病毒性肝炎手作坊

影片連結:https://en.wikipedia.org/wiki/File:Viral_hepatitis.webm

譯者姓名:林欣儀、李姿穎

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Hepatitis, meaning like this inflammation,

of the liver, most commonly comes about because

肝炎,就是肝臟發炎,

通常是因病毒感染引起。

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of a virus. These viruses tend to target the

cells in the liver, and when they get in and

病毒鎖定了肝臟的細胞,

一旦造成感染,

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infect these cells, they tend to cause them

to present these weird and abnormal proteins

受感染的細胞

會排放出異常的蛋白質。

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via their MHC class 1 molecules, and at the

same time, you’ve also got these immune

排放途徑是第一類MHC分子,

身體裡的免疫細胞也會進入肝臟,

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cells infiltrating the liver and trying to

figure out what’s going on, and so the CD8

這時體內免疫細胞也進入肝臟

好查明情況

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positive T cells recognize these abnormal

proteins as a sign that the cells are pretty

若CD8+ T細胞確認蛋白質異常

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much toast, and the hepatocytes go through

cytotoxic killing by the T cells and apoptosis.

就會將細胞毒殺。

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Hepatocytes undergoing apoptosis are sometimes

referred to as Councilman bodies, shown on

組織學上,

凋亡中的肝細胞稱為康氏小體。

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histology here, and this typically takes place

in the portal tracts and lobules of the liver.

通常出現在肝門道與肝小葉。 

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This cytotoxic killing of hepatocytes is the

main mechanism behind inflammation of the

免疫系統毒殺受感染的肝細胞

是肝臟發炎的主要原因

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liver, and eventual liver damage in viral

hepatitis! As someone’s hepatitis progresses,

甚至造成病毒性肝炎的嚴重傷害

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we’ll see a couple classic symptoms related

to your immune system mounting an attack,

免疫系統攻擊病毒

會產生各種症狀

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like fever, malaise, and nausea. Additionally

though, patients might have hepatomegaly,

像是發燒、全身不適與反胃。

此外,由於發炎,

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where their liver is abnormally large from

inflammation, which might cause some pain.

病人的肝會異常腫大,

因此可能會疼痛。

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Also, as more and more damage is done to the

liver, the amount of transaminases in their

隨著肝臟不斷受到侵擾

轉胺酶在血液中的數量就會增加。

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blood will increase. Your liver has these

transaminase enzymes so it can do its job

肝臟有了這些轉胺酶,

就開始分解各種胺基酸

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of breaking down various amino acids. Typically

the serum amino transaminase, or the amount

通常血清氨基轉胺酶成分在血液中是非常少的,

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in your blood, is pretty low, but when your

hepatocytes start getting damaged they start

但當肝細胞遭破壞

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leaking these into the blood, so a common

sign is a greater amount of both alanine aminotransferase,

便將胺基轉胺酶排放到血液中

最常見的現象就是

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or ALT, and aspartate aminotransferase, or

AST, typically even though both are elevated,

谷丙轉胺酶(ALT)

天冬胺酸氨基轉移酶(AST)

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ALT will be greater than AST in viral hepatitis

and will also be the last liver enzyme to

雖然兩者的量都會上升

但ALT含量較高,也最難恢復正常

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return to normal. Also, elevated levels of

atypical lymphocytes are common to see with

此外,病毒性肝炎另一常見現象

是非典型淋巴球數量增加

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viral hepatitis, known as atypical lymphocytosis.

The lymphocytes are usually like huge, very

最為熟知的名稱為淋巴球增多症。

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large, due to stimulation from antigens, in

our case the hepatitis virus antigens. Patients

由於受抗原體刺激,

淋巴球會腫得很大,

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often also end up developing jaundice, with

a mix of both conjugated bilirubin and unconjugated

最後形成黃疸

共軛與非共軛膽紅素相混合

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bilirubin. The conjugated bilirubin leaks

out when bile ductules are damaged or destroyed

當一些內部組成的肝細胞死亡時,

膽小管壞死,

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when the hepatocytes die, which make up some

of its lining! Also, since these hepatocytes

共軛膽紅素就會流出來補強外壁

也因為肝細胞死了,

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are dying, you start to lose the ability to

conjugate bilirubin and make it water soluble,

共軛膽紅素會失效、呈水溶性

非共軛膽紅素也是。

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and so you also end up with unconjugated bilirubin

as well. So since there’s both conjugated

因為兩種膽紅素混在血液裡

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and unconjugated bilirubin in the blood, some

of the water soluble conjugated bilirubin

膽紅素呈水溶性,會滲入尿液

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gets filtered into the urine, giving it a

darker color. Another common finding is increased

使其顏色變深。

另一種常見現象是

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urobilinogen in the urine, urobilinogen is

produced when bilirubin is reduced in the

尿液中的尿膽素原增加

原因是膽中的膽紅素減少

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gut by intestinal microbes, usually most of

it’s then reabsorbed and transported back

通常尿膽素會被肝臟再吸收

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to the liver to be converted back to bilirubin, 

or bile. If these liver cells aren’t working

或是還原成膽紅素或膽汁

若肝細胞無法正常運作,

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properly, that urobilinogen is redirected

to the kidneys and excreted, so you end up

尿膽素原就透過腎臟排泄掉。

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with more urobilinogen in your urine.

尿液中尿膽素原也因此增加。

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If symptoms continue or the virus sticks around

for more than 6 months, viral hepatitis goes

症狀延續或是病毒停留

如果超過6個月

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from being called acute to being called chronic

hepatitis. At this point, inflammation mostly

病毒性肝炎就會由急性

演變成更嚴重的慢性肝炎

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happens in the portal tract, and if inflammation

and fibrosis keep persisting, we consider

這種情況下,

發炎的部位大多是在肝門徑。

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that a bad sign, since it might be progressing

to postnecrotic cirrhosis.

若發炎和纖維化的現象持續

就可能變成肝硬化

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Now there are five known flavors or types

of hepatitis virus, that have slightly different

現在共發現五種肝炎病毒

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and unique properties. Hepatitis A is transmitted

through ingestion of contaminated food or

它們各有稍微不同的特質

A型病毒經由食物或水感染

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water, in other words the fecal-oral route,

and is known to be acquired by travelers.

換句話說,就是病從口入,

出門在外的人最容易受害

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Hepatitis A virus, or HAV, is almost always

acute only, and there is essentially no chronic

A型肝炎,或稱HAV,

為急性肝炎,並不會轉變成慢性

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HAV. If we’re talking serological markers,

an HAV-IgM antibody indicates an active infection,

若以血清指標來看,

HAV-IgM抗體表示有感染

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whereas HAV-IgG antibody is a protective antibody

and tells us that there’s been recovery

HAV-IgG抗體是保護性抗體

表示過去的感染已消除

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from HAV or vaccination in the past. Hepatitis

E virus’s actually pretty similar to HAV,

E型病毒和A型非常相似

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with the same route of transmission, oral-fecal,

and is most commonly acquired through undercooked

都是經由口食傳染,尤其是

生食海鮮或是不淨的水所造成

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seafood or contaminated water. It also doesn’t

have much of a chronic state, and HEV-IgM

通常也不會轉變成慢性肝炎

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antibodies tell us there’s an active infection

and HEV-IgG antibody is protective and signals

HEV-IgM抗體表示有感染

HEV-IgG抗體是保護性抗體

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recovery. Two big differences to note though

between these two guys, is that (1) only HAV

表示感染消除,健康恢復

HAV和HEV兩者最大的差異

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has the option for immunization. and (2) HEV

infection for pregnant women can be very serious, 

第一,人體只會對HAV有免疫力

第二,HEV對孕婦的影響非常大

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and can lead to acute liver failure, also

sometimes called fulminant hepatitis. Alright

可能造成急性肝衰竭

也稱為猛爆性肝炎

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next on the docket is Hepatis C virus, this

guy is transmitted via the blood, so could

接下來介紹C型肝炎病毒

它簡稱C肝,經由血液傳染

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be from childbirth, intravenous drug abuse,

or unprotected sex. C肝 usually does move

所以生孩子、注射毒品

或是不安全的性行為

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on to chronic hepatitis. There’re a couple

tests that we use to help diagnose C肝, one

都可能會傳染C肝

C肝診斷方法有幾種

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way is by enzyme immunoassay, so we’d screen

for the C肝-IgG antibody, if present, it doesn’t

第一種是用酶免疫測試

來看是否找到C肝抗體

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necessarily confirm acute, chronic, or resolved

infection and it isn’t regarded as a protective

但是即使找到,也不能斷言

是急性、慢性,或是已經痊癒

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antibody like HAV and HEV, to get more specific

confirmation, you might use recombinant immunoblot

C肝抗體不像HAV或HEV

要確診為C肝

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assay which helps confirm C肝, it’s more

specific but less sensitive than the immunoassay,

可以透過重組免疫墨點分析

這種方式也不如免疫分析敏銳

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and clinically doesn’t provide much usefulness

and needs an additional supplemental test

臨床上效用有限

發現陽性反應,還要做其他檢查

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if positive. That said, the gold standard

for C肝 diagnosis is an C肝 RNA test, using

診斷C肝的最準確方式

是C肝 RNA檢測

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PCR or polymerase chain reaction, this method

can detect the virus very early on, as much

這種方法

檢驗聚合酶鏈鎖反應(PCR)

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as 1 to 2 weeks after infection, basically

it detects the levels of viral RNA in the

可在感染後一兩週查出病毒

它檢測血液中病毒RNA的級數

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blood, which tells us the levels of virus

circulating. If RNA levels begin to decrease,

判斷病毒循環的週期

若RNA級數開始下降

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we know the patient’s recovering, if RNA

remains the same, the patient probably has

則可知病人正在康復中

若RNA持平,則可能為慢性C肝

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chronic C肝. Okay, on to hepatitis B, B肝’s

just like C肝 in that it’s contracted via

現在來談B型肝炎,簡稱B肝

B肝和C肝都由血液接觸感染

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blood, so the same routes like childbirth,

unprotected sex, and others. B肝, however,

包括母嬰垂直感染

或是不安全性行為等原因

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only moves on to chronic hepatitis in 20%

of cases overall, but it also depends on the

但B肝僅有20%會變成慢性

但是,跟感染的年紀也有關係

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age that someone gets infected, for example

children less than 6 years old are most likely

六歲以下孩童感染B肝

約50%會轉成慢性肝炎

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to get chronic infections, about 50%, and

that percentage increases as they get younger.

感染年紀越小

轉為慢性肝炎可能性越高

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Also, chronic B肝 is known to be linked to

liver cancer. All these things make B肝 and

慢性B肝也與肝癌有關

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the serology of B肝 a super important concept

to understand, and kind a like hepatitis C

因此B肝血清學極為重要

跟C肝檢驗一樣

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we can use a variety of testing methods, like

PCR, to look for certain markers, especially

我們也可以用PCR等方法

來檢測B肝抗體

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the B肝 antigens. And the presence or absence

of each at different time points tells us different

抗體數量多寡

在不同時間有不同的意義

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things. K so the key marker for an B肝 infection

is the B肝 surface antigen, this is like the

顯示感染B肝的最大指標

是B肝表面抗原

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supervillain in this story, and this evildoer

lives on the surface of the virus, here, and

這就是我們要談的大魔頭

它住在病毒表面

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we can call it HBsAg, meaning Hepatitis B

surface antigen. Another marker though, is

我們稱之為B肝表面抗原

也就是HBsAg

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a core antigen, meaning that these antigens

come from the core of the virus, HBcAg, think

另一個指標是一種核心抗體

存在病毒的核心,叫HBcAg

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of these like the dispensable henchmen that

work inside the villain’s evil factory.

它就像是大魔頭的嘍囉

在它的基地裡工作

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Finally there’s this other antigen called

the ‘e’ antigen, which is secreted by

最後還有一種抗原

e抗原

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infected cells and so is a marker of active

infection, these are like the byproducts of

它由感染的細胞分泌出來

是病毒的活性指標

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the factory and along with viral DNA, that

tell us it’s replicating and infecting.

它就像是毒品工廠的副產品

顯示病毒的繁殖和感染情況

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Alright, so at the onset of infection, during

the acute phase, our surface antigen villain

感染初期,也就是急性期

表面抗原開始出現

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will be positive and it’s layer will be

pumpin’ out both viral DNA and e antigen,

它的表層分泌出病毒DNA

還有e抗原

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at this point the immune system produces IgM

antibodies, which are like your basic police

這時免疫系統會製造出IgM抗體

它就是你的警察部隊

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force, against the core henchmen. These antibodies 

hack away at the core antigens and do their 

專門對付核心裡的壞蛋

這些抗體對核心抗體全力猛攻

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darndest, but in order to really defeat the

virus, you need to go for the supervillain,

但是想要真的消滅病毒

得打倒大魔頭-表面抗體

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the surface antigen, so the we need a superhero

to go after it, and in this story the IgG

為此目的,我們需要大英雄

我們的大英雄呢…

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antibody for the surface antigen is our superhero.

At this point, the host enters this spooky

當然就是IgG抗體啦

這時,患者進入病情潛伏期

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phase called the window, where neither the

supervillain or superhero can be detected,

大魔頭也好,大英雄也好

因為它們濃度太低

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because they’re so low, and this can last

from several weeks to months, it’s like

各種動態,我們都難以查覺

潛伏期可能長達數週至數月

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the war’s being waged but we don’t know

who’s coming out on top. The only thing

此時其實雙方已經開戰

只是我們看不見誰佔上風

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you can detect during this stage is the IgM

core antibodies, the police force. At this

這時期所能檢測到的

只有我們的警察部隊---IgM抗體

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point, two things can happen, if the superhero

comes out, the IgG antibodies to the surface

這時,只有兩種可能

一是大英雄IgG出現

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antigen, we’re golden, and this means the

day is saved and we win. The other possibility

表示情況受到控制

也就是危機解除,我們獲勝

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is that the supervillain wins, and surface

antigens are still again detected, there may

另一個可能性是反派獲勝

表面抗原仍然存在

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also be presence of B肝 DNA and e antigen

because it’s now replicating again, the

B肝DNA和e抗原繼續存在

還會繁殖增生

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main point though is that there will not be

the IgG for surface antigens, our superhero.

問題是大英雄IgG不見了

表面抗原就更肆無忌憚了

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Regardless of who wins, the IgM antibodies,

the police force, will be promoted to IgG

不論誰贏,我們的警察部隊IgM

六個月內都會升級成IgG

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by 6 months time, and this does not mean that

the host is protected. So it’s important

這不代表患者可以高枕無憂

所以我們得注意

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to note that we need this surface IgG superhero

to win, but we can have core IgG and still

我們只靠核心抗原IgG還不夠

獲勝關鍵是表面抗原IgG

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lose. If the battle’s lost, the host transitions

into chronic viral hepatitis, defined by it

要是不幸失敗

患者會形成慢性肝炎

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continuing after 6 months. When chronic, the

host could present as “healthy”, and will

就是說六個月後症狀仍持續存在

患者表面會看似健康

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likely have the presence of surface antigen,

core antibody, and no DNA or e antigen, basically

體內有表面抗原、核心抗體

也看不出病毒DNA或e抗原

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saying that the supervillain’s there, it’s 

just not replicating, and at this point the

表示大魔頭雖然存在

卻沒有繁殖增生

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00:10:46,480 --> 00:10:52,260

host is contagious, but there’s lower risk.

The other option is that they’re infective,

這時患者傳染性通常較低

但是有時候感染性也可能很高

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00:10:52,260 --> 00:10:58,020

meaning the whole villain force is active

along with an overwhelmed police force. This

就是說反派勢力強大

警察部隊無力壓制

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state increases the risk for postnecrotic

cirrhosis and hepatocellular carcinoma. One

這種情況下

肝硬化、肝癌的機率就會大增

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way to get around this whole fiasco is by

immunization, which skips these steps and

要避免這種情況有一種方法

就是免疫接種

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00:11:08,370 --> 00:11:15,080

gets you right to the IgG superhero antibody

for surface antigen. Alright, last but not

直接讓大英雄表面抗體保護你

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00:11:15,080 --> 00:11:21,130

least, well maybe least, I donno, anyways

Hepatits D virus is a unique in that it NEEDS

最後...可能不是絕對要緊的一點

D型肝炎病毒,得靠 B肝

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B肝, it can only infect if the host also has

B肝. If it infects at the same time, it’s

只有B肝患者才可能得D型肝炎

兩種病毒可能同時感染

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called co-infection, if it infects sometime

later, it’s called superinfection, which

若是較晚感染D型

就叫作超級感染了

66

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00:11:35,080 --> 00:11:42,250

is considered to be more severe that co-infection.

If either the IgM or IgG antibody are present,

它比同時感染更為嚴重

只要有IgM或是IgG抗體出現

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that indicates an active infection, so in

this case the IgG is not a protective antibody.

都表示發生感染現象

這時,IgG抗體就不是保護性抗體