HEPATITUS VIRUSES
Maryam Afifi
Osy Ndubaku
Lani Kwon
Case Studies: Patient A

A 55-year-old man was admitted to the
hospital with fatigue, nausea, and
abdominal discomfort. He had a slight
fever, his urine was dark yellow, and his
abdomen was distended and tender. He
had returned from a trip to Thailand
within the previous month.
Case Studies: Patient B

A 28-year-old woman was admitted to the
hospital complaining of vomiting,
abdominal discomfort, nausea, anorexia,
dark urine and jaundice. She admitted
that she was a former heroin addict and
that she had shared needles. In addition,
she was three months pregnant.
Case Studies: Patient C

A 65-year-old man was admitted with
jaundice, nausea, and vomiting six months
after undergoing coronary artery bypass
grafting.
What is hepatitis?

Hepatitis is inflammation of the liver.

Cirrhosis is scaring of the liver.
Healthy Liver
http://peer.tamu.edu/curriculum_modules/Properties/Mod
ule_5/Lesson_four/L4_topic6.htm
Liver Cirrhosis
http://www.stanford.edu/group/virus/hepadna/2004tansilvi
s/Patient%20Ed.htm
What factors may cause
inflammation?
http://hepatite-c.webhealth.com/wiki/Viral_Hepatitis
Why is the liver important?

Organ responsible for multiple metabolic functions







Bile production and excretion
Excretion of bilirubin, cholesterol, hormones, and drugs
Metabolism of fats, proteins, and carbohydrates
Enzyme activation
Storage of glycogen, vitamins,
and minerals
Synthesis of plasma proteins,
such as albumin, and clotting factors
Blood detoxification and purification
http://www.best-vitamin-supplementsguide.com/symptoms-liver-disease-health.html
Types of Hepatitis
HEPATITIS
VIRAL
Hepatitis
Hepatitis
Hepatitis
Hepatitis
Hepatitis
NON-VIRAL
A
B
C
D
E
Drug/Toxin Induced
Alcoholic Consumption
Autoimmune Disorders
Hereditary Conditions
Common Symptoms
Mild
 Moderate
 Severe


Note: A patient may only experience
fatigue, or no symptoms at all.
Common Symptoms
in Severe Hepatitis














Jaundice (yellowing of the skin & the whites of the eyes)
Muscle Aches
Headaches
Joint Pain (due to circulating immune complexes)
Fever
Diminished Appetite
Nausea
Vomiting
Diarrhea
Abdominal Pain
Dark “tea-colored” urine
Pale “clay-colored” stools
Edema (large amount of fluid collect in the abdomen beneath the skin)
Bleeding easily (decrease in levels of coagulation factors made by liver)
Initial Diagnosis

Using the patient's medical history








drug and medication use
alcohol consumption
family history
exposure to toxins
past surgeries
past travels
sexual history
Invasive diagnostic approach



palpate the liver area to look for signs of swelling or
tenderness
perform laboratory tests
order a liver biopsy
Hepatitis A Virus (HAV)

Overview



Family Picornaviridae
Has a worldwide distribution and is endemic in most
countries
HAV has an incubation period of 3 to 5 weeks




Enters the body via the gut 
Replicates in the digestive tract 
Spreads to infect the liver, where it multiplies
Only acute HAV


Symptoms often go unrecognized
However, some symptoms may be more severe

fever, tiredness, loss of appetite, nausea, abdominal
discomfort, dark urine, and jaundice
Laboratory Testing of HAV

A blood test showing the presence of IgM
anti-HAV in serum confirms the diagnosis
of acute hepatitis A infection.
HAV

Means of Viral Acquisition:




Transmission through fecal-oral contact
Acquired by drinking water or eating foods that have been
contaminated with fecal matter from an infected individual
Unprotected sex with an infected individual
Individuals at Risk:

International travelers
Sexually active homosexual men
Individuals with blood-clotting factors disease
Injecting and non-injecting drug users
Patients awaiting liver transplants
Chronic liver disease suffers
Individuals w/ risky occupations (i.e., laboratory researchers,

Children living in areas of frequent Hepatitis A outbreaks






animal handlers, daycare personnel)
HAV

Prevention:



Washing hands well with soap & water (1) before
preparing foods (2) after changing diapers or (3) using
the restroom
Short-term prevention is available from immune globulin
Treatment:



Hepatitis A vaccine
 Immunity begins about four weeks after the first
dose and lasts for at least 20 years
No infectious reoccurrence once immunity is developed
99% of those infected recover on there own
Classification of Hepatitis B Virus
(HBV)

Family Hepadnaviridae

Classified into 8 genotypes of HBV designated A to H and
are distributed in distinct geographical regions








Genotypes A and G have been divided into sub-genotypes
identified by the Arabic numerals 1 and 2
Genotype
Genotype
Genotype
Genotype
Genotype
Genotype
Genotype
A  India, Burundi, Cameroon & Norway
B  China, East Asia, Societe Island & Vietnam
C  China & Bangladesh
D  Iran, Tunisia, North Africa, Sweden & Denmark
E  Senegal & Nigeria
F  Columbia, Venezuela & Spain
G  United States
Structure of HBV





Genome is partially single-stranded circular nicked DNA
HBV is the only hepatitis causing virus that has DNA instead of RNA
HBcAg = core antigen
HBsAg = surface antigen in the outer capsid
HBeAg = antigen associated with the viral nucleocapsid
http://www.ahealthyme.com/topic/printview
Acute HBV


Symptoms don’t persist longer than 2 or 3
months
Usually asymptomatic or ‘flu-like’ symptoms




Jaundice: 20% of patients
Complete liver failure: ~ 0.1% of patients
Recovery normally takes 6 to 12 weeks after the
onset of illness.
The mortality of acute HBV infection increases
with age and with the presence of other
disorders.
Chronic HBV


HBV infection lasting longer than 6 months
25% of HBV carriers develop liver disease which
gets worse over time



Cirrhosis (scarring) of the liver occurs and is less able
to carry out its normal functions
Enlarged liver
HBV DNA is integrated chromosomally in the
hepatocytes.

Liver Cancer (hepatocellular carcinoma)
Laboratory Testing of HBV

Serological Diagnosis: Enzyme-linked
immunosorbent assays (ELISAs) and
radioimmunoassays (RIAs) are used for the
diagnosis of specific serological markers of HBV
infection in both acute and chronic stages.


HBV core antibody test
Real-Time PCR amplification and detection of
viral DNA or viral DNA polymerase are used in
diagnosis of chronic HBV.

HBV DNA test
Markers Used in HBV

IgG and IgM antibodies

HBsAg and HBeAg

HBcAg is present but undetectable due to the
appearance of anti-HBc.
Analysis of HBV

Acute – HBsAg (surface antigen) and Anti-HBc
(core antibody IgM)


Chronic – HBsAg (surface antigen) and HBeAg
(nucleocapsid antigen)


Anti-HBc appears early
HBeAg indicates viral replication
Note: If the surface antigen and/or DNA test is
positive, the carrier is contagious.
Diagnostic
Tests
for HBV
Modified from: http://www.doh.wa.gov/hsqa/fsl/Documents/LQA_Docs/Acute_hepatitis.pdf
Acute vs. Chronic HBV
http://virology-online.com/viruses/HepatitisB.htm
HBV

Means of Viral Acquisition:





Sexual activity with an infected partner
Living with a chronically infected person
Infected mother to newborn during childbirth
Sharing needles with an infected person
Individuals at Risk:









People with multiple sexual partners
People diagnosed with a sexually transmitted disease
Injecting drug users
People living with others who are chronically infected
Newborns born to infected mothers
Children of immigrants from nations w/ a higher rate of
hepatitis B
Health care and public safety workers that in contact w/
blood or bodily fluids
Hemodialysis patients
People not vaccinated for hepatitis B

Prevention:









HBV
Receive the hepatitis B vaccine
Avoid contact with blood and other body fluids of infected
individuals
Use latex condoms during every sexual encounter with
every sexual partner
Don’t share items with an infected individual that might
have their blood on it (i.e., toothbrush, razor, washcloth, or
nail clippers)
Avoid getting tattoos because transmission may occur
through unsterilized tattoo or piercing instruments.
Avoid sharing needles or syringes
If exposed to the virus, get a hepatitis B immune globulin
injection within two weeks of exposure.
To prevent passing hepatitis to your infant, get a blood test
for hepatitis B and receive appropriate injections if infected
If you are a health care or public safety worker, follow
standard barrier precautions, safely handle all sharps and
needles, and get the hepatitis vaccine.
HBV

Treatment for Acute HBV:




Immunity typically occurs after infection or vaccination
Bed rest
Eat a healthy diet
Treatment for Chronic HBV:
 Antiviral therapy  inhibit steps of viral genome replication
Viral polymerase inhibitors: lamivudine, adefovir dipivoxil,
pegylated interferon alpha & entecavir
 Reduce the risk of hepatocelluar carcinoma and viral load
 May be curative
Problems
 Emergence of HBV drug resistant mutants
 Use combination of antiviral therapy
 Certain genotypes are at higher risk for poor response to
treatment
 Genotyping prior to treatment


Hepatitis C Virus (HCV)

Overview



Blood borne disease
Spread by blood to blood contact with
infectious person
Leading cause of liver transplant in the United
States
HCV

Properties



Family Flaviviridae
Small Enveloped SS (-) strand RNA
Distinctly different genetically and clinically from
HAV and HBV.
http://www.rit.edu/~japfaa/infectious.html
HCV

Replication




High rate
No proofreading by HCV RNA polymerase
Within hepatocytes in liver
Binds 2 receptors: CD81 & SR-class B1
Acute HCV

Acute hepatitis C (First 6 months)
60-70% infected are asymptomatic
 20-30% will clear the virus at this stage
 Cleared from the body by the body's own
natural defenses
 Decreased appetite, fatigue, abdominal pain,
jaundice, itching and flu-like symptoms.

Chronic HCV

Chronic hepatitis C (After 6 months)
Can cause cirrhosis, liver failure and liver
cancer
 Those infected for 20 to 40 years are at
higher risk of developing HCV-related liver
cancer
 Displays serve symptoms (mentioned
earlier)
 Hepatic encephalopathy

Clinical Diagnosis of HCV


Acute phase diagnosis is challenging.
Chronic phase diagnosis on medical
history, related symptoms, history of
tattoos and piercing.
Laboratory Testing of HCV

Serological blood tests used to detect
antibodies and Virus
Anti-HCV test: Detect antibodies.
 HCV-RNA test: Identifies virus in the blood.
 Viral Load test: Measure viral RNA in
particles in the blood
 Viral genotyping: Determine the kind of
virus present.

HCV

Means of Viral Acquisition:


Transmission through blood contact
Individuals at Risk:









Injecting drug users
people who received clotting factors before 1987 are at
the highest risk of hepatitis C
Patients on hemodialysis
Recipients of blood and/or organs prior to 1992
People with undiagnosed liver problems
Infants born to infected mothers
Health care and public service employees
People with multiple sex partners
People having sex with infected partners are at a low risk
of infection
HCV

Prevention:




No vaccine is available
Avoid sharing of needles
Don’t share personal items that might have blood on
them
Treatment:





Combination of pegylated interferon alpha (brand names
Pegasys and PEG-Intron) and the antiviral drug Ribavirin
24-48 weeks depending on genotype
Seek a medical evaluation for liver disease
Combination drug therapy is often used
Possible Hepatitis C vaccination in the near future.
 Scientists are testing new vaccines on mice.
Epidemiology of HCV

170 million worldwide, 4 million in the United
States

35,000 to 185,000 new cases a year in the US

Co-infection rates with HIV are extremely high

10,000 to 20,000 deaths a year
www.thegicompany.com/graphics/ghepC.gif
Final Diagnosis Patient A

Clinical Clues:


Fatigue, nausea, abdominal discomfort, slight
fever, dark urine, abdomen distended and
tender
Returned from a trip
Suggests food/water contamination
 Oral-fecal contact


Final Diagnosis:

Hepatitis A
Final Diagnosis Patient B

Clinical Clues:

Vomiting, abdominal discomfort, nausea,
anorexia, dark urine, jaundice


chronic stage (HBV or HCV)
Former heroin addict (IDU)
May have been sexually active
 Eliminates HCV


Pregnant


Newborn has a chance of being infected
Final Diagnosis:

Hepatitis B
Final Diagnosis Patient C

Clinical Clues:

Jaundice, nausea, vomiting


Chronic stage (HBV or HCV)
Had surgery 6 months earlier

Suggests infection via blood transmission


Eliminates HBV
Final Diagnosis:

Hepatitis C
References

About Hepatitis A. Outbreak 2005. <http://www.about-hepatitis.com>.

Arbor A. Antiviral-resistance HBV: Can we prevent this monster from growing? Journal of Clinical
Virology 2006; S22.






Berger A., Preiser W. and Doerr H.W. The role of viral load determination for the management of
immunodeficiency virus, hepatitis B virus and hepatitis C virus infection. Journal of Clinical
Virology 2001; 23-30.
Buti M. Treatment of HBV resistance. Journal of Clinical Virology 2006; S22.
Campbell J, Hagan H, Latka M, Garfein R, Golub E, Coady M, Thomas D, Strathdee S (2006).
"High prevalence of alcohol use among hepatitis C virus antibody positive injection drug users in
three US cities.". Drug Alcohol Depend 81 (3): 259-65. PMID 16129567.
Christensen P.B., Krarup H.B., Niesters H.G.M., Norder H., Schaffalitzky de Muckadell O.B., Jeune
B. and Georgsen J. Outbreak of Hepatitis B among injecting drug users in Denmark. Journal of
Clinical Virology 2001; 22: 133-141.
Chiron Corporation Chiron Hepatitis C Research Honored with 2000 Lasker Award for Clinical
Medical Research Press release, 18 September 2000.
Choo Q, Kuo G, Weiner A, Overby L, Bradley D, Houghton M (1989). "Isolation of a cDNA clone
derived from a blood-borne non-A, non-B viral hepatitis genome.". Science 244 (4902): 359-62.
PMID 2523562.
References

De Clercq E. Antiviral drugs in current clinical use. Journal of Clinical Virology 2004; 115-133.

Diagnosing and Treating Hepatitis. Hepatitis Foundation International
2003.<http://www.hepfi.org/living/liv_diagnosis.html>.

First Principles of Gastroentrology. AstraZeneca 2005.
<http://www.gastroresource.com/GITextbook/en/Chapter14/14-5.htm>.




Gunson R.N., Shouval D., Roggendorf M., Zaaijer H., Nicholas H., Holzmann H., de Schryver
A., Renders D., Connell J., Gerlich W.H., Marinho R.T., Tsantoulas D., Rigopoulou E.,
Rosenheim M., Valla D., Puro V., Struwe J., Tedder R., Aitken C., Alter M., Schalm S.W.,
Carmen W.F. and European Consensus Group. Hepatitis B virus (HBV) and hepatitis C virus
(HCV) infections in health care workers (HCWs): guidelines for prevention of transmission of
HBV and HCV from HCW to patients. Journal of Clinical Virology 2003; 213-230.
Hahn JA (2007). "Sex, Drugs, and Hepatitis C Virus". J Infect Dis 195: 1556–9.
Hochberger S., Althof D., Gallegos de Schrott R., Nachbaur N., Rock H. and Leying H. Fully
automated quantitation of Hepatitis B virus (HBV) DNA in human plasma by the COBAS
AmpliPrep/COBAS TaqMan System. Journal of Clinical Virology 2006; 373-380.
Houghton, M., Q.-L. Choo, and G. Kuo. NANBV Diagnostics and Vaccines. European Patent
No. EP-0-3 18-216-A1. European Patent Office (filed 18 November 1988, published 31 May
1989).
References




HBV ARUP Laboratories 2007.
<http://www.arupconsult.com/Topics/InfectiousDz/Viruses/HBV.html>.
Jaeckel E, Cornberg M, Wedemeyer H, Santantonio T, Mayer J, Zankel M, Pastore G,
Dietrich M, Trautwein C, Manns MP (Nov 2001). "Treatment of acute hepatitis C with
interferon alfa-2b". New England Journal of Medicine 345 (20): 1452-1457. PMID
11794193.
Johnson R, Gretch D, Yamabe H, Hart J, Bacchi C, Hartwell P, Couser W, Corey L, Wener M,
Alpers C (1993). "Membranoproliferative glomerulonephritis associated with hepatitis C
virus infection.". N Engl J Med 328 (7): 465-70. PMID 7678440.
Kuo G, Choo Q, Alter H, Gitnick G, Redeker A, Purcell R, Miyamura T, Dienstag J, Alter M,
Stevens C (1989). "An assay for circulating antibodies to a major etiologic virus of human
non-A, non-B hepatitis.". Science 244 (4902): 362-4. PMID 2496467.

Lavanchy D. Worldwide epidemiology of HBV infection, disease burden and vaccine
prevention. Journal of Clinical Virology 2005; S1-S3.

New Vaccine for Hepatitis C in Development. SpiritIndia.com 2007
<http://www.spiritindia.com/health-care-news-articles-1624.html>.

Niesters H.G.M., Pas S. and DeMan R.A. Detection of hepatitis B virus genotypes and
mutants: current status. Journal of Clinical Virology 2005; 34: S4-S8.
References

Pascual M, Perrin L, Giostra E, Schifferli J (1990). "Hepatitis C virus in patients with
cryoglobulinemia type II.". J Infect Dis 162 (2): 569-70. PMID 2115556.

Prevention and treatment for Hepatitis A. Essortment 2002.
<http://nyny.essortment.com/hepatitis_rjds.htm>.


Rodella A., Galli C., Terlenghi L., Perandin F., Bonfanti C. and Manca N. Quantitative analysis
of HBsAg, IgM anti-HBc and anti-HBc avidity in acute and chronic hepatitis B. Journal of
Clinical Virology 2006; 206-212.
Ruiz J, Molitor F, Plagenhoef J (2002). "Trends in hepatitis C and HIV infection among
inmates entering prisons in California, 1994 versus 1999.". AIDS 16 (16): 2236-8. PMID
12409752.

Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill, pp.
551–2. ISBN 0838585299.

Thompson S, Hernberger F, Wale E, Crofts N (1996). "Hepatitis C transmission through
tattooing: a case report". Aust N Z J Public Health 20 (3): 317-8. PMID 8768424.

Tillmann H.L. Shall we treat acute hepatitis B infection? Journal of Clinical Virology 2006;
S59-S60.
References

Ulrich P, Romeo J, Lane P, Kelly I, Daniel L, Vyas G (1990). "Detection, semiquantitation,
and genetic variation in hepatitis C virus sequences amplified from the plasma of blood
donors with elevated alanine aminotransferase." (PDF & scanned pages). J Clin Invest 86
(5): 1609-14. PMID 2173725.

Villeneuve, J.P. The natural history of chronic hepatitis B virus infection. Journal of Clinical
Virology 2005; S139-S142.

Viral Hepatitis A. CDC August 9, 2007.
<http://www.cdc.gov/Ncidod/diseases/hepatitis/a/fact.htm>.

Viral Hepatitis B. CDC December 8, 2006.
<http://www.cdc.gov/Ncidod/diseases/hepatitis/b/index.htm>.


Zignego AL, Ferri C, Pileri SA, Caini P, Bianchi FB; for the Italian Association of the Study of
Liver (A.I.S.F.) Commission on Extrahepatic Manifestations of HCV infection (2006).
"Extrahepatic manifestations of Hepatitis C Virus infection: A general overview and
guidelines for a clinical approach". Dig Liver Dis.: E-publication. PMID 16884964.
Zoulim F. Entecavir: A new treatment option for chronic hepatitis B. Journal of Clinical
Virology 2006; 8-12.