Correlation between Th17 and nTreg cell frequencies and the stages of progression in chronic hepatitis B.

Several studies have suggested that the balance of T helper 17 (Th17) and natural regulatory T (nTreg) cells in the Th17­mediated immune response are critical in the pathogenesis of viral hepatitis. The aim of the present study was to examine the role of circulating Th17 and nTreg cells in the disease progression of hepatitis B virus (HBV) infection. A total of 40 patients with chronic HBV (CHB), 27 patients with HBV­associated cirrhosis, 20 patients with HBV­associated liver failure and 20 healthy controls were enrolled in the present study. The frequencies of Th17 and nTreg cells in the peripheral blood were examined using flow cytometry. Th17­associated serum cytokine levels were measured using an enzyme­linked immunosorbent assay. The results revealed a significantly higher frequency of circulating Th17 cells in the patients with CHB, cirrhosis and liver failure compared, with the normal controls, particularly in the patients with liver failure. The same trend was observed in the serum levels of interleukin (IL)­17. The frequency of Th17 cells and the serum levels of IL­17 were positively correlated with the levels of alanine aminotransferase and the prothrombin times. There was a significantly higher frequency of circulating nTreg cells in the patients with CHB, compared with the normal controls. The nTreg cell frequencies were significantly and positively correlated with plasma HBV DNA load, and were negatively correlated with Th17 frequencies in the cohort of patients with HBV. Taken together, the results suggested that Th17 cell­mediated inflammation is associated with progression from CHB to cirrhosis, and to liver failure. Peripheral Th17 cell frequency and serum levels of IL­17 may assisting in predicting the severity of liver damage and fibrosis.

Differential expression of ISG20 in chronic hepatitis B patients and relation to interferon-alpha therapy response.

The 20 kDa exonuclease encoded by the interferon-stimulated gene, ISG20, can inhibit the replication of hepatitis B virus (HBV), and may represent a clinically useful prognostic marker for response to interferon-alpha (IFN-α) antiviral therapy. The present study was designed to investigate the differential expression patterns of ISG20 in liver biopsy samples from treatment-naive patients with chronic hepatitis B and non-HBV infected controls and to determine the relation between the differential expression and IFN-α treatment outcome (responders vs. non-responders). HBV infection status was determined by measuring levels of hepatitis B surface antigen (HBsAg) by chemoluminescence immunoassay and of HBV DNA by real-time quantitative (q)PCR. ISG20 protein and mRNA expressions were assessed by immunohistochemistry and qPCR, respectively. Chronic hepatitis B responders showed significantly higher levels of ISG20 protein and mRNA expressions than either the chronic hepatitis B non-responders or the controls. Moreover, increased expression of ISG20 in both the nucleus and cytoplasm was correlated with positive response to IFN-α treatment. Thus, active transcription and translation of ISG20 may represent a marker to identify chronic hepatitis B patients likely to respond to IFN-α therapy. Prognostic clinical strategies based upon this marker may include genomic screening methods and immunohistochemical staining of liver biopsies.