Review Article

Immune Checkpoint Inhibitors and the Liver, From Therapeutic Efficacy to Side Effects

Andrea Lombardi; Mario U. Mondelli

Disclosures

Aliment Pharmacol Ther. 2019;50(8):872-884. 

In This Article

Abstract and Introduction

Abstract

Background: Immune checkpoint inhibitors have revolutionised the oncological landscape in the last few years. Possible applications include the treatment of hepatocellular carcinoma and cholangiocarcinoma. Unfortunately, new immune-related adverse effects have been associated with the use of these agents and the liver is one of the organs most frequently involved.

Aims: To provide a general overview of the potential impact of immune checkpoint inhibitors on the liver

Methods: We reviewed the literature and abstracts/presentations on immune checkpoint inhibitors at most relevant hepatology meetings over the last 5 years.

Results: The role of immune checkpoint inhibitors has been investigated both for the treatment of viral hepatitis and primary liver cancer. Hepatocellular carcinoma and chronic hepatitis B show the greatest potential for treatment with these drugs in the near future. However, immune-related adverse events involving the liver are a growing concern related to their widespread use.

Conclusions: Immune checkpoint inhibitors represent an exciting new class of drugs with currently limited application in malignant and non-malignant liver disease. Caution must be exercised on the emergence of potentially severe immune adverse reactions.

Introduction

The oncological landscape has been revolutionised over the last few years by the advent of the new class of immunomodulatory drugs termed immune checkpoint inhibitors. These agents have substantially changed the prognosis of certain cancers such as melanoma, non-small cell lung cancer and renal cell carcinoma to such an extent that many consider cancer immunotherapy as the third era of oncological therapy, after systemic chemotherapy and targeted therapy.[1] Increasing evidence supports the efficacy of checkpoint inhibitors in the treatment of advanced hepatocellular carcinoma and their possible use against cholangiocarcinoma (CCA) is mounting.[2,3] The existence of a condition of immune exhaustion due to chronic exposure to viral antigens has for long been known for chronic hepatitis C (CHC), and particularly for chronic hepatitis B (CHB), a state akin to that occurring in several oncological settings. Consequently, therapeutic approaches aiming to restore an exhausted immune system in CHB were postulated, but never really investigated beyond an animal model.[4] Unfortunately, every rose has thorns and together with their increasing usage, checkpoint inhibitor side effects have increasingly been reported. The liver is particularly prone to being involved by immune-related adverse events (irAEs), their prevalence being between 4% and 9% of patients treated with anti-CTLA-4 monoclonal antibody (mAbs), and in 18% of those treated with a combination of anti-PD-1 and anti-CTLA-4.[5]

Here, we review the immunological basis of therapy with checkpoint inhibitors, the impact of these drugs in the treatment of primary liver cancer, and liver-related side effects of systemic therapy.

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