viral hepatitis - gp cme · 2008-06-25 · viral hepatitis hav hbv hcv ... problems. up to 9 out of...
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Viral Hepatitis
Dr Melissa HainesGastroenterologist
Waikato Hospital
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Viral Hepatitis
HAV HBV HCV HDV HEV Other viral: CMV, EBV, HSV Unknown
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Hepatitis AHepatitis A
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Hepatitis A
Transmitted via the faecal-oral route Faecally contaminated food or water
Worldwide distribution
Most common cause of viral hepatitis
Causes acute infection only Asymptomatic fulminant hepatitis
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Hepatitis A Diagnosis
Prodromal symptoms Jaundice Abdominal tenderness and liver enlargement ALT elevated HAV IgM antibody positive
Symptoms resolve in majority after 2 months
Prevention Public and personal health measures Vaccination
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Hepatitis BHepatitis B
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Hepatitis B virus (HBV) is one of the world’s most common infectious agents
Serious global public health problem
One third of world’s population (~2 billion) have been infected with HBV
Estimated 350 million people (~5% of world’s population) have chronic HBV infection
25-40% (75-160 million) die of cirrhosis or liver cancer
WHO 2003
Global Importance of Hepatitis B Virus
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Worldwide Prevalence of HBV and Incidence of HCC
World prevalence of HBV carriers
HBsAg carriers-prevalence<2%2–7%>8%Poorly documented
Annual incidence of primary HCC
Cases/100,000 population1–33–1010–150Poorly documented
WHO 2003
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Impact of HBV in NZ
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Asia-Pacific
Maori, 625000
Pacific295000
Asian, 395,000
European2.7million
1.2millio
n
1.2millio
n
Estimated 90,000 HBsAg+living in New Zealand in 2006
http://www.stats.govt.nz/products-and-services/Articles/pop-proj-Jun04.htm
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National HBV Screening Programme
7.7%5.8% 6.2%6.5% 1%
45%
9%
59%59%54%
0%
25%
50%
75%
100%
Overall Maori Pacifican Asian European
HBV
Stat
us
HBsAg(-)/anti-HBs(-)= HBV naïve
anti-HBs(+) = immune to HBV
HBsAg+ = chronic HBV
177,292 Screened 177,292 Screened (July 1999 (July 1999 -- July 2002)July 2002) 11,300 HBsAg+ identified11,300 HBsAg+ identified
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EndEnd--Stage Liver Disease in New ZealandStage Liver Disease in New ZealandLiverLiver--Related MortalityRelated Mortality
HCV30%
HBV5%
other15%
HCV5%
HBV50%
other5%
USAUSA25,000 deaths per annum25,000 deaths per annum
New ZealandNew Zealand300 deaths per annum300 deaths per annum
Alcohol 50%
Alcohol 40%
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Alcohol31%
Other4%
HBV63%
HCV8%
LiverLiver--related Mortalityrelated Mortality19991999
Weir,2002Weir,2002
HCV26%
Alcohol8%
Biliary12%
Acute6%
HBV30%
Liver TransplantLiver Transplant19981998--20062006
(n=290)(n=290)
NZLTU,2006NZLTU,2006
Alcohol7% Other
9%
HBV75%
HCV9%
Hepatoma Clinic Hepatoma Clinic 20002000--20062006
(n=544)(n=544)
Gane,2006Gane,2006
Impact of HBV Infection
9090--100 cases 100 cases per annumper annum
15 cases per 15 cases per annumannum
200+ cases 200+ cases per annumper annum
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Transfusion and transplant recipients
Sexual partners of known chronic
carrier
Healthcareworkers
Newborns of long- term carriers
Intravenousdrug users
Prisoners and other institutionalised people
Transmission of Hepatitis B Infection
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Outcomes of Acute HBV Infection
Recover
Subclinical Hepatitis
Fulminant Hepatitis
Acute Hepatitis
ACUTE INFECTION
Chronic InfectionDEATH
< 1% 0.1-2.7%
5-20%
> 958010Recover< 52090Chronic carrier
Adults, %Children, %Neonates, %OutcomeRisk is Related to Age at Infection
Juszczyk J. Vaccine. 2000;18(suppl 1):S23-S25.
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They are all healthy carriers!
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Chronic hepatitis B has serious long-term consequences
HBsAg-positiveChronic Hepatitis B
Cirrhosis
Liver Failure
DeathHepatocellularcarcinoma (HCC)
Lok et al 2002
30%
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Natural History of Chronic HBV Infection
0 10 20 30 40 50 60 70Years
SerologyHBeAg Anti-HBe
ALT level
HBV DNA level
(viremia)
Disease Chronic activehepatitis
Cirrhosis/HCC
Immune tolerant (phase I)
Immune Active (phase II)
Non-Replicative(phase III)
Chronicity Stage
Minimal inflammation
Resolved
Normal to cirrhosis/HCC
HBsAg Anti-HBs
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Initial Evaluation of HBV Carriers (HBsAg+)
History and examination Assess risk factors
(coinfection) Alcohol use Family history of HBV and
HCC Physical findings of
cirrhosis
Lok AS, et al. Hepatology 2001;34:1225-1241.Tsai NC. Sem Liver Dis. 2004;24(suppl 1):71-76.
Investigations Liver disease activity Liver fibrosis/cirrhosis INR, albumin, bilirubin
Serologic and virologic markers
Screening for HCC (AFP and ultrasound)
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Is HBV Serology Confusing??
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HBV Serology
sAg determines carrier status eAg determines replication and infectivity
cAb confirms natural infection sAb confirms immunity
HBV DNA (viral load) measures infectivity and replication
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7 Taiwanese townships Individuals aged 30–65 years eligible
(n = 89,293)
Baseline HBV DNA(n = 3851)
Baseline HBsAg+(n=9800)
1991-1992: recruitment
June 2004: 43,993 PYs follow-up
Follow-up analysisFor Cirrhosis/HCC
(n = 3774)
Chen CJ ,Chen CJ , JAMA JAMA 20062006
Risk Evaluation of Viremia Elevation & Associated Liver Disease prospective, multicenter, observational cohort study (REVEAL)
Viral Load predicts Disease Progression
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Iloeje UH et al. Gastroenterology 2006; 130: 678–86.
Higher viral loads are associated with increased rate of cirrhosis
≥106cpm
Year of follow-up
Cum
ulat
ive
inci
denc
eof
live
r cirr
hosi
s
36.2%36.2%
4.5%4.5%
RR=9.6RR=9.6
0
.01
.02
.04
.03
0 21 3 4 5 6 7 8 9 10 11 12 13
105-106cpm
<300 cpm
104-105cpm300-104cpm
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>10>1066cpmcpm
101055--101066cpm cpm
101044--101055cpm cpm 300300--101044cpm cpm < 300cpm < 300cpm
Higher viral loads are associated with increased rate of hepatoma
1515%%
1.3%1.3%
RR=11RR=11
0
2
4
6
8
10
12
14
0 1 2 3 4 5 6 7 8 9 10 11 12 13Year of follow-up
Cum
ulat
ive
inci
denc
e of
HC
C %
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Year of follow-up
Yang et al. J Hepatol 2005: 42(suppl 2); 195.
Cum
ulat
ive ra
te o
f live
r fail
ure
≥105 cpm
104-105 cpm<104 cpm
00
21 3 4 5 6 7 8 9 10 11 12
5%
10%
15%
20%
25%
30%
Higher viral loads associated with increased rate of liver failure
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1.00
0.96
0.92
0.88
0.84
0.800 1 2 3 4 5 6 7 8 9 10 11 12
Cum
ulat
iev
Surv
ival
Survival Time (Years)
HBV DNA 3-5 logsRR=1.5 (0.2–11.8)
HBV DNA (-)
HBV DNA >5 logsRR=15.2 (2.1–110)
Higher viral loads associated with increased liver-related mortality
Chen G et al., Am J Gastro, 2006
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Indications for Treatment ofChronic HBV
Patients with active liver disease: Abnormal liver function tests (AST, ALT) HBeAg positive and > 105 HBV DNA HBeAg negative and > 104 HBV DNA Biopsy if HBV DNA < 104 with ALT Treat if active hepatitis (biochemical or histologic)
Lok AS, et al. Hepatology. 2001;34:1225-1241.
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Viral suppression Reduction or loss of serum HBV DNA
Immune system activation Development of antibodies against HBV
Reduction/cessation of liver injury Normalisation of liver function Improvement in liver histology
Prevention of complications Cirrhosis, liver failure, hepatoma
Improve survival
Objectives of TreatmentObjectives of Treatment
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Anti-viral agents Lamivudine Adefovir dipivoxil*
Immunomodulators Interferon-
Current approaches to treatment of Current approaches to treatment of chronic hepatitis Bchronic hepatitis B
Drug typesDrug types Continuous long term
Finite course
Undefined: dependant on response
Treatment durationTreatment duration
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Vaccination for Hepatitis B
Reducing the Burden of Chronic HBV
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Incidence of Acute Hepatitis B:United States, 1978-1995
Vaccinelicensed HBsAg screening
of pregnant women
Infantimmunization
Adolescent immunization
80
70
60
50
40
30
20
10
078 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Cas
es/1
00,0
00
Safer Injection and Sexual Practices
Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/b/. Accessed February 5, 2006.
Year
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Annual Incidence of Liver Cancer in Children Aged 6-15 Years
0.000.6190.13*0.52Total
0.310.4880.150.537
After Program Cohort
(1984-1986),Incidence per
100,000
Before Program Cohort
(1974-1984),Incidence per
100,000
Age at Diagnosis
0.000.466
Chang MH, et al. N Engl J Med. 1997;336:1855-1859.
*P < .001 for comparison between birth cohort.Vaccination program in effect since July 1984
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Babies who end up as carriers have a 1 out of 4 chance of dying from liver problems.
Up to 9 out of 10 babies born to infected mothers will end up being carriers for the rest of their lives, if they do not get the shots.
19 out of 20 babies who get the shots will be protected for life!
Infants who do not receive vaccination
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6 months oldHepatitis B
Vaccine
Baby Shots for Hepatitis Bif the mother has Hepatitis B
1 - 2 months old
Hepatitis BVaccine
+Birth
H-BIGHepatitis B
Vaccine
Infants who receive all 3 shots, plus H-BIG, have a 95% chance of being cured from hepatitis B for life.
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If you have never had hepatitis B,you can get 3 shots . . .
. . . and get long lasting protection.
321
Hepatitis B can be prevented!
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• Since hepatitis B virus can be passed to them, they should be tested to see if they have this virus in their bodies.
• If they do not have the hepatitis B virus, they should get the shots to protect themselves.
Should relatives/partners be tested for HBV?
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Issues Related to HBV Vaccination
• Poor or non-response to vaccination• Strategies to maximize likelihood of response
• Durability of vaccine response• Need for booster vaccinations?
• Missed opportunities for vaccination• Especially among adults at risk
Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2004;52:1252-1254.
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Hepatitis CHepatitis C
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25,000 New Zealanders have HCV infection Most are young, ex-IDU 9% are cirrhotic at presentation referrals to Hepatitis Clinics
detectionawareness of risk factors
demand for treatmentmore effective therapies
HBV still main cause of end-stage liver disease in NZ BUT HCV-ESLD over next decade
HCV infection
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Intravenous drug use
74%
Blood products
13%
HCV+ partner2%
Tattoo1%
Other2%
None8%
Risk factors for HCV exposure
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Natural History of Hepatitis C
Acute HCV infection
70-80% chronic HCV 20-30% spontaneous clearance
Chronic hepatitis:Minimal-severe
inflammation & fibrosisBridging fibrosis
Hepatocellularcarcinoma
Cirrhosis develops in 10-15% over 20-30yrs
Liver transplantation
Liver Failure Death
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Management Diagnosis HCV IgG antibody positive HCV RNA positive
Determine genotype 1 & 4 ‘hard to treat’: 12 months, 55% cure rate 2 & 3 ‘easy to treat’: 6 months, 80% cure rate
Treatment Pegylated interferon +ribavirin
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Conclusion
HBV and HCV are New Zealand problems
Refer patients Surveillance for HCC is necessary
Treatment is available Prevents disease progression
HBV vaccine is highly effective Reduces incidence HBV Reduces rates of liver complications