Acute Liver Failure from Anti-PD-1 Antibody Nivolumab in a Patient with Metastatic Lung Squamous Cell Carcinoma

Case Report

Austin Oncol. 2016; 1(2): 1006.

Acute Liver Failure from Anti-PD-1 Antibody Nivolumab in a Patient with Metastatic Lung Squamous Cell Carcinoma

Sarkissian Sarmen M.D. and Seery Tara M.D.

Department of Hematology/Oncology, University of California, Irvine, USA

*Corresponding author: Sarkissian Sarmen M.D, Department of Hematology/Oncology, University of California, Irvine, USA

Received: December 18, 2015; Accepted: March 21, 2016; Published: March 23, 2016


Lung cancer remains one of the leading causes of cancer related mortality worldwide. The approval of the first immune checkpoint inhibitor, nivolumab, for squamous cell carcinoma of the lung has drastically increased the treatment options. Unfortunately, checkpoint inhibitor therapy is not innocuous, with hyperinflammation a known side effect. While hepatitis has been reported with this medication across several different cancer types, fulminant hepatic failure has not been reported. We present the case of a patient with metastatic squamous cell carcinoma of the lung that developed hepatitis and ultimately fulminant hepatic failure after 2 cycles of ivolumab therapy. Immunosuppressive therapy was initiated but was futile. This is the first reported case in the literature. We present this case to not only shed light on the inflammatory side effects that can develop with this family of biologics, but also help stress the importance of prompt recognition so that corticosteroid therapy can be initiated promptly.

Keywords: Nivolumab; Liver failure; Immunotherapy; Checkpoint inhibitor


Lung cancer is the leading cause of cancer related mortality worldwide, with an estimated 221,200 new cases and 158,040 deaths in the United States for the year 2015 [1]. Primary prevention via reduced smoking prevalence has led to a drop in the annual death rate since the 1960’s [2]. 85% of lung cancer cases are non-small cell [3] with 21% of these being squamous cell carcinoma [4]. Prognosis is contingent on the stage of presentation, with a 2007 study showing a median 5 year survival of 2 percent and 17 percent for clinical and pathologic stage IV respectively [5].

The development of immune checkpoint inhibitors has changed the therapeutic landscape for squamous cell carcinoma. Nivolumab is an IgG humanized monoclonal antibody that targets the programmed cell death receptor on the surface of T lymphocytes. A pivotal phase III study in advanced squamous cell lung cancer patients from Spiegel et al. showed that second line nivolumab produced an increase in median OS from 6.0 to 9.2 months when compared head to head with docetaxel therapy [6].

The excess inflammation caused by immune checkpoint inhibitors is a well-known side effect. This includes dermatitis, colitis, cerebritis, pneumonitis, and importantly hepatitis [7]. Hepatotoxicity has been reported as less than 5% [8-10] of patients in trials with nivolumab. The time course is generally accepted to be around 6 weeks after the initiation of treatment the liver transaminase begin to elevate [11]. Recommended first line treatment includes high dose corticosteroids with at least 1-2 mg/kg daily. If there is no response to steroids then attempts with mycophenylate and infliximab can be pursued [12]. Anti-Thymocyte Globulin has also been tried in one case report [13].

While hepatitis is an uncommon but expected side effect, fulminant hepatic failure has never been reported for nivolumab in the literature. We present the case of a patient with advanced squamous cell carcinoma of the lung that developed severe hepatic impairment as a result of nivolumab therapy. He showed no response to high dose corticosteroids and was not a liver transplant candidate. He expired within 5 days of the diagnosis. We believe that his acute hepatic failure was a result of his immunotherapy. We present his case below.

Case Presentation

A 59 year old Caucasian male with squamous cell carcinoma of the lung, with metastases to the liver, was initially treated with 2 cycles of carboplatin and gemcitabine. He showed progression of disease on PET/CT and was initiated on treatment with nivolumab. The patient completed 2 infusions of nivolumab. Labs just prior to the second infusion showed normal liver function panels. The Patient presented to a community hospital emergency room, 21 days after his first infusion of nivolumab, with a 1 day history of cough, significant dyspnea on exertion and lower extremity edema. Patient denied sick contacts or traveling outside the United States.

Labs on admission were notable fora hemoglobin 7.1g/dL and a leukocytosis 21.6 x 109 cells/L. CXRay showed a right upper lobe consolidation. Patient was initially treated with azithromycin and ceftriaxone for community acquired pneumonia. Home medications at that time included metformin, insulin, fluticasone/ salmeterol inhaler, losartan, lorazepam, zolpidem, hydrocodone/ acetaminophen, aspirin, ondansetron, and fenofibrate. Liver function panel on admission was notable for mild elevations as noted in the table (day 21). Patient’s symptoms continued to decline. On hospital day #4 a bronchoscopy was performed which was unremarkable. A transthoracic echocardiogram ruled out cardiomyopathy and a pericardial effusion. Ultrasound of the abdomen showed a nodular liver with moderate hepatomegaly and mild splenomegaly (patient has a history of alcohol abuse). Patient underwent an MRCP/ERCP which showed no evidence of gallstones or biliary ductal dilation.

Citation: Sarmen S and Tara S. Acute Liver Failure from Anti-PD-1 Antibody Nivolumab in a Patient with Metastatic Lung Squamous Cell Carcinoma. Austin Oncol. 2016; 1(2): 1006.