CITY & HACKNEY ELIC EAST LONDON INTEGRATED CARE MANAGEMENT OF CHRONIC HEPATITIS B IN PRIMARY CARE Chronic Hepatitis B virus (HBV) is an important public health problem globally and a leading cause of liver related morbidity and mortality. The incidence is also increasing in the UK with 4500 cases of acute hepatitis B virus infections diagnosed per year, 75000 new cases of chronic infections diagnosed and 450 cases of hepatitis B related hepatocellular carcinoma. The estimated cost to the NHS is 26million per year. Most cases of chronic HBV infection are seen in immigrants from the Middle East, Africa and Asia. Areas with high immigrant populations such as inner city London are well placed to help prevent progression of HBV infection through monitoring and referral for treatment as well as immunising those at risk. In many people, chronic hepatitis B is inactive and does not present significant health problems, but others may progress to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The progression of liver disease is associated with hepatitis B virus (HBV) DNA levels in the blood. The aim for primary care is to: identify patients with chronic active hepatitis B identify those chronic carriers that are highly infectious (high viral replication is defined as HBV DNA levels >2000iU) and refer them to secondary care where further action can be taken to prevent the development of progressive hepatitis and fibrosis. Treatment in these phases may lead to a regression of disease. The decision to treat is based on histological evidence and thus requires a liver biopsy. Immunize at risk contacts This protocol is to help guide GPs in identifying these patients and reduce the variability of management. ABOUT CHRONIC HEPATITIS B INFECTION Hepatitis B may be transmitted by blood or sexual intercourse, perinatal spread or by prolonged close family contact. Infection may be subclinical or a self-limiting acute hepatitis. The main investigation to denote carrier status is HBsAg. Its presence indicates either a current or chronic infection. Hepatitis B carriage is the presence of HBsAg for at least 6 months Most patients are infected at birth or in early childhood and as the infection can lie dormant for decades they may show no symptoms. Those individuals who are infected in adult life are more likely to clear the infection and thus are found to be HBsAg negative after 6 months. It is important to know that when we are counselling an adult who has recently being discovered to be HBsAg positive, that it is very likely that they have acquired this in childhood. 1
Figure 1 summaries disease progression between infection acquisition in childhood compared with that in adulthood. WHO TO VACCINATE Higher risk groups where vaccination is advisable include the following: Babies born to hepatitis B carrier mothers Sexual partners of hepatitis B carriers Household contacts IVDU Male homosexuals Kidney dialysis patients Sex Workers Health care workers Garbage collectors Prisoners or other institutionalised individuals Travellers to endemic areas THE VACCINATION SCHEDULE There are three ways in which you can administer the Vaccination. You need three doses of the vaccine for full protection. 1. Preferred Method This involves giving the second dose one month after the first dose. The third dose is given five months after the second dose. A month after the third dose a blood test needs to be done to look for antibodies against the hepatitis B virus. This is because in some people 3 doses are not enough and a booster is needed after 5 years. 2
The other 2 schedules are termed Rapid. These may be necessary when a quicker immunity is required; e.g. someone sharing needles with someone with hepatitis, B, sudden travel, going to prison. 2. Alternatively, one can give three doses a month apart (0, 1, 2 months) 3. The quick schedule is the second dose given seven days after the first and the third dose given 21 days after the first (0, 7, 28 days) It is worth noting that the more rapid schedules may not be as effective at conferring long term immunity and therefore these individual will need a fourth dose 12 months after the first if they are at ongoing risk of exposure. The first rapid schedule is preferred for neonates (dose 1 within 24hrs of birth, then 1m and 2m) this is done by the paediatrics dept. These infants should be tested for infection at 1 year old (HBsAg) and given a fourth dose aged 1 year (and fifth booster at pre-school imms). RESPONSE TO VACCINATION Testing for anti-hbs after vaccination is not recommended, except in: Those at risk of occupational exposure Renal patients on haemodialysis Infants of HBV mothers Patients who need a further booster at 5yrs: Occupational risk Ongoing lifestyle risk of exposure PREGNANCY AND HEPATITIS B In 2004 an audit carried out at the Homerton revealed that 9.8% of all antenatal women booking there were carriers of hepatitis B Vertical transmission (mother to infant) is proportional to level of viral replication Most (>90%) of infected infants become chronic carriers. Infants born to infectious mothers are vaccinated from birth, usually in combination with Hepatitis B specific Immunoglobulin 200 i.u. i.m if high levels of viral replication (>2000iU). This reduces vertical transmission by ninety percent. To summarise: 3
Previously, all pregnant women identified as Hepatitis B carriers in City and Hackney were directly referred by the midwives to the Liver Clinic at the Homerton, regardless of HBV viral load. This has now changed so only those with high viral loads are referred. The Paediatricians are responsible for vaccinating and currently achieve >98% success rate in full immunisation. HEPATITIS B AND BREAST FEEDING All women with Hepatitis B can safely breast feed, as transmission of the virus by breast feeding has not been reported. All infants of Hepatitis B infected mothers should receive immunisations however. MANAGEMENT OF HEPATITIS B IN PRIMARY CARE 4
ROLE OF ULTRASOUND SCAN IN SCREENING Progression to hepatitis related cirrhosis is slow. It can be 20-30 years from onset of infection. Scans have not previously been a routine investigation in the management of HbsAg positive patients. However there is evidence to suggest that blood tests including ALT/AST do not detect early cirrhosis and ultrasound scans are more sensitive. Therefore it is recommended that all patients over 50 years of age have a one off liver scan. If the scan reveals scarring with normal AFP and LFT then they will need to have biannual surveillance with repeat ultrasound examinations. If there is evidence of cirrhosis they should be referred to gastroenterologist. SEROLOGY DEFINITIONS A brief description of some of the common serological investigations The hepatitis B surface antibody (anti-hbs) is the most common test. Its presence indicates previous exposure to HBV, but the virus is no longer present and the person cannot pass on the virus to others. The antibody also protects the body from future HBV infection. The antibodies can also be acquired from successful vaccination and therefore, this test is done to determine the need for vaccination (if anti-hbs is absent), either, following the completion of vaccination against the disease, or following an active infection. Hepatitis B surface antigen (HBsAg) is a protein antigen produced by HBV. It is the earliest indicator of acute hepatitis B and frequently identifies infected people before symptoms appear. HBsAg disappears from the blood during the recovery period. In some people (particularly those infected as children or those with a weak immune system, such as those with AIDS), chronic infection with HBV may occur and HBsAg remains positive. Hepatitis B e-antigen (HBeAg) is a viral protein associated with HBV infections. HBeAg was often used as a marker of infectivity. If HbeAg was positive then the patient was considered highly infectious. Those who are e antigen negative were considered low infectivity. However this has now been replaced by the new PCR measurements of HBV DNA HBV DNA or 'viral load', is an indicator of viral replication. Higher HBV DNA levels > 2000iU/ml are usually associated with an increased risk of liver disease and hepatocellular carcinoma and increased infectivity. AFP is a protein that is normally produced by the developing fetus. However, it can also be produced by certain tumours and disease of the liver. Raised levels of AFP are found in the majority of patients with a hepatocellular carcinoma. 5
REFERENCES Beeching, NJ, BMJ 2004:329:1059-1060 The United Kingdom National Guideline on the Management of the Viral Hepatitides A, B & C 2008 (Clinical Effectiveness Group British Association of Sexual Health and HIV NICE guidelines on Chronic Hepatitis B June 2013 (guidance.nice.org.uk/cg165) Hepatitis B: the green book, chapter 18 - Publications - GOV.UK https://www.gov.uk/government/publication/hepatitis-b-the-green-book-chapter-18 Author: Dr Rob Palmer (GP Clinical Lead), November 2013, Reviewed: May 2015 Next review: May 2017 6