OVERVIEW OF VIRAL

HEPATITIS

Lucy Mathew, NP
Cedars-Sinai Medical Center

Content Outline
„ Anatomy and Physiology of Liver
„ Laboratory Tests and Evaluation
„ Hepatitis A
„ Hepatitis B
„ Hepatitis C

Liver- Facts
„ Largest internal organ in the body
„ Weighs 3 lbs in adults
„ 2 Main Lobes-Right lobe larger than left lobe
„ Further divides into hepatic lobules-functioning
units of the liver
„ Portal circulation
„ Biliary system

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 Functions of Liver

„ What does the liver do?

„ Produces proteins; only source of albumin
„ Metabolism of protein, carbohydrate and fat
„ Source of glucose in starvation

„ Stores vitamins and minerals

„ Bile production and excretion

„ biotransforms or detoxifies substances

Types of Liver Disease

„ Acute
Abd pain, N/V, jaundice, very high liver enzymes
Can rapidly lead to fulminant liver failure
„ Chronic
No obvious symptoms
Slow progression- usually takes years or decades
Normal or slightly elevated liver enzymes

ƒ Acute flare of a chronic condition (“acute

on chronic”)

Spectrum of chronic liver disease

„ “-itis”- inflammation
„ Hepatitis- inflammation of the liver
„ Inflammation fibrosis (scar tissue)
cirrhosis Liver failure/Liver CA Liver
Transplant

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 Liver Enzymes: AST, ALT
„ Enzymes that move nitrogen from amino acids
„ Leak out of cells and make their way into blood
when liver cells are damaged
„ Poor correlation with degree of liver injury
„ Normal values vary by lab reference ranges, but
truly normal is < 30 for men, < 19 for women

Liver Function Tests

„ Indicates the synthetic function of the liver
„ Albumin, PT/INR, bilirubin

„ Albumin - protein made only by the liver

„ PT – reflection of clotting factors made by the
liver
„ Bilirubin is product of RBC breakdown -
inability to process and eliminate

Differential Diagnosis
„ Viral Hepatitis (A,B,C,D,E,G, TTV)
„ Hereditary Hemochromatosis
„ Alpha-1 antitrypsin deficiency
„ Wilson disease
„ Drug induced
„ Alcoholic Liver Disease
„ Fatty Liver/NASH
„ Autoimmune Hepatitis

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 Differential Diagnosis
„ Primary Biliary Cirrhosis
„ Primary Sclerosing Cholangitis
„ Obstructive disorders
„ Infiltrative disorders
„ Pregnancy Associated Liver Diseases

Hepatitis A
„ Fecal- oral route
„ Short, self limiting disease
„ Risk of fulminant liver failure- <1%
„ Never Chronic
„ Vaccine available- 2 shots, 6 months apart
„ Foreign born pts- majority will have immunity
„ Common in Mexico, India, other third world
countries

Viral Hepatitis
„ HEPATITIS B
„ DNA Virus discovered in 1969
„ Can live outside the body for up to 7 days
„ >300 million people worldwide
„ up to 1% of population
„ more common in Asians (10-20%)
„ up to 40% die of liver related complications if not
treated
„ High risk for Liver Cancer

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Global Distribution of Chronic HBV Infection

HBsAg Prevalence (%)

• 350 million chronic carriers worldwide ≥8: High

• Ninth leading cause of death 2-7: Intermediate
• Nearly 75% of HBV chronic carriers are Asian <2: Low

Hepatitis B: Mode of
Transmission

„ Blood and body fluid contact

„ Sexual contact
„ Vertical transmission (mother to baby)
„ Iatrogenic (very rare if universal precautions
used)

Hepatitis B
„ Chance of Chronicity
„ 90% in infants infected at birth
„ 30% in children 1-5 years of age
„ 5% in persons >5 yrs of age
„ Higher in HIV or immuno-compromised person

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 Hepatitis B

„ Hepatitis B Surface Antigen (HBsAg)

- Actively infected
„ Hepatitis B Surface Antibody (Anti-HBs)

-immunity to Hepatitis B- protective antibody

„ Hepatitis B core Antibody (Anti-HBc)

-Evidence of body being exposed to Hepatitis B ever in life- not

a protective antibody

Case studies
„ HBsAg – „ HBsAg -
Anti- HBs - Anti- HBs +
Anti- HBc - Anti- HBc -

„ HBsAg + „ HBsAg –
Anti- HBs – Anti HBs –
Anti HBc + Anti HBc +

Hepatitis B
„ HBV DNA PCR
„ quantity of virus
„ Predicts progression of disease, Risk for Liver
CA, and response to treatment

„ Hepatits B e Antigen / Hepatitis B e Antibody

-specialized tests

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 Hepatitis B Prevention
„ Screen high risk individuals
„ Screen all pregnant women
„ Some Pregnant women need to be treated in the
last trimester- Please refer for eval.
„ Vaccinate high risk and children
„ Total 3 shots- at 0, 1 and 6 months
„ ALL PATIENTS SHOULD BE SEEN BY
GASTROENTEROLOGIST/HEPATOLOGIST

Hepatitis B Treatment
„ Goal- Viral suppression
„ Not curable
„ Interferon- Injectable, 4-12 months treatment
„ Nucleoside/Nucleotide Analogues- Long term therapy
-Lamivudine
-Adefovir
-Entecavir
„ Relatively low or no side effects
„ Can develop resistance over time.

Hepatitis B core Ab
„ Hepatitis B core antibody positive- Hx of HBV
exposure

„ Can have flare of Hepatitis B if immuno-

compromised
-Chemotherapy, chronic steroid use, after organ transplant

„ Referral to Hepatologist prior to initiation of

chemotherapy

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 Hepatitis C
„ RNA virus- Discovered in 1989.
„ It can live outside the body for 1-2 days
„ Replicates trillions of virions/day
„ 5 million or 2% of population infected in the US
„ higher in Hispanics and blacks- 6-8% prevalence
„ 75% chronic infection- 25%-spontaneous
clearance in the first 6 months

HCV: A Global Challenge

East Far East Asia

West 60 M
USA Mediterranean
Europe
5M 20 M
9M
South East
Asia
30 M

South Africa
America 32 M
10 M
Australia
0.2 M

WHO, 1999.
Edlin, AASLD 2005

Risk Factors
„ IVDU - within the first year
„ Snorting cocaine
„ Controversial
„ May transmit via straw or may not admit to IVDU
„ Tattoos - rare, usually prison tattoos
„ Transfusion - 0 cases since 1992
„ Vertical transmission - 2-6%
„ 10-15% if co-infected with HIV
„ C-section and vaginal delivery are the SAME
„ Breast feeding is safe if no bleeding or cracked nipple

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 Transmission

„ Sex safe with non-infected monogamous partner

< 3% risk
„ Increased risk (15%) if co-infected with HIV
„ avoid blood contact
„ Oral sex, intimate kissing appear safe
„ Casual contact safe, but avoid…
„ sharing razor blades, toothbrushes, etc.

Risk Factors
„ Occupational:
„ Health care workers, fire fighters, paramedics, police
„ No higher prevalence than general population

„ Needle-stick
„ 3% risk (30% with HBV, 0.3% with HIV)

„ Needle size, hollow bore

Risk Factors
„ Born in a country where HCV has high
prevalence
„ Most cases are iatrogenic

„ Egypt - 20 % of the population has HCV

„ Result of a vaccination program for Schistosomiasis
in the 1970’s

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 Extra-hepatic Manifestations
„ Cryoglobulinemia
-glomerulonephritis
-vasculitis
„ Lichen planus
„ Porphyria cutanea tarda
„ Lymphoma- NHL, large B cell
„ Cardiomyopathy

Diagnostic Tests
„ HCV Ab- 99% sensitivity
„ Recommended for routine screening
„ Rarely false positive
„ False negative if immuno-compromised
„ 25% prevalence of HCV among HIV positive

HCV RNA (PCR testing)

„ Virus load
„ Lower detection limit can be 10-615 IU/ml
„ NOT a predictor of disease severity: a high viral
load does not mean the liver disease is more
severe, and a low viral load does not mean the
patient is ok and does not need therapy!
„ Helps predict response rate to treatment (lower
means a higher chance of cure with therapy)
„ Used to monitor response during treatment

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Hepatitis C: Normal Liver Enzymes
Cirrhosis
Normal
1%
12%
CAH 22%

Non-specific
25%

CPH
40%
223 patients, 10 studies
Hoofnagle, Hepatology 1997

Cirrhosis Normal Non-specific CPH CAH

Diagnostic Tests
„ Imaging- usually normal

„ Liver Biopsy- only way to assess the degree of

damage (fibrosis)

„ CBC –Very Helpful!

„ Platelets< 150K

Portal Circulation

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 Effects of cirrhosis on Liver and
Spleen
„ Congested/scarred liver-----Blood backs up-----
Portal Vein enlarges----Portal HTN----
Splenomegaly.
„ Platelet sequestration----- Thrombocytopenia

Liver
Spleen

Patient Teaching
„ Avoid ETOH
„ Avoid sharing tooth brush or razors
„ Avoid Excess Vit A, Fe supplements
„ Nutritional supplements- not helpful
„ Herbal medicines- Not helpful, some can be
harmful
„ Silymarin (milk thistle) safe but not helpful

Hepatitis C
„ 20-50% will progress to cirrhosis in 20 years
„ Some progress faster (ETOH, Co-infection)
„ Risk of liver CA if advanced Fibrosis/cirrhosis
„ Not predictable based on ALT or viral count
„ Refer to specialist
Every one should be offered treatment regardless of viral
count, ALT or Fibrosis score as long as they have
viremia. So every pt deserves to be evaluated by a
specialist.

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Impact Of HCV in the United States
APPROXIMATELY 4.0 MILLION PERSONS ARE
CHRONICALLY INFECTED WITH HCV

10-15 YEARS

20% WILL DEVELOP CIRRHOSIS

(+ 780,000 PATIENTS)

10-15 YEARS

4% WILL DEVELOP HCC

(+ 31,000 PATIENTS)

HCV Treatment
„ Goal of treatment is viral eradication- cure:
„ Not viral suppression

„ Standard of Care:
Pegylated interferon(weekly injection) and
Ribavirin(daily pills) for 6-12 months

Response Rate- ranges from 45-85%

HCV Treatment
„ Interferon-natural proteins produced by the cells of the
immune system of most animals in response to
challenges by foreign agents such as viruses, bacteria,
parasites and tumor cells. Interferons belong to the
large class of glycoproteins known as cytokines.
„ An Immune modulator- Not a direct Antiviral medicine
„ Ribavirin- Potentiates the effects of interferons, causes
mutations in the HCV virus, very large volume of
distribution (gets into every cell)

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 Milestones in Therapy of HCV
1991 1999 2001 2002
100

80

54-56
SVR (%)

60
42
39
34
40

16
20
6

0
IFN IFN IFN/RBV IFN/RBV PEG PEG/RBV
6m 12m 6m 12m 12m 12m
Strader DB et al. Hepatology. 2004;39:1147-1171.

PEGYLATION OF IFN α-2B

PEG-IFN α-2b

IFN α-2b

HCV Treatment
„ Side Effects

Flu like symptoms

Nausea/ vomiting
depression/ irritability
cytopenia
fetal wastage
opthalmologic
pancreatitis
Hypo/hyper thyroid

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 THERAPY IMPORTANT SAFETY
INFORMATION
WARNING
Alpha interferons, including PEG-INTRON®, cause or aggravate fatal or life-threatening neuropsychiatric,
autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic
clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of
these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve
after stopping PEG-INTRON therapy.
Ribavirin causes hemolytic anemia. Anemia associated with REBETOL therapy may exacerbate cardiac
disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or
unstable cardiac disease should not be treated with REBETOL®. It is advised that complete blood counts
(CBC) be obtained at baseline and at weeks 2 and 4 of therapy or more frequently if clinically indicated.
REBETOL and combination REBETOL/PEG-INTRON therapy must not be used by women, or male
partners of women, who are or may become pregnant during therapy and during the 6 months after
stopping therapy. REBETOL and combination REBETOL/PEG-INTRON therapy should not be initiated
until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy.
Women of childbearing potential and men must use effective contraception (at least two reliable forms)
during treatment and during the 6-month posttreatment follow-up period. Significant teratogenic and/or
embryocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies
have been conducted. These effects occurred at doses as low as one twentieth of the recommended
human dose of REBETOL®. If pregnancy occurs in a patient or partner of a patient during treatment or
during the 6 months after treatment stops, physicians are encouraged to report such cases by calling
(800) 727-7064.

*PEG-INTRON® (Peginterferon alfa-2b) Powder for Injection and REBETOL® (Ribavirin, USP) Capsules.

HCV Treatment
„ Close monitoring of pt
„ Avoid dose reduction or interruption in
treatment

„ Aggressive side effect management

„ Good pt and provider relationship

Summary
„ Liver is a vital organ with many important functions
„ Chronic liver diseases usually do not have any
symptoms, however can lead to cirrhosis over time.
„ Elevated liver enzyme is never normal and therefore
requires investigations
„ Goal should be to treat liver problems early to prevent
cirrhosis and the need for liver transplant

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 Summary
„ HCV and HBV are silent killers
„ HCV is the leading cause for liver transplant in
this country
„ Patients with high risk should be screened for
HCV and HBV.
„ All pts with HBV and HCV should be referred
to specialist regardless of ALT

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