Establishment and validation of a nomogram for predicting the risk of liver inflammation in chronic HBV infection

Objective:To establish a non-invasive quantitative and visual predictive model for assessing the occurrence of significant inflammation in chronic HBV infection,and to present nomogram to validate the efficacy.Methods:A total of 180 patients with chronic HBV infection that were admitted to the Department of Infectious Liver Diseases of the First Affiliated Hospital of Hainan Medical College from January 2019 to December 2021 with informed consent and underwent liver biopsy puncture were selected,and to prevent overfitting of the model,131 patients and 49 patients were randomly divided into a model group and a validation group according to randomization,to collect the clinic information,serological examination,liver elastography and liver histopathology results.The patients were divided into non-significant inflammation and significant inflammation groups in the modeling group.The R 4.1.1 package and the rms package were used to build the column line graph model,while the Bootstrap method was applied to repeat the sampling 1000 times for internal and external validation,and the H-L goodness of fit test and ROC curve were used to assess the calibration and discrimination of the column line graph model respectively.Results:A total of 180 patients with chronic HBV infection were included,and 92 patients(51.1%)had significant inflammation.In the modeling set,67 patients(51.1%)had significant inflammation.In the modeled group,comparison of HBV DNA,PLT,ALT,AST,ALP,GGT,PAB,H.A,PⅢP,CⅣ,L.N,IL-6,LSM and HBeAg for non-significant inflammation and significant inflammation showed statistically significant differences(P<0.05).Nomogram were obtained using stepwise regression analysis to establish a predictive model for the risk of significant inflammation following chronic HBV infection.The χ^(2) values of the H-L goodness-of-fit test for the modelling and validation groups were 0.279 and 2.098,respectively,corresponding to P values of 0.87 and 0.35,suggesting that the nomogram has good predictive accuracy;the area under the ROC curve of the column line plot predicting the occurrence of significant inflammation after HBV infection for the modelling and validation groups was 0.895[95%CI(0.843-0.948)]and 0.760[95%CI(0.622-0.897)],suggesting that the column line plot model has good discrimination.Conclusion:After stepwise regression analysis,it was established that PLT,Ln(HBV-DNA),AST,C桇and LSM were more closely associated with the occurrence of significant inflammation after HBV infection,and a visualization of the occurrence of significant inflammation nomogram was established by comprehensive assessment,and the effectiveness was good.

Numerical Procedure for Fractional HBV Infection with Impact of Antibody Immune

The current investigations are presented to solve the fractional order HBV differential infection system(FO-HBV-DIS)with the response of antibody immune using the optimization based stochastic schemes of the Levenberg-Marquardt backpropagation(LMB)neural networks(NNs),i.e.,LMBNNs.The FO-HBV-DIS with the response of antibody immune is categorized into five dynamics,healthy hepatocytes(H),capsids(D),infected hepatocytes(I),free virus(V)and antibodies(W).The investigations for three different FO variants have been tested numerically to solve the nonlinear FO-HBV-DIS.The data magnitudes are implemented 75%for training,10%for certification and 15%for testing to solve the FO-HBV-DIS with the response of antibody immune.The numerical observations are achieved using the stochastic LMBNNs procedures for soling the FO-HBV-DIS with the response of antibody immune and comparison of the results is presented through the database Adams-Bashforth-Moulton approach.To authenticate the validity,competence,consistency,capability and exactness of the LMBNNs,the numerical presentations using the mean square error(MSE),error histograms(EHs),state transitions(STs),correlation and regression are accomplished.

Significant increase in HBV, HCV, HIV and syphilis infections among blood donors in West Bengal, Eastern India 2004-2005: Exploratory screening reveals high frequency of occult HBV infection

AIM: To evaluate the prevalence of markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among blood donors in Kolkata, Eastern India for two consecutive years and to conduct a pilot study to explore the presence of HBV DNA among hepatitis B surface antigen (HBsAg) negative but anti-HBc positive blood donors. METHODS: Seroprevalence of HBsAg, anti-HCV and anti-HIV was studied among 113 051 and 106 695 voluntary blood donors screened in 2004 and 2005, respectively. Moreover, a pilot study on 1027 HBsAg negative donors was carried out for evaluating the presence of HBV DNA by PCR on HBsAg negative/anti- HBc positive donors. RESULTS: A statistically significant increase in the prevalence of HBV (1448 vs 1768, P < 0.001), HIV (262 vs 374, P < 0.001), HCV (314 vs 372, P = 0.003) and syphilis (772 vs 853, P = 0.001) infections was noted among blood donors of Kolkata West Bengal in 2005 as compared to 2004. Moreover, the exploratory study on 1027 HBsAg negative donors revealed that 188 (18.3%)of them were anti-HBc positive out of which 21% were positive for HBV DNA. CONCLUSION: The findings of this study underscore the significantly increasing endemicity of hepatitis viruses, syphilis and HIV among the voluntary blood donors of our community. The pilot study indicates a high rate of prevalence of HBV DNA among HBsAg negative/anti-HBc positive donors and thus emphasizes the need for a more sensitive and stringent screening algorithm for blood donations.

DYNAMICAL BEHAVIOR OF A STOCHASTIC HBV INFECTION MODEL WITH LOGISTIC HEPATOCYTE GROWTH

This paper is concerned with a stochastic HBV infection model with logistic growth. First, by constructing suitable stochastic Lyapunov functions, we establish sufficient conditions for the existence of ergodic stationary distribution of the solution to the HBV infection model. Then we obtain sufficient conditions for extinction of the disease. The stationary distribution shows that the disease can become persistent in vivo.

Prevalence of occult HBV infection in haemodialysis patients with chronic HCV

AIM： To study the prevalence and clinical effects of occult HBV infection in haemodialysis patients with chronic HCV.METHODS： Fifty chronic hemodialysis patients with negative HbsAg, and positive anti-HCV were included in the study. These patients were divided into two groups： HCV-RNA positive and HCV-RNA negative, based on the results of HCV-RNA PCR. HBV-DNA was studied using the PCR method in both groups.RESULTS： None of the 22 HCV-RNA positive patients and 28 HCV-RNA negative patients revealed HBV-DNA in serum by PCR method. The average age was 47.2±17.0 in the HCV-RNA positive group and 39.6±15.6 in the HCV-RNA negative group.CONCLUSION： The prevalence of occult HBV infection is not high in haemodialysis patients with chronic HCV in our region. This result of our study has to be evaluated in consideration of the interaction between HBsAg positivity （8%-10%） and frequency of HBV mutants in our region.

GLOBAL ASYMPTOTICAL PROPERTIES FOR A DIFFUSED HBV INFECTION MODEL WITH CTL IMMUNE RESPONSE AND NONLINEAR INCIDENCE

This article proposes a diffused hepatitis B virus （HBV） model with CTL immune response and nonlinear incidence for the control of viral infections. By means of different Lyapunov functions, the global asymptotical properties of the viral-free equilibrium and immune-free equilibrium of the model are obtained. Global stability of the positive equilibrium of the model is also considered. The results show that the free diffusion of the virus has no effect on the global stability of such HBV infection problem with Neumann homogeneous boundary conditions.

Efficiency and safety of lamivudine therapy in patients with chronic HBV infection, dialysis or after kidney transplantation

AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well tolerated and safe in patiente with renal insufficiency undergoing hemodialysis and kidney-transplantation. However, in the latter group, high incidence of YMDD mutation after lamivudine treatment was observed.

Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers

AIM： To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. METHODS： Twenty-three patients receiving anti-HBc positive liver were studied. Nine recipients were anti-HBc positive as a result of previous HBV infection. Of them, one also received HBV vaccine during the pre-liver transplantation period. Fourteen recipients were anti-HBs positive due to HBV vaccine administered during the pretransplant period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive recipients and in 4/9 anti-HBc positive recipients. RESULTS： After a mean foUow-up period of 46 months, 1 recipient with protective serum anti-HBs levels developed de novo HBV infection as a consequence of immune escape HBV mutants. Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10 patients with available liver biopsy （10%） had liver HBV-DNA at 13 mo post-liver transplantation without serum viral markers and did not develop de novo HBV infection.The vaccinated anti-HBc positive recipient without HBV vaccine response was HBV-DNA positive in serum and liver, viral DNA was continuously negative in the following tests, so a spontaneous seroconversion was diagnosed. CONCLUSION： The presence of anti-HBs as a result of HBV vaccine or past HBV infection seems to be effective at protecting patients receiving livers from anti-HBc positive donors. However, the emergence of immune escape HBV mutants, which can evade the anti-HBs protection, should be considered as a risk of HBV infection.

Synergistic Action of Clonorchiasis,HBV Infection and Alcohol Consumption on Primary Hepatocellular Carcinoma

OBJECTIVE It has been recognized that HBV infection and alcohol consumption are two important risk factors for primary hepatocellular carcinoma （HCC）. Recently, the role of clonorchiasis as a risk factor for HCC is controversial. We aimed to investigate whether these factors increase the risk of HCC in Guangxi, China. METHODS A hospital-based, case-control study of HCC was conducted from July 2005 to July 2007. We enrolled 500 consecutive patients with HCC as an experimental group and 500 patients without tumor in liver as a control group. The risk factors that the patients were exposed to were assessed. RESULTS Comparing the risks of developing the HCC, we found out the following results. The risk of developing HCC for the patients with clonorchiasis was 5 folds of that for the patients without clonorchiasis （OR = 5.0; 95% CI： 3.1-8.1）, and the risk for the patients with alcohol consumption was 3 folds of that for the patients without drinking alcohol （OR = 3.4; 95% CI： 2.3-4.9）, and similarly, the risk for the patients with HBV infection was 21 times of that for the patients without HBV infection （OR = 20.6; 95% CI： 14.3-29.7）. According to crossover analysis, there was significant interaction among clonorchiasis, HBV infection and alcohol consumption, with synergistic indices greater than 1. The etiologic fractions attributed to these interactions [EF （A × B）] are 0.7465, 0.5789 and 0.5506, respectively. CONCLUSION Clonorchiasis, HBV infection and heavy alcohol consumption are independent risk factors for developing HCC in our population in Guangxi, and as they can interact synergistically, the risk of developing HCC is increased. Data from this study may indicate new prevention strategies of developing HCC in high-risk individuals.

Establishment and Validation of a nomogram for Predicting the Risk of Liver Fibrosis in Chronic HBV Infection

Objective:To establish a non-invasive quantitative and visual predictive model for assessing the occurrence of significant fibrosis in chronic HBV infection,and to present nomogram to validate the efficacy.Methods:A total of 180 patients with chronic HBV infection that were admitted to the Department of Infectious Liver Diseases of the First Affiliated Hospital of Hainan Medical University from January 2019 to December 2021 with informed consent and underwent liver biopsy puncture were selected.131 patients and 49 patients were randomly divided into a model group and a validation group according to randomization.The patients were divided into non-significant fibrosis and significant fibrosis groups in the modeling group.To collect the clinic information,serological examination,liver elastography and liver histopathology results and to establish a rosette model to predict the risk of chronic HBV infection with significant fibrosis.Results:A total of 180 patients with chronic HBV infection were included,and 113 patients(62.7%)had significant fibrosis.In the modeling set,84 patients(64.1%)had significant fibrosis.In the modeled group,comparison of HBV DNA,PLT,ALT,AST,ALP,ALB,PAB,IL-6,HA,PⅢP,CIV,L.N and LSM for non-significant fibrosis and significant fibrosis showed statistically significant differences.The χ^(2) values of the H-L goodness-of-fit test for the modelling and validation groups were 4.988 and 0.527,respectively,corresponding to P values of 0.08 and 0.77,suggesting that the nomogram has good predictive accuracy;the area under the ROC curve of the column line plot predicting the occurrence of significant fibrosis after HBV infection for the modelling and validation groups was 0.843[95%CI(0.775-0.910)]and 0.776[95%CI(0.714-0.838)],suggesting that the column line plot model has good discrimination.Conclusion:After stepwise regression analysis,it was established that ALB,HA,PⅢP,LSM and IL-6 were more closely associated with the occurrence of significant fibrosis after HBV infection,and a visualization of the occurrence of significant fibrosis column line graph model was established by comprehensive assessment,and validation was given that all were superior to the traditional models FIB-4 and APRI.

IL-6 Plays a Crucial Role in HBV Infection

Interleukin-6(IL-6),a cytokine mainly produced by activated monocytes,has broad pleiotropic actions that affect the functions of a variety of lymphoid cells.The roles of IL-6 in regulating immunity to infections are currently being defined.Remarkably,IL-6-mediated cellular and humoral immune responses play a crucial role in determining the outcome of viral infection.This article reviews the current knowledge on the critical role of IL-6 in hepatitis B virus(HBV)infection.As a competent intermediary,IL-6 derived from activated monocytes plays an important role in promoting lymphocytes responses that are essential for effective viral control.However,as a mediator of inflammation,IL-6 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury.Overall,the current data point to IL-6 as an immunoregulatory cytokine in HBV infection.Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-6 in HBV infection may prove to be an ordeal in the future,as they should foster the strengths of IL-6 while circumventing potential drawbacks.

GLOBAL STABILITY OF ENDEMIC EQUILIBRIUM POINT OF BASIC VIRUS INFECTION MODEL WITH APPLICATION TO HBV INFECTION

In this paper, the authors first show that if Ro ≤1, the infection free steady state is globally attractive by using approaches different from those given by Min, et a1.（2008）. Then the authors prove that if Ro 〉 1, the endemic steady state is also globally attractive. Finally, based on a patient＇s clinical HBV DNA data of anti-HBV infection with drug lamivudine, the authors establish an ABVIM. The numerical simulations of the ABVIM axe good in agreement with the clinical data.

New Gene Variants Associated with the Risk of Chronic HBV Infection

Some patients with chronic hepatitis B virus(HBV)infection failed to clear HBV,even persistently continue to produce antibodies to HBV.Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV.The first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive)compared with 102 control patients(antiHBs positive,HBsAg negative).Over 80%of individual sequences displayed 209 sequence coverage.Adapters,uncertain bases[10%or low-quality base calls([50%)were filtered and compared to the human reference genome hg19.In the second stage,579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage.Although there were no significant associated gene variants in the first stage,two significant gene associations were discovered when the two stages were assessed in a combined analysis.One association showed rs506121-“T”allele[within the dedicator of cytokinesis 8(DOCK8)gene]was higher in chronic HBV infection group than that in clearance group(P=0.002,OR=0.77,95%CI[0.65,0.91]).The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9)gene that was significantly elevated in chronic HBV infection group compared to the clearance group(P=0.0003,OR=1.35,95%CI[1.15,1.58]).Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection.

New perspective on the natural course of chronic HBV infection

Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.

The Expression of CD2 in Chronic HBV Infection

It was previously reported that several kinds of intercellular adhesion molecules are closely related to chronic HBV infection. The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells, and promoting hyperplasia and activation of T lymphocytes. In this study, we detected the level of CD2 expressed on the surface of PBMC, the expression level of CD2 mRNA in PBMC and the percentage of CD2 positive cells in PBMC of patients with chronic HBV infection and compared them with the expression level of normal controls. We also determined the level of serum HBV DNA from patients with chronic HBV infection and from normal controls. The clinical characteristics of hepatic function were tested as well. The results showed that the expression of CD2 significantly increased with the severity of chronic HBV infection, which suggested that CD2 might contribute to the hepatocyte damage in chronic HBV infection. Cellular ＆ Molecular Immunology.

Dynamics of a diffusion-driven HBV infection model with capsids and time delay

In this paper, a diffusive hepatitis B virus （HBV） infection model with a discrete time delay is presented and analyzed, where the spatial mobility of both intracellular capsid covered HBV DNA and HBV and the intracellular delay in the reproduction of infected hepatocytes are taken into account. We define the basic reproduction number R0 that determines the dynamical behavior of the model. The local and global stability of the spatially homogeneous steady states are analyzed by using the linearization technique and the direct Lyapunov method, respectively. It is shown that the susceptible uninfected steady state is globally asymptotically stable whenever R0 ≤i and is unstable whenever R0 〉1. Also, the infected steady state is globally asymptotically stable when R0 〉 1. Finally, numerical simulations are carried out to illustrate the results obtained.

HBV and HCV infection and pancreatic ductal adenocarcinoma

Introduction Pancreatic ductal adenocarcinoma(PDAC)is a highly lethal malignancy,with a poor overall fiveyear survival.Its dismal prognosis,even after curative resection,depends on its advanced stage at diagnosis,early metastatic spread,aggressive biological behavior and inefficacy of available systemic therapies.[1]To date,epidemiological studies have identified some risk factors for this cancer,including cigarette smoking habit,family history as well as high dietary fat consumption,alcohol abuse,diabetes mellitus,metabolic syndrome and chronic pancreatitis history.[1]

Interest of Non-Invasive Markers (APRI, FIB-4) for Assessing Hepatic Fibrosis in Patients with Chronic Viral Hepatitis B without Cytolysis and with Low Viral Replication

Background and Objectives: The indication for treatment in HBsAg-positive patients with low viral load and normal transaminases requires an assessment of fibrosis. In resource-limited settings, free hepatic fibrosis evaluation tests can aid in therapeutic decision-making. Our study aims to demonstrate the utility of assessing hepatic fibrosis using non-invasive markers (APRI and FIB-4) in patients with chronic B viral hepatitis without cytolytic activity and low viral replication in our context. Patients and Methods: This is a retrospective cross-sectional study conducted between January 2018 and December 2021 at the University Hospital Center of Bouaké. Included were all patients aged ≥18 with normal transaminases (Results: Our study included 241 patients, with a mean age of 36.19 years (±10.52 years) and a male predominance of 52%. The mean FibroScan® value was 6.44 ± 2.3 kPa, and 68 patients (28.22%) had fibrosis >7 kPa. To exclude significant fibrosis (FS Conclusion: A significant proportion of HBV-infected patients with normal ALT and low viral load have active liver disease. Both FIB-4 and APRI biological scores are useful in identifying individuals without significant fibrosis with a good negative predictive value (>50%).

Seroprevalence of Hepatitis B Virus (HBV) among Voluntary Healthy Blood Donors at Tellewonyan Memorial Hospital Voinjama, Lofa County, Liberia

Background: The prevalence of transfusion associated hepatitis B virus (HBV) infection differs across different population geographically. Ascertaining the seroprevalence of HBV infection is vital to informing the way of precautionary and control strategies. This study sought to establish the seroprevalence of hepatitis B surface antigen (HBVsAg) among blood donors in Yelewonyan Memorial Hospital Lofa, Liberia. Methods: This was a retrospective study which involved reviewing of blood donation records for the year 2020 at Telewonyan Memorial Hospital in Lofa County. The data obtained from the records were analyzed. Data analysis was done using SPSS version 12 for windows. Results: A total of 584 voluntary blood donors were screened for donation in 2020. Out of 584, 554 (95.9%) were males while the rest were females. Prevalence of 3.3% was observed among blood donors in Telewonyan Memorial Hospital. There is a significant difference between gender and age with HBV seropositivity among blood donors. Conclusion: The findings of this study suggest that the study site is of low endemicity with HBV infection. Usually, males are more probably to be HBVsAg seropositive than their female’s counterpart. Planning more extensive study and educational programs would help minimize the spread of HBV infection among the general population.

Baseline HBV Load Increases the Risk of Anti-tuberculous Drug-induced Hepatitis Flares in Patients with Tuberculosis

Hepatitis associated anti-tuberculous treatment（HATT） has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus（HBV）. Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of 〉3, 5, and 10 times the upper limit of normal（ULN） were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin（TBil） levels that were more than 10 times the ULN（〉171 μmol/L） with or without decreased（〈40%） prothrombin activity（PTA） were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8%（n=52） and 25.3%（n=22）, respectively. The following variables were correlated with the severity of hepatotoxicity： albumin（ALB） levels, PTA, platelet counts（PLT）, and the use of antiretroviral therapies（P〈0.05）. Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio（OR） of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.