Long-term day-and-night rotating shift work poses a barrier to the normalization of alanine transaminase

Abstract

To evaluate the impact of day-and-night rotating shift work (RSW) on liver health, we performed a retrospective analysis of the association between long-term RSW exposure and the normalization of plasma alanine transaminase (ALT) levels over a five-year period. The data from physical examinations, blood tests, abdominal sonographic examinations, personal histories, and occupational records were collected from a cohort of workers in a semiconductor manufacturing company. The sample population was divided into three subgroups for analysis, according to self-reported shift work status over the five-year interval: persistent daytime workers, workers exposed intermittently to RSW (i-RSW), and workers exposed persistently to RSW (p-RSW). Records were analyzed for 1196 male workers with an initial mean age of 32.5 years (SD 6.0 years), of whom 821 (68.7%) were identified as rotating shift workers, including 374 i-RSW (31.3%) and 447 p-RSW workers (37.4%). At the beginning of the follow-up, 275 were found to have elevated ALT (e-ALT): 25.1% daytime workers, 23.0% i-RSW workers, and 21.3% p-RSW workers (p = 0.098). Of those with e-ALT at the beginning, 101 workers showed normalized serum ALT levels at the end of five-year follow-up: 40 (10.7%) of 375 daytime workers, 32 (8.6%) of 374 i-RSW workers, and 29 (6.5%) of 447 p-RSW workers (p = 0.016). Compared with the workers having persistent e-ALT at the end of follow-up, the workers normalized serum ALT levels had significantly lesser exposures to RSW during follow-up. By performing multivariate logistic regression analyses, and comparing with the persistent daytime co-workers, after controlling for confounding variables (age, occupational factors, educational levels, lifestyle factors, metabolic syndrome, hepatovirus infection, and fatty liver), analysis indicated that the workers exposed to p-RSW were 46% less likely (OR, 0.54; 95% CI, 0.30-0.95; p = 0.03) to attain normal ALT levels within a five-year interval. These observations demonstrate that persistent day-and-night RSW pose a vigorous obstacle to the normalization of e-ALT among workers with preexisting abnormal liver function. We suggest that workers and managers approach with caution the consideration of assigning or accepting long-term day-and-night RSW when an employee health screening shows evidence of abnormal liver function.

Night shift work and abnormal liver function: is non-alcohol fatty liver a necessary mediator?

“…In our study, e-ALT was found among 15.4% of the workers, and this prevalence was similar to that among Japanese male workers in a computer and printer assembly company (16.3%) 10. Lin and Chen reported that the incidence rate of e-ALT was 14.4% among Taiwanese electronic manufacturing workers after 5 years’ follow-up9; they further concluded that night shift work was attributable in the high risk of e-ALT and it hampered the normalisation of ALT 8. Our findings support that night shift work is associated with an increased risk of e-ALT and provide additional evidence concerning dose–response relationships among workers with or without NAFL and of different BMI categories, which have never been reported in previous studies.…”

A rotating light cycle promotes weight gain and hepatic lipid storage in mice

“…Recently, it has been speculated that shift work is causally associated with NAFLD (5,35), with population studies demonstrating an increased prevalence of NAFLD among shift workers; however, it is unclear whether this is because of changes in diet, the shift work per se (1,46), or some interaction between them. In the current study, HFD mice had a marked increase in hepatocyte triglyceride and glycogen content.…”

“…Epidemiological studies suggest that long-term circadian misalignment, such as occurs with shift work, is a risk factor for insulin resistance (13), type 2 diabetes (9), metabolic syndrome (27), obesity (10,16,52,55), hyperlipidemia (7), and nonalcoholic fatty liver disease (NAFLD) (34,35). There are various animal models to mimic human shift work, including altering the timing of food intake, activity, sleep, or light exposure (40).…”

Genetic and Environmental Models of Circadian Disruption Link SRC-2 Function to Hepatic Pathology

“…Collectively, these data suggest that prolonged CCD and ablation of SRC-2 create a predisposition for HCC. In fact, case studies of shift workers reveal that these individuals are at a greater risk for liver damage and liver cancer than those exposed to normal light schedules (Lin et al, 2014; Lin and Chen, 2015; Echave Llanos and Nash, 1970). Collectively, our data demonstrate that SRC-2 is at the nexus of metabolic and circadian regulation of liver gene programs.…”

“…Shift work is also associated with increased metabolic disorders including obesity, hypertriglyceridemia, hypertension, and aberrant hormone homeostasis (Karlsson et al, 2001; Scheer et al, 2009; Kiessling et al, 2010; Parsons et al, 2015). Comorbidities of the metabolic syndrome are often observed in the CCD population, which include type 2 diabetes mellitus, cardiovascular disease, and the most prevalent chronic liver disease in developed countries, non-alcoholic fatty liver disease (NAFLD) (Wang et al, 2011; Lin et al, 2014; Lin and Chen, 2015; Sookoian and Pirola, 2009). The increased incidence of NAFLD that accompanies CCD also creates a predisposition for cirrhosis and hepatocellular carcinoma (HCC) and has even been reported to accelerate aging and increase mortality (Froy, 2013; Kondratova and Kondratov, 2012).…”