Tip of the iceberg: A comprehensive review of liver disease in Inborn errors of immunity

Abstract

Inborn errors of immunity (IEIs) consist of numerous rare, inherited defects of the immune system that affect about 500,000 people in the United States.As advancements in diagnosis through genetic testing and treatment with targeted immunotherapy and bone marrow transplant emerge, increasing numbers of patients survive into adulthood posing fresh clinical challenges.A large spectrum of hepatobiliary diseases now present in those with immunodeficiency diseases, leading to morbidity and mortality in this population. Awareness of these hepatobiliary diseases has lagged the improved management of the underlying disorders, leading to missed opportunities to improve clinical outcomes. This review article provides a detailed description of specific liver diseases occurring in various inborn errors of immunity.A generalized approach to diagnosis and management of hepatic complications is provided, and collaboration with hepatologists, immunologists, and pathologists is emphasized as a requirement for optimizing management and outcomes.

Granulomatous liver diseases

“…Hepatic granulomas are a signature of CVID and chronic granulomatous disease (CGD). 107 CVID refers to a spectrum of disorders typically associated with adult-onset antibody deficiency, but a subgroup of cases have granulomas in the lung, liver, and spleen. Liver disease has been associated with higher mortality in CVID.…”

“… 156 Patients with inborn errors of immunity should be considered for hematopoietic stem cell transplant before liver disease progresses. 107 …”

Differential Diagnosis: Hepatic Complications in Inborn Errors of Immunity

“…Cryptosporidium is a water-borne protozoa that can cause prolonged infections with significant morbidity and mortality within the immunocompromised. Up to one third of patients with CD40L deficiency have liver involvement [85], with Cryptosporidium-related gastrointestinal and/or biliary tract disease affecting between 6 and 21% of CD40 ligand deficiency patients [3,70]. Chronic Cryptosporidium infection is associated with secondary sclerosing cholangitis which can significantly increase mortality [3,70].…”

“…Chronic Cryptosporidium infection is associated with secondary sclerosing cholangitis which can significantly increase mortality [3,70]. Although a proportion of patients with sclerosing cholangitis do not have detectable Cryptosporidium, this may relate to assay sensitivity [85]. Cryptosporidium is a well-recognised complication in the phenocopy hyper-IgM syndrome, autosomal recessive CD40 deficiency [86,87].…”

“…Whilst autoimmune cytopaenias are the most frequent complication, involvement of the liver is less common, with few cases reported in the literature [91]. Immune dysregulation is most commonly seen as granulomas or autoimmune hepatitis (AIH), with rare case reports of primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) [85,90,[92][93][94][95].…”