Viral Hepatitis(Useful Points for GPs in W

Herts)

Dr Alistair KingConsultant Gastroenterologist

Hemel Hempstead General Hospital

New viral hepatitis service! 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 Hepadnavirus Double strand

DNA virus Massively

overproduces envelope proteins (HBsAg, Australia antigen)

Modes of transmission Sexual Blood products IVDU Vertical

High endemnicity Transmission occurs at birth

Acute infection 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 1% of cases Encephalopathy within 8/52 of Sx Prolonged PT (>17s) or INR

(>=1.5)

Management (acute) Rest/supportive Avoid EtOH Counsel re contacts Watch for FHF Check Hep B serology in 6/12-

Should be HBsAg-ve, HBsAb+ve

Immunity HBsAb = immune

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 350 million worldwide UK prevalence < 1% risk cirrhosis, decompensation,

HCC 15-40% develop serious sequellae

3 potentially successive phases:

1. Immunotolerant phase HBV-DNA levels high HBsAg+ve, HBeAg+ve,

normal/mildly deranged LFT Patient asymptomatic Often perinatally acquired

2. Immunoactive phase HBsAg+ve HBV-DNA levels decrease Transaminases increase Patient may develop symptoms HBeAgHBeAb seroconversion

‘Inactive carrier state’ HBV DNA<105

HBsAg+ve, HBeAg-ve, normal LFTs Low infectivity, little inflammation Low risk of complications BUT- DNA levels may fluctuate

(15%)

RARELY HBsAgHBsAb seroconversion (1-2% per year)

Inactive carrier stateDo they need follow-up?

Normal LFT Antenatal screening, occupational

health Benign course 20-30% of patients may reactivate Cirrhosis HCC (+/- cirrhosis)

Precore mutants 1-5% of patients with

HBeAgHBeAb 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 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

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%

HCC and complications of cirrhosis

Hepatitis D ‘Incomplete’ virus Coinfection/superinfection Superinfection acute flare Suppresses hep B chronic hep D Drug users Mediterranean

What do we do? (HBsAg+ve) Monitor LFT Lifestyle advice ‘Screen’ for development of HCC

AFP +/- U/S 6 monthly Treatment:

Interferon Lamivudine Adefovir

Lifestyle advice Alcohol Drug users Hep A vaccination Screening/vaccination of close

contacts Barrier contraception, toothbrushes,

razors etc Occupations

Treatment Not for:

Acute hep B (FHF liver transplant) Inactive carrier state/mild disease Decompensated cirrhosis

May be considered HBV-DNA>105, persistently elevated

transaminases 2xULN (>6 months)

Antenatal screening All mothers offered Hep B, HIV,

Rubella, Syphillis screening in antenatal clinic

95-98% uptake HBsAg+ves

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

Lamivudine

Pros: Well tolerated/non-toxic Suppresses viral replication/DNA

levels Rarely may induce seroconversionCons: Viral resistance develops (YMDD) May also provoke HIV resistance in

co-infected patients

Adefovir dipivoxil

Pros: Well tolerated and effective Little resistanceCons: Expensive Can induce renal failure

Hepatitis C Flavivirus (RNA) NANB Discovered 1989 200,000 people in

UK 38,000 diagnosed No vaccine

Who gets it?

‘The silent epidemic’ Only 10% report jaundiced illness 80% go chronic Nonspecific Sx (lethargy, myalgia,

RUQ pain) Routine screening Cirrhosis/HCC

Clinical courseHCV infection

20% PCR-ve 80% chronic

7 years 30% cirrhotic

20 yrs 50% cirrhotic5% HCC

30yrs 15% death

What do we do? (HCV Ab+ve) Exclude other causes of CLD HCV-RNA PCR Lifestyle advice If RNA+ve and for treatment liver

biopsy Treatment: PEG-IFN + Ribavirin

Lifestyle advice Avoid EtOH Avoid blood donation, needle

sharing ?Barrier methods:

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++, IVDUYes: HCV-RNA PCR+ve, deranged LFT Moderate/severe hepatitis on Bx Fibrosis

Treatment PEG interferon weekly + ribavirin

bd Genotype 1 (+4): 48weeks (recheck

PCR 12 weeks) Genotype 2,3: 24 weeks

Monitor FBC Ribavirin haemolysis IFN WCC, plt

Response rates Sustained viral response:

Genotype 1: 50% Genotype 2,3: 80%

May be worse if: Male Older Infected a long time Cirrhotic HIV coinfection

Cost PEG-IFN: £120-150/wk Ribavirin: £15-20/day

24 weeks therapy: £5,500-£7,000 48 weeks therapy: £11,000-£14,000

BUT: Probably cost effective

Other follow up PCR negatives and responders

Yearly LFT and PCR Non-responders

Regular LFT, PCR, monitoring Re-biopsy after 3 years Other treatments may become

available HCV/HIV co-infection

Aggressive course cirrhosis

CMO’s infectious diseases strategy

Identified as needing ‘intensified action’ Prevention Diagnosis Treatment

Emphasis on local services

Summary 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?