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 factors Long-term follow-u
2、p studies demonstrated the close relationship between disease severity and viral factors NA has been showed to be effective in prevention and treatment of hepatitis exacerbation HBV mutation and genotypes are closely related to disease severity Immune suppressed ALF: overwhelming viral replication a
3、nd immune paralysisHBV mutation and genotyping is closely related to disease severityPrecore (G1896A) mutation /core-promoter (G1762T/G1764A) mutationsPreS2 mutations HBV genotypesFig. Frequencies of Precore/C-promoter mutations compared between pts. with FH and self-limited acute hepatitis who were
4、 infected with 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: 326-334Pathog
5、enesis of Special Fulminant Hepatitis- Immunosuppression-induced ALF(Fibrosing Cholastatic Hepatitis, FCH)Fig. Hepatitis reactivation after chemotherapyTime after exposure (w) 0 4 8 12 16 20 24 28 32 36 52 100chemotherapy Chronic hepatitis Liver cirrhosisALTRecoverAcute hepatitisHBV DNAImmuno-suppre
6、ssion Immuno-reboundALFDeathMeuleman 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 immnosuppressionA-D ALF after chemotherapy in 1 case o
7、f non-Hodgkin lymphoma E, F a case with CHBHBsAgHBcAgExtensivePositive HBsAgExtensive hepatocyteinjury and inflamationSevere architectural disruption with fibrosisand necrosisHBcAgWhy do the pts. in tolerance stage have no FCH manifestations ? Immune tolerance immune paralysis Immune tolerance： virus and host have a relationship of mutually restriction immune paralysis: host loses its restriction to the virus
