| Part1Short-term clinical outcome of severe acute exacerbation ofchronic hepatitis B after treatment with Nucleos(t)ide analogues and itsimpact factorsObjectives:To improve the long-term prognosis of patients with chronic hepatitis B (CHB)，antiviral drug should be given as soon as possible，which was recommended by almost allguidelines supposed by Chinese Medical Association. For patients with HBV-relatedcirrhosis, liver failure and HCC, Antiviral therapy with Nucleos(t)ide analogues (NAs) haveshown powerful efficacy through achieving sustained suppression of HBV replication andobvious benefit for their clinical outcome. However, antiviral therapy with NAs for patientswith severe acute exacerbation of chronic hepatitis B (AECHB) is still disputableand little research had been done. Most researches have proved that antiviral therapy withNAs could achieve better virological and biochemical response and improve the long-termoutcome, howerver, for patients with AECHB, several studies also reported that antiviraltherapy with NAs might be associated with increased short-term mortality. Therefore, it isimportant to clarify the short-term clinical outcome and analyze the predictive factors ofpatients with AECHB after treatment with NAs in a larger cohort. So, to provide referencefor indication of treatment and optimal treatment for patients with AECHB, weretrospectively retrieve the clinical data of patients with AECHB, investigate the short-termclinical outcome of patients with AECHB after treatment with NAs and analyze thepredictive factors which may impact the short-term clinical outcome.Methods:The clinical data of inpatients with AECHB of Southwest Hospital from Jan2003toDec2011were retrospectively retrieve. All of the520inpatients with AECHB were meet the following criteria: chronic HBV infection：meet research diagnostic criteria for chronichepatitis B and liver failure; severe acute exacerbation was defined as elevation of ALT tomore than5times the upper limit of normal and bilirubin to at least51μmol/L, decrease ofPTA to40%~60%; All patients had positive hepatitis B surface antigen (HBsAg) for morethan6months and18to65years old. Coinfection by HAV,HCV,HDV,HEV,HIV,autoimmune disease, metabolic diseases, pregnancy breastfeeding, severesystemic disease and psychopath were excluded.Five hundred twenty patients enrolled our study were divided into two groups，458cases were treatment with NAs and62cases refused treatment with NAs after admission.Main outcome measures including the incidence of liver failure in hospital, exacerbationrate，liver-related complications，the secondary including ALB，PLT，HBVDNA，HBeAg.Results:1. The incidence of liver failureThere was17%patients (78/458) had progressed to liver failure in antiviraltreatment group，while12.9%(8/62) in non-antiviral therapy group，and no significantdifference was found for the incidence of liver failure between the two groups(p=0.412)。The incidence of liver failure were16.2%(6/37)、16%(13/81)、16.9%(43/255)、19.2%(5/26) and18.6%(11/59) respectively in ADV，ETV，LAM，LDT，and combinationtherapy subgroup, and no significant differences were observed for the incidence of liverfailure among the five sugroups with different NAs(p>0.05). When compared with theincidence of liver failure of the control group there were also no significant differencesbetween that of the respectively NAs treatment subgroups(p>0.05).2. Exacerbation rateThere was13.8%patients (63/458) were exacerbated in antiviral treatment group，while21%(13/62) in non-antiviral therapy group，and no significant differences was foundfor the exacerbation rate between the two groups(p=0.131)。The exacerbation rate were8.1%(3/37)、11.1%(9/81)、14.1%(36/255)、11.5%(3/26) and20.3%(12/59) respectivelyin ADV、ETV、LAM、LDT and combination therapy subgroup， and no significantdifferences were observed for the exacerbation rate among the five sugroups with differentNAs(p>0.05). When compared with the exacerbation rate of the control group.There werealso no significant differences between that of the respectively NAs treatment subgroups(p>0.05).66.7%(52/78) of patients with liver failure were exacerbated in antiviraltreatment group，75%(6/8) in non-antiviral therapy group，and no significant differencesbetween the two groups(p=1.000).3. The incidence of liver-related complicationsThere was19.9%patients(91/458) had liver-related complications in antiviraltreatment group，while12.9%(8/62) in non-antiviral therapy group，and no significantdifferences was found for the incidence of liver-related complications between the twogroups(p=0.229)。The liver-related complications were13.5%(5/37)、14.8%(12/81)、22.4%(57/255)、19.2%(5/26)、20.3%(12/59) respectively in ADV、ETV、LAM、LDTand combination therapy subgroup，and no significant differences were observed for theincidence of liver-related complications among the five sugroups with differentNAs(p>0.05). When compared with the incidence of liver-related complications of thecontrol group. There were also no significant differences between that of the respectivelyNAs treatment subgroups(p>0.05).4. Analysis of influencing factorLogistic regression analysis:three risk factors for effecting the recovery/exacerbation werescreened out， liver-related complications(p=0.000，OR=0.025，95%CI:0.011-0.057)，olderpatients(p=0.000，OR=0.946，95%CI:0.917-0.975) and non-antiviral treatment(p=0.006，OR=3.876，95%CI:1.472-10.204) were negatively correlated with clinicaloutcome(p<0.05). Sex、NAs category, cirrhosis，baseline HBVDNA level，ALT，T.Bil，HBeAg state and ALB were not significantly relevant to clinical outcome(p>0.05). singlefactor analysis showed that patients with high viral load(≥6log10IU/ml) or HBeAgpositive in antiviral treatment group have significantly lower exacerbation rates comparedwith the control group(p<0.05).Conclusion1．For patient with AECHB，antiretroviral therapy did not affect their incidence ofliver failure and their short-term mortality. For patients with high viral load (≥6log10IU/mL) or HBeAg positive, NAs treatment can decreased the short-term deterioration rate andmortality.2．All of the Nucleos(t)ide analogues can be used in severe acute exacerbation ofchronic hepatitis B，since there were not significantly relevant to clinical outcome. 3. Liver-related complications, older age and non-antiviral treatment are independentrisk factors of exacerbation for SECHB.4. Once the occurrence of liver failure,patients might be associated with highmortality(up to70%) regardless of the use of NAs.5. Therefor, for patient with AECHB should receive antiviral treatment as soon aspossible and all NAs can be as a option for these patients.Part2Clinical outcome of HBV-related patients relapsed after nucleos(t)ideanalogues withdrawal and its impact factorsObjectives:Antiviral therapy is the key of HBV-related liver disease,which include nucleos(t)ideanalogues(NAs) and interferon.Long-term treatment with nucleos(t)ide analogues areeffective in achieving virological suppression、restoring liver function and preventingprogression of cirrhosis.Nucleos(t)ide analogues could inhibit viral DNA replicationthrough interferes with the reverse-transcriptase activity of hepatitis B virus (HBV) andinhibit DNA synthesis by terminating the nascent proviral DNA chain.Most patients withCHB will require long-term treatment to derive clinical benefit because the transcriptiontemplate-covalently closed circular DNA (cccDNA) which produces in the processe ofHBV replication is unable to be clear completely that induce its continued existence in thehepatic cells.Clinical observation found that HBV-related patients will relapse after NAswithdrawal even progress to liver failure in some patients. The phenomenon is commonthat patients withdrew on their own purposes including resistance, poor curative effect andeconomic reasons,but have an insufficient understanding of clinical characteristics andoutcome of patients relapsed after NAs withdrawal.Therefore,we investigate the clinicalcharacteristics and clinical outcome of HBV-related patients relapsed after Nucleos(t)ideanalogues (NAs) withdrawal and its impact factors..Methods:Retrospectively retrieve the clinical data of HBV-related inpatients of SouthwestHospital in2011. Recruit patients who meet the following criteria:18to65years old, tookNAs more than6months before withdrawal and admitted patients due to disease onset after NAs withdrawal. Observe the recovery and exacerbation rate, duration of treatment of priorNAs, time of drug withdrawal to illness onset, time of illness onset to admission andserological, biochemical and virological tests after admission.Results:1、152cases were recruited,98%of the patients withdrew on their own purposes.69.1%took NAs for1-3years before withdrawal.The median time of drug withdrawal toillness onset was6month.74.3%of patients relapsed within one year after NAs withdrawal.2、The dynamic changes of biochemical activity indexes：The ALT level in all patients showed a decreased trend after admission, whereas T.Biland PT levels showed parallel changes in each group: there were two patterns in recoverygroup, steady-then-descending pattern and progressively-descending pattern, while inexacerbated group both showed progressively-elevateing pattern only.3、Clinical outcome82.2%(125/152) of patients recovered and discharged from hospital, after one monthtreatment the total patients recovered and discharged from hospital add up to67.76%(103/152),and add up to78.3%(119/152) after two months treatment.while17.8%(27/152) of patients were exacerbated, including two dead cases.after one month treatmentthe total patients were exacerbated add up to13.8%(21/152),and add up to16.4%(25/152)after two months treatment.4、The incidence of liver-related complications17.8%(27/152) of patients had liver-related complications，including SBP、hepaticencephalopathy、hemorrhage、renal insufficiency and hepatorenal syndrome.61.3%(19/31)of patients had liver-related complications in chronic severe hepatitis B virusgroup,13.3%(8/60) in liver cirrhosis group and no complication happened in CHB.Thecomplications between the three groups showed statistically significant difference(p<0.05).5、Analysis of influencing factorsingle factor analysis：The recovery rate were35.5%,88.3%,100%in chronic severehepatitis group, liver cirrhosis group and CHB group respectively and were statisticallysignificant differences between the three groups(p<0.05); however no significantdifferences were found among different nucleoside (acid) analogue groups(p>0.05). Therecovery rate were80.7%and84.4%in HBeAg positive and negative patients relapsed after NAs withdrawal，and no significant differences between the two groups(p>0.05)。Logistic regression analysis:three risk factors were screened out,shorter time of drugwithdrawal to illness onset (p=0.000，OR=1.129，95%CI:1.056-1.208) and higher T.Billevel(p=0.008，OR=0.992，95%CI:0.986-0.998)、prolonged PT (p=0.000，OR=0.694，95%CI:0.574-0.839) were negatively correlated with clinical outcome(p<0.05). NAscategory, HBeAg state and rebounded HBVDNA level were not significantly relevant toclinical outcome(p>0.05).Conclusions:1、About20%of HBV-related inpatients relapsed after NAs withdrawal have poorclinical outcome.The dynamic changes of T.Bil and PT level have some particular patterns,and both elevated progressively predict poor clinical outcome， whilesteady-then-descending and descended progressively predict excellent clinical outcome.2、Shorter time of NAs withdrawal to illness onset indicated worse clinical outcome.NAscategory, HBeAg state and rebounded HBVDNA level were not significantly relevant toclinical outcome of patients with biochemical breakthrough. |
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