488 Case report
Pregnancies after transjugular intrahepatic portosystemic shunt for noncirrhotic portal hypertension Charlotte Nicolasa, Emma Ferranda, Louis d’Alterochea, Jean Ayoubb, Frederic Bastidesc, Jerome Potind and Jean-Marc Perarnaua With the growing role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension complications, a number of women of childbearing age are now being treated with TIPS. However, if pregnancy is unusual in patients with cirrhosis, it can occur in the case of noncirrhotic portal hypertension. To our knowledge, there are no data on pregnancy safety after TIPS insertion. We report the first case of a patient with noncirrhotic portal hypertension treated by TIPS who had two successful pregnancies. She presented with HIVassociated obliterative portopathy with recurrent variceal bleeding treated by TIPS. Pregnancies occurred later and progressed normally without maternal or fetal morbidity. There was no effect on TIPS patency, but only a moderate increase in the flow velocity in the portal vein, the stent, and
Introduction Portal hypertension is usually associated with a decrease in fertility because of the underlying liver disease [1–3], but pregnancy is possible, particularly in cases of noncirrhotic portal hypertension [1,2]. Although not clearly demonstrated, it is generally accepted that portal hypertension is increased in late pregnancy by compression of the vena cava by the gravid uterus [4]. Several cases of esophageal variceal bleeding during pregnancy have been reported, treated with the usual therapeutic resources and exceptionally by transjugular intrahepatic portosystemic shunt (TIPS) [5–7]. In contrast, no case of pregnancy has been reported in patients previously treated by TIPS so that there are currently no data on the feasibility and safety of pregnancy after TIPS insertion. We report the first case of a patient with noncirrhotic portal hypertension treated by TIPS who had two successful pregnancies later.
Case presentation A 39-year-old woman was admitted to the Department of Hepatogastroenterology of Tours University Hospital for the management of upper gastrointestinal bleeding in February 2005. This HIV-infected patient was under highly active antiretroviral therapy for 6 years. She presented an acute hematemesis with severe blood loss. Upper endoscopy showed esophageal varices with red spots and a band ligation was performed. She presented no clinical or biological signs of hepatocellular insufficiency. c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0954-691X
the hepatic artery. Thus, TIPS does not seem to impair progression of pregnancy. Eur J Gastroenterol Hepatol c 2014 Wolters Kluwer Health | Lippincott 26:488–490 Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2014, 26:488–490 Keywords: portal hypertension, pregnancy, transjugular intrahepatic portosystemic shunt Departments of aHepatogastroenterology, bUltrasound, Trousseau Hospital, Departments of cInfectious Diseases and dGynecology, Bretonneau Hospital, Tours, France Correspondence to Charlotte Nicolas, MD, Department of Hepatogastroenterology, Trousseau Hospital, 37 044 Tours Cedex 9, France Tel: + 33 2 47 47 59 65; fax: + 33 2 47 47 84 28; e-mail: [email protected] Received 17 November 2013 Accepted 8 January 2014
A transjugular hepatic biopsy showed no sinusoidal portal hypertension, with the hepatic vein pressure gradient at 4 mmHg. Anatomopathologic analysis was normal, except for some perisinusoidal fibrosis lesions. Abdominal tomodensitometry showed a distal thrombosis of the right portal branch, and an acquired protein S deficiency was diagnosed. The second endoscopy performed 4 weeks later showed grade 3 esophageal varices and gastroesophageal varices type 2 so that a TIPS procedure was preferred to subsequent variceal ligations. The portosystemic gradient was 15 mmHg before TIPS insertion and decreased to 8 mmHg after the insertion of a covered stent (Viatorr; Gore, Flagstaff, Arizona, USA), inflated to 9 mm. Another hepatic biopsy was performed during this procedure and showed obstructive portal venopathy with nodular regenerative hyperplasia. The Doppler ultrasound control at the first and fifth days after the procedure and then at 1 month confirmed shunt patency. The patient became pregnant 1 month after the procedure and a low-molecular-weight heparin regimen was initiated. The progression of pregnancy was normal and the Doppler ultrasound controls of the TIPS were satisfactory. At 37 weeks’ gestation, she delivered a healthy infant vaginally without complications, particularly without postpartum hemorrhage. The baby was a 2530 g female and the Apgar score was 10. The patient and the baby were discharged from the hospital 5 days later. Anticoagulant therapy was stopped 2 months later and the biannual ultrasound monitoring of the TIPS was continued. DOI: 10.1097/MEG.0000000000000048
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Pregnancies after TIPS Nicolas et al. 489
Fig. 1
Portal vein Velocity (cm/s)
T1
T2
Stent
Artery
T3
T1
T2
T3
Time (months after TIPS) M10 M13 M16 M23 M35 M52 M64 M67 M70 M74 M77
M1
M4
M7
Portal vein
55
48
62
63
53
43
46
32
63
45
63
59
52
44
Stent
47
89
92
75
70
67
72
59
67
96
60
80
54
66
Artery
39
44
83
66
49
36
30
23
45
38
57
67
77
46
Evolution of flow velocities during and outside of pregnancies. The pregnancy periods are shown in gray. M, month; T, pregnancy trimester; TIPS, transjugular intrahepatic portosystemic shunt.
Four years later, she had a second pregnancy. The progression of pregnancy was normal under anticoagulant therapy. No problem was observed during labor and a healthy baby boy of 3120 g was delivered. Apgar scores were 8 at 1 min and 10 at 5 min. Three years after the last delivery, TIPS remained permeable, the patient had no rebleeding, and the two children were healthy and remained negative for HIV. Figure 1 shows the evolution of the mean flow velocities during and outside of pregnancies. The mean flow velocities measured in the portal vein, the stent, and in the hepatic artery increased progressively during pregnancies until 1 month after the delivery. Therefore, comparing the flow velocities measured outside of pregnancies with those measured during the last trimester of pregnancies, we observed a mean increase of 22% in the portal vein (49–60 cm/s), 30% in the stent (66–86 cm/s), and 63% in the hepatic artery (46–75 cm/s).
Discussion Pregnancy in patients with portal hypertension is a rare situation because the most common cause of portal hypertension is cirrhosis [1]. Cirrhosis usually occurs after the reproductive years and leads to hormonal deficiency with anovulation and infertility, so that pregnancy in cirrhotic women is uncommon [1,2]. Noncirrhotic portal hypertension is less frequent, but fertility rates are normal in this case [2]. Both pregnancies that we observed occurred in a patient initially diagnosed with a noncirrhotic portal hypertension, described later by Mallet et al. [8] as nodular regenerative hyperplasia or by Schiano et al. [9] as hepatoportal sclerosis. Portal hypertension complications such as variceal bleeding seem to be more frequent during pregnancy,
especially during the second and third trimesters [2,10]. The main explanations are the compression of the inferior vena cava by the uterus, and the increased cardiac output and blood volume [3,4,10]. Variceal bleeding during pregnancy is associated with increased maternal mortality [2], abortion, and perinatal death [11]. The management of an acute variceal hemorrhage during pregnancy consists of hemodynamic stabilization and endoscopic variceal ligation [12] or injection sclerotherapy [3,11]. Vasoactive drugs might be avoided during pregnancy: vasopressin and terlipressin are contraindicated because they may induce labor [3] or cause fetal malformations [1,2], and no data are available on the safe use of somatostatin and its analogs during pregnancy. Three cases of TIPS for acute variceal bleeding during pregnancy have been reported [5–7]. Each time, TIPS was a rescue procedure for recurrent bleeding after an endoscopic treatment failure. In the three cases, the fetal radiation exposure was considered negligible because of radiation-sparing techniques and did not justify abortion for medical reasons [5–7]. Considering the maternal and fetal risk of variceal bleeding during pregnancy and the limited therapeutic possibilities, a prophylactic treatment could be relevant. b-Blocking agents such as propranolol are not contraindicated during pregnancy, although they are associated with neonatal hypoglycemia and bradycardia. However, the efficiency of b-blockers for the prevention of variceal bleeding during pregnancy is unknown. There is no recommendation for a prophylactic treatment and some authors propose an endoscopic control during the third trimester [1] with an endoscopic therapy (band ligation or sclerotherapy) in case of varices. For others, endoscopic sclerotherapy should be performed before conception and
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
490 European Journal of Gastroenterology & Hepatology 2014, Vol 26 No 4
an endoscopic evaluation should be repeated every trimester [12]. All agree that portosystemic shunt is a second-line treatment [5,6,12]. To our knowledge, the consequences of TIPS insertion on progression of pregnancy are unknown. This is the first report of two pregnancies after the TIPS procedure for noncirrhotic portal hypertension. We observed no effect of the pregnancy on TIPS patency, but only a moderate increase in the mean flow velocity in the portal vein, the stent, and the hepatic artery, which corrects itself postpartum. These small changes in flow remained without clinical consequences; no hemorrhage was observed. In contrast, no deleterious effect of the TIPS on pregnancy, labor, or delivery was observed. Finally, more data should be collected to confirm this first experience, but TIPS does not seem to prevent a successful pregnancy and can therefore be considered in the management of portal hypertension in women of childbearing age.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1
D’Alteroche L, Perarnau JM, Perrotin F, Bacq Y. Portal hypertension and pregnancy. Gastroenterol Clin Biol 2008; 32:541–546. 2 Russell MA, Craigo SD. Cirrhosis and portal hypertension in pregnancy. Semin Perinatol 1998; 22:156–165. 3 Lee WM. Pregnancy in patients with chronic liver disease. Gastroenterol Clin North Am 1992; 21:889–903. 4 Thornburg KL, Jacobson SL, Giraud GD, Morton MJ. Hemodynamic changes in pregnancy. Semin Perinatol 2000; 24:11–14. 5 Wildberger JE, Vorwerk D, Winograd R, Stargardt A, Busch N, Gu¨nther RW. New TIPS placement in pregnancy in recurrent esophageal varices hemorrhage – assessment of fetal radiation exposure. Rofo 1998; 169:429–431. 6 Savage C, Patel J, Lepe MR, Lazarre CH, Rees CR. Transjugular intrahepatic portosystemic shunt creation for recurrent gastrointestinal bleeding during pregnancy. J Vasc Interv Radiol 2007; 18:902–904. 7 Lodato F, Cappelli A, Montagnani M, Colecchia A, Festi D, Azzaroli F, et al. Transjugular intrahepatic portosystemic shunt: a case report of rescue management of unrestrainable variceal bleeding in a pregnant woman. Dig Liver Dis 2008; 40:387–390. 8 Mallet V, Blanchard P, Verkarre V, Vallet-Pichard A, Fontaine H, LascouxCombe C, et al. Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients. AIDS 2007; 21:187–192. 9 Schiano TD, Kotler DP, Ferran E, Fiel MI. Hepatoportal sclerosis as a cause of noncirrhotic portal hypertension in patients with HIV. Am J Gastroenterol 2007; 102:2536–2540. 10 Britton RC. Pregnancy and esophageal varices. Am J Surg 1982; 143: 421–425. 11 Aggarwal N, Sawhney H, Vasishta K, Dhiman RK, Chawla Y. Non-cirrhotic portal hypertension in pregnancy. Int J Gynaecol Obstet 2001; 72:1–7. 12 Starkel P, Horsmans Y, Geubel A. Endoscopic band ligation: a safe technique to control bleeding esophageal varices in pregnancy. Gastrointest Endosc 1998; 48:212–214.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Pregnancies after transjugular intrahepatic portosystemic shunt for noncirrhotic portal hypertension Charlotte Nicolasa, Emma Ferranda, Louis d’Alterochea, Jean Ayoubb, Frederic Bastidesc, Jerome Potind and Jean-Marc Perarnaua With the growing role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension complications, a number of women of childbearing age are now being treated with TIPS. However, if pregnancy is unusual in patients with cirrhosis, it can occur in the case of noncirrhotic portal hypertension. To our knowledge, there are no data on pregnancy safety after TIPS insertion. We report the first case of a patient with noncirrhotic portal hypertension treated by TIPS who had two successful pregnancies. She presented with HIVassociated obliterative portopathy with recurrent variceal bleeding treated by TIPS. Pregnancies occurred later and progressed normally without maternal or fetal morbidity. There was no effect on TIPS patency, but only a moderate increase in the flow velocity in the portal vein, the stent, and
Introduction Portal hypertension is usually associated with a decrease in fertility because of the underlying liver disease [1–3], but pregnancy is possible, particularly in cases of noncirrhotic portal hypertension [1,2]. Although not clearly demonstrated, it is generally accepted that portal hypertension is increased in late pregnancy by compression of the vena cava by the gravid uterus [4]. Several cases of esophageal variceal bleeding during pregnancy have been reported, treated with the usual therapeutic resources and exceptionally by transjugular intrahepatic portosystemic shunt (TIPS) [5–7]. In contrast, no case of pregnancy has been reported in patients previously treated by TIPS so that there are currently no data on the feasibility and safety of pregnancy after TIPS insertion. We report the first case of a patient with noncirrhotic portal hypertension treated by TIPS who had two successful pregnancies later.
Case presentation A 39-year-old woman was admitted to the Department of Hepatogastroenterology of Tours University Hospital for the management of upper gastrointestinal bleeding in February 2005. This HIV-infected patient was under highly active antiretroviral therapy for 6 years. She presented an acute hematemesis with severe blood loss. Upper endoscopy showed esophageal varices with red spots and a band ligation was performed. She presented no clinical or biological signs of hepatocellular insufficiency. c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0954-691X
the hepatic artery. Thus, TIPS does not seem to impair progression of pregnancy. Eur J Gastroenterol Hepatol c 2014 Wolters Kluwer Health | Lippincott 26:488–490 Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2014, 26:488–490 Keywords: portal hypertension, pregnancy, transjugular intrahepatic portosystemic shunt Departments of aHepatogastroenterology, bUltrasound, Trousseau Hospital, Departments of cInfectious Diseases and dGynecology, Bretonneau Hospital, Tours, France Correspondence to Charlotte Nicolas, MD, Department of Hepatogastroenterology, Trousseau Hospital, 37 044 Tours Cedex 9, France Tel: + 33 2 47 47 59 65; fax: + 33 2 47 47 84 28; e-mail: [email protected] Received 17 November 2013 Accepted 8 January 2014
A transjugular hepatic biopsy showed no sinusoidal portal hypertension, with the hepatic vein pressure gradient at 4 mmHg. Anatomopathologic analysis was normal, except for some perisinusoidal fibrosis lesions. Abdominal tomodensitometry showed a distal thrombosis of the right portal branch, and an acquired protein S deficiency was diagnosed. The second endoscopy performed 4 weeks later showed grade 3 esophageal varices and gastroesophageal varices type 2 so that a TIPS procedure was preferred to subsequent variceal ligations. The portosystemic gradient was 15 mmHg before TIPS insertion and decreased to 8 mmHg after the insertion of a covered stent (Viatorr; Gore, Flagstaff, Arizona, USA), inflated to 9 mm. Another hepatic biopsy was performed during this procedure and showed obstructive portal venopathy with nodular regenerative hyperplasia. The Doppler ultrasound control at the first and fifth days after the procedure and then at 1 month confirmed shunt patency. The patient became pregnant 1 month after the procedure and a low-molecular-weight heparin regimen was initiated. The progression of pregnancy was normal and the Doppler ultrasound controls of the TIPS were satisfactory. At 37 weeks’ gestation, she delivered a healthy infant vaginally without complications, particularly without postpartum hemorrhage. The baby was a 2530 g female and the Apgar score was 10. The patient and the baby were discharged from the hospital 5 days later. Anticoagulant therapy was stopped 2 months later and the biannual ultrasound monitoring of the TIPS was continued. DOI: 10.1097/MEG.0000000000000048
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Pregnancies after TIPS Nicolas et al. 489
Fig. 1
Portal vein Velocity (cm/s)
T1
T2
Stent
Artery
T3
T1
T2
T3
Time (months after TIPS) M10 M13 M16 M23 M35 M52 M64 M67 M70 M74 M77
M1
M4
M7
Portal vein
55
48
62
63
53
43
46
32
63
45
63
59
52
44
Stent
47
89
92
75
70
67
72
59
67
96
60
80
54
66
Artery
39
44
83
66
49
36
30
23
45
38
57
67
77
46
Evolution of flow velocities during and outside of pregnancies. The pregnancy periods are shown in gray. M, month; T, pregnancy trimester; TIPS, transjugular intrahepatic portosystemic shunt.
Four years later, she had a second pregnancy. The progression of pregnancy was normal under anticoagulant therapy. No problem was observed during labor and a healthy baby boy of 3120 g was delivered. Apgar scores were 8 at 1 min and 10 at 5 min. Three years after the last delivery, TIPS remained permeable, the patient had no rebleeding, and the two children were healthy and remained negative for HIV. Figure 1 shows the evolution of the mean flow velocities during and outside of pregnancies. The mean flow velocities measured in the portal vein, the stent, and in the hepatic artery increased progressively during pregnancies until 1 month after the delivery. Therefore, comparing the flow velocities measured outside of pregnancies with those measured during the last trimester of pregnancies, we observed a mean increase of 22% in the portal vein (49–60 cm/s), 30% in the stent (66–86 cm/s), and 63% in the hepatic artery (46–75 cm/s).
Discussion Pregnancy in patients with portal hypertension is a rare situation because the most common cause of portal hypertension is cirrhosis [1]. Cirrhosis usually occurs after the reproductive years and leads to hormonal deficiency with anovulation and infertility, so that pregnancy in cirrhotic women is uncommon [1,2]. Noncirrhotic portal hypertension is less frequent, but fertility rates are normal in this case [2]. Both pregnancies that we observed occurred in a patient initially diagnosed with a noncirrhotic portal hypertension, described later by Mallet et al. [8] as nodular regenerative hyperplasia or by Schiano et al. [9] as hepatoportal sclerosis. Portal hypertension complications such as variceal bleeding seem to be more frequent during pregnancy,
especially during the second and third trimesters [2,10]. The main explanations are the compression of the inferior vena cava by the uterus, and the increased cardiac output and blood volume [3,4,10]. Variceal bleeding during pregnancy is associated with increased maternal mortality [2], abortion, and perinatal death [11]. The management of an acute variceal hemorrhage during pregnancy consists of hemodynamic stabilization and endoscopic variceal ligation [12] or injection sclerotherapy [3,11]. Vasoactive drugs might be avoided during pregnancy: vasopressin and terlipressin are contraindicated because they may induce labor [3] or cause fetal malformations [1,2], and no data are available on the safe use of somatostatin and its analogs during pregnancy. Three cases of TIPS for acute variceal bleeding during pregnancy have been reported [5–7]. Each time, TIPS was a rescue procedure for recurrent bleeding after an endoscopic treatment failure. In the three cases, the fetal radiation exposure was considered negligible because of radiation-sparing techniques and did not justify abortion for medical reasons [5–7]. Considering the maternal and fetal risk of variceal bleeding during pregnancy and the limited therapeutic possibilities, a prophylactic treatment could be relevant. b-Blocking agents such as propranolol are not contraindicated during pregnancy, although they are associated with neonatal hypoglycemia and bradycardia. However, the efficiency of b-blockers for the prevention of variceal bleeding during pregnancy is unknown. There is no recommendation for a prophylactic treatment and some authors propose an endoscopic control during the third trimester [1] with an endoscopic therapy (band ligation or sclerotherapy) in case of varices. For others, endoscopic sclerotherapy should be performed before conception and
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
490 European Journal of Gastroenterology & Hepatology 2014, Vol 26 No 4
an endoscopic evaluation should be repeated every trimester [12]. All agree that portosystemic shunt is a second-line treatment [5,6,12]. To our knowledge, the consequences of TIPS insertion on progression of pregnancy are unknown. This is the first report of two pregnancies after the TIPS procedure for noncirrhotic portal hypertension. We observed no effect of the pregnancy on TIPS patency, but only a moderate increase in the mean flow velocity in the portal vein, the stent, and the hepatic artery, which corrects itself postpartum. These small changes in flow remained without clinical consequences; no hemorrhage was observed. In contrast, no deleterious effect of the TIPS on pregnancy, labor, or delivery was observed. Finally, more data should be collected to confirm this first experience, but TIPS does not seem to prevent a successful pregnancy and can therefore be considered in the management of portal hypertension in women of childbearing age.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1
D’Alteroche L, Perarnau JM, Perrotin F, Bacq Y. Portal hypertension and pregnancy. Gastroenterol Clin Biol 2008; 32:541–546. 2 Russell MA, Craigo SD. Cirrhosis and portal hypertension in pregnancy. Semin Perinatol 1998; 22:156–165. 3 Lee WM. Pregnancy in patients with chronic liver disease. Gastroenterol Clin North Am 1992; 21:889–903. 4 Thornburg KL, Jacobson SL, Giraud GD, Morton MJ. Hemodynamic changes in pregnancy. Semin Perinatol 2000; 24:11–14. 5 Wildberger JE, Vorwerk D, Winograd R, Stargardt A, Busch N, Gu¨nther RW. New TIPS placement in pregnancy in recurrent esophageal varices hemorrhage – assessment of fetal radiation exposure. Rofo 1998; 169:429–431. 6 Savage C, Patel J, Lepe MR, Lazarre CH, Rees CR. Transjugular intrahepatic portosystemic shunt creation for recurrent gastrointestinal bleeding during pregnancy. J Vasc Interv Radiol 2007; 18:902–904. 7 Lodato F, Cappelli A, Montagnani M, Colecchia A, Festi D, Azzaroli F, et al. Transjugular intrahepatic portosystemic shunt: a case report of rescue management of unrestrainable variceal bleeding in a pregnant woman. Dig Liver Dis 2008; 40:387–390. 8 Mallet V, Blanchard P, Verkarre V, Vallet-Pichard A, Fontaine H, LascouxCombe C, et al. Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients. AIDS 2007; 21:187–192. 9 Schiano TD, Kotler DP, Ferran E, Fiel MI. Hepatoportal sclerosis as a cause of noncirrhotic portal hypertension in patients with HIV. Am J Gastroenterol 2007; 102:2536–2540. 10 Britton RC. Pregnancy and esophageal varices. Am J Surg 1982; 143: 421–425. 11 Aggarwal N, Sawhney H, Vasishta K, Dhiman RK, Chawla Y. Non-cirrhotic portal hypertension in pregnancy. Int J Gynaecol Obstet 2001; 72:1–7. 12 Starkel P, Horsmans Y, Geubel A. Endoscopic band ligation: a safe technique to control bleeding esophageal varices in pregnancy. Gastrointest Endosc 1998; 48:212–214.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
