The use of biologics in the treatment of autoimmune liver disease

ABSTRACT

Introduction: Autoimmune liver diseases include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and juvenile autoimmune hepatitis (JAIH). The pathophysiologic features of each disease vary, but generally include presence of autoantibodies, cytokine abnormalities, and/or T and B cell autoreactivity.

Areas covered: This article compares conventional therapy with newer biologics available for treatment of autoimmune liver diseases. Conventional therapy involves the use of immunosuppressive agents, or other treatment modalities for specific autoimmune liver diseases such as ursodeoxycholic acid and fibrates for PBC. Biologics were developed to target the production of autoantibodies by B cells, the presence of proinflammatory cytokines, adhesion molecules or T and B cell activation.

Expert opinion: Despite the promise of biologics being able to target specific cellular and humoral pathways, results have been generally poor, and safety has not been as expected. Cases of autoimmune hepatitis have also developed with the use of these biologicals. Reasons for the lack of success of biologics in treating autoimmune liver disease has led to a reevaluation of our understanding of underlying pathogenesis, demonstrating that while our knowledge of the immunity has improved over the past two decades, it is far from complete.

KEYWORDS:

• Autoimmune hepatitis
• primary biliary cholangitis
• primary biliary cirrhosis
• primary sclerosing cholangitis
• autoantibodies
• biological modifiers
• monoclonal antibodies
• immunosuppressive agents

Article Highlights

• Our knowledge of the mechanisms of autoimmunity has increased exponentially in recent years but is still incomplete.

• Biologics have been trialed in the treatment of autoimmune liver disease based on our current knowledge of the immune system.

• The success of biologics in the treatment of autoimmune liver disease has been disappointing so far.

• A better understanding of how the immune system works to develop tolerance will help to guide future development of biologic therapies for autoimmune liver disease.

• Because our knowledge of immune function is incomplete, the risks of unintended adverse effects exists with all studies regarding biologics, so great care should be taken to ensure patient safety during clinical trials.

• The ultimate goals of developing new treatments such as biologics for autoimmune liver disease are to minimize tissue injury, improve quality of life and increase life expectancy.

This box summarizes key points contained in the article.

Declaration of Interest

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 or other relationships to disclose

Additional information

Funding

This paper was not funded.