Oxaliplatin-induced portal hypertension in colorectal cancer: A systematic review of incidence, mechanisms, and predictive markers.

117 Background: Oxaliplatin remains a cornerstone of colorectal cancer (CRC) chemotherapy but is frequently complicated by chemotherapy-associated liver injury (CALI). This manifests as sinusoidal obstruction syndrome (SOS), nodular regenerative hyperplasia (NRH), or porto-sinusoidal vascular disorder (PSVD). These microvascular changes lead to portal hypertension (PH), splenomegaly, and thrombocytopenia, interrupting chemotherapy delivery and compromising survivorship. Despite increasing recognition, the incidence, spectrum, and management of oxaliplatin-induced portal hypertension (OIPH) remain undefined. Methods: We systematically reviewed PubMed, Embase, and Cochrane through August 2025 for prospective and retrospective cohorts of oxaliplatin-treated CRC patients reporting OIPH incidence, pathology, radiology, or interventional management. Case reports were excluded. Outcomes included incidence, latency, complications, misdiagnosis, and interventions such as bevacizumab and partial splenic embolization (PSE). Results: Eight studies including 730 patients were analyzed. OIPH developed in ~20–30% of patients, with 2–5% progressing to clinically overt disease requiring variceal banding, Transjugular Intrahepatic Portosystemic Shunt (TIPS), PSE, or management of liver failure. Latency to presentation was typically 4–10 years after oxaliplatin exposure. Common features included splenomegaly, thrombocytopenia, varices, and ascites. Histopathology consistently showed sinusoidal dilatation, congestion, perisinusoidal fibrosis, NRH, and microthrombi, confirming endothelial-mediated injury. Up to half of chronic cases were misclassified as metabolic dysfunction–associated steatotic liver disease (MASLD/NAFLD) or cryptogenic cirrhosis. Bevacizumab demonstrated consistent hepatoprotection, delaying splenic enlargement and reducing thrombocytopenia, likely via preservation of sinusoidal endothelial integrity and reduction of von Willebrand factor–mediated platelet microthrombi. Interventional radiology provided therapeutic options: in a prospective phase II study, PSE restored platelet counts >130×10⁹/L in 94% and enabled chemotherapy resumption within a median of 14 days, with no grade ≥3 adverse events. Conclusions: OIPH is an under-recognized complication of CRC chemotherapy, with latency spanning years after treatment. Splenomegaly and thrombocytopenia serve as early clinical signals, while misdiagnosis as MASLD or cirrhosis is common. Bevacizumab provides hepatoprotection, and PSE offers a safe and effective option for chemotherapy-limiting thrombocytopenia. Routine monitoring of spleen volume and platelet trends should be integrated into follow-up, and prospective validation of prophylactic and interventional strategies is urgently needed.