病毒性肝炎治疗之困惑如何评价抗炎保肝价值？课件.pptx

病毒性肝炎治疗之困惑如何评价抗炎保肝价值? 肝脏炎症有何意义? 肝脏免疫反应的独特性能?先天性免疫: 大量独特的免疫细胞群: KC 、 NK 、 NK-T 肠道 PAMPs 的暴露肝脏分泌 DAMPs 的暴露 HSC 和纤维化的活性限制?临床结局: Inflammation! Inflammation ! Inflammation ! Inflammation ! M etabolic S yndrome Ischemia/Reperfusion Necrotic lesion Inflammation in ans Natural History of Chronic Hepatitis B Normal liver Chronic hepatitis B ESLD No further progression HBV-related ESLD or HCC are responsible for > -1 million deaths per yr and currently represent 5% to 10% of cases of liver transplantation Not all patients have progressive disease Cirrhosis HCC Cumulative Incidence of Cirrhosis by Serum HBV DNA Level at Study Entry Iloeje UH, et al. Gastroenterology. 2006;130:678-686. N = 3582 Taiwanese patients Yr of Follow-up Cumulative Incidence of Liver Cirrhosis (%) Log-rank P < .001 40302010013 0123456789101112 Baseline HBV DNA Level, copies/mL ≥ x 10 x 10 5 - x 10 x 10 4 - x 10 4 300- x 10 3 < 300 REVEAL: Relationship Between Baseline HBV DNA and Cirrhosis ? Baseline HBV DNA predicted progression to cirrhosis – Relationship independent of HBeAg status Adjusted RR *0 * With 42,115 patient-yrs of follow-up and adjusted for sex, age, anti-HCV levels, smoking, and alcohol use. ? 1 IU/mL equals approximately genomes/mL. P = NS HBeAg-Negative Patients < 10 4 (n = 2132) HBeAg-Positive Patients P < .01 P < .001 ≥ 10 4 to < 10 5 (n = 631) ≥ 10 5 (n = 451) < 10 4 (n = 22) ≥ 10 5 (n = 520) ≥ 10 4 to < 10 5 (n = 18) BL HBV DNA, c/mL ?: Adjusted RR * P < .001 P < .001 0 Cases of Cirrhosis: 104 55 9623 135 Chen CJ, et al. EASL 2005. Abstract 476. Cumulative Incidence of HCC by Serum HBV DNA Level at Study Entry Cumulative Incidence of HCC (%) 0 2 4 6 8 10 12 14012345678910111213 Baseline HBV DNA Level, copies/mL ≥ 1 million 100,000-999,999 10,000-99,999 300-9999 < 300 N = 3653 Taiwanese patients Yr of Follow-up Chen CJ, et al. JAMA. 2006;295:65-73. es