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Lyu C, Han J, Kang N, Zeng D, Davgadorj C, Ge L, Zhou M, Mao R, Yan Y. Etiology and Prognostic Criteria for Liver Failure in Southeast China: A Multicenter Retrospective Cohort Study Between 2018 and 2020. Gastroenterol Res Pract 2024; 2024:5512889. [PMID: 39723429 PMCID: PMC11669432 DOI: 10.1155/grp/5512889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 11/05/2024] [Accepted: 11/14/2024] [Indexed: 12/28/2024] Open
Abstract
Background: The prognosis of patients with liver failure (LF) depends significantly on the etiology and clinical indicators. This analysis of these basic indicators can help provide a basis for the study of predictive outcome indicators. Methods: We collected the data from multiple centers in Southeast China, including subclasses of acute liver failure (ALF), subacute liver failure (SLF), acute-on-chronic liver failure (ACLF), subacute-on-chronic liver failure (SALF), and chronic liver failure (CLF). Multivariate logistic regression analysis was used to screen for clinical indicators of nonsurvivors. We analyzed receiver operating characteristic (ROC) curves and cutoff values to assess the prognostic criteria. Results: Hepatitis B virus (HBV) infection is the leading etiology of patients with LF (64.52% (411/637)). SALF (41.36%) and CLF (32.30%) are the main subclasses of the hepatitis B virus-related liver failure (HBV-LF) group and the non-HBV-related LF group in Southeast China, respectively. Between 2018 and 2020, the incidence of HBV-LF decreased significantly, ranging from 72.36% to 59.74%, and the spontaneous survival rates of patients with HBV-LF were substantially lower than those of non-HBV-LF patients (36.43%~44.93% vs. 58.97%~63.64%). Infection and cirrhosis were the leading causes of death in both groups. The age and total bilirubin value of the nonsurvivors with HBV-LF were significantly higher, and the number of days of hospitalization was significantly shorter than that of the survivors. The ages of the nonsurvivors in the non-HBV-LF group were significantly higher than those of the survivors. The prothrombin time-international normalized ratio (PT-INR) is 2.05, 1.92, or 2.11, and antithrombin III (AT III) is 24.50%, which are proposed as prognostic criteria for the HBV-SALF (hepatitis B virus-related subacute-on-chronic liver failure), non-HBV-SLF (non-hepatitis B virus-related subacute liver failure), non-HBV-ACLF (non-hepatitis B virus-related acute-on-chronic liver failure), and HBV-ALF (hepatitis B virus-related acute liver failure) subclasses, respectively. Conclusions: The incidence of HBV-LF is decreasing annually. AT III, as an independent prognostic criterion, has excellent discriminative ability for the outcomes of the HBV-ALF subclass.
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Affiliation(s)
- Chunyan Lyu
- Clinical Medical Research Center, The Fifth People's Hospital of Wuxi, Wuxi, China
- Clinical Medical Resarch Center, Wuxi Clinical College of Nantong University, Wuxi, China
| | - Jun Han
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, China
| | - Naling Kang
- Department of Infectious Diseases, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Dawu Zeng
- Department of Infectious Diseases, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | | | - Lina Ge
- Clinical Medical Research Center, The Fifth People's Hospital of Wuxi, Wuxi, China
| | - Meifang Zhou
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, China
| | - Richeng Mao
- Department of Infectious Diseases, Huashan Hospital Affiliated With Fudan University, Shanghai, China
| | - Yan Yan
- Clinical Medical Research Center, The Fifth People's Hospital of Wuxi, Wuxi, China
- Clinical Medical Resarch Center, Wuxi Clinical College of Nantong University, Wuxi, China
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Wang X, Yang Z, Pu Z, Zheng Y, Chen H, Huang Y, Fan X, Yi P. Development and validation of a novel prognostic nomogram for hepatitis B virus-related acute-on-chronic liver failure patients receiving artificial liver therapy. Eur J Med Res 2024; 29:556. [PMID: 39568078 PMCID: PMC11580634 DOI: 10.1186/s40001-024-02141-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 11/04/2024] [Indexed: 11/22/2024] Open
Abstract
BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is frequently accompanied by short-term morbidity and mortality. However, there have been no studies on the associations between baseline clinicopathologic characteristics at hospital admission and clinical prognosis after receiving artificial liver therapy. Therefore, the current study aimed to develop a prognostic nomogram for predicting the outcomes of patients with HBV-ACLF following artificial liver support. METHODS A retrospective study of 110 consecutive patients who were diagnosed with HBV-ACLF between January 2018 and August 2022 was conducted. First, univariate and multivariate logistic regression analyses were performed to determine the independent prognostic factors significantly associated with patient outcomes. Moreover, a predictive nomogram model underlying the prognostic factors was established and further evaluated. The area under the curve (AUC) was used to gauge the predictive accuracy. The calibration curve and decision curve analysis (DCA) were employed to assess the discriminability and clinical effectiveness, respectively. RESULTS In patients with HBV-ACLF, multivariate logistic analysis revealed that age ≥ 40 years (OR 6.76, p = 0.025), middle-stage liver failure (OR 49.96, p < 0.001), end-stage liver failure (OR 19.27, p = 0.002), hepatic encephalopathy (OR 7.06, p = 0.032), upper gastrointestinal hemorrhage (OR 47.24, p = 0.047), and artificial liver therapy consisting of plasma exchange (PE) + plasma exchange double plasma molecular adsorption system (DPMAS) (OR 0.26, p = 0.04) were identified as prognostic factors. Then, we established and evaluated a predictive nomogram with an AUC of 0.885, which showed better predictive accuracy than the model for end-stage liver disease (MELD) score (AUC of 0.634) and the Child-Pugh score (AUC of 0.611). Moreover, the calibration curve showed good agreement between the ideal and bias-corrected curves. Decision curve analysis confirmed the better clinical utility of this approach. CONCLUSIONS We developed and evaluated a unique nomogram that was more accurate than conventional prognostic models for predicting the clinical prognosis of HBV-ACLF patients receiving artificial liver therapy. As a result, the nomogram may be a helpful tool in clinical decision-making to predict the outcomes of patients with HBV-ACLF.
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Affiliation(s)
- Xiaofang Wang
- Department of Infectious Disease, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan Province, China
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Ziyue Yang
- Department of Blood Transfusion, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Health Commission (NHC) Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Zhangya Pu
- Department of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang Province, China
| | - Yixiang Zheng
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Haiou Chen
- Department of Infectious Disease, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan Province, China
| | - Yan Huang
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xuegong Fan
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Panpan Yi
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Huang J, Xu T, Quan G, Li Y, Yang X, Xie W. Current progress on the microbial therapies for acute liver failure. Front Microbiol 2024; 15:1452663. [PMID: 39479215 PMCID: PMC11521890 DOI: 10.3389/fmicb.2024.1452663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 09/30/2024] [Indexed: 11/02/2024] Open
Abstract
Acute liver failure (ALF), associated with a clinical fatality rate exceeding 80%, is characterized by severe liver damage resulting from various factors in the absence of pre-existing liver disease. The role of microbiota in the progression of diverse liver diseases, including ALF, has been increasingly recognized, with the interactions between the microbiota and the host significantly influencing both disease onset and progression. Despite growing interest in the microbiological aspects of ALF, comprehensive reviews remain limited. This review critically examines the mechanisms and efficacy of microbiota-based treatments for ALF, focusing on their role in prevention, treatment, and prognosis over the past decade.
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Affiliation(s)
- Jiayuan Huang
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Tianyu Xu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Guoqiao Quan
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Yuange Li
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Xiaoya Yang
- Department of Physiology, Guangzhou Health Science College, Guangzhou, China
| | - Wenrui Xie
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
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Bai J, Xu M, Peng F, Gong J, Song X, Li Y. A nomogram based on psoas muscle index predicting long-term cirrhosis incidence in non-cirrhotic patients with HBV-related acute‑on‑chronic liver failure. Sci Rep 2023; 13:21265. [PMID: 38040786 PMCID: PMC10692120 DOI: 10.1038/s41598-023-47463-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 11/14/2023] [Indexed: 12/03/2023] Open
Abstract
There is a lack of scoring system to predict the occurrence of cirrhosis in individuals with acute-on-chronic liver failure (ACLF) in the absence of cirrhosis. The goal of this study was to develop a psoas muscle index (PMI)-based nomogram for cirrhosis risk in non-cirrhotic patients with HBV-related ACLF. We included 274 non-cirrhotic HBV-ACLF patients who were randomly assigned to training and validation groups. Logistic analyses were performed to identify risk factors for cirrhosis. A nomogram was then constructed. The predictive performance of the nomogram was assessed using the area under the receiver operating characteristic curve (AUROC), calibration curve, and decision curve analysis (DCA). During the 360-day follow-up, 44.5% (122/274) of non-cirrhotic HBV-ACLF patients developed cirrhosis. A higher PMI at the L3 level was correlated with a decreased risk of long-term cirrhosis occurrence (OR 0.677, 95% CI 0.518-0.885, P = 0.004). The nomogram incorporating PMI, age, neutrophil-to-lymphocyte ratio (NLR), and international normalized ratio (INR), indicated satisfactory predictive performance for cirrhosis risk stratification in ACLF population. The nomograms had an AUROC of 0.812 (95% CI 0.747-0.866) and 0.824 (95% CI 0.730-0.896) in the training and validation cohorts, respectively. The calibration curves displayed excellent predictive accuracy of the nomogram in both sets. In both cohorts, the DCA verified the nomogram's clinical efficacy. In non-cirrhotic HBV-ACLF patients, a greater PMI appears to protect against long-term cirrhosis occurrence. Strong predictive performance has been demonstrated by PMI-based nomograms in assessing the likelihood of 1-year cirrhosis in those with HBV-ACLF.
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Affiliation(s)
- Jie Bai
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Manman Xu
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Fengling Peng
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Junwei Gong
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaodong Song
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Yongguo Li
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Ke C, Shu L, Cai L, Yujun Z, Qiang W. IGF2BP3/HIF1A/YAP signaling plays a role in driving acute-on-chronic liver failure through activating hepatocyte reprogramming. Cell Signal 2023:110727. [PMID: 37257765 DOI: 10.1016/j.cellsig.2023.110727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 05/03/2023] [Accepted: 05/18/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a syndrome with both high prevalence and mortality. However, the underlying mechanisms remain elusive and there is no effective therapeutic approach available. Here we aim to uncover novel molecular mechanisms of ACLF and identify potential therapeutic targets. METHOD We performed integrative analysis of 3 transcriptomic datasets and subsequent bioinformatic analysis aiming for potential genes of significance in ACLF development, identifying a critical role of IGF2BP3/HIF1A signaling in development of ACLF. Expression of molecules in IGF2BP3/HIF1A pathway and hepatocyte reprogramming markers in clinical samples were then determined by western blot and quantitative PCR. N6-methyladenosine (m6A) RNA modification of HIF1A was analyzed by m6A dot assay and PCR following m6A-antibody precipitation. The molecular mechanisms among IGFBP3, HIF1α and YAP1 were further validated by gene overexpression and knockdown experiments in HepG2 and Hep3B cells. Cell phenotypes of hepatocyte reprogramming were determined by EdU staining, sphere formation assay and immunoblotting of relevant markers. RESULTS Our data demonstrated that IGF2BP3 recognized m6A modification in HIF1A mRNA as an m6A reader, thereby promoting expression of HIF1A by increasing RNA stability. HIF1A activated Rho GTPases (RhoA) and suppressed phosphorylation of YAP via inhibiting LATS1/2, promoting translocation of non-phosphorylated YAP into the nucleus, resulting in fetal liver programme and ultimate hepatic injury in ACLF patients. CONCLUSION We reveal a novel molecular mechanism that IGF2BP3/HIF1A/YAP signaling promotes hepatocyte reprogramming, causing hepatic injury in ACLF. Our study provides potential targets for treatment of ACLF.
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Affiliation(s)
- Cheng Ke
- Department of Transplantation, The Third Xiangya Hospital, Central South University, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, China
| | - Liu Shu
- Department of Transplantation, The Third Xiangya Hospital, Central South University, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, China
| | - Li Cai
- Department of Transplantation, The Third Xiangya Hospital, Central South University, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, China
| | - Zhao Yujun
- Department of Transplantation, The Third Xiangya Hospital, Central South University, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, China
| | - Wang Qiang
- Department of Transplantation, The Third Xiangya Hospital, Central South University, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, China.
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Zhang P, Li H, Peng B, Zhang Y, Liu K, Cheng K, Ming Y. Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis. Front Endocrinol (Lausanne) 2023; 14:1132085. [PMID: 36817578 PMCID: PMC9932584 DOI: 10.3389/fendo.2023.1132085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 01/23/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Alcoholic and hepatitis B virus (HBV)-related liver cirrhosis has placed a tremendous burden on the healthcare system with limited treatment options. This study explored the differences in the immune status of alcoholic and HBV-related liver cirrhosis. METHODS A total of 15 human liver samples from the Third Xiangya Hospital of Central South University, including five healthy controls (HC group), five alcoholic cirrhosis patients (ALC group), and five HBV-related cirrhosis patients (HBV group) were used. Of these, eight samples, including 3 HC group, 2 ALC group and 3 HBV group, were randomly collected to do single-cell RNA sequencing (scRNA-seq). The degree of steatosis was assessed by H&E staining and the presence of intrahepatic immune cells was evaluated by immunochemistry (IHC). RESULTS The immune status of alcoholic and HBV-related liver cirrhosis differed significantly. ScRNA-seq analysis identified a higher ratio of intrahepatic monocyte/macrophages and an obvious decreased ratio of T cells and B cells in the ALC group than in the HBV group. IHC staining of intrahepatic monocyte/macrophages, T and B cell exhibited similar results with scRNA-seq analysis. CD5L+ Kupffer cells, a cell type involved in lipid metabolism, were the major monocyte/macrophage subset in ALC liver tissue. H&E staining indicated that the level of steatosis was more severe in the ALC than in the HBV group. Ligand/receptor analysis showed that the T cell exhaustion observed in the ALC liver may be related to the expression of Galectin-9 on Kupffer cells. Fewer B cells were also found in the ALC group and most had higher lipid metabolism, reduced ribosomal activity, and a dysregulated mitochondrial oxidative phosphorylation system. Moreover, scRNA-seq showed a significantly lower ratio of plasma B cells, indicating that the humoral immune response in the ALC liver was similarly dysfunctional. Ligand/receptor analysis also discovered that Galectin-9 expressed on Kupffer cells may inhibit humoral immunity. CONCLUSION Patients with ALC have different immune characteristics than those with HBV-induced cirrhosis, including an increased ratio of intrahepatic monocyte/macrophages and a dysfunctional adaptive immune response in the liver. Galectin-9 could serve as a potential therapeutic target for ALC treatment.
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Affiliation(s)
- Pengpeng Zhang
- The Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Engineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, China
| | - Hao Li
- The Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Engineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, China
| | - Bo Peng
- The Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Engineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, China
| | - Yu Zhang
- The Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Engineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, China
| | - Kai Liu
- The Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Engineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, China
| | - Ke Cheng
- The Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Engineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, China
| | - Yingzi Ming
- The Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Engineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, China
- *Correspondence: Yingzi Ming,
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You S, Zhu B, Xin S. Clinical Manifestations of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:185-197. [PMID: 37223867 DOI: 10.1007/978-981-99-1304-6_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
The clinical manifestations of hepatitis E are similar to those of other types of viral hepatitis. While acute hepatitis E is usually self-limited, pregnant women and chronic liver disease patients suffering from acute hepatitis E usually present with severe clinical manifestations that may develop into fulminant hepatic failure. Chronic HEV infection is typically seen in organ transplant patients; most HEV cases are asymptomatic and rarely display jaundice, fatigue, abdominal pain, fever, fatigue, or ascites. The clinical manifestations of HEV infection in neonates are diverse and have varied clinical signs, biochemistry, and virus-biomarkers. Lastly, the extrahepatic manifestations and complications of hepatitis E are in need of further study.
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Affiliation(s)
- Shaoli You
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Bing Zhu
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shaojie Xin
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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Yin J, Xu X, Pu R, Su H, Wang J, Liu W, Tong J, Chen J, Chen X, Mu X, Zhang H, Zhai X, Liu X, Pang F, Wang Y, Wang H, Cao G, Hu J. A Lower HCC Incidence in Chronic HBV-Infected Patients Recovered from Acute-on-Chronic Liver Failure: A Prospective Cohort Study. JOURNAL OF ONCOLOGY 2022; 2022:5873002. [PMID: 36339647 PMCID: PMC9633202 DOI: 10.1155/2022/5873002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/08/2022] [Accepted: 10/10/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Activation of chronic hepatitis B virus (HBV) infection is an important cause of acute-on-chronic liver failure (ACLF). However, the effect of HBV-ACLF episode on hepatocellular carcinoma (HCC) occurrence remains largely unknown. METHODS A total of 769 HBV-ACLF patients and 2114 HBV-related chronic liver disease (HBV-CLD) patients diagnosed between August 1998 and December 2011 were enrolled in this prospective cohort study. Of the HBV-CLD patients, 380 received lifetime antiviral treatment with nucleos(t)ide analogues. Propensity score matching was applied to reduce baseline differences between HBV-ACLF and HBV-CLD cohorts. RESULTS The survival rate of HBV-ACLF patients was 53.6%, 50.3%, 47.8%, and 46.2% at 90-day, 1-year, 5-year, and 10-year, respectively. The cumulative incidence of HCC was lower in HBV-ACLF cohort with 369 eligible patients survived for >90 days than in HBV-CLD cohort with the 380 patients (5.77/1,000 vs. 9.78/1,000 person-years, p = 0.0497). HBV-ACLF episode decreased HCC risk regardless of liver cirrhosis, and in patients without family history of HCC. Multivariate Cox analyses indicated that male, increasing age, liver cirrhosis, and platelet count (≤100 × 109/L) increased, whereas HBV-ACLF episode decreased, HCC risk independently. In the propensity score-matched cohorts, HBV-ACLF episode reduced HCC incidence (10.20/1,000 vs. 4.66/1,000 person-years, p = 0.0326). The area under curve of nomogram was 0.812 for 3-year HCC probability. CONCLUSIONS HBV-ACLF episode decreases HCC occurrence in chronic HBV patients. Older age and liver cirrhosis independently increased HCC occurrence. A nomogram-enrolled episode of ACLF reliably predicts the occurrence of HCC.
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Affiliation(s)
- Jianhua Yin
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Xiang Xu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Laboratory of Translational Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China
| | - Rui Pu
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Haibin Su
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Junxue Wang
- Department of Infectious Diseases, The 2nd Affiliated Hospital, Second Military Medical University, Shanghai, China
| | - Wenbin Liu
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Jingjing Tong
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jing Chen
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Xi Chen
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Xiuying Mu
- Peking University 302 Clinical Medical School, Beijing, China
| | - Hongwei Zhang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Xingran Zhai
- Peking University 302 Clinical Medical School, Beijing, China
| | - Xiaoyan Liu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Fei Pang
- Qilu Hospital of Shandong University (Qingdao), Qingdao, China
| | - Yu Wang
- Department of Infectious Diseases, The 2nd Affiliated Hospital, Second Military Medical University, Shanghai, China
| | - Huifen Wang
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Guangwen Cao
- Department of Epidemiology, Second Military Medical University, Shanghai, China
- Ministry of Education Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Shanghai Key Laboratory of Hepato-Biliary Tumor Biology, Shanghai, China
| | - Jinhua Hu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Peking University 302 Clinical Medical School, Beijing, China
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Serum Interleukins as Potential Prognostic Biomarkers in HBV-Related Acute-on-Chronic Liver Failure. Mediators Inflamm 2022; 2022:7794890. [PMID: 36117587 PMCID: PMC9477565 DOI: 10.1155/2022/7794890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/06/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is relatively common in China and has complex pathogenesis, difficult clinical treatment, and poor prognosis. Immune status is an important factor affecting ACLF prognosis. Interleukins are a family of secreted lymphocyte factors that interact with a host of cell types including immune cells. These signaling molecules play important roles in transmitting information; regulating immune cells; mediating the activation, proliferation, and differentiation of T and B cells; and modulating inflammatory responses. Many studies have investigated the correlation between interleukin expression and the prognosis of HBV-ACLF. This review focuses on the potential use of interleukins as prognostic biomarkers in HBV-ACLF. References were mainly identified through PubMed and CNKI search, including relevant studies published until December 2021. We have summarized reports of several promising diagnostic interleukin biomarkers that predict susceptibility to HBV-ACLF. The use of biomarkers to understand early prognosis can help devise different therapeutic measures and improve patient survival. Ongoing research on prognostic biomarkers of HBV-ACLF is promising, and future preclinical and clinical studies are warranted.
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Zhuo H, Fan J, Zhang B, Shi Y, Zheng L, Chai Y, Yao L. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure. Open Med (Wars) 2022; 17:1455-1465. [PMID: 36128448 PMCID: PMC9449690 DOI: 10.1515/med-2022-0549] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 08/03/2022] [Accepted: 08/10/2022] [Indexed: 11/16/2022] Open
Abstract
Genetic variation in UDP-glucuronosyltransferase 1A1 gene (UGT1A1) is a lithogenic risk factor for gallstone formation. This study aimed to assess genotype and allele frequencies of common UGT1A1 variants in patients with gallstone and hepatitis B virus (HBV)-related hepatic failure. This study enrolled 113 healthy individuals (CTRL), 54 patients with HBV infection (HBV), 134 patients with gallstone-free hepatic failure and HBV infection, and 34 patients with gallstone-related hepatic failure and HBV infection (GRHF). Peripheral venous blood samples were collected for genomic DNA isolation. Polymerase chain reaction amplification was carried out for UGT1A1, followed by direct sequencing. Analysis for genotype and allele frequencies of UGT1A1 variants (UGT1A1*6, UGT1A1*27, UGT1A1*28, and UGT1A1*60) was performed. The allele distributions of the four groups did not deviate from Hardy–Weinberg equilibrium. Allele (A) and genotype (CA) frequency distributions of UGT1A1*27 were significantly different between GRHF and CTRL, or between GRHF and HBV. GRHF and CTRL exhibited significant differences in allele (A) and genotype (CA) frequency distributions of UGT1A1*28. Linkage disequilibrium analysis suggested that haplotype G-G-[TA]7-T may be associated with gallstone in HBV-related hepatic failure. Our data reveal that UGT1A1*27 and UGT1A1*28 variants are significantly observed in patients with GRHF compared to healthy individuals.
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Affiliation(s)
- Haiyan Zhuo
- Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University , No. 312 Xihong Road , Fuzhou , Fujian, 350025 , P. R. China
| | - Jinhai Fan
- Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou , Fujian, 350025 , P. R. China
| | - Bifeng Zhang
- Department of Gastroenterology, Quanzhou First Hospital , Quanzhou , Fujian, 362000 , P. R. China
| | - Yixian Shi
- Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou , Fujian, 350025 , P. R. China
| | - Liqing Zheng
- Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou , Fujian, 350025 , P. R. China
| | - Yihong Chai
- Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou , Fujian, 350025 , P. R. China
| | - Lvfeng Yao
- Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University , No. 312 Xihong Road , Fuzhou , Fujian, 350025 , P. R. China
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11
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Wang L, Zhu S, Liu Y, Zheng L, Xu W, Luo Q, Zhang Y, Deng H, Li X, Xie C, Peng L. Prognostic value of decline in model for end-stage liver disease score and hepatic encephalopathy in hepatitis B-related acute-on-chronic liver failure patients treated with plasma exchange. Scand J Gastroenterol 2022; 57:1089-1096. [PMID: 35435091 DOI: 10.1080/00365521.2022.2063032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/25/2022] [Accepted: 04/01/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate the prognostic value of Model for End-Stage Liver Disease (MELD) score and Hepatic Encephalopathy (HE) for short-term prognosis of Hepatitis B virus-related Acute-on-Chronic Liver Failure (HBV-ACLF) patients treated with plasma exchange (PE). METHODS A total of 108 patients with HBV-ACLF treated with PE were retrospectively enrolled between January 2014 to December 2020. Based on survival at 28 days, patients were divided into survival (N = 87) and death groups (N = 21). Clinical data and laboratory indicators were analyzed. RESULTS Compared with the survival group, the death group was associated with higher ACLF grade and incidence of HE. The levels of total bilirubin, prothrombin time, creatinine, blood urea nitrogen, MELD score, and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH II) score were significantly higher in the death group than in the survival group (p < .05). Grade 1 ACLF and the MELD score after PE treatment at one week were independent risk factors for 28-day liver transplantation-free mortality (OR = 0.062, 95%CI: 0.005-0.768; OR = 1.328, 95%CI: 1.153-1.531). A MELD score at one week of at least 25.5 was associated with a poor short-term prognosis. Of note, HE was a strong independent risk factor for a decline in MELD score at one week. (OR = 11.815, 95%CI: 3.187-43.796, p < 0.001). CONCLUSION We found patients with HE at admission and MELD score of at least 25.5 at one week after PE treatment had a poor short-term prognosis and should prompt preparation for liver transplantation. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565). Registered 13 May 2020.
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Affiliation(s)
- Lu Wang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shu Zhu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ying Liu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China
| | - Lihua Zheng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China
| | - Qiumin Luo
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yeqiong Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hong Deng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xinhua Li
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chan Xie
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China
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12
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Yang R, Li K, Zou C, Wee A, Liu J, Liu L, Li M, Wu T, Wang Y, Ma Z, Wang Y, Liu J, Huang A, Sun Y, Chang B, Liang Q, Jia J, Zou Z, Zhao X. Alanine Aminotransferase and Bilirubin Dynamic Evolution Pattern as a Novel Model for the Prediction of Acute Liver Failure in Drug-Induced Liver Injury. Front Pharmacol 2022; 13:934467. [PMID: 35935831 PMCID: PMC9355525 DOI: 10.3389/fphar.2022.934467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 06/08/2022] [Indexed: 11/13/2022] Open
Abstract
Aims: To develop, optimize, and validate a novel model using alanine aminotransferase (ALT) and total bilirubin (TB) dynamic evolution patterns in predicting acute liver failure (ALF) in drug-induced liver injury (DILI) patients.Methods: The demographics, clinical data, liver biopsy, and outcomes of DILI patients were collected from two hospitals. According to the dynamic evolution of ALT and TB after DILI onset, the enrolled patients were divided into ALT-mono-peak, TB-mono-peak, double-overlap-peak, and double-separate-peak (DSP) patterns and compared. Logistic regression was used to develop this predictive model in both discovery and validation cohorts.Results: The proportion of ALF was significantly higher in patients with the DSP pattern than in the ALT-mono-peak pattern and DOP pattern (10.0 vs. 0.0% vs. 1.8%,p < 0.05). The area under receiver operating characteristic curve (AUROC) of the DSP pattern model was 0.720 (95% CI: 0.682–0.756) in the discovery cohort and 0.828 (95% CI: 0.788–0.864) in the validation cohort in predicting ALF, being further improved by combining with international normalized ratio (INR) and alkaline phosphatase (ALP) (AUROC in the discovery cohort: 0.899; validation cohort: 0.958). Histopathologically, patients with the DSP pattern exhibited a predominantly cholestatic hepatitis pattern (75.0%, p < 0.05) with a higher degree of necrosis (29.2%, p = 0.084).Conclusion: DILI patients with the DSP pattern are more likely to progress to ALF. The predictive potency of the model for ALF can be improved by incorporating INR and ALP. This novel model allows for better identification of high-risk DILI patients, enabling timely measures to be instituted for better outcome.
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Affiliation(s)
- Ruiyuan Yang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Kexin Li
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Cailun Zou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Aileen Wee
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jimin Liu
- Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Liwei Liu
- Fourth Department of Liver Disease (Difficult and Complicated Liver Diseases and Artificial Liver Center), Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Min Li
- Clinical Epidemiology and Evidence Base Medicine Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ting Wu
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Yu Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Zikun Ma
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Yan Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jingyi Liu
- Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Ang Huang
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Ying Sun
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Binxia Chang
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Qingsheng Liang
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Zhengsheng Zou
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xinyan Zhao
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
- *Correspondence: Xinyan Zhao,
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Zhang Q, Shi B, Wu L. Characteristics and risk factors of urinary tract infection in patients with HBV-related acute-on-chronic liver failure: A retrospective study. Medicine (Baltimore) 2022; 101:e29913. [PMID: 35839063 PMCID: PMC11132332 DOI: 10.1097/md.0000000000029913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 06/13/2022] [Indexed: 12/24/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation, organ failures, and high short-term mortality. Hepatitis B virus (HBV) is the main cause of liver failure in China. Urinary tract infection (UTI) is one of the common bacterial infections in patients with HBV-ACLF. However, few studies concerning the risk factors and epidemiology have been published. A retrospective analysis of 539 patients with HBV-ACLF was performed. The prevalence, bacterial profile, and antibiotic susceptibility pattern were investigated and associated risk factors of UTI in patients with HBV-ACLF were evaluated with a logistic regression model. The overall prevalence of UTI among the study participants was 26.53% (143/539), and 64.34% (92/143) of them were asymptomatic. One hundred thirty-five strains of bacteria, including 74.07% (100/135) gram-negative bacteria and 53.33% (72/135) multidrug-resistant organisms, were cultivated from 143 patients with HBV-ACLF. Escherichia coli 46.67% (63/135) and Klebsiella pneumoniae 13.33% (18/135) were the most common bacteria. The antibiotic susceptibility test pattern showed that 92.93%, 81.63%, and 81.63% of the gram-negative isolates were sensitive to imipenem, tigecycline, and piperacillin/tazobactam, respectively. Meanwhile, all the gram-positive isolates were sensitive to linezolid, teicoplanin, and vancomycin. Compared with non-UTI group, the patients with UTI had higher serum creatinine, lower educational status, total bilirubin, direct bilirubin, and albumin. Finally, educational status and albumin were independent risk factors in the prevalence of UTI in patients with HBV-ACLF. UTI is one of the common bacterial infections seen in patients with HBV-ACLF. Gram-negative bacteria account for the majority of cultured bacteria, and multidrug-resistant bacteria are common. UTI is determined by a diverse set of complex factors, which lower educational status and hypoalbuminemia predict the more prevalence of UTI.
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Affiliation(s)
- Qian Zhang
- Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Baoxian Shi
- Department of Chemistry and Environmental Engineering, Wuhan Polytechnic University, Wuhan, Hubei, People’s Republic of China
| | - Liang Wu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
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14
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Zhang Q, Shi B, Wu L. Characteristics and risk factors of infections in patients with HBV-related acute-on-chronic liver failure: a retrospective study. PeerJ 2022; 10:e13519. [PMID: 35811816 PMCID: PMC9266584 DOI: 10.7717/peerj.13519] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 05/09/2022] [Indexed: 01/17/2023] Open
Abstract
Background Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation, organ failures, and high short-term mortality whose main cause in China is the Hepatitis B virus (HBV). Moreover, one of the most important causes of morbidity and mortality in HBV-ACLF patients is bacterial infection. Therefore, we investigate the clinical features, risk factors, prophylaxis and management of infections in patients with HBV-ACLF. Methods We conducted a retrospective analysis of 539 patients with HBV-ACLF in Wuhan Tongji Hospital from October 2015 to May 2018. Differences among groups were compared with Student's t test, Mann-Whitney U test, χ2 test, or Fisher exact test as appropriate. Univariate and Multivariate logistic regression analysis was used for modeling the relationship between infection and clinical characteristics of HBV-ACLF. Results In total 58.81% (317/539) of patients with HBV-ACLF became complicated with infections, and the most common types were spontaneous bacterial peritonitis, urinary tract infection and pulmonary infection. Additionally, 32.18% (102/317) of patients suffered multi-organ infections, and 95.73% (516/539) of patients received anti-infective therapy. We detected a total of 202 isolates in all infected patients, and Escherichia coli (36.14%, 73/202) was the most common causative organism. Moreover, antibiotic susceptibility test patterns showed that 52.97% (107/202) of pathogens were MDR bacteria and 4.95% (10/202) were XDR bacteria. Univariate analysis indicated that patients with infection had a higher proportion of females, taking alcohol, diuretics, hepatic encephalopathy (HE), hepatorenal syndrome (HS), cirrhosis, a long-time in bed and mechanical ventilation, lower prothrombin activity (PTA), alanine aminotransferase (ALT), albumin, total cholesterol (TC), estimated glomerular filtration rate (eGFR), hemoglobin (Hb) and platelet (PLT) and higher age, model for end-stage liver disease (MELD) scores and ACLF grade than patients without infection. Multivariate logistic regression analysis showed that taking alcohol, HE, HS, cirrhosis, albumin and eGFR were risk factors for the development of infection. Conclusions Bacterial infections were very common in patients with HBV-ACLF. Taking alcohol, the occurrence of complications (HE, HS and cirrhosis), hypoalbuminemia and poor renal function often predict the higher prevalence of infections in patients with HBV-ACLF. It is important to focus on exploring the early recognition of infection and early intervention of those risk factors in patients with HBV-ACLF.
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Affiliation(s)
- Qian Zhang
- Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Baoxian Shi
- Department of Chemistry and Environmental Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Liang Wu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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15
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Ahmed Z, Shetty A, Victor DW, Kodali S. Viral hepatitis: A narrative review of hepatitis A–E. World J Meta-Anal 2022; 10:99-121. [DOI: 10.13105/wjma.v10.i3.99] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/27/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis continues to be a major health concern leading to hepatic decompensation ranging from acute hepatitis to cirrhosis and hepatocellular carcinoma. The hepatic and extrahepatic manifestations are not only debilitating but also associated with a significant economic burden. Over the last two decades, the field of virology has made significant breakthroughs leading to a better understanding of the pathophysiology of viral hepatitis, which in turn has led to new therapeutic options. The advent of direct-acting antiviral agents changed the landscape of hepatitis C virus (HCV) therapy, and new drugs are in the pipeline for chronic hepatitis B virus (HBV) treatment. There has also been a significant emphasis on screening and surveillance programs, widespread availability of vaccines, and linkage of care. Despite these efforts, significant gaps persist in care, and there is a pressing need for increased collaboration and teamwork across the globe to achieve a reduction of disease burden and elimination of HBV and HCV.
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Affiliation(s)
- Zunirah Ahmed
- Division of Gastroenterology and Hepatology, Underwood Center for Digestive Disorders, Houston Methodist Hospital, Houston, TX 77030, United States
| | - Akshay Shetty
- Department of Gastroenterology and Hepatology, University of California, Los Angeles, CA 90095, United States
| | - David W Victor
- Department of Hepatology, J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston, TX 77030, United States
| | - Sudha Kodali
- Department of Hepatology, J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston, TX 77030, United States
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16
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Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure. J Clin Med 2022; 11:jcm11102910. [PMID: 35629036 PMCID: PMC9143330 DOI: 10.3390/jcm11102910] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/18/2022] [Accepted: 05/19/2022] [Indexed: 12/02/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is an acutely decompensated cirrhosis syndrome with high short-term mortality. Very little is known about the relationship between the lymphatic system and ACLF. We explored the role of hepatic lymphatic vessels (LVs) and lymphatic endothelial cells (LyECs) in ACLF using human liver samples with the help of single-cell RNA-sequencing (scRNA-seq) technology. Here, ACLF exhibited more severe liver injury and inflammation than cirrhosis, as indicated by significant increases in plasma levels of alanine/aspartate aminotransferases and total bilirubin. Compared with cirrhosis cases, the number of intrahepatic LVs was decreased significantly in ACLF patients. ScRNA-seq revealed that many monocyte/macrophages infiltrated into the liver of ACLF cases. Meanwhile, scRNA-seq revealed a group of apoptotic and dysfunctional LyECs, which were the result of secreted phosphoprotein 1 (SPP1) released from infiltrating monocyte/macrophages. In vitro, SPP1 increased the proportion of dead LyECs significantly and impaired the ability of tube formation of LyECs in a dose- and time-dependent manner. In conclusion, ACLF is associated with less LV and LyEC dysfunction, at least in part mediated by SPP1 released from infiltrating monocyte/macrophages. Hepatic LVs and LyECs can be a novel therapeutic strategy for ACLF.
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17
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Tong J, Wang H, Xu X, Wan Z, Fang H, Chen J, Mu X, Liu Z, Chen J, Su H, Liu X, Li C, Huang X, Hu J. Granulocyte Colony-Stimulating Factor Accelerates the Recovery of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure by Promoting M2-Like Transition of Monocytes. Front Immunol 2022; 13:885829. [PMID: 35651610 PMCID: PMC9148949 DOI: 10.3389/fimmu.2022.885829] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/20/2022] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIM Acute-on-chronic liver failure (ACLF) has a high mortality rate. The role of granulocyte colony-stimulating factor (G-CSF) in ACLF remains controversial. Monocytes/macrophages are core immune cells, which are involved in the initiation and progression of liver failure; however, the effect of G-CSF on monocytes/macrophages is unclear. The study aimed to verify the clinical efficacy of G-CSF and explore the effect of it on monocytes in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) paitents. METHODS We performed a large randomized controlled clinical trial for the treatment of HBV-ACLF using G-CSF. A total of 111 patients with HBV-ACLF were prospectively randomized into the G-CSF group (5 μg/kg G-CSF every day for 6 days, then every other day until day 18) or the control group (standard therapy). All participants were followed up for at least 180 days. The relationship between monocyte count and mortality risk was analyzed. The effect of G-CSF on the phenotype and function of monocytes from patients with HBV-ACLF was evaluated using flow cytometry in vivo and in vitro experiments. RESULTS The survival probability of the G-CSF group at 180 days was higher than that of the control group (72.2% vs. 53.8%, P = 0.0142). In the G-CSF-treated group, the monocyte counts on days 0 and 7 were independently associated with an evaluated mortality risk in the fully adjusted model (Model 3) [at day 0: hazard ratio (HR) 95% confidence interval (CI): 15.48 (3.60, 66.66), P = 0.0002; at day 7: HR (95% CI): 1.10 (0.50, 2.43), P=0.8080]. Further analysis showed that after treatment with G-CSF in HBV-ACLF patients, the expression of M1-like markers (HLA-DR and CD86) in monocytes decreased (HLA-DR: P = 0.0148; CD86: P = 0.0764). The expression of MerTK (M2-like marker) increased (P = 0.0002). The secretion of TNF-α, IL-6, and IL-10 from monocytes decreased without lipopolysaccharide (LPS) stimulation (TNF-α: P < 0.0001; IL-6: P= 0.0025; IL-10: P = 0.0004) or with LPS stimulation (TNF-α: P = 0.0439; P = 0.0611; IL-10: P = 0.0099). Similar effects were observed in vitro experiments. CONCLUSION G-CSF therapy confers a survival benefit to patients with HBV-ACLF. G-CSF can promote the anti-inflammatory/pro-restorative phenotype (M2-like) transition of monocytes, which may contribute to the recovery of ACLF.Clinical Trial Registration Number: ClinicalTrials.gov, identifier (NCT02331745).
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Affiliation(s)
- Jingjing Tong
- Chinese PLA Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
- Department of Infectious Diseases, Beijing Jishuitan Hospital, Beijing, China
| | - Hongmin Wang
- Peking University 302 Clinical Medical School, Beijing, China
| | - Xiang Xu
- Laboratory of Translational Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China
| | - Zhihong Wan
- Center for Drug Evaluation, National Medical Products Administration, Beijing, China
| | - Hongbin Fang
- Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC, United States
| | - Jing Chen
- Chinese PLA Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xiuying Mu
- Peking University 302 Clinical Medical School, Beijing, China
| | - Zifeng Liu
- Chinese PLA Medical School, Beijing, China
| | - Jing Chen
- Chinese PLA Medical School, Beijing, China
| | - Haibin Su
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xiaoyan Liu
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Chen Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | | | - Jinhua Hu
- Chinese PLA Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
- Peking University 302 Clinical Medical School, Beijing, China
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Wang L, Xu W, Li X, Chen D, Zhang Y, Chen Y, Wang J, Luo Q, Xie C, Peng L. Long-term prognosis of patients with hepatitis B virus–related acute-on-chronic liver failure: a retrospective study. BMC Gastroenterol 2022; 22:162. [PMID: 35366805 PMCID: PMC8976971 DOI: 10.1186/s12876-022-02239-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 03/25/2022] [Indexed: 01/02/2023] Open
Abstract
Abstract
Background
The long-term prognosis of patients with hepatitis B virus–related acute-on-chronic liver failure (HBV-ACLF) is not well characterised. We assessed long-term outcomes and the associated risk factors of HBV-ACLF patients in southern China.
Methods
We retrospectively analysed clinical data, adverse events, and clinical endpoint events of HBV-ACLF patients treated at our department between January 2014 and December 2018.
Results
A total of 616 (52.3%) patients with cirrhosis and 561 (47.7%) patients without cirrhosis were included. In 973 (83%) patients, the disease was associated only with HBV, while 204 (17%) patients had two or more aetiological factors. The proportion of patients receiving antiviral treatment for HBV was low (20.3%). Further analyses indicated that patients without cirrhosis had a significantly lower 90-day liver transplantation–free mortality and higher 5‐year survival rate than those with cirrhosis (59.5% vs. 27.6%; 62% vs. 36%; P < 0.05). Remarkably, self-withdrawal of nucleos(t)ide analog (NA) was an independent risk factor for short-term prognosis. Age, cirrhosis at admission, and platelet level were closely related to long-term prognosis of HBV-ACLF patients.
Conclusion
The proportion of HBV-ACLF patients receiving antiviral treatment is very low in south China. Cirrhosis at admission has a significant effect on both short-term and long-term prognosis. No significant improvement in the short-term prognosis of HBV-ACLF patients was observed compared with previous studies. More comprehensive access to antiviral treatment and long-term surveillance of HBV patients are key imperatives to reduce the incidence of HBV-ACLF and improve the prognosis.
Trial Registration The trial was registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565) on May 13, 2020: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009OZY&selectaction=Edit&uid=U00036P1&ts=2&cx=27seqt
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19
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Li S, Zhang X, Li Q, Lv B, Zhang Y, Jia J, Yue X, Lu W. Development and validation of the nomogram based on INR and eGFR for estimation of mortality in patients with acute-on-chronic hepatitis B liver failure. BMC Gastroenterol 2021; 21:474. [PMID: 34911462 PMCID: PMC8675499 DOI: 10.1186/s12876-021-02054-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 12/01/2021] [Indexed: 11/10/2022] Open
Abstract
AIMS AND OBJECTIVES Acute-on-chronic hepatitis B liver failure (ACHBLF) is a critical clinical syndrome with a high short-term mortality evolved from chronic hepatitis B (CHB)-related liver disease. Prediction of mortality risk and early intervention can improve the prognosis of patients. This study aimed to develop and validate the nomogram for short-time mortality estimation in ACHBLF patients defined according to Asian Pacific Association for the Study of the Liver (APASL). METHODS A study of 105 ACHBLF patients with 90-day follow up was performed to develop the nomogram. Patients were randomly assigned to derivation cohort (n = 75) and validation cohort (n = 35) according to 7:3. Concordance index (C-index), calibration curve and decision curve analysis (DCA) were used to evaluate the nomogram. We also compared the nomogram with APASL ACLF research consortium (AARC) score, model for end-stage liver disease (MELD) score, MELD with serum sodium (MELD-Na) score and albumin-bilirubin (ALBI) score. The nomogram was validated using an external cohort including 40 patients. RESULTS The 28-day and 90-day mortality of 105 patients were respectively 49.52% and 55.24%. Albumin (ALB), international normalized ratio (INR) and estimated glomerular filtration rate (eGFR) were independent predictors for 28-day mortality; INR and eGFR were independent predictors for 90-day mortality. C-index of Nomogram-1 for 28-day mortality and Nomogram-2 for 90-day mortality were respectively 0.82 and 0.81. Calibration curve and Hosmer-Lemeshow test (Nomogram-1, 0.323; Nomogram-2, 0.231) showed optimal agreement between observed and predicted death. Areas under receiver operator characteristic curve(AUROC) of Nomogram-1(0.772) and Nomogram-2(0.771) were larger compared with AARC, MELD, MELD-Na and ALBI score. The results were well estimated in the external validation cohort. CONCLUSIONS This study highlighted the predictive value of eGFR, and the nomogram based on INR and eGFR could effectively estimate individualized risk for short-term mortality of ACHBLF patients defined according to APASL.
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Affiliation(s)
- Shengnan Li
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China
| | - Xiehua Zhang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
- Department of Infectious Diseases, The First Affiliated Hospital of Baotou Medical College, Baotou, Neimenggu, China
| | - Qian Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China
| | - Binyue Lv
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China
| | - Yefan Zhang
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China
| | - Jianwei Jia
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China
| | - Xiaofen Yue
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China
| | - Wei Lu
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
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20
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Hu N, Xie XC, Liu LL, Lai WD. Aberrant methylation of UBE2Q1 promoter is associated with poor prognosis of acute-on-chronic hepatitis B pre-liver failure. Medicine (Baltimore) 2021; 100:e26066. [PMID: 34032735 PMCID: PMC8154380 DOI: 10.1097/md.0000000000026066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 04/27/2021] [Indexed: 01/04/2023] Open
Abstract
Acute-on-chronic hepatitis B liver failure (ACHBLF) is one severe liver disease with rapid progression and high mortality. Identification of specific markers for the prediction of ACHBLF has important clinical significance. We explored the feasibility of UBE2Q1 gene promoter methylation as an early prediction and prognosis biomarker of ACHBLF.UBE2Q1 promoter methylation frequency was detected in 60 patients with acute-on-chronic hepatitis B pre-liver failure (Pre-ACHBLF), 40 patients with chronic hepatitis B and 20 cases of healthy control (HC). The UBE2Q1 mRNA was detected by quantitative real-time polymerase chain reaction.The methylation frequency of the UBE2Q1 promoter in pre-ACHBLF patients was 38.33%, which was significantly lower than that in chronic hepatitis B patients (60.00%) and HCs (65.00%). The UBE2Q1 mRNA expression in pre-ACHBLF patients with UBE1Q1 non-methylation was significantly higher than that in patients with UBE1Q1 promoter methylation. Further analysis showed that hypomethylation of the UBE2Q1 promoter was positively correlated with total bilirubin and international normalized ratio levels in patients with pre-ACHBLF, but negatively correlated with PTA level. COX multivariate analysis showed that the model for end-stage liver disease score and UBE2Q1 promoter hypomethylation status were potential early warning factors that can predict the progression of pre-ACHBLF to ACHBLF. The sensitivity and specificity of UBE2Q1 promoter methylation status combined with the model for end-stage liver disease score for early diagnosis of ACHBLF were 92.9% and 75.0%, respectively. The area under the receiver-operating characteristic curve was 0.895.The hypomethylation of UBE2Q1 promoter is associated with severity of Pre-ACHBLF, which could serve as a potential prognostic biomarker for pre-ACHBLF.
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Affiliation(s)
- Na Hu
- Department of Internal Medicine of Shandong Medical College
| | - Xian-ci Xie
- Department of Gastroenterology, Affiliated Hospital of Shandong Medical College
| | - Lin-lin Liu
- Medical Laboratory Department of Shandong Medical College
| | - Wei-dong Lai
- Department of Surgery, Shandong Medical College, Shangdong, China
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21
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Li J, Gong QM, Xie PL, Lin JY, Chen J, Wei D, Yu DM, Han Y, Zhang XX. Prognostic value of anti-HBc quantification in hepatitis B virus related acute-on-chronic liver failure. J Gastroenterol Hepatol 2021; 36:1291-1299. [PMID: 33091955 DOI: 10.1111/jgh.15310] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/02/2020] [Accepted: 10/16/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM It has been reported that serum quantification of anti-HBc (qAnti-HBc) could predict antiviral response in chronic hepatitis B (CHB) patients, while its role in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Its implication in HBV-ACLF was evaluated in this study. METHODS Baseline serum qAnti-HBc levels were retrospectively detected in HBV-ACLF and CHB patients using recently developed double-sandwich immunoassay. The association of qAnti-HBc level with clinical outcomes was evaluated by multiple logistic regression. Nomogram was adopted to formulate an algorithm incorporating qAnti-HBc for the prediction of survival in HBV-ACLF. The post-hospitalization of HBV-ACLF patients were followed-up for 1 year. RESULTS Eighty-eight HBV-ACLF as training set, 80 HBV-ACLF as validation set and 216 CHB cases were included. Serum qAnti-HBc level was significantly higher in HBV-ACLF (4.95 ± 0.54 log10 IU/mL) than CHB patients (4.47 ± 0.84 log10 IU/mL) (P < 0.01). Among HBV-ACLF cases, both in training and validation set, patients with poor outcomes had lower qAnti-HBc level. Area under receiver operating characteristic curve of the novel qAnti-HBc inclusive model was 0.82, superior to 0.73 from model for end-stage liver disease scores (P = 0.018), which was confirmed in validation set. During follow-up, the qAnti-HBc level declined at month 3 and month 6, then plateaued at 3.84 log10 IU/mL. CONCLUSIONS Serum qAnti-HBc level was associated with disease severity and might be served as a novel biomarker in the prediction of HBV-ACLF clinical outcomes. The underlying immunological mechanism warrants further investigation.
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Affiliation(s)
- Jing Li
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qi-Ming Gong
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Pei-Lin Xie
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun-Yu Lin
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jia Chen
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dong Wei
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - De-Min Yu
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yue Han
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Sino-French Research Centre for Life Sciences and Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xin-Xin Zhang
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Sino-French Research Centre for Life Sciences and Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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22
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Li Q, Wang J, Lu M, Qiu Y, Lu H. Acute-on-Chronic Liver Failure From Chronic-Hepatitis-B, Who Is the Behind Scenes. Front Microbiol 2020; 11:583423. [PMID: 33365018 PMCID: PMC7750191 DOI: 10.3389/fmicb.2020.583423] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/13/2020] [Indexed: 12/12/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is an acute syndrome accompanied with decompensation of cirrhosis, organ failure with high 28-day mortality rate. Systemic inflammation is the main feature of ACLF, and poor outcome is closely related with exacerbated systemic inflammatory responses. It is well known that severe systemic inflammation is an important event in chronic hepatitis B (CHB)-ACLF, which eventually leads to liver injury. However, the initial CHB-ACLF events are unclear; moreover, the effect of these events on host immunity as well as that of immune imbalance on CHB-ACLF progression are unknown. Here, we investigate the initial events of ACLF progression, discuss possible mechanisms underlying ACLF progression, and provide a new model for ACLF prediction and treatment. We review the characteristics of ACLF, and consider its plausible immune predictors and alternative treatment strategies.
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Affiliation(s)
- Qian Li
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
| | - Jun Wang
- Center of Clinical Laboratory, The Fifth People's Hospital of Wuxi, Jiangnan University, Wuxi, China
| | - Mengji Lu
- Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
| | - Yuanwang Qiu
- Department of Hepatology, The Fifth People's Hospital of Wuxi, Jiangnan University, Wuxi, China
| | - Hongzhou Lu
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
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23
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Zhu B, You S, Rong Y, Yu Q, Lv S, Song F, Liu H, Wang H, Zhao J, Li D, Liu W, Xin S. A novel stem cell therapy for hepatitis B virus-related acute-on-chronic liver failure. ACTA ACUST UNITED AC 2020; 53:e9728. [PMID: 33053116 PMCID: PMC7552894 DOI: 10.1590/1414-431x20209728] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 08/07/2020] [Indexed: 12/20/2022]
Abstract
The aim of this study was to propose a stem cell therapy for hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) based on plasma exchange (PE) for peripheral blood stem cell (PBSC) collection and examine its safety and efficacy. Sixty patients (n=20 in each group) were randomized to PE (PE alone), granulocyte colony-stimulating factor (G-CSF) (PE after G-CSF treatment), and PBSC transplantation (PBSCT) (G-CSF, PE, PBSC collection and hepatic artery injection) groups. Patients were followed-up for 24 weeks. Liver function and adverse events were recorded. Survival analysis was performed. PBSCT improved blood ammonia levels at 1 week (P<0.05). The level of total bilirubin, international normalized ratio, and creatinine showed significant differences in the 4th week of treatment (P<0.05). The survival rates of the PE, G-CSF, and PBSCT groups were 50, 65, and 85% at 90 days (P=0.034). There was a significant difference in 90-day survival between the PE and PBSCT groups (P=0.021). The preliminary results suggested that PBSCT was safe, with a possibility of improved 90-day survival in patients with HBV-ACLF.
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Affiliation(s)
- Bing Zhu
- Medical School of Chinese PLA, Beijing, China.,Liver Failure Treatment and Research Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shaoli You
- Liver Failure Treatment and Research Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yihui Rong
- Department of Infection and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Qiang Yu
- Department of Interventional Therapy, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Sa Lv
- Liver Failure Treatment and Research Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Fangjiao Song
- Liver Failure Treatment and Research Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Hongling Liu
- Liver Transplantation Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Huaming Wang
- Department of Interventional Therapy, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jun Zhao
- Liver Failure Treatment and Research Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Dongze Li
- Liver Failure Treatment and Research Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wanshu Liu
- Liver Failure Treatment and Research Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shaojie Xin
- Medical School of Chinese PLA, Beijing, China.,Liver Failure Treatment and Research Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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24
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Zhou C, Zhang N, He TT, Wang Y, Wang LF, Sun YQ, Jing J, Zhang JJ, Fu SN, Wang X, Liang XX, Li X, Gong M, Li J. High levels of serum interleukin-6 increase mortality of hepatitis B virus-associated acute-on-chronic liver failure. World J Gastroenterol 2020; 26:4479-4488. [PMID: 32874059 PMCID: PMC7438191 DOI: 10.3748/wjg.v26.i30.4479] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/24/2020] [Accepted: 07/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) present a complex and poor prognosis. Systemic inflammation plays an important role in its pathogenesis, and interleukin-6 (IL-6) as a pro-inflammatory cytokine is related with severe liver impairment and also plays a role in promoting liver regeneration. Whether serum IL-6 influences HBV-ACLF prognosis has not been studied.
AIM To determine the impact of serum IL-6 on outcome of patients with HBV-ACLF.
METHODS We performed a retrospective study of 412 HBV-ACLF patients. The findings were analyzed with regard to mortality and the serum IL-6 level at baseline, as well as dynamic changes of serum IL-6 within 4 wk.
RESULTS The serum IL-6 level was associated with mortality. Within 4 wk, deceased patients had significantly higher levels of IL-6 at baseline than surviving patients [17.9 (7.3-57.6) vs 10.4 (4.7-22.3), P = 0.011]. Patients with high IL-6 levels (> 11.8 pg/mL) had a higher mortality within 4 wk than those with low IL-6 levels (≤ 11.8 pg/mL) (24.2% vs 13.2%, P = 0.004). The odds ratios calculated using univariate and multivariate logistic regression were 2.10 (95% confidence interval [CI]: 1.26-3.51, P = 0.005) and 2.11 (95%CI: 1.15-3.90, P = 0.017), respectively. The mortality between weeks 5 and 8 in patients with high IL-6 levels at 4 wk was 15.0%, which was significantly higher than the 6.6% mortality rate in patients with low IL-6 levels at 4 wk (hazard ratio = 2.39, 95%CI: 1.05-5.41, P = 0.037). The mortality was 5.0% in patients with high IL-6 levels at baseline and low IL-6 levels at 4 wk, 7.5% in patients with low IL-6 levels both at baseline and at 4 wk, 11.5% in patients with low IL-6 levels at baseline and high IL-6 levels at 4 wk, and 16.7% in patients with high IL-6 levels both at baseline and at 4 wk. The increasing trend of the mortality rate with the dynamic changes of IL-6 was significant (P for trend = 0.023).
CONCLUSION A high level of serum IL-6 is an independent risk factor for mortality in patients with HBV-ACLF. Furthermore, a sustained high level or dynamic elevated level of serum IL-6 indicates a higher mortality.
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Affiliation(s)
- Chao Zhou
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Ning Zhang
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Ting-Ting He
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yao Wang
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Li-Fu Wang
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yong-Qiang Sun
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Jing Jing
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Jing-Jing Zhang
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Shuang-Nan Fu
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Xuan Wang
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Xiao-Xiao Liang
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Xin Li
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Man Gong
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Jun Li
- Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
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25
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Li TP, Guan SH, Wang Q, Chen LW, Yang K, Zhang H. Soluble mannose receptor as a predictor of prognosis of hepatitis B virus-related acute-on-chronic liver failure. World J Gastroenterol 2019; 25:5667-5675. [PMID: 31602166 PMCID: PMC6785521 DOI: 10.3748/wjg.v25.i37.5667] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 08/21/2019] [Accepted: 09/10/2019] [Indexed: 02/06/2023] Open
Abstract
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 HBV-ACLF (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.
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Affiliation(s)
- Tai-Ping Li
- Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Shi-He Guan
- Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Qin Wang
- Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Li-Wen Chen
- Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Kai Yang
- Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Hao Zhang
- Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
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26
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Accuracy of pipeline blood glucose monitoring in patients with severe liver injury undergoing artificial liver support system treatment. Hepatobiliary Pancreat Dis Int 2019; 18:484-487. [PMID: 31477524 DOI: 10.1016/j.hbpd.2019.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 08/15/2019] [Indexed: 02/05/2023]
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27
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Serin A, Sahin T, Arikan BT, Emek E, Bozkurt B, Tokat Y. A Changing Etiologic Scenario in Liver Transplantation: A Single-Center Cohort Study From Turkey. Transplant Proc 2019; 51:2416-2419. [PMID: 31402253 DOI: 10.1016/j.transproceed.2019.01.190] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Accepted: 01/28/2019] [Indexed: 01/01/2023]
Abstract
PURPOSE Nonalcoholic steatohepatitis (NASH) is an increasing cause of liver transplantation (LT) worldwide, especially in Europe and North America. In this study, we aimed to investigate the changing pattern of etiologic causes of LT in our center for the past 15 years. MATERIALS AND METHODS A cohort of 967 consecutive adult patients with history of LT between 2004 and 2018 in our center was reviewed regarding etiologies for LT. All patients who had a transplant during this time frame were divided into 3 time periods as follows: 2004 to 2009, 2010 to 2013, and 2014 to 2018. All explanted liver samples were sent to pathology for establishment of a definitive etiologic cause. RESULTS Chronic hepatitis B virus (HBV) infection was the leading cause of LT in the overall cohort (37%), followed by hepatitis C virus (HCV) infection (11%), and alcoholic liver disease (9.5%). NASH accounted for 7.5% of the cases. While HBV decreased from 44% in 2004 to 2009 to 36% in 2014 to 2018, NASH increased from 1.1% to 9.4% in overall transplants during the same period, accounting for one-third of the etiologies for LT following HBV and HCV. CONCLUSIONS There might be a global changing figure regarding etiology for LT in Turkey, especially NASH, which is the fastest growing cause of LT. However, this topic needs to be evaluated in large cohort series from collaborative multicenter studies from Turkey.
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Affiliation(s)
- Ayfer Serin
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey.
| | - Tolga Sahin
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Bahadir Turkmen Arikan
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Ertan Emek
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Birkan Bozkurt
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Yaman Tokat
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
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28
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Tong JJ, Zhao W, Mu XY, Xu X, Su HB, Liu XY, Chen J, Zhai XR, Wang Y, Hu JH. 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. Chin Med J (Engl) 2019; 132:1541-1549. [PMID: 31188162 PMCID: PMC6616238 DOI: 10.1097/cm9.0000000000000298] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Indexed: 12/21/2022] Open
Abstract
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 COSSH-ACLFs with classical scores. Different COX multivariate regression models were used to confirm the relationship between COSSH-ACLFs 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 short-term prognosis in Chinese patients with HBV-ACLF.
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Affiliation(s)
- Jing-Jing Tong
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Wei Zhao
- Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029, China
| | - Xiu-Ying Mu
- Peking University 302 Clinical Medical School, Beijing 100039, China
| | - Xiang Xu
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hai-Bin Su
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Xiao-Yan Liu
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Jing Chen
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- Medical School of Chinese PLA, Beijing 100853, China
| | - Xing-Ran Zhai
- Peking University 302 Clinical Medical School, Beijing 100039, China
| | - Yu Wang
- Medical School of Chinese PLA, Beijing 100853, China
| | - Jin-Hua Hu
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- Peking University 302 Clinical Medical School, Beijing 100039, China
- Medical School of Chinese PLA, Beijing 100853, China
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Wu J, Li YY, Hu JH, Jia L, Shi M, Meng FP, Li J, Zhao J, Wang FS, Meng QH. Differential characteristics and prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure defined by European Association for the Study of the Liver - Chronic Liver Failure criteria. Hepatol Res 2018; 48:153-164. [PMID: 28456135 DOI: 10.1111/hepr.12909] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2017] [Revised: 04/18/2017] [Accepted: 04/28/2017] [Indexed: 12/18/2022]
Abstract
AIM To determine the differential characteristics and prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) detected using Asian Pacific Association for the Study of the Liver (APASL) criteria and then classified using European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria. METHODS We retrospectively reviewed 316 HBV-related APASL ACLF patients treated at Beijing 302 Hospital or Beijing You'An Hospital (both Beijing, China) between February 2015 and February 2016. Clinical characteristics and mortality rates were compared among patients with different EASL-CLIF ACLF severity grades (no ACLF, and ACLF grades 1-3). RESULTS According to the EASL-CLIF criteria, 138 patients had no ACLF, 123 had ACLF at enrollment, and 55 developed ACLF during hospitalization. Both 28-day and 90-day transplant-free mortality were dramatically lower in patients without EASL-CLIF ACLF (0.7% and 5.1%, respectively) than in patients with EASL-CLIF ACLF (40.7% and 63.2%, respectively; both P < 0.001). Liver failure rates were similar in patients with and without EASL-CLIF ACLF, but extrahepatic organ failure was rare in patients without EASL-CLIF ACLF. Baseline serum creatinine, new bacterial infection and new acute kidney injury during hospitalization, maximum rising rates of CLIF-C ACLF score, and Model for End-stage Liver Disease score were independent predictors of EASL-CLIF ACLF after enrollment. CONCLUSIONS The EASL-CLIF ACLF classification can accurately prognosticate the short-term mortality of patients with HBV-related APASL ACLF. It can also distinguish distinct clinical characteristics and prognoses in patients with and without EASL-CLIF ACLF.
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Affiliation(s)
- Juan Wu
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Yuan-Yuan Li
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Jin-Hua Hu
- Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China
| | - Lin Jia
- Department of Critical Care Medicine of Liver Disease, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Ming Shi
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Fan-Ping Meng
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Juan Li
- Department of Critical Care Medicine of Liver Disease, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Juan Zhao
- Department of Critical Care Medicine of Liver Disease, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Fu-Sheng Wang
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Qing-Hua Meng
- Department of Critical Care Medicine of Liver Disease, Beijing You'An Hospital, Capital Medical University, Beijing, China
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Melgaço JG, Gardinali NR, de Mello VDM, Leal M, Lewis-Ximenez LL, Pinto MA. Hepatitis E: Update on Prevention and Control. BIOMED RESEARCH INTERNATIONAL 2018; 2018:5769201. [PMID: 29546064 PMCID: PMC5818934 DOI: 10.1155/2018/5769201] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 11/28/2017] [Accepted: 12/13/2017] [Indexed: 12/20/2022]
Abstract
Hepatitis E virus (HEV) is a common etiology of acute viral hepatitis worldwide. Recombinant HEV vaccines have been developed, but only one is commercially available and licensed in China since 2011. Epidemiological studies have identified genotype 3 as the major cause of chronic infection in immunocompromised individuals. Ribavirin has been shown to be effective as a monotherapy to induce HEV clearance in chronic patients who have undergone solid organ transplant (SOT) under immunosuppressive therapy. Efforts and improvements in prevention and control have been made to reduce the instances of acute and chronic hepatitis E in endemic and nonendemic countries. However, this review shows that further studies are required to demonstrate the importance of preventive vaccination and treatment worldwide, with emphasis on hepatitis E infection in the public health system.
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Affiliation(s)
- Juliana Gil Melgaço
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Noemi Rovaris Gardinali
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Vinicius da Motta de Mello
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Mariana Leal
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Lia Laura Lewis-Ximenez
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Marcelo Alves Pinto
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
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Wan YM, Li YH, Xu ZY, Yang J, Yang LH, Xu Y, Yang JH. Therapeutic plasma exchange versus double plasma molecular absorption system in hepatitis B virus-infected acute-on-chronic liver failure treated by entercavir: A prospective study. J Clin Apher 2017; 32:453-461. [PMID: 28304106 DOI: 10.1002/jca.21535] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 02/04/2017] [Accepted: 03/05/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Therapeutic plasma exchange (TPE) and double plasma molecular absorption system (DPMAS) were two extracorporeal liver support systems. Few studies compared their efficacy profile. OBJECTIVE This study was to compare the efficacy of TPE and DPMAS on acute-on-chronic liver failure (ACLF) caused by hepatitis B virus (HBV-ACLF). METHODS 60 HBV-ACLF patients were enrolled and prospectively studied. All patients received entecavir therapy, and were assigned to TPE group (n = 33) and DPMAS group (n = 27). Primary end-points were the effects of TPE and DPMAS on liver function and serum inflammatory markers. RESULTS Serum procalcitonin, interleukin (IL)-6, and high sensitive C-reactive protein (hsCRP) were significantly elevated in patients with HBV-ACLF. TPE achieved significantly higher removal rates of total bilirubin (TBIL, P = .002), direct bilirubin (DBIL, P = .006), and hsCRP (P = .010) than DPMAS, but DPMAS displayed lower loss rate of albumin (P = .000). TPE and DPMAS resulted in similarly increased serum IL-6 levels and comparable 12-week survivals (P > .05). Multivariate analysis showed that hospital stay (Relative Risk [RR]: 1.062, 95% Confidence Interval [CI]: 1.011-1.115, P = .016), prothrombin time (RR: 1.346, 95% CI: 1.077-1.726, P = .010), and international normalized ratio (RR: 0.013, 95% CI: 0.006-0.788, P = .041) were independent predictors for 12-week survival. Both TPE and DPMAS treatments were well-tolerated. CONCLUSION Compared to DPMAS, TPE was more efficient in eliminating TBIL, DBIL, and hsCRP, but it was associated with higher loss rate of albumin. TPE and DPMAS were similar in improving 12-week survivals in HBV-ACLF.
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Affiliation(s)
- Yue-Meng Wan
- Gastroenterology Department II or Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, 650101, Yunnan Province, China.,Graduate Department of Kunming Medical University, Kunming City, 650500, Yunnan Province, China
| | - Yu-Hua Li
- Gastroenterology Department II or Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, 650101, Yunnan Province, China
| | - Zhi-Yuan Xu
- Gastroenterology Department II or Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, 650101, Yunnan Province, China
| | - Jing Yang
- Gastroenterology Department II or Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, 650101, Yunnan Province, China
| | - Li-Hong Yang
- Gastroenterology Department II or Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, 650101, Yunnan Province, China
| | - Ying Xu
- Gastroenterology Department II or Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, 650101, Yunnan Province, China
| | - Jin-Hui Yang
- Gastroenterology Department II or Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, 650101, Yunnan Province, China
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Herrine SK, Moayyedi P, Brown RS, Falck-Ytter YT. American Gastroenterological Association Institute Technical Review on Initial Testing and Management of Acute Liver Disease. Gastroenterology 2017; 152:648-664.e5. [PMID: 28061338 DOI: 10.1053/j.gastro.2016.12.027] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Steven K Herrine
- Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania.
| | | | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, New York
| | - Yngve T Falck-Ytter
- Division of Gastroenterology and Hepatology, Department of Medicine, Case and VA Medical Center, Case Western Reserve University, Cleveland, Ohio
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Shi X, Zhu P, Yan G, Liu C, Zhang C, Huang G, Zhang Y, Yan Z, Wang Y. Clinical characteristics and long-term outcome of acute kidney injury in patients with HBV-related acute-on-chronic liver failure. J Viral Hepat 2016; 23:920-929. [PMID: 27397610 DOI: 10.1111/jvh.12566] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Accepted: 06/07/2016] [Indexed: 12/15/2022]
Abstract
Acute kidney injury (AKI) is a common complication in patients with decompensated cirrhosis and is also an important cause for poor outcome. This study aimed at investigating the clinical characteristics and long-term prognosis of AKI in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). A total of 1167 patients with HBV-related ACLF from January 2010 to January 2015 were enrolled and divided into two groups, AKI group (n=308) and non-AKI group (n=859). All patients were followed up to investigate clinical characteristics, long-term overall survival (OS) and risk factors. AKI occurrence was found to be 26.4% in patients with HBV-related ACLF. The patients in the AKI group and the non-AKI group had a 30-day OS of 44.8% and 70.3%, 90-day OS of 17.9% and 55.4%, and 1-year OS of 15.6% and 51.2%, respectively. Significant differences were observed in the 30-day, 90-day and 1-year OS among subgroups with different AKI stages. It was found that high WBC, neutrophil, ALT and MELD score were risk factors for 30-day mortality, whereas hepatic encephalopathy, high MELD score, mean arterial pressure and PLT were risk factors for 90-day mortality. Two criteria, the KDIGO and AKIN, showed parallel results in staging AKI in patients with HBV-related ACLF (κ=0.807, P<.001). AKI is closely associated with increased short-term mortality in Chinese HBV-related ACLF patients, particularly in those with infection and high MELD score. Both KDIGO and AKIN criteria can be used for staging AKI in patients with HBV-related ACLF.
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Affiliation(s)
- X Shi
- Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - P Zhu
- Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - G Yan
- Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - C Liu
- Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - C Zhang
- Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - G Huang
- Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Y Zhang
- Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Z Yan
- Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Y Wang
- Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Cytokines elevated in patients with HBV-related acute-on-chronic liver failure promote NK cell mediated cytotoxicity through TRAIL. Dig Liver Dis 2016; 48:528-535. [PMID: 26860239 DOI: 10.1016/j.dld.2016.01.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Revised: 01/08/2016] [Accepted: 01/14/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS The role of NK cells on inducing liver injury in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) is not well understood. The aim of this study was to determine the cytotoxicity of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-expressed NK cells from HBV-ACLF patients and facilitate a better understanding of the immune pathogenesis of HBV-ACLF. METHODS Peripheral blood samples were obtained from HBV-ACLF patients, mild chronic hepatitis B (CHB) patients and healthy controls (HC). Circulating NK cells phenotype was determined using flow cytometry. Serum cytokine concentrations were ascertained using the CBA Inflammation kit. Cell apoptosis was analyzed using the FITC-annexin V Apoptosis Detection Kit. RESULTS Peripheral NK cells from HBV-ACLF expressed higher levels of TRAIL than those from CHB and HC. Expression of TRAIL on NK cells was correlated positively with serum IL-6 and IL-8 concentrations in HBV-ACLF patients, which is further confirmed by cytokines stimulation in vitro. NK cells caused a significant increase of apoptotic hepatocytes, and further increased the frequency of apoptosis in IL-6 and IL8-stimulated hepatocytes; the apoptosis was then inhibited partially by an anti-TRAIL monoclonal antibody. CONCLUSION These results suggested that inflammation cytokines elevated in patients with HBV-ACLF may promote NK cell mediated cytotoxicity through TRAIL pathway.
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Hu F, Bi S, Yan H, Shi Y, Sheng J. Associations between hepatitis B virus basal core promoter/pre-core region mutations and the risk of acute-on-chronic liver failure: a meta-analysis. Virol J 2015; 12:87. [PMID: 26063382 PMCID: PMC4485863 DOI: 10.1186/s12985-015-0313-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 05/25/2015] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Several studies have suggested a relationship between hepatitis B virus (HBV) basal core promoter/pre-core mutations and HBV-induced acute-on-chronic liver failure (ACLF). Therefore, we evaluated this potential relationship using a meta-analysis. METHODS Chinese or English studies from 1966 to January 31, 2014 were included in the analysis. A random or fixed-effects model was used to merge the odds ratios (ORs). RESULTS We identified 31 case-control studies containing a total population of 1995 ACLF and 3822 chronic hepatitis B (CHB) patients. Several mutations were significantly correlated with ACLF: T1753V (1.889, 95 % confidence interval (CI) [1.357-2.631]), A1762T (2.696 [2.265-3.207]), G1764A (3.005 [2.077-4.347]), A1762T/G1764A (2.379 [1.519-3.727]), C1766T (1.849 [1.403-2.437]), T1768A (2.440 [1.405-3.494]), A1846T (3.163 [2.157-4.639]), G1896A (2.181 [1.800-2.642]), G1899A (3.569 [2.906-4.385]) and G1896A/A1762T/G1764A (1.575 [1.172-2.116]). Additionally, HBeAg-negative status was also statistically significant for the progression to ACLF (OR = 2.813, 95 % CI = 2.240-3.533, p < 0.001). However, there was no association between ACLF development and HBV genotype. CONCLUSIONS The HBV basal core promoter/pre-core mutations T1753V, A1762T, G1764A, C1766T, T1768A, A1846T, G1896A and G1899A, and an HBeAg-negative status correlate with an increased risk of HBV-ACLF.
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Affiliation(s)
- Feishu Hu
- State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital of Medical School, Zhejiang University, Hangzhou, 310000, China.
| | - Sheng Bi
- State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital of Medical School, Zhejiang University, Hangzhou, 310000, China.
| | - Huadong Yan
- Department of Hepatology, Ningbo No. 2 Hospital, Ningbo, 315010, China.
| | - Yu Shi
- State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital of Medical School, Zhejiang University, Hangzhou, 310000, China.
| | - Jifang Sheng
- State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital of Medical School, Zhejiang University, Hangzhou, 310000, China.
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Usefulness of serum thyroid-stimulation hormone (TSH) as a prognostic indicator for acute-on-chronic liver failure. Ann Hepatol 2015. [DOI: 10.1016/s1665-2681(19)30784-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Combining serum cystatin C with total bilirubin improves short-term mortality prediction in patients with HBV-related acute-on-chronic liver failure. PLoS One 2015; 10:e0116968. [PMID: 25629773 PMCID: PMC4309543 DOI: 10.1371/journal.pone.0116968] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 12/17/2014] [Indexed: 02/06/2023] Open
Abstract
Background & Aims HBV-related acute-on-chronic liver failure (HBV-ACLF) is a severe liver disease which results in a high mortality in China. To early predict the prognosis of the patients may prevent the complications and improve the survival. This study was aimed to develop a new prognostic index to estimate the survival related to HBV-ACLF. Methods Consecutive patients with HBV-ACLF were included in a prospective observational study. Serum Cystatin C concentrations were measured by using the particle-enhanced immunonephelometry assay. All of the patients were followed for at least 3 months. Cox regression analysis was carried out to identify which factors were predictive of mortality. The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of the variates for early predicting mortality. Results Seventy-two patients with HBV-ACLF were recruited between January 2012 and January 2013. Thirty patients died (41.7%) during 3-months followed up. Cox multivariate regression analysis identified serum cystatin C (CysC) and total bilirubin (TBil) were independent factors significantly (P < 0.01) associated with survival. Our results further showed that new prognostic index (PI) combining serum CysC with TBil was a good indicator for predicting the mortality of patients with HBV-ACLF. Specifically, the PI had a higher accuracy than the CTP, MELD, or MELD-Na scoring for early prediction short-term survival of HBV-ACLF patients with normal levels of serum creatinine (Cr). The survival rate in low risk group (PI < 3.91) was 94.3%, which was markedly higher than those in the high-risk group (PI ≥ 3.91) (17.4%, P < 0.001). Conclusion We developed a new prognostic index combining serum CysC with TBil which early predicted the short-term mortality of HBV-ACLF patients.
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Wang K, Wu ZB, Ye YN, Liu J, Zhang GL, Su YJ, He HL, Zheng YB, Gao ZL. Plasma Interleukin-10: A Likely Predictive Marker for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure. HEPATITIS MONTHLY 2014; 14:e19370. [PMID: 25147572 PMCID: PMC4139694 DOI: 10.5812/hepatmon.19370] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Revised: 05/27/2014] [Accepted: 06/22/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND The pathogenesis of HBV-related acute-on-chronic liver failure (HBV-ACLF) is mainly based on a heightened immune-inflammatory reaction; however, the intimate underlying mechanism remains unclear. OBJECTIVES The aim of the study was to explore potential key immune molecular targets that could serve as early predictive markers for HBV-ACLF. PATIENTS AND METHODS Twenty-seven patients with acute exacerbation of chronic hepatitis B (CHB) (defined by: alanine transaminase ≥ 20 ULN, total bilirubin ≥ 5 ULN, 40% < prothrombin time activity ≤ 60%) and without cirrhosis were divided into 18 cases which did not progress to HBV-ACLF (defined by: prothrombin time activity < 40% and development within four weeks of hepatic encephalopathy and/or ascites) and nine cases that developed HBV-ACLF. Nine healthy people defined the normal control group (NC). Interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-α and IFN-γ protein levels were assayed by Cytometric Bead Array (CBA) in blood plasma. The ELISA method was applied to confirm IL-10 detection using the CBA method. RESULTS IL-4, IL-12p70 and IFN-γ were undetectable; IL-1β, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher than in NC. Moreover, cytokines reached the highest levels in acute exacerbation of CHB, with the exception of IL-2 and IL-8. When comparing the HBV-ACLF patients prior to and at the time of ACLF diagnosis, IL-10 was the only cytokine that exhibited a significant decrease (P = 0.008). IL-10 concentrations were positively correlated to ALT levels (r = 0.711, P < 0.001). CONCLUSIONS The assessment of plasma IL-10 levels in chronic hepatitis B acute exacerbation may provide an early predictive marker for progression to HBV-ACLF.
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Affiliation(s)
- Ke Wang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhe-bin Wu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yi-nong Ye
- Department of Infectious Diseases, Foshan Hospital of Sun Yat-sen University, Foshan, China
| | - Jing Liu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Geng-lin Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yu-jie Su
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hong-liang He
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yu-bao Zheng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhi-liang Gao
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Corresponding Author: Zhi-liang Gao, Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600 # Tianhe Road, Guangzhou 510630, China. Tel: +86-2085252373, Fax: +86-2085252250, E-mail:
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Zhu B, You SL, Wan ZH, Liu HL, Rong YH, Zang H, Xin SJ. Clinical characteristics and corticosteroid therapy in patients with autoimmune-hepatitis-induced liver failure. World J Gastroenterol 2014; 20:7473-7479. [PMID: 24966618 PMCID: PMC4064093 DOI: 10.3748/wjg.v20.i23.7473] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 01/15/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the clinical features, response to corticosteroids, and prognosis of autoimmune hepatitis (AIH)-induced liver failure in China.
METHODS: A total of 22 patients (19 female and 3 male; average age 51 ± 15 years) with AIH-induced liver failure treated in our hospital from 2004 to 2012 were retrospectively analyzed. Clinical, biochemical and pathological characteristics of the 22 patients and responses to corticosteroid treatment in seven patients were examined retrospectively. The patients were divided into survivor and non-survivor groups, and the clinical characteristics and prognosis were compared between the two groups. The t test was used for data analysis of all categorical variables, and overall survival was calculated by the Kaplan-Meier method.
RESULTS: At the time of diagnosis, mean IgG was 2473 ± 983 mg/dL, with three (18.8%) patients showing normal levels. All of the patients had elevated serum levels of antinuclear antibody (≥ 1:640). Liver histology from one patient showed diagnostic pathological changes, including massive necrosis and plasma cell infiltration. Four patients survived (18.2%) and 18 died (81.8%) without liver transplantation. The results showed that patients with low admission Model for End-Stage Liver Disease (MELD) scores (21.50 ± 2.08 vs 30.61 ± 6.70, P < 0.05) and corticosteroid therapy (100% vs 16.7%, P < 0.05) had better prognosis. A total of seven patients received corticosteroid therapy, of whom, four responded and survived, and the other three died. Survivors showed young age, shorter duration from diagnosis to corticosteroid therapy, low MELD score, and absence of hepatic encephalopathy at the time of corticosteroid administration. Six patients who were administered corticosteroids acquired fungal infections but recovered after antifungal therapy.
CONCLUSION: Early diagnosis and corticosteroid therapy are essential for improving the prognosis of patients with AIH-induced liver failure without liver transplantation.
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Wan ZH, Wang JJ, You SL, Liu HL, Zhu B, Zang H, Li C, Chen J, Xin SJ. Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure. World J Gastroenterol 2013; 19:9432-9438. [PMID: 24409073 PMCID: PMC3882419 DOI: 10.3748/wjg.v19.i48.9432] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 11/04/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury (AKI) in patients with acute-on-chronic liver failure (ACLF).
METHODS: Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine (Cr) level (< 1.2 mg/dL in men, or < 1.1 mg/dL in women) were enrolled in the Liver Failure Treatment and Research Center of Beijing 302 Hospital between August 2011 and October 2012. Thirty patients with chronic hepatitis B (CHB) and 30 healthy controls in the same study period were also included. Measurement of serum cystatin C (CysC) was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer system. The ACLF patients were followed during their hospitalization period.
RESULTS: In the ACLF group, serum level of CysC was 1.1 ± 0.4 mg/L, which was significantly higher (P < 0.01) than those in the healthy controls (0.6 ± 0.3 mg/L) and CHB patients (0.7 ± 0.2 mg/L). During the hospitalization period, eight ACLF patients developed AKI. Logistic regression analysis indicated that CysC level was an independent risk factor for AKI development (odds ratio = 1.8; 95%CI: 1.4-2.3, P = 0.021). The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/L. The baseline CysC-based estimated glomerular filtration rate (eGFRCysC) was significantly lower than the creatinine-based eGFR (eGFRCG and eGFRMDRD) in ACLF patients with AKI, suggesting that baseline eGFRCysC represented early renal function in ACLF patients while the Cr levels were still within the normal ranges.
CONCLUSION: Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.
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Zhang A, Wan Z, You S, Liu H, Zhu B, Chen J, Rong Y, Zang H, Li C, Wang H, Xin S. Association of Hepatitis B Virus Mutations of A1846T and C1913A/G With Acute-on-Chronic Liver Failure Development From Different Underlying Chronic Liver Diseases. HEPATITIS MONTHLY 2013; 13:e12445. [PMID: 24282424 PMCID: PMC3830524 DOI: 10.5812/hepatmon.12445] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Revised: 07/23/2013] [Accepted: 08/12/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND As most HBV-related acute-on-chronic liver failure (ACLF) have concurrent cirrhosis, it is important to clarify the association of viral factors with ACLF with or without cirrhosis. OBJECTIVES The aim of this study was to analyze the association of HBV genotypes and mutations with ACLF development underlying different chronic liver diseases. PATIENTS AND METHODS Eighty-seven ACLF patients including 29 patients with chronic hepatitis (ACLF-CHB) and 58 patients with liver cirrhosis (ACLF-LC) were enrolled. Age and sex matched patients with chronic hepatitis (CHB) and liver cirrhosis (LC) were enrolled as controls. The genotypes and mutations at HBV basic core promoter (BCP), precore (PC), and partial C regions were determined by nested PCR and direct sequencing. RESULTS Our results revealed significantly higher incidences (P < 0.05) of genotype B with C1913A/G or A1846T in patients with ACLF-CHB than those with CHB; genotype C with C1913A/G or A1846T in patients with ACLF-CHB and ACLF-LC than those with CHB and LC, respectively. Multivariable analysis indicated that A1846T and C1913A/G mutations were independent factors for ACLF (OR = 2.86 and 5.93, respectively), suggesting an association between the mutations and development of ACLF. In addition, there were no significant differences in mutations at T1753V, A1762T, G1764A, G1896A, and G1899A which were found between either CHB and ACLF-CHB or LC and ACLF-LC patients， suggesting no associations of these mutations with ACLF development. CONCLUSIONS Our findings suggest that CHB or LC patients infected with HBV A1846T and C1913A/G mutants are more susceptible to develop ACLF.
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Affiliation(s)
- Aimin Zhang
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
| | - Zhihong Wan
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
| | - Shaoli You
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
| | - Hongling Liu
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
| | - Bing Zhu
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
| | - Jing Chen
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
| | - Yihui Rong
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
| | - Hong Zang
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
| | - Chen Li
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
| | - Huifen Wang
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
- Corresponding authors: Huifen Wang, Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China. Tel: +86-1066933433; Fax: +86-1066933434, E-mail: ; Shaojie Xin, Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China. Tel: +86-1066933433; Fax: +86-1066933434, E-mail:
| | - Shaojie Xin
- Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
- Corresponding authors: Huifen Wang, Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China. Tel: +86-1066933433; Fax: +86-1066933434, E-mail: ; Shaojie Xin, Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China. Tel: +86-1066933433; Fax: +86-1066933434, E-mail:
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