Demographic and Clinical Characteristics of 156 Patients with Type 1 AIH.

<p>Values are expressed as median (range) unless otherwise noted.</p><p>Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ANA, anti-nuclear antibody; SMA, anti-smooth muscle antibody.</p

Influence of Three Amino Acid Positions in HLA-DRβ1 Associated with AIH Risk or Protection.

<p>Abbreviations: HLA, human leukocyte antigen; AIH, autoimmune hepatitis; OR, odds ratio; CI, confidence interval.</p

Statistical Analysis of Representative HLA Alleles among Patients with Type 1 AIH and Healthy Subjects.

<p>Abbreviations: Pc, corrected P; OR, odds ratio; CI, confidence interval.</p

Relative amino acid positions at β11, β13, and β57 on the HLA-DRB1 molecule.

<p>Three-dimensional structure of HLA-DRB1 adapted from Stern et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100565#pone.0100565-Stern1" target="_blank">[40]</a> The molecule is composed of 2 opposing α-helices and a series of supporting β-pleated sheets. The relative positions of the 3 amino acids discussed in this study are indicated by black spots.</p

Number of Individuals with Haplotypes Containing HLA-DRB1*04:05-DQB1*04:01.

<p>x represents any allele at that locus, including A*24:02, C*01:02, B*54:01, and DPB1*05:01.</p

Changes in serum levels of autotaxin with direct-acting antiviral therapy in patients with chronic hepatitis C - Fig 6

<p><b>Changes in serum levels of (A) HCV RNA, (B) ALT, (C) ATX, (D) FIB-4 index, and (E) APRI before, during, and after IFN-DAA therapy in 9 female patients without a SVR.</b> PT: post-treatment. *, <i>P</i> < 0.05; **, <i>P</i> < 0.01.</p

<i>KIR</i> gene profile frequencies in 56 patients with a sustained virological response (SVR) and 59 patients with a non-SVR to pegylated interferon and ribavirin therapy of chronic hepatitis C.

<p>Numerical data represent the number of individuals (%). The presence of <i>KIR</i> genes is indicated by gray shading. Cen, centromeric; Tel, telomeric. </p

<i>KIR</i>, <i>HLA</i>, and <i>IL28B</i> Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan

<div><p>Natural killer cell responses play a crucial role in virus clearance by the innate immune system. Although the killer immunoglobulin-like receptor (KIR) in combination with its cognate human leukocyte antigen (HLA) ligand, especially <i>KIR2DL3-HLA-C1</i>, is associated with both treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection in Caucasians, these innate immunity genes have not been fully clarified in Japanese patients. We therefore investigated 16 KIR genotypes along with <i>HLA-B</i> and <i>-C</i> ligands and a genetic variant of interleukin (IL) 28B (rs8099917) in 115 chronic hepatitis C genotype 1 patients who underwent pegylated-interferon-α2b (PEG-IFN) and ribavirin therapy. <i>HLA-Bw4</i> was significantly associated with a sustained virological response (SVR) to treatment (<i>P</i> = 0.017; odds ratio [OR] = 2.50, ), as was the centromeric A/A haplotype of <i>KIR</i> (<i>P</i> = 0.015; OR 3.37). In contrast, SVR rates were significantly decreased in patients with <i>KIR2DL2</i> or <i>KIR2DS2</i> (<i>P</i> = 0.015; OR = 0.30, and <i>P</i> = 0.025; OR = 0.32, respectively). Multivariate logistic regression analysis subsequently identified the <i>IL28B</i> TT genotype (<i>P</i> = 0.00009; OR = 6.87, 95% confidence interval [CI] = 2.62 - 18.01), <i>KIR2DL2/HLA-C1</i> (<i>P</i> = 0.014; OR = 0.24, 95% CI = 0.08 - 0.75), <i>KIR3DL1/HLA-Bw4</i> (<i>P</i> = 0.008, OR = 3.32, 95% CI = 1.37 - 8.05), and white blood cell count at baseline (<i>P</i> = 0.009; OR = 3.32, 95% CI = 1.35 - 8.16) as independent predictive factors of an SVR. We observed a significant association between the combination of <i>IL28B</i> TT genotype and <i>KIR3DL1</i>-<i>HLA-Bw4</i> in responders (<i>P</i> = 0.0019), whereas <i>IL28B</i> TT along with <i>KIR2DL2-HLA-C1</i> was related to a non-response (<i>P</i> = 0.0067). In conclusion, combinations of <i>KIR3DL1/HLA-Bw4</i>, <i>KIR2DL2/HLA-C1</i>, and a genetic variant of the <i>IL28B</i> gene are predictive of the response to PEG-IFN and ribavirin therapy in Japanese patients infected with genotype 1b HCV.</p> </div

Changes in serum levels of autotaxin with direct-acting antiviral therapy in patients with chronic hepatitis C - Fig 2

<p><b>Changes in serum levels of (A) HCV RNA, (B) ALT, (C) ATX, (D) FIB-4 index, and (E) APRI before, during, and after IFN-DAA therapy in 15 patients without a SVR.</b> PT: post-treatment. *, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001.</p

Receiver operating characteristic analysis of the 3 cell death biomarkers (M30, M65, and M65ED) for the prediction of (A) significant fibrosis (≥F2), (B) severe fibrosis (≥F3), and (C) cirrhosis (F4).

<p>Receiver operating characteristic analysis of the 3 cell death biomarkers (M30, M65, and M65ED) for the prediction of (A) significant fibrosis (≥F2), (B) severe fibrosis (≥F3), and (C) cirrhosis (F4).</p