Acute Fatty Liver Disease of Pregnancy: Updates in Pathogenesis, Diagnosis, and Management

Abstract

Acute fatty liver of pregnancy (AFLP) is an obstetric emergency characterized by maternal liver failure and may have complications for the mother and fetus, including death. This review examines recent literature on the epidemiology, pathogenesis, diagnosis, and treatment of acute fatty liver of pregnancy. Pathogenesis of this disease has been linked to defects in fatty acid metabolism during pregnancy, especially in the setting of fetal genetic defects in fatty acid oxidation. The value of screening all patients for these genetic defects remains to be determined. Distinguishing AFLP from other high-risk liver diseases of pregnancy that have overlap features, such as HELLP and preeclampsia, can be challenging. Although sensitive diagnostic tools such as the Swansea criteria have been developed, further work is needed to diagnose AFLP more quickly. Although survival rates have improved in the past 30 years, delay in diagnosis and treatment of AFLP has life-threatening consequences; an algorithmic approach to AFLP may be a valuable resource for clinicians. Future epidemiological and long-term studies will improve our prediction of women at risk for developing AFLP and determine the long-term consequences of this condition.

Maternal Death due to Acute Fatty Liver of Pregnancy

“…Then the accumulation of these fatty acids and their toxic metabolic intermediates lead to activation of reactive oxygen species, inflammatory pathways and cellular necrosis, which have adverse effects to hepatocytes [6][7][8][9][10]. FAOD in a mother or/and a fetus can induce AFLP [6][7][8][9][10]. This pathogenesis would be consistent with the histologic findings identified in our case, and it is presumed that the metabolic abnormality or stress might give rise to sudden death.…”

“…FAOD increases the demand for fatty acids due to changes in physiological metabolism during pregnancy and affects the mother [6][7][8][9][10]. Long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) is a well-known risk factor of AFLP [6][7][8][9][10]. The maternal hormone-sensitive lipase (in adipose tissue, adrenal gland, gonads, heart, and skeletal muscle) with insulin resistance, and lipoprotein lipase in the placenta increases the level of triglycerides and finally the level of free fatty acids in maternal blood [7].…”

“…Long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) is a well-known risk factor of AFLP [6][7][8][9][10]. The maternal hormone-sensitive lipase (in adipose tissue, adrenal gland, gonads, heart, and skeletal muscle) with insulin resistance, and lipoprotein lipase in the placenta increases the level of triglycerides and finally the level of free fatty acids in maternal blood [7]. Then the accumulation of these fatty acids and their toxic metabolic intermediates lead to activation of reactive oxygen species, inflammatory pathways and cellular necrosis, which have adverse effects to hepatocytes [6][7][8][9][10].…”

Review article: drug‐induced liver injury in the context of nonalcoholic fatty liver disease – a physiopathological and clinical integrated view

“…For example, microvesicular steatosis occurs in acute fatty liver of pregnancy, a rare but potentially fatal condition where pericentral microvesicular steatosis is one of the hallmark histological findings . In this case, homozygous enzymatic defects in foetal and placental β‐oxidation of FFAs would lead to accumulation of FFAs and toxic metabolic intermediates that are transferred via maternal circulation to a heterozygous mother; this creates a lipotoxic environment that increases hepatocyte ROS, activates inflammatory pathways, and triggers hepatocellular death, thus leading to acute maternal hepatic failure …”

Liver Diseases in the Perinatal Period: Interactions Between Mother and Infant

“…AFLP is an uncommon (1:7,000‐15,000) and potentially fatal disease that typically occurs in the third trimester, but may present as early as 22 weeks of gestation, and in up to 20% postnatally. Incidence of AFLP is increased in multigravidas, male fetus, first pregnancy, previous AFLP (recurrence rate of 20%), maternal metabolic disorders (e.g., type 2 diabetes), and fetal fatty acid oxidation disorders (FAODs) with deficiencies of specific enzymes involved in mitochondrial metabolism of fatty acids . FAODs are autosomal recessive, with the mother a heterozygous carrier.…”