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Predictive value of the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score in the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure

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Chinese Medical Journal 2019年第13期132卷 1541-1549页

作者： Jing-Jing Tong Wei Zhao Xiu-Ying Mu Xiang Xu Hai-Bin Su Xiao-Yan Liu Jing Chen Xing-Ran Zhai Yu Wang Jin-Hua Hu Liver Failure Treatment and Research Center The Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Clinical Laboratory China-Japan Friendship HospitalBeijing 100029China Peking University 302 Clinical Medical School Beijing 100039China Medical School of Chinese PLA Beijing 100853China

Background:As a large,prospective,multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF),the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score(COSSH-ACLFs),has been approved by some foreign scholars;however,its predictive value needs to be verified.This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF.Methods:This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014.Spearman method was used to assess the correlation of COSSHACLFs with classical scores.Different COX multivariate regression models were used to confirm the relationship between COSSHACLFs and short-term prognosis in patients with HBV-ACLF,and stratified analysis was used to further verify the stability of this relationship.We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve(AUROC)and Z-test.Results:A total of 975 patients with HBV-ACLF were screened,and 751 were analyzed(623 male and 128 female).COSSH-ACLFs was the highest in patients with end-stage ACLF,followed by those with middle-and early-stage ACLF(H=211.8,P<0.001).In the fully adjusted model,COX multivariate regression analysis revealed that COSSH-ACLFs(as a continuous variable)was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days(hazard ratio[HR]:1.37[1.22,1.53],P<0.001)and 90 days(HR:1.43[1.29,1.58],P<0.001).The same trend could be observed in the crude model and minimally adjusted model.The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792,respectively,indicating a stronger predictive accuracy than those of classic models.Conclusions:COSSH-ACLFs,with a superior predictive accuracy compared with other classical scores,can strongly predict sh

关键词： Hepatitis B virus-related acute-on-chronic liver failure COSSH-ACLF score Predictive value Prognosis

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Role of dihydroceramides in the progression of acute-on-chronic liver failure in rats

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Chinese Medical Journal 2020年第2期133卷 198-204页

作者： Fang-Fang Li Ning Liu Wei Liu Mei Li Fan Zhang Zhen Dong Jin-Lan Zhang Hua Sun State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Background:Previously,dihydroceramide(d18:0/24:0)(dhCer(d18:0/24:0))was reported to be a potential biomarker for acute-onchronic liver failure(ACLF)prognosis.In this study,we further explored the role of dhCer(d18:0/24:0)in the progression of ACLF to validate the biomarker using ACLF rat model.Methods:ACLF rats were sacrificed at 4 and 8 h post-D-galactosamine(D-gal)/lipopolysaccharide(LPS)administration to investigate the liver biochemical markers,prothrombin time and liver histopathology.Change in dhCer and other sphingolipids levels were investigated by high-performance liquid chromatography coupled to tandem mass spectrometry(HPLC-MS/MS).Rats were treated with N-(4-hydroxyphenyl)retinamide(4-HPR)to examine the mortality rate and its role in improving ACLF.Results:LPS/D-gal administration resulted in significant elevation in alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels.Prothrombin time was prolonged and histopathological examination showed abnormality.HPLC-MS/MS results showed total dhCer levels in ACLF group(64.10±8.90 pmol/100 mL,64.22±6.78 pmol/100 mL for 4 and 8 h,respectively)were decreased significantly compared with control group(121.61±23.09 pmol/100 mL)(P<0.05).In particular,dhCer(d18:0/24:0),dhCer(d18:0/20:0),and dhCer(d18:0/22:0)levels were decreased.Treatment with 4-HPR significantly increased the levels of dhCers,including dhCer(d18:0/24:0)compared with ACLF group,for the level of dhCer(d18:0/24:0)in 4-HPR group was 20.10±8.60 pmol/100 mL and the level of dhCer(d18:0/24:0)in ACLF group was 9.74±2.99 pmol/100 mL(P<0.05).This was associated with reduced mortality rate and prolonged survival time.The ALT and AST in 4-HPR group were significantly decreased compared with ACLF group.The prothrombin time of 4-HPR group(41.49 s)was significantly lower than the prothrombin time of ACLF group(57.96 s)(P<0.05).4-HPR also decreased plasma ammonia levels slightly,as the plasma ammonia levels in 4-HPR group and ACLF group were 207.37±60.43,209.15±60.43 mmol/L,respectively.Further,4-HPR

关键词： N-(4-hydroxyphenyl)retinamide acute-on-chronic liver failure Ceramides Dihydroceramides

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The immunological roles in acute-on-chronic liver failure:An update

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Hepatobiliary & Pancreatic Diseases International 2019年第5期18卷 403-411页

作者： Ping Chen Yun-Yun Wang Chao Chen Jun Guan Hai-Hong Zhu Zhi Chen State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated Hospital Zhejiang University School of Medicine

Background: acute-on-chronic liver failure (ACLF) refers to the acute deterioration of liver function that occurs in patients with chronic liver disease. ACLF is characterized by acute decompensation, organ failure and high short-term mortality. Numerous studies have been conducted and remarkable progress has been made regarding the pathophysiology and pathogenesis of this disease in the last decade. The present review was to summarize the advances in this field. Data sources: A comprehensive search in PubMed and EMBASE was conducted using the medical subject words “acute-on-chronic liver failure”,“ACLF”,“pathogenesis”,“predictors”, and “immunotherapy” combined with free text terms such as “systemic inflammation” and “immune paralysis”. Relevant papers published before October 31, 2018, were included. Results: ACLF has two marked pathophysiological features, namely, excessive systemic inflammation and susceptibility to infection. The systemic inflammation is mainly manifested by a significant increase in the levels of plasma pro-inflammatory factors, leukocyte count and C-reactive protein. The underlying mechanisms are unclear and may be associated with decreased immune inhibitory cells, abnormal expression of cell surface molecules and intracellular regulatory pathways in immune cells and increased damageassociated molecular patterns in circulation. However, the main cause of susceptibility to infection is immune paralysis. Immunological paralysis is characterized by an attenuated activity of immune cells. The mechanisms are related to elevations of immune inhibitory cells and the concentration of plasma antiinflammatory molecules. Some immune biological indicators, such as soluble CD163, are used to explore the pathogenesis and prognosis of the disease, and some immunotherapies, such as glucocorticoids and granulocyte colony-stimulating factor, are effective on ACLF. Conclusions: Overwhelming systemic inflammation and susceptibility to infection are two key features of ACLF. A better understanding of the state

关键词： acute-on-chronic liver failure Pathogenesis Predictors Immunotherapy

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Soluble mannose receptor as a predictor of prognosis of hepatitis B virus-related acute-on-chronic liver failure

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World Journal of Gastroenterology 2019年第37期25卷 5667-5675页

作者： Tai-Ping Li Shi-He Guan Qin Wang Li-Wen Chen Kai Yang Hao Zhang Department of ClinicalLaboratory The Second Hospital of Anhui Medical University

BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To investigate the clinical value of soluble mannose receptor(sMR)in predicting the 90-day mortality of HBV-ACLF patients.METHODS A total of 43 patients were diagnosed with HBV-ACLF between October 2017 and October 2018 at the Second Hospital of Anhui Medical University,and all of them were enrolled in this retrospective study.Their serum sMR levels were determined using an enzyme-linked immunosorbent assay.Demographic and clinical data,including gender,age,albumin level,total bilirubin(TBIL)level,international normalized ratio,HBV-DNA level,HBV serological markers,procalcitonin level,interleukin-6 level,and model for end-stage liver disease(MELD)score were accessed at the time of diagnosis of HBV-ACLF.A multivariate logistic regression analysis was used to analyze the independent risk factors for mortality.RESULTS Serum sMR level was significantly increased in HBV-ACLF patients compared with chronic hepatitis B patients and healthy controls(P<0.01).When compared with surviving patients,it was higher in those patients who succumbed to HBVACLF(P<0.05).Serum sMR level was positively correlated with MELD score(rs=0.533,P=0.001),HBV-DNA level(rs=0.497,P=0.022),and TBIL level(rs=0.894,P<0.001).Serum sMR level(odds ratio=1.007,95%confidence interval:1.004–1.012,P=0.001)was an independent risk factor for the 90-day mortality in the HBV-ACLF cases.The patients with HBV-ACLF were stratified into two groups in accordance with their serum sMR levels at the baseline(low risk:<99.84 pg/mL and high risk:≥99.84 pg/mL).The 90-day mortality rates were 27.3%in the low-risk group and 87.5%in the high-risk group.Furthermore,sMR level apparently improved the performance of MELD score for predicting the prognosis of patients with HBV-ACLF.CONCLUSION Serum sMR level may be a predictor of the prognosis of HBV-ACLF patients.

关键词： acute-on-chronic liver failure Mannose receptor Model for end-stage liver disease Prognosis Risk factor

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acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis

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World Journal of Gastroenterology 2018年第21期24卷 2300-2310页

作者： Qun-Qun Jiang Mei-Fang Han Ke Ma Guang Chen Xiao-Yang Wan Semvua Bukheti Kilonzo Wen-Yu Wu Yong-Li Wang Jie You Qin Ning Department and Institute of Infectious Disease Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology

AIM To evaluate the differences in acute kidney injury(AKI) between acute-on-chronic liver failure(ACLF) and decompensated cirrhosis(DC) patients. METHODS During the period from December 2015 to July 2017, 280 patients with hepatitis B virus(HBV)-related ACLF(HBV-ACLF) and 132 patients with HBV-related DC(HBV-DC) who were admitted to our center were recruited consecutively into an observational study. Urine specimens were collected from all subjects and the levels of five urinary tubular injury biomarkers were detected,including neutrophil gelatinase-associated lipocalin(NGAL), interleukin-18(IL-18), liver-type fatty acid binding protein(L-FABP), cystatin C(CysC), and kidney injury molecule-1(KIM-1). Simultaneously, the patient demographics, occurrence and progression of AKI, and response to terlipressin therapy were recorded. All patients were followed up for 3 mo or until death after enrollment. RESULTS AKI occurred in 71 and 28 of HBV-ACLF and HBV-DC patients, respectively(25.4% vs 21.2%, P = 0.358). Among all patients, the levels of four urinary biomarkers(NGAL, CysC, L-FABP, IL-18) were significantly elevated in patients with HBV-ACLF and AKI(ACLF-AKI), compared with that in patients with HBV-DC and AKI(DC-AKI) or those without AKI. There was a higher proportion of patients with AKI progression in ACLF-AKI patients than in DC-AKI patients(49.3% vs 17.9%, P = 0.013). Fortythree patients with ACLF-AKI and 19 patients with DC-AKI were treated with terlipressin. The response rate of ACLFAKI patients was significantly lower than that of patients with DC-AKI(32.6% vs 57.9%, P = 0.018). Furthermore, patients with ACLF-AKI had the lowest 90 d survival rates among all groups(P < 0.001).CONCLUSION AKI in ACLF patients is more likely associated with structural kidney injury, and is more progressive, with a poorer response to terlipressin treatment and a worse prognosis than that in DC patients.

关键词： Decompensated cirrhosis acute-on-chronic liver failure acute kidney injury Biomarker Etiology Treatment Prognosis

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Incidence of infectious complications is associated with a high mortality in patients with hepatitis B virus-related acute-on-chronic liver failure

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World Journal of Clinical Cases 2019年第16期7卷 2204-2216页

作者： Chen Wang De-Qiang Ma Sen Luo Chuan-Min Wang De-Ping Ding You-You Tian Kang-Jian Ao Yin-Hua Zhang Yue Chen Zhong-Ji Meng Department of Infectious Diseases Taihe HospitalHubei University of MedicineShiyan 442000Hubei ProvinceChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyan 442000Hubei ProvinceChina

BACKGROUND In China,hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is the most common liver failure characterized by serious clinical syndromes of liver decompensation with a very high mortality.Bacterial and/or fungal infections are the most common complications that are associated with high short-term mortality.Bacterial translocation from the intestine,impaired hepatic clearance,and immune paralysis of circulating immune cells are thought to contribute to infectious complications in liver failure.The control of bacterial and fungal infections is the key to improving HBV-ACLF outcomes.Active prevention,early diagnosis,and timely treatment of bacterial and fungal infections are essential for treating HBV-ACLF.AIM To investigate the frequency and role of bacterial and fungal infections in patients with HBV-ACLF.METHODS Patients with HBV-ACLF hospitalized at Taihe Hospital,Hubei University of Medicine from January 2014 to December 2017 were retrospectively enrolled.Patient-related information was retrieved from the hospital case database,including general information,blood biochemistry,complications,etc.According to the occurrence of secondary infection or not,the patients were divided into an infection group and a non-infection group.The sites,types,and incidences of bacterial and fungal infections and the influence of infections on the prognosis of HBV-ACLF were statistically analyzed.The risk factors for infections were assessed by unconditional logistic regression.RESULTS There were 174 cases of HBV-ACLF that met the enrollment criteria,of which 114 (65.52%) were diagnosed with infectious complications.Infections occurred in the abdominal cavity (87 cases),respiratory tract (51 cases),urinary tract (18 cases),and biliary tract (10 cases).Patients with infectious complications had a significantly higher 28-d mortality (70.18%,80/114) than those without (40.00%,24/60)(70.18% vs 40.00%,P < 0.05).And patients with infectious complications had a much higher incidence of non-infectious complicat

关键词： Hepatitis B acute-on-chronic liver failure Bacterial infection Fungal infection Prognosis

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Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection

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World Journal of Gastroenterology 2019年第19期25卷 2327-2337页

作者： Ling Yuan Bai-Mei Zeng Lu-Lu Liu Yi Ren Yan-Qing Yang Jun Chu Ying Li Fang-Wan Yang Yi-Huai He Shi-De Lin Department of Infectious Diseases Affiliated Hospital of Zunyi Medical University Department of Gastroenterology Jiangsu Province Hospital Pukou Branch Department of Respiratory Medicine the Fifth People’s Hospital of Chongqing

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 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.

关键词： acute-on-chronic liver failure chronic hepatitis B Hepatic decompensation Liver cirrhosis Risk factors Severe acute exacerbation

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Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure

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World Journal of Clinical Cases 2020年第6期8卷 1042-1055页

作者： Chen Li Hai-Bin Su Xiao-Yan Liu Jin-Hua Hu Liver Failure Treatment and Research Center The Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China

BACKGROUND acute-on-chronic liver failure(ACLF),which includes hepatic and multiple extrahepatic organ failure,is a severe emergency condition that has high mortality.ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation.Bacterial infections(BIs)trigger ACLF and play pivotal roles in the deterioration of clinical course.AIM To investigate the clinical characteristics and 28-d outcomes of first BIs either at admission or during hospitalization in patients with hepatitis B virus(HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B(COSSH).METHODS A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016.The characteristics of BIs,the 28-d transplant-free survival rates,and the independent predictors of the 28-d outcomes were evaluated.RESULTS A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF.Among the episodes,13.4%were community-acquired,46.4%were healthcare-associated,and 40.2%belonged to nosocomial BIs.Pneumonia(40.7%),spontaneous bacterial peritonitis(SBP)(34.5%),and bloodstream infection(BSI)(13.4%)were the most prevalent.As the ACLF grade increased,the incidence of SBP showed a downward trend(P=0.021).Sixty-one strains of bacteria,including 83.6%Gramnegative bacteria and 29.5%multidrug-resistant organisms,were cultivated from 50 patients with ACLF.Escherichia coli(44.3%)and Klebsiella pneumoniae(23.0%)were the most common bacteria.As the ACLF grade increased,the 28-d transplant-free survival rates showed a downward trend(ACLF-1,55.7%;ACLF-2,29.3%;ACLF-3,5.4%;Pacute kidney injury(HR=2.187),BSI(HR=2.339),prothrombin activity(HR=0.967),and invasive catheterization(HR=2.173).CONCLUSION For patients with HBV-ACLF combined with fir

关键词： Hepatitis B virus acute-on-chronic liver failure Bacterial infections Outcomes chronic liver disease Spontaneous bacterial peritonitis

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acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

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World Journal of Gastroenterology 2019年第28期25卷 3684-3703页

作者： Wiwat Chancharoenthana Asada Leelahavanichkul Immunology Unit Department of Microbiology Faculty of Medicine Chulalongkorn University Bangkok 10330 Thailand Translational Research in Inflammation and Immunology Research Unit (TRIRU) Department of Microbiology Faculty of Medicine Chulalongkorn University Bangkok 10330 Thailand

acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.

关键词： acute kidney injury acute-on-chronic liver failure chronic liver disease Hepatorenal syndrome Plasma perfusion and bilirubin adsorption and double plasma molecular absorption system Fractionated plasma separation and adsorption Molecular adsorbent recycling system Single-pass albumin dialysis

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Prognosis of acute-on-chronic liver failure patients treated with artificial liver support system

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World Journal of Gastroenterology 2015年第32期21卷 9614-9622页

作者： Pi-Qi Zhou Shao-Ping Zheng Min Yu Sheng-Song He Zhi-Hong Weng Department of Integrated Traditional and Chinese Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Department of Ultrasonography Union Hospital Tongji Medical College Huazhong University of Science and Technology Department of Internal Medicine Wuhan Eleventh Hospital Department of Infectious Diseases Union Hospital Tongji Medical College Huazhong University of Science and Technology

AIM: To establish a new model for predicting survival in acute-on-chronic liver failure(ACLF) patients treated with an artificial liver support system. METHODS: One hundred and eighty-one ACLF patients who were admitted to the hospital from January 1, 2012 to December 31, 2014 and were treated with an artificial liver support system were enrolled in this retrospective study, including a derivation cohort(n = 113) and a validation cohort(n = 68). Laboratory parameters at baseline were analyzed and correlatedwith clinical outcome. In addition to standard medical therapy, ACLF patients underwent plasma exchange(PE) or plasma bilirubin adsorption(PBA) combined with plasma exchange. For the derivation cohort, KaplanMeier methods were used to estimate survival curves, and Cox regression was used in survival analysis to generate a prognostic model. The performance of the new model was tested in the validation cohort using a receiver-operator curve.RESULTS: The mean overall survival for the derivation cohort was 441 d(95%CI: 379-504 d), and the 90- and 270-d survival probabilities were 70.3% and 58.3%, respectively. The mean survival times of patients treated with PBA plus PE and patients treated with PE were 531 d(95%CI: 455-605 d) and 343 d(95%CI: 254-432 d), respectively, which were significantly different(P = 0.012). When variables with bivariate significance were selected for inclusion into the multivariate Cox regression model, number of complications, age, scores of the model for end-stage liver disease(MELD) and type of artificial liver support system were defined as independent risk factors for survival in ACLF patients. This new prognostic model could accurately discriminate the outcome of patients with different scores in this cohort(P < 0.001). The model also had the ability to assign a predicted survival probability for individual patients. In the validation cohort, the new model remained better than the MELD.CONCLUSION: A novel model was constructed to predict prognosis and accurately discriminate survival

关键词： acute-on-chronic liver failure Artificial liver su

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