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