Hepatitis
Content
viral hepatitis
Dr. khaled Jadallah
ﺗوﻛﻠت ﻋﻠﻰ ﷲ
***awal eshi…..hai awal mo7adara bktobha l7ali…..l2no "zi ma kolko bt3rfo"….6
mo7adrat kan eli elsharaf enni aktob eljoz2 eltani fehom daymn b3d 7bebi w a5oi
hadi…...basmt eldof3a….fa kan lazem ahdi hai elmo7adra elo, w akeed elehda2 ma bkml
bdon ma a8dem shokr mn el8lb la5oi "eltani "3bdulla…..3la kol eld3m elfnni elli 8adamo
eli w la hadi bel 6 mo7adrat…….so thanx for both of you guys… .
And now let's begin……
In the first 15 minutes of the lecture…our cr. Hashem and the Dr. said very imp.
notes about this course "internal medicine"….
***Now, our subject today is about viral hepatitis….from "A "to "E"….so we are
concerned to learn about hepatotropic viruses, and those are the viruses with
predilection to the liver rather than any other organ, and those are hepatitis
viruses"A,B,C,D,E ."By the way, we have other viruses that may infect the liver, but
they aren't hepatotropic, like CMV, EPV, adenovirus and even mumps virus.
>>>first of all we should know the objectives of this lecture…..
Outline the epidemiology of viral hepatitis
List causative agents for viral hepatitis
Recognize the clinical features of acute and chronic viral hepatitis and their complications… .
By the way this isn't very complex issue….anyway there is nothing specific about clinical
manifestations of hepatitis weither it's acute or chronic…means that the symptoms of hepatitis can be
caused by other diseases .
Interpret serologic tests to accurately diagnose the specific cause of viral hepatitis…bcoz we
can't depend on the clinical manifestation to diagnose as we said…so serology will be the best way for
diagnosis .
Outline the treatment of acute and chronic hepatitis…not much for us as 4th year medical
students.
Identify appropriate candidates for vaccination against HAV and HBV…by the way we don't
have vaccines for HCV, HDV or HEV.
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viral hepatitis
Dr. khaled Jadallah
***now, we classify these viruses according to the route of transmission
into….Enterically transmitted through feces" A,E "…,and Parenterally
transmitted through serum" B,C,D", and we have others like G….anyway, you will
notice that the enterically transmitted types almost always cause acute infection,
while the opposite occur with the parenterally transmitted ones.
>>here in the following table we can learn the differences between the different
types…..
----------Source of
virus
Route of
transmission
A
feces
C
Blood,
Body fluids
Percutaneous,
Permucosal
D
Blood,
Body fluids
Percutaneous,
permucosal
E
feces
fecaloral
B
Blood,
Body fluids
Percutaneous,
permucosal
Chronic
infection
prevention
No
Yes
Yes
Yes
No
fecaloral
Pre/postPre/postBlood donor
Pre/post-Exposure
Ensure Safe
Screening, risk
Drinking
Exposure
Exposure
Immunization, risk
immunization immunization Behavior modification Behavior modification water
>>>some notes about the table:
Dr .emphasize about the importance of the chronicity of the disease…he
said that the chronic disease is much more imp .bcoz of epidemiologic
burden and the cost on community.
HAV and HEV never cause chronic disease.
Pre-exposure immunizationby vaccines.
Post-exposure immunizationby immunoglobulins.
There is no immunization (pre -or post) -against HCV.
HDV can't survive without HBV, so we don't have pure HDV infection.
HEV is most dangerous in pregnant women, but we don't have a lot of
cases in our region….or let's say we don't diagnose it usually…bcoz there is
no serological test available, even in USA, there is CDC serological test
only, but it isn't that common.
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viral hepatitis
Dr. khaled Jadallah
###Clinical Manifestations of Acute Hepatitis:
Acute HAV mostly symptomatic, especially in adults…actually it's the most
symptomatic infection among all hepatitis types, and again it's more symptomatic among
adults….why? bcoz immune system in adults is more developed…knowing that the
symptoms in hepatitis infection in general is caused by the immune reaction, not by the
cytopathic effect of the virus "means that hepatitis virus doesn't cause cytopathic effect, so
it doesn't kill the cell, what kills the cell is the immune systemleads to symptoms"
The dr .gives us here a very important info…..HAV is the most icteric
type…means that it's the most common cause of jaundice among hepatitis
types….you should know that not all cases of hepatitis are associated with
jaundice, and this causes some difficulty in diagnosis .For example HAV
which is the most icteric type as we said causes jaundice only in 60 %of
cases .So the message is that the absence of jaundice doesn't rule out the
presence of hepatitis .
Acute HEV is most symptomatic and severe in pregnant women…mortality rate in
infected pregnant ladies reaches 30%.
Acute HCV is the least symptomatic
Acute HBV can present with a serum sickness-like picture (fever, arthritis, urticaria,
angioedema)…anyway it may occur also with some drugs reactions.
Generally, symptoms improve after jaundice appears.
the most typical symptoms of hepatitis are jaundice and upper abdominal pain…..again
sometimes we don't have both and symptoms are just what we call the viral syndrome "nonspecific symptoms" and these are (fever, malaise, anorexia, RUQ pain, diarrhea, pruritis).
###LAB investigations of acute hepatitis…as we said, we depend on this to
diagnose hepatitis, bcoz of non-specific symptoms .To diagnose the case as
acute viral hepatitis, the liver enzymes must be elevated 10 times more
than the upper limit, means that if the upper limit is 30 U/L then the liver
enzymes must be more than 300 U/L.
Hepatocellular injury" injury in the hepatic cells themselves" typically shows
marked elevation in liver enzymes especially AST " Aspartate transaminase" and
ALT" Alanine transaminase" enzymes….this injury could be viral, drug-induced or
ischemic .
Cholestatic injury "damage primarily in ductules and canaliculi, bcoz of
obstruction "also causes elevation but less than that of hepatocellular injury,
and mainly in AP" Alkaline phosphatase", bilirubin and GGT" Gamma glutamyl
transpeptidase "rather than the enzymes .
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viral hepatitis
Dr. khaled Jadallah
some drugs like oral contraceptive pills raise the cholestatic factors, others
like diclofenac "Voltaren " raise hepatocellular factors.
Other causes of modest elevation "other than cholestatic injury "include
acute or chronic hepatocellualr injury" but usually it causes high elevation
as we said", infiltrative diseases, acute alcoholic hepatitis, and metastatic
diseases.
---Note :when we say marked elevation means…>500U/L, while modest
means <300U/L.
WBC :may show leucopenia .Why? Bcoz it's viral inection.
From slides… .Bilirubin and AP may or may not be elevated.
###Stigmata of Chronic Liver Disease :the followings features typically found
in CLD:
Spider Agiomas " spider nevus"is a type of telangiectasis found slightly beneath the skin
surface, often containing a central red spot and reddish extensions which radiate outward like a
spider's web
Palmar erythema is reddening of the palms at the thenar and hypothenar eminences.
Clubbing of fingers
Dupuytren contractures is a fixed flexion contracture of the hand where the fingers bend
toward the palm and cannot be fully extended.
Gynecomasita (male) or breast atrophy (female)….why males is the opposite of
females here? Bcoz of disturbed mechanisms of metabolism of hormones.
Testicular atrophy, the same reason as the previous point.
***note :definitions are from Wikipedia.
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viral hepatitis
Dr. khaled Jadallah
-This is spider angioma….it's
typically has a raised center
with branching light capillaries.
-When press on it, it will
disappear, unlike vasculitis.
-Typically, they are found on
the face, or on the chest,
anyway it will never appear in
an area below the line
connecting the two nipples,
bcoz its pathology is related to
the circulation of SVC .
-This is palmar erythema, many
normal people may have this,but
here it's more prominent on thenar
& hypothenar sides.
-it may be found in other
situations like pregnancy, steroid
treatment, any RS disease with
CO2 retention.
Here on the left, we have Dupuytren contractures, and on the right we have clubbing,
and we should know that clubbing may occur in all digits…upper or lower.
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viral hepatitis
Dr. khaled Jadallah
Now, we will start talking about each type of hepatitis viruses one by one…
Hepatitis A
***the incubation period of this virus is 25 days in average (15-50 days), and we
said that it's the most symptomatic among "his brothers", and we said that the
appearance of symptoms depends on age "the older you are, the more symptoms
you will get", for example jaundice appear in <10% in children younger than 6
years old, while those with age between 6 and 14 years, have jaundice in 40-50 %
of cases, while if you are 14 years old or older than that , you have a chance of
70-80 %to get jaundice.
As we said, this type will never lead to chronic infection, but in few cases may
lead to certain complications .It may lead to fulminant hepatitis in 0.1 %of cases,
and this occurs usually in elderly people with poor health, rarely in young people .
Prolonged cholestasis is another complication, it means prolonged jaundice for
5-6 months, and it isn't really harmful .And sometimes the infection may be
complicated with autoimmune hepatitis "see lecture 6 by hadi radaideh ."
Now regarding serological tests,we ask for
different liver enzymes like ALT .But the most
important thing is to ask for IgM anti-HAV titer,
bcoz it's an acute infection, so if it's +ve IgM,
then it's +ve infection, and the opposite is
true…….see the adjacent picture .
HAV
"e.g.,
may
transmit
through
multiple
ways….1Close personal contact
household contact, sex contact, child day care centers", 2 Contaminated food, water
infected food handlers, raw shellfish", 3 and rarely through blood"e.g., injecting drug use,
"e.g.,
transfusion ".
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viral hepatitis
Dr. khaled Jadallah
the distribution is related mainly to
the level of hygiene.
Although Jordan here is labeled with
red"means high prevalence",but this
isn't actually true, dr. said"we see just
one case every one or two month".
If you want to go to areas of high
prevalence, you have to be careful,
and if you want to stay for long time,
you have to be vaccinated.
Now let's go back to the serologic tests, as we said IgM Ab is used to diagnose
current infection, while IgG anti-HAV is used to diagnose immunization, either
through past infection or vaccination .
Regarding vaccination "pre-exposure prevention", it's given to some people
that are at high risk, and those are…Travelers to endemic regions "here it must be given
2-3 weeks before travel", Homosexual men, Injecting drug users .We have many cases of
infection occur in community wide outbreaks, and in most of cases in these
outbreaks *there is no definite risk factor, and *the outbreak affects mainly the
age group from 5-14 years old, and *children serve as reservoir of the infection .
The post-exposure prevention" by vaccines or by IG "is given within 14 days
of exposure .It's given routinely in household and other intimate contacts, and is
given also in other selected situations like in day care centers & and in case of
exposure to food prepared by infected handler.
Hepatitis B
In HBV infection, the incubation period is 60-90 days in average (45-180 days), and again the
older you are the more symptoms you will have, jaundice appear in <10 %in age younger than
5 years, and 30-50 % in age older than 5 years old. Fatality rate in acute phase (bcoz of
fulminant hepatitis ) reaches 0.5-1%. The opposite of the clinical manifestation, chance to turn
into chronic phase decrease with age, it may reach 30-90 % in <5 years old, and 2-10 %in >5
years old, why? that is with developed immunity , it's hard for the disease to become chronic.
The chance of premature death bcoz of chronic liver disease caused by HBV is 4 times more
than healthy people, so it may reach about 15-25 .%
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viral hepatitis
Dr. khaled Jadallah
Now regarding the epidemiological facts about HBV, you have to know that 2
billion (1/3 of the world ) is current or past infected, 1/5 of them (around 350-400
million) are currently infected (chronic or carriers), 40 million in eastern
Mediterranean region, and this makes HBV the most common chronic infection
worldwide. In Jordan we have 4-8 % of population are infected. 25-40 %of HBV
infected people die from HCC or cirrhosis. Over 300,000 cases/year of HBVrelated HCC worldwide, you should know that HBV is 2nd most common
carcinogenic factor just after smoking.
HBV is 100 times more contagious than HIV, dr .then talked about what we call
the rule of three…..that is if you have a patient with 1HIV, the chance to get the
disease from him is 0.3%, with 2HCV……it's 3%, and with 3HBV…..it's 30% .
Here you can see that HBV is the 7th
most common cause of death among
infectious diseases, and HCV is the
10th, anyway if you grouped them
together viral hepatitis will become
the 5th in this list. And the problem
isn't only the mortality rate, also
the morbidity and the cost of
management are also problems in this
disease.
Clinically, we have an acute phase and a chronic phase…..in acute phase it may
lead to fulminant hepatitis and death .Chronic infection may lead to HCC,
cirrhosis, liver failure, and very important and disabling extrahepatic
manifestation "we will talk about them later".
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viral hepatitis
Dr. khaled Jadallah
Look carefully at the table above… and try to memorize it…
Here are some notes about it…..
The main difference in investigation between the immune tolerant & the carrier is the amount
of the virus in the serum "HBV DNA "and this is the main way to differentiate between them .
But why is it so imp .to differentiate? Bcoz 1the chance of immune tolerant case to become
chronic is much more, and 2we don't treat immune tolerant cases, bcoz the liver isn't yet
damaged .
Now if anti-HBs is +ve and nothing else is +ve, then the patient is vaccinated.
***the following notes are written by the dr .in the notes below the slide.
Most patients presenting to clinicians in practice fall into 1 of 4 groups .All of these individuals have
chronic HBV infection as indicated by the presence of HBsAg .Those in the immune tolerant phase are
HBeAg positive, have normal ALT levels, high levels of HBV DNA, and mild or normal histology .Current
treatment strategies are not focused on these patients.
Two groups have active disease :those with HBeAg-positive chronic hepatitis B and those with HBeAgnegative chronic hepatitis B with promoter mutations .Both groups exhibit abnormal ALT levels, elevated
HBV DNA levels, and necroinflammation with varying degrees of fibrosis .Because these patients are at
the greatest risk for disease progression and liver disease complications, they are the target groups for
treatment .
Finally, patients with inactive chronic HBV infection carry HBsAg but lack HBeAg .They are anti-HBe
positive but exhibit normal ALT levels, low HBV DNA levels, and may have residual fibrosis on histology .
Now we should go back to talk about extrahepatic manifestations, these
manifestations varies according to the state of the infection "if it's acute or
chronic"….. the ones which are associated with the acute infection include
Arthralgias, Papular acrodrmatitis "Gianotti-Crosti syndrome", and the ones which are
associated with the Chronic infection are Glomerulonephritis, Arthrlalgias (so it may
come with acute or chronic), Polyarteritis nodosa (PAN).
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viral hepatitis
Dr. khaled Jadallah
These are two pictures of Papular acrodrmatitis, which is associated with multiple
small papules, and it's a rare condition.
On the other hand, this is common, this is Polyarteritis nodosa, this is a case of
vasculitis, so it disappears with pressure, it's so painful, it occurs mostly on the
extremeties, but may also affect the visceral arteries.
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viral hepatitis
Dr. khaled Jadallah
Look carefully at the adjacent pic .And here are some
notes
:
This is in case of recovery.
The first thing to appear is HBsAg, followed by
HBV DNA "this occurs in all cases, with or
without recovery".
in case of recovery anti-HBs will appear, so
it's the last one to appear.
The importance of IgM anti-HBc "core antigen"
is used for the diagnosis of acute HBV
infction.
Again look, and here are some notes…
This is in case of progression into chronic
case.
Here HBsAg remains high, and the antibodies
against it don't appear at all.
And bcoz it turns into chronic, IgM anti-HBc
regress after a while, but we can see that total
anti-HBc is high, this means that IgG is high, so
we use it in diagnosis of chronic infection.
***it seems somehow complex now, later in this lec., we will talk further about this topic, maybe it will be more
simple then.
Here, we can see what we said before…..syptomatic
infection increase with age… .In contrast with the
chronic infection which decrease with age.
Can you now tell me why? You should know now…☺.
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viral hepatitis
Dr. khaled Jadallah
In the picture above, we can see that there is a relation between epidemiological burden
and the clinical manifestation, so areas of high endemicity like Asia and sub-Sahara, have
high prevalence of the disease in newborn (perinatal root)and toddler(horizontal root) so
chronicity is higher and complications(like HCC )is higher .In case of low endemicity like
in Europe, the infection affects mostly young adults (percutaneous "IV drugs "and sexual
root), so less chronicity and less complications .
HBV can be detected in any biological fluid, and it presents in variable amount, for
example; it presents in high amount in blood, serum and wound exudate .On the
other hand it presents in moderate amount in semen, vaginal fluid and saliva .And
in low amount in urine, feces, sweat, tears and breast milk .So as a general
precaution, try to avoid any direct contact with any biological fluid.
Modes of transmission….multiple ways include:
Sexual promiscous heterosexuals" multiple sexual partners" and homosexuals are
particular at risk.
Parenteral IV drug abuser, Health Workers are at increased risk
Perinatal Mothers who are HBeAg positive are much more likely to transmit to their
offspring than those who are not. Perinatal transmission is the main means of
transmission in high prevalence populations, and bcoz of that, we start to do screening
tests for pregnant ladies, so if she is infected, they vaccinate the baby and give him/her Ig
as soon as he/she is delivered, and this decreases the chance of the newborn to be infected
by 95%.
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viral hepatitis
Dr. khaled Jadallah
The initial evaluation of HBV infection includes:
i. History …we should focus on Q's about the possible routes of acquisition the infection
ii.
iii.
to estimate the duration of infection and predict the risk of complications, so you should
ask about family history of HBV infection or HCC, alcohol use should be discussed
further if it's positive.
Physical examination… .focus on determining disease stage and the possible presence
of cirrhosis or decompensated liver disease.
Investigation …focus on assessing liver disease activity, serologic and virologic markers
of disease, screening tests for HCC (AFP" α-fetoprotein" and ultrasound) and tests for HCV
& HIV.
Diagnosis, as we said before it depends on serology….as follows :
HBsAg -used as a general marker of infection.
HBsAb -used to document recovery and/or immunity to HBV infection
anti-HBc IgM -marker of acute infection
anti-HBc IgG -past or chronic infection
HBeAg -indicates active replication of virus and therefore infectiveness
Anti-HBe - virus no longer replicating .However, the patient can still be positive
for HBsAg which is made by integrated HBV
HBV-DNA -indicates active replication of virus, more accurate than HBeAg
especially in cases of escape mutants .Used mainly for monitoring response to
therapy
here we have very
important table …
which
explain
again what we
said before
try to memorize it,
dr .said that it's
very imp .
١٣
viral hepatitis
Dr. khaled Jadallah
Treatment…in case of acute infection, we don't do anything unless the patient
has signs of liver failure .In chronic infection, there are certain drugs…
dr .said "I don't think it's fair to ask you as 4th year medical students
about treatment and investigations"…7elo el2dwye m7zofe…☺
So I copy these info. From slides:
Interferon -for HBeAg +ve carriers with chronic active hepatitis .Response rate is 30
to 40%
Lamivudine -a nucleoside analogue reverse transcriptase inhibitor .Well tolerated,
most patients will respond favorably .However, tendency to relapse on cessation of
treatment .Another problem is the rapid emergence of drug resistance
Successful response to treatment will result in the disappearance of HBsAg, HBVDNA, and seroconversion to HBeAb
prevention…dr .didn't talk a lot about it….he just talked about the importance of getting
vaccinated to protect yourself, bcoz you will face a lot of patients with this disease…so take
care. I will put the slide of vaccination…read it .
Done by:
Saleh abo-libDeh
www.shifa2006.com
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Continue to viral and autoimmune hepatitis
ﺑﺴﻢ اﷲ اﻟﺮﺣﻤﻦ اﻟﺮﺣﯿﻢ
Short summary about the types of hepatitis:
Hepatitis A : Self-limited viral disease of worldwide distribution caused by
hepatitis A virus, more common in areas of poor hygiene and low socioeconomic
standards, transmitted almost exclusively by the fecal-oral route, although parenteral
transmission is possible; no carrier state. Incubation period is approximately 25 days,
with a range of 15 to 50 days. Most cases are clinically inapparent or have mild
flulike symptoms; jaundice, if present, is usually mild. Massive hepatic necrosis
(fulminant hepatitis) can occur but much less commonly than with hepatitis B.
Previously called epidemic hep., MS-1 hep., jaundice infectious hep., and shortincubation hepatitis.
Hepatitis B: Viral disease caused by the hepatitis B virus that is endemic
worldwide. The virus is shed in all body fluids by individuals with acute or chronic
infections and by asymptomatic carriers, and is transmitted primarily by parenteral
routes, such as by blood transfusion or by sharing of needles among drug users; oral
transmission can occur but has low efficiency, and it can be spread by intimate
personal contact, especially sexual contact, and by vertical transmission from mother
to neonate. Incubation period averages about 90 days, with a range of 45 to 180
days, the clinical course is more variable than in hepatitis A. During the prodromal
phase there may be fever, nausea, malaise, anorexia, and vomiting, which lessens
with the onset of clinical jaundice. Most patients recover completely and become HBS
Ag-negative in 3 to 4 months, some will remain chronic carriers or develop chronic
active hepatitis or chronic persistent hepatitis. Massive hepatic necrosis (fulminant
hepatitis) is an infrequent complication. In areas of high endemicity a relationship
has been shown between hepatitis and virus infection, cirrhosis, and primary
hepatocellular carcinoma, with the latter being one of the most common neoplasms.
Previously called inoculation hepatitis, long incubation hepatitis, MS2 hepatitis, serum
hepatitis, and homologous serum hepatitis or jaundice.
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Continue to viral and autoimmune hepatitis
Hepatitis C Virus (HCV)
We have around 6 different genotypes (1,2,3,4,5,6) , here in our
region we are concerned about 1 & 4 (50% of the types) , 2 & 3 more in
Europe, 5 & 6 scattered in south Africa and some countries. The
important thing about these genotypes is that each one of them has it's
way of response to treatment, for example 2 & 3 genotypes have a very
good response and the duration of treatment is short (about 6 months),
but in case of 1 & 4 (unfortunately in our region) the response to
treatment is 20%-30% less than 2 & 3 and the duration of treatment is
12 months, this in case of poor economy will double the cost (the cost to
treat the viral hepatitis around 14,000-18,000 JD).
In this diagram NS2 & NS3 ….etc are structural proteins in which all
the drugs that are being generated acting against these structural
proteins. The problem is in the hypervariable region that changes in it's
structure always, so this make a challenge to produce a vaccine for this
type of virus ( like HIV, influenza virus).
So the problems that we face in case of hepatitis C :
- More than one genotype (we have 6)
- The treatment is very expensive
- The presence of the hypervariable region in the genetic material.
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Continue to viral and autoimmune hepatitis
Clinical features of hepatitis C:
- The incubation period is around 4-7 weeks (from the slides the
range from 2-27weeks).
- Clinical jaundice occurre in 20%-30% of cases (less than A & B).
- The chronicity is very high from 75%-85% in all age groups.
- There is no immunity against the virus C unlike to the hepatitis A
& hepatitis B which they are immunogenic and produce Abs , but
virus C is not immunogenic and if you get it once tou can have it
again and again because no Abs will formed.
Also hepatitis C has extrahepatic manifestations :
- Mixed cryoglobulinemia that causes Vasculitis, non-deforming
arthritis, membranous GN.
- Porphyria cutanea tarda: (not very common)hyperpigmentation
and photosensitivity with blistering skin lesions.
- Sjogren-like syndrome : (Extra info: The syndrome of dry eyes
(keratoconjuntivitis sicca) in the absence of rheumatoid arthritis or any of the
autoimmune diseases is known as 'primary sjogren's syndrome'. There is an
association with HLA B2 DR3. Dryness of mouth, skin or vagina may also be a
problem. Salivary and paroyid gland enlargement is seen.
).
In this picture(Porphyria cutanea tarda): those pts suffering from
recurrent attacks of these lesions, they go to the dermatologists and
take hydrocortisone creams but without good result , in this case you
have to check for hepatitis C.
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Continue to viral and autoimmune hepatitis
The serological profile for hepatitis C:
It's not much complicated, you get the symptoms of the acute infection
then subside after that ALT fluctuates and this is typical for hepatitis C
(if you measure ALT two times weekly you will find it 40 then 50 then
60 and can go even to normal value). Also the normal liver function
test doesn't roll out chronic hepatitis C
HCV RNA (Hepatitis C Virus RNA) you find it in the acute and chronic
infections, and Anti-HCV Abs are the whole mark of the disease, so if
the pt has Anti-HCV and has not HCV RNA this means that the pt is
recently cured by the treatment.
Risk Factors for HCV:
They are similar for HBV including:
Transfusion or transplant from infected donor
Injecting drug use
Hemodialysis (yrs on treatment)
Accidental injuries with needles/sharps
Sexual/household exposure to anti-HCV-positive contact(not
important here, it's less than 3%)
Multiple sex partners
Birth to HCV-infected mother
The distribution of HCV: it's very high in Egypt because in 1930-1940
they were have the bilharzias and were sharing the same needle to
treat many pts because of that they have a high prevalence of
CHRONIC HEPATITIS C VIRUS.
Here in Jordan the HCV prevalence is 0.9%-1.3% which is less than HBV
(around 4%-8% in the general population).
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Continue to viral and autoimmune hepatitis
Laboratory diagnosis: (the dr. didn't talk a lot about them)
As we said we have:
HCV antibody - generally used to diagnose hepatitis C infection.
Not useful in the acute phase as it takes at least 4 weeks after
infection before antibody appears.
HCV-RNA - various techniques are available e.g. PCR and
branched DNA. May be used to diagnose HCV infection in the
acute phase. However, its main use is in monitoring the response
to antiviral therapy.
HCV-antigen - an EIA for HCV antigen is available. It is used in
the same capacity as HCV-RNA tests but is much easier to carry
out.
The treatment:
Interferon - may be considered for patients with chronic active
hepatitis. The response rate is around 50% but 50% of responders
will relapse upon withdrawal of treatment. What the interferon
does actually is enhancing the NK cells the attack and eat the
virus infected hepatocytes.
Ribavirin(nucleotide analogue) -Combination of Interferon and
Ribavirin is more effective than interferon alone.
The prevention:
You have just to avoid the virus(by being away from the risk factors) ,
because there is no vaccines or immunoglobulin for HCV.
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Continue to viral and autoimmune hepatitis
Hepatitis D Virus (HDV)
HDV is the cousin of HBV it can't live without it, because it's incomplete
virus (RNA virus) it has to use the HBsAg to live and this is why it can't
exist without HBV infection.
Clinical Features about HDV:
There are two types of infections:
1) Co-infection: (the pt gets both viruses at the same time HBV&HDV).
– severe acute disease
– low risk of chronic infection
2) Super infection:
– usually develop chronic HDV infection
– high risk of severe chronic liver disease
– may present as an acute hepatitis
-About the modes of transmission they are similar to HBV (check them
above).
-The Anti-HDV is not measured in routine laboratory tests( just in CDC).
-The distribution is in South America, Central Africa and in south
Europe. (these regions with high prevalence).
Hepatitis E Virus (HEV)
This virus is similar to HAV, the incubation period 40 days (range from
15-60 days). The fatality rate very high among pregnant women (15%25%). As in hepatitis A it's more severe with age and there is no chronic
stage.
-Anti-HEV Abs are the whole mark for the acute infection
-The epidemiology varies in many countries like; Mexico, North Africa
and in some Arab countries.
Hepatitis G: the dr. didn't talk about it. (No human pathology)
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Continue to viral and autoimmune hepatitis
Organism
Acute
Chronic
Recovered/latent
Vaccinated
HAV
•
Anti-HAV
IgM
•
NA
•
Anti-HAV
IgG
•
Anti-HAV
IgG
HBV
•
Anti-HBc
IgM
•
Anti-HBc
IgG
•
Anti-HBc
IgG
•
Anti-HBs
•
HBeAG
•
HBsAg
•
Anti-HBs
•
HBV DNA
•
HBeAg
HBeAb
•
All
tests
possibly
negative
•
Anti-HCV
Ab
•
Anti-HCV
Ab
•
NA
•
HCV RNA
•
Anti-HCV
Ab
•
HCV RNA
•
Anti-HDV
IgM
•
Anti-HDV
•
Anti-HDV
•
NA
•
HDV Ag
•
HD Ag
•
HBsAg
HCV
HDV
or
Here this table shows the serological profile for all hepatitis viruses, this
profile is important because the clinical manifestations in the hepatitis
infections are so non-specific and non of them is really pathgnomonic or
even sometimes they are asymptomatic.
AS A SUMMARY
All hepatotropic viruses are RNA viruses, except for HBV (DNA)
Only HBV, HDV and HCV can cause chronic liver disease.
Not all the chronic hepatitis are viral it could be(ABCDE) :
-A: Autoimmune
-B: HBV
-C: HCV
-D: Drugs
-E: Etcetera as alcohol, alpha1-AT(Antitrypsin) deficiency,
Wilson's disease, NAFLD and NASH (Non-Alcoholic SeroHepatitis).
٧
Continue to viral and autoimmune hepatitis
Accurate diagnosis of viral hepatitis depends on proper
interpretation of specific serological tests.
Initial management of acute hepatitis is supportive, with
monitoring for signs of liver failure.
Antiviral therapy is effective in selected patients with chronic
HCV or HBV.
Immune globulins and vaccine are given to selected contacts of
the patient with acute hepatitis A or B.
Autoimmune Hepatitis (AIH)
Autoimmune hepatitis is not something you see every day, but it's not
very rare. AIH is connected always with viral hepatitis and the reason
behind that is you should not treat any pt with viral hepatitis without
excluding the autoimmune hepatitis, because if we give interferon
(they are immune enhancer as you know) to the pt who has AIH we
will worsen his condition. Also if the pt has viral hepatitis and we treat
him as he has AIH and give him steroids we will worsen his condition.
Definition: AIH is a necroinflammatory disease of the liver
characterized by the presence of specific autoantibodies and, in
general, a favorable response to immunosuppressive treatment.
Epidemiology: 170/milion individuals (less than the viral).
Etiology: largely unknown. Sometimes it can follow HAV or HCV
infection.
Autoantibodies: (they are important)
Antinuclear antibody (ANA) for type 1 AIH
Anti-smooth muscle antibody (ASMA) more specific for
type 1 hepatitis
Anti-liver/kidney microsomal antigen antibody (A-LKM)
this more typical for pediatric AIH (type 2 AIH).
Anti-soluble liver antigen antibody (A-SLA) for type 3 AIH.
٨
Continue to viral and autoimmune hepatitis
Autoimmune hepatitis usually comes in full package with other
autoimmune diseases like hypothyroidism, thyroiditis, Addison's disease,
Vasculitis, vitiligo…etc. and they are more common in females rather than
males
Clinical features for AIH
Manifestations: usually insidious and non specific (e.g. fatigue,
malaise, arthralgias, RUQ pain and fluctuating jaundice).
LAB tests: hypergammaglobulinemia; in the LFT (Liver Function
Test) there is total proteins and albumins, and if we subtract the
albumin from the total proteins what we get is the gamma
globulins, in case of these gamma globulins are more than 40 it
means that we have what we call it hypergammaglobulinemia
and it's highly suggestive for AIH (also in HCV we can see it).
The diagnosis and the treatment
The diagnostic process is complex in AIH, as an example : if you have a
young female with chills, unexplained fatigue then you check the liver
enzymes and the serological profile, also we can take liver biopsy and
establish the diagnosis. In case she responded to the steroids this mean
that she has the AIH.
The treatment for AIH is done by steroids and immune suppressive
agents because the whole problem is immunogenic. And finally you
have to warn the pts that one day they may need liver transplantation
because sometimes every thing failed.
From the slides:
The mainstay of treatment is glucocorticoids, with azathioprine or
mercaptopurine as steroid-sparing agents
Type 1 is more responsive to steroids than type 2 or 3
A significant proportion of patients will ultimately progress to
cirrhosis despite treatment
Liver transplantation is an option for selected patients
٩
Continue to viral and autoimmune hepatitis
At the end of the lecture the dr. presented those two cases without
discussing them.
A 28-year-old woman has had fatigue for 8 months and dark urine , which she first
noticed 6 weeks ago. Physical exam revealed scleral icterus, spider nevi and
hepatosplenomegaly. AST elevated at 420 U/L, ALT 530, bilirubin 15 mg/dl, AP 130,
albumin 2.8 gm/dl, globulins 8.2 gm/dl INR 2.3.
Q: What is going on with this patient?
A: Chronic hepatitis
Q: What kind of chronic hepatitis you think is this?
A: Autoimmune
Q:What further tests should be done to confirm the diagnosis?
A: autoantibodies (ANA, ASMAS, Anti-LKM). Do not forget to R/O viral
and metabolic hepatitis. Consider liver biopsy
A 30-y-old man is referred to you for further investigation of abnormal liver
chemistries. The patient’s AST was 90 U/L and his ALT was 100. An anti-HCV was
positive. Tests for other viruses were negative. The patient admits to casual IV drug
use 20 yrs ago. Physical exam was WNL.
Q: What further test is indicated to confirm his infection?
A: None. The patient is high risk and thus high pre-test probability
Q: What if the patient was low risk?
A: Anti-HCV RIBA (Recombinant Immuno Blot Assay) should be done to
confirm the diagnosis)
Q: When's HCV RNA testing indicated?
A: When treatment is contemplated or when acute infection is suspected
but Anti-HCV Ab test is negative
FINALLY; THANK YOU FOR READING THE LECTURE……☺
If there is any comment just tell me o enshallah ma ba8a9er..☻
DONE BY: HADI RADAIDEH
١٠
Dr. khaled Jadallah
ﺗوﻛﻠت ﻋﻠﻰ ﷲ
***awal eshi…..hai awal mo7adara bktobha l7ali…..l2no "zi ma kolko bt3rfo"….6
mo7adrat kan eli elsharaf enni aktob eljoz2 eltani fehom daymn b3d 7bebi w a5oi
hadi…...basmt eldof3a….fa kan lazem ahdi hai elmo7adra elo, w akeed elehda2 ma bkml
bdon ma a8dem shokr mn el8lb la5oi "eltani "3bdulla…..3la kol eld3m elfnni elli 8adamo
eli w la hadi bel 6 mo7adrat…….so thanx for both of you guys… .
And now let's begin……
In the first 15 minutes of the lecture…our cr. Hashem and the Dr. said very imp.
notes about this course "internal medicine"….
***Now, our subject today is about viral hepatitis….from "A "to "E"….so we are
concerned to learn about hepatotropic viruses, and those are the viruses with
predilection to the liver rather than any other organ, and those are hepatitis
viruses"A,B,C,D,E ."By the way, we have other viruses that may infect the liver, but
they aren't hepatotropic, like CMV, EPV, adenovirus and even mumps virus.
>>>first of all we should know the objectives of this lecture…..
Outline the epidemiology of viral hepatitis
List causative agents for viral hepatitis
Recognize the clinical features of acute and chronic viral hepatitis and their complications… .
By the way this isn't very complex issue….anyway there is nothing specific about clinical
manifestations of hepatitis weither it's acute or chronic…means that the symptoms of hepatitis can be
caused by other diseases .
Interpret serologic tests to accurately diagnose the specific cause of viral hepatitis…bcoz we
can't depend on the clinical manifestation to diagnose as we said…so serology will be the best way for
diagnosis .
Outline the treatment of acute and chronic hepatitis…not much for us as 4th year medical
students.
Identify appropriate candidates for vaccination against HAV and HBV…by the way we don't
have vaccines for HCV, HDV or HEV.
١
viral hepatitis
Dr. khaled Jadallah
***now, we classify these viruses according to the route of transmission
into….Enterically transmitted through feces" A,E "…,and Parenterally
transmitted through serum" B,C,D", and we have others like G….anyway, you will
notice that the enterically transmitted types almost always cause acute infection,
while the opposite occur with the parenterally transmitted ones.
>>here in the following table we can learn the differences between the different
types…..
----------Source of
virus
Route of
transmission
A
feces
C
Blood,
Body fluids
Percutaneous,
Permucosal
D
Blood,
Body fluids
Percutaneous,
permucosal
E
feces
fecaloral
B
Blood,
Body fluids
Percutaneous,
permucosal
Chronic
infection
prevention
No
Yes
Yes
Yes
No
fecaloral
Pre/postPre/postBlood donor
Pre/post-Exposure
Ensure Safe
Screening, risk
Drinking
Exposure
Exposure
Immunization, risk
immunization immunization Behavior modification Behavior modification water
>>>some notes about the table:
Dr .emphasize about the importance of the chronicity of the disease…he
said that the chronic disease is much more imp .bcoz of epidemiologic
burden and the cost on community.
HAV and HEV never cause chronic disease.
Pre-exposure immunizationby vaccines.
Post-exposure immunizationby immunoglobulins.
There is no immunization (pre -or post) -against HCV.
HDV can't survive without HBV, so we don't have pure HDV infection.
HEV is most dangerous in pregnant women, but we don't have a lot of
cases in our region….or let's say we don't diagnose it usually…bcoz there is
no serological test available, even in USA, there is CDC serological test
only, but it isn't that common.
٢
viral hepatitis
Dr. khaled Jadallah
###Clinical Manifestations of Acute Hepatitis:
Acute HAV mostly symptomatic, especially in adults…actually it's the most
symptomatic infection among all hepatitis types, and again it's more symptomatic among
adults….why? bcoz immune system in adults is more developed…knowing that the
symptoms in hepatitis infection in general is caused by the immune reaction, not by the
cytopathic effect of the virus "means that hepatitis virus doesn't cause cytopathic effect, so
it doesn't kill the cell, what kills the cell is the immune systemleads to symptoms"
The dr .gives us here a very important info…..HAV is the most icteric
type…means that it's the most common cause of jaundice among hepatitis
types….you should know that not all cases of hepatitis are associated with
jaundice, and this causes some difficulty in diagnosis .For example HAV
which is the most icteric type as we said causes jaundice only in 60 %of
cases .So the message is that the absence of jaundice doesn't rule out the
presence of hepatitis .
Acute HEV is most symptomatic and severe in pregnant women…mortality rate in
infected pregnant ladies reaches 30%.
Acute HCV is the least symptomatic
Acute HBV can present with a serum sickness-like picture (fever, arthritis, urticaria,
angioedema)…anyway it may occur also with some drugs reactions.
Generally, symptoms improve after jaundice appears.
the most typical symptoms of hepatitis are jaundice and upper abdominal pain…..again
sometimes we don't have both and symptoms are just what we call the viral syndrome "nonspecific symptoms" and these are (fever, malaise, anorexia, RUQ pain, diarrhea, pruritis).
###LAB investigations of acute hepatitis…as we said, we depend on this to
diagnose hepatitis, bcoz of non-specific symptoms .To diagnose the case as
acute viral hepatitis, the liver enzymes must be elevated 10 times more
than the upper limit, means that if the upper limit is 30 U/L then the liver
enzymes must be more than 300 U/L.
Hepatocellular injury" injury in the hepatic cells themselves" typically shows
marked elevation in liver enzymes especially AST " Aspartate transaminase" and
ALT" Alanine transaminase" enzymes….this injury could be viral, drug-induced or
ischemic .
Cholestatic injury "damage primarily in ductules and canaliculi, bcoz of
obstruction "also causes elevation but less than that of hepatocellular injury,
and mainly in AP" Alkaline phosphatase", bilirubin and GGT" Gamma glutamyl
transpeptidase "rather than the enzymes .
٣
viral hepatitis
Dr. khaled Jadallah
some drugs like oral contraceptive pills raise the cholestatic factors, others
like diclofenac "Voltaren " raise hepatocellular factors.
Other causes of modest elevation "other than cholestatic injury "include
acute or chronic hepatocellualr injury" but usually it causes high elevation
as we said", infiltrative diseases, acute alcoholic hepatitis, and metastatic
diseases.
---Note :when we say marked elevation means…>500U/L, while modest
means <300U/L.
WBC :may show leucopenia .Why? Bcoz it's viral inection.
From slides… .Bilirubin and AP may or may not be elevated.
###Stigmata of Chronic Liver Disease :the followings features typically found
in CLD:
Spider Agiomas " spider nevus"is a type of telangiectasis found slightly beneath the skin
surface, often containing a central red spot and reddish extensions which radiate outward like a
spider's web
Palmar erythema is reddening of the palms at the thenar and hypothenar eminences.
Clubbing of fingers
Dupuytren contractures is a fixed flexion contracture of the hand where the fingers bend
toward the palm and cannot be fully extended.
Gynecomasita (male) or breast atrophy (female)….why males is the opposite of
females here? Bcoz of disturbed mechanisms of metabolism of hormones.
Testicular atrophy, the same reason as the previous point.
***note :definitions are from Wikipedia.
٤
viral hepatitis
Dr. khaled Jadallah
-This is spider angioma….it's
typically has a raised center
with branching light capillaries.
-When press on it, it will
disappear, unlike vasculitis.
-Typically, they are found on
the face, or on the chest,
anyway it will never appear in
an area below the line
connecting the two nipples,
bcoz its pathology is related to
the circulation of SVC .
-This is palmar erythema, many
normal people may have this,but
here it's more prominent on thenar
& hypothenar sides.
-it may be found in other
situations like pregnancy, steroid
treatment, any RS disease with
CO2 retention.
Here on the left, we have Dupuytren contractures, and on the right we have clubbing,
and we should know that clubbing may occur in all digits…upper or lower.
٥
viral hepatitis
Dr. khaled Jadallah
Now, we will start talking about each type of hepatitis viruses one by one…
Hepatitis A
***the incubation period of this virus is 25 days in average (15-50 days), and we
said that it's the most symptomatic among "his brothers", and we said that the
appearance of symptoms depends on age "the older you are, the more symptoms
you will get", for example jaundice appear in <10% in children younger than 6
years old, while those with age between 6 and 14 years, have jaundice in 40-50 %
of cases, while if you are 14 years old or older than that , you have a chance of
70-80 %to get jaundice.
As we said, this type will never lead to chronic infection, but in few cases may
lead to certain complications .It may lead to fulminant hepatitis in 0.1 %of cases,
and this occurs usually in elderly people with poor health, rarely in young people .
Prolonged cholestasis is another complication, it means prolonged jaundice for
5-6 months, and it isn't really harmful .And sometimes the infection may be
complicated with autoimmune hepatitis "see lecture 6 by hadi radaideh ."
Now regarding serological tests,we ask for
different liver enzymes like ALT .But the most
important thing is to ask for IgM anti-HAV titer,
bcoz it's an acute infection, so if it's +ve IgM,
then it's +ve infection, and the opposite is
true…….see the adjacent picture .
HAV
"e.g.,
may
transmit
through
multiple
ways….1Close personal contact
household contact, sex contact, child day care centers", 2 Contaminated food, water
infected food handlers, raw shellfish", 3 and rarely through blood"e.g., injecting drug use,
"e.g.,
transfusion ".
٦
viral hepatitis
Dr. khaled Jadallah
the distribution is related mainly to
the level of hygiene.
Although Jordan here is labeled with
red"means high prevalence",but this
isn't actually true, dr. said"we see just
one case every one or two month".
If you want to go to areas of high
prevalence, you have to be careful,
and if you want to stay for long time,
you have to be vaccinated.
Now let's go back to the serologic tests, as we said IgM Ab is used to diagnose
current infection, while IgG anti-HAV is used to diagnose immunization, either
through past infection or vaccination .
Regarding vaccination "pre-exposure prevention", it's given to some people
that are at high risk, and those are…Travelers to endemic regions "here it must be given
2-3 weeks before travel", Homosexual men, Injecting drug users .We have many cases of
infection occur in community wide outbreaks, and in most of cases in these
outbreaks *there is no definite risk factor, and *the outbreak affects mainly the
age group from 5-14 years old, and *children serve as reservoir of the infection .
The post-exposure prevention" by vaccines or by IG "is given within 14 days
of exposure .It's given routinely in household and other intimate contacts, and is
given also in other selected situations like in day care centers & and in case of
exposure to food prepared by infected handler.
Hepatitis B
In HBV infection, the incubation period is 60-90 days in average (45-180 days), and again the
older you are the more symptoms you will have, jaundice appear in <10 %in age younger than
5 years, and 30-50 % in age older than 5 years old. Fatality rate in acute phase (bcoz of
fulminant hepatitis ) reaches 0.5-1%. The opposite of the clinical manifestation, chance to turn
into chronic phase decrease with age, it may reach 30-90 % in <5 years old, and 2-10 %in >5
years old, why? that is with developed immunity , it's hard for the disease to become chronic.
The chance of premature death bcoz of chronic liver disease caused by HBV is 4 times more
than healthy people, so it may reach about 15-25 .%
٧
viral hepatitis
Dr. khaled Jadallah
Now regarding the epidemiological facts about HBV, you have to know that 2
billion (1/3 of the world ) is current or past infected, 1/5 of them (around 350-400
million) are currently infected (chronic or carriers), 40 million in eastern
Mediterranean region, and this makes HBV the most common chronic infection
worldwide. In Jordan we have 4-8 % of population are infected. 25-40 %of HBV
infected people die from HCC or cirrhosis. Over 300,000 cases/year of HBVrelated HCC worldwide, you should know that HBV is 2nd most common
carcinogenic factor just after smoking.
HBV is 100 times more contagious than HIV, dr .then talked about what we call
the rule of three…..that is if you have a patient with 1HIV, the chance to get the
disease from him is 0.3%, with 2HCV……it's 3%, and with 3HBV…..it's 30% .
Here you can see that HBV is the 7th
most common cause of death among
infectious diseases, and HCV is the
10th, anyway if you grouped them
together viral hepatitis will become
the 5th in this list. And the problem
isn't only the mortality rate, also
the morbidity and the cost of
management are also problems in this
disease.
Clinically, we have an acute phase and a chronic phase…..in acute phase it may
lead to fulminant hepatitis and death .Chronic infection may lead to HCC,
cirrhosis, liver failure, and very important and disabling extrahepatic
manifestation "we will talk about them later".
٨
viral hepatitis
Dr. khaled Jadallah
Look carefully at the table above… and try to memorize it…
Here are some notes about it…..
The main difference in investigation between the immune tolerant & the carrier is the amount
of the virus in the serum "HBV DNA "and this is the main way to differentiate between them .
But why is it so imp .to differentiate? Bcoz 1the chance of immune tolerant case to become
chronic is much more, and 2we don't treat immune tolerant cases, bcoz the liver isn't yet
damaged .
Now if anti-HBs is +ve and nothing else is +ve, then the patient is vaccinated.
***the following notes are written by the dr .in the notes below the slide.
Most patients presenting to clinicians in practice fall into 1 of 4 groups .All of these individuals have
chronic HBV infection as indicated by the presence of HBsAg .Those in the immune tolerant phase are
HBeAg positive, have normal ALT levels, high levels of HBV DNA, and mild or normal histology .Current
treatment strategies are not focused on these patients.
Two groups have active disease :those with HBeAg-positive chronic hepatitis B and those with HBeAgnegative chronic hepatitis B with promoter mutations .Both groups exhibit abnormal ALT levels, elevated
HBV DNA levels, and necroinflammation with varying degrees of fibrosis .Because these patients are at
the greatest risk for disease progression and liver disease complications, they are the target groups for
treatment .
Finally, patients with inactive chronic HBV infection carry HBsAg but lack HBeAg .They are anti-HBe
positive but exhibit normal ALT levels, low HBV DNA levels, and may have residual fibrosis on histology .
Now we should go back to talk about extrahepatic manifestations, these
manifestations varies according to the state of the infection "if it's acute or
chronic"….. the ones which are associated with the acute infection include
Arthralgias, Papular acrodrmatitis "Gianotti-Crosti syndrome", and the ones which are
associated with the Chronic infection are Glomerulonephritis, Arthrlalgias (so it may
come with acute or chronic), Polyarteritis nodosa (PAN).
٩
viral hepatitis
Dr. khaled Jadallah
These are two pictures of Papular acrodrmatitis, which is associated with multiple
small papules, and it's a rare condition.
On the other hand, this is common, this is Polyarteritis nodosa, this is a case of
vasculitis, so it disappears with pressure, it's so painful, it occurs mostly on the
extremeties, but may also affect the visceral arteries.
١٠
viral hepatitis
Dr. khaled Jadallah
Look carefully at the adjacent pic .And here are some
notes
:
This is in case of recovery.
The first thing to appear is HBsAg, followed by
HBV DNA "this occurs in all cases, with or
without recovery".
in case of recovery anti-HBs will appear, so
it's the last one to appear.
The importance of IgM anti-HBc "core antigen"
is used for the diagnosis of acute HBV
infction.
Again look, and here are some notes…
This is in case of progression into chronic
case.
Here HBsAg remains high, and the antibodies
against it don't appear at all.
And bcoz it turns into chronic, IgM anti-HBc
regress after a while, but we can see that total
anti-HBc is high, this means that IgG is high, so
we use it in diagnosis of chronic infection.
***it seems somehow complex now, later in this lec., we will talk further about this topic, maybe it will be more
simple then.
Here, we can see what we said before…..syptomatic
infection increase with age… .In contrast with the
chronic infection which decrease with age.
Can you now tell me why? You should know now…☺.
١١
viral hepatitis
Dr. khaled Jadallah
In the picture above, we can see that there is a relation between epidemiological burden
and the clinical manifestation, so areas of high endemicity like Asia and sub-Sahara, have
high prevalence of the disease in newborn (perinatal root)and toddler(horizontal root) so
chronicity is higher and complications(like HCC )is higher .In case of low endemicity like
in Europe, the infection affects mostly young adults (percutaneous "IV drugs "and sexual
root), so less chronicity and less complications .
HBV can be detected in any biological fluid, and it presents in variable amount, for
example; it presents in high amount in blood, serum and wound exudate .On the
other hand it presents in moderate amount in semen, vaginal fluid and saliva .And
in low amount in urine, feces, sweat, tears and breast milk .So as a general
precaution, try to avoid any direct contact with any biological fluid.
Modes of transmission….multiple ways include:
Sexual promiscous heterosexuals" multiple sexual partners" and homosexuals are
particular at risk.
Parenteral IV drug abuser, Health Workers are at increased risk
Perinatal Mothers who are HBeAg positive are much more likely to transmit to their
offspring than those who are not. Perinatal transmission is the main means of
transmission in high prevalence populations, and bcoz of that, we start to do screening
tests for pregnant ladies, so if she is infected, they vaccinate the baby and give him/her Ig
as soon as he/she is delivered, and this decreases the chance of the newborn to be infected
by 95%.
١٢
viral hepatitis
Dr. khaled Jadallah
The initial evaluation of HBV infection includes:
i. History …we should focus on Q's about the possible routes of acquisition the infection
ii.
iii.
to estimate the duration of infection and predict the risk of complications, so you should
ask about family history of HBV infection or HCC, alcohol use should be discussed
further if it's positive.
Physical examination… .focus on determining disease stage and the possible presence
of cirrhosis or decompensated liver disease.
Investigation …focus on assessing liver disease activity, serologic and virologic markers
of disease, screening tests for HCC (AFP" α-fetoprotein" and ultrasound) and tests for HCV
& HIV.
Diagnosis, as we said before it depends on serology….as follows :
HBsAg -used as a general marker of infection.
HBsAb -used to document recovery and/or immunity to HBV infection
anti-HBc IgM -marker of acute infection
anti-HBc IgG -past or chronic infection
HBeAg -indicates active replication of virus and therefore infectiveness
Anti-HBe - virus no longer replicating .However, the patient can still be positive
for HBsAg which is made by integrated HBV
HBV-DNA -indicates active replication of virus, more accurate than HBeAg
especially in cases of escape mutants .Used mainly for monitoring response to
therapy
here we have very
important table …
which
explain
again what we
said before
try to memorize it,
dr .said that it's
very imp .
١٣
viral hepatitis
Dr. khaled Jadallah
Treatment…in case of acute infection, we don't do anything unless the patient
has signs of liver failure .In chronic infection, there are certain drugs…
dr .said "I don't think it's fair to ask you as 4th year medical students
about treatment and investigations"…7elo el2dwye m7zofe…☺
So I copy these info. From slides:
Interferon -for HBeAg +ve carriers with chronic active hepatitis .Response rate is 30
to 40%
Lamivudine -a nucleoside analogue reverse transcriptase inhibitor .Well tolerated,
most patients will respond favorably .However, tendency to relapse on cessation of
treatment .Another problem is the rapid emergence of drug resistance
Successful response to treatment will result in the disappearance of HBsAg, HBVDNA, and seroconversion to HBeAb
prevention…dr .didn't talk a lot about it….he just talked about the importance of getting
vaccinated to protect yourself, bcoz you will face a lot of patients with this disease…so take
care. I will put the slide of vaccination…read it .
Done by:
Saleh abo-libDeh
www.shifa2006.com
١٤
Continue to viral and autoimmune hepatitis
ﺑﺴﻢ اﷲ اﻟﺮﺣﻤﻦ اﻟﺮﺣﯿﻢ
Short summary about the types of hepatitis:
Hepatitis A : Self-limited viral disease of worldwide distribution caused by
hepatitis A virus, more common in areas of poor hygiene and low socioeconomic
standards, transmitted almost exclusively by the fecal-oral route, although parenteral
transmission is possible; no carrier state. Incubation period is approximately 25 days,
with a range of 15 to 50 days. Most cases are clinically inapparent or have mild
flulike symptoms; jaundice, if present, is usually mild. Massive hepatic necrosis
(fulminant hepatitis) can occur but much less commonly than with hepatitis B.
Previously called epidemic hep., MS-1 hep., jaundice infectious hep., and shortincubation hepatitis.
Hepatitis B: Viral disease caused by the hepatitis B virus that is endemic
worldwide. The virus is shed in all body fluids by individuals with acute or chronic
infections and by asymptomatic carriers, and is transmitted primarily by parenteral
routes, such as by blood transfusion or by sharing of needles among drug users; oral
transmission can occur but has low efficiency, and it can be spread by intimate
personal contact, especially sexual contact, and by vertical transmission from mother
to neonate. Incubation period averages about 90 days, with a range of 45 to 180
days, the clinical course is more variable than in hepatitis A. During the prodromal
phase there may be fever, nausea, malaise, anorexia, and vomiting, which lessens
with the onset of clinical jaundice. Most patients recover completely and become HBS
Ag-negative in 3 to 4 months, some will remain chronic carriers or develop chronic
active hepatitis or chronic persistent hepatitis. Massive hepatic necrosis (fulminant
hepatitis) is an infrequent complication. In areas of high endemicity a relationship
has been shown between hepatitis and virus infection, cirrhosis, and primary
hepatocellular carcinoma, with the latter being one of the most common neoplasms.
Previously called inoculation hepatitis, long incubation hepatitis, MS2 hepatitis, serum
hepatitis, and homologous serum hepatitis or jaundice.
١
Continue to viral and autoimmune hepatitis
Hepatitis C Virus (HCV)
We have around 6 different genotypes (1,2,3,4,5,6) , here in our
region we are concerned about 1 & 4 (50% of the types) , 2 & 3 more in
Europe, 5 & 6 scattered in south Africa and some countries. The
important thing about these genotypes is that each one of them has it's
way of response to treatment, for example 2 & 3 genotypes have a very
good response and the duration of treatment is short (about 6 months),
but in case of 1 & 4 (unfortunately in our region) the response to
treatment is 20%-30% less than 2 & 3 and the duration of treatment is
12 months, this in case of poor economy will double the cost (the cost to
treat the viral hepatitis around 14,000-18,000 JD).
In this diagram NS2 & NS3 ….etc are structural proteins in which all
the drugs that are being generated acting against these structural
proteins. The problem is in the hypervariable region that changes in it's
structure always, so this make a challenge to produce a vaccine for this
type of virus ( like HIV, influenza virus).
So the problems that we face in case of hepatitis C :
- More than one genotype (we have 6)
- The treatment is very expensive
- The presence of the hypervariable region in the genetic material.
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Continue to viral and autoimmune hepatitis
Clinical features of hepatitis C:
- The incubation period is around 4-7 weeks (from the slides the
range from 2-27weeks).
- Clinical jaundice occurre in 20%-30% of cases (less than A & B).
- The chronicity is very high from 75%-85% in all age groups.
- There is no immunity against the virus C unlike to the hepatitis A
& hepatitis B which they are immunogenic and produce Abs , but
virus C is not immunogenic and if you get it once tou can have it
again and again because no Abs will formed.
Also hepatitis C has extrahepatic manifestations :
- Mixed cryoglobulinemia that causes Vasculitis, non-deforming
arthritis, membranous GN.
- Porphyria cutanea tarda: (not very common)hyperpigmentation
and photosensitivity with blistering skin lesions.
- Sjogren-like syndrome : (Extra info: The syndrome of dry eyes
(keratoconjuntivitis sicca) in the absence of rheumatoid arthritis or any of the
autoimmune diseases is known as 'primary sjogren's syndrome'. There is an
association with HLA B2 DR3. Dryness of mouth, skin or vagina may also be a
problem. Salivary and paroyid gland enlargement is seen.
).
In this picture(Porphyria cutanea tarda): those pts suffering from
recurrent attacks of these lesions, they go to the dermatologists and
take hydrocortisone creams but without good result , in this case you
have to check for hepatitis C.
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Continue to viral and autoimmune hepatitis
The serological profile for hepatitis C:
It's not much complicated, you get the symptoms of the acute infection
then subside after that ALT fluctuates and this is typical for hepatitis C
(if you measure ALT two times weekly you will find it 40 then 50 then
60 and can go even to normal value). Also the normal liver function
test doesn't roll out chronic hepatitis C
HCV RNA (Hepatitis C Virus RNA) you find it in the acute and chronic
infections, and Anti-HCV Abs are the whole mark of the disease, so if
the pt has Anti-HCV and has not HCV RNA this means that the pt is
recently cured by the treatment.
Risk Factors for HCV:
They are similar for HBV including:
Transfusion or transplant from infected donor
Injecting drug use
Hemodialysis (yrs on treatment)
Accidental injuries with needles/sharps
Sexual/household exposure to anti-HCV-positive contact(not
important here, it's less than 3%)
Multiple sex partners
Birth to HCV-infected mother
The distribution of HCV: it's very high in Egypt because in 1930-1940
they were have the bilharzias and were sharing the same needle to
treat many pts because of that they have a high prevalence of
CHRONIC HEPATITIS C VIRUS.
Here in Jordan the HCV prevalence is 0.9%-1.3% which is less than HBV
(around 4%-8% in the general population).
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Continue to viral and autoimmune hepatitis
Laboratory diagnosis: (the dr. didn't talk a lot about them)
As we said we have:
HCV antibody - generally used to diagnose hepatitis C infection.
Not useful in the acute phase as it takes at least 4 weeks after
infection before antibody appears.
HCV-RNA - various techniques are available e.g. PCR and
branched DNA. May be used to diagnose HCV infection in the
acute phase. However, its main use is in monitoring the response
to antiviral therapy.
HCV-antigen - an EIA for HCV antigen is available. It is used in
the same capacity as HCV-RNA tests but is much easier to carry
out.
The treatment:
Interferon - may be considered for patients with chronic active
hepatitis. The response rate is around 50% but 50% of responders
will relapse upon withdrawal of treatment. What the interferon
does actually is enhancing the NK cells the attack and eat the
virus infected hepatocytes.
Ribavirin(nucleotide analogue) -Combination of Interferon and
Ribavirin is more effective than interferon alone.
The prevention:
You have just to avoid the virus(by being away from the risk factors) ,
because there is no vaccines or immunoglobulin for HCV.
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Continue to viral and autoimmune hepatitis
Hepatitis D Virus (HDV)
HDV is the cousin of HBV it can't live without it, because it's incomplete
virus (RNA virus) it has to use the HBsAg to live and this is why it can't
exist without HBV infection.
Clinical Features about HDV:
There are two types of infections:
1) Co-infection: (the pt gets both viruses at the same time HBV&HDV).
– severe acute disease
– low risk of chronic infection
2) Super infection:
– usually develop chronic HDV infection
– high risk of severe chronic liver disease
– may present as an acute hepatitis
-About the modes of transmission they are similar to HBV (check them
above).
-The Anti-HDV is not measured in routine laboratory tests( just in CDC).
-The distribution is in South America, Central Africa and in south
Europe. (these regions with high prevalence).
Hepatitis E Virus (HEV)
This virus is similar to HAV, the incubation period 40 days (range from
15-60 days). The fatality rate very high among pregnant women (15%25%). As in hepatitis A it's more severe with age and there is no chronic
stage.
-Anti-HEV Abs are the whole mark for the acute infection
-The epidemiology varies in many countries like; Mexico, North Africa
and in some Arab countries.
Hepatitis G: the dr. didn't talk about it. (No human pathology)
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Continue to viral and autoimmune hepatitis
Organism
Acute
Chronic
Recovered/latent
Vaccinated
HAV
•
Anti-HAV
IgM
•
NA
•
Anti-HAV
IgG
•
Anti-HAV
IgG
HBV
•
Anti-HBc
IgM
•
Anti-HBc
IgG
•
Anti-HBc
IgG
•
Anti-HBs
•
HBeAG
•
HBsAg
•
Anti-HBs
•
HBV DNA
•
HBeAg
HBeAb
•
All
tests
possibly
negative
•
Anti-HCV
Ab
•
Anti-HCV
Ab
•
NA
•
HCV RNA
•
Anti-HCV
Ab
•
HCV RNA
•
Anti-HDV
IgM
•
Anti-HDV
•
Anti-HDV
•
NA
•
HDV Ag
•
HD Ag
•
HBsAg
HCV
HDV
or
Here this table shows the serological profile for all hepatitis viruses, this
profile is important because the clinical manifestations in the hepatitis
infections are so non-specific and non of them is really pathgnomonic or
even sometimes they are asymptomatic.
AS A SUMMARY
All hepatotropic viruses are RNA viruses, except for HBV (DNA)
Only HBV, HDV and HCV can cause chronic liver disease.
Not all the chronic hepatitis are viral it could be(ABCDE) :
-A: Autoimmune
-B: HBV
-C: HCV
-D: Drugs
-E: Etcetera as alcohol, alpha1-AT(Antitrypsin) deficiency,
Wilson's disease, NAFLD and NASH (Non-Alcoholic SeroHepatitis).
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Continue to viral and autoimmune hepatitis
Accurate diagnosis of viral hepatitis depends on proper
interpretation of specific serological tests.
Initial management of acute hepatitis is supportive, with
monitoring for signs of liver failure.
Antiviral therapy is effective in selected patients with chronic
HCV or HBV.
Immune globulins and vaccine are given to selected contacts of
the patient with acute hepatitis A or B.
Autoimmune Hepatitis (AIH)
Autoimmune hepatitis is not something you see every day, but it's not
very rare. AIH is connected always with viral hepatitis and the reason
behind that is you should not treat any pt with viral hepatitis without
excluding the autoimmune hepatitis, because if we give interferon
(they are immune enhancer as you know) to the pt who has AIH we
will worsen his condition. Also if the pt has viral hepatitis and we treat
him as he has AIH and give him steroids we will worsen his condition.
Definition: AIH is a necroinflammatory disease of the liver
characterized by the presence of specific autoantibodies and, in
general, a favorable response to immunosuppressive treatment.
Epidemiology: 170/milion individuals (less than the viral).
Etiology: largely unknown. Sometimes it can follow HAV or HCV
infection.
Autoantibodies: (they are important)
Antinuclear antibody (ANA) for type 1 AIH
Anti-smooth muscle antibody (ASMA) more specific for
type 1 hepatitis
Anti-liver/kidney microsomal antigen antibody (A-LKM)
this more typical for pediatric AIH (type 2 AIH).
Anti-soluble liver antigen antibody (A-SLA) for type 3 AIH.
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Continue to viral and autoimmune hepatitis
Autoimmune hepatitis usually comes in full package with other
autoimmune diseases like hypothyroidism, thyroiditis, Addison's disease,
Vasculitis, vitiligo…etc. and they are more common in females rather than
males
Clinical features for AIH
Manifestations: usually insidious and non specific (e.g. fatigue,
malaise, arthralgias, RUQ pain and fluctuating jaundice).
LAB tests: hypergammaglobulinemia; in the LFT (Liver Function
Test) there is total proteins and albumins, and if we subtract the
albumin from the total proteins what we get is the gamma
globulins, in case of these gamma globulins are more than 40 it
means that we have what we call it hypergammaglobulinemia
and it's highly suggestive for AIH (also in HCV we can see it).
The diagnosis and the treatment
The diagnostic process is complex in AIH, as an example : if you have a
young female with chills, unexplained fatigue then you check the liver
enzymes and the serological profile, also we can take liver biopsy and
establish the diagnosis. In case she responded to the steroids this mean
that she has the AIH.
The treatment for AIH is done by steroids and immune suppressive
agents because the whole problem is immunogenic. And finally you
have to warn the pts that one day they may need liver transplantation
because sometimes every thing failed.
From the slides:
The mainstay of treatment is glucocorticoids, with azathioprine or
mercaptopurine as steroid-sparing agents
Type 1 is more responsive to steroids than type 2 or 3
A significant proportion of patients will ultimately progress to
cirrhosis despite treatment
Liver transplantation is an option for selected patients
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Continue to viral and autoimmune hepatitis
At the end of the lecture the dr. presented those two cases without
discussing them.
A 28-year-old woman has had fatigue for 8 months and dark urine , which she first
noticed 6 weeks ago. Physical exam revealed scleral icterus, spider nevi and
hepatosplenomegaly. AST elevated at 420 U/L, ALT 530, bilirubin 15 mg/dl, AP 130,
albumin 2.8 gm/dl, globulins 8.2 gm/dl INR 2.3.
Q: What is going on with this patient?
A: Chronic hepatitis
Q: What kind of chronic hepatitis you think is this?
A: Autoimmune
Q:What further tests should be done to confirm the diagnosis?
A: autoantibodies (ANA, ASMAS, Anti-LKM). Do not forget to R/O viral
and metabolic hepatitis. Consider liver biopsy
A 30-y-old man is referred to you for further investigation of abnormal liver
chemistries. The patient’s AST was 90 U/L and his ALT was 100. An anti-HCV was
positive. Tests for other viruses were negative. The patient admits to casual IV drug
use 20 yrs ago. Physical exam was WNL.
Q: What further test is indicated to confirm his infection?
A: None. The patient is high risk and thus high pre-test probability
Q: What if the patient was low risk?
A: Anti-HCV RIBA (Recombinant Immuno Blot Assay) should be done to
confirm the diagnosis)
Q: When's HCV RNA testing indicated?
A: When treatment is contemplated or when acute infection is suspected
but Anti-HCV Ab test is negative
FINALLY; THANK YOU FOR READING THE LECTURE……☺
If there is any comment just tell me o enshallah ma ba8a9er..☻
DONE BY: HADI RADAIDEH
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