【文章內(nèi)容簡介】 病毒的復(fù)制過程中，病毒 DNA進(jìn)入宿主細(xì)胞核，在 DNA聚合酶的作用下，正鏈的缺口均被補(bǔ)齊，形成超螺旋的共價(jià)閉合環(huán)狀 DNA分子 ? cccDNA是乙肝病毒前基因組 RNA復(fù)制的原始模板，雖然其含量較少〔每個(gè)肝細(xì)胞內(nèi)只有約 5～ 50個(gè)拷貝〕，但對(duì)乙肝病毒的復(fù)制以及感染狀態(tài)的建立具有十分重要的意義，只有去除了細(xì)胞核內(nèi)的 cccDNA，才能徹底消除乙肝患者病毒攜帶狀態(tài)，是抗病毒治療的目標(biāo) 第三十六頁，共九十四頁。 37 Pathogenesis: Hepatitis B ? 肝損傷機(jī)制 ? 細(xì)胞免疫介導(dǎo) ? 自身免疫介導(dǎo) ? 細(xì)胞因子介： TNF、 IL1 第三十七頁，共九十四頁。 38 Pathogenesis: Hepatitis B ? 不同臨床表現(xiàn)的發(fā)病機(jī)制 ? 免疫功能正常 急性肝炎 ? 不完全免疫耐受、免疫功能低下、 病毒變異逃防止疫去除、產(chǎn)生自身免疫反響慢性肝炎 ? 超敏反響 重型肝炎 ? 免疫耐受，圍生期，無免疫應(yīng)答 攜帶者 第三十八頁，共九十四頁。 39 Pathogenesis: Hepatitis C ? Is similar to that of HB ? HCV infection is related to chronic hepatitis closely (50~85%) ? Direct attack ? Immunologic mechanism ? Autoimmune reaction ? HCVRNA在復(fù)制過程中有很高的異變率形成一系列變異的病毒株，造成特異性細(xì)胞毒 T細(xì)胞不能識(shí)別其表位，是的抗病毒免疫失效，為 HCV感染容易轉(zhuǎn)為慢性的主要原因 第三十九頁，共九十四頁。 40 Clinical manifestation ? Incubation period Type Range Average HA 2~6w 4w HB 28~160d 70~80d HC 2~26w 8w HD 6~12w HE 15~75d 6w 第四十頁，共九十四頁。 41 Clinical manifestation ? Clinical types ? Acute viral hepatitis: icteric or anicteric ? Chronic viral hepatitis ? Mild, Moderate, Severe ? Hepatitis gravis ? Acute, Subacute, Chronic ? Cholestatic viral hepatitis ? Postnecrotic cirrhosis 第四十一頁，共九十四頁。 42 Clinical manifestation ? Acute viral hepatitis: icteric ? Course： may be 24m and divided into 3 periods ? Preicteric period ? In HA, HE, the onset is abrupt with fever。 but HB, HC, the onset is insidious ? The initial symptoms: anorexia, nausea, vomiting, fatigue, abdominal pain and diarrhea, urine darker ? The duration of this period: 57d 第四十二頁，共九十四頁。 43 Clinical manifestation ? Acute viral hepatitis: icteric ? Icteric period ? Symptoms relief but the urine deepens continuously and jaundice appears on the skin and sclera ? Liver and spleen palpable ? Abnormal liver function ? The period lasts 26w 第四十三頁，共九十四頁。 44 Clinical manifestation ? Acute viral hepatitis: icteric ? Convalescent period ? The jaundice disappear gradually, symptoms relief or disappear ? Liver and spleen retract, liver function return to normal ? The period lasts 2~4w 第四十四頁，共九十四頁。 45 Clinical manifestation ? Acute viral hepatitis: anicteric ? All of 5 kinds of hepatitis virus can cause acute anicteric hepatitis. This type is most mon. ? Important source of infection 第四十五頁，共九十四頁。 46 Clinical manifestation ? Chronic viral hepatitis ? Only appear in HBV, HCV and HDV infection ? The course is more than half year, or had a history of HBV, HCV, HDV or HBsAg (+), the symptoms, signs and liver function are relapsed ? Mild, moderate, severe 第四十六頁，共九十四頁。 47 Clinical manifestation ? Degree of damage of liver in chronic viral hepatitis Item mild moderate severe ALT(u) ≤3X 3X 3X TBIL(umol/L) ≤2X 2~5X 5X ALB(g/L) ≥35 3334 ≤32 A/G ≥ ≤ ?globulin ≤21 2225 ≥26 PTA(%) 70 6070 4060 CHE 5400 4500~5400 ≤ 4500 第四十七頁，共九十四頁。 48 Clinical manifestation ? Hepatitis gravis ? All of five kinds of hepatitis virus can cause this type of hepatitis. The incidence is only %, but the mortality is the highest. 第四十八頁，共九十四頁。 49 Clinical manifestation ? Acute hepatitis gravis ? The onset may begin in a typical acute icteric hepatitis, but within 14 days ? Jaundice deepens rapidly ? Vomit is frequent ? Obvious anorexia ? Hemorrhage ? The liver shrinks in size ? Prothrombin time is prolonged ? Acute renal failure ? Hepatic encephalopathy 第四十九頁，共九十四頁。 50 Clinical manifestation ? Subacute hepatitis gravis ? The course of AIH is more than 10 days (15d~24w) ? The hepatic encephalopathy appear later ? The course may be several months ? The postnecrotic cirrhosis may develop ? Chronic hepatitis gravis ? History of chronic hepatitis, cirrhosis 第五十頁，共九十四頁。 51 Clinical manifestation ? Cholestatic hepatitis ? Intra hepatic cholestatic jaundice for a long time ? Pruritus ? Pale feces ? Hepatomegaly ? TBIL, DBIL, ALP, GGT ↑ 第五十一頁，共九十四頁。 52 Laboratory examination ? Liver function ? Serum transaminase ? ALT(alanine transferase) ↑ ? AST(aspartase transferase) ↑ ? ALP (Alkaline phosphatase) ↑ ? in chronic hepatitis, LDH (Lactate dehydrogenase) ↑ ? Serum protein ? Albumin ↓ ? In chronic hepatitis, Ig ↑↑ ? The ratio of A/G ↓ 第五十二頁，共九十四頁。 53 Laboratory examination ? Liver function ? Bilirubin ? Urobilinogen ↑in early stage of Acute icteric hepatitis ? Urobilinogen and urobilin ↑in icteric stage ? Urobilin is positive and