严重乙肝相关肝病发病机理和治疗英文版 PPT课件.ppt
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1、HBV-associated Severe Liver Diseases:Progress on Pathogenesis and Treatment Yuming WangInstitute for Infectious Diseases of PLASouthwest HospitalThird Military Medical UniversityChongqing,P.R.ChinaThe Progress of Pathogenesis Viral FactorsEvidence for the role of viral factorsLong-term follow-up stu
2、dies demonstrated the close relationship between disease severity and viral factorsNA has been showed to be effective in prevention and treatment of hepatitis exacerbationHBV mutation and genotypes are closely related to disease severityImmune suppressed ALF:overwhelming viral replication and immune
3、 paralysisHBV mutation and genotyping is closely related to disease severityPrecore(G1896A)mutation/core-promoter(G1762T/G1764A)mutationsPreS2 mutations HBV genotypes Fig.Frequencies of Precore/C-promoter mutations compared between pts.with FH and self-limited acute hepatitis who were infected with
4、HBV/Bj or Ce Ozasa A,et al.Hepatology.2006,44:326-334Outcome of acute hepatitis B virus infectionPts with FH were older(34y)FH was frequent(13%)and associated with Bj and CeLack of HBeAgHigh replication due to precore mutationOzasa A,et al.Hepatology.2006,44:326-334Pathogenesis of Special Fulminant
5、Hepatitis-Immunosuppression-induced ALF(Fibrosing Cholastatic Hepatitis,FCH)Fig.Hepatitis reactivation after chemotherapyTime after exposure(w)0481216202428323652100chemotherapychemotherapyChronic Chronic hepatitishepatitisLiver cirrhosisLiver cirrhosisALTALTRecoverRecoverAcute hepatitisAcute hepati
6、tisHBV DNAHBV DNAImmuno-suppressionImmunoImmuno-rebound-reboundALFALFDeathDeathMeuleman P,et al.J Virol,2006,80(6):2797-2807.Actually there are 2 kinds of responses:immune rebound and immune paralysisOcama P,et al.Am J Med,2005,118,Dec:e15-1413.e22 Fig.Overwhelming HBV infection with immnosuppressio
7、nA-D ALF after chemotherapy in 1 case of non-Hodgkin lymphoma E,F a case with CHBHBsAgHBcAgExtensivePositive HBsAgExtensive hepatocyte injury and inflamationSevere architectural disruption with fibrosis and necrosisHBcAgWhy do the pts.in tolerance stage have no FCH manifestations?Immune tolerance im
8、mune paralysisImmune tolerance:virus and host have a relationship of mutually restrictionimmune paralysis:host loses its restriction to the virusMedical strategy for two categories of ALFImmune suppression induced ALF -Inhibition of virusImmune mediated ALF -Immune suppression by using steroids -Inh
9、ibition of virus,ceasing of Immune mediated liver necrosisThe Progress of Treatment Antiviral therapy by NAHospitalized pts.with HBV-associated hepatic failure in Our Dept.through 1991-2005 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005(人人)Fig.Hospitalized liver failure p
10、atient of hepatitis B and nucleoside analogue usage in South-West hospitalZhang N,et al.Oral presentation at the Annual Conference of APASL,Kyoto 2007 Outcome of severe hepatitis patients after LAM treatment CasesCure or improved(%)Inefficacy or death(%)495(control)291(58.8)204(41.2)541(treatment)p0
11、.0001389(71.9)152(28.1)Zhang N,et al.Oral presentation at the Annual Conference of APASL,Kyoto 2007 Fig.Patients condition and prognosis of anti-HBV therapy within 1 week after onset of symptoms*P=0.000张绪清,等,待发表张绪清,等,待发表Year(n)improvement/total(%)Pstage:earlylate2000(19)2/5(40.0)2/14(14.3)1.86840.17
12、172001(49)6/15(40.0)4/34(11.8)5.10480.02382002(74)12/24(50.0)7/50(14.0)11.01290.00092003(100)15/31(48.4)16/69(23.1)6.34970.01172004(167)28/52(53.9)29/115(25.2)13.05440.00032005(189)31/51(56.1)39/132(29.5)5.09750.02402006(212)40/69(58.0)49/143(34.3)4.17040.0411Tab.Curative effect of 810 liver failure
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