Fukushima et al.

JA Clinical Reports (2019) 5:1

https://doi.org/10.1186/s40981-018-0219-5

CASE REPORT Open Access

A case of chronic hepatitis B merged with

acute fatty liver of pregnancy with severe
coagulopathy
Risa Fukushima* , Kotoe Kamata, Fumiko Ariyoshi, Masashi Yanaki, Minoru Nomura and Makoto Ozaki

Abstract
Background: Acute fatty liver of pregnancy (AFLP) is a life-threatening disorder, and its relevance to viral hepatitis B
(HB) remains unknown. This case presents an initial experience of treating a patient with HB progressing to AFLP
throughout pregnancy; anesthesiologists should also recognize its clinical feature for perioperative management.
Case presentation: A 28-year-old parturient was diagnosed as chronic HB (CHB) at 21 weeks gestation. Liver and
kidney dysfunction appeared rapidly at 34 weeks gestation, suspected as acute exacerbation of either CHB or AFLP.
Emergency cesarean section was carried out, after which maternal disseminated intravascular coagulation and
hypothermia persisted. With multidisciplinary management, the patient and infant were discharged on postpartum
days 64 and 12, respectively.
Conclusions: Active CHB develops into AFLP. Antiviral therapy should be considered for parturient patients with
CHB, particularly for those with high viral load. The most favorable outcome is prompt and accurate diagnosis to
establish suitable termination method.
Keywords: Acute fatty liver of pregnancy, Hepatitis B, Parturient, Hypothermia

Background hepatitis B (CHB) was merged with AFLP, requiring

Acute fatty liver of pregnancy (AFLP) is rare liver dis- emergency cesarean section. As there have been no re-
order that occurs in approximately 5 cases per 100,000 ports examining such cases in term of the attention and
maternities [1]. Since the development of forced delivery preparatory points for anesthesia, our report also con-
techniques and intensive transfusion therapy, maternal siders these aspects.
mortality rate has dramatically decreased from 75 to
1.8% whereas neonatal mortality remains as high as 104 Case presentation
deaths per 1000 deliveries [1, 2]. Factors frequently re- A Chinese 28-year-old female, previously a healthy 49 kg,
ported as being associated with AFLP include elderly Gravida 2 Para 0 at 21 weeks gestation, was diagnosed
primigravida, multiple gestations, preeclampsia, and with liver dysfunction during a routine health checkup
male fetus [1, 3]. AFLP etiology has been suggested as (Table 1). She was referred to our institution due to sus-
defective fatty acid oxidation in the fetus, but a method pected hepatitis B (HB). Detailed examination revealed
for prevention has not yet been established [3–5]. On IgM anti-HBc was negative. However, excess levels of
the other hand, fulminant hepatitis (FH), a type of viral HBe-antigen (1017.6 S/CO), HBs-antigen (> 250 S/CO),
infection, shares a number of similar clinical features. and HB virus DNA (> 9.0 Logcopies/mL) indicated she
Both diseases occur mainly in late pregnancy and mani- suffered from CHB. HB virus genotype was proved B.
fest with jaundice, liver dysfunction, and rapidly progres- Intravenous monoammonium glycyrrhizinate therapy,
sing severe coagulopathy [3, 6]. In this case, chronic started at 25 weeks gestation, was effective and decreased
alanine aminotransferase (ALT) levels to within normal
range. However, at 35 weeks and 4 days gestation, the
* Correspondence: rfukushima-twmu@umin.ac.jp
Department of Anesthesiology, Tokyo Women’s Medical University, 8-1 patient required hospitalization when she presented severe
Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan malaise with elevated transaminase levels and coagulopathy
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
Fukushima et al. JA Clinical Reports (2019) 5:1 Page 2 of 4

Table 1 Blood sampling data

Reference 21 weeks 28 weeks 35-4/7 weeks 35-5/7weeks Pre-operative Post-operative POD 4 POD 7 POD 62 Post-operative
range 9 a.m. /5 p.m. (35-6/7) 1 year
1 a.m.
T-Bil (mg/dL) 0.2–1.2 1.2 1.3 4.6 5.7/NE NE 3.6 13.5 19.0 4.6 0.9
ALT (U/L) 6–30 214 29 41 44/NE NE 23 28 28 16 20
ALB (g/dL) 3.8–5.1 3.5 NE NE 2.2/NE NE 2.2 3.2 3.5 3.5 4.1
NH3 (μ/dL) 12–66 NE NE NE 132/NE NE NE 70 65 56 NE
Cre (mg/dL) 0.48–0.79 0.38 0.44 0.63 0.68/NE NE 0.62 0.60 2.29 0.51 0.53
UA (mg/dL) 2.4–5.9 2.6 NE NE NE/NE NE 3.8 1.8 NE NE 3.6
PT (%) 70–130 90.9 NE 31.6 29.1/27.0 56.7 47.3 29.3 37.0 56.0 NE
APTT (sec) 25.5–39.5 34.6 NE NE NE/64.2 42.0 61.2 > 150 42.9 NE NE
AT-III (%) 80–130 NE NE NE NE/< 10 99 60 52 88 NE NE
Fib (mg/dL) 150–350 NE NE NE NE/< 50 142 146 199 185 NE NE
WBC (/μL) 4000–8600 8050 7950 9330 10,180/7310 6000 5950 11,290 18,480 1880 2320
Hb (g/dL) 12.0–16.0 11.7 10.1 11.1 11.7/9.4 8.8 7.4 9.1 9.3 10.5 8.4
PLT (K/μL) 150–350 167 165 62 59/50 37 52 75 35 41 66
NE not examined, T-Bil total bilirubin, ALT alanine aminotransferase, ALB albumin, NH3 ammonia, Cre creatinine, UA uric acid, PT prothrombin time, APTT activated
partial thromboplastin time, AT-III antithrombin, Fib fibrinogen, WBC white blood cell, Hb hemoglobin, PLT platelet count

(Table 1). She was diagnosed with acute exacerbation of consideration of the severe coagulopathy as well as pos-
CHB and was started on 300 mg of oral tenofovir (300 sible leukoencephalopathy, we avoided using neuraxial
mg, daily) and intravenous vitamin K (20 mg, daily). block despite the massive preoperative transfusion.
The next morning, she presented systemic edema. The Rapid sequence induction with thiopental 250 mg, fen-
following afternoon she complained of abdominal pain tanyl 100 μg, and suxamethonium 50 mg was selected.
and nausea. Transabdominal ultrasonography showed The trachea was easily intubated. General anesthesia was
ascites and a fatty liver, suggesting AFLP. At this time, maintained with 65% nitrous oxide and 1.0% sevoflurane
she showed blood pressure of 117/68 mmHg, pulse of until delivery. Though fluid-warming devices and a
86 beats/min, and body temperature of 36.7 °C. Consider- forced-air warmer were prepared, patient rectal
ing the progressive somnolence and sufficient gestational temperature dropped to 34.8 °C after induction. A fe-
age without cervical dilatation, emergency cesarean sec- male infant of 2773 g with good APGAR scores (8 and 9
tion was selected, before referral to anesthesiologists for a at 1 and 5 min, respectively) was delivered 7 min after
detailed preoperative evaluation. The Swansea Criteria, anesthesia induction. The mother showed hypoglycemia
which defines AFLP at 6 points or more [1, 4, 7], scored at of 65 mg/dL, which was corrected by 10 g of dextrose.
least 7 points at this time (abdominal pain, elevated biliru- Despite appropriate uterine contraction, additional trans-
bin, ascites or bright liver on ultrasound scan, elevated fusion was required to maintain hemostasis during the op-
transaminase, elevated ammonia, coagulopathy, and eration. Four units of packed red blood cell (RBC), 5 bags
vomiting were positive; hypoglycemia, elevated uric acid, of cryoprecipitate, 10 units of PC, and 800 mL normal sa-
and liver biopsy were not examined; polydipsia or poly- line were administered on the intraoperative anesthesiolo-
uria, encephalopathy, leukocytosis, and renal impairment gist’s decision. Estimated blood loss, ascites, amniotic
were negative). To control coagulopathy, 24 units of fresh fluid, and urine output were 2020 mL, 300 mL, 450 mL,
frozen plasma (FFP) and 3000 units of antithrombin for- and 650 mL, respectively. The total duration of surgery
mula were administrated according to the obstetricians’ was 69 min, and anesthesia time was 81 min. Prolonged
estimations. Additionally, 20 units of platelet concentrate hypothermia was recorded as her rectal temperature had
(PC) were given due to severe thrombocytopenia (Table 1; dropped to 34.3 °C by the end of the surgery.
35 5/7 weeks, 5 p.m.). The patient’s vital signs following After cesarean section, the patient was transferred to
preoperative blood transfusions were blood pressure of the intensive care unit (ICU) with tracheal intubation.
97/46 mmHg, pulse rate of 86 beats/min, body Vaginal hemorrhage persisted for 12 h, despite transfu-
temperature of 36.0 °C, and peripheral oxygen saturation sion of 18 units of packed RBCs 16 units of FFP and 10
(SpO2) of 97% in room air. The patient was classified as units of PC. Eventually, active hemorrhage was con-
American Society of Anesthesiologists Physical Status trolled by uterine artery embolization. She was extubated
Class 3E. The fetus showed reassuring status. In on postoperative day (POD) 2 and was well orientated
Fukushima et al. JA Clinical Reports (2019) 5:1 Page 3 of 4

with stable vital status. At one point, liver transplant- their third trimester [10]. This treatment not only benefits
ation was planned, due to that the Model for End-stage the mother, but also the fetus by preventing mother-to-
Liver Damage score for acute disseminated intravascu- child transmission. In addition, HB virus vaccination and
lar coagulation (DIC) and liver dysfunction [8] on POD HB immunoglobulin are recommended for neonates as in
4 was 24 points; however, 4 days of therapeutic plasma this case [10]. More in-depth research is expected to de-
exchange (POD 3–6) and 6 days of hemodiafiltration termine if the levels of transaminase and HBV-DNA and
(POD 3–8) were highly effective. Glycerin fructose was virus genotype are related to AFLP and if antiviral agents
used for 9 days (on POD 2–10) because of cerebral are able to prevent AFLP onset.
edema, but she showed no neurological sequelae. Regarding anesthesia, some reports have shown the
Neither infection, sepsis, major respiratory complica- key to perioperative management of AFLP to be as fol-
tions, nor pancreatitis was remarked. Liver biopsy was lows: early diagnosis, prompt termination, strict fluid
not performed in consideration of coagulopathy. The management, correct coagulopathy, and care for
patient was discharged from ICU and hospital on POD hypoglycemia [1, 3]. These warnings were of course ap-
13 and 64, respectively. HB virus vaccination and HB plied for the current case, but body temperature proved
immunoglobulin given at birth prevented vertical trans- difficult to control. There are few reports concerning
mission of HB, and the infant did not show any devel- perioperative body temperature in AFLP patients. Al-
opmental delay. The infant was discharged from the though mild hypothermia control of 32 to 35 °C is
hospital on postpartum day 12. For 1-year follow-up sometimes carried out in hepatic encephalopathy pa-
after discharge, ALT level of the patient has been kept tients, hypothermia may cause coagulopathy [11, 12].
in normal range and her HBV-DNA level as less than As the relationship between infection or hemorrhage
3.0 Logcopies/mL (Table 1). and body temperature are still under investigation, we
concluded normothermia to be acceptable, providing
Discussion hepatic encephalopathy was not present. During sur-
Viral hepatitis patients generally have higher levels of gery, we aimed to keep the patient’s body temperature
serum transaminases, with values exceeding 1000 U/L. over 36 °C; however, we failed to achieve this, despite
The level of uric acid is rarely elevated in FH patients, using fluid-warming devices and a forced-air warmer.
and signs of preeclampsia are absent in viral hepatitis Preoperative temperature control would have been better
[3]. Compared to AFLP, multiorgan failure is more likely as the massive transfusion prior to operation could be the
to coexist with viral hepatitis. On the other hand, inci- cause of hypothermia. Close-knit integration and suffi-
dences of hypercreatinemia, DIC, and digestive tract cient communication with obstetric and clinical staff on
hemorrhage are less common in patients with viral the ward are also required. It is sometimes difficult to
hepatitis than in those with AFLP [9]. It is also suggested keep core temperature in severe liver dysfunction status
that AFLP patients tend to show hypoglycemia [4]. patients stable due to dilation of peripheral blood vessels.
These clinical features may be supportive in distinguish-
ing between viral hepatitis, FH and AFLP. Termination
Conclusions
is selected as a basic treatment for both AFLP and FH;
Active CHB develops into AFLP. Antiviral therapy
however, especially in early preterm FH cases, careful
should be considered for pregnant patients with CHB,
observation with antiviral drug therapy may be an alter-
especially in the cases with high viral load. Prompt and
native in consideration of neonatal outcomes. In fact, as
accurate diagnosis is favorable in order to evaluate how
both AFLP and FH commonly reveal in the late preg-
urgent termination should be carried out. However, in
nancy [1, 3, 6], accurate differential diagnosis is not al-
cases of late preterm period without cervical dilatation,
ways as important as it was for this case. Our judgment
elected urgent cesarean section should be selected. If
to carry out an urgent cesarean section, without accurate
normothermia is to be maintained during surgery, peri-
diagnosis, can be considered reasonable and necessary,
operative management on the ward before admission to
given the sufficient gestational age, severity of liver dys-
the operating room is necessary.
function and reassuring fetal status. Moreover, antiviral
agent therapy has been commonly utilized in pregnant
Abbreviations
cases. Tenofovir, a kind of nucleoside reverse transcriptase AFLP: Acute fatty liver of pregnancy; ALT: Alanine aminotransferase;
inhibitor that works by decreasing the amount of HB virus CHB: Chronic hepatitis B; DIC: Disseminated intravascular coagulation;
in the blood, has been confirmed as safe for use with fe- FFP: Fresh frozen plasma; FH: Fulminant hepatitis; HB: Hepatitis B;
ICU: Intensive care unit; PC: Platelet concentrate; POD: Postoperative day;
tuses, as evidenced by its level B status given by the Food RBC: Red blood cell; SpO2: Pulse oximetry
and Drug Administration [10]. The latest report recom-
mended the use of antiviral drugs to a pregnant patient Acknowledgements
with a high viral load (100,000–200,000 IU/mL) during Not applicable.
Fukushima et al. JA Clinical Reports (2019) 5:1 Page 4 of 4

Funding 10. Chamroonkul N, Piratvisuth T. Hepatitis B during pregnancy in endemic areas:

No funding was received for support of this case study. screening, treatment, and prevention of mother-to-child transmission. Pediatr
Drugs. 2017;19:173–81.
Availability of data and materials 11. Stravitz RT, Larsen FS. Therapeutic hypothermia for acute liver failure. Crit
All data generated or analyzed during this study are included in this Care Med. 2009;37:S258–64.
published article. 12. Karvellas CJ, Stravitz TR, Battenhouse H, Lee WM, Schilsky ML. Therapeutic
hypothermia in acute liver failure: a multicenter retrospective cohort analysis.
Liver Transpl. 2015;21:4–12.
Authors’ contributions
RF prepared the manuscript and obtained the written consent from the
patient. KK managed anesthetic care of the patient and prepared the
manuscript. FA and MY managed anesthetic care of the patient and helped
to draft the manuscript. MN and MO also helped to draft the manuscript. All
authors read and approved the final manuscript.

Authors’ information
RF is an assistant professor in the Department of Anesthesiology at
Tokyo Women’s Medical University. KK is an assistant professor in the
Department of Anesthesiology at Tokyo Women’s Medical University. FA
is an assistant professor in the Department of Anesthesiology at Tokyo
Women’s Medical University. MY is an assistant professor in the
Department of Anesthesiology at Tokyo Women’s Medical University. MN
is a professor in the Department of Anesthesiology at Tokyo Women’s
Medical University. MO is a professor in the Department of
Anesthesiology at Tokyo Women’s Medical University.

Ethics approval and consent to participate

This report was approved by the institutional review board of the
corresponding author’s institution.

Consent for publication

Informed consent was obtained from the patient for publication of this case
report and any accompanying images. A copy of the written consent is
available for review from the Editor-in-Chief of this journal.

Competing interests
The authors declare that they have no competing interests.

Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.

Received: 21 October 2018 Accepted: 17 December 2018

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