title: Prognoses of patients with acute-on-chronic hepatitis B liver failure are closely associated with altered SOCS1 mRNA expression and cytokine production following glucocorticoid treatment.
abstract: Suppressor of cytokine signaling (SOCS) 1 plays a crucial role in the immune response and might contribute to the prognoses of liver failure treated with glucocorticoid. We recruited 47 acute-on-chronic hepatitis B liver failure (ACHBLF) patients receiving glucocorticoid treatment and 30 healthy controls to determine the potential effects of glucocorticoid on the transcriptional level of SOCS1 in peripheral blood mononuclear cells. On the third and twenty-eighth days of glucocorticoid treatment, SOCS1 expression was negatively correlated with model for end-stage liver disease (MELD) score. Interleukin-6 (IL-6) and tumor-necrosis factor-α (TNF-α) levels were statistically lower, while the SOCS1 transcription level was higher in survivors than non-survivors both in pre- and post-treatment ACHBLF patients. The methylation rate of the SOCS1 promoter in ACHBLF patients was higher than in healthy control patients as determined by methylation-specific polymerase chain reaction. The mRNA level of SOCS1 in methylated promoters was significantly lower than from patients with unmethylated SOCS1 promoters. interferon (IFN)-γ-responsive and STAT1-dependent gene expression was higher in survivors and was dramatically decreased with rising expression of SOCS1 after glucocorticoid treatment. Mortality rates were significantly higher in methylated patients than for those without methylation at the end of a 90-day follow-up. Furthermore, we found that five in six surviving patients displayed demethylated SOCS1 on the twenty-eighth day after treatment, while that number was 3 in 10 in the non-survivors. These findings suggested that ACHBLF patients without SOCS1 methylation may have a favorable response to corticosteroid treatment.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: 1] Department of Hepatology, Qilu Hospital of Shandong University, Ji'nan, China [2] Institute of Hepatology, Shandong University, Ji'nan, China.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Fan
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Ze-Hua
authors.initials: ZH
authors.lastname: Zhao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Dou
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.affiliation: 1] Department of Hepatology, Qilu Hospital of Shandong University, Ji'nan, China [2] Institute of Hepatology, Shandong University, Ji'nan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000328:Adult; D016207:Cytokines / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D017093:Liver Failure / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D015850:Interleukin-6; D012333:RNA, Messenger; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha
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