Clinical Features Of Chronic Hepatitis B Relapse After Nucleos(T)Ide Analogues Withdrawal

BACKGROUND AND OBJECTIVE Chronic hepatitis B (CHB) is an high incidences infectious disease in our country. It threats public health seriously. One epidemiology survey of our country about hepatitis B in2006shows that hepatitis B surface antigen (HBsAg) carrier rate was7.18%in1-59years old general population, this figure was0.96%while in children under five years old. According to estimation, the number of hepatitis B virus (HBV) infection people is93million, and there were20million CHB patients in it.When HBV invade human body, it activate immune system to eliminate infected liver cells, which can lead to hepatocyte degeneration and necrosis. The main reason of HBV result in chronic hepatitis is HBV persistent infection. Therefore, antiviral treatment is the key treatment of chronic hepatitis B. At present, interferon and nucleos(t)ide analogues are two primary anti-HBV drugs. Course of interferon treatment is short, but most patients not only have poor curative effect, but also with more side effects. Therefore, patients often need to take a long time treatment of nucleos(t)ide analogues. However, drug treatment was terminated, virus may replicate again and virus loads bounce, which may lead to deterioration of diseases, even fatal hepatic failure. However, the research about the clinical characteristic and related factors of these drug withdrawl and recurrence patients is unknow.In order to give us great insight about these recurrence CHB patients, we have done this study.METHORDS This is an cross-sectional study with retrospective data, we investigated those chronic hepatitis B patients who withdrew nucleos(t)ide analogues and recurrence, between20111-12months in jinan infectious disease hospital. The following indexes were investigated:gender, age, census register, medical insurance types, course of disease before taking drugs, species of nucleos(t)ide analogues, course of treatment, efficacy, reason of drug withdrawal, serology and viral indexes at the time of drug withdrawal and recurrence periods respectively, biochemistry index after recurrence. The same time hospitalized chronic hepatitis B patients that treated first as control groups. We compared epidemiological data, demographic data,biochemistry index, serology and virology index of HBV in this two groups, when they admitted to hospital. On the basis of whether rapid recurrence and have or not liver failure later on, we split patients into two other groups.The data was analysised with SPSS13.0, measurement data using Mann-Whitney inspection. We analysis related factors of recurrence rapidly and have or not liver failure later on, with many factors Logistic regression analysis. Hypothesis testing with double side inspection, inspection level a=0.05. If P<0.05, the difference have statistical significance.RESULTS Recurrence people were384cases and initial cure patients were1127. In recurrence group, male patients were315cases and female patients were69cases, median age is42(19～78) years old, there were56(14.6%),48(12.5%),100cases (26%) with the history of smoking, drinking and liver cirrhosis respectively. Median value (minimum-maximum) of interval time from drug withdrawal to recurrence in taking lamivudine(LAM), adefovir(ADV), entecavir(ETV), Telbivudine (LDT), LAM and ADV combined patients were5(1-60) months,4(1～46) months,7(2～24) months,4(2～21) months,4(1～33) months respectively. In recurrence population,57(14.8%) cases appear liver failure. In these384patients, value (minimum-maximum)of ALT, AST, TBil, ALB, PTA and HBV DNA were280(11～4454) U/L,204(14～2972) U/L,30.15(4.4～901)μmol/L,41.2(17～54) g/L,76%(11%～119%),3.7×106(1.8×103～4.3×108) copy/ml respectively, when admission to hospital.Comparison clinical feature between drug withdrawal and initial treatment patients. Compared with initial treatment patients, the drug withdrawal group has higher male/female ratio but lower drinking and smoking history, they also have different age distribution(P<0.001). Remarkablely, drinking history have statistical significance (P<0.001). While the Smoking history difference was on the edge (P=0.056).The drug withdrawal group also has fewer liver cirrhosis patients (P=0.038) and higher liver failure ratio (P=0.018). They also have higher level of ALT, AST, TBIL but lower level PTA (P<0.001) when admission to hospital. Prognosis of these two groups do not have obvious difference (P=0.429).The clinical feature and related factors in drug withdrawal and rapid recurrence patients.187(48.7%) cases recur rapidly in384drug withdrawal patients. Compared with patients who recur not rapidly, these187patients have older median age (44vs41years old, P=0.006) and higher proportion of drinking (16%VS9.1%,P=0.041), but they have lower drugs withheld for ETV (2.1%compared with9.1%, P=0.003). The two groups have no statistically significant in proportion of liver cirrhosis and incidence of liver failure after stop taking drugs. The rapid recurrence patients have higher mortality (6.0%vs3.0%, P=0.013) and ALT, AST, TBil, AKP level (P<0.05), the proportion of hypertension and smoking is higher also (9.6%vs4.6%,18.2%vs11.2%), the difference has the edge meaning, P value were0.053,0.052respectively. Adjust gender, liver cirrhosis, family history of HBV, time of taking nucleos(t)ide analogues, the multivariate Logistic regression analysis shows that drinking and older than60years are risk factors of rapid recurrence after nucleos(t)ide analogues withdrawal. Nevertheless, taking ETV as antiviral drug is protective factor. Odds ratio (95%CI) were2.21(1.11-4.4, P=0.024),3.29(1.19-9.13, P=0.022),0.16(0.05-0.52, P=0.002) respectively.The clinical feature and related factors of patients that are complicated by liver failure after drug withdrawal.57cases are complicated by liver failure in384drug withdrawal patients, the median age is older than those are not (48vs42years old, P=0.002), proportion of cirrhosis is also higher (49.1%vs22%, P<0.001).The two groups have different age distribution and this difference have statistical significance(P=0.017).The proportion of liver failure after withdraw LAM, ADV,ETV,LDT, LAM and ADV combination therapy were22%,8.8%,13.6%, 10.5%,23.5%respectively, the difference have statistically significant (P=0.012). Adjust gender, family history of HBV, time of taking nucleos(t)ide analogues and rapid recurrence, the multivariate Logistic regression analysis shows that liver cirrhosis and taking LAM as antiviral drug are independent risk factors of liver failure after drug withdrawal. The odds ratio (95%CI) were2.83(1.5-5.31, P=0.001),2.29(1.26-4.18, P=0.007) respectively.CONCLUSION The liver damage is more severe in drug withdrawal and recurrence CHB patients than those who have not take any antiviral drugs people. Drinking history and older than60years are risk factors of rapid recurrence after withdraw nucleos(t)ide analogues. Nevertheless, taking ETV as antiviral drug is protective factor. Liver damage is more serious in rapid recurrence patients than not, the mortality is higher too. Liver cirrhosis and taking LAM as antiviral drug are independent risk factors of liver failure after drug withdrawal.