Links Between Shift Work, Personal and Lifestyle Factors, Body Measurements, and Fatty Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a highly prevalent chronic liver condition that affects over 30% of the global population, posing a significant public health burden [1] and imposing considerable economic costs on healthcare systems [2]. It is characterized by excessive hepatic fat accumulation (hepatic steatosis) in the absence of significant alcohol intake or other secondary causes of liver disease [3]. MASLD arises from complex interactions among genetic, environmental, and cardiometabolic factors, with insulin resistance and adipose tissue dysfunction playing central pathophysiological roles. The condition encompasses a broad clinical spectrum, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), formerly referred to as non-alcoholic steatohepatitis (NASH) [4], hepatic fibrosis [5], and, in more advanced stages, cirrhosis [6] and hepatocellular carcinoma [7]. Due to its strong association with metabolic syndrome [8] and other non-communicable chronic diseases, MASLD represents a research priority for the development of effective preventive and therapeutic strategies. Despite the recent advances in understanding its pathophysiology, the disease progression and treatment response remain heterogeneous. In this context, the Liver Disease Nomenclature Development Initiative proposed a more accurate and less stigmatizing terminology to better reflect the underlying causes of the disease, improve the diagnostic clarity, raise awareness, and facilitate more appropriate allocation of resources for research and clinical care [9].

The escalating prevalence of MASLD parallels the global rise in obesity and sedentary behaviors, but it is also increasingly evident that social determinants of health and work-related factors play a crucial role in shaping metabolic outcomes. In particular, shift work—a form of employment scheduling that diverges from the traditional diurnal work pattern—has been associated with circadian rhythm disruption, metabolic dysregulation, and the increased risk of cardiometabolic diseases [10,11]. Shift work includes night shifts, rotating schedules, and irregular hours, and it is prevalent in essential sectors such as healthcare, manufacturing, transportation, and security. The chronobiological alterations induced by shift work, including sleep deprivation, hormone imbalance, and altered eating patterns, may exacerbate metabolic dysfunction and inflammation, thus potentiating the development of MASLD [12,13].

Several studies have established associations between shift work and the components of metabolic syndrome, including obesity, hypertension, impaired glucose metabolism, and dyslipidemia [14,15,16]. However, relatively few large-scale epidemiological investigations have explored the potential link between shift work and MASLD, particularly using validated non-invasive indices of hepatic steatosis. Moreover, previous research has often focused on specific occupational groups or lacked detailed sociodemographic and lifestyle data, limiting the generalizability of findings and impeding the development of comprehensive preventive strategies.

Importantly, the influence of shift work on the MASLD risk may not be uniform across population subgroups. Sociodemographic characteristics such as sex, age, and occupational category, as well as health behaviors including smoking, alcohol consumption, diet, and physical activity, may modulate the relationship between work schedule and liver health. Blue-collar workers, who are more likely to be engaged in manual labor and irregular work hours, may face compounded risks due to higher rates of smoking, poor diet, and limited access to healthcare services [17,18]. Women, on the other hand, may exhibit differential susceptibility to metabolic disturbances depending on their hormonal status, caregiving responsibilities, and social stressors. As such, disaggregated analyses by sex and employment sector are essential to capture the full complexity of MASLD risk profiles in the context of shift work.

Given the subclinical nature of MASLD in its early stages, the use of surrogate biomarkers and composite indices is indispensable for population-level screening. A number of non-invasive scoring systems have been developed to estimate the presence of hepatic steatosis or fibrosis using routine clinical and biochemical parameters. These include the fatty liver index (FLI) [19], hepatic steatosis index (HSI) [20], Zhejian University (ZJU) index [21], fatty liver disease (FLD) index [22], lipid accumulation product (LAP) [23], and the BARD score for liver fibrosis [24]. Such tools provide valuable epidemiological insights and allow for the identification of at-risk individuals in occupational health settings without the need for imaging or liver biopsy.

Despite the availability of these validated indices, few studies have systematically applied multiple MASLD risk scales to large, heterogeneous working populations. This approach offers the advantage of cross-validation and may reveal distinct patterns depending on the components included in each index. For example, indices incorporating waist circumference and triglycerides may be more sensitive to dietary and physical activity changes, while those emphasizing AST/ALT ratios may better reflect liver-specific injury. Moreover, the comparison of these indices across work schedules and sociodemographic strata can shed light on the potential mechanisms and intervention targets.

In the present study, we sought to evaluate the association between shift work and the risk of MASLD in a large, diverse cohort of Spanish workers. Utilizing data from over 53,000 employed adults undergoing routine occupational health examinations across multiple regions and sectors, we examined six established MASLD indices to assess the potential impact of shift work on liver health. Our objectives were fourfold: (1) to compare sociodemographic characteristics, anthropometric measurements, clinical and biochemical markers, and lifestyle factors between shift and non-shift workers; (2) to analyze the mean values and prevalence of high-risk scores for each MASLD index according to shift status and sex; (3) to evaluate the independent contribution of shift work to an elevated MASLD risk through multivariable logistic regression models adjusting for key confounders; and (4) to explore the modifying role of age, sex, occupational class, and lifestyle behaviors on these associations.

To our knowledge, this is one of the largest occupational health studies to date examining the relationship between shift work and MASLD using a comprehensive panel of non-invasive indices. The integration of detailed demographic, anthropometric, biochemical, and lifestyle data allows for a nuanced understanding of the interplay between work patterns and liver health. Furthermore, the inclusion of both male and female workers across white- and blue-collar occupations enables the identification of vulnerable subgroups and informs tailored intervention strategies. The findings from this study hold relevance for occupational medicine practitioners, public health policymakers, and employers aiming to mitigate the metabolic risk in shift-working populations.

Each of the MASLD indices used in this study captures different aspects of hepatic pathology. For instance, the FLI and LAP primarily emphasize anthropometric and lipid parameters, making them sensitive to adiposity and dyslipidemia. The HSI and ZJU indices include liver enzyme ratios (e.g., AST/ALT), which better reflect hepatocellular injury. The FLD and FSI incorporate broader metabolic indicators, while the BARD score combines the AST/ALT ratio, BMI, and diabetes status to estimate the fibrosis risk. These differences may account for the varying strength of the associations observed among the indices, highlighting the value of a multimodal assessment approach.

In summary, this study addresses a critical gap in the literature by providing robust evidence on the association between shift work and MASLD in a representative working population. In the context of increasing MASLD prevalence and rising demands for non-standard work schedules, understanding the occupational determinants of liver disease is imperative for effective prevention and health promotion. The use of validated indices for early detection, coupled with targeted workplace interventions, may offer a pathway to reduce the burden of MASLD and improve the long-term outcomes among at-risk workers.

Table 2 reveals the significant differences in anthropometric, clinical, and biochemical variables between shift and non-shift workers. Among men, shift workers were slightly younger and shorter but presented higher values of systolic and diastolic blood pressure, total cholesterol, fasting glucose, AST, ALT, and GGT. In women, shift work was also associated with a more unfavorable metabolic profile, including lower HDL cholesterol and higher waist circumference, triglycerides, glucose, and hepatic enzyme levels. Age distribution and occupational classification showed notable disparities: shift workers were more frequently younger and predominantly engaged in blue-collar occupations. These findings support the hypothesis that shift work contributes to the clustering of cardiometabolic risk factors, particularly in socioeconomically disadvantaged groups.

The mean values across all the MASLD indices (FLI, HSI, ZJU, FLD, FSI, LAP, and BARD) were consistently higher among shift workers, in both sexes. Although some differences were modest in absolute terms, their consistency across all the scales strengthens the observed association. Women showed lower absolute values overall; however, the relative increase associated with shift work was more pronounced, particularly in the BARD and LAP scores. This may indicate that women are more metabolically sensitive to the physiological disruptions caused by shift work (). Table S1

This table confirms a significantly higher prevalence of elevated risk scores in all the indices among shift workers. For example, in men, the proportion of individuals with high ZJU scores increased from 41.2% to 53.2%, and for BARD, from 43.5% to 71.5%. In women, the increases were even more striking, with high ZJU scores rising from 27.3% to 50.1% and BARD from 49.9% to 85.7%. These results not only reinforce the relationship between shift work and hepatic risk but also suggest potential sex-based differences in vulnerability (Table 3).

Importantly, although the group means for several indices were near the diagnostic thresholds, the prevalence data presented in Table 4 clarify that a substantial proportion of individuals exceeded the established high-risk cut-offs for each NAFLD index. These thresholds are widely accepted as indicative of a clinically relevant likelihood of MASLD (metabolic dysfunction-associated steatotic liver disease). For instance, among male shift workers, over 70% had a BARD score ≥2 and more than 50% surpassed the high-risk cut-off for the ZJU index. In women, the increases were similarly marked, with 85.7% showing elevated BARD scores and 50.1% exceeding the ZJU threshold. These findings confirm that the observed differences are not limited to borderline elevations but reflect a true excess in the proportion of high-risk individuals meeting the clinical criteria for suspected MASLD.

The multivariate analysis confirmed that shift work is independently associated with an increased risk in all the MASLD indices, with particularly high odds ratios for HSI (OR = 7.83) and ZJU (OR = 5.91). Male sex, older age, smoking, blue-collar status, and shift work were consistently associated with a higher probability of elevated risk scores. These associations highlight a cumulative effect of biological, behavioral, and social vulnerability factors converging to increase the liver disease risk among shift workers (Table 4).

This study, which included over 53,000 workers from various professional sectors across Spain, provides robust evidence linking shift work to an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Utilizing six validated non-invasive indices (FLI, HSI, ZJU index, FLD index, FSI, LAP, and BARD score), our analysis demonstrated consistently higher risk scores among shift workers compared to non-shift workers. Moreover, significant differences were observed in anthropometric, clinical, and biochemical parameters. In male workers, those engaged in shift work exhibited higher systolic and diastolic blood pressures, and elevated levels of fasting glucose, total cholesterol, and liver enzymes, while among females, shift work was associated with lower HDL cholesterol and higher waist circumference and triglyceride levels. These findings underscore the hypothesis that non-standard work schedules may contribute to adverse metabolic profiles, ultimately increasing the risk of MASLD [30,31].

Prior research has established the association between shift work and metabolic derangements, including insulin resistance, dyslipidemia, and obesity [32]. However, few studies have specifically examined the relationship between shift work and MASLD using multiple screening indices simultaneously. Our findings extend the previous literature by confirming that shift work is an independent risk factor for MASLD, after the adjustment for potential confounders such as age, sex, socioeconomic status, and lifestyle habits [33]. In contrast to earlier studies that often focused on specific occupational groups or single risk markers, the present investigation adopts a comprehensive approach by integrating a suite of non-invasive indices. This methodological refinement enables cross-validation and provides more granular insights into the potential hepatic impact of shift work [34]. Furthermore, our data reveal that the prevalence of high-risk scores across indices is markedly greater among shift workers, corroborating earlier reports that linked circadian disruption to liver steatosis and fibrosis [35].

The pathophysiological mechanisms underlying the association between shift work and metabolic dysfunction-associated steatotic liver disease (MASLD) appear to be multifactorial. One of the primary mechanisms involves the disruption of the circadian rhythm [36]. Circadian misalignment—resulting from factors such as night shifts, exposure to artificial light during nighttime, and irregular sleep and feeding schedules—profoundly affects hepatic homeostasis, altering key processes such as lipid metabolism, insulin signaling, and inflammatory responses [37].

The liver is a highly circadian organ, regulated both by the central clock located in the suprachiasmatic nucleus (SCN) and by autonomous peripheral clocks influenced by factors like the feeding–fasting cycle. Recent studies have shown that desynchronization between these clocks disrupts the rhythmic expression of the key genes involved in lipogenesis and β-oxidation, such as Srebp-1c, Fasn, Acc1, Pparα, and Cpt1a. This dysregulation leads to ectopic lipid accumulation in the liver, predisposing individuals to hepatic steatosis and mitochondrial dysfunction [38]. Moreover, circadian disruption impairs insulin signaling by dysregulating proteins such as Akt, IRS-1, and FoxO1, thereby reducing the hepatic insulin sensitivity and promoting inappropriate gluconeogenesis, even in postprandial states.

This contributes to the development of hepatic insulin resistance, a key feature of metabolic syndrome and type 2 diabetes. From an inflammatory standpoint, the liver also displays circadian rhythmicity in the expression of cytokines and immune mediators. Circadian disruption fosters a pro-inflammatory environment, characterized by the activation of the NF-κB pathway, increased production of IL-6, TNF-α, and other pro-inflammatory cytokines, and enhanced infiltration of M1-polarized hepatic macrophages. This inflammatory microenvironment not only exacerbates liver injury but also further impairs insulin signaling, creating a vicious cycle of inflammation, insulin resistance, and metabolic dysfunction that promotes hepatic fat accumulation [39,40].

Evidence from murine models has demonstrated that the hepatocyte-specific deletion of circadian clock genes such as Bmal1 or Clock leads to severe disturbances in lipid and insulin metabolism, even in the absence of dietary modifications. In humans, circadian misalignment has been associated with altered metabolic profiles, particularly among night shift workers, who show a higher prevalence of non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and hepatic inflammation [41]. Additionally, sleep deprivation—commonly observed in shift workers—has been linked to increased sympathetic activity, elevated cortisol levels, and systemic inflammation, all of which may further exacerbate liver injury and steatosis [42].

Altered dietary patterns and irregular meal timings, frequently seen in shift work populations, further contribute to metabolic disturbances. Erratic eating habits can result in postprandial hyperglycemia and dysregulated lipid profiles, which are critical in the development of hepatic steatosis. Moreover, shift workers often report lower consumption of healthy foods such as fruits and vegetables, coupled with a higher intake of processed and high-calorie foods [43]. These lifestyle factors, in conjunction with physical inactivity, synergistically increase the risk of MASLD [44]. Finally, the stress associated with irregular work schedules might also play a role; chronic stress can lead to endocrine abnormalities and increased pro-inflammatory cytokine production, promoting hepatic injury and fibrogenesis [45].

These findings underscore the importance of circadian alignment for liver health, suggesting that interventions such as time-restricted feeding, controlled light exposure, and regular sleep patterns may represent effective therapeutic strategies to restore hepatic rhythmicity and prevent chronic metabolic diseases.

Our analysis reveals notable differences in how shift work impacts male versus female workers, as well as distinctions based on occupational categories. Although the absolute risk scores for MASLD tend to be lower among women, the relative change associated with shift work is more pronounced. This could be due to hormonal differences that modulate metabolic responses or the dual burden of caregiving and occupational demands that many women experience [46]. Furthermore, blue-collar workers, who are more frequently exposed to shift work schedules, show a particularly adverse profile with higher risk scores and an increased prevalence of metabolic derangements [47]. These findings suggest that both biological sex and the nature of occupational roles may modify the impact of circadian disruption on liver health, warranting targeted preventive strategies for these vulnerable subgroups [48].

In summary, our study provides robust evidence that shift work is significantly associated with an increased risk of MASLD, as determined by multiple validated non-invasive indices. The association remains significant after adjusting for potential confounders, indicating that shift work independently contributes to hepatic risk. Notably, women and blue-collar workers appear particularly vulnerable, highlighting the need for tailored interventions in these groups. Given the cross-sectional design of the study, causal relationships cannot be established; therefore, although the associations between shift work and MASLD risk are evident, longitudinal studies are required to clarify the temporal direction of these associations. These findings have important implications for occupational health policies, suggesting that routine screening and preventive strategies should be integrated into workplace health programs. Future longitudinal and mechanistic studies are warranted to further elucidate the causal pathways and to evaluate the effectiveness of targeted interventions in reducing the burden of MASLD among shift workers.