▎WuXi AppTec Content Team Editor
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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related death worldwide. Past epidemiological findings suggest that the incidence of HCC is related to viral hepatitis and alcohol consumption, but in recent years, the proportion of HCC cases caused by these two factors has been decreasing. At the same time, more and more research evidence shows that the pathogenesis of HCC can be caused by a combination of factors, including genetic factors, dietary factors, and the composition of intestinal flora.
Recently, Gastroenterology, a well-known journal in the field of gastrointestinal diseases, published a blockbuster study, pointing out that serum total bile acid (TBA) level may be related to the risk of liver cancer. Based on the analysis data of the ATBC prospective cohort, the study found that the baseline serum TBA level of the subjects with liver cancer was 2 times higher than that of the normal control population; in addition, the TBA level Those with higher levels (> 2 μmol/L) had a 3.2-fold increased risk of liver cancer compared with those with lower levels of TBA (≤ 1 μmol/L).
Notably, this study also found that higher dietary fiber intake (median >17.85 g/day) was associated with liver cancer in people with lower serum TBA 29% lower risk. However, for people with higher serum TBA, higher dietary fiber intake can increase the risk of liver cancer by 40%.
Screenshot source: Gastroenterology
The liver plays a role in the human body as the firewall in the computer, it can filter and detoxify the toxic metabolites and microbial products from the gut. However, if a large amount of microbial products from the gut influx into the liver through the gut-liver axis (i.e. “leakage” of the gut-liver axis), it may cause chronic hepatitis and liver cell damage, thereby mediating tumor progression. occur. This is also the reason why dietary factors and the composition of intestinal flora may have an impact on the pathogenesis of HCC.
The paper highlights that host-produced gut metabolites, especially bile acids, may also contribute to HCC. The results of exploratory studies in previous animal models suggest that secondary bile acids (deoxycholic acid, ω-mouse cholic acid) may promote the occurrence of HCC by inhibiting anti-tumor immunity. Therefore, experts infer that the excessive exposure of hepatocytes to bile acids in the state of vascular leakage may also promote the occurrence of HCC.
Image source: 123RF
The current team has pioneered the discovery based on animal model studies that the elevation of serum TBA is not only related to HCC, but may also be one of the necessary factors for the occurrence of HCC. So does this phenomenon also exist in humans? To get the answer, the research team conducted a prospective cohort of Finnish ATBC(the ATBC study aimed to evaluate the effect of vitamin E and β-carotene supplementation on the incidence of lung cancer and other cancers, recruiting nearly 30,000 smoking men aged 50-69 years old subjects) serum TBA data of subjects were analyzed.
The study collected blood samples from subjects at baseline from 1985 to 1988 and prospectively followed up for liver cancer (through 2014). The current research team analyzed serum samples from 224 subjects with subsequent primary liver cancer (median time from baseline to liver cancer diagnosis, 15.6 years) and 224 matched controls without liver cancer.
Analysis showed: Subjects with advanced liver cancer had 2-fold higher serum TBA levels at baseline than controls. Based on a multivariate correction model, the results suggest that subjects in the highest TBA level group (TBA > 2 μmol/L) were compared with those in the lowest TBA level group (TBA ≤ 1 μmol/L) The risk of liver cancer increased by 3.2 times (OR=4.23, 95%CI = 2.21-8.12, p-trend
Not only that, but the analysis also found that serum total cholesterol levels were negatively correlated with the risk of subsequent liver cancer. Overall, the analysis results showed that hypercholesterolemia and hypocholesterolemia can be further explored as independent risk factors for liver cancer.
In addition, the current research team also explored the relationship between dietary fiber intake (ie total fiber intake, including fermentable dietary fiber and non-fermentable dietary fiber) and bile acid levels, liver cancer associations with risk of developing morbidity. The results of the analysis indicated that the total fiber intake of the control group was significantly higher, which is consistent with the widely held view that dietary fiber can promote health.
It is interesting to note that the results of the analysis that stratified the cohort of subjects based on TBA level showed that:In the lowest TBA group (lowest quartile) of subjects , higher dietary fiber intake (median > 17.85 g/days) was associated with a 29% lower risk of liver cancer (OR=0.71, 95%CI=0.25-2.05). However, Higher dietary fiber intake (median >17.85 g/day) was associated with a 40% increased risk of liver cancer in subjects with the highest TBA levels (highest quartile) strong>(OR=1.40, 95%CI=0.50-3.96).
In other words, higher dietary fiber intake may not prevent HCC in individuals with higher serum TBA levels, which is also consistent with findings in animal models. The conclusions are consistent, that is, high intake of dietary fiber in hyperbile acidemia mice may promote the development of liver cancer.
The paper emphasizes that the results of the current study provide important insights for us to better predict and prevent the development of HCC. We may be able to identify individuals with a higher risk of liver cancer through serum bile acid levels and reduce this risk with simple dietary modifications.
Based on research findings, simple blood tests for bile acids may be warranted as part of routine screening programs for health monitoring. In addition, individuals with serum bile acid levels higher than normal may also need to have bile acid levels regularly tested and pay attention to daily dietary fiber intake.