Total serum bile acids may be elevated up to 100 times the normal concentration in patients with liver disease. This increase comprises mainly conjugated bile acids. In liver malfunction one or more steps of the enterohepatic circulation may be impaired, which results in abnormal serum total bile acids (TBA) values. Increased serum TBA levels are associated with diseases such as acute and chronic hepatitis, intrahepatic cholestasis of pregnancy (ICP), liver sclerosis, cirrhosis, and cancer, whereas decreased serum TBA levels are associated with ileal dysfunction, malabsorption, diarrhea or Crohn’s disease. Although TBA levels enable an early diagnosis of hepatobiliary deficiencies, they do not allow the differentiation between various diseases. Additionally, serum TBA is used to monitor treatment response of patients suffering from liver disease [1-3, 6-14].

Liver disease comprises a wide range of complex conditions that affect the liver and prevent the organ from functioning effectively. Some liver diseases are associated with increased risk for cancer, including cirrhosis and fatty liver disease (FLD) while others can be genetic or caused by a variety of factors that damage the liver [15]. The main types of liver diseases occur due to infections, autoimmune diseases, genetics, cancer and other reasons. One example is the non-alcoholic fatty liver disease (NAFLD). It is one of the most common liver diseases, with a rapidly increasing prevalence of currently 30% [16]. NAFLD is a metabolic disorder caused by hepatic lipogenesis due to insulin resistance.

Alcoholic liver disease (ALD) is a leading cause of liver-related morbidity and mortality and encompasses a spectrum of disorders ranging from asymptomatic steatosis, alcoholic steatohepatitis, fibrosis, cirrhosis, and its related complications.

Some types of liver disease, especially those that are genetically induced, present early in life and progress rapidly. In most cases, liver disease develops over many years and often goes unnoticed until significant liver damage has already occurred.

Liver diseases lead to over two million deaths per year (cirrhosis, viral hepatitis, and liver cancer), accounting for about 4% of all deaths worldwide. However the number of deaths related to liver diseases might be underestimated, these diseases are the eleventh-leading cause of death [17].

The determination of TBA levels in pregnant women is considered to be the most important biomarker for diagnosis and monitoring of ICP, also known as obstetric cholestasis (OC) [12-14].

ICP is the most common liver disease that occurs during pregnancy; usually during the third trimester of pregnancy. The cause of ICP is not fully understood but it is believed to be multifactorial with genetic, environmental and hormonal factors being involved [18]. The reversible type of hormonally influenced cholestasis leads to a restricted bile flow through the gallbladder and thereby, to an accumulation of bile acids in the liver and possibly in the bloodstream [9,19].

The intrahepatic cholestasis of pregnancy is characterized by strong itching (pruritus) [13]. During ICP, TBA levels rise up to 220 µmol/L [14], leading to an increased risk of fetal distress, premature birth or even stillbirth. TBA concentrations above 40 µmol/L may be fetotoxic [13].

The incidence of ICP varies from 0.02% to 2.4% of pregnancies and about 70% of them present in the third trimester [18]. In addition, the incidence also varies significantly, depending on geographical location and ethnicity, with rates up to 15% in Chile and Bolivia and less than 1% in Europe [20, 21]. A higher incidence is seen in twin pregnancies, following in-vitro fertilization, in women older than 35 years with history of cholestasis in previous pregnancies and in women with history of biliary disease [21-23].