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Galectin-9 （Gal-9） is a member of the galectin family that can specifically recognize and bind to galactosides. Recent studies have shown that Gal-9 is highly expressed in the liver and can help to maintain intrahepatic immune homeostasis and perform biological functions in various liver diseases. This article reviews the immunomodulatory functions of Gal-9 and its role in different liver diseases. Studies have shown that Gal-9 has important biological functions in different liver diseases through multiple pathways. Research on the specific immunomodulatory mechanisms and functions of Gal-9 may help to discover the therapeutic role of Gal-9 in liver diseases.
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The liver is easily affected by a variety of factors to induce liver damage, which can cause disorders in the synthesis, detoxification, metabolism, and biotransformation functions of the liver in severe cases, and at present, there is still a lack of efficient clinical treatment methods for end-stage liver diseases such as liver failure and decompensated liver cirrhosis. Recent studies have confirmed the clinical efficacy of stem cells, and treatment methods based on stem cell-derived exosomes have become a research hotspot. This article introduces the advantages of treatment based on stem cell-derived exosomes, the research advances in related mechanisms, and the current status of preclinical research. Current research findings suggest that treatment based on stem cell-derived exosomes has a good application prospect in the treatment of liver diseases, but it is still needed to conduct in-depth preclinical and clinical studies.
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Objective To investigate the application value of transjugular liver biopsy (TJLB) in the diagnosis and treatment of complicated and severe liver diseases. Methods A retrospective analysis was performed for the clinical data of 31 patients who underwent TJLB in The Fifth Medical Center of Chinese PLA General Hospital, including indication for puncture, success rate, and final diagnosis. Results Among the 31 patients, there were 15 male patients and 16 female patients. Percutaneous liver biopsy was unsuitable for 8 patients with liver failure and disturbances of blood coagulation, 13 with liver cirrhosis and ascites, and 10 with liver cirrhosis and thrombocytopenia (< 50×10 9 /L), which were the indications for TJLB. The success rate of TJLB puncture was 100%, with 2-4 passes for puncture. No serious adverse event was observed. Of all 31 patients, 26 (83.87%) had a definite diagnosis at discharge, among whom there were 5 patients with idiopathic portal hypertension, 9 patients with drug-induced liver failure or liver cirrhosis, 5 patients with autoimmune liver disease, and 7 patients with liver cirrhosis or liver failure due to other causes, and 5 patients had unknown etiology. In addition, 3 patients underwent biopsy to confirm the diagnosis and decision of whether liver transplantation should be performed. Conclusion TJLB plays an important role in the diagnosis and treatment of complicated and severe liver diseases and still has certain limitations, and therefore, suitable patients should be selected in clinical practice.
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Objective@#To investigate the concept of hepatitis B virus (HBV)-related acute-on-chronic pre-liver failure (pre-ACLF), and to develop and evaluate the diagnostic criteria for this disease.@*Methods@#A retrospective analysis was performed for the clinical data of 754 patients with severe acute exacerbation (SAE) of HBV-related chronic liver disease, and their clinical features were identified. A multivariate logistic regression analysis was used to determine the risk factors for acute-on-chronic liver failure (ACLF). The inclusion rate of patients with SAE-HBV-related chronic liver disease and the detection rate of ACLF patients were analyzed to evaluate the value of four different versions of diagnostic criteria for pre-liver failure. The t-test, an analysis of variance, the Mann-Whitney U test, and the chi-square test were used for statistical analysis based on data type.@*Results@#The incidence rate of ACLF in the patients with SAE-HBV-related chronic liver disease was 9.9% and the time to progression to ACLF was 12.0 ± 6.7 days. The multivariate logistic regression analysis showed that HBV reactivation (odds ratio [OR] = 5.118), direct bilirubin ratio (D/T) (OR = 1.041), age (OR = 1.033), total bilirubin (TBil) (OR = 1.005), prothrombin activity (PTA) (OR = 0.880), and serum sodium (Na) (OR = 0.918) were independent risk factors for ACLF. Group B (51.3 μmol/L < TBil < 171.1 μmol/L and 40%≤PTA < 60%, 4.2%) had a significantly lower incidence rate of ACLF than group A (51.3 μmol/L < TBil < 171.1 μmol/L and PTA < 40%, 13.7%) and group C (TBil > 171.1 μmol/L and 40% < PTA < 60%, 20.3%) (P < 0.001). Group C had a significantly shorter time to progression to ACLF than group A (10.5 ± 6.1 days vs 15.6 ± 7.4 days, P = 0.008). A total of 45 patients met the diagnostic criteria developed by Chongqing and the incidence rate of ACLF was 2.2%; 154 patients met the diagnostic criteria developed by Zhejiang and the incidence rate of ACLF was 7.1%; 188 patients met the diagnostic criteria in the Chinese guidelines and the incidence rate of ACLF was 6.4%; 117 patients met the diagnostic criteria for SAE-CHB and the incidence rate of ACLF was 9.4%.@*Conclusion@#At present, these four versions of diagnostic criteria for pre-liver failure are not fully applicable to the clinical practice in China. The diagnostic criteria for HBV-related pre-ACLF should include important assessment indices which affect its progression to ACLF.
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Liver failure is one of the most serious diseases in clinical practice and has a low treatment success rate. The concept of precision medicine provides more enlightenment for the treatment of liver failure. An accurate understanding of the scientific connotation of precision medicine and the application of advanced techniques can improve the accurate diagnosis of liver failure. This article elaborates on the search for new treatment targets, blockade of hepatocyte necrosis, and the application of genetic technology to realize accurate medication and individualized biotherapy for liver failure. It is pointed out that the accurate diagnosis and treatment of liver failure can improve the level of treatment.
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Objective@#To study the long-term prognosis of the convalescent patients with hepatitis B virus (HBV) associated acute-on-chronic liver failure (HBV-ACLF).@*Methods@#A 72-month follow-up study of HBV-ACLF recovery patients recruited between January 2005 and December 2009 was performed in our hospital. According to the results of imaging examination at the first visit, the enrolled patients were divided into two groups, the liver cirrhosis ACLF (Lc-ACLF) group and chronic hepatitis B related ACLF (CHB-ACLF) group. In both groups, the occurrence of cirrhosis, decompensated cirrhosis or ACLF and hepatocellular carcinoma (HCC) were observed.@*Results@#The media time of cirrhosis formation, decompensated cirrhosis and HCC occurrence in CHB-ACLF group were 12.5, 23 and 43 months, respectively. However, the median time of LC-ACLF patients developing to decompensated cirrhosis and HCC were 7 and 14 months, which was significantly shorter than that in CHB-ACLF group (P=0.009, 0.040, with statistical significance). Furthermore, the blood chemical parameters including serum albumin (ALB), cholinesterase (CHE) and total cholesterol (TC), triglyceride (TG), as well as platelet count (PLT), the anti-viral treatment compliance and the virus mutation were significantly related to the clinical endpoint events, respectively (P<0.05). Moreover, results from the logistic regression model demonstrated that the patient age, with or without liver cirrhosis, HBV mutation and the anti-viral treatment compliance were the independent risk factors for the long-term prognosis of patients with hepatitis B associated liver failure (OR=1.035, 0.510, 2.462, respectively. P< 0.05). The cumulative risk of Lc-ACLF patients progressed to decompensate cirrhosis, acute-on-chronic liver failure or HCC was significantly higher than that of CHB-ACLF patients (χ2=21.603, 4.423, P=0.000, 0.035, respectively).@*Conclusions@#Considering the importance of patients with or without liver cirrhosis, HBV mutation and the anti-viral treatment compliance in the long-term prognosis of HBV-ACLF patients, it is necessary and important to monitor the virus mutation and anti-viral treatment compliance of HBV- ACLF patients during antiviral therapy and those processes would benefit the improvement of long term prognosis of the patients with ACLF.
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Objective@#To study the clinical value of serum cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase (MMP)-9/NGAL-1 measurements for early diagnosis of acute kidney injury (AKI) in patients with acute-on-chronic liver failure (ACLF).@*Methods@#This study included 102 patients with hepatitis B virus related ACLF and 31 patients with chronic hepatitis B (CHB) were enrolled as controls. Biomarkers including serum cystatin C, NGAL and MMP-9/NGAL-1 were measured twice in the patients with ACLF at admission and at the time progressed to AKI and once in the controls.@*Results@#In patients with ACLF, serum cystatin C levels was higher than that of the CHB control (t=3.609, P=0.000), whereas NGAL and MMP-9/NGAL-1 levels were lower in patients with ACLF than that of CHB controls (t=3.016, P=0.003; t=7.514, P=0.000, respectively). Thirty-three patients (32.4%) progressed to AKI during hospitalization period. In AKI group of the patients serum cystatin C levels was higher than that of non-AKI group of the patents (t=4.543, P=0.000). MMP-9/ NGAL-1 and NGAL levels were not different in patients with and without AKI (t=0.905, P=0.368; t=0.061, P=0.952). Serum cystatin C in patients with mild AKI (serum creatinine<1.5 mg/dl) and AKI serum creatinine>1.5 mg/dl were 33.59± 9.19 ng/ml and 43.32±9.02 ng/ml respectively. That was higher than that of non-AKI patients (27.94±7.93 ng/ml, P=0.022, 0.000, respectively). Serum cystatin C was the independent risk factors associated with development of AKI by a multivariate logistic regression in patients with ACLF.@*Conclusions@#Serum cystatin C measurement may contribute to more earlier diagnosis of AKI even in patients with S. creatinine<1.5 mg/dl. NGAL and MMP-9/NGAL-1 may be the biomarker of progress for ACLF.
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Objective To evaluate the feasibility and safety of transjugular liver biopsy( TJLB) by using the LABS 200 liver access and biopsy set ( Cook Inc, USA) .Methods Five minipigs were operated though TJLB puncture under the imaging guidance.The liver biopsies were analyzed by histological examination.Results Technical success of TJLB was achieved in all the 5 minipigs.No procedure-related complications occurred, and sufficient amount of specimen for histological examination was obtained in all cases.Conclusions Our preliminary results indicate that transjugular liver biopsy with the use of Cook LABS 200 liver access and biopsy set is clinically safe and feasible, and provide technical support for its clinical application.
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Objective To establish a method for the rapid detection of hepatitis E virus (HEV)from serum samples based on fluorescence quantitative PCR.Methods (1 )One-hundred HEV sequences including our country popular three major genotypes were obtained from the GeneBank with the Vector NTI software.The proper sequence was selected to design and synthesize the primers of the fluorescence quantitation and the Taqman probe.(2)The amplification region PCR fragment was transcribed in vitro to synthesize cRNA standard,at the same time the trace serum virus lysate was introduced into a universal real-time TaqMan PCR assay.(3)10 clinical serum samples were collected from the patients with clinical hepatitis E and detected by using the established method for further verifying this method.Results This detection technique could effectively detect the serum samples in the pa-tients with genotype I and genotype IV hepatitis E positive,while the serum detection in the patients with other virus infectious dis-eases had the negative results,which verified that this RT-PCR detection technique had higher specificity and good reliability.The detection results from 10 clinical serum samples further verified that this method was rapid,convenient and sensitive with good re-peatability.Conclusion A fluorescence quantitative RT-PCR detection technique suitable for detecting main genotypes of HEV in China population is established,which can meet the demand of early and rapid diagnosis for HEV.
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<p><b>OBJECTIVE</b>To study the clinical characteristics of patients with alcoholic liver disease (ALD).</p><p><b>METHODS</b>The records of the 302 Hospital of People's Liberation Army (Beijing, China) were searched to identify patients diagnosed with liver disease for retrospective analysis of ALD. Measurement data was summarized as mean +/- standard deviation and intergroup comparisons were made using ANOVA; count data was assessed using the chi-square test.</p><p><b>RESULTS</b>Among the total 4132 ALD cases, 97.68% were male and 2.32% were female; ages ranged from 18 to 95 years-old,with the average age being 48.11+/-10.58 years and the range of 40 to 60 years-old being the most frequently represented.Considering all patients with liver disease from 2003 to 2012,ALD cases increased over time (from 2.00% in 2003 to 5.05% in 2012). The overall ALD cases were represented by alcoholic cirrhosis (70.35%), alcoholic hepatitis (19.26%), alcoholic fatty liver (6.29%), and alcoholic liver failure (4.09%). Among the ALD patients between 40 and 60 years of age, 73.81% had cirrhosis,compared to 50.42% of ALD patients less than 40 years-old (P less than 0.001). Comparison of ALD cases in 5-year increments showed increasing trends in rates of alcoholic cirrhosis and alcoholic hepatic failure;moreover, there was an increasing annual trend in the percentage of alcoholic liver failure cases among the total cases of liver failure in our hospital.</p><p><b>CONCLUSION</b>From 2003 to 2012,our hospital admissions increased for patients with alcoholic liver disease, and the patients were primarily in the age range of 40-60 years-old. In general, incidences of alcoholic liver failure and cirrhosis increased in recent years, and cirrhosis has been common among the elderly patients with ALD.</p>
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Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Pequim , Fígado Gorduroso Alcoólico , Epidemiologia , Hepatite Alcoólica , Epidemiologia , Incidência , Cirrose Hepática , Epidemiologia , Hepatopatias Alcoólicas , Epidemiologia , Falência Hepática , Epidemiologia , Estudos RetrospectivosRESUMO
A high proportion of the causes of liver failure remain unknown. This paper reviews the progress in the epidemiology, etiology, treatment, and prognosis of liver failure of unknown etiology. The possible causes of liver failure of unknown etiology may include occult hepatitis B virus infection, herpesvirus infection, transfusion-transmitted virus infection, hepatitis G virus infection, human parvovirus Bl9 infection, autoimmune and hepatitis. Aciclovir can be considered in the empirical treatment for patients with liver failure of unknown etiology. The mortality in patients with liver failure of unknown etiology is high. The research on the etiology and treatments should be strengthened.
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Objective To explore the function of the baseline model for end-stage liver disease (MELD) scores,MELD-Na scores and iMELD scores in short-term prognosis in the initial treatment of hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF) patients.Methods 232 HBV-related ACLF patients who received initial treatment in 302 Military Hospital of China from January 2011 to January 2013 were enrolled in this prospective clinical follow-up.The relationship between the baseline MELD scores,MELD-Na scores,iMELD scores and clinical outcomes were analyzed,and the value of these three models for short term prognosis was assessed.Results Finally the 12-week clinical follow-up was completed in 191 patients,with the completion rate of 82.33％.Eighty-five patients died,with the fatality rate of 44.50％.Compared with the survival group,in non-survival group,the baseline of MELD scores (26.65 ± 7.75 vs.21.19 ± 5.42,t=-5.720,P=0.000),MELD-Na scores (29.16 ± 11.35 vs.21.72 ± 6.33,t=-5.729,P=0.000),iMELD scores (47.19 ± 10.96 vs.38.02 ±7.01,t=-7.011,P=0.000),total bilirubin [TBil (μmol/L):374.3 ± 150.1 vs.305.5 ± 147.1,t=-3.182,P=0.002],creatinine [Cr (μmol/L):110.7 ±90.1 vs.71.1 ± 35.1,t=-4.157,P=0.000] and international normalized ratio (INR:2.3 ± 0.9 vs.2.0 ± 0.6,t=-2.754,P=0.006) were significantly increased,but the baseline of serum Na+ (mmol/L:132.8 ± 6.1 vs.136.7 ± 5.1,t=4.861,P=0.000) was significantly lowered.It was shown by Spearman correlation analysis thai the baseline MELD scores,MELD-Na scores and iMELD scores all had positive correlation with the short-term prognosis of patients (r value was 0.398,0.404,and 0.470,respectively,all P=0.000),the baseline of serum Na+ had a negative correlation with the short-term prognosis of patients (r=-0.365,P=0.000).It was shown by receiver operating characteristic curve (ROC curve) that the cut-off scores of the baseline of MELD scores,MELD-Na scores and iMELD scores were 25.07,25.43 and 43.11 respectively,and the area under ROC curve (AUC) of the baseline of MELD scores,MELD-Na scores and iMELD scores were 0.731,0.735 and 0.773,respectively.The sensitivity of the three models was 55.3％,57.7％,63.5％,and the specificity was 84.9％,84.0％,84.9％ respectively.The value of the three models had no difference in short-term prognostic prediction.According to the respective cut-off score,the three prediction models were divided into four groups,and all of them had differences in fatality rate on the whole (x2 for MELD scores was 34.740,P=0.000; x2 for MELD-Na scores was 36.861,P=0.000; x2 for iMELD scores was 50.127,P=0.000).The mortality was elevated gradually as the equation scores increased.Conclusion The baseline of MELD scores,MELD-Na scores and iMELD scores can predict well the short-term prognosis of the initial treatment in HBV-related ACLF patients,and have relatively good clinical value for guiding therapy.
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Objective To investigate the value of liver function indexes(AApea index) in evaluation of chronic hepatitis pathohistological grading.Methods The biochemical tests and histopathological data of 800 patients who underwent liver biopsy with step discriminant screen,serum ALT,TBil,AST,A/G,EP,PA,and ALB were assayed.A liver function index(AApea index) was calculated according to these biochemical tests,and compared with histopathological data in each patient.Results The AApea index had a significantly positive correlation with the histological inflammatory grading,fibrosis staging,and severe degree(correlation coefficient were 0 559,0 545 and 0 529 respectively,P
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Objective To explore the clinical features of severe acute respiratory syndrome (SARS). Methods Clinical data of 70 patients with SARS were retrospectively analyzed. Results The age of the patients ranged from 10 to 74 years old (mean age 33.81?12.73 years). Severe type of SARS was diagnosed in 38 patients and 32 as common type of SARS. The most common symptoms included fever(98.57%), malaise(80.00%), cough(74.28%), shortness of breath (55.71%), headache(38.57%). The fever lasted for 7.20?4.57d. Based on the symptoms and chest X-ray examination, the disease was classified into early stage, progressive stage, and recovery stage with a mean duration of 3.19?2.32d, 8.18?4.36d, and 8.82?7.01d, respectively. It was found that the incidence of severe type of SARS was higher with the increase of age. Compared with common type of SARS, the fever in patients with severe type of SARS was more difficult to control (the mean highest fever 38.74?0.97℃, 38.02?0.14℃, respectively). The duration of fever after treatment (4.12?3.19d, 2.37?1.75d, respectively) was longer in the illness course (27.78?9.99d, 14.93?5.80d, respectively). The ALT, LDH and HBDH in patients with severe type of SARS were higher than those in patients with common type of SARS (ALT:78.95%,50.00%, respectively; LDH, HBDH:42.11%, 18.75%, respectively). Advanced age, pre-existing chronic disease, and elevation of LDH and HBDH were the factors of poor prognosis. Combination therapy was the first choice for the treatment of SARS. Empirical use of glucocorticoid was useful in preventing progression of the disease. Conclusion Although severe type of SARS had a high mortality, combination therapy could be very effective in the treatment of the majority of patients.
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Objective To appraise the clinical therapeutic effects of lamivudine in patients with chronic hepatitis B, and the recurrence of the disease after withdrawal of the drug. Method 122 patients with chronic hepatitis B treated with lamivudine were followed-up for over half a year after withdrawal. Result It was shown that, among the 9 cases in immunological tolerance stage and received lamivudine treatment, 4 showed effective result and ineffective in 5. All the 4 patients with effective result recurred within 6 months after lamivudine withdrawal. Among the 113 patients in non-immunological tolerance, 13 showed notable effective result (11.50%), 90 effective (79.65%) and 10 showed ineffective result (8.85%), respectively. The disease in 11 patients showing effective result recurred during the treatment. The rate of recurrence was 53.85% and 87.34% respectively in patients with notable effective and effective results. The level of ALT before lamivudine treatment showed no significant difference between the patients with abrupt and gradual withdrawal of lamivudine treatment, but it was significantly different after lamivudine withdrawal. The rate of recurrence showed no significant difference between patients with abrupt and gradual withdrawal of the drug. Conclusion The therapeutic effect of lamivudine is poor in immunological tolerant patients. Patients with chronic hepatitis B are likely to recur after lamivudine withdrawal. Lamivudine should be given for a long-term to inhibit persistent HBVDNA replication.
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To investigate MT 1 MMP mRNA expression in the development of liver fibrosis and during the reversal of liver fibrosis ,we undertook a dynamic observation by situ hybridization. Liver fibrosis model was established by intraperitoneal injection with CCl 4 in Wistar rats, then allowed them fo recover spontaneously to observe the reversal of liver fibrosis .The results showed that MT 1 MMP mRNA was expressed mainly in mesenchymal cells(such as hepatic stellate cell), also in a part of hepatocytes.The levels of MT 1 MMP mRNA expression were increased gradually in the development of liver fibrosis and decreased gradually during reversal of liver fibrosis. These results suggest that the expression of MT 1 MMP may have an important role in the development of liver fibrosis and its reversal.