Non-cirrhotic portal hypertension in pregnancy due to schistosomiasis: A case series

Abstract

The presence of non-cirrhotic portal hypertension in pregnancy poses a challenging clinical scenario as it predisposes women to several life-threatening complications such as variceal haemorrhage, splenic artery aneurysm, pulmonary hypertension and bacterial peritonitis. The haemodynamic changes in pregnancy along with the demands of a growing fetus may worsen the severity of pre-existing non-cirrhotic portal hypertension. In this case series, we discuss four cases of non-cirrhotic portal hypertension in pregnancy in a low to middle income setting and review the literature related to this condition.

Keywords

Non-cirrhotic portal hypertension varices variceal haemorrhage

Introduction

Portal hypertension is characterised by an abnormal increase in pressure in the portal system. While this is commonly associated with liver cirrhosis, this can occur in its absence.¹ This condition is known as non-cirrhotic portal hypertension (NCPH) and it can be particularly challenging to manage when it occurs during pregnancy.

In this article, we present four cases of NCPH associated with schistosomiasis that occurred during pregnancy. We discuss the medical, endoscopic and obstetric management options for this condition and the importance of a patient-centred, multidisciplinary approach to managing pregnant women with portal hypertension.

Case series

Patient 1

A 33-year-old woman in her second pregnancy, presented at 6 weeks’ gestation. The patient had previously been diagnosed with NCPH due to hepatic schistosomiasis, complicated by hypersplenism and thrombocytopenia. She had undergone endoscopic band ligation two years prior to her presentation, but subsequently been lost to follow-up. In addition, the patient had a history of longstanding epilepsy that was diagnosed in childhood and has been controlled on levetiracetam.

During the pregnancy, the patient experienced no variceal haemorrhage, however she underwent three surveillance endoscopies. The first was performed at five weeks’ gestation; and four columns of grade 3 varices and features of portal hypertensive gastropathy were noted, and the varices were banded with minimal bleeding. At weeks 12 and 35, three columns of moderate-sized varices with collapsibility on insufflation were noted, but no stigmata of recent or current bleeding.

The patient was treated with a non-selective beta-blocker, propranolol, and diuretics (furosemide and spironolactone). She continued taking levetiracetam throughout. Her thrombocytopenia persisted throughout pregnancy.

Due to the previous caesarean section, an elective caesarean section was planned for 36 weeks of gestation. The patient went into preterm labour at 35 weeks and 3 days of gestation and required an emergency caesarean section under general anaesthesia with platelet cover as her platelet count at delivery was 50 × 10⁹/L. A healthy female neonate weighing 2400 g was delivered, and the patient discharged 2 days later. Postpartum liver elastography confirmed the absence of hepatic fibrosis.

Patient 2

A 41-year-old woman in her third pregnancy, living with HIV and known with NCPH secondary to hepatic schistosomiasis, for routine follow-up at 10 weeks’ gestation. She had previously been diagnosed with iron deficiency anaemia, thrombocytopaenia and grade 2 oesophageal varices.

Throughout her pregnancy, the patient was maintained on furosemide, propranolol and oral iron supplementation. Endoscopy was performed at 10 weeks’ gestation as the patient had no recent endoscopic surveillance prior to conceiving. Endoscopy revealed 2 columns of grade 2 oesophageal varices, which were successfully treated with band ligation. Portal hypertensive gastropathy and enteropathy were also noted.

At 13 weeks’ gestation, the patient had an uncomplicated spontaneous miscarriage. Platelet count at the time was 35 × 10⁹/L. Post-pregnancy liver elastography confirmed the absence of hepatic fibrosis.

Patient 3

A 26-year-old woman in her second pregnancy presented to the Antenatal Clinic (ANC) at 26 weeks’ gestation with severe iron deficiency anaemia and thrombocytopenia as well as clinical features of portal hypertension. Endoscopy at this time revealed large grade 3 oesophageal varices with features of portal hypertensive gastropathy. Endoscopic band ligation was performed, and the patient was initiated on propranolol, spironolactone, a proton pump inhibitor and received parenteral and oral iron supplementation.

Further investigations confirmed positive schistosomiasis serology and abdominal ultrasound revealed ascites and massive splenomegaly. The patient received a single therapeutic dose of praziquantel while hospitalised.

Repeat endoscopy at 31 weeks’ gestation revealed large grade 3 varices, which were re-banded. The patient was advised to undergo repeat endoscopy 6 weeks postpartum and kept on a non-selective beta-blocker (carvedilol) and spironolactone.

The patient underwent an elective caesarean section at 39 weeks’ gestation under neuraxial anaesthesia without complications. The platelet count at the time of delivery was 71 × 10⁹/L. A healthy male neonate weighing 2680 g was delivered. However, after discharge the patient was lost to follow up.

Patient 4

A 31-year-old woman in her third pregnancy, presented at 27 weeks’ gestation to the ANC with ascites, splenomegaly, iron deficiency anaemia and thrombocytopenia. Endoscopy revealed five columns of large grade 3 varices with portal gastroenteropathy and high-risk endoscopic features of imminent bleeding. Five bands were deployed with good effect and the patient was commenced on propranolol.

Tests for viral hepatitis, HIV and autoimmune hepatitis were negative. However, the patient had a strong history of swimming in freshwater lakes and schistosomiasis serology was positive. She received a single dose of praziquantel upon diagnosis.

At 35 weeks’ gestation, the patient presented with haematemesis, and endoscopy revealed five columns of grade 3 varices, which were banded despite the absence of an active bleeding site. On admission the patient was started on an octreotide infusion, prophylactic ceftriaxone and two units of packed red cells.

After the initial presentation, she received parenteral doses of iron, a non-selective beta-blocker and oral iron supplementation. She had a normal liver profile and a normal coagulation profile throughout the course of her pregnancy.

Delivery occurred at 36 weeks’ gestation via an emergency caesarean section for fetal distress. A well female neonate weighing 2090 g was delivered. The caesarean section was done under general anaesthesia with platelet cover. There was significant blood loss of 700 ml, and the patient required two units of packed red blood cells. The patient was planned to follow up at the Liver Clinic for workup for a possible trans-jugular intrahepatic porto-systemic shunt (TIPSS) due to the high risk of bleeding and high-risk varices; however, she was subsequently lost to follow-up.

Discussion

Pathophysiology of portal hypertension

Portal hypertension, defined as a hepatic venous pressure gradient (HVPG) greater than 5 mmHg, is caused by resistance to blood flow within the portal venous system. In high-income countries this is usually caused by liver cirrhosis, however, in many parts of the world, Africa included, NCPH due to hepatic schistosomiasis predominates.² Causes of NCPH can be classified according to their location in relation to the liver: pre-, intra- and post-hepatic. Pre-hepatic causes of portal hypertension are primarily caused by an obstruction occurring in the vascular system proximal to the liver, such as portal or splenic vein thrombosis whilst post-hepatic causes occur as a result of obstruction distal to the liver, commonly due to inferior vena cava or hepatic vein obstruction.² Intrahepatic causes of portal hypertension are further divided into pre-, intra- and post-sinusoidal causes and are listed in Table 1.

Table 1.

Causes of intra-hepatic portal hypertension.²

Pre-sinusoidal	Sinusoidal	Postsinusoidal
Congenital (adult polycystic liver disease, congenital hepatic fibrosis, arteriovenous fistulas)	Metabolic, i.e., non-alcoholic fatty liver disease	Budd-Chiari syndrome
Biliary disease	Inflammatory, i.e., viral hepatitis	Vascular malignancies, i.e., epithelioid haemangioendothelioma
Neoplastic portal vein obstruction	Drug or toxin related	Granulomatous phlebitis, i.e., sarcoidosis
Granulomatous liver lesions	Infiltrative diseases, i.e., gauchers, mastocytosis	Hepatic vein phlebosclerosis
Idiopathic non-cirrhotic portal hypertension	Acute fatty liver of pregnancy
Schistosomiasis (S. Mansoni)	Amyloidosis

Clinical features of portal hypertension most commonly include the development of varices and ascites as well as splenomegaly. Common complications include variceal bleeding, spontaneous bacterial peritonitis (SBP) and hypersplenism, and rarer complications such as hepatorenal and hepatopulmonary syndromes as well as portopulmonary hypertension can also occur.

In sub-Saharan Africa, Schistosoma mansoni affects more than 54 million people.³ Approximately 10% of patients infected will develop hepatosplenic schistosomiasis (HSS) and subsequent portal hypertension.^3,4 During the early stages of infection, the mechanism is driven by pre-sinusoidal intrahepatic infection. However, as the disease progresses periportal (Symmers) fibrosis occurs, with architectural distortion at the sinusoidal level. Synthetic liver dysfunction is uncommon in the setting of HSS alone, but may occur in the setting of co-existing liver disease.³ Mortality may occur in up to 29% of patients with a delayed presentation. It is important to note that 42% of patients with longstanding HSS will go on to develop peri-portal fibrosis (PPF)³ and this must not be mistaken for cirrhosis. This differentiation may be made with various modalities, such as liver elastography where the findings of HSS are usually that of mild PPF.⁴

Changes in liver physiology in pregnancy

As a result of increased plasma volume as well as portal venous blood flow, the liver volume increases throughout pregnancy. This may be associated with worsening portal hypertension particularly in patients who have underlying chronic liver disease. Splenic size also increases significantly, and all these changes need to be considered when we evaluate patients with suspected or confirmed portal hypertension. Elastography has also shown that liver stiffness and steatosis increases throughout pregnancy and returns to normal by two months post-partum.¹

The effect of pregnancy on portal hypertension

Clinicians should be aware that an increase in plasma volume in the second trimester, compression of the inferior vena cava by the gravid uterus in the third trimester as well as repeated Valsalva manoeuvres during labour and delivery may all result in increased pressure in the splanchnic circulation. These increase the risk of variceal bleeding in women with portal hypertension.^5,6 Furthermore, increased levels of progesterone during pregnancy result in a significant increase in systemic vascular resistance, which contributes largely towards a ‘high-output’ state.⁷ Whilst variceal bleeding may occur in 4.3% to 34% of pregnancies it is important to note that patients with NCPH are at a lower risk of mortality (2–6%) and termination of pregnancy (29%) when compared to patients with cirrhosis (18–50%).^8,9 Fetal mortality rates in patients with cirrhotic portal hypertension vary from 10–66%. Ascites is uncommon in pregnant patients with NCPH when compared to patients with cirrhosis (0.8–10%) and usually resolves in the post-partum period. Splenic artery aneurysm is a rare but life-threatening complication, with the highest risk being in the third trimester. Fetal and maternal mortality rates are reported as 95% and 75% respectively.⁹ Additionally, the incidence of pulmonary hypertension in patients with hepato-splenic schistosomiasis is relatively low (5–10%) but it is associated with significant maternal mortality.^10,11

Diagnosis

Patients with NCPH may present with abdominal discomfort related to splenomegaly or the incidental finding of a cytopenia. This may be related to congestion, in the setting of portal hypertension, or due to reticuloendothelial hyperplasia. Importantly, as the pathology in NCPH is pre-sinusoidal, features of chronic liver disease such as spider telangiectasia, gynaecomastia and palmar erythema or features of decompensated liver failure such as jaundice, bleeding diathesis and encephalopathy are rare. Clinically significant portal hypertension (CSPH) is defined as the development of oesophageal varices and ascites, which typically arise when the HVPG is above 10 mmHg. As portal pressure increases, this is associated with variceal bleeding and further increases predict the development of complications such as decompensation events such as SBP and hepatorenal syndrome.^12,13

The normal range for portal pressure is 4–8 mmHg. The HVPG is the current gold standard for diagnosis and a HVPG value of 5 mmHg is diagnostic of intra-sinusoidal portal hypertension. It has no use in the diagnosis of pre-sinusoidal portal hypertension, such as that which occurs in HSS. A normal value, however, can differentiate between pre- and intra-hepatic portal hypertension.¹⁴

While HPVG is the gold standard for measurement of portal hypertension it is invasive and seldom performed outside expert centres. Various non-invasive tests using serological and clinical parameters correlate with cirrhosis. They are widely used in clinical practice in the setting of viral hepatitis and fatty liver disease and may predict portal hypertension and the risk of developing complications. Von Willebrand Factor (vWF), osteopontin and the VITRO score (vWF/Thrombocyte ratio) are serological markers that are predictors of CSPH. These parameters are not in widespread use in clinical practice and are yet to be validated in pregnancy.^15,16

Ultrasound features such as splenic size, ascites, development of collaterals, recanalization of the umbilical veins as well as Doppler evaluation of splenic and hepatic artery resistance indices are specific signs of CSPH. Their presence, particularly in cirrhosis, is almost diagnostic of portal hypertension. The sensitivity however is only 40–70% so their absence does not rule out CSPH. Transient elastography, acoustic wave force impulse, shear-wave elastography and magnetic resonance elastography are non-invasive measures of liver stiffness and the latter three have added benefit of assessing the liver parenchyma which may be helpful in surveillance for hepatocellular carcinoma particularly in patients with cirrhosis. These modalities are also safe in pregnancy, but appropriate thresholds must be evaluated in this population.^15,16

Oesophagogastroduodenoscopy remains the most important for diagnosis and management of portal hypertension. It is safe in pregnancy but may be appropriate to defer until the second trimester when there is maximal increase in portal hypertension. However, endoscopy is recommended on presentation in cases where there has been no preconceptual screening.⁹ Care should be taken to avoid fetal bradycardia by careful positioning in the left lateral position and avoiding over-sedation and the patient should be carefully co-managed with a multidisciplinary team comprising obstetricians, gastrohepatologists, obstetric physicians and anaesthetists.

Medical management of portal hypertension in pregnancy

The medical management of portal hypertension focuses on the prevention of complications related to the disease; the prevention of bleeding from varices and reduction in ascitic fluid production, as well management of the underlying cause of the portal hypertension. Ideally, women of childbearing age with established portal hypertension should be diagnosed, appropriately counselled, and their therapy optimised prior to pregnancy.

Prevention of variceal bleeding

Given that bleeding from gastroesophageal varices carries a high maternal mortality rate, the prevention of this complication is a key aspect in the care of pregnant women with portal hypertension.⁵ The American Association for the Study of Liver Diseases (AASLD) recommends that all women with liver cirrhosis undergo preconception screening for oesophageal varices within one year prior to conception.^5,17 Alternatively, endoscopic screening can be done in the second trimester as the highest risk for variceal haemorrhage occurs in the second and third trimesters.¹⁷ Guidance does not extend to NCPH, likely due to the fact that mortality rates are lower in this group compared to patients with cirrhosis as noted above.⁹ However, in patients with known portal hypertension this approach is feasible.⁵

Non-selective beta-blockers, including carvedilol, propranolol and nadolol, are the only drugs currently recommended for primary prophylaxis of variceal bleeding. These drugs act by decreasing cardiac output and by causing splanchnic vasoconstriction resulting in a reduction in portal pressure. They also lead to a 50% reduction in first variceal bleed in patients with portal hypertension.^7,18 The use of beta-blockers in pregnant women with portal hypertension has been extrapolated from non-pregnant patient populations and concerns have been raised given the risk of intrauterine growth restriction (IUGR), fetal bradycardia and neonatal hypoglycaemia.^9,19 The benefit of reducing variceal bleeding in pregnant women with portal hypertension outweighs the risks associated with beta-blockers and, following counselling and shared decision making, these drugs should be continued..^9,20,21 Furthermore, the newer carvedilol may be more effective in reducing portal pressures²⁰ and is associated with a lower incidence of IUGR thus making it an appealing drug for the primary and secondary prevention of variceal haemorrhage in pregnant women²²

Management of variceal bleeding

Variceal bleeding in pregnancy should be managed according to international guidelines, with a focus on early endoscopy and appropriate medical management. Medical therapy with vasoactive agents should be initiated while endoscopy is planned and continued for 2–5 days from onset of bleeding.¹⁴ These drugs, including terlipressin, vasopressin and octreotide, work by decreasing blood flow through the portal system and have been shown to improve haemostasis, reduce length of stay and reduce mortality in the setting of cirrhotic portal hypertension. Terlipressin is not recommended for use in pregnancy as it has an oxytocic effect and can cause uterine contractions and impair uterine blood flow. Furthermore, it may be associated with congenital abnormalities.²³ Octreotide has been used safely in a series of pregnant mothers with acromegaly and is thus the drug of choice in this patient population.^5,19,24,25

Outside of pregnancy, a conservative transfusion strategy (aimed at achieving a haemoglobin level between 7 and 8 g/dL) is associated with lower transfusion related adverse events as well as a lower risk of rebleeding.¹⁴ However, in pregnancy higher transfusion targets may be appropriate. Antibiotic prophylaxis is indicated in patients with hepatocellular dysfunction and cirrhosis.

Management of ascites

Ascites is rare in pregnancy and less commonly seen in NCPH (when compared to cirrhotic portal hypertension); its development is considered a poor prognostic sign.¹ When ascites is present treatment consists of dietary sodium restriction and the use of diuretics. Despite proven efficacy in the management of ascites, the mineralocorticoid receptor antagonists (MRAs) spironolactone is not currently recommended for use in pregnancy due to the theoretical risk of feminisation of male fetuses given spironolactone's affinity for androgen receptors. However, these recommendations arise from animal studies where an association between feminisation of male fetuses was seen in rats exposed to spironolactone, in late gestation, at five times the recommended human dose. Furthermore, in 17 published case reports, one pregnancy, with spironolactone exposure from conception to 5 weeks’ gestation, resulted in a male infant born with ambiguous genitalia.²⁶ Eplerenone has a lesser affinity for androgen receptors thus, in theory, is less likely to cause feminisation of male fetuses.¹¹ Clinicians are advised to counsel women in their care on the known risks and benefits of the MRAs and engage in shared decision making when considering their use.²⁷ Furosemide, however, can be used with caution taking into account the potential for electrolyte disturbances and the risk of hypovolaemia.^23,28

Specific management

The underlying cause of the portal hypertension should be identified, ideally prior to conception, and managed accordingly. This includes the treatment of schistosomiasis, as antihelminthic therapy is readily available and, praziquantel in particular, safe in pregnancy.^29,30 However, whilst therapy with praziquantel reduces the incidence of hepatic disease and portal hypertension, data is limited for its use in chronic schistosomiasis and those with established CSPH.³¹

Endoscopic and surgical management of portal hypertension in pregnancy

Endoscopic management of portal hypertension

Endoscopy can be performed safely in pregnancy.^17,32 During endoscopic procedures, the patient should be placed in the left lateral position to minimize compression of the aorta and inferior vena cava with subsequent reduction in uterine and placental perfusion.^17,23 Conscious sedation with benzodiazepines (midazolam), propofol or ketamine is preferred. These drugs should be administered at the lowest effective dose and the duration of the endoscopy should be limited as far as possible.^23,32 When high-grade varices with endoscopic features of imminent variceal haemorrhage are present, prophylactic endoscopic band ligation is a feasible management strategy^14,32 particularly in resource poor settings where access to emergency expert endoscopy services may be limited. Endoscopic sclerotherapy is less favourable in pregnancy due to a risk of sclerosant embolism to the placenta resulting in placental insufficiency,²³ however it remains the endoscopic therapeutic modality of choice in the management of bleeding gastric varices. Endoscopic variceal band ligation of oesophageal varices is associated with lower rebleeding and mortality rates when compared to sclerotherapy.³²

In the event of ongoing or recurrent variceal haemorrhage despite endoscopic band ligation, temporary tamponade by placement of a balloon tamponade device or a self-expanding lumen apposing metal stent (LAMS) should be performed as a secondary endoscopic procedure.¹⁴ These devices can be placed without fluoroscopy therefore minimising radiation exposure to the patient and fetus. Oesophageal balloon tamponade devices are associated with complications such as aspiration pneumonia, rebleeding with balloon deflation and oesophageal perforation and should be deflated within 24 h of placement. In recent years, the oesophageal LAMS has become the preferred method of oesophageal tamponade and salvage therapy and offers the following advantages: lower risk of oesophageal perforation, longer duration of placement (up to 7 days) and allows early reinitiation of enteral feeding.³³ Placement of an oesophageal LAMS allows the medical team to optimize patients for procedures aimed at definitive management of portal hypertension such as radiological or surgical interventions.

Trans-jugular intrahepatic porto-systemic shunt

In the management of oesophageal varices, TIPSS is a salvage strategy for patients in whom pharmacological and endoscopic strategies have failed to achieve or maintain haemostasis. The utility of TIPSS in pregnancy is limited by maternal and fetal radiation exposure and care should be taken to minimize the duration of fluoroscopy during TIPSS placement. In NCPH due to HSS, TIPSS has been associated with an increased risk of shunt dysfunction and occlusion with higher rates of repeat intervention.¹²

Surgical management of portal hypertension

Several surgical procedures can be performed to reduce portal pressures. These include distal splenorenal shunts and oesophagogastric devascularization with splenectomy.^12,14,17 There is limited data regarding the use of these procedures in pregnancy and they should only be considered in discussion with the patient and a multidisciplinary team when medical and endoscopic therapies have failed.

Splenic artery aneurysm

The development of a splenic artery aneurysm can be present in 0.1–0.2% of patients with portal hypertension.^6,20 The physiological changes that occur in pregnancy, including increased oestrogen levels and plasma blood volume can result in splenic artery aneurysm rupture in 25% of pregnant women with portal hypertension.^6,20 The risk of rupture is highest in the second and third trimester and is associated with maternal mortality of up to 80%.^19,20 When a splenic artery aneurysm is identified pre-conception, interventional transcatheter embolization is a less invasive management strategy that can be considered. Surgical resection of the aneurysm with splenectomy is recommended for management of imminent or established aneurysmal rupture.

Pulmonary hypertension

Pulmonary hypertension can complicate HSS with a prevalence ranging from 8 to 20%, depending on the diagnostic modality.^34–36 [This condition arises by multifactorial mechanisms including Schistosoma ova migration into the pulmonary vasculature (resulting in pulmonary arterial vasculopathy) as well as portopulmonary hypertension.³⁷] The presence of pulmonary hypertension in pregnancy is associated with adverse fetal and maternal outcomes and current guidance is that pregnancy should be avoided. We recommend referral to a specialist centre for management of these patients.³⁸

Liver transplantation

Liver transplantation is the definitive management of cirrhotic portal hypertension. However, in NCPH with preserved hepatocellular function, HSS in particular, liver transplantation is not routinely indicated.³⁹ Only 19 cases of liver transplantation during pregnancy have been reported.⁴⁰

Obstetric management of women with NCPH

Preconceptual care

The majority of pregnant women with NCPH are diagnosed prior to pregnancy, with only 10–15% of patients diagnosed during pregnancy.⁹ Women with well-compensated NCPH, with normal synthetic liver function, have normal fertility.⁹ It is thus imperative that they are counselled on the risks associated with portal hypertension in pregnancy, namely an increased risk of fetal growth restriction, preterm birth and postpartum haemorrhage (PPH). Miscarriage, stillbirths and preeclampsia are not increased in stable disease.¹⁹ Barrier contraception and intrauterine contraceptive devices are recommended for fertility regulation while oestrogen-containing contraceptives are contraindicated due to the risk of hepatic cholestasis.⁹ Endoscopy, echocardiography and imaging modalities (both ultrasound and cross-sectional) are indicated for surveillance in patients with CSPH and can assist in identifying complications.

Antenatal care

Women with portal hypertension should be managed in a tertiary institution by a multidisciplinary team comprising of obstetricians, obstetric physicians, maternal and fetal medicine specialists, gastroenterologists, hepatologists, obstetric anaesthetists and neonatologists.

Baseline and monthly complete blood count, liver chemistry tests, renal function tests and coagulation profiles are imperative. NCPH often manifests with a bicytopenia (red cells and platelets) necessitating the need for iron replacement to prevent and/or treat iron deficiency anaemia.^9,19 Antenatal visits at least every 2 to 4 weeks are recommended.

As noted above, non-selective beta-blockers are recommended and should be continued throughout the pregnancy after discussion with the patient on risks and benefits. Routine fetal anatomy assessments at 12 and 20 weeks of gestation by a fetal medicine specialist are the standard of care. Given the increased risk of fetal growth restriction, serial ultrasound scans to assess fetal growth should be performed at 24, 28, 32 and 36 weeks. The effect of portal hypertension on uterine artery Doppler indices is unknown. While expression of pregnancy-associated plasma protein A (PAPP-A), and beta-human chorionic gonadotrophin (β-hCG) are increased in liver disease, the impact of this on screening for aneuploidies and preeclampsia is not known.⁹ There is also a non-significant increase in alpha-feto protein levels in pregnant women with schistosomiasis.³⁴

Delivery

Delivery should be planned by the multidisciplinary team in conjunction with the patient and should take place in an institution capable of administering intensive obstetric care and with the availability of blood products. In the absence of complications, there is no routine indication for preterm delivery.¹⁹ No mode of delivery has been shown to be superior, however the Asian Pacific Association for the Study of the Liver (APASL) recommend vaginal delivery for most women.¹⁹ Similarly, AASLD recommend an assisted vaginal delivery to reduce the risk of variceal rupture due to an increase in intra-abdominal pressure with straining. Caesarean section is recommended for obstetric indications, but care should be taken to identify abdominal wall varices, as there is a risk of bleeding from direct injury to these vessels. An increased risk of postpartum ascites has also been noted in these women.⁵ A platelet count of at least 50 × 10⁹/L is recommended for caesarean section.⁴¹ Anaesthetic concerns should also be considered in pregnant women with portal hypertension. As liver synthetic function, and thus coagulation, is usually maintained in women with schistosomiasis-related NCPH neuraxial anaesthesia can be considered for both caesarean and vaginal delivery, provided platelets counts are above the thresholds recommended by local and international guidelines.^42,43

Postpartum care

There is an increased risk for PPH in women with cirrhosis, likely due to thrombocytopenia or an increased rate of caesarean deliveries. While it is unclear whether this translates to an increased risk in NCPH, vigilant monitoring for PPH is recommended.^5,19 The management of PPH is similar as for patients without portal hypertension; however, ergometrine is contraindicated as it can cause a significant rise in portal pressure.¹⁹ Blood product replacement should be guided by coagulation tests and platelet counts.¹⁰ Women with portal hypertension are also at risk for the development of postpartum ascites, which may become complicated by secondary bacterial peritonitis. Antibiotic therapy is recommended postpartum to reduce this risk.¹⁹

Common therapies for treatment of portal hypertension and its complications are generally safe for use in breastfeeding women. Clinicians must be mindful of the use of diuretics, particularly furosemide, which can cause hypovolaemia and subsequently lead to decreased lactation. Consideration of dose reduction or alternate-day dosing is recommended.⁴⁴

Conclusion

NCPH is rare in pregnancy but should be considered in women presenting with unexplained liver dysfunction, features of portal hypertension, unexplained thrombocytopenia and oesophageal or rectal bleeding. Women with pre-existing NCPH should be appropriately counselled on the risks associated with pregnancy in the setting of their disease and of optimized prior to pregnancy.

In three of the four cases presented above, the prompt diagnosis and management of NCPH led to successful pregnancies and deliveries. This highlights the importance of a multidisciplinary approach to NCPH in pregnancy.

Footnotes

Acknowledgements

We would like to thank Dr Manoko Seabi and Professor Lawrence Chauke for allowing us permission to conduct the case series in their respective department as well as Professor Adam Mahomed for his guidance and advice.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

This study was approved by The WITS Human Research ethics committee.

Informed consent

Written consent was obtained from all participants.

Guarantor

MF Carrim.

Contributorship

MFC and ZR collected the relevant data and wrote the case summaries. ZR and RBN described the obstetrics management in the discussion. MM, DM and JZ all contributed towards the discussion of the medical management of non-cirrhotic portal hypertension in pregnancy. MFC gained written consent and recruited participants for the case series.

Trial registration

Permission to conduct the case series was provided by the Charlotte Maxeke Johannesburg academic hospital. This was not a clinical trial and thus no trial registration was needed.

ORCID iDs

Mohammed Farhaan Carrim

Jarrod Zamparini

Correction (April 2024):

Affiliation list corrected.

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