Navigating abdominal surgery in extrahepatic portal vein obstruction: new insights and remaining issues

Extrahepatic portal vein obstruction (EHPVO), characterized by occlusion of the main portal vein and often leading to cavernoma formation, presents unique challenges in clinical management (1). Although considered a rare disease, it is a significant cause of portal hypertension (PH), often in patients with preserved liver function. A critical yet poorly understood area has been associated with abdominal surgery in this population. Historically, it has been considered a very high bleeding risk, and robust data to guide clinical decision-making are scarce.

In this context, a multicenter retrospective study by Elkrief et al. published in Hepatology (2) provided valuable and much-needed data. The authors meticulously evaluated the postoperative outcomes of 76 patients with EHPVO (78 interventions) across 12 European university tertiary centers. Importantly, they compared these outcomes between a subgroup of 63 patients with EHPVO and 126 matched controls without EHPVO undergoing similar procedures.

This study confirms the long-held concern regarding perioperative complications, particularly when patients are compared with controls. In this matched cohort analysis, major bleeding occurred in 16% of the patients with EHPVO during or within one month postoperatively, a rate markedly higher than the 2% observed in controls. Furthermore, PH-related complications (primarily ascites) occurred in 18% of these EHPVO patients within three months, compared to none in the control group. An “unfavorable outcome”, defined compositely as major bleeding, grade ≥3 postoperative complications (Dindo-Clavien classification), PH-related complications, or death within 12 months, affected 33% of EHPVO patients in the comparison group, significantly more than the 18% in controls. Importantly, by analyzing the full EHPVO cohort (n=78 interventions), the study identified two key predictors of this unfavorable outcome: history of ascites and surgery other than cholecystectomy or abdominal wall repair. The rate of unfavorable outcomes in patients with neither factor is only 15%, which increases dramatically when one or both factors are present.

However, the study also offers some positive findings regarding abdominal surgeries in patients with EHPVO, especially concerning severe complications and mortality relative to controls. Despite increased morbidity, the incidence of severe (grade ≥3) postoperative complications unrelated to PH (18%) was not significantly different from that of controls (14%) in the matched analysis. Interestingly, the mortality within 12 months was low (5%) in the EHPVO comparison group and statistically similar to that in the control group (3%). This suggests that while morbidity, particularly bleeding, is elevated, the risk of death may not be as prohibitive as previously feared, especially when compared with surgery in patients with cirrhosis.

Normal liver function in patients might be associated with a low death rate despite the high risk of PH-related complications, including ascites and variceal bleeding. Indeed, the observed mortality rate seems lower than that reported for patients with compensated cirrhosis or even portosinusoidal vascular disorder (PSVD) or idiopathic noncirrhotic PH (3,4). This highlights that prehepatic PH alone, without the concomitant liver dysfunction seen in cirrhosis, may have a different impact on surgical mortality.

The findings have several important clinical implications. The identified risk factors, history of ascites, and surgical complexity beyond cholecystectomy and wall repair provide simple and readily available criteria for pre-operative risk stratification and patient counseling.

Although Elkrief et al. (2) found that PH-related complications were relatively common, they were mostly transient episodes that were managed medically. Notably, only two instances of variceal bleeding have been reported in patients without adequate prophylaxis. This study did not focus primarily on variceal management, prophylaxis for risky intestinal varices should be highlighted. Considering the frequency and potential severity of portal hypertensive complications in patients with EHPVO, the prophylaxis and treatment of esophagogastric variceal bleeding remain crucial. As suggested by other reports (5), patients with EHPVO and esophagogastric varices may achieve a favorable prognosis if variceal prophylaxis is performed appropriately. Therefore, comprehensive preoperative prophylaxis for postoperative esophagogastric variceal bleeding, including endoscopic treatment and nonselective beta-blockers where indicated (6), will likely contribute to better outcomes. Furthermore, clinicians managing EHPVO should consider the high prevalence of ectopic varices in this condition (7,8). Additionally, nonsteroidal anti-inflammatory drugs (NSAIDs), which are widely used for perioperative pain management, are known to potentially cause variceal bleeding in patients with PH (9). In patients with significant PH, the perioperative avoidance of NSAIDs is prudent.

Interestingly, prior portal decompression, including interventional radiology procedures and surgery, did not significantly alter the outcomes in a small subgroup (n=9) of this cohort (2). While this observation from a small, heterogeneous group is noted, it stands in contrast to a growing body of evidence from studies specifically designed to evaluate endovascular portal vein recanalization (PVR). These modern techniques are emerging as a pivotal alternative to surgical shunts for managing PH in EHPVO. A recent key study (10) on PVR without a transjugular intrahepatic portosystemic shunt (TIPS) in 31 patients reported a technical success rate of 87% and a 5-year primary patency of 73%. Crucially, in their cohort, PVR was performed on four patients specifically as a preparatory step for abdominal surgery, directly suggesting its potential to mitigate the perioperative risks noted by Elkrief et al. This approach aims to restore physiological portal flow, potentially avoiding long-term complications of TIPS such as encephalopathy. For more complex cases, PVR with TIPS has also demonstrated high technical success and efficacy in pressure reduction, though it may carry a higher risk of complications and mortality (11). The feasibility of these techniques is rapidly expanding, with successful applications reported even in challenging scenarios like chronic total occlusions and in pediatric populations (12). This evolving paradigm underscores the need for multidisciplinary decision-making for abdominal surgery in EHPVO, where PVR is considered not only as a primary therapy for portal decompression but also as a strategic tool to optimize patients and potentially improve surgical outcomes.

Given that an inherent prothrombotic state is often associated with EHPVO, the unexpectedly low rate of postoperative thrombotic complications reported in this cohort (limited to a single case of jugular thrombosis and one instance of thrombotic extension) raises questions. Managing adult EHPVO presents significant challenges, largely stemming from its frequent association with underlying thrombophilia and the resultant therapeutic dilemma of balancing the thrombotic and hemorrhagic risks. This therapeutic balance is a constant dilemma in EHPVO management. It is arguably the central and most critical concern in the management of EHPVO. Maintaining this delicate equilibrium must be a constant consideration for clinicians as its disruption can lead to an intractable state. This vigilance is paramount not only during the perioperative period but also throughout the routine long-term follow-up of these patients. Underlying thrombophilia, particularly myeloproliferative neoplasms (MPNs) driven by the JAK2V617F mutation (prevalent in approximately 30% of adult EHPVO cases), is a major contributing factor (7,8). This inherent prothrombotic state significantly affects the treatment strategies and patient outcomes.

The management of antithrombotic therapy in patients with EHPVO adds another layer of complexity. Although long-term anticoagulation [e.g., vitamin K antagonists and direct oral anticoagulants (DOACs)] is generally indicated for EHPVO (6), the substantial risk of procedure-related hemorrhage or variceal bleeding creates a difficult therapeutic balance. This challenge is particularly pronounced for MPN-associated EHPVO. Given that JAK2V617F clonal hematopoiesis may contribute to arterial thrombosis, including systemic events, such as myocardial or cerebral infarction, and may involve mechanisms responsive to aspirin. A combination of antiplatelet therapy (aspirin) and anticoagulation is sometimes considered, especially in patients with EHPVO and essential thrombocythemia or polycythemia vera, a subtype of MPNs (13), despite the inevitably increased risk of bleeding due to varices or procedures. Indeed, clinical practice often presents perplexing challenges for gastroenterologists managing EHPVO, who must balance complex antithrombotic needs with the critical imperative to prevent or control bleeding. Considering institutional experience, including our own, of young patients with EHPVO developing major systemic thrombotic events, such as myocardial infarction, pulmonary embolism, or stroke, multidisciplinary collaboration involving cardiologists, neurologists, and hematologists is critical (14,15).

This study provides the most comprehensive data to date but several limitations are worth considering (2). The retrospective design is associated with potential biases. The data were collected from expert centers, potentially limiting generalizability. Furthermore, the higher rate of emergency surgery in the control group complicates direct comparison, potentially underestimating the relative mortality risk of EHPVO in elective settings. Nevertheless, this study provides the groundwork for future prospective research. The validation of these findings and prospective risk factors is essential. Investigating the optimal perioperative antithrombotic strategies and refining risk prediction models could further improve the perioperative management of patients with EHPVO.

In conclusion, Elkrief et al. (2) advanced our understanding of abdominal surgery risks in EHPVO patients, confirming increased bleeding and PH-related complications, especially with ascites or complex procedures. However, their study suggests severe complication and mortality rates may not be prohibitive compared to controls, offering a more optimistic outlook. It also underscores the evolving role of less-invasive interventions as a crucial preparatory strategy to improve surgical outcomes. This landmark study provides clinicians with vital data to inform risk assessments, guide perioperative management, and facilitate shared decision-making for this complex population.

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.