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Antenatal lamivudine to reduce perinatal hepatitis B

transmission: a cost-effectiveness analysis
Unzila A. Nayeri, MD; Erika F. Werner, MD; Christina S. Han, MD; Christian M. Pettker, MD;
Edmund F. Funai, MD; Stephen F. Thung, MD
OBJECTIVES: This study aimed to determine whether administration of
lamivudine to pregnant women with chronic hepatitis B in the third trimester is a cost-effective strategy in preventing perinatal transmission.
STUDY DESIGN: We developed a decision analysis model to compare

the cost-effectiveness of 2 management strategies for chronic hepatitis

B in pregnancy: (1) expectant management or (2) lamivudine administration in the third trimester. We assumed that lamivudine reduced perinatal transmission by 62%.
RESULTS: Our Markov model demonstrated that lamivudine adminis-

tration is the dominant strategy. For every 1000 infected pregnant

women treated with lamivudine, $337,000 is saved and 314 qualityadjusted life-years are gained. For every 1000 pregnancies with maternal hepatitis B, lamivudine prevents 21 cases of hepatocellular carcinoma and 5 liver transplants in the offspring. The model remained
robust in sensitivity analysis.
CONCLUSION: Antenatal lamivudine administration to pregnant pa-

tients with hepatitis B is cost-effective, and frequently cost-saving, under a wide range of circumstances.
Key words: hepatitis B, lamivudine, perinatal transmission,
pregnancy

Cite this article as: Nayeri UA, Werner EF, Han CS, et al. Antenatal lamivudine to reduce perinatal hepatitis B transmission: a cost-effectiveness analysis. Am J
Obstet Gynecol 2012;207:231.e1-7.

epatitis B infection poses a significant global health problem with

about 350 million chronically infected
individuals. Responsible for approximately 30% of cirrhosis and over 50%
of hepatocellular carcinoma worldwide,
carriers of hepatitis B are at risk for complications of progressive liver disease.1-3
Although the prevalence of hepatitis B is
relatively low in the United States, infection still results in significant morbidity
and mortality. The Centers for Disease
Control estimates that 1.2 million AmerFrom the Department of Obstetrics,
Gynecology, and Reproductive Sciences (Drs
Nayeri, Han, and Pettker), Yale University
School of Medicine, New Haven, CT; the
Department of Gynecology and Obstetrics (Dr
Werner), Johns Hopkins School of Medicine,
Baltimore, MD; and the Division of MaternalFetal Medicine, Department of Obstetrics and
Gynecology (Drs Funai and Thung), Ohio State
University College of Medicine, Columbus, OH.
Received Feb.1, 2012; revised April 22, 2012;
accepted June 1, 2012.
The authors report no conflict of interest.
Presented as a poster at the 32nd annual
meeting of the Society for Maternal-Fetal
Medicine, Dallas, TX, Feb. 8-11, 2012.
Reprints not available from the authors.
0002-9378/$36.00
2012 Mosby, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2012.06.001

icans are chronic carriers of hepatitis B,

and an additional 5000 to 8000 individuals become chronically infected each
year.4
Perinatal transmission is the most
common mode of hepatitis B transmission worldwide. Framing the importance of perinatal transmission in the
overall health burden of hepatitis B, the
risk of progression to chronic hepatitis B
is inversely related to the age of acquired
infection. In the absence of intervention,
90% of infants born to hepatitis B e antigen positive mothers become chronic
carriers, with a subsequent 25-30% lifetime risk of serious liver disease.5 Current guidelines recommend that infants
of women who are hepatitis B surface antigen positive receive both the hepatitis B
immunoglobulin and first dose of the
hepatitis B vaccine series within 12 hours
of birth.5-11 Although the combination of
passive and active immunization reduces
the risk of perinatal hepatitis B infection
by 85-95%, neonatal immunoprophylaxis
does not prevent all vertical transmission
and does not interrupt an infection that
occurs in the antenatal period before
9, 12-15
birth.
Currently, antepartum antiviral prophylaxis to decrease hepatitis B perinatal
transmission rates is not the standard of

care. Previous small trials have evaluated

the risk of perinatal transmission after
maternal antenatal treatment with lamivudine and/or hepatitis B immunoglobulin.16-25 A recent metaanalysis by Shi et
al26 demonstrated that lamivudine treatment in the third trimester reduced the
risk of perinatal transmission in a Chinese population. The mechanism of action of lamivudine involves incorporation of the synthetic nucleoside analog
into hepatitis B viral DNA by viral polymerase resulting in DNA chain termination. Usual dosing for chronic hepatitis B
is 100 mg daily and common adverse effects include mild diarrhea, nausea, and
headaches. Lamivudine appears to cross
the term placenta by simple diffusion
and interrupts intrauterine hepatitis B
infection by decreasing maternal viral
load.27
For every 1000 pregnant women in the
US, 1-2 have hepatitis B. Despite passive
and active immunization of the neonate,
1 in 20 infants acquires hepatitis B
through perinatal transmission.4,9,12-15
With a relative risk reduction of 0.38
provided by lamivudine treatment, approximately 50 women with hepatitis B
would need to be treated with lamivudine to prevent 1 case of chronic hepatitis B in a child.26

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231.e1

SMFM Papers
Although prevention of hepatitis B infection is undoubtedly desirable, it is uncertain if the resources needed to achieve
this through routine antenatal administration of lamivudine are cost-effective.
Therefore, using a decision analysis model,
we chose to estimate whether third-trimester administration of lamivudine to pregnant patients with chronic hepatitis B is a
cost-effective strategy in preventing perinatal transmission.

M ATERIALS AND M ETHODS

Using a decision analysis model, we
compared the cost-effectiveness of 2
management strategies during the final
trimester of pregnancy for women with
hepatitis B. The first strategy involved
expectant management without antepartum maternal prophylaxis. In the second strategy, women with chronic hepatitis B were treated with lamivudine in
the third trimester. In both strategies,
neonates received the currently recommended hepatitis B immunoglobulin
and the hepatitis B vaccine series. The
analysis was performed from the perspective of the health care system.
A Markov model was created to estimate lifetime costs in 2011 US dollars
and quality-adjusted life years (QALYs)
for offspring with vertically transmitted
hepatitis B. We included a variety of
shifting health states and assigned uses,
costs, and probabilities to these specific
health states. Both costs and QALYs were
discounted at a 3% annual rate. A strategy was considered cost-effective at a ratio less than $50,000/QALY.28 The decision tree was created and analysis was
performed using TreeAge Pro 2009
(TreeAge Software, Williamstown, MA).
The baseline probabilities and outcomes for each strategy were obtained
based on a comprehensive English literature review and bibliographic survey.
We used the following search terms in
PubMed (from 1947-2011): hepatitis B,
pregnancy, perinatal/in utero transmission, lamivudine treatment, chronic hepatitis B, cirrhosis, liver transplantation, and
combinations of these terms. Point estimates were determined preferentially
from systematic reviews and metaanalyses, and prospective and retrospective
231.e2

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cohort studies. Review studies and other
decision models were used when no
other sources for the necessary data were
available. In addition, we relied on data
from large organizations that follow various long-term outcomes incorporated
in the model (Organ Procurement Transplant Network, United Network for Organ
Sharing).
In a recent metaanalysis, Shi et al26
demonstrated that the efficacy of lamivudine in reducing perinatal transmission was 62% as indicated by newborn
hepatitis B surface antigen testing. Thus,
our estimate of the relative risk of perinatal transmission was 0.38 in patients
treated with antenatal lamivudine. In addition, because our model assumed that
neonates born to mothers with hepatitis B
received both the hepatitis B vaccine series
and the hepatitis B immune globulin, we
approximated the perinatal transmission
rate to be 5% (a range of 310% was used
in the sensitivity analysis).9,12-15
We chose to offer lamivudine to all
hepatitis B women regardless of e antigen
positivity, appreciating that if the analysis for the whole group proved to be costeffective, offering it to only those at highest risk (hepatitis B e antigen positive)
would certainly be even more cost-effective. We also estimated that 90% of infants infected would potentially have longterm consequences of chronic hepatitis B.
It is well-established in the literature that
perinatal transmission leads to much
higher rates of chronic hepatitis B than infections during adulthood.5,8-11,29-31
The probability estimates and references used in support of our model are
reported in Table 1. Our model focused
on long-term consequences of chronic
infection such as cirrhosis, hepatocellular carcinoma, and need for liver transplantation. The rate of progression from
1 heath state to the next was determined
by annual transition probabilities derived from the published literature.
All uses in our model were assigned a
value from 0 to 1. Zero defined no quality of life (death) and 1 defined a perfect
health state. Based on previously published cost-effectiveness analyses and
systematic reviews, we derived uses for
the various health states associated with
hepatitis B.

American Journal of Obstetrics & Gynecology SEPTEMBER 2012

Table 2 lists these health states and

their uses. Chronic hepatitis B was assigned a use of 0.99. Although these patients are relatively healthy, they still require physician visits, surveillance of
liver function tests, and imaging studies,
and, furthermore, likely exhibit a slightly
lesser quality of life because of the
chronic nature of their disease.32-36 We
assigned a use of 0.8 to compensated cirrhosis and a use of 0.7 to hepatocellular
carcinoma. Decompensated cirrhosis was
given a use of 0.6 to reflect the high level of
morbidity and mortality associated with
this disease state.32-36 Typical complications of decompensated cirrhosis include
ascites, variceal hemorrhage, encephalopathy, and spontaneous bacterial peritonitis. These complications require immediate
medical attention and acute interventions,
which are reflected in the relatively low use
score.
We designated a use of 0.86 for patients
with liver transplants because they have received definitive therapy and have presumably overcome their end-stage liver
disease. Nonetheless, their condition requires multiple medications (including antirejection medications), laboratory testing, and physician visits. After
liver transplant, various outcomes are possible; patients may either continue to be
stable or deteriorate and become unstable.32-36 Unstable disease reflects a worsening disease state, most likely because of
damage from recurrent hepatitis B. Although the risk of hepatitis B recurrence is
declining with the use of hepatitis B immunoglobulin and antiviral medications, this
is still an important contributor to morbidity and mortality after transplantation.29,37 If patients remained stable after
liver transplantation, the use remained
constant at 0.86. However, once their clinical condition deteriorated, we assumed
that the use of their unstable disease was
equivalent to the use of decompensated
cirrhosis as worsening disease after transplant is usually associated with a more rapidly progressive course of hepatitis B.29,37
Costs were derived from the published
literature and were adjusted to reflect
2011 US dollar amounts (Table 3). The
cost of lamivudine was estimated from
the average wholesale price as listed by
Cardinal Health in 2011 and the Red

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TABLE 1

Variable estimates
Base case

Rangea

Reference

Risk of perinatal transmission in setting of neonatal immunoprophylaxis

0.05

0.030.10

9,12-15

Relative risk of perinatal transmission of hepatitis B with maternal lamivudine

0.38

0.200.80

Risk of chronic hepatitis B after perinatal transmission

0.90

0.850.95

Variable
b

................................................................................................................................................................................................................................................................................................................................................................................
26
................................................................................................................................................................................................................................................................................................................................................................................
5,8-11
................................................................................................................................................................................................................................................................................................................................................................................

Annual probability of disease progression

.......................................................................................................................................................................................................................................................................................................................................................................
29,34,41,47

Chronic hepatitis B to compensated cirrhosis

0.05

0.020.10

Compensated cirrhosis to decompensated cirrhosis

0.04

0.020.10

Compensated cirrhosis to hepatocellular carcinoma

0.03

0.010.10

Compensated cirrhosis to death

0.02

0.010.10

Decompensated cirrhosis to compensated cirrhosis

0.08

00.16

Decompensated cirrhosis to hepatocellular carcinoma

0.07

0.010.10

Decompensated cirrhosis to liver transplant

0.03

0.010.10

Decompensated cirrhosis to death

0.13

0.050.25

Hepatocellular carcinoma to liver transplant

0.10

00.40

.......................................................................................................................................................................................................................................................................................................................................................................
29,34,41,47
.......................................................................................................................................................................................................................................................................................................................................................................
29,34,41,47
.......................................................................................................................................................................................................................................................................................................................................................................
29,34,47
.......................................................................................................................................................................................................................................................................................................................................................................
29,34
.......................................................................................................................................................................................................................................................................................................................................................................
34,37,41,47
.......................................................................................................................................................................................................................................................................................................................................................................
29,30,34,37,41,48,49
.......................................................................................................................................................................................................................................................................................................................................................................
29,34,41,47
.......................................................................................................................................................................................................................................................................................................................................................................
29,30,34,37,41,48,49
.......................................................................................................................................................................................................................................................................................................................................................................
29,34,41,47

Hepatocellular carcinoma to death

0.43

0.200.60

Liver transplant to unstable disease (hepatitis B recurrence)

0.05

00.13

Liver transplant to death (1st year after liver transplant)

0.14

0.100.20

Stable disease (no hepatitis B recurrence) after successful liver transplant to death

0.05

0.020.12

Unstable disease (hepatitis B recurrence) after successful liver transplant to death

0.18

0.050.20

.......................................................................................................................................................................................................................................................................................................................................................................
c
29,34
.......................................................................................................................................................................................................................................................................................................................................................................
34,41,48
.......................................................................................................................................................................................................................................................................................................................................................................
29,34
.......................................................................................................................................................................................................................................................................................................................................................................
29,34
................................................................................................................................................................................................................................................................................................................................................................................
a

The specified ranges were used in the univariate sensitivity analyses and the Monte Carlo simulations; b This risk assumes that the neonate exposed to maternal hepatitis B received the hepatitis
B vaccine series and hepatitis B immunoglobulin; c Adjusted to account for decreasing mortality over time from transplant.

Nayeri. Cost-effectiveness of antenatal lamivudine administration. Am J Obstet Gynecol 2012.

Book in 2010.38,39 Medication costs assumed that patients received 100 mg of

lamivudine daily from 28 weeks until delivery (averaged to 3 months). In our
model, we assumed that the cost of unstable disease after liver transplantation
is similar to the cost of decompensated
cirrhosis as both disease states similarly
represent an acute progression of worsening liver disease and its complications.33-36,40-43 Both of these disease
states require a multitude of tests, procedures, and therapies including hospital
admission, imaging (ultrasound, computed tomographic scan, magnetic resonance imaging/MRCP), serial laboratory
tests, endoscopy, liver biopsy, and medications, all of which contribute to the
high costs associated with these health
states.

ing 1000 pregnant women with chronic

hepatitis B with lamivudine in the third
trimester prevents 21 cases of hepatocellular carcinoma and 5 cases of liver
transplantation in the offspring. In addi-

tion, the treatment of these 1000 women

results in a gain of 314 QALYs. Our
model also demonstrates that lamivudine administration during the third trimester of pregnancy is less expensive

TABLE 2

Use estimates
Variable

Base case Range

Healthy state

1.0

N/A

Death

N/A

Chronic hepatitis

0.99

0.900.99

Compensated cirrhosis

0.8

0.700.90

Decompensated cirrhosis

0.6

0.500.70

Hepatocellular carcinoma

0.7

0.500.80

Liver transplant

0.86

0.700.90

Reference

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
32-36,40
..............................................................................................................................................................................................................................................
32-36,40
..............................................................................................................................................................................................................................................
32-36,40
..............................................................................................................................................................................................................................................
32-36,40
..............................................................................................................................................................................................................................................
32-36,40
..............................................................................................................................................................................................................................................
32-36,40

Stable disease (no HBV recurrence) after liver transplant 0.86

0.700.90

Unstable disease (HBV recurrence) after liver transplant 0.6

0.500.70

..............................................................................................................................................................................................................................................
a
32-36,40

R ESULTS
The results for the base-case model are
presented in Table 4. Our model predicts
that, under baseline assumptions, treat-

..............................................................................................................................................................................................................................................

HBV, hepatitis B virus; N/A, not applicable.

a

Use of unstable disease following liver transplant was assumed to be equivalent to use of decompensated cirrhosis.

Nayeri. Cost-effectiveness of antenatal lamivudine administration. Am J Obstet Gynecol 2012.

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TABLE 3

Cost estimates
Variablea

Average, $

Cost of death

Range, $

N/A

N/A

Reference

..............................................................................................................................................................................................................................................

Cost of healthy life

..............................................................................................................................................................................................................................................
38,39

Cost of lamivudine (100 mg daily for 3 mo)

1300

3001800

250

1001000

..............................................................................................................................................................................................................................................
33,34,36,40-43

Cost of diagnosis of chronic hepatitis B

..............................................................................................................................................................................................................................................
33,34,36,40-43

Cost of liver transplant

160,000

80,000200,000

..............................................................................................................................................................................................................................................

Annual costs

.....................................................................................................................................................................................................................................
33,34,36,40-43

Stable chronic hepatitis B

150

100500

Compensated cirrhosis

300

1201200

.....................................................................................................................................................................................................................................
33,34,36,40-43
.....................................................................................................................................................................................................................................
33,34

Decompensated cirrhosis

30,000

10,00050,000

Hepatocellular carcinoma

45,000

10,00090,000

Liver transplant after initial first year

costs/stable disease

25,000

10,00050,000

Unstable disease (HBV recurrence)

after liver transplant

30,000

.....................................................................................................................................................................................................................................
33,34,36,40-43
.....................................................................................................................................................................................................................................
33,34,36,40-43

.....................................................................................................................................................................................................................................
33,34,36,40-43

10,00050,000

..............................................................................................................................................................................................................................................

HBV, hepatitis B virus; N/A, not applicable.

a

All costs are presented in 2011 US dollars.

Nayeri. Cost-effectiveness of antenatal lamivudine administration. Am J Obstet Gynecol 2012.

than expectant management and could

result in total cost savings of $337,000 for
every 1000 women treated. Therefore,
lamivudine administration is the dominant strategy, which is not only more effective, but also less costly.
We performed a series of univariate
sensitivity analyses to determine the effects on the primary outcome by changing each probability and cost estimate
across their plausible ranges. The strategy of lamivudine administration continued to be cost-effective at all the
plausible ranges. When the efficacy of
lamivudine was 40%, treatment transitioned from cost-saving to cost-effective.
Even at a conservative estimate of 20%

efficacy, treatment was cost-effective.

The nature of the model also depended
on the risk of perinatal transmission. At a
minimum perinatal transmission rate of
3%, the model remained cost-effective.
Varying the probabilities of the annual
rate of progression to compensated cirrhosis from chronic hepatitis and the
rate of progression to death from compensated cirrhosis also affected the
model, but at all ranges the model remained at least cost-effective, if not costsaving. The cost of lamivudine was the
only cost variable that affected the models cost-savings nature. If the cost of
lamivudine was increased to $1800 for 3
months, administration of the medica-

TABLE 4

Summary of results for baseline estimates (per 1000 patients)

Variable
Hepatocellular carcinoma

No treatment

Treatment

39

18

Marginal difference
21

..............................................................................................................................................................................................................................................

Liver transplantation

9.7

4.5

..............................................................................................................................................................................................................................................

Total QALY

29,304

29,618

2,604,500

2,267,500

314

..............................................................................................................................................................................................................................................
a
b

Total cost, $

(337,000)

..............................................................................................................................................................................................................................................

QALY, quality-adjusted life-years.

a

Costs presented in 2011 US dollars; b Parentheses indicate cost savings.

Nayeri. Cost-effectiveness of antenatal lamivudine administration. Am J Obstet Gynecol 2012.

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American Journal of Obstetrics & Gynecology SEPTEMBER 2012

tion was still cost-effective. The antiviral

medication would have to cost $17,700
(for 3 months) for the model to no longer be cost-effective. During the series of
univariate sensitivity analyses, the model
remained robust and at all extremes was
cost-effective or cost-saving.
To explore whether there were other
conditions under which the screening
strategy would not remain cost-effective,
we performed bivariate sensitivity analyses by altering variables in combination
with the relative risk of lamivudine. The
majority of combinations resulted in the
treatment strategy either being dominant or cost-effective. When lamivudine
costs and its efficacy were simultaneously varied, the treatment continued to
be cost-effective even at the maximum
costs of lamivudine. To identify a threshold when the strategy was not cost-effective, we allowed the relative risk (RR) of
perinatal transmission with lamivudine
to vary to a RR of 1. At a RR of 0.95
(modest 5% reduction), lamivudine was
no longer cost-effective at its maximum
cost.
Monte Carlo Simulation, a computational algorithm that relies on repeated
random sampling, was also used to simultaneously vary all variables across
extreme ranges listed in Tables 1-3. With
100,000 simulations, the screening strategy was cost-saving 82% of the time and
was cost-effective the remainder of the
time (Table 5).

C OMMENT
Our model demonstrates that, under a
wide variety of circumstances, third-trimester administration of lamivudine is
not only cost-effective, but also cost-saving, although improving long-term outcomes of infants at risk of perinatal hepatitis B transmission. These results are
due to several factors: the reduction in
risk of perinatal transmission with lamivudine administration, the baseline risk
of perinatal hepatitis B transmission, the
risk of chronic disease in the setting of
perinatal infection, the relatively low
cost of lamivudine, and the long-term
consequences and costs of progressive
liver disease. The sensitivity analyses revealed that most changes in the values of

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these variables did not alter our findings.
The model was most sensitive to the risk
reduction in perinatal hepatitis B transmission provided by lamivudine. As expected, the cost-effectiveness of treatment decreased as treatment became less
efficacious. However, the model remained
cost-saving at a wide variety of efficacy levels and costs and transitioned to cost-effectiveness at higher costs and lower efficacy
rates.
Although there is evidence that multiple antepartum injections of hepatitis B
immunoglobulin (HBIG) reduce hepatitis B perinatal transmission rates, an approach that has never been a part of practice, we chose to use lamivudine in our
decision model.44 The metaanalysis by
Shi et al26 suggests that lamivudine,
when compared with HBIG, may be
more effective in interrupting perinatal
viral transmission and more efficient in
decreasing maternal hepatitis B viral levels. In addition, there is substantial evidence of the safety profile of lamivudine,
as it has been well-studied in pregnant
patients with HIV. The Antiviral Pregnancy Registry has demonstrated that
the risk of congenital defects is no higher
than the baseline birth defect rate.45
Although there is data linking the longterm use of lamivudine to the development of resistant hepatitis B mutants, the
mutation rate is not elevated over a 3-4
month period. Therefore, we believe that
our model did not need to adjust for possible adverse effects of lamivudine as
women were only on the medication for
3 months. Finally, we chose to focus on
lamivudine as it is administered in the
form of a tablet and not an injection, which
would involve increased administration
costs with longer office visits and increased
staff time as well as the potential for patient
discomfort and nonadherence.
Our findings are consistent with the
only other study that has evaluated maternal treatment of patients with chronic
hepatitis B in preventing perinatal hepatitis B virus transmission.45,46 Although
this prior study by Unal et al46 examined
the various hepatitis B health states as final endpoints, it did not include a
Markov analysis to account for the transition that occurs among the various
health states. It is well-established that

TABLE 5

Monte Carlo analysis with 100,000 simulations

Variable

IC, $

IE, QALY

ICER, $/QALY

Frequency, %

Cost-savings

SUPERIOR

82

Cost-effective

50,000

18

Not cost-effective

50,000

Not cost-effective

50,000

Not cost-effective

50,000

Not cost-effective

INFERIOR

..............................................................................................................................................................................................................................................
b
..............................................................................................................................................................................................................................................
c
..............................................................................................................................................................................................................................................
c
..............................................................................................................................................................................................................................................
c
..............................................................................................................................................................................................................................................
c
..............................................................................................................................................................................................................................................

IC, incremental cost; IE, incremental effectiveness; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life
years.
a

Cost-savings refers to reduced costs with improved quality of life; b Cost-effective refers to ICER $50,000/QALY with improved
quality of life; c Not cost-effective refers to ICER $50,000/QALY and/or poorer quality of life.

Nayeri. Cost-effectiveness of antenatal lamivudine administration. Am J Obstet Gynecol 2012.

there is no uniform sequence of events

leading up to liver transplant. Patients
with compensated cirrhosis, decompensated cirrhosis, or hepatocellular carcinoma can meet criteria for liver transplantation, albeit with different probabilities.
In addition, these health states are not necessarily permanent. Patients with decompensated cirrhosis can improve and return
to a relatively healthier state of compensated cirrhosis. We also took into account
possible disease states following liver transplantation as it is not a definitive endpoint
and patients can deteriorate as a result of
hepatitis B virus recurrence. Our Markov
model reflects these health states in the truest form and therefore represents a realistic
model for chronic hepatitis B and its longterm implications.
The model by Unal et al46 also incorporated a perinatal hepatitis B transmission rate of 15.7%, whereas we used a
more conservative estimate of 5% assuming 100% adherence with the currently
recommended active-passive immunization protocol for neonates born to women
with chronic hepatitis B. Despite our conservative estimate of 5%, our model demonstrates the cost-effectiveness of antepartum lamivudine administration.
As with any decision analysis, the accuracy of our outcomes depends on the
quality of the data used within the
model. We were fortunate to have a systematic review and metaanalysis that
demonstrated a relative risk reduction in
perinatal transmission with administration of third-trimester lamivudine. Ide-

ally, US-based randomized-controlled

trials would be performed to confirm the
effect of lamivudine use in the third trimester in women with chronic hepatitis
B, but data from Chinese randomizedcontrolled trials are certainly compelling. In addition, we had access to other
decision analyses models in the medicine
literature that incorporated costs, uses,
and probabilities of chronic hepatitis B
infection and serious sequelae of liver
disease, such as cirrhosis, hepatocellular
carcinoma, and death. We tried to accommodate the broad range of costs in
the literature by including a wide cost
range within our decision model. Our
sensitivity analyses demonstrated that
these costs would have little effect on the
ultimate results.
Additional limitations include our
models exclusion of fulminant acute
hepatitis B. Our model focused on the
consequences of chronic hepatitis B infection; the risk of fulminant hepatitis is
less than 1% and it is unlikely that this
would have drastically altered our findings. If anything, incorporating acute
fulminant hepatitis B would have likely
biased the model toward our conclusion
given the consequences of fulminant
liver failure and immediate need for
transplantation.
In our model, we also made certain baseline assumptions regarding end-stage liver
disease, specifically various states following
liver transplantation. Patients status post
liver transplant because of hepatitis B are at
risk of hepatitis B recurrence, and it is this

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recurrence that contributes to the significant morbidity and mortality associated
with liver transplant. Our model took into
consideration the risk of recurrence of
hepatitis B after liver transplant as well as
the associated morbidity and mortality.
After hepatitis B recurrence, patients may
be candidates for second liver transplants.
We did not incorporate this into our
model but feel that these additional longterm consequences of hepatitis B and liver
disease would further strengthen our
model as these sequelae are associated with
increased costs and diminished uses.
We consider our study to adequately
demonstrate that the administration of
lamivudine in the third trimester of
pregnancy to women with chronic hepatitis B is a cost-effective, and frequently
cost-saving, strategy under a wide variety
of circumstances. Treatment of pregnant
patients with lamivudine would reduce
perinatal transmission rates and subsequent chronic hepatitis B infection. This
would translate into a large-scale reduction of end-stage liver diseases, including
cirrhosis, hepatocellular carcinoma, and
liver transplants. In addition to the economic cost-savings, there are certainly nonmonetary benefits of quality of life without
chronic disease on an individual level that we
may not have assessed but would strengthen
our conclusions. A universal policy implementing the routine administration of lamivudine in the third trimester of pregnancy in
patients with chronic hepatitis B should be
considered.
f
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