| BackgroundViral hepatitis is a major public health problem in China and the most common cause of liver disease.And chronic viral hepatitis is the most usual cause of chronic liver disease. The rate of hepatitis B (HB) is high in our country, and about 150 million of people were with chronic infection, of which 20 million were with chronic hepatitis B, thus resulting in about 500 thousand deaths per year.Diagnosis of chronic HBV infection mainly is depended on the detection of virus marker-HBsAg. The positive history of HBV-DNA or HBsAg is more than 6 months, besides HBsAg and/or HBV-DNA is still positive, which can be diagnosed with chronic HBV infection. According to the serology, virology, HBV infection of biochemistry test and other clinical and auxiliary examination results, it can be divided into several types:chronic hepatitis B, cirrhosis after hepatitis B, hepatitis B virus carriers and occult chronic hepatitis B.Although no drug can effectively clear HBV now, but the existing drugs can reduce the serum HBV of patients from high level to low level, even down to undetectable level. Nucleoside analogues are widely used for hepatic B patients with liver decompensation because of their oral administration, strong virus inhibition, less and mild side effects.However,the disadvantages are that the treatment time is relatively fixed, HBeAg seroconversion rate is low, the efficacy of the drug is not permanent.Long-term use of a drugcan produce the mutant.The condition may deteriorate when stop taking the drug. Common nucleoside analogues include lamivudine (LAM), telbivudine (LDT), entecavir (ETV), adefovir (ADV) and so on.The outcomes of chronic HBV infection varied from an inactive carrier state to chronic hepatitis, liver cirrhosis, liver decompensation, hepatocellular carcinoma and death. In our country, the number of dead caused by end stage HBV-related liver diseases each year is nearly 300-500 thousand, the incidence of liver cirrhosis can be as high as 3.6 million. The present therapies, including operation, liver artery interventional chemoembolization and radiofrequency ablation of liver tumor, mostly can not cure end stage hepatocellular carcinoma, espectially with viral hepatitis, liver cirrhosis and portal hypertension.Liver transplantation is currently considered as the only effective treatment for end stage liver disease.Selecting patients with viral hepatitis B as recipients was once controversial. The main reason is that the rate of viral hepatitis recurrence after transplantation is higher, and recurrent hepatitis B may progress faster, cirrhosis and liver failure may occur in the short term. With the continuous study of antiviral therapy in recent years, the rate of hepatitis B recurrence after transplantation has been greatly reduced. In our country, patients with end-stage hepatitis B related liver diseases have become the main crowd in liver transplant recipients.Although liver transplantation has been widely used as the final treatment of end stage liver disease, but behind the success of operation, complications occurre as the shadow after operation, which seriously affect recovery and survival of patients after transplantation.Hepatitis B recurrence caused by HBV reinfection is one of the major factors that affect the long-term survival rate of the patients after liver transplantation. Until the 1980s, as a result of the limitation of medical technology, the HBV reinfection rate of patients with end stage liver disease after liver transplantation could reach 80%,2 year survival rate is only 50%.In order to reduce hepatitis B recurrence after liver transplantation, so as to improve the long term survival rate of patients, people constantly explore various methods for prevention and treatment of hepatitis B recurrence.This study retrospectively reviewed,during the period from January 2008 to December 2011,the clinical and follow-up data patients with HBV related end-stage liver disease and received liver transplantation in the Department of Hepatobiliary Surgery, Nanfang Hospital of Southern Medical University.We analyze the characteristics of after liver transplantation and the related risk factors, as the single center clinical experience to provide clinical reference for future liver transplantation; at the same time,we compare different kinds of preventions and treatments of HBV reinfection in liver transplantation.Data and methodWe collected clinical datas of the patients undergoing allogeneic liver transplantation operation during from January 2008 to December 2011 in Department of Hepatobiliary Surgery, Nanfang Hospital of Southern Medical University.The total number of cases is 155,of which 104 cases are studied.Inclusion criteria:(l)patients with diagnosis of end-stage HBV related liver disease before transplantation; (2) patients which are the first time to accept liver transplantation;(3) postoperative follow-up is more than 1 month; (4) patients can completely accept anti-rejection and prevention of hepatitis B recurrence’treatment program;(5) data integrity.Clinical data collection including:1.preoperative data:the basic situation of the donor:whether there is viral hepatitis and other liver disease or not; the age,sex, primary disease (benign or malignant), Child-Pugh score, preoperative HBeAg (+or-),preoperative HBV-DNA quantity, other viral hepatitis, antiviral therapy;2.post-operative datas:anti-rejection immunosuppressiveregimen, prevention of HBV reinfection, follow-up time,the results of HBsAg and HBV-DNA, the time of infection, immune rejection, the recurrence of hepatocellular carcinoma,the time of HCC recurrence.Diagnosis standard of HBV reinfection after liver transplantation:according to the" the prevention of hepatitis B recurrence after Liver Transplantation Sym-posium "standards which are sponsored by Organ Transplantation Association belongs to Chinese Medical Association.The HBV infection again defined as that post-operative virus markers (HBsAg) are failed to turning negative,or being negative then anyone of these followings becomes positive:serum HBsAg;serum HBV DNA; HBsAg and (or) HBcAg of the the liver tissue; HBV-DNA of the the liver tissue.Depending on the standards of HBV reinfection after liver transplantation, all cases included in thestatistical analysis were divided into reinfection group and uninfection group.The gender, age, the Child classification, preoperative HBeAg (+/-),preoperative primary disease (benign or malignant), antiviral therapy,preoperative serum HBV-DNA level, acute rejection and postoperative reaction are tested as related risk factors for analysis.Statistics processing:the SPSS 13.0 software was used for statistical processing. It computes offrequency, median, and percentage. Measurement data were compared with Kolmogorv-Smirnov test of normality, consistent with the measurement data of normal distribution, compared with two independent samples t test; do not meet the measurement data of normal distribution, using two independent sa-mple Wilcoxon rank sum test to compare. Count datas were compared with chi-square test or Fisher’s exact probability calculation. According to α=0.05 level of test, P< 0.05 is considered the difference that is statistically significant.Result104 cases were included, of which 93 cases were male (89.4%),11 cases were female (10.6%), the average age was 51.01±10.42 years, and were followed up for 3-70 months.Before transplantation, the diagnosis of 26 cases is hepatitis B cirrhosis, the diagnosis of malignant tumor of liver disease were in 78 cases, in which the primary hepatocellular carcinoma (HCC) of 76 cases,2cases of bile duct cancer cells. Accordign to Child grade of preoperative liver function,45 cases were A grade,40 cases were B grade,19 cases were C grade.2 cases were combined with hepatitis C.1 case was combined with hepatitis E.15 cases occured HBV reinfecton after liver transplantation in 104 patients.The rate of HBV reinfection is 14.4%, which is in accordance with related reports, and is lower than groups that take no preventive measures or single LAM or HBIC.Among them, preoperative serum HBeAg of 4 cases (26.7%) were positive; 11 cases (73.3%) was negative; patient with preoperative benign liver disease (LC) was 1 case(6.7%); patients with HCC were 13 patients (86.6%), patient with bile duct cancer was 1 case(6.7%); patients wth serum HBV-DNA< 103copy/L were 2cases (13.3%);patients with serum HBV-DNA of 103-105copy/L were 2 cases (13.3%);patients with serum HBV-DNA>105copy/L were 11 cases (73.4%); patients with preoperative antiviral were 4 cases (26.7%); patients without antiviral therapy were 11 cases (73.3%); patients with acute rejection after operation were 8 cases (53.3%);patients without acute rejection occurredin were 7 cases (46.7%).The Times of HBV reinfection were 1-63 months after transplantation.The median time is 9 months. There is no significant difference between HBV reinfe-ction group and uninfection group according to age, gender, Child classification of liver function, HBeAg(+/-) before transplantation. The HBV reinfection rate of the group of preoperative serum HBV-DNA>105copy/L was the highest (64.7%);the second is the group of serum HBV-DNA of 103-105copy/L (10.5%);the rate of the group of serum HBV-DNA< 103copy/L is the lowest (3.8%), P< 0.001.In the the 26 patients with preoperative diagnosis of benign disease, lcase occured HBV reinfection (3.8%);in the 78 patients complicated with malignant tumor before operation (76 cases wew complicated with HCC,and 2 cases were complicated with bile duct carcinoma),14 cases (13 cases were with HCC,1 case was with bile duct carcinoma) occured HBV reinfection after transplantation(17.9%), P< 0.01.In the 13 patients with HCC,5 cases have HCC recurrence after transplantation,among which 3 cases are found after HBV reinfection.In the 63 patients with antiviral prophylaxis and treatment before transplantation,4 cases occured HBV reinfection (6.3%); 11 cases of 41 patients without antiviral prophylaxis occured HBV reinfection(26.8%), P< 0.01. After transplantation,30 patients occurred at least once immune rejection.We use high dose of MP for pulse therapy,or increase the dose of FK506 at the same time.We also change other anti rejection drugs when the results are poor.In the 30 patients,8 cases occurred HBV infection (26.7%), only 7cases in 74 patients without acute rejection occurred HBV reinfection (9.5%), P< 0.05.Conclusion1.As an replication status of patient before liver transplantation, HBV-DNA is an important risk factor of HBV re infection after liver transplantation. The patients with HBV-DNA> 105copy/L have a higher risk of HBV reinfection, and preventive therapy before transplantation can reduce postoperative HBV reinfection rate.2. Primary disease complicated with liver malignant tumor before liver transplantation, such as HCC, is a high risk factor of HBV reinfection after liver transplantation. The occurrence of acute rejection may make HBV reinfection rate increased with the use of a huge amount of immune inhibitor after liver transplantation.3. Prevention programs of nucleoside analogue drug combined with HBIG ca n effectively reduce the transplantation of HBV reinfection rate. Patients after liv er transplantation should at least every 3 months detect HBsAg and HBV-DNA once, to monitor whether the HBV reinfection and resistace occur. |
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