P1940 - An Unusual Case of Hepatic Venous Outflow Obstruction: Sequelae of Immune Check Point Inhibitors

Rahul Karna, MD, Thayer Nasereddin, MD, Ariel Sandhu, MD, Cristina Strahotin, MD
Allegheny Health Network, Pittsburgh, PA

Introduction: The use of immune check point inhibitors (ICPIs) in cancer treatment has increased over the last decade. Studies have implicated increased risk of arterial and venous thrombosis from ICPIs. Here, we describe a challenging case of hepatic venous outflow obstruction (HVOO) due to the use of ICPIs.

Case Description/Methods: A 69 year old female with history of stage IV SCC lung, on nivolimumab and ipilimumab therapy for a year, presented with sudden onset of ascites, a month ago. She had no prior history of alcoholism, hematologic, hepatic, or cardiac disease. Labs revealed Hb 14 gm/dl, MCV 89 fL, WBC 10800/µL, platelets 200,000/µL, AST/ALT 89/ 91 U/L, ALP 499 IU/L, T.Bil.1.1 mg/dl and INR 1.2. US showed heterogenous liver without cirrhotic morphology or splenomegaly. Duplex US showed appropriate flow in hepatic artery, veins and portal veins. Main and right hepatic artery resistive index (RI) was elevated at 0.84 and 0.85 respectively (normal: 0.55-0.8). CLD work up was negative. Ascitic fluid analysis revealed SAAG 2.9 g/dl, no concern for SBP. CT venogram of abdomen showed patent hepatic, portal, SMV, IMV and splenic veins (Image A-B). Transjugular liver catheterization revealed elevated porto-systemic gradient of 13 mm Hg. There was no concern for congestive hepatopathy based on clinical features. Liver biopsy showed sinusoidal congestion, biliary stasis, hepatocyte atrophy, and hepatic vein thrombus (Image C-F). She developed sepsis leading to multi-organ failure and placed on hospice care before biopsy resulted.

Discussion: Despite new onset ascites and portal hypertension, our patient did not have any clinical or pathological evidence cirrhosis. Pathology showed a loosely organized thrombus in sublobular hepatic vein, raising concern of Budd-Chiari syndrome, but there was no evidence of the same on imaging. Some hepatic venules showed mural edema and fibrosis, without obliteration but, the severity of sinusoidal congestion was much less than typically seen with sinusoidal obstruction syndrome. Marked perivenular hepatocyte atrophy raised possibility of suboptimal portal vein and/or hepatic artery inflow. Ductular metaplasia of periportal hepatocytes on CK7 raises the possibility of suboptimal biliary drainage. High hepatic artery RI suggested microvascular disease. The patient’s symptoms were attributed to HVOO in setting of multifocal phenomenon of thrombogenecity. A high clinical suspicion for HVOO should be considered in patients on ICPIs that develop sudden onset portal hypertension.


Figure: Image: CT venogram of abdomen showing (A) patent IVC and (B) portal vein. (C) H&E stain, 100X: The portal areas show lymphocytic inflammation with cholangitis (black arrow) adjacent to congested perivenular sinusoids (red arrow). (D) H&E stain, 100X: A mid-sized sublobular vein showing a loosely organized thrombus (black arrow) intermixed with inflammatory cells (red arrow). The surrounding hepatocytes are atrophic. (E) CK-7 immunostain, 100X: The atrophied perivenular hepatocytes show prominent CK-7 positivity indicative of biliary ductular metaplasia. (F) PAS immunostain with diastase, 400X showing hepatocellular hyaline globules in perivenular area (red arrow) and perisinusoidal fibrosis (green arrow). The atrophic background hepatocytes showing abundant nuclear glycogenation (black arrow) and yellow lipofuscin pigment (blue arrow).


Disclosures:
Rahul Karna indicated no relevant financial relationships.
Thayer Nasereddin indicated no relevant financial relationships.
Ariel Sandhu indicated no relevant financial relationships.
Cristina Strahotin indicated no relevant financial relationships.


Rahul Karna, MD, Thayer Nasereddin, MD, Ariel Sandhu, MD, Cristina Strahotin, MD. P1940 - An Unusual Case of Hepatic Venous Outflow Obstruction: Sequelae of Immune Check Point Inhibitors, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.