Elevated TGF-β1/IL-31 Pathway Is Associated with the Disease Severity of Hepatitis B Virus–Related Liver Cirrhosis

Abstract

The proinflammatory cytokines transforming growth factor beta 1 (TGF-β1) and interleukin (IL)-31 have been implicated in tissue injury. However, whether TGF-β1/IL-31 are stimulated and elevated in response to liver injury that leads to fibrogenesis in hepatitis B virus-related liver cirrhosis (HBV-LC) remains unclear. To investigate the association between TGF-β1/IL-31 and stages of chronic HBV infection, serum TGF-β1, IL-9, IL-10,IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were determined among patients with chronic hepatitis B (CHB; n=19), HBV-LC (n=20), and a normal control population (NC; n=18). Disease severity in patients with HBV-LC was assessed using model for end-stage liver disease (MELD) scores. Serum TGF-β1 and IL-31 levels were strongly positively linked in all subjects, and both correlated positively with IL-22, IL-33, and IL-17. TGF-β1 and IL-31 levels in the blood were both significantly higher in CHB and HBV-LC patients than in NC subjects. Elevated serum TGF-β1 and IL-31 levels were positively associated with albumin, alpha-fetoprotein, creatinine, white blood cell count, and platelet levels. Serum TGF-β1 and IL-31 were markedly higher in HBV-LC patients who did not have esophageal varices, and IL-31 had the highest sensitivity and specificity (90.9% and 66.7%, respectively) for indicating the absence of this complication. In summary, TGF-β1 and IL-31 were linked to progression from CHB to LC, and correlated well with the severity of HBV-LC. These findings suggest possible roles of the TGF-β1/IL-31 pathway in the pathogenesis of liver fibrosis during chronic HBV infection.

High serum resistin associates with intrahepatic inflammation and necrosis: an index of disease severity for patients with chronic HBV infection

“…Recently, Ming et al found that the upregulation of the TGF-β1/IL-31 pathway is associated with disease severity in LC-B, since elevated serum TGF-β1 and IL-31 levels were positively associated with albumin, alpha-fetoprotein, creatinine, white blood cell, and platelet levels among LC-B patients [30]. Furthermore, TGF-β1/IL-31 pathway may also play an important role in the pathogenesis of liver injury during chronic HBV infection, since increased activity of the TGF-β1/IL-31 pathway has been found well correlated with the extent of liver injury, disease severity, and nonsurvival among ACLF patients, whereas reduced activity of this pathway has been detected during the recovery from liver injury in CHB cases [31].…”

Mechanisms of Accelerated Liver Fibrosis Progression during HIV Infection

“…TGF-β expression has also been associated to liver fibrosis in HBV-infected patients, but a role in HIV co-infected patients has not been demonstrated 92. Differing from HCV/HIV co-infections, liver fibrosis mediated through apoptosis-related receptors does not seem to play a major role in HBV/HIV co-infection.…”

Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a

“…Studies have shown that HBV and its viral proteins are at least partially responsible for over-activation of TGF-β signaling in HBV-related HCC [13, 14]. Lee et al found that HBx enhanced phosphorylation of pSmad2/3C by binding with Smad4 and amplified TGF-β signal pathway in several HCC cell lines, which led to the enhanced transcriptional activation of TGF-β-responsive genes [15].…”