Dr. RABIE IBRAHIMSUPERVISED BY Dr.ABDALLA AL-SHAHRANI

Hepatitis A B C D E

Virus HAV HBV HCV HDV HEV

Family Picornavirus Hepadnavirus Flavivirus Satellite Calicivirus

Genome ssRNA dsDNA ssRNA ssRNA ssRNA

Spread Fecal-oralparenteral, sexual,perinatal

parenteral, ?sexual

parenteral, ?sexual Fecal-oral

Antigens HAV-Ag HbsAg,HBcAg,HBeAg HCV-Ag HDV-Ag HEV-Ag

Antibodies Anti_HAV Anti-HBs,Anti-HBc,Anti-HBe Anti-HCV Anti-HDV Anti-HEV

Virus markers HAV RNAHBV DNA, DNA polymerase

HCV RNa HDV RNa viruslike partiacles

c

serology

• HBsAg: surface antigen• HBeAg: e antigen (a component of HBV core); marker of viral replication• HBcAg: core antigen (cannot be measured in serum)• both HBsAg and HBeAg are present during acute hepatitis B• anti-HBs follows HBsAg clearance and confers long-term immunity• anti-HBe and anti-HBc appear during the acute and chronic phases of the illness but do notprovide immunity• anti-Hbe indicates low infectivity

Possible Outcomes of HBV Infection

Acute hepatitis B infection

Chronic HBV infection

3-5% of adult-acquired infections

95% of infant-acquired infections

Cirrhosis

Chronic hepatitis

12-25% in 5 years

Liver failure Hepatocellular carcinoma

Liver transplant

6-15% in 5 years 20-23% in 5 years

DeathDeath

Symptoms

HBeAg anti-HBe

Total anti-HBc

IgM anti-HBc anti-HBsHBsAg

0 4 8 12 16 20 24 28 32 36 52 100

Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course

Weeks after Exposure

Titre

IgM anti-HBc

Total anti-HBc

HBsAg

Acute(6 months)

HBeAg

Chronic(Years)

Anti-HBe

0 4 8 12 16 20 24 28 32 36 52 Years

Weeks after Exposure

Tit

erAcute HBV Infection with Progression to

Chronic Infection: Typical Serologic Course

、 Laboratory Diagnosis

Hepatitis B virus

HBV belongs to the Hepadnaviridae family of viruses.

Diagram of hepatitis B virus.

Hepatitis B surface Ag. Hepatitis core Ag. Hepatitis e Ag. HBV-DNA. HBV-DNA polymerase.

Laboratory Markers for HBV Infection

Hepatitis B surface antigen (HBsAg):

present in acute or chronic infection.

It appears 4-12 week after infection

Hepatitis B surface antibody (anti-HBs):

marker of immunity acquired through natural HBV infection, vaccination, or passive antibody (immune globulin) , It appears 4-10 month after infection

Hepatitis B core antibody (anti-H Bc):

Ig M--indicative of infection in the previous six months,

It appears 6-14 week after infection

Ig G--indicative of more distant HBV infection that may have

been cleared by the immune system or that may persist.

positive HBsAg and anti-HB c Ig G--indicative of persistent

chronic HBV infection

Laboratory Markers for HBV Infection

Laboratory Markers for HBV Infection

Hepatitis B e antigen (HBeAg) : correlates with a high level of viral replication;

often called a "marker of infectivity"

Hepatitis B e antibody (anti-HBe): correlates with low rates of viral replication.It appears 8-16 week after infection

HBV DNA: correlates with active replication; useful in

monitoring response to treatment of HBV infection, especially in HBeAg-negative mutants

Interpretation of HBV Tests

Test Result Interpretation

Test Result InterpretationHBsAg Negative Susceptible (not

immune) to HBV infection

Anti-HBc NegativeAnti-HBs NegativeHBsAg Negative Immune because of

natural infectionAnti-HBc PositiveAnti-HBs PositiveHBsAg Negative Immune because of

hepatitis B vaccinationAnti-HBc NegativeAnti-HBs PositiveHBsAg Positive Acute HBV infectionAnti-HBc PositiveIgM anti-HBc PositiveAnti-HBs NegativeHBsAg Positive Chronic HBV infectionAnti-HBc PositiveIgM anti-HBc NegativeAnti-HBs NegativeHBsAg NegativeAnti-HBc PositiveAnti-HBs Negative

Possible Interpretations: (1) patient may be recovering from acute

infection; (2) patient may be distantly immune--testing

does not detect very low level of anti-HBs;(3) patient may be susceptible, with a false-

positive anti-HBc; or(4) there may be an undetectable level of

HBsAg in the serum, and the patient is actually a carrier

Diagnostic criteria for HBV infection

Acute Infection

Acute HBV infection is subclinical in 70 percent of adults and 90 percent of children younger than five years.

The incubation period after infection lasts one to four months. Symptoms of acute HBV infection include nausea, anorexia,

fatigue, low-grade fever, and right upper quadrant or epigastric pain.

Clinical jaundice appears as constitutional symptoms are resolving

Hepatic transaminase levels [ALT] and [AST]) reflect

hepatocellular injury and range from several hundred to

20,000 IU per L.

Serum bilirubin values are usually less than 20 mg per dL (342

µmol per L).

Mild anemia is common, as is relative lymphocytosis.

More severe disease results in an elevation in the prothrombin

time and a decrease in the serum albumin level.

HBV is not cytopathic, and liver injury is caused by the host's

immune response against infected hepatocytes

Diagnostic criteria for HBV infection

Chronic disease HBsAg positive for longer than six

months. Serum HBV DNA > 100,000 copies per

mL. Persistent or intermittent elevation of

alanine transaminase and aspartate transaminase levels

Liver biopsy showing chronic hepatitis

Inactive HBsAg carrier state

HBsAg positive for longer than six months. HB e Ag negative, anti-HB e positive Serum HBV DNA < 100,000 copies per mL Persistently normal alanine transaminase or

aspartate transaminase levels Liver biopsy to confirm absence of significant

hepatitis

Resolved disease

History of acute or chronic hepatitis B. Presence of anti-HBc, with or without

anti-HBs HBsAg negative Normal alanine transaminase level

CASE 1

A 25-yr-old male patient presented to your clinic for pre-employment evaluation and his lab results show the following :

HBsAg Negative, Anti-HBc Negative, Anti-HBs Positive.What is your interpretation of his lab results?

Immune because of previous hepatitis B vaccination.

Case 2: A 35 years old man presented with complain of fever,

abdominal pain associated with nausea. Investigations showed : CBC : HB 10.5 g%, WBC 8.5, ESR 100, CRP 20 mg/dl . LFT : bilirubin 14 mg/dl , AST (SGOT) 900 u/L, ALT

(SGPT) 1500 u/l. Hepatitis profile: HBsAg –ve, Anti HBc IgM –ve, HBeAg

+ve, Anti HBs –ve. VDRL +ve.QUESTION:1. What is your interpretation?2. Explain your findings.

Answer : Acute recent hepatitis infection, HBsAg should be

positive but in occasional cases it appears later than the HBe Ag.

You should repeat the test to detect the HBsAg . VDRL is false positive. Hepatitis is one of the causes of false positive VDRL.

Case 3: A 30 years old healthy hospital worker reported to

check the results of his hepatitis screening test: HBsAg –ve. Anti HBs +ve. Anti HBc +ve. HBe Ag -ve. Anti HBe -ve. Anti HCV -ve

QUESTION: Interpret this test.

Answer: Past hepatitis infection. Immune and not infective

Case 4: A 20 years old reported for pre-employment examination and

investigations, all his systems were free apart from 2cm BCM hepatomeglay and he reported a painless lesion on his penis since 2 weeks.

Investigations: CBC HB 12.5mg%, WBC 12.5. LFT : ALT 120 u/l, AST 100 u/l, Alk Phos 300 u/l. Hepatitis profile: HBsAg +ve, Anti HBc IgG +ve, HBe Ag +ve , Anti HBs –ve. HBDNA >100.000 copies. VDRL –ve. Question: How would you interprete this tests. What is the diagnosis?

Answer : Chronic persistent hepatitis, did not develop immunity

yet still infective. ? First stage Syphlitic lesion with –ve VDRL in early

phase . Needs : Repeat LFT and hepatitis profile regularly. Liver US and liver biobsy. Repeat VDRL after 1 week, if +ve, perform the TP

specific tests. Do HIV screening and screen for other STD

Case 5: A 25 years old female who had an attack of fever and

epigastric pain 3 months ago, her husband was found to be hepatitis positive.

She presented to check her investigations she did last week.

CBC HB 10.5 g%, WBC 7.8, ESR 30 LFT ALT 70 U/l , AST 85 U/l, alk phosp 120 U/lز Hepatitis profile: HBsAg –ve ,anti HBc+ve , HBeAg –ve , anti HBs –ve.

Question:1. How would you interpret her findings?2. What is your next step?

Answer: Window stage. Repeat after 1month

Case 6

A 26 years old woman seen by her GP because she was jaundiced and feeling unwell.

She had a history of drug addiction.

A hepatitis screen was done, the results are: Anti-HAV NEGATIVE. Anti HBs POSITIVE. Anti-HbsAg NEGATIVE. HbsAg NEGATIVE. Hbe Ag NEGATIVE Anti-HCV NEGATIVE. Anti-HBc POSITIVE.

Questions

Which of the following is the most likely cause of her jaundice.

A. Acute hepatitis C.

B. Chronic hepatitis B and acute hepatitis C.

C. Hepatitis E

D. Chronic Hepatitis E

E. Acute hepatitis B

Answer 6

The picture suggests previous exposure TO hepatitis B but this would not give a clinical picture of jaundice, so another cause needs to be considered.

History of drug addiction suggest hepatitis C. Antibody against hepatitis C takes about 3 months, the

PCR testing is test used to reach the diagnosis in the acute phase.

Question 7

During pre-employment screening. A 26 year old male has the following hepatitis serology HBs Ag

negative HBs Ab

positiveHbe Ag

negativeHbe Ab

positiveHBc Ab

positive A.What is your interpretation ?

Immune by past infection

Answer 7

Case 8 :Highly infective chronic hepatitis B is suggested by:  

1. normal liver enzymes, HBeAg+, anti-HBc IgG+

2. elevated liver enzymes, HBeAg+, anti-HBc IgM+

3. normal liver enzymes, HBeAg-, anti-HBc IgG+

4. elevated liver enzymes, HBeAg+, anti-HBc IgG+

Highly infective chronic hepatitis B is suggested by:  

•1 normal liver enzymes, HBeAg+, anti-HBc IgG+ F

•2 elevated liver enzymes, HBeAg+, anti-HBc IgM+ F

•3 normal liver enzymes, HBeAg-, anti-HBc IgG+ F

•4 elevated liver enzymes, HBeAg+, anti-HBc IgG+ T