Introduction
Terminology | Definition |
---|---|
Alanine aminotransferase (ALT) | |
High normal | Serum ALT levels between 0.5 and 1 times upper limit of normal reference (ULN). |
Low normal | Serum ALT ≤ 0.5 times ULN |
Minimally raised | Serum ALT levels between 1 and 2 times ULN |
Biochemical response | Normalization of serum ALT levels |
Chronic HBV infection | HBsAg seropositive ≥ 6 months |
Clinical breakthrough | Virologic breakthrough with increased ALT levels or worsening histology |
Drug resistance | |
Genotypic resistance | Detection of mutations in the HBV genome, known to confer resistance, which develop during antiviral therapy |
Phenotypic resistance | Decreased susceptibility (in vitro testing) to inhibition by antiviral drugs associated with genotypic resistance |
Cross resistance | Mutation selected by one antiviral agent that also confers resistance to other antiviral agents |
Hepatic decompensation | Significant liver function abnormality as indicated by raised serum bilirubin level and prolonged prothrombin time or occurrence of complications such as ascites |
Hepatitis flare | Increase of serum ALT level to ≥ 5 times ULN |
Inactive chronic HBV infection | HBsAg (+) anti-HBe (+) with persistent normal serum ALT and HBV-DNA < 2,000 IU/ml (104 copies/ml) |
Undetectable serum HBV-DNA | Serum HBV-DNA levels below detection limit of a PCR-based assay |
Virological response | |
Maintained virologic response | Undetectable serum HBV-DNA and HBeAg seroconversion, if applicable, during therapy |
Primary treatment failure | Reduction of serum HBV-DNA < 1 log IU/ml at 12 weeks of oral antiviral therapy in a compliant patient |
Viral breakthrough | >1 log IU/ml increase in serum HBV-DNA from nadir of initial response during therapy as confirmed 1 month later |
Secondary treatment failure | Viral breakthrough in a compliant patient (due to drug resistance) |
Sustained virologic response | Serum HBV-DNA < 2,000 IU/ml (104 copies/ml) and HBeAg seroconversion, if applicable, for at least 6 months after stopping therapy |
Complete response | Sustained virologic response with HBsAg seroclearance |
Conceptual background
HBV, pathogenesis, and natural course
Concurrent infection with other virus(es)
Goals of treatment for chronic HBV infection
Currently available treatments
IFN-based therapy
Conventional IFN
PegIFN-α
IFN combination with other agents
IFN-based therapy: overall conclusions
Other immunomodulating agents
Thymosin α-1
Therapeutic vaccines
Direct antiviral agents
Lamivudine | Adefovir dipivoxil | Entecavir | Telbivudine | |||||
---|---|---|---|---|---|---|---|---|
e(+) | e(−) | e(+) | e(−) | e(+) | e(−) | e(+) | e(−) | |
HBV-DNA (-log) | ||||||||
Year 1 | 5.4a
| 4.5b
| 3.6 | 3.7 | 6.9a
| 5.0b
| 5.7c
| 4.4c
|
5.4c
| 4.1c
| [1.0] | [1.4] | |||||
Undetectable | ||||||||
Year 1 | 36%a
| 72%b
| 21% | 61% | 67%a
| 90%b
| 60%c
| 88%c
|
40%c
| 71%c
| [0%] | [0%] | |||||
Year 2 | 39%*d
| NA | NA | 71% | 80%*d
| NA | 56%c
| 82%c
|
39%c
| 57%c
| |||||||
Year 3 | 20% | 40% | NA | 77%** | 89%* | NA | NA | NA |
HBeAg seroconversion | ||||||||
Year 1 | 18%a
| NA | 12% | NA | 21%a
| NA | 23%c
| NA |
22%c
| [6%] | |||||||
Year 2 | 26%* | NA | 29% | NA | 31%* | NA | 30%e
| NA |
25%e
| ||||||||
Year 3 | 40% | NA | NA | NA | NA | NA | NA | NA |
Genotypic resistance | ||||||||
Year 1 | 13%a
| 6%b
| 0% | 0%* | 0%a
| 0%b
| 5%c
| 2%c
|
11%c
| 11%c
| |||||||
Year 2 | 38%d
| 31% | NA | 3%* | 0%d
| NA | 25%e
| 11%e
|
40%e
| 26%e
| |||||||
Year 3 | 57% | 57% | NA | 11%* | ∼1% | NA | NA | NA |