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 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 2 o to past infection HBsAb+ve, HBcAb-ve = immune 2 o 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 HBeAg  HBeAb seroconversion

‘Inactive carrier state’ HBV DNA<10 5 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? Normal LFT Antenatal screening, occupational health Benign course 20-30% of patients may reactivate Cirrhosis HCC (+/- cirrhosis)

Precore mutants 1-5% of patients with HBeAg  HBeAb seroconversion HBV-DNA levels >10 5 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 % 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>10 5, 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 ,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 course HCV infection 20% PCR-ve80% chronic 7 years 30% cirrhotic 20 yrs50% 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++, 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: £ /wk Ribavirin: £15-20/day 24 weeks therapy: £5,500-£7, 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?