The Hepatitis Foundation runs a national monitoring programme for people living with chronic hepatitis B. Approximately 25,000 individuals are enrolled. People infected with chronic hepatitis B (CHB) are at risk of liver failure and liver cancer. Long-term regular blood test monitoring (and, in specific situations, abdominal ultrasounds), has been shown to reduce morbidity and mortality from CHB.
Hepatitis B risk factors
• New Zealanders of Maori, Pacific or Asian ethnicity, unless they are known to have been fully vaccinated as an infant.
• People born in an area of high hepatitis B endemicity, including Asia, the Pacific Islands, Africa, the Middle East, southern Europe or the northern or eastern parts of New Zealand’s North Island.
• Living with someone who has hepatitis B
• Being born to a woman with hepatitis B or having a close family member with the virus
• Unprotected sexual contact with someone who has hepatitis B
• Having a tattoo performed with unsterile equipment.
Natural history of chronic hepatitis B infection
In determining when to start anti-viral therapy it is helpful to consider the natural history of CHB. Most are infected in infancy or early childhood and for many years the virus is present at very high titres (>10^8). The virus itself is not hepatotoxic and there is minimal damage occurring to the liver during this period.
This may be followed, often in later childhood or early adulthood, by a period of active hepatitis when the immune system tries to destroy the virus by killing infected liver cells (known as HBeAg-positive chronic hepatitis or immune-active CHB). A person may then become HBeAg-negative and move into a prolonged phase of normal liver function and a much lower viral load (HBeAg-negative chronic infection or inactive chronic hepatitis B).
Chronic hepatitis B is often a lifelong condition. Not everyone living with the virus needs anti-viral therapy; the decision to begin treatment depends on several factors including age, serial ALT and HBV DNA levels and severity of liver disease (degree of fibrosis). The three major international societies for the study of liver disease (APASL1, EASL2, AASLD3) have recently published updated guidelines on the management of hepatitis B. The degree of fibrosis present is an important factor in making treatment decisions in some scenarios. In most cases this can be obtained non-invasively with a FibroScan. In a small number of cases a liver biopsy may be useful.
Our medical director Dr Chris Moyes and clinical director Dr Alex Lampen-Smith have co-authored a document outlining the situations in which anti-viral therapy could be considered.
The goal of therapy for patients with chronic hepatitis B infection is to improve survival and quality of life by preventing disease progression and consequently HCC development. Additional goals of antiviral therapy are to prevent mother-to-child transmission, hepatitis B reactivation and the prevention and treatment of HBV-associated extra-hepatic manifestations.
The rationale for pegylated interferon is to induce long-term immunological control with a finite duration of therapy. Pre-treatment predictors of response include HBeAg positive, HBV DNA < x10^8, elevated ALT and genotype A (more likely to be present in Asians). In patients with favourable pre-treatment characteristics approximately 30% will experience HBeAg seroconversion and 3-7% HBsAg seroconversion. Treatment is via once weekly subcutaneous injection for 48 weeks.
Entecavir sandoz (0.5mg) and tenofovir disoproxil (245mg) are once-daily oral tablets for chronic hepatitis B. They are potent antiviral agents with a high barrier to resistance leading to long-term undetectable HBV DNA levels (viral load) in the vast majority of adherent patients.
Apart from requiring dose adjustments in renal impairment there are no contra-indications to therapy. Entecavir and tenofovir have been used internationally for >10 years and have very good safety profiles. Minimal rates of renal function decline have been reported during long-term therapy with entecavir and slightly more so with tenofovir. It is recommended to monitor creatinine and phosphate annually.
These agents are only effective in suppressing viral replication while a patient adheres to their use. Upon discontinuation the viral load rises within days to weeks. Viral reactivation can lead to severe hepatitis and subsequent hepatic decompensation, which can be fatal (especially in those with advanced liver disease at the time of treatment initiation). Close clinical and laboratory monitoring should be undertaken for several months after discontinuation and resumption of antiviral medication may be required.
Entecavir should be taken on an empty stomach, at least two hours after a meal and at least two hours before the next meal. Tenofovir can be taken with or without food. It is also used in combination with other antiviral agents, for the long-term management of HIV. If someone has HIV/HBV co-infection, tenofovir should not be used as a single agent and their care should be supervised by a specialist.
Studies assessing sensitive markers of bone turnover have reported a decline in bone mineral density in patients treated with tenofovir.
Lamivudine, adefovir and telbivudine are also licensed for the treatment of CHB. Due to their low barrier to resistance, these are no longer preferred first line agents. Small numbers of patients may remain on these agents and, while they are achieving effective viral suppression, they do not need to be switched. If a person has been on any prior nucleos(t)ide analogue therapy and develop resistance they should be switched to tenofovir.