Detectable levels of tetrachloroethylene is associated with the presence and severity of liver fibrosis, new research suggests.
A recent American study suggests that occasional, non-occupational exposure to a common product used in dry cleaning and other industrial environments could lead to liver fibrosis.
Tetrachloroethylene (PCE) is a common solvent used in dry cleaning and other industrial products.
It has been listed as a probable or suspected carcinogen by many outlets, including the International Agency for Research on Cancer and Worksafe Australia due to reports linking PCE to bladder cancer, multiple myeloma and non-Hodgkin lymphoma.
Now, new US research has linked the volatile organic compound to liver fibrosis, a precursor to liver cancer, reporting that individuals with a detectable amount of PCE in their blood had three times the odds of having significant liver fibrosis, and that the association between PCE exposure and the extent of the fibrosis was dose dependent.
The new findings were published in Liver International.
“Although PCE has recently been of interest in the context of liver cancer, no studies to date have examined this association between blood PCE levels and liver fibrosis,” the researchers wrote.
“Previous studies focus on occupational exposures, which are often at higher levels, and have had limitations, including small sample size and selection bias.”
Researchers used questionnaire and clinical data from the US National Health and Nutrition Examination Survey, a nationally representative survey of the American population, to explore the association between blood PCE levels and liver fibrosis. There were 1614 adults included in the final analysis.
People with hepatitis were excluded from the current study, as were past and current smokers. Liver fibrosis was defined as a liver stiffness measurement of more than 8.2kPa as assessed by vibration-controlled transient elastography.
Across all participants, 116 (weighted percentage 7.4%) had detectable levels of PCE in the blood sample collected for the NHANES. Compared to people who did not have PCE detected in their blood sample, a greater proportion of people in the detectable PCE group had metabolic syndrome (34.4% versus 18.5%) and liver fibrosis (12.6% versus 7.1%).
“For context, established risk factors for liver fibrosis such as chronic hepatitis B and chronic hepatitis C have estimated global prevalences of 4.1% and 0.7%, respectively,” the researchers noted.
After controlling for the effects of age, sex, race/ethnicity, education level, poverty status, alcohol use and the presence of metabolic syndrome, people with detectable levels of PCE in their blood had 3.2 times the odds of having significant liver fibrosis (95% confidence interval 1.2-8.2) compared to people without PCE in their blood. A dose-response association was also found; the odds of fibrosis increased 5.1-fold for each 1ng/mL increase in PCE concentration in the blood (95% confidence interval 1.1-24.3).
Related
Additional sensitivity analyses – where people with metabolic syndrome or heavy alcohol use were excluded – yielded similar results. Detectable PCE levels in blood were associated with liver fibrosis (4.4, 1.7-11.2) and increasing amounts of PCE were associated with greater odds of liver fibrosis (4.0, 1.1-14.3).
PCE is metabolised in two main ways, the researchers explained. The first involves oxidation via cytochrome P450s – namely CYP2E1 – while the second features conjugation with glutathione.
“Oxidation via CYP450s yields trichloroacetic acid (TCA) as a major metabolite. In vivo studies indicate that TCA can affect PPAR-α, a nuclear receptor that is expressed in the liver, with roles in lipid metabolism, glucose homeostasis, cell differentiation and proliferation,” they said.
“PCE also conjugates with glutathione to form dichloro- or trichloro-glutathione conjugates, which are further metabolised via hepatic and kidney gamma-glutamyl transferase and di-peptidase to form cysteine conjugates.
“Other environmental xenobiotics such as bisphenol A and per- and polyfluoroalkyl substances, which have been linked to hepatotoxicity, are also thought to act through altering the activity of PPAR-α.”
The researchers noted the cross-sectional nature of the research prevented them from establishing causality, and the subsequent need for further assessment of the association through prospective, longitudinal studies. The researchers also highlighted a potential link from their more nationally representative sample that other less generalisable studies may have missed.
“Previous analyses of PCE in NHANES data has also indicated that participants with higher family incomes had higher exposures to PCE, attributing this to participants with higher incomes being more likely to utilise dry-cleaning services, resulting in higher exposures,” they wrote.
