guangzhou and Nanfang Hospital of Southern Medical University between January 2010 and December 2012 were included in this retrospective analysis. The short-term predictive values of MELD-Na and CTP scores were compared for this patient population.

RESULTSThe mean MELD-Na score in the advanced stage of liver failure was significantly higher than those in the early and middle stages, respectively (both P less than 0.01). The mean MELD-Na score in the middle stage of liver failure was also significantly higher than that in the early stage (P less than 0.01). In contrast, the mean CTP scores for the three stages of liver failure were not significantly different (all P more than 0.05). The MELD-Na score showed a stronger correlation with the stage of liver failure (rs =0.485, P less than 0.01) than did the CTP score (rs =0.306, P less than 0.01). The short-term mortality rates were significantly different for the three stages of liver failure (P less than 0.01). The mean MELD-Na score of the death group was significantly higher than that of the survival group (P less than 0.01). The CTP scores, however, were not significantly different between the death and survival groups (P more than 0.05).The short-term mortality rate of liver failure was significantly higher for patients with increased scores for the MELD-Na and CTP systems (both P less than 0.01). The areas under the curve of the MELD-Na and CTP scores were 0.813 and 0.823, respectively. The MELD-Na and CTP score have similar predictive values (P more than 0.05).

CONCLUSIONThe MELD-Na scoring system is slightly superior to the CTP scoring system for predicting short-term prognosis of acute-on-chronic hepatitis B liver failure.The predictive value may improve for both the MELD-Na score and the CTP score when combined with expert clinical practice and experience.

Acute-On-Chronic Liver Failure ; etiology ; Hepatitis B ; Hepatitis B, Chronic ; complications ; Humans ; Prognosis ; Retrospective Studies ; Sodium

INTRODUCTIONThere have been intermittent reports of peroneal neuropathy (PN) occurring after liver transplantation. Although PN may not be viewed as a serious complication by liver transplant (LT) recipients who require the transplant for survival, PN can significantly reduce quality of life. The incidence of PN appears to have increased after the use of gel pads was introduced. These gel pads, which are placed under patients' knees during surgery, are used to reduce lower back strain and prevent contact between the peroneal nerve at the fibular head and the hard surface of the operating table. The aim of the present study was to investigate the association, if any, between the use of gel pads and the incidence of PN.

METHODSThe medical records of 261 adult LT recipients were retrospectively reviewed. The recipients were divided into gel pad (n = 167) and non-gel pad (n = 94) groups. The incidence and possible risk factors of PN were compared between the two groups.

RESULTSThe overall incidence of PN was 8.0% (21/261). The occurrence of PN was significantly higher in the gel pad group than in the non-gel pad group (10.8% vs. 3.2%; p < 0.05). Other possible risk factors were comparable between the two patient groups.

CONCLUSIONAs the use of gel pads may increase the incidence of PN, we recommend against the use of gel pads under the knees of LT recipients.

Adult ; Female ; Gels ; Humans ; Incidence ; Liver Failure ; complications ; surgery ; Liver Transplantation ; adverse effects ; Low Back Pain ; prevention & control ; Male ; Middle Aged ; Peroneal Neuropathies ; etiology ; prevention & control ; Postoperative Complications ; prevention & control ; Protective Devices ; Quality of Life ; Retrospective Studies ; Risk Factors ; Treatment Outcome

BACKGROUND/AIMS: A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal. METHODS: The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis. RESULTS: Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD. CONCLUSIONS: Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.
Acute Kidney Injury/*epidemiology/etiology/mortality ; Adult ; Aged ; Cohort Studies ; Female ; Hospital Mortality ; Humans ; Kidney Failure, Chronic/*epidemiology/etiology/mortality ; Liver Cirrhosis/complications/*diagnosis ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Severity of Illness Index ; Survival Rate