Prof Ming-Yang Lai
Long-term Management of
Chronic Hepatitis B
Prof Ming-Yang Lai
Long-term Management of
Chronic Hepatitis B
Long-term Management
of Chronic Hepatitis B
Prof M Y Lai
Director, Graduate Institute of Clinical
Medicine
National Taiwan University College of
Medicine
Considerations for Treatment
• Patient history and status
– Age
• Endpoints required
• Compliance
• Patient monitoring
• Resistance
Patient Cases
• Case 1: 21 yrs, HBeAg +ve patient
with compensated CHB and slightly
raised serum ALT
• Case 2: 41 yrs, HBeAg +ve patient
with compensated CHB and ALT
11xULN
• Case 3: 51 yrs, HBV carrier with
ALT 2xULN and borderline AFP
Patient Cases
• Case 1: 21 yrs, HBeAg +ve patient
with compensated CHB and slightly
raised serum ALT
• Case 2: 41 yrs, HBeAg +ve patient
with compensated CHB and ALT
11xULN
• Case 3: 51 yrs, HBV carrier with
ALT 2xULN and borderline AFP
Case 1, Q 1: What Did You
Recommend for Management?
4.6
16.3
27.6
62.8
0
25
50
75
100
Annual
review
Treatment
without
further
investigation
Liver biopsy
Biochemical
monitoring for
6 months
Proportion
of delegates
(%)
No of responses:
196
Case 1 – Slightly Raised ALT
at Presentation
Recommendation
• Biochemical monitoring over 6
months
Reasons
• Unlikely to achieve HBeAg
seroconversion
• Unlikely to have serious liver damage
Case 1 – ALT Increased
During Follow Up
Causes
• Chinese herbal medicine
• Progressive liver disease
(fibrosis score 2)
Solutions
• Herbal medicine stopped – ALT
level improved but still elevated
• Lamivudine therapy started
Case 1, Q 2: When Did You
Decide to Stop Therapy?
7.3
15
82.9
0
25
50
75
100
ALT normal for 6
months
At least 12 months Confirmed HBeAg
seroconversion
Proportion
of delegates
(%)
No of responses:
193
Case 1 – Progress on
Treatment
• 16 months
therapy
• ALT normal
• Still HBeAg +ve
Case 1, Q 3: What was Your
Management Choice?
3.2
86.6
11.8
0
25
50
75
100
Stop
lamivudine
Continue
lamivudine
Add a second
agent
Proportion
of delegates
(%)
No of responses:
186
Case 1 – Outcome
• HBeAg seroconversion at
Month 24
• Confirmed at Month 27
• Lamivudine therapy stopped
Case 1 – Key Learnings
• Consider all possibilities for ALT
elevation prior to treatment, eg.
herbal medicines
• Emphasise importance of compliance
• Continue lamivudine until confirmed
HBeAg seroconversion
Patient Cases
• Case 1: 21 yrs, HBeAg +ve patient
with compensated CHB and slightly
raised serum ALT
• Case 2: 41 yrs, HBeAg +ve patient
with compensated CHB and ALT
11xULN
• Case 3: 51 yrs, HBV carrier with
ALT 2xULN and borderline AFP
Case 2, Q 1: What Did You
Recommend for Management?
2.5
61.4
46.2
7.6
0
25
50
75
100
Annual
review
Treatment
without
further
investigation
Liver biopsy Biochemical
monitoring
for 6 months
Proportion
of delegates
(%)
No of responses:
197
Case 2 – Very High ALT at
Presentation
Liver biopsy recommended
•
Purpose of liver biopsy
– Confirm liver disease due to CHB – exclude
other causes, especially alcohol and NASH
– Diagnosis cirrhosis/stage 3 chronic
hepatitis prognosis; surveillance for HCC,
varices
•
Always?
– Unnecessary if clinical or radiological
evidence of cirrhosis
– ? Need to perform liver biopsy if patient
<25 yrs age
Case 2 – Very High ALT at
Presentation
• Liver biopsy recommended
• A 6-month course of IFN
given
• ALT decreased but HBeAg
seroconversion did not occur
Case 2, Q 2: What Was Your
Management Choice at This
Stage?
15.4
85.1
3.7
0
25
50
75
100
Add lamivudine
Stop IFN and
start lamivudine
Continue IFN at
increased dose
Proportion
of delegates
(%)
No of responses:
188
Case 2 – Management
• IFN failure with rising ALT
• Lamivudine therapy for 6 months
led to HBeAg seroconversion and
ALT normalisation
• Lamivudine extended 6 months
post-HBeAg seroconversion
Case 2, Q 3: When Did You
Suggest Stopping Therapy?
2.8
81.5
16.3
0
25
50
75
100
Now
In 3 months
Never
Proportion
of delegates
(%)
No of responses:
178
Case 2, Q 4: What Did You
Recommend for Further
Management?
95
2.2
3.9
0
25
50
75
100
Restart
lamivudine
Observe with
liver biopsy in
12 months
Start IFN and
lamivudine in
combination
Proportion
of delegates
(%)
No of responses:
180
Case 2 – Key Learnings
• Lamivudine treatment can usually be
stopped after confirmed HBeAg
seroconversion 3–6 months later
• Individualise patient management due
to special circumstances:
– Age
– Relapse rates
– Family history
– Previous flares
– Cirrhosis
Patient Cases
• Case 1: 21 yrs, HBeAg +ve patient
with compensated CHB and slightly
raised serum ALT
• Case 2: 41 yrs, HBeAg +ve patient
with compensated CHB and ALT
11xULN
• Case 3: 51 yrs, HBV carrier with ALT
2xULN and borderline AFP
Case 3, Q 1: What Assessments
Did You Consider Essential?
No of responses:
107
70.1
87.9
49.5
0
25
50
75
100
HBV DNA
Hepatic imaging
anti-HCV,
Proportion
of delegtes
(%)
anti-
HDV
Case 3 – Management
ALL THREE TESTS ARE ESSENTIAL !!
• HBV DNA – to define HBeAg
negative, chronic hepatitis B
• No HCV or HDV – exclude other
causes of disease
• CT scan – to exclude HCC, and find
evidence of cirrhosis
Case 3, Q 2: What was Your
Approach to Long-term
Management?
19.4
78.7
2.8
0
25
50
75
100
Lamivudine for
12m
Lamivudine
indefinitely
Don't treat
Proportion
of delegtes
(%)
No of responses:
108
Long-term Management
• Despite concerns of YMDD
emergence, it is important to
suppress hepatitis activity in
patients with cirrhosis
– at least temporary improvements
in liver function
– buys time for the patient while
waiting for new treatments
Long-term Management
Conclusions
• Consider all possibilities for ALT elevation
prior to treatment, eg. herbal medicines
• Emphasize importance of compliance
• Lamivudine treatment can be stopped after
confirmed HBeAg seroconversion 3-6 months
later
• Individualise patient management
• For active cirrhotic HBeAg-ve patients,
initiate lamivudine therapy and continue
indefinitely with close monitoring