Associations of severe liver diseases with cataract using data from UK Biobank: a prospective cohort study

**Background:** Liver disease is a global health burden associated with extrahepatic multisystem manifestations, but its relationship with cataract—the leading cause of blindness—has been poorly studied. Previous research focused only on viral hepatitis with cross-sectional designs or insufficient adjustment. This study aimed to systematically investigate whether severe NAFLD, ALD, viral hepatitis, and liver fibrosis/cirrhosis increase cataract risk.

**Methods:** The UK Biobank prospective cohort enrolled over 500,000 participants aged 37–73 years between 2006 and 2010. After excluding those with baseline cataract (n=14,238), unconfirmed cataract records (n=2,721), missing covariate data (n=157,997), and loss to follow-up (n=856), 326,558 participants were included. Severe liver diseases were defined by hospital admission using ICD-9/10 codes. Incident cataract was ascertained from multiple sources (self-report, primary care, hospital, death register) with explicit clinical confirmation. Cox proportional hazards models with age as time-axis were used, treating each liver disease as a binary time-varying variable (exposed vs. unexposed) and as a ternary time-varying variable (recent ≤5 years vs. long-term >5 years). Models were adjusted for demographics (model 1), lifestyle factors (model 2), and metabolic factors including BMI, HDL-C, triglycerides, hypertension, and diabetes (model 3). Combined models included all four liver diseases simultaneously. Subgroup and sensitivity analyses were performed.

**Key Results:** After a median follow-up of 13.3 years (IQR 12.5–14.0), 37,064 participants developed cataract. In the fully adjusted model (model 3), severe NAFLD (HR 1.47; 95% CI 1.33–1.61), ALD (HR 1.57; 95% CI 1.28–1.94), and liver fibrosis/cirrhosis (HR 1.58; 95% CI 1.35–1.85) were significantly associated with increased cataract risk. Viral hepatitis showed no association when treated as binary (HR 1.20; 95% CI 0.95–1.53; P=0.13), but recently diagnosed viral hepatitis (≤5 years) was associated with higher risk (HR 1.55; 95% CI 1.07–2.23; P=0.019). Long-term states (>5 years) for NAFLD (HR 1.52; 95% CI 1.31–1.78), ALD (HR 1.51; 95% CI 1.14–2.00), and liver fibrosis/cirrhosis (HR 1.48; 95% CI 1.17–1.88) remained significant. Combined models confirmed independent effects. Subgroup analyses showed physical activity attenuated viral hepatitis risk (P interaction=0.002), hypertension amplified it (P interaction=0.021), and diabetes reduced NAFLD effect (P interaction=0.0043). Sensitivity analyses, including E-values (2.30–2.53), supported robustness.

**Clinical Implications:** Severe liver diseases—NAFLD, ALD, liver fibrosis/cirrhosis, and recently diagnosed viral hepatitis—are independent risk factors for cataract. These findings expand the extrahepatic disease spectrum of liver disease and emphasize the need for ophthalmic surveillance in patients with severe liver disease. Early cataract screening and intervention may be warranted in this population, especially given global aging. The study also suggests potential mechanistic links (metabolic derangement, systemic inflammation) that require further investigation.