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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. China,The Progress of Pathogenesis Viral Factors,Evidence for the role of viral factors,Long-term follow
2、-up studies 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 an
3、d immune paralysis,HBV mutation and genotyping is closely related to disease severity,Precore (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 we
4、re infected with HBV/Bj or Ce,Ozasa A, et al. Hepatology. 2006, 44: 326-334,Outcome of acute hepatitis B virus infection,Pts with FH were older (34y)FH was frequent (13%) and associated with Bj and CeLack of HBeAgHigh replication due to precore mutation,Ozasa A, et al. Hepatology. 2006, 44: 326-334,
5、Pathogenesis of Special Fulminant Hepatitis- Immunosuppression-induced ALF(Fibrosing Cholastatic Hepatitis, FCH),Fig. Hepatitis reactivation after chemotherapy,Time after exposure (w),0,4,8,12,16,20,24,28,32,36,52,100,chemotherapy,Meuleman P, et al. J Virol, 2006, 80(6):2797-2807.,Actually there are
6、 2 kinds of responses: immune rebound and immune paralysis,Ocama P, et al. Am J Med, 2005, 118, Dec:e15-1413.e22,Fig. Overwhelming HBV infection with immnosuppression,A-D ALF after chemotherapy in 1 case of non-Hodgkin lymphoma E, F a case with CHB,HBcAg,Why do the pts. in tolerance stage have no FC
7、H manifestations ?,Immune tolerance immune paralysisImmune tolerance：virus and host have a relationship of mutually restrictionimmune paralysis: host loses its restriction to the virus,Medical strategy for two categories of ALF,Immune suppression induced ALF - Inhibition of virusImmune mediated ALF
8、- Immune suppression by using steroids - Inhibition of virus, ceasing of Immune mediated liver necrosis,The Progress of Treatment Antiviral therapy by NA,Hospitalized pts. with HBV-associated hepatic failure in Our Dept. through 1991-2005,Fig. Hospitalized liver failure patient of hepatitis B and nu
9、cleoside analogue usage in South-West hospital,Zhang N, et al. Oral presentation at the Annual Conference of APASL, Kyoto 2007,Outcome of severe hepatitis patients after LAM treatment,Zhang N, et al. Oral presentation at the Annual Conference of APASL, Kyoto 2007,Fig. Patients condition and prognosi
10、s of anti-HBV therapy within 1 week after onset of symptoms,*P=0.000,张绪清，等，待发表,Tab. Curative effect of 810 liver failure patients of hepatitis B after nucleoside analogue treatment,Zhang N, et al. Oral presentation at the Annual Conference of APASL, Kyoto 2007,Fig.1 Survival Curve of 215 liver failu
11、re of hepatitis B after lamivudine treatment,Zhang N, et al. Oral presentation at the Annual Conference of APASL, Kyoto 2007,Fig. liver failure of Chronic Hepatitis B Virus Infection After Withdrawal of Lamivudine Therapy in South-West hospital,Zhang N, et al. Oral presentation at the Annual Confere
12、nce of APASL, Kyoto 2007,Fig. Anti-HBV therapy by NA of 276 liver failure patients of Hepatitis after anti-HBV therapy by NA,Zhang N, et al. Oral presentation at the Annual Conference of APASL, Kyoto 2007,Fig. The disease cause of 1 patients with severe hepatitis B after treatment,38y male； HBsAg (+
13、) 4 years, jaundice for 2 weeks was transferred to our department after 8 weeks treatment from local hospital,LAM,liver failure,peritonitis,death,admission,Zhang X, et al. Oral presentation at the Annual Conference of APASL, Kyoto 2007,HBV DNA (log10 copies/ml),100,200,300,400,500,600,700,800,IU/ml,
14、LAM 100mg/d 36m,LAM50mg/d,6m,LAM,停药后复发,month,ETV,ADV,Fig. One pts. with decompensated liver cirrhosis showed multi-drug resistance,YVDD,Wang Y, et al. unpublished data,Target sequence: 394 bp. located in the Rt region of the polymerase gene in HBV genome All known mutation loci associated with nucle
15、oside analog resistance were included,Fig. Nested-PCR for the amplification of P Rt sequence,Xia J, et al. Oral presentation at the Annual Conference of APASL, Kyoto 2007,Agarose gel electrophoresis of PCR products,TA cloning,PCR verification of white colonies,Xia J, et al. Oral presentation at the
16、Annual Conference of APASL, Kyoto 2007,Patient I,Dynamics of serum HBV DNA, ALT and HBV quasispecies population,Liu L et al. Oral presentation at the Annual Conference of APASL, Kyoto 2007,VM breakthrough,Quasispecies memory,Patient J,Dynamics of serum HBV DNA, ALT and HBV quasispecies population,VM breakthrough,Quasispecies memory,Liu L et al. Oral presentation at the Annual Conference of APASL, Kyoto 2007,
