Environmental Microcystin Exposure Increases Liver Injury Risk Induced by Hepatitis B Virus Combined with Aflatoxin: A Cross-Sectional Study in Southwest China

Abstract

Three liver hazards, two confirmed-hepatitis B virus (HBV) and aflatoxin (AFB), and one rarely studied in populations-microcystin (MC), simultaneously exist in tropical and humid areas; however, there are no epidemiological data on their risks in the same population. We conducted a community-based cross-sectional survey among 5493 adults in two rural towns and statistically analyzed the comparative and combinative effects of the three factors after detecting HBsAg and HBV DNA titers, determining estimated daily intakes (EDIs) of AFB1 and MC-LR and testing serum AST and ALT as liver injury markers for each participant. We observed a HBsAg(+) rate of 7.6%, a relatively high AFB1 exposure level (mean EDI = 471.30 ng/d), and a relatively low MC-LR exposure level (mean EDI = 228.25 ng/d). ORs for abnormal AST (2.42, 95%CI = 1.69-3.45) and ALT (2.87, 95%CI = 1.91-4.29) increased in HBV infections compared with HBV-unexposed participants but did not increase in participants with separate or combined exposure to AFB1 and MC-LR (EDIs ≥ mean). Meanwhile, after adjustment for confounding factors, means of AST and ALT and ORs of abnormal AST and ALT were successively elevated after exposure to HBV, HBV&AFB1 (or HBV&MC-LR), and HBV&AFB1&MC-LR, especially in the group with detectable HBV DNA (AST: OR = 11.38, 95%CI = 3.91-33.17; ALT: OR = 17.09, 95%CI = 5.36-54.53). Notably, ORs for abnormal AST and ALT in the HBV exposed group were not significantly different from those in HBV&AFB1 or in the HBV&MC-LR exposed group but were significantly higher in the HBV&AFB1&MC-LR exposed group (P = 0.029 and P = 0.037, respectively). Our study indicated that microcystin may have the potential to increase the risk of liver injury induced by combined exposure to HBV and aflatoxin. However, in consideration of the uncertainties in the detection of the toxins and evaluation of the EDIs, more epidemiological data are expected to determine the increasing toxic effects of microcystins.

HBx combined with AFB1 triggers hepatic steatosis via COX‐2‐mediated necrosome formation and mitochondrial dynamics disorder

“…Instead, exposure to AFB1 would also exacerbate and accelerate the disease progression of HBV infection, perhaps via affecting susceptibility to infection or viral replication . In tropical and humid area such as Southern China, many people are chronically infected with HBV while also exposing AFB1 in their diet . Individuals with HBV infection were much more susceptible to AFB1‐associated HCC risk compared with those without these aetiological factors .…”

“…For example, exposure to 0.5 and 1 mg/kg of AFB1 for 7 days induced liver damage and dysregulation of genes associated with lipid metabolism in rats . Notably, HBV‐infected patients would be more susceptible to liver injury induced by AFB1 . However, just one study in zebrafish showed that combination of HBx and AFB1 promoted hepatic steatosis and increased the expression of lipogenic factors and genes related to lipid metabolism yet .…”

Serum microcystin levels positively linked with risk of hepatocellular carcinoma: A case‐control study in southwest China

“…Our previous study, conducted in a general population in the Three Gorges region, found that estimated daily intake of microcystins was positively correlated with liver injury in Chongqing, a warm and humid area with severe microcystin and aflatoxin contamination in southwest China . In our recently published article, we found that microcystins may have the potential to increase the risk of liver injury induced by combined exposure to HBV and aflatoxin …”

“…(19,20) In our recently published article, we found that microcystins may have the potential to increase the risk of liver injury induced by combined exposure to HBV and aflatoxin. (21) Currently, there is no direct linkage between microcystins and HCC risk due to a lack of extensive epidemiological data on serum MC-LR in human. Therefore, we embarked on a case-control study to determine serum MC-LR so as to assess the independent effects of MC-LR and its interaction effects with the known risk factors for HCC risk in southwest China.…”

Aflatoxins: History, Significant Milestones, Recent Data on Their Toxicity and Ways to Mitigation

“…Microcystin-LR (MC-LR), a toxin that is produced by cyanobacteria Microcystis aeruginosa, has been observed to possibly increase the liver damage risk in people suffering from hepatitis B simultaneously exposed to AFB 1 [94]. Enhanced effects of AFB 1 and MC-LR interaction on genotoxicity and cytotoxicity have been observed on the human liver cell line (HL7702) in vitro [138].…”