Yonsei Med J.  2016 May;57(3):652-657. 10.3349/ymj.2016.57.3.652.

Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B

• Shin SY
• Jeong SH
• Sung PS
• Lee J
• Kim HJ
• Lee HW
• Shin EC

• KMID: 2374085
• DOI: http://doi.org/10.3349/ymj.2016.57.3.652

Abstract

PURPOSE
Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines.
MATERIALS AND METHODS
Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels.
RESULTS
Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level.
CONCLUSION
We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.

Keyword

Hepatitis A virus; hepatitis B virus; liver injury; cytokines; chemokines

MeSH Terms

Acute Disease
Adult
Alanine Transaminase/blood
Biomarkers/blood
Cytokines/*blood
Enzyme-Linked Immunosorbent Assay
Fas Ligand Protein/blood
Female
Hepatitis A/blood/virology
Hepatitis A virus/*genetics/immunology
Hepatitis B/blood/virology
Hepatitis B virus/*genetics/immunology
Humans
Interleukin-6/blood
Interleukin-8/blood
Interleukins/blood
Liver Failure/immunology/metabolism/*pathology
Male
Middle Aged
T-Lymphocytes, Cytotoxic/immunology/*metabolism
Alanine Transaminase
Biomarkers
Cytokines
Fas Ligand Protein
Interleukin-6
Interleukin-8
Interleukins

Figure

• 

  Fig. 1 Serum levels of cytokines, chemokines, and T-cell cytotoxic proteins in AHA and AHB. The data represent the serum proteins that were elevated in patients with AHA or AHB compared to healthy controls. Horizontal lines indicate mean values; n=46 for AHA, n=16 for AHB, and n=14 for healthy controls. p values are presented as *p<0.01 or †p<0.001, based on the unpaired Student's t-test. IL, interleukin; AHA, acute hepatitis A; AHB, acute hepatitis B.

• 

  Fig. 2 Correlation between the serum levels of CXCR3 chemokines and the degree of liver injury. Serum concentrations of CXCL10 (A) and CXCL9 (B) correlated to peak ALT levels in samples drawn from patients with AHA (left) or AHB (right). Correlation coefficients (r) are based on Pearson (AHA) or Spearman (AHB) analyses. p values <0.05 are considered statistically significant. AHA, acute hepatitis A; AHB, acute hepatitis B; ALT, alanine aminotransferase.

• 

  Fig. 3 Correlation between the serum levels of cytokines or T-cell cytotoxic proteins and the degree of liver injury. Serum concentrations of granzyme B (left), sFasL (center), or IL-18 (right) correlated to peak ALT levels (A and B) or peak total bilirubin levels (C and D) in samples drawn from patients with AHA (A and C) or AHB (B and D). Correlation coefficients (r) are based on Pearson (AHA) or Spearman (AHB) analyses. p values<0.05 are considered statistically significant. n.s., non-significant; sFasL, soluble Fas ligand; IL, interleukin; AHA, acute hepatitis A; AHB, acute hepatitis B; ALT, alanine aminotransferase.

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