The Study For Short-term Prognosis With The Hepatitis B Surface Antigen Level And Viral Loads In Patients With Acute-on-chronic Hepatitis B Liver Failure

BackgroundHepatitis B virus(HBV) infection is epidemic worldwide. According to the world health organization (WHO) reported,there were 2 billion people infected,with approximately 350 million people chronically infected. Our country is high endemic area of HBV infection, of 93 million people in chronic HBV infection, of them about 20 million people with chronic hepatitis B patients, including 10-20% progress to liver cirrhosis, liver failure. Many scholars think, liver failure is a state of severe damage to the liver and regeneration is insufficient, is also caused by excessive systemic inflammatory cytokine expression resulting in a dynamic process of multiple organ failure. According to the pathological and histological characteristics of hepatic failure and illness development speed, hepatic failure can be divided into four categories:acute liver failure(ALF), subacute liver failure (SALF), acute-on chronic liver failure(ACLF), chronic liver failure (CLF). Acute-on chronic liver failure (ACLF) is on the basis of chronic liver disease in a clinical manifestation of acute decompensated liver function, of the most common clinical type in liver failure. In China, ACLF is mostly caused by hepatitisB virus infection,which was estimatedover 90% of ACLF, called hepatitis B related to acute on chronic liver failure (HB-ACLF), is the important part of hospitalized patients with liver disease in our country. These patients were in a critical condition, with the high cost of treatment, poor prognosis, many complications, high mortality of 50-80% [A12 or B4], lack of effective specific interventions. Currently, the most effective treatment is liver transplantation. How to forecast the prognosis of HB-ACLF is clinical key question, therefore, analysis of HB-ACLF prognosis factors helps us to provide further reference for clinical treatment strategies. From more than 40 years ago the Child-Pugh (CTP) established, Kamath et al.created prognosis prediction model of end-stage liver disease provided a new evaluation system in 2001, the model for end-stage liver diseases(MELD), and in 2002 formally adopted as the predicted survival of patients with liver transplantation model. Child-Pugh and MELD score are still the most widely used and reported as the prognosis of liver failure assessment system.But the limitations of CTP classification is used two subjective indicators: ascites and hepatic encephalopathy; MELD score mainly depends on clinical measurements, but does not take into account the different causes of liver failure.In our country, most of live failure associated with HBV infection, such as liu xiaoyan et al. summarized 1977 cases of liver failure in our country, which had 90.29% HB-ACLF,.But the MELD and CTP score do not analyse HBV infection in detail. Seeking to accurately apply evaluation of HB-ACLF prognostic indicators, it can provide basis to select the appropriate treatment and improve the reliable basis for rational allocation of health resources。It is generally believed that both host factors and hepatitis B virus are involved in the pathogenesis of HB-ACLF, though the mechanism remains unclear. It has been reported that the strength of the virus virulence and the body’s immune system are associated with the development of disease. It has been reported that the strength of the virus virulence and the body’s immune system are associated with the development of disease. Serum HBsAg is a major sign of HBV infection, with the development of the research, HBsAg is more important in the treatment of chronic hepatitis B. Hepatitis B virus can influence the progress of ACLF prognosis,however different opinions exist. Recently,few researches has investigated the relationship between HBsAg level and HBVDNA loads with the prognosis of HB-ACLF with existing controversial.So it need further study to confirm. In addition, how these factors play a role of ACLF evolution process, is also not clear.In the present study, we collected samples from HB-ACLF patients during January 2009 to January 2013 with retrospective statistical analysis. According to the different prognosis of patients, we analysed the relationship of serum HBsAg levels or serum HBV DNA loads and the development of acute-on-chronic liver failure,analyzing the difference with the common hepatic failure assessment system of MELD or Child-Pugh score to HB-ACLF prognosis prediction. We try to search for HB-ACLF early warning indicators,and explore the possible mechanism of these factors in the process of disease development.Chapter One:Relationship of serum HBsAg level and short-term prognosis of patients with acute on chronic liver failure related to hepatitis BObjectiveTo analyse the serum HBsAg levels of HB-ACLF patients between survival and deterioration group with retrospective statistical analysis, to investigate whether the serum HBsAg level has early warning to recent prognosis of HB-ACLF.MethodsA total of 177 patients with HBV-related acute-on-chronic liver failure were enrolled from Guangzhou Eighth People’s Hospital during January 2009 to January 2013, and the diagnosis liver failure was followed by The Prevention and Treatment Proposal of Liver failure established in 2012. The patients needed medical treatment more than 10 days. Exclusion criteria:the other overlapping etiological liver virus infection, HIV infection, alcoholic liver disease, poisoning, autoimmune disease or genetic metabolic liver disease, drug-induced liver damage; liver cancer patients; long-term anticoagulation for other diseases; kidney disease and renal failure. Illness prognosis judgement standard:since the recent prognosis refers to the patients admitted to hospital after 12 weeks of outcome, divided into survival and deterioration group. Deterioration group is refers to the patient condition worsens, give up the treatment or death in hospital; survival group means the patients improve in the hospital and more than 12 weeks back to hospital, or no back to hospitall to make a phone call to the patients or family members to determine the survival or death.The research collected patients clinical data and baseline clinical examination indexes in the peak of total bilirubin. clinical data included:age(year)、gende、hostipal stays、serum total bilirubin(TB,μmol/L)、serum albumin(ALB,g/l)、 prothrombin(PTA,%)、international normalized ratio(INR)、serum creatinine(Cr, μmol/l)、serum sodium (Na+, mmol/l)、white blood cells (WBC,109/L)、platelet (PLT,109/L)、HBsAg quantification(COI)、ultrasound. For reducing the deviations, the measurement data included HBsAg quantification (COI) was transformed logarithm with base 10,and calculated MELD score and Child-pugh score. Measurement data results were given as mean ±SD. Independent sample T test was used by measurement data comparison between two groups. The normal distribution of the variable data used Pearson correlation analysis, but not normal distribution used spearman inspection. The receiver-operating characteristic curve (ROC) about HBsAg levels is used to assess the prognosis,and calculated the area under the ROC curve (AUC). P-value of< 0.05 was considered statistically significant.ResultsThe study enrolled 177 patients with HBV-related acute-on-chronic liver failure, including deterioration group 61 cases, survival group 116 cases.139 patients had the detection of HBsAg levels, including deterioration group 47 cases, survival group 92 cases.(1) 177 patients of ACLF included 156 cases (88.1%) of men and 21 cases (11.9%) of women, survival groups:102 cases (87.9%) of men and 14 cases (12.1%) of women,; deterioration groups:man 54 cases (88.5%), women 7 cases (11.5%),the prognosis in gender differences between the two groups has no statistical significance (x2=0.013, P=0.013).The age of survival group was 46.56±12.21, the age of deterioration groups was 40.42±11.66, the differences between the two groups has no statistical significance (P=0.882).(2) The relationship with prognosis between MELD and Child-Pugh scoreMELD score of deterioration group with 61 cases is higher than the survival group(32.17±7.42 vs 25.64±5.44), the difference was statistically significance (P< 0.005); MELD score of deterioration group is higher than the survival group (12.43± 1.47 vs.11.31+/-1.09), the difference was statistically significance (P<0.005)。(3) The relationship between recent prognosis and serum HBsAg levelThe study enrolled 139 patients with detecting HBsAg level with HBV-related acute-on-chronic liver failure, including deterioration group of 47 patients,with the average quantity for HBsAg level is 3.54±0.36Log10 (COI); survival group of 92 patients, with the average quantity for HBsAg level is 3.67±0.41Logio(COI). The average of HBsAg level of survival group is significantly higher than deterioration group (t=-3.138, P<0.05), through correlation analysis, quantitaty of HBsAg level and recent survival were positively correlated (r=0.259, P=0.002)(4) The correlation between serum HBsAg level and MELD、Child-Pugh scoreHBsAg level and MELD score was significantly negative correlation (r=-0.450. P均<0.001), HBsAg level and Child-Pugh score was significantly negative correlation (r=-0.397, P<0.001)。(5) The evaluation of HBsAg level to deterioration or survival group to the short-term prognosis of patients with ACLF predictionTo establish the ROC curve of HBsAg level, area under the curve (AUC), the area under the curve (AUC) of our model is 0.657 (95%CI:0.564-0.751, P=0.002), the cut-off to distinguish the critical value of HBsAg levels between the two groups was 6261 COI, the sensitivity was 0.587,the specificity was 0.745.Conclusion(1) The relationship with prognosis between MELD and Child-Pugh score The higher the MELD or Child-Pugh score, poor prognosis, the same as the results of previous studies.(2)Survival group of patients with HBsAg levels higher than the deterioration group of patients.(3) According to the serum HBsAg level, MELD and Child-Pugh score, it have certain reference value to the short-term prognosis of patients with ACLF.Chapter two:Relation of serum HBVDNA load and short-term prognosis of patients with acute on chronic liver failure related to hepatitis BObjectiveTo analyse the serum HBVDNA loads of HB-ACLF patients between survival and deterioration group and try to discuss the relation of HBVDNA load and short-term prognosis of patients with HB-ACLF for providing objective prediction of new indicators.MethodsA total of 177 patients with HBV-related acute-on-chronic liver failure were enrolled from Guangzhou Eighth People’s Hospital during January 2009 to January 2013, and the diagnosis liver failure was followed by The Prevention and Treatment Proposal of Liver failure established in 2012. Patient data, disease prognosis judgement standards and statistical methods refer to the chapter One.Results(1) The relation of HBVDNA loads and HB-ACLF recent prognosis.The average HBVDNA loads of deterioration group with 61 cases was 5.88±1.73Log10 (IU/ml).The average HBVDNA loads of survival group with 116 cases was 5.64±1.65Logio (IU/ml). There was no significant difference on HBV DNA loads between deterioration and survival groups (t=0.921, P>0.05), through correlation analysis, there was no association between HBVDNA loads and recent prognosis (r=-0.07, P=0.357)(2) The correlation between HBVDNA loads and MELD-. Child-Pugh scoreThere was no association between HBVDNA loads and MELD score (r=0.022, P=0.774, P>0.05). There was no association between HBVDNA loads and Child-Pugh score (r=-0.23, P=0.761, P>0.05)。(3) The influence of Nucleotide drugs treatment and HB-ACLF recent prognosisA total of 161 cases in hospital taking nucleoside drugs therapy, with deterioration group 55 cases, survival group 106 cases. No taking nucleotide drugs treatment was 16 cases with deterioration group of 6 cases, and survival group of 10 cases. Whether taking nucleoside drugs had no statistical difference for HB-ACLF short-term prognosis (P>0.05)Conclusion(1)The influence of HBVDNA loads to HB-ACLF short-term prognosiswas not obvious, there was no obvious association between HBVDNA loads and MELD or Child-Pugh score.(2)HBVDNA load in ACLF after start-up condition might have a role in the process of evolution, but not the important influential factors of short-term prognosis.(3)Whether taking nucleoside drugs had no statistical difference for HB-ACLF short-term prognosis.