Hepatic Sinusoidal Obstruction Syndrome (SOS) Associated with Checkpoint Inhibitor Therapy

Abstract

Sinusoidal obstruction syndrome (SOS) is a distinctive and potentially fatal form of hepatic injury that mainly occurs after hematopoietic-stem cell transplantation but also due to many other conditions including drug or toxin exposure. Recently, immune checkpoint inhibitors (ICIs) have revolutionised the treatment of many solid organ malignancies. Furthermore, as their use has become more widespread, rare toxicities have emerged. The difficulty lies in diagnosing these unusual toxicities with an incidence of as low as less than 1% hence defined as SOS. The development of the disease can be rapid and unpredictable. The severe forms of SOS may result in multi-organ dysfunction with a high mortality rate (>80%). We present the case of a patient with metastatic lung adenocarcinoma treated with the ICI pembrolizumab who developed SOS with marked portal hypertension as a rare severe, toxic side effect of immunotherapy. This report highlights the importance of considering SOS in patients who develop liver dysfunction and/or portal hypertension during or after immunotherapy for neoplastic disease. Early identification and severity assessment is crucial in facilitating prompt diagnosis and timely treatment, improving the prognosis of our patients.

Learning points: Understand less common side effects of immunotherapy, now used in daily clinical practice.Consider sinusoidal obstruction syndrome (SOS) in patients who develop liver dysfunction and/or portal hypertension during or after immunotherapy for neoplastic disease.Early identification and severity assessment is crucial in facilitating prompt diagnosis and timely treatment, improving the prognosis of patients.

Keywords: SOS; Sinusoidal obstruction syndrome; immune checkpoint inhibitors; pembrolizumab.

Figure 1

Computed tomography scan (portal phase). Hepatomegaly with a non-homogeneous intrahepatic vascularization and abundant intra-abdominal effusion.

Figure 2

Dilatation and congestion of sinusoids are located in centrilobular zones around the terminal hepatic vein. Endothelial cells of veins and sinusoids are damaged, leading to hematic deposition in the space of Disse and to hepatocyte necrosis around the central veins. A) Haematoxylin and eosin (H&E) stain; B e C) Masson’s trichrome stain; C) Silver stain.