BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-...BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.展开更多
AIM:To compares the clinical features of patients infected with hepatitis E virus(HEV) with or without severe jaundice.In addition,the risk factors for HEV infection with severe jaundice were investigated.METHODS:We e...AIM:To compares the clinical features of patients infected with hepatitis E virus(HEV) with or without severe jaundice.In addition,the risk factors for HEV infection with severe jaundice were investigated.METHODS:We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group.Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum.We used χ2 analysis,Fisher's exact test,and Student's t test where appropriate in this study.Significant predictors in the univariate analysis were then included in a forward,stepwise multiple logistic regression model.RESULTS:No significant differences in symptoms,alanine aminotransferase,aspartate aminotransferase,al-kaline phosphatase,or hepatitis B virus surface antigen between the two groups were observed.HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase(GGT)(median:170.31 U/L vs 237.96 U/L,P = 0.007),significantly lower ALB levels(33.84 g/L vs 36.89 g/L,P = 0.000),significantly lower acetylcholine esterase(CHE) levels(4500.93 U/L vs 5815.28 U/L,P = 0.000) and significantly higher total bile acid(TBA) levels(275.56 μmol/L vs 147.03 μmol/L,P = 0.000) than those without severe jaundice.The median of the lowest point time tended to be lower in patients with severe jaundice(81.64% vs 96.12%,P = 0.000).HEV infected patients with severe jaundice had a significantly higher viral load(median:134 vs 112,P = 0.025) than those without severe jaundice.HEV infected patients with severe jaundice showed a trend toward longer median hospital stay(38.17 d vs 18.36 d,P = 0.073).Multivariate logistic regression indicated that there were significant differences in age,sex,viral load,GGT,albumin,TBA,CHE,prothrombin index,alcohol overconsumption,and duration of admission between patients infected with acute hepatitis E with and without severe jaundice.CONCLUSION:Acute hepatitis E patients may naturally present with severe jaundice.展开更多
Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ ...Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death, lts complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.展开更多
AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to t...AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and Octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic indexes.RESULTS: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and Octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis.展开更多
AIM: To establish a clinical scoring model to predict risk of acute-on-chronic liver failure(ACLF) in chronic hepatitis B(CHB) patients.METHODS: This was a retrospective study of 1457 patients hospitalized for CHB bet...AIM: To establish a clinical scoring model to predict risk of acute-on-chronic liver failure(ACLF) in chronic hepatitis B(CHB) patients.METHODS: This was a retrospective study of 1457 patients hospitalized for CHB between October 2008 and October 2013 at the Beijing Ditan Hospital, Capital Medical University, China. The patients were divided into two groups: severe acute exacerbation(SAE) group(n = 382) and non-SAE group(n = 1075). The SAE group was classified as the high-risk group based on the higher incidence of ACLF in this group than in the non-SAE group(13.6% vs 0.4%). Two-thirds of SAE patients were randomly assigned to risk-model derivation and the other one-third to model validation. Univariate risk factors associated with the outcome were entered into a multivariate logistic regression model for screening independent risk factors. Each variable was assigned an integer value based on the regression coefficients, and the final score was the sum of these values in the derivation set. Model discrimination and calibration were assessed using area under the receiver operating characteristic curve and the Hosmer-Lemeshow test. RESULTS: The risk prediction scoring model includedthe following four factors: age ≥ 40 years, total bilirubin ≥ 171 μmol/L, prothrombin activity 40%-60%, and hepatitis B virus DNA > 107 copies/m L. The sum risk score ranged from 0 to 7; 0-3 identified patients with lower risk of ACLF, whereas 4-7 identified patients with higher risk. The Kaplan-Meier analysis showed the cumulative risk for ACLF and ACLF-related death in the two risk groups(0-3 and 4-7 scores) of the primary cohort over 56 d, and log-rank test revealed a significant difference(2.0% vs 33.8% and 0.8% vs 9.4%, respectively; both P < 0.0001). In the derivation and validation data sets, the model had good discrimination(C index = 0.857, 95% confidence interval: 0.800-0.913 and C index = 0.889, 95% confidence interval: 0.820-0.957, respectively) and calibration demonstrated by the Hosmer-Lemeshow test(χ2 = 4.516, P = 0.808 and χ2 = 1.959, P = 0.923, respectively).CONCLUSION: Using the scoring model, clinicians can easily identify patients(total score ≥ 4) at high risk of ACLF and ACLF-related death early during SAE.展开更多
Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregn...Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregnancy is terminated, and significant complications, such as acute pancreatitis, can occur. Pancreatic involvement typically only occurs in severe cases after the development of hepatic and renal impairment. To date, little knowledge is available regarding how the disease causes pancreatitis. Treatment involves supportive measures and pregnancy interruption. In this report, we describe a case of a previously healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted with severe abdominal pain and vomiting. This case illustrates the clinical and laboratory overlap between acute fatty liver of pregnancy and pancreatitis, highlighting the difficulties in differentiating each disease. Furthermore, the hypothesis for this overlapping is presented, and the therapeutic options are discussed.展开更多
To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) thro...To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.展开更多
The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of whi...The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).展开更多
BACKGROUND Dengue-associated acute liver failure(PALF)accounts for a high mortality rate in children admitted to the pediatric intensive care unit(PICU).To date,there is a lack of data on clinical algorithms for estim...BACKGROUND Dengue-associated acute liver failure(PALF)accounts for a high mortality rate in children admitted to the pediatric intensive care unit(PICU).To date,there is a lack of data on clinical algorithms for estimating the risk of mortality in pediatric patients with dengue-induced severe hepatitis(DISH).AIM To determine the prevalence of PALF and identify the predictors of mortality among patients with DISH.METHODS This single-institution retrospective study was performed at a tertiary pediatric hospital in Vietnam between 2013 and 2022.The primary outcome was in-hospital mortality in pediatric patients with DISH,which was defined as either aspartate aminotransferase>350 IU/L or alanine aminotransferase>400 IU/L.Prognostic models for estimating the risk of death among patients with DISH were developed using a predefined set of clinical covariables and hepatic biomarkers on PICU admission and during the first 72 hours of admission.Area under the curve,multivariable logistic regression,and multiple imputation using the chained equation for missing values were performed.Backward stepwise model selection based on the Akaike information criterion was employed.Bootstrapping,calibration slope,and Brier score were used to assess the final models.RESULTS A total of 459 children with DISH were included in the analysis.The median patient age was 7.7 years(interquartile range:4.3-10.1 years).The prevalence of dengue-associated PALF in children with DISH was 18.3%.Thirty-nine DISH patients developing PALF(8.5%)died.Hepatic biomarkers,including the international normalized ratio(INR)≥2.11 and total serum bilirubin(≥1.7 mg/dL),showed high predictive values for mortality(all P values<0.001).Multivariable models showed the significant clinical predictors of death from dengue-induced PALF in patients with DISH,including reduced level of consciousness(pain and unresponsive levels on the Alert,Verbal,Pain,Unresponsive scale),high vasoactive-inotropic score(>30),and elevated levels of blood lactate,INR,and serum bilirubin.The final prognostic model demonstrated high discrimination,Brier score,and an acceptable calibration slope.CONCLUSION The prevalence of PALF in children with DISH is 18.3%.We developed robust prognostic models to estimate the risk of death in hospitalized children with severe dengue-induced hepatitis.展开更多
AIM: To undertake analysis of hepatitis A viral load, alanine aminotransferase (ALT), and viral genotypes with duration of viremia, and to correlate these parameters with CD4^+/ CD8^+ lymphocyte populations that ...AIM: To undertake analysis of hepatitis A viral load, alanine aminotransferase (ALT), and viral genotypes with duration of viremia, and to correlate these parameters with CD4^+/ CD8^+ lymphocyte populations that control cell-mediated immunity. METHODS: Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus (HAV) RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS: Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis (s-AH) and the remainder had a self-limited acute hepatitis A (AHA), with one patient with fulminant disease (encephalopathy Grade IV) dying on the 4^th d. The ALT level was significantly higher both in AHA (1070.9±894.3; P = 0.0014) and s-AH (1713.9±886.3; P = 0.001) compared to normal controls (23.6±7.2). The prothrombin time in s-AH patients (21.0 ±2.0; P=0.02) was significantly higher than in AHA (14.3±1.1;P = 0.44). The CD4^+/CD8^+ ratio in AHA patients (1.17 + 0.11; P = 0.22) and s-AH (0.83 + 0.12; P = 0.0002) were lower than seen in normal healthy controls (1.52). Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15TM or 30^th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and AIT values collected during the entire course of the selflimited infection were directly correlated but this was not the case for s-AH patients.CONCLUSION: Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.展开更多
Since October 2021 in Alabama,the United States,and March 2022 in central Scotland,the United Kingdom,the number of cases of severe acute hepatitis of unknown etiology/causes in children was found to increase,and the ...Since October 2021 in Alabama,the United States,and March 2022 in central Scotland,the United Kingdom,the number of cases of severe acute hepatitis of unknown etiology/causes in children was found to increase,and the total number of cases has reached 920 worldwide by June 22 this year,45 cases(5%)required liver transplantation,and 18 cases(2%)died according to World Health Organization(WHO).To understand the basic characteristics of this disease/syndrome,a literature search was performed at PubMed,websites of WHO,UK Health Security Agency,and US and European Centers for Disease Control and Prevention,and more than 20 reports were enrolled as references for this review.The main clinical manifestations are anorexia,vomiting,fatigue,jaundice,and so forth.Most of the cases seemed to have a self-limited course of the disease,about 6%of cases may develop life-threatening acute liver failure.The disease seems to be transmissible from person to person.Human adenovirus was detected in up to 75%of cases,but this virus seems not to be the only and major etiologic agent,other cofactors probably are involved.Researchers proposed many hypotheses concerning the etiology and pathogenesis,and many important works and studies are ongoing.This mini-review is aimed at summarizing,reviewing,and further understanding the characteristics of the disease,raising some clinically relevant questions,and trying to discuss some questions that may be related to the treatment of the disease for consideration.展开更多
Recently,cases of severe acute hepatitis of unknown cause(SAHUC)in children have suddenly increased in the United States,the United Kingdom,and other countries.In order to understand the progress in the diagnosis and ...Recently,cases of severe acute hepatitis of unknown cause(SAHUC)in children have suddenly increased in the United States,the United Kingdom,and other countries.In order to understand the progress in the diagnosis and treatment of this disease,and to prepare for the relevant plans in advance,the“Expert Symposium on the Severe Acute Hepatitis of Unknown Cause in Children”was successfully held on May 13,2022,online organized by Beijing Children's Hospital(BCH),Capital Medical University,Beijing Institute of Pediatrics Integrated Chinese and Western Medicine,Futang Research Center of Pediatric Development,and Branch of Hepatobiliary Diseases,China Association of Chinese Medicine.More than 9200 people watched the meeting online.Professors Yan Hu,Yan Yang,and Jing Hao,from the Department of Traditional Chinese Medicine(TCM),BCH,Capital Medical University,hosted the symposium.展开更多
Around 450 cases of acute severe hepatitis of unknown origin in children have been reported in 21 countries and region globally since April 2022,which has exceeded the past annual incidences of related regions,and has...Around 450 cases of acute severe hepatitis of unknown origin in children have been reported in 21 countries and region globally since April 2022,which has exceeded the past annual incidences of related regions,and has aroused wide concern.Affected patients were predominantly children under 16years of age,presented with symptoms of acute hepatitis with markedly elevated liver enzymes,and had been ruled out of common viral infections such as hepatitis A,B,C,D,and E.Similar cases have not been reported in China yet.However,considering that the severe acute hepatitis has involved worldwide areas,still with unknown origin,and incidences of severity is relatively high,we formulated this recommendation to standardize diagnosis and treatment of acute severe hepatitis of unknown origin in Peking Union Medical College Hospital,to get fully prepared to the possible public health events.展开更多
1|OUTBREAK OF SEVERE ACUTE HEPATITIS OF UNKNOWN ORIGIN IN CHILDREN Severe acute hepatitis of unknown origin in children was first reported by the United Kingdom to the World Health Organization on April 5,2022.Subsequ...1|OUTBREAK OF SEVERE ACUTE HEPATITIS OF UNKNOWN ORIGIN IN CHILDREN Severe acute hepatitis of unknown origin in children was first reported by the United Kingdom to the World Health Organization on April 5,2022.Subsequently,650 probable cases were reported worldwide by May 26,2022,1 and four patients were analyzed after reviewing the clinical records of a children's hospital in Alabama since October 1,2021.2 Although most patients recovered,the disease progressed to acute liver failure in several patients,who further required liver transplantation;thus,additional research is required to determine the disease pathogenesis.展开更多
BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever,with more than 400 million cases being reported annually,worldwide.Even though hepatic involvement is common,acute liver failure(ALF)is a rar...BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever,with more than 400 million cases being reported annually,worldwide.Even though hepatic involvement is common,acute liver failure(ALF)is a rare complication of dengue fever.AIM To analyze the demographic profile,symptomology,hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports.METHODS A systematic search was performed from multiple databases including PubMed,Reference Citation Analysis,Science Direct,and Google Scholar.The search terms used were"dengue"OR"severe dengue"OR"dengue shock syndrome"OR"dengue haemorrhagic syndrome"OR"dengue fever"AND"acute liver failure"OR"hepatic failure"OR"liver injury".The inclusion criteria were:(1)Case reports or case series with individual patient details;(2)Reported acute liver failure secondary to dengue infection;and(3)Published in English language and on adult humans.The data were extracted for patient demographics,clinical sympto-matology,clinical interventions,hospital and intensive care unit course,need for organ support and clinical outcomes.RESULTS Data from 19 case reports fulfilling the predefined inclusion criteria were included.The median age of patients was 38 years(inter quartile range:Q3-Q126.5 years)with a female preponderance(52.6%).The median days from diagnosis of dengue to development of ALF was 4.5 d.The increase in aspartate aminotransferase was higher than that in alanine aminotransferase(median 4625 U/L vs 3100 U/L).All the patients had one or more organ failure,with neurological failure present in 73.7%cases.42.1%patients required vasopressor support and hepatic enceph-alopathy was the most reported complication in 13(68.4%)cases.Most of the patients were managed conser-vatively and 2 patients were taken up for liver transplantation.Only 1 death was reported(5.3%).CONCLUSION Dengue infection may rarely lead to ALF.These patients may frequently require intensive care and organ support.Even though most of these patients may improve with supportive care,liver transplantation may be a therapeutic option in refractory cases.展开更多
Recent reports of acute hepatitis of unknown origin in previously healthy children have been increasing worldwide.The main characteristics of the affected children were jaundice and gastrointestinal symptoms.Their ser...Recent reports of acute hepatitis of unknown origin in previously healthy children have been increasing worldwide.The main characteristics of the affected children were jaundice and gastrointestinal symptoms.Their serum aminotransaminase levels were above 500 IU/L,with negative tests for hepatitis viruses A–E.By 31 May 2022,the outbreak had affected over 800 children under the age of 16 years in more than 40 countries,resulting in acute liver failure in approximately 10%,including at least 21 deaths and 38 patients requiring liver transplantation.There was still no confirmed cause or causes,although there were several different working hypotheses,such as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),adenovirus serotype 41,or SARS-CoV-2 superantigen-mediated immune cell activation.Here,we review early observations of the 2022 outbreak which may inform diagnosis,treatment,and prevention in the context of an overlapping COVID-19 pandemic.展开更多
The UK raised an alert with the World Health Organization(WHO)in April 2022 concerning a significant surge in the num-ber of children diagnosed with acute hepatitis of unknown origin(AHUO).Despite an ongoing investiga...The UK raised an alert with the World Health Organization(WHO)in April 2022 concerning a significant surge in the num-ber of children diagnosed with acute hepatitis of unknown origin(AHUO).Despite an ongoing investigation attributing its etiology to adenovirus infection,the absence of adenovirus inclusions in liver biopsies and the remarkably low viral load raised doubts.Concurrently,reports of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections in children coincided with the surge in acute hepatitis cases,prompting the need for a thorough examination of the poten-tial connection between current or past SARS-CoV-2 infections and pediatric hepatitis epidemics.Epidemiological data suggests that acute hepatitis is a notable manifestation of the multiple-system inflammatory syndrome in children following the global SARS-CoV-2 pandemic.However,the precise role of the SARS-CoV-2 virus in liver injury etiology remains uncertain.To shed light on the potential association between SARS-CoV-2 and AHUO in children,we conduct-ed a systematic review of epidemiological links,potential pathogenesis,and recent research findings,aiming to raise awareness and vigilance among clinicians.Convincing and definitive evidence will be essential in the future to confirm the direct impact of SARS-CoV-2 infection on children with AHUO.展开更多
基金Supported by the National Natural Science Foundation of China,No.81460124 and No.81860114
文摘BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.
基金Supported by Basic and Clinical Research of Capital Medical University,No. 2010JL10,to Xu B
文摘AIM:To compares the clinical features of patients infected with hepatitis E virus(HEV) with or without severe jaundice.In addition,the risk factors for HEV infection with severe jaundice were investigated.METHODS:We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group.Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum.We used χ2 analysis,Fisher's exact test,and Student's t test where appropriate in this study.Significant predictors in the univariate analysis were then included in a forward,stepwise multiple logistic regression model.RESULTS:No significant differences in symptoms,alanine aminotransferase,aspartate aminotransferase,al-kaline phosphatase,or hepatitis B virus surface antigen between the two groups were observed.HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase(GGT)(median:170.31 U/L vs 237.96 U/L,P = 0.007),significantly lower ALB levels(33.84 g/L vs 36.89 g/L,P = 0.000),significantly lower acetylcholine esterase(CHE) levels(4500.93 U/L vs 5815.28 U/L,P = 0.000) and significantly higher total bile acid(TBA) levels(275.56 μmol/L vs 147.03 μmol/L,P = 0.000) than those without severe jaundice.The median of the lowest point time tended to be lower in patients with severe jaundice(81.64% vs 96.12%,P = 0.000).HEV infected patients with severe jaundice had a significantly higher viral load(median:134 vs 112,P = 0.025) than those without severe jaundice.HEV infected patients with severe jaundice showed a trend toward longer median hospital stay(38.17 d vs 18.36 d,P = 0.073).Multivariate logistic regression indicated that there were significant differences in age,sex,viral load,GGT,albumin,TBA,CHE,prothrombin index,alcohol overconsumption,and duration of admission between patients infected with acute hepatitis E with and without severe jaundice.CONCLUSION:Acute hepatitis E patients may naturally present with severe jaundice.
基金Project supported by the Administration of Traditional Chinese Medicine of Zhejiang Province (Nos. 2003C130 and 2004C142)the Medical Science and Technology of Health Department of Zhejiang Province (No. 2003B134)the Technology and Development of Technological Bureau of Hangzhou (No. 2003123B19), China
文摘Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death, lts complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.
基金Supported by Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang province, No. 2003C130 and No. 2004C142Foundation Project For Medical Science and Technology of Zhejiang province, No. 2003B134+3 种基金Grave Foundation Project for Technological and Development of Hangzhou, No. 2003123B19Intensive Foundation Project for Technology of Hangzhou, No. 2004Z006Foundation Project for Medical Science and Technology of Hangzhou, No. 2003A004Foundation Project for Technology of Hangzhou, No. 2005224
文摘AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and Octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic indexes.RESULTS: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and Octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis.
基金Supported by Grants from National Natural Science Foundation of China,No.81273743,No.81473641and 215 Program,No.2013-2-11
文摘AIM: To establish a clinical scoring model to predict risk of acute-on-chronic liver failure(ACLF) in chronic hepatitis B(CHB) patients.METHODS: This was a retrospective study of 1457 patients hospitalized for CHB between October 2008 and October 2013 at the Beijing Ditan Hospital, Capital Medical University, China. The patients were divided into two groups: severe acute exacerbation(SAE) group(n = 382) and non-SAE group(n = 1075). The SAE group was classified as the high-risk group based on the higher incidence of ACLF in this group than in the non-SAE group(13.6% vs 0.4%). Two-thirds of SAE patients were randomly assigned to risk-model derivation and the other one-third to model validation. Univariate risk factors associated with the outcome were entered into a multivariate logistic regression model for screening independent risk factors. Each variable was assigned an integer value based on the regression coefficients, and the final score was the sum of these values in the derivation set. Model discrimination and calibration were assessed using area under the receiver operating characteristic curve and the Hosmer-Lemeshow test. RESULTS: The risk prediction scoring model includedthe following four factors: age ≥ 40 years, total bilirubin ≥ 171 μmol/L, prothrombin activity 40%-60%, and hepatitis B virus DNA > 107 copies/m L. The sum risk score ranged from 0 to 7; 0-3 identified patients with lower risk of ACLF, whereas 4-7 identified patients with higher risk. The Kaplan-Meier analysis showed the cumulative risk for ACLF and ACLF-related death in the two risk groups(0-3 and 4-7 scores) of the primary cohort over 56 d, and log-rank test revealed a significant difference(2.0% vs 33.8% and 0.8% vs 9.4%, respectively; both P < 0.0001). In the derivation and validation data sets, the model had good discrimination(C index = 0.857, 95% confidence interval: 0.800-0.913 and C index = 0.889, 95% confidence interval: 0.820-0.957, respectively) and calibration demonstrated by the Hosmer-Lemeshow test(χ2 = 4.516, P = 0.808 and χ2 = 1.959, P = 0.923, respectively).CONCLUSION: Using the scoring model, clinicians can easily identify patients(total score ≥ 4) at high risk of ACLF and ACLF-related death early during SAE.
基金Supported by The Department of Internal Medicine,Gastroenterology Division,Botucatu Medical School,Sao Paulo State University-UNESP,Botucatu/SP,Brazil
文摘Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregnancy is terminated, and significant complications, such as acute pancreatitis, can occur. Pancreatic involvement typically only occurs in severe cases after the development of hepatic and renal impairment. To date, little knowledge is available regarding how the disease causes pancreatitis. Treatment involves supportive measures and pregnancy interruption. In this report, we describe a case of a previously healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted with severe abdominal pain and vomiting. This case illustrates the clinical and laboratory overlap between acute fatty liver of pregnancy and pancreatitis, highlighting the difficulties in differentiating each disease. Furthermore, the hypothesis for this overlapping is presented, and the therapeutic options are discussed.
基金National 973 project of Chnia for SARS study (2003CB514112) Ministry of Education of China for SARS study (2003-18) National Science Fund for Distinguished Young Investigators (30225040,. 30123019).
文摘To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.
文摘The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).
基金approved by the Scientific Committee and Institutional Review Board of the Children’s Hospital 2,Ho Chi Minh City,Vietnam(approval No.391/QD-BVND2,March 22,2022).
文摘BACKGROUND Dengue-associated acute liver failure(PALF)accounts for a high mortality rate in children admitted to the pediatric intensive care unit(PICU).To date,there is a lack of data on clinical algorithms for estimating the risk of mortality in pediatric patients with dengue-induced severe hepatitis(DISH).AIM To determine the prevalence of PALF and identify the predictors of mortality among patients with DISH.METHODS This single-institution retrospective study was performed at a tertiary pediatric hospital in Vietnam between 2013 and 2022.The primary outcome was in-hospital mortality in pediatric patients with DISH,which was defined as either aspartate aminotransferase>350 IU/L or alanine aminotransferase>400 IU/L.Prognostic models for estimating the risk of death among patients with DISH were developed using a predefined set of clinical covariables and hepatic biomarkers on PICU admission and during the first 72 hours of admission.Area under the curve,multivariable logistic regression,and multiple imputation using the chained equation for missing values were performed.Backward stepwise model selection based on the Akaike information criterion was employed.Bootstrapping,calibration slope,and Brier score were used to assess the final models.RESULTS A total of 459 children with DISH were included in the analysis.The median patient age was 7.7 years(interquartile range:4.3-10.1 years).The prevalence of dengue-associated PALF in children with DISH was 18.3%.Thirty-nine DISH patients developing PALF(8.5%)died.Hepatic biomarkers,including the international normalized ratio(INR)≥2.11 and total serum bilirubin(≥1.7 mg/dL),showed high predictive values for mortality(all P values<0.001).Multivariable models showed the significant clinical predictors of death from dengue-induced PALF in patients with DISH,including reduced level of consciousness(pain and unresponsive levels on the Alert,Verbal,Pain,Unresponsive scale),high vasoactive-inotropic score(>30),and elevated levels of blood lactate,INR,and serum bilirubin.The final prognostic model demonstrated high discrimination,Brier score,and an acceptable calibration slope.CONCLUSION The prevalence of PALF in children with DISH is 18.3%.We developed robust prognostic models to estimate the risk of death in hospitalized children with severe dengue-induced hepatitis.
文摘AIM: To undertake analysis of hepatitis A viral load, alanine aminotransferase (ALT), and viral genotypes with duration of viremia, and to correlate these parameters with CD4^+/ CD8^+ lymphocyte populations that control cell-mediated immunity. METHODS: Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus (HAV) RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS: Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis (s-AH) and the remainder had a self-limited acute hepatitis A (AHA), with one patient with fulminant disease (encephalopathy Grade IV) dying on the 4^th d. The ALT level was significantly higher both in AHA (1070.9±894.3; P = 0.0014) and s-AH (1713.9±886.3; P = 0.001) compared to normal controls (23.6±7.2). The prothrombin time in s-AH patients (21.0 ±2.0; P=0.02) was significantly higher than in AHA (14.3±1.1;P = 0.44). The CD4^+/CD8^+ ratio in AHA patients (1.17 + 0.11; P = 0.22) and s-AH (0.83 + 0.12; P = 0.0002) were lower than seen in normal healthy controls (1.52). Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15TM or 30^th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and AIT values collected during the entire course of the selflimited infection were directly correlated but this was not the case for s-AH patients.CONCLUSION: Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.
文摘Since October 2021 in Alabama,the United States,and March 2022 in central Scotland,the United Kingdom,the number of cases of severe acute hepatitis of unknown etiology/causes in children was found to increase,and the total number of cases has reached 920 worldwide by June 22 this year,45 cases(5%)required liver transplantation,and 18 cases(2%)died according to World Health Organization(WHO).To understand the basic characteristics of this disease/syndrome,a literature search was performed at PubMed,websites of WHO,UK Health Security Agency,and US and European Centers for Disease Control and Prevention,and more than 20 reports were enrolled as references for this review.The main clinical manifestations are anorexia,vomiting,fatigue,jaundice,and so forth.Most of the cases seemed to have a self-limited course of the disease,about 6%of cases may develop life-threatening acute liver failure.The disease seems to be transmissible from person to person.Human adenovirus was detected in up to 75%of cases,but this virus seems not to be the only and major etiologic agent,other cofactors probably are involved.Researchers proposed many hypotheses concerning the etiology and pathogenesis,and many important works and studies are ongoing.This mini-review is aimed at summarizing,reviewing,and further understanding the characteristics of the disease,raising some clinically relevant questions,and trying to discuss some questions that may be related to the treatment of the disease for consideration.
文摘Recently,cases of severe acute hepatitis of unknown cause(SAHUC)in children have suddenly increased in the United States,the United Kingdom,and other countries.In order to understand the progress in the diagnosis and treatment of this disease,and to prepare for the relevant plans in advance,the“Expert Symposium on the Severe Acute Hepatitis of Unknown Cause in Children”was successfully held on May 13,2022,online organized by Beijing Children's Hospital(BCH),Capital Medical University,Beijing Institute of Pediatrics Integrated Chinese and Western Medicine,Futang Research Center of Pediatric Development,and Branch of Hepatobiliary Diseases,China Association of Chinese Medicine.More than 9200 people watched the meeting online.Professors Yan Hu,Yan Yang,and Jing Hao,from the Department of Traditional Chinese Medicine(TCM),BCH,Capital Medical University,hosted the symposium.
文摘Around 450 cases of acute severe hepatitis of unknown origin in children have been reported in 21 countries and region globally since April 2022,which has exceeded the past annual incidences of related regions,and has aroused wide concern.Affected patients were predominantly children under 16years of age,presented with symptoms of acute hepatitis with markedly elevated liver enzymes,and had been ruled out of common viral infections such as hepatitis A,B,C,D,and E.Similar cases have not been reported in China yet.However,considering that the severe acute hepatitis has involved worldwide areas,still with unknown origin,and incidences of severity is relatively high,we formulated this recommendation to standardize diagnosis and treatment of acute severe hepatitis of unknown origin in Peking Union Medical College Hospital,to get fully prepared to the possible public health events.
基金National Natural Science Foundation,Grant/Award Number:82172254 and 1.3.5 project for disciplines of excellenceWest China Hospital,Sichuan University,Grant/Award Number:ZYGD20009。
文摘1|OUTBREAK OF SEVERE ACUTE HEPATITIS OF UNKNOWN ORIGIN IN CHILDREN Severe acute hepatitis of unknown origin in children was first reported by the United Kingdom to the World Health Organization on April 5,2022.Subsequently,650 probable cases were reported worldwide by May 26,2022,1 and four patients were analyzed after reviewing the clinical records of a children's hospital in Alabama since October 1,2021.2 Although most patients recovered,the disease progressed to acute liver failure in several patients,who further required liver transplantation;thus,additional research is required to determine the disease pathogenesis.
文摘BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever,with more than 400 million cases being reported annually,worldwide.Even though hepatic involvement is common,acute liver failure(ALF)is a rare complication of dengue fever.AIM To analyze the demographic profile,symptomology,hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports.METHODS A systematic search was performed from multiple databases including PubMed,Reference Citation Analysis,Science Direct,and Google Scholar.The search terms used were"dengue"OR"severe dengue"OR"dengue shock syndrome"OR"dengue haemorrhagic syndrome"OR"dengue fever"AND"acute liver failure"OR"hepatic failure"OR"liver injury".The inclusion criteria were:(1)Case reports or case series with individual patient details;(2)Reported acute liver failure secondary to dengue infection;and(3)Published in English language and on adult humans.The data were extracted for patient demographics,clinical sympto-matology,clinical interventions,hospital and intensive care unit course,need for organ support and clinical outcomes.RESULTS Data from 19 case reports fulfilling the predefined inclusion criteria were included.The median age of patients was 38 years(inter quartile range:Q3-Q126.5 years)with a female preponderance(52.6%).The median days from diagnosis of dengue to development of ALF was 4.5 d.The increase in aspartate aminotransferase was higher than that in alanine aminotransferase(median 4625 U/L vs 3100 U/L).All the patients had one or more organ failure,with neurological failure present in 73.7%cases.42.1%patients required vasopressor support and hepatic enceph-alopathy was the most reported complication in 13(68.4%)cases.Most of the patients were managed conser-vatively and 2 patients were taken up for liver transplantation.Only 1 death was reported(5.3%).CONCLUSION Dengue infection may rarely lead to ALF.These patients may frequently require intensive care and organ support.Even though most of these patients may improve with supportive care,liver transplantation may be a therapeutic option in refractory cases.
基金support from the National Key Research and Development Program of China(2021YFC2700802)the National Natural Science Foundation of China(81873565,82170593)。
文摘Recent reports of acute hepatitis of unknown origin in previously healthy children have been increasing worldwide.The main characteristics of the affected children were jaundice and gastrointestinal symptoms.Their serum aminotransaminase levels were above 500 IU/L,with negative tests for hepatitis viruses A–E.By 31 May 2022,the outbreak had affected over 800 children under the age of 16 years in more than 40 countries,resulting in acute liver failure in approximately 10%,including at least 21 deaths and 38 patients requiring liver transplantation.There was still no confirmed cause or causes,although there were several different working hypotheses,such as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),adenovirus serotype 41,or SARS-CoV-2 superantigen-mediated immune cell activation.Here,we review early observations of the 2022 outbreak which may inform diagnosis,treatment,and prevention in the context of an overlapping COVID-19 pandemic.
基金supported by Wuxi Municipal Medical Innovation Team (CXTD2021013).
文摘The UK raised an alert with the World Health Organization(WHO)in April 2022 concerning a significant surge in the num-ber of children diagnosed with acute hepatitis of unknown origin(AHUO).Despite an ongoing investigation attributing its etiology to adenovirus infection,the absence of adenovirus inclusions in liver biopsies and the remarkably low viral load raised doubts.Concurrently,reports of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections in children coincided with the surge in acute hepatitis cases,prompting the need for a thorough examination of the poten-tial connection between current or past SARS-CoV-2 infections and pediatric hepatitis epidemics.Epidemiological data suggests that acute hepatitis is a notable manifestation of the multiple-system inflammatory syndrome in children following the global SARS-CoV-2 pandemic.However,the precise role of the SARS-CoV-2 virus in liver injury etiology remains uncertain.To shed light on the potential association between SARS-CoV-2 and AHUO in children,we conduct-ed a systematic review of epidemiological links,potential pathogenesis,and recent research findings,aiming to raise awareness and vigilance among clinicians.Convincing and definitive evidence will be essential in the future to confirm the direct impact of SARS-CoV-2 infection on children with AHUO.