Biological therapies in patients with liver disease: are they really lifesavers?

ABSTRACT

Introduction

The liver plays a key role in the setting of immune tolerance. Targeting antigens for presentation by antigen-presenting cells in the liver can induce immune tolerance to either autoantigens from the liver itself or organs outside of the liver. Despite its non-conventional capacity for tolerance induction, the liver remains a target organ for autoimmune diseases. Whereas chronic inflammation and intra-hepatic immuno-suppressive microenvironment occurring during liver fibrosis lead to hepatocellular carcinoma. Monoclonal antibodies have revolutionized the therapeutic strategies of many autoimmune diseases and some cancers.

Areas covered

We review data from literature regarding the safety and efficacy of biologics in treating hepatobiliary autoimmune diseases and primary liver cancers. Furthermore, we describe their potential use in the setting of liver transplants and their main immune-related liver adverse events.

Expert opinion

Biological therapies have changed the natural history of main autoimmune diseases and solid cancers. Compared to other organs and disease settings, the liver lags behind in biologics and their applications. The development of novel diagnostic and therapeutic strategies based on the immunological and antigenic characteristics of the hepatobiliary system could reduce mortality and transplant rates linked to chronic liver diseases.

KEYWORDS:

• Biological therapies
• autoimmune liver diseases
• autoimmune hepatitis
• primary biliary cholangitis
• primary sclerosing cholangitis
• liver cancer
• liver transplant

Article highlights

● Available data from clinical trials and real-world retrospective analyses on biological therapies in AILDs, primary liver cancers, and liver transplantation have been reported.

● We describe the different types of biologics used in the liver setting, their mechanisms of action, efficacy, and safety.

● The results of the use of biological drugs in liver cancer are promising since nivolumab represents the first immunotherapy approved for the treatment of hepatocellular carcinoma.

● Biologics have a recognized role in liver transplantation as inducers in the primary and secondary prevention of rejection.

● The use of immunotherapy in AILDs is disappointing since the EMA or the FDA has approved no one biological drug for their treatment.

● The failure of biologics in AILDs can be explained by using single biological molecules alone when a combined approach is probably needed to block the immune response at several critical points in the process. However, the benefits of combined biologics must be carefully balanced with the risks of adverse events such as opportunistic infections.

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Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.