NAFLD, Viral Hepatitis Among Liver Diseases Associated With Risk of Incident Cataract

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Liver diseases and their comorbid conditions extend well beyond the liver – extrahepatic manifestations often present as a result of the metabolic alterations and immune-mediated inflammation associated with liver disease, although findings from a recent study are providing novel insight into the association between hepatic and ophthalmic diseases.¹

Results published in The Lancet support the concept of a liver-eye connection and emphasize the need for ophthalmic care in the management of liver disease, showing severe nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), liver fibrosis and cirrhosis, and recently diagnosed viral hepatitis were associated with an increased risk of cataract.¹

According to the American Liver Foundation, more than 100 million people in the US have some form of liver disease. Both hepatic and extrahepatic complications are frequently seen in individuals with liver disease. Although its associations with metabolic syndrome, type 2 diabetes, cardiovascular disease, and chronic kidney disease are well established, the connection between liver disease and ophthalmic complications, namely cataracts, is not well established.^1,2,3

“Liver disease may increase the risk of cataract development owing to the metabolic and immune alternations,” wrote Xiangjia Zhu, MD, ophthalmologist at the Eye & ENT Hospital of Fudan University in China, and colleagues.¹ “However, to the best of our knowledge, the association between liver disease and cataract has merely been investigated in viral hepatitis limited by cross-sectional design or insufficient variable adjustment.”

Seeking to gain a more comprehensive understanding of this association, investigators collected patient data for participants in the UK Biobank, excluding those diagnosed with cataract at baseline, who had records of cataract without explicit clinical confirmation, or were missing data on covariates. In total, 326,558 participants were included in the present analysis.¹

The exposures of interest were severe liver diseases, including NAFLD, ALD, viral hepatitis, and liver fibrosis and cirrhosis, defined by hospitalization due to liver disease based on ICD-9 and ICD-10 codes. The primary outcome was incident cataract, assessed using the “first occurrences” fields provided by the UK Biobank and mapped to unified ICD codes. Investigators noted each liver disease was first treated as a binary time-varying variable to investigate its association with cataract, and then was treated as a ternary time-varying variable to examine the recent and long-term state associations with the risk of cataract.¹

Among the cohort, 51.9% of participants were female and the mean age at enrollment was 56.1 (Standard deviation [SD], 8.1) years. At baseline and during follow-up, 6376 participants were diagnosed with ≥ 1 liver disease, mostly NAFLD (n = 327 cases at baseline; n = 3902 cases during follow-up), liver fibrosis and cirrhosis (n = 198 cases at baseline; n = 1143 cases during follow-up), and ALD (n = 282 cases at baseline; n = 781 cases during follow-up).¹

After a median follow-up of 13.3 (interquartile range [IQR], 12.5–14.0) years, 37,064 individuals were documented as developing cataract. Upon analysis, participants with NAFLD had a 47% increased risk of cataract (Hazard ratio [HR], 1.47; 95% CI, 1.33–1.61; P <.0001), although investigators pointed out this risk grew 5 years post-NAFLD diagnosis (HR, 1.52; 95% CI, 1.31–1.78; P <.0001) compared with the first 5 years (HR, 1.43; 95% CI, 1.26–1.62; P <.0001).¹

An increased risk of cataract was also observed among individuals with ALD (HR, 1.57; 95% CI, 1.28–1.94) and liver fibrosis and cirrhosis (HR, 1.58; 95% CI, 1.35–1.85). Unlike NAFLD, this risk was greater during the first 5 years of diagnosis (ALD: HR, 1.66; 95% CI, 1.22–2.27; P = .0013; Liver fibrosis and cirrhosis: HR, 1.67; 95% CI, 1.35–2.06; P <.0001) rather than 5 years after ALD (HR, 1.51; 95% CI, 1.14–2.00; P = .0042) or liver fibrosis and cirrhosis (HR, 1.48; 95% CI, 1.17–1.88; P = .0013) diagnosis.¹

Of note, viral hepatitis was not associated with cataract when treated as a binary time-varying exposure (HR, 1.20; 95% CI, 0.95–1.53; P = .13). When investigators assessed viral hepatitis as a ternary time-varying variable, they observed an association for recently diagnosed viral hepatitis (HR, 1.55; 95% CI, 1.07–2.23; P = .019) but not after 5 years (HR, 1.03; 95% CI, 0.75–1.41; P = .86).¹

“Considering that liver disease is increasingly advocated as a multisystem disease, these results are of significance for the comprehensive management of liver disease. Our work also provided evidence for early intervention in those with liver disease for prevention of cataract in the context of global population aging,” investigators concluded.¹

References:

1. ^{Chen C, Wei L, Zhang Y, et al. Associations of severe liver diseases with cataract using data from UK Biobank: a prospective cohort study. https://doi.org/10.1016/j.eclinm.2024.102424}
2. ^{American Liver Foundation. How Many People Have Liver Disease?. About Your Liver. September 11, 2023. Accessed February 23, 2024. https://liverfoundation.org/about-your-liver/facts-about-liver-disease/how-many-people-have-liver-disease/}
3. ^{Glass LM, Hunt CM, Fuchs M, Su GL. Comorbidities and Nonalcoholic Fatty Liver Disease: The Chicken, the Egg, or Both?. Fed Pract. 2019;36(2):64-71.}