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31 July 2008

"The Other Hepatitis" - An Update on Hepatitis B.

Concord Dependency Seminar Tuesday 23 July 2008 "The Other Hepatitis" - An Update on Hepatitis B. Dr Gail Matthews, St Vincents Hospital Darlinghurst

Summary Part 1. Epidemiology, natural history, assessment.

This seminar was titled The Other Hepatitis, reflecting the lower prevalence of Hepatitis B compared with Hepatitis C among people using addiction treatment services, and the lower profile of HBV in the community.

In contrast to the vigorous response in recent years to hepatitis C (HCV) in Australia, the response to hepatitis B (HBV) has lagged behind, despite important recent developments in understanding of HBV, in diagnostic tests and antiviral treatments, and desite its large disease burden, especially chronic liver disease and liver cancer.

There are many contrasts between HBV and HCV. Whereas HCV in Australia consists of two 'epidemics' - an older group of people born overseas in endemic areas and a younger group of injecting drug users - about half the prevalence of HBV is among Australians born overseas in endemic areas, especially China and SE Asia but also the Middle east and Mediterranean. Only 5% of chronic HBV is among IDUs; another 8% among men who have sex with men (MSM) and a staggering 16% among indigenous Australians.

The picture is different for new infections (incidence) of HBV in Australia: 44% of these happen among IDU (showing the importance of catch-up vaccination for non-immune people in this risk group) and 35% are through sexual transmission, disproportionately among MSM, but the majority still through heterosexual sex.

The total number of people in Australia with chronic HCV is fairly reliably estimated to be between 200,000 and 250,000, while estimates for HBV range more widely between 90,000 and 160,000, reflecting in part poor knowledge of HBV and low levels of testing among some of the high risk groups.

HBV is a DNA virus, where HCV is an RNA virus. HCV is essentially blood-to-blood transmission, particularly by unsafe injecting, and rarely by sexual transmission, while HBV is spread by contact with infected body fluids including blood, semen and saliva. HBV is thus sexually transmitted, but also by vertical transmission (mother to child), horizontally (close personal contact especially in childhood eg cuts, sores) and by IDU.

Of people infected with HCV, 20-30% spontaneously clear the virus, usually within 6 months, and regardless of their age at infection, without however developing immunity (ie they can be reinfected with HCV). Few people develop clinically evident acute hepatitis. By contrast, for HBV progression to chronic infection is strongly related to age at infection: 80-90% of children infected perinatally develop chronic HBV, with lower rates (30%) of chronicity after infection under the age of 5 years; only 6% of older children and adults develop chronic HBV. Most adults who are infected with HBV develop clinically evident acute hepatitis.

Unlike HCV where late clearance of the virus is unknown, a small percentage of people with chronic HBV clear the virus and develop immunity each year.

HBV and HVC are similar in that a subset of people develop chronic liver inflammation which may slowly progress to cirrhosis and liver failure in a minority of cases, and which increases the risk of development of hepatocellular carcinoma (HCC).

The diagnostic tests for HBV, and the natural history of the disease, while rather more complicated than for HCV, have become clearer in recent years. Chronic HBV is now though of as having 4 phases, with gradual progression through the first 2 phases "immune tolerant" and "immunoactive" into the third phase called "immune control" and sometimes progression into a fourth phase called "immune escape".

In the "immune tolerant" phase, there are high levels of HBV-DNA in the blood but little inflammation of the liver (so liver enzymes like ALT are low or normal). The body is not really fighting the virus. This phase is prolonged in people who get HBV perinatally (20 years or more) but is usually much shorter in adult infections.

In the "immunoactive" phase, DNA levels and liver inflammation (ALT) tend to fluctuate. The body is fighting the virus and the liver is in the wars. This can go on for many years, and this is when much of the liver damage from HBV develops.

If the body develops "immune control", viral DNA drops to undetectable levels and the liver function tests normalise. This phase can go on for decades and is associated with no progression of liver disease.

Unfortunately in some people HBV escapes from immune control. In the "immune escape" phase, viral DNA is detectable again and the ALT indicates liver inflammation. People in this phase of HBV often have the most seriously progressive disease.

In making a diagnosis of HBV and working out which phase a person is in, 3 types of tests are used: serological tests, liver function tests (especially ALT for inflammation), and viral DNA measurement (in Australia until recently only specialists could order this expensive test).

There are five commonly used serological tests for HBV. The surface antigen (HBsAg) indicates current Hepatitis B infection. It says "you have hep B now". It is found in serum during the incubation period before symptoms, and persists unless antibodies develop to the surface antigen (anti-HBs). Persistence of HBsAg defines chronic HBV and presence of anti-HBs indicates immunity to HBV infection (either by clearance of surface antigen, or by vaccination). Anti-HBs says "you don't have hep B and you can't get it anymore". * Sometimes anti-HBs wanes to undetectable levels in a person who has immunity to HBV, but there is still immune memory and anti-HBs rises to any immune challenge.

(* but see exceptions below)

The HBV core antibody (anti-HBc) develops early after HBV exposure and generally persists for ever: it just indicates previous exposure, and doesn't imply immunity (in this way it resembles HCV antibody). It says "HBV was here - and may still be here".

There are also tests for the HBV "e" antigen and its antibody (HBeAg and anti-HBe). HBeAg is a marker of viral replication and infectivity, and means there are high levels of HBV DNA in the blood. The person with HBeAg is either in the "immune tolerant" or the "immunoactive" phase of HBV. Loss of the HBeAg with appearance of anti-HBe generally indicates that the HBV DNA levels have been suppressed, the so-called "immune control phase" of hepatitis B - in this case the liver function tests will usually be normal.

However absence of HBeAg and presence of anti-HBe also occurs when a person moves into the "immune escape phase", where HBV-DNA levels and the ALT rise again.

Putting these tests together, HBsAg with HBeAg means chronic HBV with high infectivity. HBsAg with anti-HBe generally means low infectivity, undetectable DNA and "immune control" but can point to "immune escape phase", with high HBV-DNA levels and liver inflammation.

HBV is an oncogenic virus, and unlike HCV, can cause hepatocellular carcinoma (HCC) in the absence of cirrhosis. Of all people with chronic HBV, about 30% will go on to cirrhosis, and 5-10% will go on to HCC. Of people with HBV cirrhosis, about 1 in 4 will go on to liver failure within 5 years.

Numerous factors negatively influence HBV natural history and prognosis: host factors (male gender, older age, obesity and diabetes); viral factors (high viral load, genotype C); coinfection (HIV, HCV, hepatitis D); tobacco smoking and alcohol use. Mortality from liver failure or HCC is much higher when there is HIV coinfection.

Primary prevention for HBV depends on screening and vaccination of high risk individuals and universal vaccination of infants. People who may have poor immune response (HIV/haemodialysis patients) or who may be at higher risk (people with existing liver disease, health care workers) should have anti-HBs checked after the usual 3-vaccine course, and may need a booster. People, including infants, who have accelerated HBV vaccination schedules should also have a booster at 12 months. Immunocompetent people generally do not need boosters even if anti-HBs wanes. However, 5-10% of people fail to respond to vaccination, and these people should be advised that they may need passive vaccination with HBV immunoglobulin (HBIG) within 72 hours if they are exposed to HBV.

HBIG should be given to babies of HBsAg mothers within 12 hrs of delivery, and standard vaccination carried out.

The second part of this summmary will present treatment issues and case studies: