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Viral Hepatitis ( Useful Points for GPs in W Herts). Dr Alistair King Consultant Gastroenterologist Hemel Hempstead General Hospital. New viral hepatitis service!. West Herts Chronic hepatitis B and hepatitis C All referrals (Watford, Hemel, St Albans) AK
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Viral Hepatitis(Useful Points for GPs in W Herts) Dr Alistair King Consultant 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
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 seroconversion Cons: • Viral resistance develops (YMDD) • May also provoke HIV resistance in co-infected patients
Adefovir dipivoxil Pros: • Well tolerated and effective • Little resistance Cons: • Expensive • Can induce renal failure
Hepatitis C • Flavivirus (RNA) • NANB • Discovered 1989 • 200,000 people in UK • 38,000 diagnosed • No vaccine
‘The silent epidemic’ • 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 80% chronic 7 years 30% cirrhotic 20 yrs 50% cirrhotic 5% 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++, IVDU Yes: • 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