Recurrent hepatocellular carcinoma in pregnancy: A case report and literature review

Short abstract

The incidence of hepatocellular carcinoma in pregnancy is rare, and we present the first reported case of a pregnancy complicated by pre-existing advanced hepatocellular carcinoma. We describe the case of a 39-year-old woman in her second pregnancy, with a diagnosis of hepatocellular carcinoma. This was discovered in 2013 incidentally following hepato-splenectomy and pancreatectomy for a presumed hepatic adenoma in the context of multiple arterio-venous malformations. Recurrent hepatocellular carcinoma, in conjunction with co-existing pulmonary hypertension was successfully managed in a multi-disciplinary setting, resulting in a spontaneous vaginal delivery of a live female infant with maternal and neonatal survival six months following delivery.

Introduction

The incidence of hepatocellular carcinoma (HCC) in pregnancy is rare, with less than 50 cases reported in the literature over the past 60 years.¹ We describe the first published case of pregnancy complicated by recurrent, advanced and inoperable HCC. We delineate the management challenges, highlighting the importance of multi-disciplinary care in women with complex medical conditions in pregnancy.

Case report

A 39-year-old Eastern European woman presented to a tertiary-level maternity hospital in her second pregnancy at 11 weeks’ gestation and was referred to the Perinatal Medicine Clinic. Her first pregnancy 15 years previous was uncomplicated, resulting in a term spontaneous vaginal delivery (SVD). Antenatal serology (hepatitis/HIV) was negative. Subsequently, investigations for epistaxis in 2012 revealed a diagnosis of hereditary haemorrhagic telangiectasia (HHT; Osler-Weber-Rendu syndrome). The following year, HHT surveillance diagnosed multiple hepato-splenic aneurysms and a presumed hepatic adenoma in conjunction with a congenital non-hypoxaemic porto-caval shunt. There were no cerebral or pulmonary arterio-venous malformations (AVMs). Following a right hepato-splenectomy and distal pancreatectomy, a 20 cm well-differentiated HCC was identified, with positive margins. Despite a complex post-operative course involving renal and respiratory failure, sepsis and hyperammonaemic encephalopathy, she made a good recovery. However, an ultrasound-guided biopsy 10 months later revealed a recurrence of HCC, with multiple lesions in the left hepatic lobe (largest measuring 2.3 cm). Treatment with chemotherapy (Sorafenib) was unsuccessful, and transplantation or trans-arterial chemo-embolization was contra-indicated due to intricate hepato-portal vasculature. Magnetic resonance imaging (MRI) at 24 months post-diagnosis showed disease progression with nodules increasing up to 4 cm in size. This was further complicated by the discovery of moderate to severe pulmonary hypertension (PH) (pulmonary artery pressure of 55 mmHg).

An unplanned pregnancy was confirmed 46 months after the initial diagnosis of HCC. Multi-disciplinary team (MDT) involvement from surgery, hepatology, radiology, cardiology and anaesthetics was initially sought. MDT meetings were held throughout the pregnancy by hepato-biliary, oncology and perinatal medicine teams. Following extensive counselling around the risks of continuing pregnancy, as well as the option of termination of pregnancy, she opted to continue with the pregnancy. Antenatal serial clinical assessment was performed by hepatology and surgery to assess disease progression, in addition to two surveillance MRIs (at 17 and 33 weeks’ gestation). The former identified multiple hepatic masses, the largest measuring 10 × 7 × 6 cm, which increased at follow-up (Figure 1). Serial cardiology review involved clinical assessment, three echocardiograms and a right cardiac catheterisation at 17 weeks’ gestation, confirming persistence of PH. The patient remained asymptomatic of PH throughout pregnancy, requiring no additional therapy. Anaesthetic review in the second and third trimester evaluated options for analgesia, with MRI demonstrating absence of spinal AVMs, allowing epidural anaesthesia. Thromboprophylaxis was commenced at 22 weeks’ gestation on balancing of the risk of haemorrhage due to hepatic rupture and thromboembolic disease and PH. HHT did not pose any complications to the pregnancy. Table 1 demonstrates the haematological and biochemical indices in pregnancy. Hepatic transaminases were elevated but remained stable, increasing only in the post-partum period (see Table 1). Conversely, alpha-fetoprotein (AFP) increased initially, and then decreased in the postnatal period. Haematological and coagulation profiles remained stable. Following idiopathic spontaneous onset of labour at 33 weeks’ gestation, the patient had an spontaneous vaginal delivery of a live female infant weighing 2.35 kg under epidural anaesthesia with an estimated blood loss of 800 ml. Intrapartum measures to monitor the clinical situation involved cardiology and anaesthetic review, as well as one-on-one midwifery care. Postnatal thromboprophylaxis was continued and hepatology follow-up arranged. Six months postnatally, the patient remains stable without further complications or disease progression and continues under surveillance by the MDT.

Figure 1.

MRI showing the hepatic mass.

Table 1.

Change in haematological and biochemical parameters.

Weeks’ gestation	Post chemotherapy (three years pre-conception)	Two months pre-conception	11	17	26	30	33	Three weeks postnatal	Six months postnatal
Haemoglobin (g/dL)	a	a	13.8	13.1	12.1	11.5	11.5	11.2	a
Platelets (×109/L)	a	a	445	405	305	345	297	560	a
Alanine aminotransferase (IU/L)	48	40	50	21	19	19	20	56	45
Aspartate aminotransferase (IU/L)	a	44	a	21	a	a	72	62	54
Gamma-glutamyl transferase (IU/L)	a	380	a	248	132	130	n/a	339	249
Alkaline phosphatase (IU/L)	247	220	248	198	172	174	350	271	181
Alpha fetoprotein (ng/ml)	a	<2.0	a	53.2	123.6	150.2	a	16.3	2.7
Activated partial thromboplastin time ratio	a	a	a	1.1	1.0	1.20	1.20	1.2	a

^aNot tested.

Discussion

The incidence of HCC worldwide in women is 5.5/10,000,² being typically more common in Asia and Africa. It is strongly associated with liver cirrhosis, often attributed to Hepatitis B and C, with anti-HCV antibodies reported in up to 70% of Europeans with HCC.³ It is an aggressive disease; 54% of patients have a recurrence by 22 months following resection,⁴ with a median survival in those inoperable and symptomatic of eight weeks.⁵ In previous cases of HCC in pregnancy, it has been postulated that increased oestrogen and liver vascularity expedite the progression of HCC and deterioration, which was not ultimately evident in our case.⁶ AFP is typically utilised as a diagnostic and surveillance tool in HCC;⁷ however, it can increase in normal pregnancy. In this case, a low AFP pre-pregnancy reverted to normal in the late postnatal period, and as such is not a good marker for disease progression in pregnancy. HCC in pregnancy is also implicated with poorer obstetric outcomes, with a 12.5% risk of spontaneous hepatic rupture in pregnancy⁸ and shorter median maternal survival than non-pregnant counterparts.^9,10

Hung et al. have reported a case of recurrent HCC following a pregnancy but noted the absence of evidence surrounding long-term survival of palliative HCC which is present prior to pregnancy.¹¹ Pregnant women who are affected by malignancy often have concomitant medical conditions, needing MDT involvement. Associated conditions, such as PH, can have a significant clinical impact on maternal and fetal morbidity and mortality.¹² In addition, there is significant morbidity (2.2%) and mortality (1%) in pregnancies complicated by HHT, usually attributable to AVMs.¹³ Pregnancies complicated by hepatic disorders have been associated with adverse pregnancy outcomes, potentially due to factors such as altered retinoid metabolism.¹⁴

We have demonstrated in the first case report of recurrent, inoperable HCC in pregnancy that with dedicated MDT involvement, maternal and fetal outcome can be optimised, with favourable outcomes possible.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was carried out at the Irish Centre for Fetal and Neonatal Translational Research (INFANT), which is in part funded by Science Foundation Ireland (12/RC/2272).

Ethical approval

Informed patient consent was obtained for the publication of this article and associated images.

Guarantor

KO’D INFANT, University College Cork.

Contributorship

All authors have made a substantial contribution to this paper and have reviewed the final version of the manuscript.