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Watch a video presentation of this article Answer questions and earn CME A 55-year-old woman with a medical history of colon adenocarcinoma status post sigmoid resection presented to the hospital with hematemesis. The patient woke up feeling unwell and had sudden-onset large-volume hematemesis. She denied any abdominal pain, fevers, or chills. She denied any recent travel abroad. She denied any history of heartburn or peptic ulcer disease. She denied any use of nonsteroidal anti-inflammatory medications or anticoagulation. Her medical history was significant for stage 3a colon adenocarcinoma status post 12 cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin), which was completed 5 years ago. Her surgical history was notable for a sigmoid resection in 2014, cholecystectomy in 2013, and a partial hysterectomy in 2011. She had no smoking or illicit drug use history. She endorsed drinking two to three glasses of wine, two to three times a week. Her father had alcohol-related cirrhosis. She had no other family history of gastrointestinal or liver disease. She denied any travel outside of the United States. She did not take medications. She denied any supplements or over-the-counter medications. On arrival to the emergency department the patient was afebrile with a heart rate of 101 beats/min and a blood pressure of 98/52 mm Hg. Her oxygen saturation was 95% on room air. The patient was sitting comfortably in bed and able to speak in complete sentences. Her physical examination was otherwise notable for blood in the oropharynx. She had no signs of scleral icterus, jaundice, palmar erythema, spider angioma, organomegaly, abdominal ascites, or asterixis. Her admission laboratory tests revealed a hemoglobin level of 11.3 g/dL and a platelet count of 177 cells/L. Her white blood cell count and basic metabolic panel were within normal limits. Her liver chemistries were notable for an aspartate aminotransferase concentration of 22 IU/L, an alanine aminotransferase of 28 IU/L, an alkaline phosphatase of 86 IU/L, and a total bilirubin of 1.0 mg/dL. Her coagulation studies were unremarkable. The patient was started on intravenous pantoprazole drip and underwent an emergent upper endoscopy that revealed small esophageal varices and gastroesophageal varices (GOV) extending along the greater curvature of the stomach with high-risk stigmata of recent bleeding (Fig. 1). Hemostatic spray was deployed in anticipation of the need for TIPS, and the patient was started on an octreotide drip. A liver ultrasound with Doppler imaging was obtained and revealed mild surface nodularity of the liver concerning for hepatic cirrhosis and patent hepatic vasculature with normal directional flow of the portal veins. A follow-up computed tomography of the abdomen and pelvis (Fig. 2) showed that the liver was normal in size without cirrhotic morphology. The portal vein branches were patent. A few GOV were present, and a small recannulized paraumbilical vein was noted. A transhepatic liver biopsy with portal pressures was obtained (Fig. 3). The right atrial pressure (RAP) was 5 mm Hg. The wedged hepatic venous pressure (WHVP) was 10 mm Hg. The RAP was 5 mm Hg. The liver biopsy showed mild macrovesicular fat without fibrosis. The portal tracts were unremarkable. Given high clinical suspicion for portal hypertension despite a normal hepatic venous pressure gradient (HVPG), a direct portal vein pressure was obtained and demonstrated a portal vein pressure of 17 mm Hg with a portosystemic gradient of 12 mm Hg. The patient subsequently underwent a TIPS procedure with embolization of the gastrorenal shunt and reduction of the portosystemic gradient from 12 to 1 mm Hg (Fig. 4). The patient was diagnosed with noncirrhotic portal hypertension associated with oxaliplatin administration. This patient presented with hematemesis secondary to type 2 GOV (GOV2) secondary to noncirrhotic portal hypertension. The Sarin classification of gastric varices categorizes varices based on their location and relationship to esophageal varices, and divides varices into GOV1 and GOV2 and isolated gastric varices (IGV; type 1 and type 2). GOV were characterized by the extension of esophageal varices along the lesser curvature (GOV1) or the greater curvature (GOV2). GOV1 is the most common type, accounts for 75% of all gastric varices, and can be managed the same as isolated esophageal varices (endoscopic variceal ligation). GOV2, however, require treatment with sclerotherapy using cyanoacrylate- or interventional radiology-guided TIPS, as in this case versus balloon-occluded retrograde transvenous obliteration, depending on the clinical scenario. Portal hypertension is a clinical syndrome defined as the elevation of the hepatic vein pressure gradient (HVPG) to more than 5 mm Hg that results in the development of ascites, splenomegaly, gastrointestinal varices, and encephalopathy.1, 2 Although cirrhosis is a common cause of portal hypertension, portal hypertension can develop in the absence of cirrhosis. Noncirrhotic portal hypertension (NCPH) can occur at different levels of the hepatic circulation and is categorized as prehepatic, intrahepatic, and posthepatic, each with different portal venous pressure measurements (Table 1); for example, see fig. 3 of Koh et al.1 The majority of NCPH occurs at the intrahepatic level and is often the result of injury to the prehepatic or presinusoidal structures of the liver.2 Because of this, HVPG values tend to be normal or only mildly elevated, as seen in our patient; for example, see table 1 of Etzion et al.2 Oxaliplatin is a third-generation platinum derivative that has become the cornerstone of chemotherapy regimens for the treatment of colorectal cancer, both as adjuvant therapy and for metastatic disease. Its use has been associated with significant improvement in clinical outcomes when compared with 5-fluorouracil alone.3 However, oxaliplatin has been associated with significant toxicity. Common toxicities include peripheral neuropathy, splenic enlargement, thrombocytosis, hepatic steatosis, and portal-sinusoidal vascular disease (PSVD) with resultant portal hypertension, in the absence of cirrhosis. Oxaliplatin-associated noncirrhotic portal hypertension is a well-recognized complication of oxaliplatin use that is thought to be the result of PSVD. Sinusoidal damage related to oxaliplatin use was first described by Rubbia-Brandt et al.4 in 2004 and has been confirmed in subsequent case studies.5 Its incidence rate is estimated to range from 19% to 52%.6 Portosinusoidal injury can range in severity from mild sinusoidal dilation to hepatic sinusoidal obstructive syndrome. The proposed mechanism of sinusoidal injury is thought to be the result of increased permeability of the sinusoidal endothelium, resulting in the release of free radicals and depletion of glutathione transferase. This allows for the passage of erythrocytes into the space of Disse and the subsequent formation of perisinusoidal fibrosis. The resultant hypoxia leads to the release of angiogenic factors such as vascular endothelial factor and the activation of metalloproteinases, which results in further vascular damage. It is then believed that the resultant endothelial cell damage obstructs the sinusoids, resulting in hepatic congestion and elevated portal pressures.7 In addition, nodular regenerative hyperplasia is thought to be the result of chronic, long-term hypoxia in the centrilobular areas. A study in 2010 revealed the relationship between the cumulative dose of oxaliplatin with an increase in the size of the spleen and associated thrombocytopenia during treatment and the development of sinusoidal obstructive syndrome.8 In addition, further studies have suggested that the concomitant use of bevacizumab, an inhibitor of vascular endothelial growth factor A, may have protective effects on the development of portal hypertension.9 Oxaliplatin-associated portal hypertension should be suspected in any individual treated with oxaliplatin who has clinical signs of portal hypertension in the absence of underlying chronic liver disease and after the exclusion of both portal or hepatic vein thrombosis and other conditions associated with noncirrhotic portal hypertension (congenital liver fibrosis, sarcoidosis, schistosomiasis). There are three typical histological findings suggestive of PSVD. These findings can be observed in isolation or in combination and include: (1) phlebosclerosis and hepatoportal sclerosis affecting medium and small branches, (2) nodular regenerative hyperplasia, (3) and incomplete septal fibrosis.10 Our patient was diagnosed with oxaliplatin-associated noncirrhotic portal hypertension 5 years after the completion of her chemotherapy. She is now status post TIPS and has been doing well for more than a year without any complications.