Autoimmune Diseases Affecting Both Liver and Eyes
The primary autoimmune disease that affects both the liver and eyes is autoimmune hepatitis (AIH), which commonly occurs alongside other autoimmune conditions including autoimmune thyroiditis, inflammatory bowel disease (particularly ulcerative colitis associated with primary sclerosing cholangitis), and systemic lupus erythematosus—all of which can have ocular manifestations. 1
Direct Liver-Eye Autoimmune Connections
Autoimmune Hepatitis with Systemic Associations
AIH is associated with a wide variety of other autoimmune or immune-mediated diseases that mirror the full range of known autoimmune conditions. 1 The most clinically relevant connections include:
Autoimmune thyroiditis is the most common concurrent autoimmune disease in AIH patients, accounting for approximately 10.2-14.1% of all concomitant autoimmune diseases, and thyroid eye disease (Graves' ophthalmopathy) can affect the eyes. 2
Inflammatory bowel disease (IBD), particularly ulcerative colitis, carries a nearly 10% risk of developing primary sclerosing cholangitis (PSC), and IBD itself is associated with ocular manifestations including uveitis, episcleritis, and scleritis. 1
Systemic lupus erythematosus (SLE) occurs in approximately 2.2-3% of patients with autoimmune liver disease and commonly causes retinal vasculitis, keratoconjunctivitis sicca, and other ocular complications. 2
Overlap Syndromes
Overlap syndromes between different autoimmune liver diseases are increasingly recognized, including AIH-primary biliary cholangitis (PBC) overlap occurring in 8-10% of AIH patients, and AIH-PSC overlap. 2, 3, 4 These conditions can coexist with systemic autoimmune diseases that have ocular involvement.
Specific Autoimmune Conditions with Liver-Eye Involvement
Sjögren Syndrome
- Affects approximately 2.8-7% of patients with autoimmune conditions and causes severe dry eyes (keratoconjunctivitis sicca) while also potentially causing autoimmune hepatitis or primary biliary cholangitis. 2
Autoimmune Polyendocrinopathy Syndrome Type 1 (APS-1/APECED)
- This rare autosomal recessive condition caused by AIRE gene mutations is characterized by chronic mucocutaneous candidiasis, ectodermal dystrophy, and autoimmune destruction of multiple endocrine organs, and can present with AIH as part of its spectrum. 1 Ocular involvement occurs through the ectodermal dystrophy component.
Rheumatoid Arthritis
- Develops in approximately 2-4% of patients with autoimmune hepatitis and can cause scleritis, episcleritis, and keratoconjunctivitis sicca. 2
IgG4-Associated Disease
- IgG4-associated cholangitis affects the liver and can be part of systemic IgG4-related disease, which frequently involves orbital pseudotumors and dacryoadenitis affecting the eyes. 1, 5
Clinical Implications and Screening
Extended diagnostic screening for other autoimmune diseases, especially autoimmune thyroiditis, is reasonable in patients with AIH, both at diagnosis and at regular intervals during follow-up. 1 This screening should include:
- Thyroid function tests and thyroid antibodies (given the 10-14% prevalence of concurrent thyroid disease) 2
- Assessment for IBD symptoms, particularly in younger patients 1
- Evaluation for sicca symptoms suggesting Sjögren syndrome 2
- Careful family history, as first-degree relatives of AIH patients have increased occurrence of immune-mediated diseases 1
Important Caveats
The occurrence of autoimmune diseases is more frequent in first-degree relatives of AIH patients, necessitating careful family history. 1 When evaluating patients with liver disease for potential ocular involvement, consider that:
- Ocular manifestations may precede, coincide with, or follow the diagnosis of autoimmune liver disease
- The severity of liver disease does not necessarily correlate with the severity of ocular involvement
- Immunosuppressive treatment for AIH may improve some ocular manifestations but can increase risk of opportunistic ocular infections
Approximately one-third of patients with AIH already have cirrhosis at presentation, emphasizing the importance of early recognition of both hepatic and extra-hepatic manifestations. 1