Hepatocellular carcinoma in pregnancy: A systematic review

Abstract

Introduction: Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis or chronic hepatitis B virus infection. Ultrasound evaluation, CT scan, and MRI are used to detect HCC. α-fetoprotein (AFP) is a common marker used to detect HCC in the non-pregnant population, which notoriously increases in pregnant women in relation to gestational age. Treatment is driven by the extent of the disease and the severity of underlying liver disease. Pregnancy may represent an obstacle to diagnosis and appropriate treatment of HCC. The aim of this descriptive systematic review was to describe the clinical features and maternal and neonatal outcomes of HCC in pregnancy.

Material and methods: We performed a systematic review of the literature about HCC diagnosed in pregnancy and the postpartum period, with signs or symptoms arising in pregnancy. We included case reports and case series describing the clinical features of women diagnosed with HCC, fibrolamellar variant of HCC, and mixed HCC and cholangiocarcinoma during pregnancy or the postpartum period (with onset of symptoms during pregnancy), from inception to March 2023. The study protocol was registered with the PROSPERO database (Registration number: ID CRD42021275584).

Results: We identified 180 records. The articles included in this systematic review were 47 case reports and 5 case series, for a total of 63 pregnancies. The two most frequent predisposing conditions were hepatitis B virus infection (30/63; 47%) and liver cirrhosis (14/63; 22%). Ultrasound evaluation was the most used technique to detect HCC. AFP was higher than normal in 28/46 patients tested (61%). Surgical treatment was the most used therapy, both during pregnancy and after delivery. Twenty-six patients (26/63; 42%) died within 6 months of diagnosis. Survival >24 months was 9% (4/46) in symptomatic and 29% (5/17) in asymptomatic women. No patient with cirrhotic liver survived more than 12 months. Thirty-eight newborns were alive at 28 days of age (38/63; 61%).

Conclusions: Hepatocellular carcinoma in pregnancy is associated with a high risk of maternal and neonatal mortality. Diagnosis in asymptomatic high-risk women or following abnormal maternal serum AFP screening is associated with better maternal outcomes.

Keywords: cirrhosis; hepatitis B virus infection; hepatocellular carcinoma; pregnancy; α‐fetoprotein.

FIGURE 1

PRISMA 2020 flow chart and steps of studies selection. Citations of excluded studies are provided in Table S3.

FIGURE 2

Maternal α‐fetoprotein (AFP) serum concentrations in pregnant women with hepatocellular carcinoma. The blue and orange lines represent lower and higher normal values of AFP levels in pregnancy, derived from Hay et al. 1976.