Exploring causal links between autoimmune liver diseases, chronic hepatitis C, and thyroid disorders: Evidence from NHANES and GWAS studies

Autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), often have complex interactions with thyroid diseases (TDs), such as hypothyroidism, hyperthyroidism, and Hashimoto thyroiditis (HT). These conditions frequently coexist and may share common autoimmune mechanisms, but their exact relationship remains poorly understood. Chronic hepatitis C (CHC), a viral liver disease, also affects thyroid function, but its interaction with TD is still under investigation. This study explores the causal links between AILD, CHC, and TD using data from the National Health and Nutrition Examination Survey (NHANES) and Mendelian randomization (MR) analysis. Data were sourced from NHANES (2013-2018) and various genome-wide association studies. The NHANES analysis included 8978 participants after applying inclusion and exclusion criteria. Logistic regression models were used to assess associations between CHC and TD. MR analysis employed single-nucleotide polymorphisms as instrumental variables to investigate causal relationships between AILD, CHC, and TD. NHANES analysis revealed no significant association between CHC and TD. Forward MR analysis indicated significant causal relationships between PBC and hypothyroidism (inverse variance weighting [IVW] odds ratio [OR] = 1.004, 95% confidence intervals [CI] 1.002-1.006, P < .001), PSC and hyperthyroidism (IVW OR = 1.002, 95% CI 1.002-1.003, P < .001), and PBC and HT (IVW OR = 1.05, 95% CI 1.012-1.089, P = .010). Reverse MR analysis suggested causal links between hypothyroidism, hyperthyroidism, HT, thyroid cancer, and AIH, as well as hypothyroidism with PBC and PSC. Multivariable MR confirmed significant associations between AIH and hypothyroidism (P < .001), hyperthyroidism (P = .008) across IVW method. The IVW method also revealed another significant causal relationship between PSC and hyperthyroidism (P < .001), HT (P = .013). Multivariable MR also analysis to investigate the association between TD as exposures and AILD as outcomes; the IVW method revealed a noteworthy causal association solely between HT and AIH (P = .035). The study identified significant causal associations between AILD (particularly PBC and PSC) and specific TD, emphasizing the need for regular thyroid monitoring in AILD patients. However, no significant causal link was found between CHC and TD.