Disease Prevalence and Incidence
Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of small, enveloped, primarily hepatotropic DNA viruses. HBV has nine genotypes, A to J, with different prevalence in geographic regions, i.e., genotype A is seen mainly in northwest Europe, North America, India, and Africa.1,2 In low-endemic regions, transmission is primarily through high-risk sexual behaviour and intravenous drug use, and, therefore, the infection is found predominantly in adolescents and adults.1 Globally, approximately 2 billion people have serological evidence of HBV, and 250 million are chronically infected.2 Approximately one-third of all cases of liver cirrhosis and half of all cases of hepatocellular carcinoma are attributable to chronic hepatitis B (CHB).3 There do not appear to be any reliable estimates of prevalence and incidence of CHB in Canada; however, the estimated combined prevalence of CHB and chronic hepatitis C is approximately 600,000.4–6
Standards of Therapy
The Canadian Association for the Study of the Liver consensus guidelines recommend antiretroviral treatment for CHB patients with the following clinical characteristics: hepatitis B e antigen (HBeAg)-positive patients with high levels of HBV DNA (> 20,000 IU/mL) with elevated alanine aminotransferase (ALT) greater than the upper limit of normal (ULN) for three to six months;
HBeAg-negative patients with lower levels of HBV DNA (> 2,000 IU/mL) and ALT greater than the ULN for three to six months; and patients with either HBeAg-positive or HBeAg-negative status who have significant liver inflammation and fibrosis.7 These recommendations are in agreement with those of other major organizations such as the European Association for the Study of the Liver (EASL)8 and the American Association for the Study of the Liver Disease (AASLD).9 A summary of the natural history of disease, diagnosis, management, and prognosis of HBV can be found in Appendix 7. The preferred first-line antiretroviral treatments for CHB patients in Canada have been tenofovir disoproxil fumarate (TDF), entecavir, and pegylated interferon, according to the clinical expert consulted by CDR for this review.
Drug
Tenofovir alafenamide (TAF) is a prodrug of tenofovir. The antiviral properties of tenofovir are due to its inhibition of HBV polymerase, which, in turn, inhibits DNA synthesis and viral replication. TAF is indicated for the treatment of chronic hepatitis B in adults with compensated liver disease. The Health Canada–recommended dose for TAF is one 25 mg tablet once daily, taken with or without food.
Table 2Key Characteristics of Tenofovir Alafenamide, Tenofovir Disoproxil Fumarate, Entecavir, Lamivudine, Telbivudine, Pegylated Interferon, and Adefovir Dipivoxil
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| Tenofovir Alafenamide | Tenofovir Disoproxil Fumarate | Entecavir |
|---|
| Mechanism of Action | Inhibits HBV polymerase, causes chain termination, inhibiting HBV DNA synthesis | Inhibits HBV polymerase, causes chain termination, inhibiting HBV DNA synthesis | Inhibits HBV polymerase, inhibiting HBV DNA synthesis |
|---|
| Indicationa | Treatment of CHB in adults with compensated liver disease | Treatment of CHB infection in patients 18 years of age and older, with:compensated liver disease, with evidence of active viral replication, with elevated serum ALT levels or evidence of fibrosis (based on liver biopsy or a noninvasive procedure) evidence of lamivudine-resistant HBV decompensated liver disease.
Also: HIV-1 | Treatment of CHB virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease |
|---|
| Route of Administration | Oral | Oral | Oral |
|---|
| Recommended Dose | 25 mg once daily | 300 mg once daily | 0.5 mg once daily |
|---|
| Serious Side Effects / Safety Issues | | | Acute exacerbations of hepatitis B Lactic acidosis and severe hepatomegaly with steatosis Resistance to HIV nucleoside reverse transcriptase inhibitors if used to treat HBV infection in patients with HIV infection that is not being treated
|
|---|
| Mechanism of Action | Inhibits HBV viral polymerase | Inhibits HBV viral polymerase | Immune modulator |
|---|
| Indicationa | Treatment of patients with CHB and evidence of HBV replication
Due to high rates of resistance that developed in treated patients, lamivudine treatment should be considered only when the use of an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate. | Treatment of chronic CHB in adults of 16 years and older with compensated liver disease with evidence of viral replication and active liver inflammation
Points to be considered when initiating therapy:
For HBeAg-positive patients, treatment should be initiated only in patients with baseline HBV DNA < 9 log10 copies/mL and baseline ALT > 2 × ULN.
For HBeAg-negative patients, treatment should be initiated only in patients with baseline HBV DNA < 7 log10 copies/mL.
On-treatment response should guide continued therapy. | For the treatment of both HBeAg-positive and HBeAg-negative chronic hepatitis B in patients with compensated liver disease, liver inflammation, and evidence of viral replication (both cirrhotic and non-cirrhotic disease) |
|---|
| Route of Administration | Oral | Oral | Injection (subcutaneous) |
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| Recommended Dose | 100 mg once daily | 600 mg once daily | 180 mcg once weekly |
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| Serious Side Effects / Safety Issues | Lactic acidosis and severe hepatomegaly with steatosis Post-treatment exacerbation of hepatitis HIV resistance may emerge in CHB patients with unrecognized or untreated HIV infection
| | May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders
|
|---|
| Mechanism of Action | Inhibits viral polymerases by direct binding competition with the natural substrate (deoxyadenosine triphosphate) and, after incorporation into viral DNA, results in DNA chain termination | | |
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| Indicationa | Treatment of CHB in adults with compensated and decompensated liver disease with evidence of active viral replication and evidence of either histologically active disease or elevation in serum aminotransferases (ALT or AST) | | |
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| Route of Administration | Oral | | |
|---|
| Recommended Dose | 10 mg once daily | | |
|---|
| Serious Side Effects / Safety Issues | Lactic acidosis and severe hepatomegaly with steatosis Post-treatment exacerbation of hepatitis Nephrotoxicity HIV resistance may emerge in CHB patients with unrecognized or untreated HIV
| | |
|---|
ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMD = bone mineral density; CHB = chronic hepatitis B; HBeAg = hepatitis B e antigen; HBV = hepatitis B virus; ULN = upper limit of normal.
- a
Health Canada indication.
Source: Product monographs from e-CPS.12
