Background Pain symptoms are common in liver disease patients, but the temporal relationship between liver disease onset and pain development, as well as specific risk factors for pain in this population, remains poorly characterized. Objective This study aimed to examine the longitudinal trajectories of pain symptoms and identify risk factors for pain in patients with incident liver disease using a nationwide cohort. Methods We analyzed data from 16,159 participants without baseline liver disease in the China Health and Retirement Longitudinal Study (2011–2020). Incident liver disease was defined as new-onset physician-diagnosed liver disease during follow-up. Pain at 15 body sites was assessed dichotomously. Generalized estimating equations identified risk factors for pain symptoms post-diagnosis, adjusting for demographics, health status, lifestyle, and comorbidities. Time interactions, subgroup analysis by gender and residence, and sensitivity analysis including multiple imputation and different model specifications were performed. Results Among participants, 1150 (7.1%) developed incident liver disease over 9 years. At baseline, future incident cases showed significantly higher pain prevalence across all sites compared to those remaining disease-free (waist pain: 28.7% vs 17.9%, P < 0.001; leg pain: 20.7% vs 13.9%, P < 0.001; headache: 20.6% vs 12.4%, P < 0.001). Post-diagnosis pain prevalence increased substantially, with waist pain rising from 28.1% to 45.3%. Arthritis emerged as the strongest risk factor (OR range: 1.42–4.99), particularly for musculoskeletal pain. Depression (CESD-10) was consistently associated with increased pain risk (OR: 1.03–1.08, all P < 0.05), while self-rated health showed protective effects (OR: 0.72–0.82). Significant interactions revealed stronger depression-pain associations in males and urban residents. Kidney disease effects on back pain intensified over time (interaction OR = 1.47, P = 0.003). Conclusions Pain symptoms precede liver disease diagnosis and progressively worsen thereafter, with arthritis and depression as key modifiable risk factors requiring targeted management strategies in this vulnerable population.

Longitudinal analysis of pain symptoms and risk factors in patients with incident liver disease: a nationwide cohort study

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2026年2月9日

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Ke Pu,
Xiaodi Zhu

摘要

Background

Pain symptoms are common in liver disease patients, but the temporal relationship between liver disease onset and pain development, as well as specific risk factors for pain in this population, remains poorly characterized.

Objective

This study aimed to examine the longitudinal trajectories of pain symptoms and identify risk factors for pain in patients with incident liver disease using a nationwide cohort.

Methods

We analyzed data from 16,159 participants without baseline liver disease in the China Health and Retirement Longitudinal Study (2011–2020). Incident liver disease was defined as new-onset physician-diagnosed liver disease during follow-up. Pain at 15 body sites was assessed dichotomously. Generalized estimating equations identified risk factors for pain symptoms post-diagnosis, adjusting for demographics, health status, lifestyle, and comorbidities. Time interactions, subgroup analysis by gender and residence, and sensitivity analysis including multiple imputation and different model specifications were performed.

Results

Among participants, 1150 (7.1%) developed incident liver disease over 9 years. At baseline, future incident cases showed significantly higher pain prevalence across all sites compared to those remaining disease-free (waist pain: 28.7% vs 17.9%, P < 0.001; leg pain: 20.7% vs 13.9%, P < 0.001; headache: 20.6% vs 12.4%, P < 0.001). Post-diagnosis pain prevalence increased substantially, with waist pain rising from 28.1% to 45.3%. Arthritis emerged as the strongest risk factor (OR range: 1.42–4.99), particularly for musculoskeletal pain. Depression (CESD-10) was consistently associated with increased pain risk (OR: 1.03–1.08, all P < 0.05), while self-rated health showed protective effects (OR: 0.72–0.82). Significant interactions revealed stronger depression-pain associations in males and urban residents. Kidney disease effects on back pain intensified over time (interaction OR = 1.47, P = 0.003).

Conclusions

Pain symptoms precede liver disease diagnosis and progressively worsen thereafter, with arthritis and depression as key modifiable risk factors requiring targeted management strategies in this vulnerable population.