P0843 - Breast Cancer and New Portal Hypertension: Is There a Link?

Sarvanand Patel, , Vinay Sundaram, MD, MSc, Maha Guindi, MD
Cedars-Sinai Medical Center, Los Angeles, CA

Introduction: Nodular regenerative hyperplasia (NRH) is one of the causes of noncirrhotic portal hypertension (NCPH) characterized by hepatic regenerative nodules with the absence of fibrotic tissue. The diagnosis of NRH is challenging since the clinical presentation is variable and a majority of patients present without symptoms. Patients with NRH can have evidence of portal hypertension, and the prognosis in these cases is largely dependent on its presence and severity. Here we present a case of a patient with breast cancer who was diagnosed with NRH.

Case Description/Methods: A 41-year-old women with a history of breast cancer diagnosed at age 40 was evaluated for elevated liver enzymes. She was treated initially with immunotherapy involving Paclitaxel, Trastuzumab and Pembrolizumab. She was then switched to trastuzumab-emtansine (Kadcyla) 12 months prior to presentation, taken every 3 weeks for 14 doses. Her medical history was otherwise unremarkable.

Her liver enzymes at the time of presentation were characterized by an ALT of 58 U/l, AST of 42 U/l, total bilirubin of 1.6 mg/dl, and ALP of 132 U/l. Her LFT's were noted to be elevated for 5 months prior to presentation, with peak ALT level of 95 U/l and AST level of 67 U/l. Her platelet count fluctuated between 118 to 200 x10³/UL.

Evaluation included an MRI with contrast that revealed a normal appearing liver but with portal hypertension, as demonstrated by splenomegaly and a large recanalized umbilical vein. A CT scan 18 months prior showed no evidence of portal hypertension. Transjugular biopsy demonstrated nodular hyperplastic parenchyma around small portal tracts with atrophic zones around the hepatic veins.

This was most likely from Kadcyla-induced NRH. After diagnosis, our patient was transitioned to exemestine and her aminotransferases decreased 3 months after her last dose. An endoscopy to screen for varices was normal. A fibroscan will be obtained annually to ensure improvement of portal hypertension.

Discussion: Kadcyla is a microtubule inhibitor that is taken up into HER2 expressing cells resulting in cell cycle arrest. In 2019, the FDA further approved Kadcyla for adjuvant treatment of patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant therapy. Drug-induced NRH is a rare event and typically occurs after months or years of treatment and complications of hypersplenism, ascites, and variceal bleeding can occur. Management involves therapy interruption and dose adjustments.


Figure: Figure 1: Liver biopsy with NRH
a). Low power view showing nodularity of liver parenchyma (reticulin stain magnification 40x). The asterisk depicts the nodular hyperplastic parenchyma. The arrow points to the nodular expanding border of the hyperplastic parenchyma. The blue star depicts atrophic zone 3 around hepatic vein
b) Small portal tract (arrow)with loss of portal vein (H&E stain magnification 100x)
c) Low power view showing nodularity of liver parenchyma less obvious than on reticulin stain. The arrow points to the nodular expanding border of the hyperplastic parenchyma unbound by fibrosis (trichrome stain magnification 100x)
d) Low power view showing no fibrosis (H&E stain magnification 20x)

Figure 2 MRI: Reveals portal venous hypertension as demonstrated by splenomegaly and a large recanalized umbilical vein, without evidence of portal or hepatic vein thrombosis


Disclosures:
Sarvanand Patel indicated no relevant financial relationships.
Vinay Sundaram indicated no relevant financial relationships.
Maha Guindi indicated no relevant financial relationships.


Sarvanand Patel, , Vinay Sundaram, MD, MSc, Maha Guindi, MD. P0843 - Breast Cancer and New Portal Hypertension: Is There a Link?, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.