Proactive Approaches to Prevent Gestational Alloimmune Liver Disease

Introduction

Gestational alloimmune liver disease, also known as fetal or neonatal hemochromatosis, is a rare but serious condition that can occur during pregnancy. It is characterized by the presence of maternal antibodies that target and damage the fetal liver, leading to liver dysfunction and potentially life-threatening complications for the baby. Preventing gestational alloimmune liver disease requires a comprehensive approach involving early detection, close monitoring, and appropriate interventions. In this article, we will explore various strategies and measures that can help in preventing gestational alloimmune liver disease, ensuring the best possible outcomes for both mother and baby.

What Is Gestational Age?

Gestational age is the time from when a baby is conceived and is being developed in the womb till birth. It is calculated from the first day of the woman's last menstrual cycle to the current consult date. Ultrasound scan provides measurements of the head, abdomen, and thigh bone, which help to determine the gestational age.

What Is Alloimmune?

Alloimmune refers to an immune response that occurs when the immune system of an individual recognizes and responds to antigens from another individual of the same species. It occurs when there is a mismatch between the antigens present in the donor and recipient, leading to an immune reaction.

Why Is the Liver Important?

The liver is a vital organ of the human body as it filters the blood and produces various hormones for other body parts, thereby important for regular body functions.

What Is Alloimmune Liver Disease?

It is when the immune system targets the liver cells.When a severe liver injury is accompanied by extrahepatic siderosis (iron deposition outside the liver) in a newborn, the condition is termed neonatal hemochromatosis. It may happen during the gestation period following liver cell injury.

The condition was not necessarily found in siblings for an affected patient. Women affected with neonatal hemochromatosis had healthy births as well. Hence, it was proven not to be hereditary.

GALD is the primary cause of liver failure in most cases of neonatal hemochromatosis.

How Does Gestational Alloimmune Liver Disease Occur?

The mechanism of how the foreign antigen gets into circulation is yet to be determined. Some studies believe that antigen crosses the placenta either when it gets in/on an external transport cell (exocytic vesicle) or when a soluble protein escapes during apoptosis (programmed cell death) during rapid liver development.

Regardless of which speculative theory is correct when the mother's blood detects a foreign antigen, the mother's immunoglobulin-G antibodies attack the fetus's liver cells, resulting in liver injury and death. The specific antigen that the body reacts to is still unknown. This reaction may occur as early as 12 weeks of gestational age.

What Are the Clinical Findings for Gestational Alloimmune Liver Disease?

The gestational alloimmune liver disease continues to be challenging since it is not often suspected to be the case because of its rare occurrence or because one gets diagnosed late.

The doctor must always suspect a case of gestational alloimmune liver disease when signs of liver injury are seen. Mothers may present a history of stillbirth or neonatal diseases in previous pregnancies. A proper clinical observation and medical history may help diagnose the disease faster and provide the appropriate preventive treatment.

Gestational Alloimmune Liver Disease May Show the Following Clinical Findings:

• Antenatal (Before Birth) Findings:

• Growth restriction (smaller than actual gestational age).

• Premature birth ( before 37 weeks of gestation).

• Hydrops fetalis (the abnormal amount of fluid build-up in two or more areas of the fetus).

• Oligohydramnios (an abnormal volume of amniotic fluid).

• Fetal hepatomegaly (longer liver than usual).

• Ascites (fluid collection in abdomen spaces).

• Postnatal (After Birth) Findings:

  • Subacute liver injury.

  • Congenital cirrhosis (scarring of the liver shortly after birth).

  • Coagulopathy (blood coagulation is impaired).

  • Recurrent hypoglycemia within a few hours or days after birth (low blood sugar level).

  • Progressive edema (swelling).

  • Renal impairment (impaired kidney function).

  • Jaundice.

  • Hepatic or extrahepatic siderosis (iron deposition in or outside the liver).

• Laboratory Findings:

  • Aminotransferase levels- relatively low.

  • Hypoalbuminemia- low albumin levels.

  • Elevated bilirubin levels.

  • Elevated ferritin levels.

  • Elevated iron levels.

  • Elevated transferrin saturation levels.

  • Elevated alpha-fetoprotein is also present.

Positive MRI or biopsy finding of extrahepatic siderosis confirms the diagnosis of gestational alloimmune liver disease.

What Is the Treatment for Gestational Alloimmune Liver Disease?

Intravenous immunoglobulin (IVIG) and exchange transfusion (ET) have replaced conventional therapy. Earlier, gestational alloimmune liver disease was considered a fatal disease. Recently, few treatment modalities have shown an improved prognosis and decreased mortality rate for diagnosed neonates. The treatments used on the affected neonates at birth are:

• Chelation-Antioxidant Treatment - It is a treatment to reduce the toxic effect of metal (iron). Studies have shown that chelation-antioxidant treatment alone does not help neonates suffering from liver failure.

• Exchange Transfusion - The individual's blood is removed from the body with a thin catheter and replaced with fresh prewarmed blood from a donor until the required blood volume is replaced.

• Intravenous Immunoglobulin (IVIG) - Intravenous administration of immunoglobulin antibodies (90 percent being immunoglobulin G), which is obtained from the plasma of healthy donors. It may help with the following:

  • Inhibition or activation of the immune response.

  • Modulation of FcgR expression on B cells.

  • Induce phagocytosis or cytotoxicity.

  • Regulate apoptosis.

  • Modulation of antigen-presenting cells.

• Liver Transplantation - Suggested when medications fail to revive the infant's liver, and liver transplant is the only option for the survival of the neonate.

  • A reduced-size liver from a living or cadaver donor is used.

  • Done in infants as young as three months of age.

How to Prevent Gestational Alloimmune Liver Disease?

Recurrence of gestational alloimmune liver disease was seen in subsequent pregnancies for most cases. Intravenous immunoglobulin therapy may prevent this with timely diagnosis and intervention during pregnancy. The alloimmune injury is believed to begin as early as 12 weeks of gestation. In the following weeks of gestation, the developing liver cells get damaged, leading to liver failure. Prevention of gestational alloimmune liver disease focuses on controlling this immune-mediated process by intervening during the early stages of pregnancy (as early as 12 weeks of gestation). This has been shown to have positive effects and the birth of a healthy baby.

• Administration of intravenous immunoglobulin (IVIG) for the mother (before childbirth) has been shown to prevent gestational alloimmune liver disease, which otherwise has a recurrence risk above 90 percent in subsequent pregnancies.

• Administration of IVIG during pregnancy to mothers with previous infants affected with gestational alloimmune liver disease may reduce the risk of liver injury and mortality.

• Administration of IVIG may be done weekly starting from the second trimester to reduce the risk of this life-threatening disease.

Are There Any Risks in IVIG Administration?

Intravenous immunoglobulin (IVIG) is best known for its immunomodulatory, anti-inflammatory, and immune-protective effects. However, some rare cases may show side effects such as thrombosis (blood clots in blood vessels) or allergic reactions (anaphylaxis). Nevertheless, the benefits usually outweigh the rare side effects, and intravenous immunoglobulin therapy is often recommended.

Conclusion

With recent advancements in medicine and the continued research on gestational alloimmune liver diseases, suspecting the possibility of gestational alloimmune liver disease in pregnancy and timely intervention can prevent the disease and save subsequent pregnancies, thereby reducing the mortality rate.