Case 1:
29 y/o female came to your clinic with:
Jaundice, Abdominal pain, Nausea / Vomiting
AST-2,000 ALT- 2,500, Total bili 1.8
She denies IVDA or any recent drug/medicine exposure, but
had unprotected sex about 6 weeks ago
Ultrasound shows normal appearing liver and blood flow
Her diagnosis is
Viral Hepatitis
Drugs
A, B/D, C, E
EBV
CMV & HSV
Ethanol
Tylenol
Halothane
Toxins
Vascular
Hypotension
Budd-Chiari
Autoimmune
Hepatitis
Metabolic
Wilson's Disease
A1AT
Case:
38 y/o male with past medical history of abnormal ALT for
past 4 years. He had a blood tx as a child due to MVA.
Patient came to your clinic with:
ALT 150, AST 100
HBsAb +, HBcAb +
HCV Ab +
HAV IgG +
What is your dx?
Viral Hepatitis
Hep B
Hep C
Drugs
MTX
INH
Amiodarone
Alcohol
NAFLD
Autoimmune
AIH
PBC
PSC
Metabolic
A1AT
HHC
Wilson's
Abbreviations:
NAFLD: nonalcoholic fatty liver disease; AIH: autoimmune hepatitis; PBC: primary biliary cirrhosis
PSC: primary sclerosing cholangitis, A1AT: alpha-1 antitrypsin deficiency, HHC:hereditary hemochromotosis
34%
47%
16%
3%
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis
Non-ABC
Hepatitis A Virus
27 nm
HAV Prevalence
High
Intermediate
Low
Very Low
Symptoms
Total anti-HAV
Titer
ALT
Fecal
HAV
IgM anti-HAV
12
24
Hepatitis E Virus
32 nm
Hepatitis E
Clinical Characteristics
Similar to hepatitis A
Dx: IgG anti-HEV (seroconversion)
Can cause severe acute hepatitis
Subclinical infection is common
Attenuated virus from animal reservoirs
Low-dose infections often asymptomatic
No chronic infection
Up to 20% mortality among pregnant women (esp. third
trimester)
Hepatitis B Virus
HBsAg
42 nm
HBcAg
HBV DNA
Cirrhosis in 20%
(75 - 100 million)
HCC in 5 - 10%
(20 - 40 million)
HBsAg Prevalence
8% - High
2-7% - Intermediate
<2% - Low
Hepatitis B Prevalence
Overall U.S. prevalence: 0.3%
Asian Americans: ~10-13%
Multiple sex
partners, 24%
IDU, 20%
Jaundice
Fatigue
Abdominal Pain
Loss of Appetite
Nausea, vomiting
Joint pain
Dark Urine
Clay-colored bowel
movements
Average: 60 90 days
Range: 45 180 days
0.5 1%
Chronic infection
15 25%
Chronic
(Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titer
HBV DNA
IgM anti-HBc
8 12 16 20 24 28 32 36
52
Years
(may clear)
Anti-HBs
Chronic
HBeAg +
disease
Chronic
HBeAG
disease
Anti-HBc
IgM
Anti-HBc
HBeAg
(may be
only
marker
during
window
period)
Successful
Vaccination
Resistance
to antiviral
agents
(in some
cases)
Anti-HBe
DNA (PCR
if required)
Recovery
from acute
hepatitis B
(sequence
pol region)
Chronic
Infection
90% in perinatal
30-90% in children<5yrs old
5% in healthy adults
Higher in HIV, immune suppressed
Cirrhosis
10-30% 1
Liver Failure
(Decompensation)
23% within 5 years
1.
2.
3.
4.
Liver
Transplantation
Death
Non-hepatitis B Cirrhosis
Hepatitis C
Alcoholic cirrhosis
Genetic hemochromatosis
Primary biliary cirrhosis
Other (? efficacy)
A1AT deficiency
NAFLD
Autoimmune hepatitis
Virologic Response
Approved Treatments
35-37nm
Clinical features
- Fulminant: 2 7.5%
- Chronic infection
Superinfection: 80%
Coinfection: < 5%
Diagnostic tests
-Acute infection: IgM anti-HDV
-Chronic infection:IgG anti-HDV, HBsAg +
Coinfection
D
Superinfection
B
D
Cell Binding
and Infection
Immune
Recognition
Replication
HCV
Immune
Response
Effector
CD4
CD8
NK
DC
Cytokines
Viral Packaging
and Release
HSC
HSC
Fibrosis
Fibrosis
ALT (IU/L)
800
600
400
200
Normal ALT
6 8 10 12 24 1 2 3 4 5
Weeks
Months
Time After Exposure
Hoofnagle JH. Hepatology. 1997;26:15S. Carithers RL Jr, et al. Semin Liver Dis.
2000;20:159-171. Pawlosky JM. Hepatology. 2002;36(suppl 1):S65-S73. NIH Management
of Hepatitis C Consensus Conference Statement. June 10-12, 2002. Available at:
http://consensus.nih.gov/2002/2002HepatitisC2002116html. Accessed April 10, 2007.
Cirrhosis
7%
100
80
60
40
20
0
56%
Asymptomatic
80
Fatigue
43
40
15
20
0
Persistently
Normal ALT
Intermittently
Elevated ALT
Persistently
Elevated ALT
Quantitative assays
High sensitivity
( 50 IU/mL)
Genotype
assays
What type of HCV is present?
Hemophilia
IVDA
Prison
HIV
Blood transfusion prior to 90
Infants to HCV+ Mothers
Sexual Partner
General Population
74-90%
72-89%
40%
30-40%
5-9%
5%
0.5-3%
1.8%
Mexican
American
3.5%
Anti-HCV+ (%)
African
American
3.2%
5
4
3
Caucasian
1.1%
2
1
0
611
1219
2029
4049
3039
Age (yr)
5059
6069
70+
HCV infection
60-85%1
Chronic HCV
Cirrhosis
20%-50%2
Hepatic Failure
~ 20%3
~20%4
Liver Cancer
1. NIH Consensus Development Conference Statement; March 24-26, 1997.
2. Davis GL et al. Gastroenterol Clin North Am. 1994;23:603-613.
3. Koretz RL et al. Ann Intern Med. 1993;119:110-115.
4. Takahashi M et al. Am J Gastroenterol. 1993;88:240-243.
Liver Transplant
Candidates
No fibrosis
Fibrosis Stage
Amount of fibrous scar tissue
0-4 (METAVIR)
Stage 4 = cirrhosis
Indicates long-term disease progression
Cirrhosis
Decision to Treat
Identification
Identification
and Planning
and Planning
Treatment
Stage
Diagnosis
Prognosis
Treatment
Duration
Assess Response
and Resistance
Liver biopsy
Genotyping
Quant HCV
RNA
Assay
Serological
Qual HCV
RNA
2001
2002
Sustained Virologic
Response (%)
1991
IFN
6m
Strader DB et al. Hepatology 2004;39:1147-1171
IFN
12m
IFN/RBV
6m
IFN/RBV
12m
Peg-IFN
12m
Peg-IFN/
RBV 12m
HCV-2,3
Peg-IFN+ RBV
1000/1200 mg/day
Peg-IFN +
RBV 800 mg/day
for 24 weeks
Stop or re-evaluate
therapy
48 weeks