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The second part of hepatitis viruses,
肝炎病毒第二节
HBV, HCV and HDV.
HBV, HCV以及HDV
Case 1 patient may have been infected
考虑到病毒是通过粪口途径传播的
by HAV or HEV since the virus was
案例1的患者
transmitted by fecal-oral route.
也许是被HAV或者HEV感染
The acute illness was followed by
这种急性病
recovery a few weeks later.
几周后会痊愈
How about case 2?
那么案例2呢?
Which virus could have caused
是什么病毒会引起
the chronic hepatitis?
慢性肝炎?
Right, HBV or HCV.
对,HBV或者HCV
Let's get to know hepatitis B virus,
我们来学习乙型肝炎病毒
HBV.
HBV
HBV is the major member of
HBV是
the hepadnaviruses,
嗜肝病毒
which is a small enveloped DNA virus.
是一种小型的有包膜DNA病毒
The virion,
病毒体
also called the Dane particle,
也被叫做Dane颗粒
is spherical and 42 nm in diameter.
直径42nm的球形颗粒
The genome is small,
基因组是
circular, partial dsDNA.
环状的不完全双链DNA
Although a DNA virus,
尽管是DNA病毒
it encodes a reverse transcriptase
但它编码逆转录酶
and replicates through
并且通过RNA中间体
a RNA intermediate.
来复制
Capsid is icosahedral,
衣壳是二十面体,
formed by the hepatitis B core
由乙型肝炎核心抗原(HBcAg)
antigen (HBcAg).
组成
The envelope contains three forms
包膜上有三种
(L, M, S) of the glycoprotein
乙型肝炎表面抗原(HBsAg)糖蛋白(L,M,S)
hepatitis B surface antigen (HBsAg).
A hepatitis B e antigen (HBeAg)
e抗原(HBeAg)
shares most of its protein sequence
与HBcAg蛋白质序列大部分相同
with HBcAg but expresses different
但表达出不同的
antigenic determinants.
抗原决定簇
The virions are unusually stable
乙肝病毒的病毒体是有包膜的,
for an enveloped virus.
但比一般的包膜病毒稳定
They resist treatment with ether,
对乙醚,
low pH, freezing,
低pH,冰冻
and moderate heating.
以及中度加热具有耐受性
HBV- Antigenicity.
HBV抗原性
HBsAg,
HBsAg
originally termed the Australia antigen,
起初称为澳大利亚抗原
is on the surface of the virion
存在于病毒体表面
and secreted into the blood
并在病毒复制的过程中
during viral replication.
被分泌入血液
It is a marker for HBV infection.
是HBV感染的标志物
Anti-HBs antibody is a neutralizing
抗HBs抗体是一种保护性的
and protective antibody.
中和抗体
HBcAg cannot be detected in serum.
血清中检测不到HBcAg
Anti-HBc antibody
抗HBc抗体
is not a neutralizing antibody,
不是中和抗体
and is a marker of viral replication.
而是病毒复制的标志物
IgM anti-HBc is the marker
抗HBc-IgM是近期急性感染
of recent acute infection.
的标志物
HBeAg, hepatitis B e antigen,
HBeAg,e抗原
is secreted into the blood
可以分泌到血液中
and indicates viral replication.
是病毒复制的标志
The detection of HBeAg implies
检测到HBeAg意味着
the presence of infectious virus.
病毒存在于体内
Anti-HBe antibody
抗HBe抗体
is partially protective.
具有一定的保护性
Detection of both the HBsAg
同时在血液中检测到
and the HBeAg components
HBsAg和HBeAg
of the virion in the blood indicate
表明
an ongoing active infection.
正在发生急性感染
Initial infection with HBV occurs
HBV感染可以通过
through shared needles,
共用针头
unprotected sex, and delivery.
不安全性行为以及分娩的途径
The virus then goes to the liver,
病毒随后进入肝脏
replicates and induces a viremia.
复制并形成病毒血症
It is then transmitted
随后通过
through various body fluid
各种体液
and secretions such as blood,
以及分泌物,比如血液
semen, saliva, breast milk,
精子,唾液,母乳,
vaginal secretions and menstruation.
阴道分泌物和月经等传播
Symptoms are caused
症状是由
by cell-mediated immunity (CMI)
细胞介导免疫
and immune complexes between
以及抗体
antibody and hepatitis B surface
和乙肝病毒表面抗体(HBsAg)的
antigen (HBsAg).
免疫复合物引起
Sources of infection are patients
传染源是
with acute and chronic hepatitis
急性和慢性乙肝患者
and asymptomatic chronic carriers.
以及无症状的慢性携带者
The virus is most commonly
传播途径还有
transmitted from mother to child
通过分娩过程
during delivery,
由母亲传给孩子
as well as through contact with
通过接触
blood or other body fluids.
血液或其他体液传播
Hepatitis B is also spread
乙型肝炎也可以通过
by needle-stick injury, tattooing,
针刺伤,纹身,
piercing and exposure to infected blood
穿孔以及暴露在有感染者的血液和体液的环境中,
and body fluids, such as saliva,
例如唾液
vaginal, and seminal fluids.
阴道分泌液以及精液传播
Sexual transmission of hepatitis B
也可以通过性传播
may occur,
particularly in unvaccinated men
特别是没打过疫苗的男性
who have sex with men
与男性发生性行为
and heterosexual persons
以及异性恋人群
with multiple partners or
与多个伴侣的性行为
contact with sex workers.
或者与性工作者接触
HBV - clinical diseases
HBV-临床疾病
Acute infection:
急性感染:
Long incubation period:
长潜伏期:
75 days on average,
平均在75天
but can vary from 30 to 180 days.
但可以30到180天不等
Prodromal symptoms include fever,
前驱症状包括发热
malaise, anorexia,
萎靡不振,厌食
followed by nausea, vomiting,
随后有恶心,呕吐
abdominal discomfort, and chills.
腹部不适以及发冷等症状
Typical symptoms of liver dysfunction:
典型肝功能受损的症状:
jaundice, dark urine, pale stool
黄疸,深色尿,苍白的粪便
In some people,
在某些人群中
the hepatitis B virus can also
乙型肝炎病毒也可以
cause a chronic infection that
引起慢性感染
can later develop into hepatic cirrhosis
并后续发展成肝硬化
(scarring & hardening) or liver cancer.
(瘢痕和硬化)或者肝癌
Chronic infection:
慢性感染:
Usually after mild
通常在轻微
or unapparent initial disease.
隐性感染后发生
Initial infection in adulthood leads
成人初次感染后得慢性肝炎的概率
to chronic hepatitis in less than 5%,
低于5%
whereas 80–90% of infants infected
然而婴儿感染者中80-90%
during the first year of life
在第一年
and 30–50% of children infected before
儿童感染者中30-50%的
the age of 6 years
在6岁前
develop chronic infections.
发展成慢性
20–30% of adults who are chronically
慢性感染的成人患者中20-30%的
infected will develop cirrhosis
会发展成肝硬化
and/or liver cancer.
和/或肝癌
primary hepatocellular carcinoma (HCC)
原发性肝细胞癌(HCC)
It is estimated that 80% of all
据估计,全部HCC患者中
HCC can be attributed
80%患有
to chronic HBV infections.
慢性HBV感染
Lab diagnoses of HBV include:
HBV的实验室检查包括:
1. Serologic markers by ELISA
1.ELISA检测血清学标志物
2. HBV DNA by PCR
2. PCR检测HBV的DNA
The serology of HBV infection describes
HBV感染的血清学
the natural course of the disease.
描述了这种病的自然病程
The table shows you the interpretation
这张表格展示了
of serologic markers in HBV infection.
HBV感染中的血清标志物
For example,
例如
acute HBV infection is characterized by
急性HBV感染特点是
the presence of HBsAg and IgM anti-HBc.
血清中出现HBsAg和抗Hbc-IgM
During the initial phase of infection,
感染的初期
patients are also seropositive
患者的HBeAg
for HBeAg,
阳性
which is usually a marker
HBeAg是
of high viral replication.
病毒高度复制的标志物
Chronic infection is characterized by
慢性感染的特点是
the persistence of HBsAg
HBsAg持续存在
for at least 6 months
至少6个月
(with or without concurrent HBeAg).
(有或没有HBeAg存在)
The treatment of HBV
HBV的治疗
Acute infection
急性感染
There is no specific treatment
对于急性乙型肝炎
for acute hepatitis B.
没有特异性的治疗
Hepatitis B immunoglobulin may
可以对暴露在乙肝病毒后一周内的人群
be administered within a week
和对HBsAg阳性母亲的新生儿
of exposure and to newborn infants
使用乙肝免疫球蛋白
of HBsAg-positive mothers to prevent
以达到预防
and ameliorate disease.
和改善疾病的目的
Chronic HBV
慢性HBV
Chronic HBV infection can be treated
慢性HBV感染的治疗
with drugs targeted at the polymerase
作用于聚合酶的药物
(e.g., lamivudine)
例如拉米夫定
or the nucleoside analogs
或者核苷酸类似物
adefovir dipivoxil and famciclovir.
阿德福韦酯和泛昔洛韦来治疗
IFN-α can also be effective.
IFN-α也很有效
Preventive measures –
预防措施-
Interrupt the transmission route
献血血液筛查
by screening all donated blood,
切断传播途径
avoid sex with HBV carriers
避免与HBV携带者发生性行为
and shun lifestyles that facilitate
并且避免任何能促进HBV传播的
spread of HBV.
生活方式
Vaccination is recommended for infants,
建议给以下人群接种疫苗:婴儿
children, and high-risk groups such
儿童以及高危人群
as people who frequently require
例如频繁需要
blood or blood products,
血及血制品的人群
healthcare workers who frequently
频繁需要处理血及血制品的
handle blood and blood products,
医疗从业人员
people with multiple sexual partners,
有多个性伴侣的人群
etc.
等等
Next one is hepatitis C virus, HCV.
下一个是丙型肝炎病毒,HCV
Family: Flaviviridae;
科:黄病毒科
Genus: hepacivirus
属:丙型肝炎病毒属
Positive sense RNA genome,
基因组为正链RNA
enveloped.
有包膜
HCV infects only humans
HCV只感染人类
and chimpanzees.
以及黑猩猩
Antigenic variability makes
抗原的变异性
the development of a vaccine
使疫苗的研制
very difficult.
非常困难
Pathogenicity
致病性
Source of infection:
传染源:
acute,
急性
chronic and asymptomatic carriers
慢性以及无症状携带者
HCV is transmitted primarily through
HCV主要通过血液
blood and sexual contact.
以及性接触传播
HCV is the major cause
HCV是输血后肝炎的
of post-transfusion hepatitis.
主要病因
Clinical diseases.
临床疾病
Three types of diseases:
三种疾病:
15%: Acute hepatitis with resolution
15%的急性肝炎
of the infection and recovery.
可治愈
70%: Chronic persistent infection
70%的慢性持续性感染
with possible progression
可进展
to disease later in life.
15%: Severe with rapid progression
15% 严重疾病,发展迅速
to cirrhosis.
可引起肝硬化
More commonly (>70%),
更常见的(多于70%)
the initial disease is asymptomatic
最初无症状
but results in chronic
但最终导致
persistent disease.
慢性持续性感染
The predominant symptom
其主要的症状
is chronic fatigue.
是慢性乏力
Lab diagnosis.
实验室检查
The diagnosis of HCV infection are based
HCV感染的诊断
on the presence of anti-HCV antibody
检查抗HCV抗体
or detection of the HCV RNA.
或者HCV RNA
Anti-HCV antibody is used for screening
抗HCV抗体用于筛查
all donated blood in the blood bank.
献血的血液
Treatment and prevention.
治疗以及预防措施
IFN-αalone, ribavirin,
可使用IFN-α,病毒唑
and protease inhibitors are available.
以及蛋白酶抑制剂等药物
There is currently no effective
目前没有抗丙型肝炎的
vaccine against hepatitis C.
有效疫苗
Hepatitis D virus, HDV
丁型肝炎病毒,HDV
Defective virus,
缺陷病毒
HBsAg is essential for packaging
HBsAg在病毒组装时
the virus.
必不可少
Source of the infection
传染源
is HBV/HDV patients.
HBV/HDV患者
Transmission route sare the same as HBV.
传播方式与HBV一样
Co-infection: HDV and HBV co-infection
联合感染:HDV和HBV同时感染
Super-infection: a person with chronic
重叠感染:HBV患者
HBV is infected by HDV;
再被HDV感染
more severe & more rapid
比联合感染
progression than co-infection
更严重和更快进展
HDV is responsible for causing 40%
40%的急性重型肝炎感染
of fulminant hepatitis infections,
是由HDV感染导致
which is a very severe form of hepatitis
这是一种严重的肝炎
causing altered cerebral functions,
会导致大脑功能的改变
extensive jaundice
严重黄疸
and massive hepatic necrosis
以及大范围的肝坏死
Fatality rate is 80%.
致死率80%
Lab tests include detecting
实验室检测包括检测RNA
the RNA genome or anti-HDV antibodies.
或抗HDV抗体
No specific treatment.
没有特异性的治疗
Immunization with HBV vaccine can
通过HBV疫苗免疫
prevent this disease.
可以预防本病
The last one is HGV,
最后一个是HGV
resembling HCV in many ways.
类似于HCV
It is a flavivirus, transmitted in blood,
是黄病毒属的病毒,通过血液传播
and has a predilection
易于发生
for chronic hepatitis disease.
慢性肝炎
Identified by detection
实验室检查采用
of the genome by RT-PCR.
RT-PCR检测基因组
I will leave you to summarize
肝炎病毒小结
the hepatitis viruses.
的任务留给你们自己完成
This table may give you some clues.
这张表格提供了一些线索
This is the “hepatitis virus” branch.
这便是“肝炎病毒”
Hope you have enjoyed this session.
祝大家开心
See you soon.
再见
-Learning Objectives & References
-Assessment Plan of Medical Virology
-To apply basics to clinical case
-1.1 Viral Structure and Composition
--Viral Structure and Composition
--Shapes and relative sizes of viruses
-1.2 Viral Replication
-1.3 Viral Genetics and Classification
--Viral Genetics and Classification
-1.4 Pathogenesis of Viral infection
--Pathogenesis of Viral infection
-1.5 Lab Diagnosis and Host Rsponse to Viral Infection
--Lab Dignosis and Host Rsponse to Viral Infection
-General Virology Quiz
-2.1 Influenza Virus: Biological Properties 1
--Influenza Virus: Biological Properties 1
-2.2 Influenza Virus: Biological Properties 2
--Influenza Virus: Biological Properties 2
-2.3 Influenza Virus: Biological Properties 3
--Influenza Virus: Biological Properties 3
-2.4 Influenza Virus: Lab, Treatment and Prevention
--Influenza Virus: Lab, Treatment and Prevention
-2.5 Paramyxovirus
-2.6 Coronavirus and Rubella virus
--Coronavirus and Rubella virus
-Viruses Transmitted Through Respiratory Route Quiz
-3.1 Diseases Caused by Enteroviruses
--Diseases Caused by Enteroviruses
-3.2 Poliovirus Infection and Viron of Enterovirus
--Poliovirus Infection and Viron of Enterovirus
-3.3 Lab Diagnosis & Prevention of Enterovirus
--Lab Diagnosis & Prevention of Enterovirus
-3.4 Viruses Causing Acute Gastroenteritis
--Viruses Causing Acute Gastroenteritis
-Viruses Transmitted Through Fecal-oral Route Quiz
-4.1 General Properties of HIV
-4.2 Replication of HIV
-4.3 Pathogenesis and Immunity of HIV
--Pathogenesis and Immunity of HIV
-4.4 Epidemiology and Lab Diagnosis of HIV/AIDS
--Epidemiology and Lab Diagnosis of HIV/AIDS
-4.5 Treatment, Prevention and Control of HIV/AIDS
--Treatment, Prevention and Control of HIV/AIDS
-HIV Quiz
-5.1 HSV
--HSV
-5.2 VZV
--VZV
-5.3 EBV, CMV and HHV 6-8
-Herpes Viruses Quiz
-6.1 HAV and HEV
-6.2 HBV, HCV and HDV
-Hepatitis Viruses Quiz
-7.1 Arbovirus
-7.2 Hemorrhagic Fever Virus
-7.3 Rabies Virus
-7.4 HPV
--HPV
-7.5 Prion
--Prion
-Other Important Human Viruses Quiz