Obstetric cholestasis with elevated gamma glutamyl transpeptidase: incidence, presentation and treatment

Obstetric cholestasis (OC) may cause severe pruritus in the mother and lead to fetal distress and stillbirth. The etiology of OC is multifactorial, but includes inherited dysfunction of bile canalicular transporters. One of these, multidrug resistant protein 3 (MDR3), a phospholipid transporter, when dysfunctional is associated with elevated levels of gamma glutamyl transpeptidase (GGT). The aim of the present study was to assess the incidence of OC associated with elevated GGT. We compared the natural history of a cholestatic pregnancy and the efficacy of ursodeoxycholic acid (URSO) in OC patients grouped according to a normal or raised GGT level.

Eighty-one patients with OC were analyzed. OC was diagnosed in patients with pruritus and elevated serum bile acids (SBA). Fifty-seven consenting volunteer patients (70%) were treated with URSO.

Elevated GGT at presentation was found in 21 patients (30%) and was associated with significantly higher serum levels of aspartate transaminase (AST), bilirubin (BIL) and SBA. OC presented at approximately the same gestation week in both groups of patients. In patients not treated with URSO, liver function tests (LFT) showed no significant change from the time of diagnosis to delivery. Patients from both groups responded to URSO with significant improvement in their AST and alanine aminotransferase (ALT) levels, but SBA fell significantly only in the normal GGT group.

An elevated GGT occurs in less than one-third of patients with OC in the UK and, when present, is associated with greater impairment of LFT, but no difference in gestational age at onset. Treatment with URSO appears to be safe and significantly improves LFT in patients with OC, with the exception of SBA in the high GGT group.