In the name of GOD

Hyperemesis Gravidarum

Hyperemesis and liver disease -Usually consisting of mild serum transaminase elevation, occurs in almost 50% of patients with HG. -While multiple risk factors have been proposed, the etiology is remains unclear. -Risk factors: multiple gestations, molar pregnancies, fetal anomalies (hydrops, trisomy 21) -3 hypotheses: starvation injury, release of inflammatory cytokines, impairment of fatty acid oxidation.

Hyperemesis and liver disease -Unfortunately, despite the high incidence of liver disease in HG, clinical methods to predict which patients with HG are at risk for liver involvement are lacking. -With the exception of rare cases of jaundice, the clinical presentation of HG with and without liver involvement is nearly identical. -Mild aminotransferase elevation (up to 200 U/L) is the most common liver laboratory abnormality seen in HG, although increased ALP up to twice normal values and mild hyper-bilirubinemia (mixed direct & indirect) up to 4 mg/dl may also occur.

Hyperemesis and liver disease -There are rare case reports of aminotransferase elevation greater than 1600 U/L, but fulminant liver failure has not been reported. -HG with liver involvement is almost never fatal. No long term sequelae of liver dysfunction have been described. -Liver biopsy: show the histopathologic changes of necrosis, steatosis and bile plugs. -LFT abnormalities usually return to normal levels within a few days of volume expansion and the cessation of vomiting.

Hyperemesis and liver disease -Before the diagnosis can be made, disease states unrelated to pregnancy such as gastrointestinal disorders (e.g., viral hepatitis and cholecystitis), metabolic disease (e.g., diabetes and hyperthyroidism), and medication effects, must be ruled out. -Other pregnancy-related conditions such as AFLP and HELLP typically present in the third trimester of gestation and thus are readily distinguished from HG in most cases.

Hyperemesis and liver disease -The placental cytokine hypothesis: -Over-expression of cytokine-producing cells has long been proposed as a potential cause of numerous pregnancy-associated diseases including preeclampsia and HG. -While TNF induced hepatotoxicity in viral hepatitis and alcoholic liver disease is relatively well-characterized, the hepatotoxic role inflammatory cytokines play in other conditions such as pregnancy remains unclear. -TNF may directly lead to T-cell apoptosis within the liver which in turn could cause liver damage.

Hyperemesis and liver disease -The impaired mitochondrial fatty acid oxidation defect hypothesis: -Patients heterozygous for mutations in the FAO cascade are usually phenotypically normal except during periods of oxidative stress such as starvation and pregnancy.

Hyperemesis and liver disease -The starvation commonly seen in patients with HG can lead to enhanced peripheral lipolysis and an increased influx of FFA into mitochondria. Heterozygous mothers, while usually phenotypically normal, have limited capacity for mitochondrial FAO which subsequently leads to increased level of plasma FFA intermediates and causes enhanced extra-mitochondrial FAO leading to the generation of reactive oxygen species. The maternal derived FFA intermediates which accumulate in the circulation of the obligate heterozygous mothers could induce free radical damage of placental endothelium with the subsequent release of inflammatory cytokines,resulting in maternal liver damage.

-Reference: -NCBI bookshelf. A service of the National Library of Medicine, National Institutes of Health. -Author: William M,2013,Section on gastroenterology, Department of Internal Medicine, North Carolina.