Download HBV DNA - Scioto County Medical Society

S
1
S
2
S
3
S
Hepatitis A virus(HAV)
VIRUS

Classical infectious hepatitis

27nm RNA picornavirus

Single strand RNA
4
S
5
EPIDEMIOLOGY HEPATITIS A

10-20% of Americans Ab by age 20

50% Ab age 50 and 75% no hx of illness

90% underdeveloped countries age 10

Fecal-oral transmission
S
Geographic Distribution of HAV
Centers for Disease Control and Prevention. Health Information
for International Travel, 2003-2004.;2003.
6
S
Risk Factors for Hepatitis A
United States, 1990–2000
CDC. Epidemiology and Prevention of Vaccine-Preventable
Diseases. 8th ed. 2004.
7
S
Overview of HAV Transmission




Primary route of transmission: fecal-oral
HAV is spread by:
 Person-to-person contact
 Eating or drinking contaminated food or water
HAV can persist in the environment for months
Incubation period: 15-50 days
1.Centers for Disease Control and Prevention Hepatitis A. In: Epidemiology and Prevention of VaccinePreventable Diseases. 9th ed., 2006. 2. Centers for Disease Control and Prevention. Prevention of
hepatitis A through active or passive immunization: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR. 1999;48(RR-12):1-37.
8
S
Clinical Characteristics of HAV



Symptoms are age related and more severe in adults than children

Asymptomatic in >70% of children <6 years

Symptomatic in >70% of older children and adults
Clinical illness generally lasts up to 2 months

10%-15% of patients have symptoms lasting up to 6 months
High morbidity/low mortality

More severe complications in patients with chronic liver disease
CDC. Epidemiology and Prevention of Vaccine-Preventable Diseases. 9th ed. 2006:193-206
9
S
10
DIAGNOSIS-HEPATITIS A
HAV IgM positive
Occasionally relapsing course
Chronic liver disease doesn’t occur
TREATMENT -HEPATITIS A

Non-specific- bedrest,good diet,no alcohol

No effective antiviral therapy

Prevention- good sanitation

Immunization-active and passive
S
11
S
12
HBV Markers
 HBsAg: First viral marker to appear, indicates
viral DNA presence in body
 HBeAg: Associated with viral particles; some
mutants do not produce
 HBV DNA: Associated with viral particles; most
reliable marker of circulating infectious virus
S
13
HBV Antibodies
 Anti-HBc: First antibody to appear, lasts for
life, does not give immunity
 Anti-HBs: Indicates immunity; only marker
after vaccination
 Anti-HBe: Appears with loss of infectious virus;
with mutants, not reliable marker of clearance
Estimated Burden of HBV Infection in the
United States

New HBV infections
78,000 per year

Chronic HBV infections
>1-1.25 million

New Chronic HBV infections 5,000-8,000 per year

Deaths
5,000 per year
TYZEKA® (telbivudine) is not indicated to treat acute hepatitis B.
TYZEKA® (telbivudine) is not indicated to prevent mortality associated with hepatitis B.
http://www.cdc.gov/ncidod/diseases/hepatitis/b/bfact.pdf. Accessed 1/23/07.
14
Transmission of HBV Infection
Transfusion
(blood, blood
products)
Fluids
(blood, semen)
Organs and
tissue transplantation
Mother to baby
HEPATITIS B
Contaminated
needles
and syringes
Child to child
15
16
17
18
Signs & Symptoms: Chronic Hepatitis B




Usually Asymptomatic
Malaise/Fatigue
Extrahepatic Symptoms
Signs & Symptoms of Liver Failure
 Hepatocellular Carcinoma and/or Death
Pathophysiologic Cascade of Chronic
HBV Infection
HBV Replication
(Measured by
Serum HBV DNA)
19
Liver
Inflammation
ALT
Elevation
Worsening Histology
• Necroinflammation
• Fibrosis
• Cirrhosis
Disease Progression
• Liver Failure
• Liver Cancer
• Transplant
• Death
TYZEKA® (telbivudine) is not indicated to treat or prevent liver failure or liver cancer.
Adapted from: Lavanchy D. Journal of Viral Hepatitis, 2004, 11, 97–107. Chen JC, et al. JAMA. 2006;295:65-73. Iloeje
U. H, et al. Gastroenterology. 2006;130:678-86.
S
20
21
22
S
23
S
24
US Treatment Algorithm:
Patients With Compensated Disease
HBeAg-Positive
HBV DNA
<20,000 IU/mL
HBV DNA
≥20,000 IU/mL
(~5 Log10)
(~5 Log10)
Normal ALT
 No treatment
 Monitor every 6-12
months
 Monitor every 3-12
months (immune
tolerant)
 Consider biopsy,
especially if age>35-40
years, and treat if
significant disease
Adapted from Keeffe E et al. Clin Gastroenterol Hepatol 2006;4:936-962.
ALT elevated
 Treat
25
US Treatment Algorithm:
Patients With Compensated Disease
HBeAg-Negative
HBV DNA
< 2,000 IU/mL
HBV DNA
≥2,000 IU/mL
(~4 Log10)
(~4 Log10)
Normal ALT
ALT elevated
 No treatment
 Monitor ALT, or
 Treat
 Monitor every 6-12
months
 Consider biopsy, since
ALT often fluctuates,
and treat if significant
disease
 Long-term treatment
required
 Long-term treatment
required
Adapted from Keeffe E et al. Clin Gastroenterol Hepatol 2006;4:936-962.
26
S
27
The Twin Pillars of HBV Therapy
Viral
suppression
Avoidance
of resistance
S
Treatment of Established Resistance:
Choose One Drug From Each Class
Nucleosides
Nucleotides
LAM
ADV
LdT
TDF*
ETV
FTC*†
*off label
†
available in combination tablet with TDF
Guidance based on clinical data and author’s experience
28
S
Chronology of Events in Patients
Developing Resistance
Emergence of genotypic resistance
Virologic breakthrough
Biochemical breakthrough
Time on Therapy
29
S
Possible Algorithm to Assist in
Determining Which Strategy to Use
Low HBV DNA*
at Week 24
Low genetic
barrier drug
Add on
or
switch
High HBV DNA†
at Week 24
(any drug)
Any detectable
HBV DNA at Week
48 (any drug) ‡
Add on
Add on ‡
High genetic
barrier drug
Continue
*Low HBV DNA < 2000 IU/mL
†High HBV DNA ≥ 2000 IU/mL
‡If viral level very low on ETV or TDF (off label) can continue with further observation
Guidance based on clinical data and author’s experience
Slide courtesy of Ira Jacobson, MD.
30
S
Consequences of antiviral-resistance

Loss of initial virologic, biochemical and histological response

Virologic and biochemical breakthrough

Hepatitis flares, hepatic decompensation and death

Increased risk of HBV recurrence post-liver transplant

Limit future treatment options

Transmission to treatment-naïve persons → public health problem
31
S
32
S
33
S
34
Hepatitis C Virus
Transmission
Rate (%)
High Risk Profile
40
30
20
10
0
~5
2-3
Sexual Contact
With
Infected
Individuals
Organ
Transplant
Recipients
Prior to July
1992
2
Health Care
Workers,
Including
NeedleStick Injury
Transmission Factor
Other cohorts at increased risk include immigrants from areas where
where
universal precautions are not practiced, Vietnam veterans, and p atients with a
history of incarceration—
incarceration—likely due to the overlap in the highhigh-risk profile
Alter et al. N Engl J Med. 1999;341:556-562.
NIH Consensus Development Conference Statement. 2002.
Ohto et al. N Engl J Med. 1994:330:744-750.
S
35
S
36
S
37
S
38
S
39
S
40
S
Extrahepatic Manifestations of Hepatitis C

Hematologic: Mixed cryoglobulinemia
(10%–25% of HCV patients)*

Renal: Glomerulonephritis

Dermatologic:

Porphyria cutanea tarda

Cutaneous necrotizing vasculitis

Lichen planus
Management of Hepatitis C. NIH Consensus Statement, 2002.
41
Factors Associated With
Disease Progression
• Alcohol consumption
– 30 g/day in men
– 20 g/day in women
~ 2 drinks per day
• Disease acquisition at >40 years
• Male gender
• HIV coinfection
• Hepatitis B virus coinfection
• Immunosuppression
NIH Consensus Development Conference Statement. 2002.
Poynard et al. Lancet. 1997;349:825-832.
S
42
Factors Not
Influencing Progression
• Alanine aminotransferase level
(ALT)
• Viral load
• Mode of transmission
• Genotype
NIH Consensus Development Conference Statement. 2002.
Poynard et al. Lancet. 1997;349:825-832.
S
43
S
44
S
45
PEG IFN Alfa-2a + RBV
SVR in Genotype 1
PEG IFN alfa-2a 180 μg + RBV
SVR (%)
60
40
41
51
40
29
20
0
n=101
n=118
RBV
RBV
800 mg 1000-1200 mg
24 Weeks
n=250
n=271
RBV
RBV
800 mg 1000-1200 mg
48 Weeks
PEGASYS® (peginterferon alfa-2a) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002. (Study 5).
Hadziyannis et al. EASL; April 18-21, 2002; Madrid, Spain. Abstract 536.
S
46
S
47
S
48
S
49
Clinical Significance of
Sustained Virologic Response
• > 90% maintain response during 1 - 6
years of follow-up
• Liver histology improves or stabilizes
Lindsay et al. Hepatology. 1997;26(suppl 1):71S-77S.
S
50
S
Contraindications
Ribavirin
PEG IFN Alfa-2a
•
Hypersensitivity
•
Hypersensitivity
•
Autoimmune hepatitis
•
•
Hepatic decompensation
(Child-Pugh class B and
C) before or during
treatment
Women who are
pregnant
•
Men whose female
partners are pregnant
•
Patients with
hemoglobinopathies
(eg, thalassemia major
or sickle-cell anemia)
•
Neonates and infants
*Ribavirin must not be used alone because ribavirin monotherapy
is not effective for the treatment of chronic hepatitis C.
PEGASYS® (peginterferon alfa-2a) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002.
51
S
PEG IFN Alfa-2a + RBV Warnings
• Neuropsychiatric
• Pulmonary disorders
• Infections
• Colitis
• Bone marrow toxicity
• Pancreatitis
• Cardiovascular
• Ophthalmologic
• Hypersensitivity
• Pregnancy
• Endocrine disorders
• Anemia
• Autoimmune disorders
• Renal
disorders
disorders
COPEGUS™ (ribavirin, USP) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002.
PEGASYS® (peginterferon alfa-2a) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002.
52
S
53
Side Effects of Interferon
• Flu-like symptoms
– Headache
– Fatigue or asthenia
– Myalgia, arthralgia
– Fever, chills
• Neuropsychiatric
disorders
– Depression
– Mood lability
Alopecia
Thyroiditis
Nausea
• Diarrhea
• Injection-site reaction
• Lab alterations
•
•
•
– Neutropenia
– Anemia
– Thrombocytopenia
PEGASYS® (peginterferon alfa-2a) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002.
PEG-Intron™ (peginterferon alfa-2b) [package insert]. Kenilworth, NJ: Schering Corporation; 2001.
S
54
Side Effects of Ribavirin
• Hemolytic anemia
• Teratogenicity
• Cough and dyspnea
• Rash and pruritus
• Insomnia
• Anorexia
COPEGUS™ (ribavirin, USP) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002.
S
55
S
56
S
57
S
58
S
59
ACUTE HEPATITIS

Viral-A,B,C,D,E and nonA-E

Alcohol induced abnormalities

Autoimmune hepatitis

Viral-CMV,Herpes,Rubella,EBV

Drug-induced
S
60






Wilson’s Ds
Reye’s Syndrome
Acute fatty liver of pregnancy
Hypoperfusion States
Hepatic Vein occlusion(Budd-Chiari)
Malignancy(esp lymphoproliferative)
S
61
CLINICAL PRESENTATION OF CHRONIC HEPATITIS

Failure to resolve acute hepatitis(10%)

Abnormal LFT’S(80%)

Stigmata of complications of chronic liver disease(10%)
S
62
CLINICAL SPECTRUM

Abnormal transaminases may fluctuate and even return to normal

May be asymptomatic to markedly symptomatic

Non-specific-fatigue, malaise,or anorexia

Portal hypertension and/or hepatic failurejaundice,ascites,coagulopathy, GI bleed
S
63
DIFFERENTIAL DIAGNOSIS OF CHRONIC HEPATITIS
Autoimmune(10%)
Viral-Hepatitis B (25%)
-Delta Hepatitis(10%)
-Hepatitis C(50%)
Drugs(5%)
Wilson’s Disease
S
64
SIMILAR PRESENTATION TO CHRONIC HEPATITIS

Alpha 1 antitrypsin deficiency

Hemochromatosis

Primary biliary cirrhosis

Primary Sclerosing cholangitis

Alcoholic liver disease

NAFLD/NASH