Therapeutic plasma exchange as a novel treatment for severe intrahepatic cholestasis of pregnancy: Case series and mechanism of action

Abstract

Introduction Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids. The pruritus can be severe, and pharmacological options achieve inconsistent symptomatic improvement. Raised bile acids are linearly associated with adverse fetal outcomes, with existing management of limited benefit. We hypothesised that therapeutic plasma exchange removes pruritogens and lowers total bile acid concentrations, and improves symptoms and biochemical abnormalities in severe cases that have not responded to other treatments. Methods Four women with severe pruritus and hypercholanemia were managed with therapeutic plasma exchange. Serial blood biochemistry and visual analogue scores of itch severity were obtained. Blood and waste plasma samples were collected before and after exchange; individual bile acids and sulfated progesterone metabolites were measured with HPLC‐MS, autotaxin activity and cytokine profiles with enzymatic methods. Results were analysed using segmental linear regression to describe longitudinal trends, and ratio t tests. Results Total bile acids and visual analogue itch scores demonstrated trends to transiently improve following plasma exchange, with temporary symptomatic benefit reported. Individual bile acids (excluding the drug ursodeoxycholic acid), and the sulfated metabolites of progesterone reduced following exchange (P = .03 and P = .04, respectively), whilst analysis of waste plasma demonstrated removal of autotaxin and cytokines. Conclusions Therapeutic plasma exchange can lower potentially harmful bile acids and improve itch, likely secondary to the demonstrated removal of pruritogens. However, the limited current experience and potential complications, along with minimal sustained symptomatic benefit, restrict its current use to women with the most severe disease for whom other treatment options have been exhausted.

Intrahepatic cholestasis of pregnancy resistant to both therapeutic plasma exchange and albumin dialysis

“… 12 Since then, there have been various attempts to use this therapy in cases resistant to pharmaceutical treatment with encouraging results. 10 11 However, Covach and colleagues first reported a case of ICP resistant even to repeated plasma exchange. 9 Similarly, our patient also showed a lack of improvement with plasma exchange and albumin dialysis, thus raising the question of how effective this therapy truly is.…”

“…In some case studies, therapeutic plasma exchange has shown good effects while other investigators reported no improvement by this therapy. [9][10][11][12] To this day, the rate of successful plasma exchange or the factors influencing it are unknown.…”

Pregnancy complicated by refractory severe hypercholanaemia from sodium taurocholate co‐transporting polypeptide deficiency

“…Therapeutic plasma exchange involves the extracorporeal separation of blood components for the targeted removal of pathogenic plasma components. Its safety has been demonstrated in pregnancy, and more recently has been shown to be an effective adjunct therapy in the treatment of ICP with severe refractory hypercholanaemia 16,17 . For this reason, TPE was trialed for this patient, as BA levels were unable to be controlled by conventional therapies (ursodeoxycholic acid, rifampicin, cholestyramine).…”

“…Its safety has been demonstrated in pregnancy, and more recently has been shown to be an effective adjunct therapy in the treatment of ICP with severe refractory hypercholanaemia. 16,17 For this reason, TPE was trialed for this patient, as BA levels were unable to be controlled by conventional therapies (ursodeoxycholic acid, rifampicin, cholestyramine). As shown in Figure 3, BA levels initially were successfully lowered post-TPE, with an associated reduction in fasting BA levels over time.…”

Effect of ursodeoxycholic acid therapy due to pregnant intrahepatic cholestasis on chemerin and irisin levels

“…ICP pharmacotherapy aims to eliminate or lower the effects of subjective symptoms, as well as bringing back the correct levels of bile acids and intrahepatic transaminase (Ökdemir et al, ). One of the recommended therapies is treatment with ursodeoxycholic acid (Ovadia et al, ). This drug is characterized by a high safety profile for both the mother and the fetus (Chappell et al, ), also when applied in high doses (1.5–2 g/24 hr; Lee, Incerpi, Miller, Pathak, & Goodwin, ).…”