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

Abstract

Background: Liver disease is linked to series of extrahepatic multisystem manifestations. However, little is known about the associations between liver and eye diseases, especially cataract, the global leading cause of blindness. We aimed to investigate whether severe liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, and liver fibrosis and cirrhosis, were associated with an increased risk of the cataract.

Methods: A total of 326,558 participants without cataract at baseline enrolled in the UK Biobank between 2006 and 2010 were included in this prospective study. The exposures of interest were severe liver diseases (defined as hospital admission), including NAFLD, ALD, viral hepatitis and liver fibrosis and cirrhosis. The outcome was incident cataract. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). 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 (liver disease within 0-5 years) vs. long-term (liver disease > 5 years) state associations with the risk of cataract.

Findings: After a median follow-up of 13.3 years (interquartile range, 12.5-14.0 years), 37,064 individuals were documented as developing cataract. Higher risk of cataract was found in those with severe NAFLD (HR, 1.47; 95% CI, 1.33-1.61), ALD (HR, 1.57; 95% CI, 1.28-1.94) and liver fibrosis and cirrhosis (HR, 1.58; 95% CI, 1.35-1.85), but not in individuals with viral hepatitis when exposure was treated as a binary time-varying variable (P = 0.13). When treating exposure as a ternary time-varying variable, an association between recently diagnosed viral hepatitis and cataract was also observed (HR, 1.55; 95% CI, 1.07-2.23). Results from the combined model suggested they were independent risk factors for incident cataract. No substantial changes were found in further sensitivity analyses.

Interpretation: Severe liver diseases, including NAFLD, ALD, liver fibrosis and cirrhosis and recently diagnosed viral hepatitis, were associated with cataract. The revelation of liver-eye connection suggests the importance of ophthalmic care in the management of liver disease, and the intervention precedence of patients with liver disease in the early screening and diagnosis of cataract.

Funding: National Natural Science Foundation of China, Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission, Clinical Research Plan of Shanghai Shenkang Hospital Development Center, Shanghai Municipal Key Clinical Specialty Program, the Guangdong Basic and Applied Basic Research Foundation and Shenzhen Science and Technology Program.

Keywords: Alcoholic liver disease; Cataract; Cirrhosis; Liver fibrosis; Non-alcoholic fatty liver disease; Viral hepatitis.

Fig. 1

Flowchart showing the criterion of the study cohort from participants in the UK Biobank. NAFLD, non-alcoholic fatty liver disease; ALD, alcoholic liver disease.

Fig. 2

Associations between severe liver diseases and cataract in the combined model. The hazard ratios for developing cataract were estimated using Cox proportional hazards models adjusted for sex, year of birth, ethnicity, Townsend deprivation index, alcohol intake, smoking status, physical activity, body mass index, concentration of HDL-C, concentration of triglycerides, history of hypertension and history of diabetes with all four liver diseases modeled together. Each liver disease was treated as a binary or ternary time-varying variable and age was used as the time-axis. A P value below 0.05 was considered statistically significant. HR, hazard ratio; CI, confidence interval; HDL-C, high-density lipoprotein cholesterol.

Fig. 3

Associations between severe liver diseases and cataract in the combined model according to potential risk factors. The effects of each liver disease on incident cataract according to (A) physical activity, (B) history of hypertension, and (C) history of diabetes were estimated by combined Cox proportional hazards models adjusted for sex, year of birth, ethnicity, Townsend deprivation index, alcohol intake, smoking status, physical activity, body mass index, concentration of HDL-C, concentration of triglycerides, history of hypertension and history of diabetes except for the strata factor in each subgroup. Age was used as the time-axis. Physical activity that met the 2017 UK Physical activity guidelines (150 min of walking or moderate activity per week or 75 min of vigorous activity) was defined as above recommendation. A P value below 0.05 was considered statistically significant. HR, hazard ratio; CI, confidence interval; P_int, P value for interaction; HDL-C, high-density lipoprotein cholesterol.