Beruflich Dokumente
Kultur Dokumente
• Chair
• Pietro Lampertico
• Panel members
• Kosh Agarwal, Thomas Berg,
Maria Buti, Harry LA Janssen,
George Papatheodoridis, Fabien
Zoulim, Frank Tacke (EASL
Governing Board representative)
• Reviewers
• Maurizia Brunetto, Henry Chan,
Markus Cornberg
• Epidemiology of HBV
Background • New nomenclature for chronic phases
• New biomarkers
The future for HBV • Future treatments
• Unresolved issues
Grade of evidence
I Randomized, controlled trials
II-1 Controlled trials without randomization
II-2 Cohort or case-control analytical studies
II-3 Multiple time series, dramatic uncontrolled experiments
III Opinions of respected authorities, descriptive epidemiology
Grade of recommendation
1 Strong recommendation: Factors influencing the strength of the recommendation
included the quality of the evidence, presumed patient-important outcomes, and cost
2 Weaker recommendation: Variability in preferences and values, or more uncertainty:
more likely a weak recommendation is warranted
Recommendation is made with less certainty: higher cost or resource consumption
Background
Epidemiology of HBV
New nomenclature for chronic phases
Epidemiology and public health burden1
• Worldwide ≈250 million chronic HBsAg carriers2,3
• 686,000 deaths from HBV-related liver disease and HCC in 20134
HBsAg prevalence, adults (1949 years), 20053
<2% Decreasing prevalence in
some endemic countries,
24%
e.g. Taiwan7
57%
Possible reasons:
≥8% • Improved
Not applicable socioeconomic status
• Vaccination
• Effective treatments
Anti-HBe
Main endpoint
I 1
• Induction of long-term suppression of HBV DNA
Valuable endpoint
• Induction of HBeAg loss (± anti-HBe seroconversion) II-1 1
in HBeAg-positive patients with chronic hepatitis B*
Additional endpoint
II-1 1
• ALT normalization (biochemical response)†
Optimal endpoint
II-1 1
• HBsAg loss (± anti-HBs seroconversion)‡
Indications for treatment
• Primarily based on the combination of 3 criteria
• HBV DNA, serum ALT and severity of liver disease
Should be treated
NO
Consider
Risk of HCC, risk of HBV
reactivation, extrahepatic In case of immunosuppression,
manifestations, risk of YES start oral antiviral prophylaxis
HBV transmission or monitor
Current treatment strategies for chronic
hepatitis B:PegIFNα
Features
main concepts and features
ETV, TDF, TAF
Route of administration Subcutaneous injections Oral
Treatment duration 48 weeks Long-term until HBsAg loss*
Tolerability Low High
Very rarely persistence of
Long-term safety concerns Probably not‡
on-treatment AEs†
Contraindications Many§ None‖
Induction of a long-term immune
Strategy Inhibition of viral replication
control
Level of viral suppression Moderate Universally high
Effect on HBeAg loss Moderate¶ Low in first year, moderate over long term
Effect on HBsAg levels Variable¶ Low**
Moderate if consolidation treatment provided
Low for those with sustained
Risk of relapse after treatment after HBeAg seroconversion. High for HBeAg-
response 6–12 months after therapy
negative disease
Early stopping rules Yes No
Risk of viral resistance No Minimal to none††
Prevention of resistance should rely on the use of
first-line NAs with a high barrier to resistance*
Cumulative incidence of HBV resistance to NAs in pivotal trials
in NA-naïve patients with chronic hepatitis B†
80
70
1 year
70 67 2 years
3 years
60
4 years
49 5 years
50
40 38
29
30
24
20 18 17
11
10
3 4 1.2
0 0.2 0.5 0 0 0 0 0 0 0
0
LAM ADV TBV ETV TDF† TAF
Indications for selecting ETV or TAF over TDF*
• In some circumstances ETV or TAF may be a more
appropriate treatment choice than TDF
NOT recommended
• De novo combination therapy of two NAs with a high barrier to I 1
resistance (ETV, TDF, TAF)
Drug switch or combination may be considered
• In treatment-adherent patients with incomplete HBV suppression III 2
reaching a plateau during ETV or TDF/TAF long-term therapy
Recommendations (NA plus PegIFN)
NOT recommended
• De novo combination of NA and PegIFN I 1
• Short-term pretreatment with an NA before PegIFN in
II 1
treatment-naïve HBeAg-positive patients
• Adding PegIFN or switching to PegIFN in patients with
II 1
long-term HBV DNA suppression on NA therapy