Heptites A Flashcards
What is etiologic agent of hepatitis A?
Hepatitis A Virus (HAV). HAV is highly infectious.
Is HAV infectious?
HAV is highly infectious.
What is Reservoir and transmission?
- Humans are the nearly exclusive reservoir of HAV (with rare exceptions of chimpanzees and other
primates). - The virus is extensively shed with feces.
- Infection is most commonly by the fecal–oral route.
- Transmission occur from physical contact with an infectious individual or sewage contamination in
waterborne outbreaks. - Sexually transmitted infection that includes oral-anal contact.
- Transmission through contaminated needles are also possible (the latter mainly in injection drug
users).
What are risk factors of hav?
Risk factors:
- Traveling to endemic areas.
- Close contact with infected individuals (eg, household contacts.)
- Close contact (household or professional) with children attending nursery or preschool.
- Consumption of seafood (shellfish»_space;> raw oysters.) - Sex (especially men who have sex with men [MSM]). - Waste or sewage management, as well as maintenance of equipment used for such purposes.
- Epidemics caused by the consumption of contaminated food and water may also occur.
What is the Incubation and contagious period of ha?
Incubation period is usually from 15 to 50 days (on average ~28 days).
- The virus is shed with feces for 1 to 2 weeks before and ~1 week after the onset of signs and
symptoms (the contagious period).
- Patients are no longer contagious 7 days after jaundice occurs.
When patients who have HAV stop being contagious?
Patients are no longer contagious 7 days after jaundice occurs.
** HAV does not cause chronic hepatitis.***
What is thr clicial features of HAV? ( meet all other Hepatitis acute infection)
A non-specific prodromal illness characterized:
1. Headache
2. Myalgia
3. Arthralgia
4. Nausea
5. Anorexia
6. Jaundice.
7. Dark urine and pale stools
8. Vomiting
9. Diarrhea
10. Abdominal discomfort.
• Physical signs:
1. The liver is often tender but only minimally enlarged.
2. Mild splenomegaly
3. Cervical lymphadenopathy
When do we say this is an acute hepatitis?
Less than 6 months
What is the investigations needed in acute hepatitis?
- Liver function test (LFT):
• A hepatitic pattern of LFTs develops (ALT and AST»_space; ALP and GGT.)
• Sometime cholestatic pattern develops (HAV) (ALP and GGT»_space; ALT and AST)
• Serum transaminases typically between 200 and 2000 U/L in an acute infection
(usually lower and fluctuating in chronic infections).
• The ALP rarely exceeds twice the upper limit of normal.
• The plasma bilirubin reflects the degree of liver damage.
• Prolongation of the PT indicates the severity of the hepatitis but rarely exceeds 25
seconds, except in rare cases of acute liver failure.
• The white cell count is usually normal with a relative lymphocytosis. - Serological tests confirm the etiology of the infection
How to diagnose HAV?
- Serologic tests: - The basis for diagnosis is the finding of positive serum anti-HAV IgM antibodies.
- The antibodies confirm a recent infection.
- They may persist for up to 4 to 6 months and are gradually replaced by anti-HAV IgG antibodies, which
persist for life (indicates immunity.)
How do we know if this patient has immunity to HAV?
They may persist for up to 4 to 6 months and are gradually replaced by anti-HAV IgG antibodies, which
persist for life (indicates immunity.)
How to treat HAV?
Most individuals do not need hospital care.
• Supportive therapy.
• Drugs such as sedatives and narcotics, which are metabolized in the liver
should be avoided.
• No specific dietary modifications are required. • Elective surgery should be avoided in cases of acute viral hepatitis, as
there is a risk of post-operative liver failure.
• Liver transplantation is very rarely indicated.
What is the prevention of HAV?
Vaccination is the key method of primary prevention (People travelling to endemic area, close
contacts of HAV-infected patients, individuals with chronic hepatitis B or C infections.)
- Strict hand hygiene
What do you know about HB antigens?
- Hepatitis B surface antigen (HBsAg): is an indicator of active infection.
- Hepatitis B core antigen (HBcAg):
- Not found in the blood, but antibody to it (anti-HBc) appears early in the illness which subside
gradually but then persists: - Two types of anti-HBc : IgM (acute infection) and IgG (chronic infection)
- Anti-HBc is initially of IgM type, with IgG antibody appearing later.
- Anti-HBc (IgM) can sometimes reveal an acute HBV infection when the HBsAg has disappeared and
before anti-HBs has developed (Window period). - Hepatitis B e antigen (HBeAg) is an indicator of active viral replication.
What etiologic agent of HBV?
Etiologic agents: Hepatitis B virus (HBV.)
What is Reservoir and transmission of HBV?
- The only HBV reservoir is individuals with active disease or carriers.
- Routes of transmission include parenteral* (contact with infected blood and blood-contaminated
instruments), sexual, and perinatal transmission
What is the Incubation and contagious period of HBV?
- The incubation period is from 28 to 160 days (average, 70-80 days).
- Patients with positive serum HBeAg tend to be more contagious because of the presence of high
levels of HBV DNA in the blood.
What is the risk factor of HBV?
- Close contact with a person with HBV infection (household contacts, sexual contacts)
- Treatment with blood products, hemodialysis, multiple sexual partners,
- IV drug use
- Occupational exposure to blood and body fluids (health-care professionals),
- Being a prison inmate.
• The risk of vertical mother-to-child transmission without interventions:
- ~90% for HBeAg-positive mothers
- ~10% for HBeAg-negative HBsAg-positive mothers
What is the clinical symptoms and signs of acute HBV?
A non-specific prodromal illness characterized:
1. Headache
2. Myalgia
3. Arthralgia
4. Nausea
5. Anorexia
6. Jaundice.
7. Dark urine and pale stools
8. Vomiting
9. Diarrhea
10. Abdominal discomfort.
• Physical signs:
1. The liver is often tender but only minimally enlarged.
2. Mild splenomegaly
3. Cervical lymphadenopathy
How to diagnose acute HBV?
- Virologic tests: Measurements of serum HBV DNA levels.
- Serologic tests:
- HBV antigens (HBsAg, HBeAg)
- specific antibodies (anti-HBc IgM and IgG, anti-HBe, anti-HBs)
• Anti-HBc IgM positivity being an important marker of acute hepatitis B
in the “window period” (the period between disappearance of HBsAg
and appearance of anti-HBs antibodies).
There is a pic for HEPATITIS B VIRUS
What is the complications of acute HBV?
- Acute liver failure: (rapid development of encephalopathy and impaired liver synthetic function)
- The most serious complication (~1% of patients)
- More frequently in young women and in 30%-40% of patients with hepatitis D virus [HDV] coinfection.
- The risk is also higher in patients with preexisting hepatitis C virus [HCV] infection.
- Extrahepatic complication (caused by immune complexes) include:
- Systemic vasculitides (eg, polyarteritis nodosa), polymyalgia rheumatica, erythema nodosum,
glomerulonephritis and nephritic syndrome (more common in children),
- Mixed cryoglobulinemia (abnormal proteins that thicken and clump together at cold temperatures) ?
- Myocarditis.
- Guillain-Barré syndrome.
How to treat patients with acute HBV?
Supportive therapy.
High rates of spontaneous HBV clearance in adult.
What is the prognosis of acute HBV?
Acute hepatitis B may progress to chronic hepatitis B in:
- 90% of neonates and infants .
- 30% of children aged 1 to 5 years .
- 2% to 5% of older children and adults.
• Risk factors for progression to chronic disease include perinatal or early childhood
infection, high exposure to the virus, male sex, advanced age, immunosuppression, and use of glucocorticoids.
• Mortality is <1% and is mainly due to fulminant liver failure.
The course is more severe in patients with HCV or HDV coinfection
How to prevent acute HBV?
Vaccination is the key method of
primary prophylaxis.
•Passive immunoprophylaxis with
hepatitis B immunoglobulin (HBIG) is used mostly to prevent vertical transmission to the newborn.
What is chronic HBV?
• Chronic hepatitis B is a chronic (>6 months) liver disease that is characterized by
necroinflammatory lesions
• HBV DNA can integrate into the host’s genome of hepatocytes and other cells.
• Signs and symptoms: Most patients have no symptoms for a long time.
What is the complications of chronic HBV?
a) Cirrhosis
b) HCC
b) Extrahepatic complications caused by immune complexes: Polyarteritis nodosa, leukocytoclastic vasculitis, glomerulonephritis, and polymyalgia rheumatica.
Chronic HBV infection can cause hepatocellular carcinoma (HCC) with or without cirrhosis.
How to manage a patient with chronic HVB?
Treatments are still limited, as no drug is consistently able to eradicate hepatitis B infection completely.
• The goals of treatment are HBeAg seroconversion, reduction in HBV-DNA and
normalization of the LFTs.
• The indication for treatment is a high viral load in the presence of active hepatitis, as
demonstrated by elevated serum transaminases and/or histological evidence of inflammation and fibrosis. (see next slide)
There are Two different types of drugs are used to treat chronic hepatitis B:
- Direct-acting nucleoside/nucleotide analogues (Lamivudine, Entecavir and tenofovir)
- Pegylated interferon-alfa.
When the treatment of chronic HBV indicated?
Treatment is indicated in
1-immune reactive &
2-HBeAg-negative chronic hepatitis B
There is a pic in photos.
What is importanat in follow up patients with chronic HBV?
• Monitoring for HCC is usually done every 6 months.
• Screening modality: Abdominal ultrasonography +/- Alpha-fetoprotein (AFP) every
6 months remains the standard.
• In patients not currently meeting the criteria for therapy, monitoring of liver function
tests and liver enzymes (ALT) should be performed every 3 to 6 months and HBV DNA every 6 months.
• Ideally, evaluation of liver fibrosis should be updated every 1 to 3 years, depending on
the HBeAg status and HBV DNA.
is Acute HCV often ? And what is its etiologic agent?
Acute symptomatic infection with hepatitis C is rare .
Etiologic agent: Hepatitis C virus (HCV).
What is Reservoir and transmission?x
- The only HCV reservoir is patients with hepatitis C.
- The routes of transmission include contact with blood, blood products, nonsterile medical
instruments or nonmedical equipment, such as razor blades, needles and syringes in injection
drug users, toothbrushes). - The risk of HCV transmission to a sexual partner is uncommon.
Is it common to have sexual transmission of HCV?
- The risk of HCV transmission to a sexual partner is uncommon.
What are the risk factors of HCV?
Injection drug use.
- The risk of neonatal infection from a seropositive mother is ~2%.
- 4% to 7% in the case of mothers with positive serum HCV RNA on the day of delivery.
- 15% in mothers with HIV coinfection.
What is the incubation and contagious period of HCV ?
- The incubation period is 15 to 160 days (average, 50 days).
- Patients are contagious starting ≥1 week before the onset of symptoms and remain
contagious as long as HCV RNA is positive. - HCV particles are contagious on environmental surfaces for up to 6 weeks.
Clinical features and natural history of HVC?
- Most patients with HCV infection are asymptomatic.
- HCV clearance in acute hepatitis C is observed in 15% to 20% of patients.
- The remaining patients develop chronic hepatitis C, out of which 5% to 20% may progress to
liver cirrhosis within 20 to 25 years.
How to diagnose a HCV patient?
1- Virologic tests:
- HCV RNA can be detected in serum as early as 1 to 3 weeks from infection (because it is
detectable intermittently, HCV infection cannot be excluded on the basis of a single test result
and repeat testing is necessary).
- Serologic tests:
- Anti-HCV antibodies are detected 4 to 10 weeks from infection (average, 7 weeks).
- At the onset of symptoms, anti-HCV are detectable in 50% to 70% of patients, and at
3 months, in >90%.
- The results may be negative in patients who are immunocompromised or treated with
hemodialysis.
How to treat HCV virus?
- Antiviral treatment:
- Was previously recommended after 24 weeks of diagnosis and the regimen was similar
to chronic hepatitis C. (see slide 37).
- However, the 2017 guidelines from the European Association for the Study of the
Liver (EASL) recommend treatment at the time of diagnosis with a direct-acting
antiviral (DAA) regimen that is similar to that used in chronic hepatitis .. (slide 37)
Follow up of HCV?
• Perform follow-up virologic studies (HCV RNA levels) at 6 months to exclude chronic
hepatitis even if ALT levels are normal.
• Patients should be tested for hepatitis B virus, HIV, and other sexually transmitted
infections, if appropriate.
• Provide education and counseling regarding prevention of further transmission,
especially avoiding blood donation and avoiding sharing needles in IV drug users.
• Encourage vaccination against hepatitis A and B if the patient is not immune.
What are the complications and prognosis of HCV?
• Complications:
1. Acute liver failure (<1% of patients).
2. Complications caused by immune complexes: Glomerulonephritis, mixed
cryoglobulinemia (more frequent in patients with chronic hepatitis C).
3. Progression to chronic hepatitis C.
• Prognosis:
- Mortality is low and mainly due to the rare fulminant hepatitis (primarily in
patients with HCV and hepatitis virus A or B coinfection).
How to prevent HCV ?
.No specific vaccines or immunoglobulins are available.
• The key prevention method is adherence to the general rules of prevention of blood-
borne infections.
• Instruct the patient how to reduce the risk of infecting others by preventing contact with the patient’s personal belongings that may be contaminated with blood (eg,
toothbrushes, razors, needles, syringes).
• Patients should adhere to safe-sex practices.
• HCV-positive women may continue breastfeeding.
• HCV-positive women may continue breastfeeding.
What do we know about CHRONIC HCV?
• Chronic hepatitis C is a chronic (>6 months) disease characterized by hepatic
necroinflammatory changes.
What are the complication of chronic HCV if left untreated?
a) Cirrhosis.(Risk factors for progression from chronic hepatitis to cirrhosis include male gender,
immunosuppression (such as co-infection with HIV), prothrombotic states and heavy alcohol misuse.
)
b) HCC (HCC without liver cirrhosis is rare).
c) Extrahepatic complications caused by immune complexes: Polyarteritis nodosa, vasculitis, glomerulonephritis, and polymyalgia rheumatica.
How to treat chronic HCV?
• The aim of treatment is to eradicate infection • The viral clearance achieved 6 months after finishing treatment (termed sustained virological
response, SVR) have risen from less than 40% a decade ago to levels approaching 100%.
• The infection is cured in more than 99% of patients who achieve an SVR.
What medication used to treat chronic HCV?
Medications: A combination of direct-acting antiviral (DAA) agents is the current standard
of therapy (+/- ribavirin). (see next slide)
• DAA monotherapy is unacceptable due to the risk of selection of resistant strains.
• pegylated interferon-alfa were used treat HCV in the past but anymore.
• Response to treatment: Negative serum HCV RNA levels
What is etiologic factor of HDV( delta virus)?
- Hepatitis D (delta) virus (HDV)
- RNA virus that is capable of replication only in the presence of hepatitis B virus (HBV).
- Acute hepatitis D may be a result of coinfection (simultaneous infection with HBV and
HDV) or HDV superinfection in an HBV carrier. - The virus is present worldwide, affecting about 5% of all HBV patients.
- The reservoir, route of transmission, and risk factors are as in hepatitis B.
What is he incubation of HDV?
21 to 140 days (average, 35 days).
What is Clinical features and natural history?
The course of HBV/HDV coinfection is similar to that of hepatitis B.
• HDV superinfection in a patient with chronic HBV infection leads to exacerbation of the
disease, resulting in progression to acute liver failure (particularly in asymptomatic HBV carriers).
• HDV can cause chronic hepatitis.
• Chronic HDV infection develops in 70% to 90% of patients with superinfection.
Haw to diagnose HDV patient?
• Hepatitis delta antigen [HDAg]) is present in the blood only in the first few days of disease.
• The diagnosis of HBV/HDV coinfection is made in patients with high serum anti-HBc IgM and anti-HDV IgM levels.
• Anti-HDV IgM persist for ~6 weeks (in exceptional cases for 12 weeks) and are then
replaced by anti-HDV IgG.
• Levels of HBsAg are low or undetectable (due to suppression by HDV; often this also
affects anti-HBc IgM).
• In the case of HDV superinfection in an HBV-infected patient, anti-HDV IgM are
detected, which are subsequently replaced by anti-HDV IgG; for some time both antibody classes can be detected in serum.
*Anti-HBc IgM are not detected.
How to treat in patients with HDV?
• There are no guidelines for the treatment of acute HDV infection.
• In patients with chronic HDV infection, the recommended treatment is pegylated
interferon alpha-2a administered for 48 weeks.
• In those with HBV DNA, nucleoside analogue (NA) therapy may be of benefit. • The prognosis is worse in individuals with HBV-HDV coinfection compared with HBV
infection alone in terms of rapid progression to cirrhosis and development of hepatocellular carcinoma.
How to prevent HDV?
hepatitis B vaccination
What is the etiologic agent for HEV?
Etiologic agent: Hepatitis E virus (HEV).
Eight genotypes are known in this group.
- Genotypes 1 and 2 cause human infections only.
- Transmitted in contaminated water sources by the fecal-oral route.
- Outbreaks tend to occur in areas with poor hygiene.
- Genotypes 3 and 4 are zoonotic, most commonly found in pigs (true primary host).
- Humans become infected when they consume infected meat.
- Pathogenesis is not fully known. The primary site of viral replication is probably the
gastrointestinal tract.
What is Clinical features, natural history, and prognosis?
- In the majority of patients (up to 80%) HEV infection is asymptomatic.
- Manifestations of symptomatic HEV infection are as in other types of acute viral hepatitis.
Mortality rates in HEV?
• Estimated mortality rates:
- 0.2% to 4% in young adults
- Up to ~10% in children <2 years
- 10%-25% in pregnant women due to obstetric complications and fulminant liver failure).
- In middle-aged and elderly men rarely fatal.
• The antibodies that develop after HEV clearance are nonprotective and reinfections can occur.
• Chronic infections (only in the case of HEV genotype 3) may occur, particularly in
immunosuppressed patients.
How to diagnose HEV?
• Laboratory test results are the same as in other types of acute viral hepatitis.
• Diagnosis is usually based on the detection of serum anti-HEV antibodies (IgM antibodies
appear in the prodromal period and are then replaced by IgG antibodies).
• The most reliable finding for hepatitis E is a positive serum HEV RNA test result. • Chronic infection is diagnosed in patients with serum HEV RNA persisting >3 months.
How to treat and prevent HEV patients?
• Most cases of acute HEV infection are self-limiting and do not require antiviral therapy.
• In patients with severe acute HEV or acute-on-chronic liver failure, the use of ribavirin may be
considered for 3 months.
• In addition, patients with primary liver disease infected with HEV genotype 3 and those receiving
immunosuppressive drugs in doses that cannot be reduced or in whom dose reduction is ineffective
may consider ribavirin 600 to 800 mg/d for ≥3 months as monotherapy or in combination with
peginterferon alpha.
• Prevention:
- In endemic regions improvement of hygiene standards, including water supply, is necessary.
- Hepatitis E vaccine against genotype 4 HEV is approved in China but does not provide immunity.
