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. 2025 Aug 29;104(35):e44112.
doi: 10.1097/MD.0000000000044112.

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

Qilong Nie  1 , Yongwen Jiang  1 , Qiuyan Liang  1 , Mingyang Li  1 , Caiyang Huang  1   2 , Yongwei Yuan  1 , Tengyu Qiu  1   2 , Xiaojun Ma  1   2 , Jianhong Li  1   2
Affiliations

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

Qilong Nie et al. Medicine (Baltimore). .

V体育平台登录 - Abstract

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 VSports手机版. 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. .

Keywords: GWAS; Mendelian randomization; NHANES; autoimmune liver disease; chronic hepatitis C; thyroid disease V体育安卓版. .

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Flowchart of participants’ inclusion. HCV = hepatitis C virus, NHANES = National Health and Nutrition Examination Survey.
Figure 2.
Figure 2.
Foundations of Mendelian genetics: the 3 assumptions of randomization.
Figure 3.
Figure 3.
Flowchart of forward and reverse Mendelian randomization methods. AIH = autoimmune hepatitis, AILD = autoimmune liver disease, GWAS = genome-wide association studies, IV = instrumental variable, LD = linkage disequilibrium, MR =Mendelian randomization, PBC = primary biliary cholangitis, PSC = primary sclerosing cholangitis, SNPs = single-nucleotide polymorphisms.
Figure 4.
Figure 4.
Forest plot of forward two-sample Mendelian randomization analysis for exposure effects. AIH = autoimmune hepatitis, OR = odds ratio, PBC = primary biliary cholangitis, PSC = primary sclerosing cholangitis.
Figure 5.
Figure 5.
Visual summary of key causal associations identified by Mendelian randomization. AIH = autoimmune hepatitis, HT = Hashimoto thyroiditis, PBC = primary biliary cholangitis, PSC = primary sclerosing cholangitis.
See this image and copyright information in PMC

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