Download Hepatitis B for GPs

Viral Hepatitis
(Useful Points for GPs in W Herts)
Dr Alistair King
Consultant Gastroenterologist
Hemel Hempstead General
Hospital
New viral hepatitis service!
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West Herts
Chronic hepatitis B and hepatitis C
All referrals (Watford, Hemel, St
Albans) AK
Local care, rather than referral to Royal
Free
Hepatitis B
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Hepadnavirus
Double strand DNA
virus
Massively
overproduces
envelope proteins
(HBsAg, Australia
antigen)
Modes of transmission
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Sexual
Blood products
IVDU
Vertical
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High endemnicity
Transmission occurs at birth
Acute infection
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Incubation 60-180 days
Self limiting jaundiced illness
HBsAg, HBeAg, HBV DNA detectable
IgM anti-HBc. Anti-HBs confirms
resolving infection
Raised ALT (>AST) & Bilirubin
Should resolve within 6 months
Fulminant hepatic failure
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1% of cases
Encephalopathy within 8/52 of Sx
Prolonged PT (>17s) or INR (>=1.5)
Management (acute)
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Rest/supportive
Avoid EtOH
Counsel re contacts
Watch for FHF
Check Hep B serology in 6/12- Should
be HBsAg-ve, HBsAb+ve
Immunity
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HBsAb = immune
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Reassure ++ no further action
HBsAb+ve, HBcAb+ve = immune 2o to
past infection
HBsAb+ve, HBcAb-ve = immune 2o to
vaccination
Serological course
Chronic hepatitis B
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350 million worldwide
UK prevalence < 1%
 risk cirrhosis, decompensation, HCC
15-40% develop serious sequellae
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3 potentially successive phases:
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1. Immunotolerant phase
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HBV-DNA levels high
HBsAg+ve, HBeAg+ve, normal/mildly
deranged LFT
Patient asymptomatic
Often perinatally acquired
2. Immunoactive phase
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HBsAg+ve
HBV-DNA levels decrease
Transaminases increase
Patient may develop symptoms
HBeAgHBeAb seroconversion
‘Inactive carrier state’
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HBV DNA<105
HBsAg+ve, HBeAg-ve, normal LFTs
Low infectivity, little inflammation
Low risk of complications
BUT- DNA levels may fluctuate (15%)
RARELY HBsAgHBsAb seroconversion
(1-2% per year)
Inactive carrier state
Do they need follow-up?
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Normal LFT
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Antenatal screening, occupational health
Benign course
20-30% of patients may reactivate
Cirrhosis
HCC (+/- cirrhosis)
Precore mutants
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1-5% of patients with HBeAgHBeAb
seroconversion
HBV-DNA levels >105
HBsAg+ve, HBeAg-ve, elevated
transaminases
Due to mutation in viral precore region
which prevents production of HBeAg
Otherwise behave like ‘immunoactive’
chronic hep B
Cirrhosis
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2-5.5% per year – HBeAg+ve
8-10% per year– HBeAg-ve chronic hep
Diagnosed 41-52yrs
3.3% decompensate (ascites, jaundice,
variceal bleed)
HCC
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Without cirrhosis 0.2-0.6% per year
With cirrhosis 2% per year
Mortallity
5-year mortallity:
 Without cirrhosis 0-2%
 Compensated cirrhosis 14-20%
 Decompensated 70-86%
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HCC and complications of cirrhosis
Hepatitis D
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‘Incomplete’ virus
Coinfection/superinfection
Superinfection acute flare
Suppresses hep B chronic hep D
Drug users
Mediterranean
What do we do? (HBsAg+ve)
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Monitor LFT
Lifestyle advice
‘Screen’ for development of HCC
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AFP +/- U/S 6 monthly
Treatment:
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Interferon
Lamivudine
Adefovir
Lifestyle advice
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Alcohol
Drug users
Hep A vaccination
Screening/vaccination of close contacts
Barrier contraception, toothbrushes,
razors etc
Occupations
Treatment
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Not for:
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Acute hep B (FHF liver transplant)
Inactive carrier state/mild disease
Decompensated cirrhosis
May be considered
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HBV-DNA>105, persistently elevated
transaminases 2xULN (>6 months)
Antenatal screening
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All mothers offered Hep B, HIV, Rubella,
Syphillis screening in antenatal clinic
95-98% uptake
HBsAg+ves
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Vaccinate babies at birth
HBIG
Interferon (IFN)
Previously ‘first line’
Cons:
 Sc injection 5mU daily for 6mths-2yrs
 Poorly tolerated
 Suppress viral replication but rarely
induce seroconversion
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Lamivudine
Pros:
 Well tolerated/non-toxic
 Suppresses viral replication/DNA levels
 Rarely may induce seroconversion
Cons:
 Viral resistance develops (YMDD)
 May also provoke HIV resistance in coinfected patients
Adefovir dipivoxil
Pros:
 Well tolerated and effective
 Little resistance
Cons:
 Expensive
 Can induce renal failure
Hepatitis C
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Flavivirus (RNA)
NANB
Discovered 1989
200,000 people in
UK
38,000 diagnosed
No vaccine
Who gets it?
‘The silent epidemic’
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Only 10% report jaundiced illness
80% go chronic
Nonspecific Sx (lethargy, myalgia, RUQ
pain)
Routine screening
Cirrhosis/HCC
Clinical course
HCV infection
20% PCR-ve
7 years
20 yrs
30yrs
80% chronic
30% cirrhotic
50% cirrhotic
5% HCC
15% death
What do we do? (HCV Ab+ve)
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Exclude other causes of CLD
HCV-RNA PCR
Lifestyle advice
If RNA+ve and for treatment liver
biopsy
Treatment: PEG-IFN + Ribavirin
Lifestyle advice
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Avoid EtOH
Avoid blood donation, needle sharing
?Barrier methods:
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Monogamous relationships- No (<5%)
Multiple sexual partners- Yes (?11.7%)
Vertical transmission rare
Breast feeding OK
Who do we treat?
No:
 HCV-RNA PCR-ve
 Mild hepatitis on Bx
 Decompensated cirrhosis
 Current EtOH++, IVDU
Yes:
 HCV-RNA PCR+ve, deranged LFT
 Moderate/severe hepatitis on Bx
 Fibrosis
Treatment
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PEG interferon weekly + ribavirin bd
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Genotype 1 (+4): 48weeks (recheck PCR
12 weeks)
Genotype 2,3: 24 weeks
Monitor FBC
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Ribavirin haemolysis
IFN WCC, plt
Response rates
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Sustained viral response:
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Genotype 1: 50%
Genotype 2,3: 80%
May be worse if:
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Male
Older
Infected a long time
Cirrhotic
HIV coinfection
Cost
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PEG-IFN: £120-150/wk
Ribavirin: £15-20/day
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24 weeks therapy: £5,500-£7,000
48 weeks therapy: £11,000-£14,000
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BUT: Probably cost effective
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Other follow up
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PCR negatives and responders
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Non-responders
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Yearly LFT and PCR
Regular LFT, PCR, monitoring
Re-biopsy after 3 years
Other treatments may become available
HCV/HIV co-infection
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Aggressive course cirrhosis
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CMO’s infectious
diseases strategy
Identified as needing
‘intensified action’
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Prevention
Diagnosis
Treatment
Emphasis on local
services
Summary
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Chronic HBV relatively rare and need for
treatment rarer
Most are ‘inactive carrier state’
HCV common – IVDU – Rx makes
pharmaco-economic sense
Cirrhosis/HCC transplantation/death
New W Herts clinic for viral hepatitis
Questions?