HMGB1 and SEPP1 as predictors of hepatocellular carcinoma in patients with viral C hepatitis: Effect of DAAs

Clin Biochem. 2019 Aug:70:8-13. doi: 10.1016/j.clinbiochem.2019.05.017. Epub 2019 May 31.

Abstract

Background: Hepatitis C viral infection (HCV) and hepatocellular carcinoma (HCC) are potential health problems. New directly acting antivirals (DAAs) changed HCV treatment strategies. Selenoprotein P1 (SEPP1) is a hepatokine implicated in HCC pathogenesis. High mobility group box1 (HMGB1), a nuclear DNA-binding protein, involved in immune and inflammatory responses in HCV and HCC. Therefore, the aim of current study was to investigate HMGB1 and SEPP1 levels in HCV and HCV + HCC patients and exploring DAAs effect on them.

Methods: 15 healthy volunteers, 25 HCV and 25 HCV + HCC patients were included. Liver function tests, alpha fetoprotein (AFP), SEPP1 and HMGB1 serum levels were evaluated. For HCV group blood samples before and after treatment with sofosbuvir/daclatasvir combination were collected.

Results: HMGB1 was significantly higher in HCV + HCC group than in control and HCV groups (p < .05). SEPP1 decreased significantly in HCV and HCV + HCC groups compared to control group (p < .001). SEPP1 significantly elevated after treatment with DAAs (p = .001). HMGB1 and SEPP1 were negatively correlated with each other in HCV group (p = .047). Logistic regression analysis showed that HMGB1 and SEPP1 could be used as predictors for HCC in HCV infected patients (p = .02,p = .002) respectively. Receiver operating characteristic curve (ROC) revealed HMGB1 had 32% sensitivity and 100% specificity in differentiating HCV from HCV + HCC patients, both SEPP1 and HMGB1 had high sensitivity (92%,60%) and 93% specificity in differentiating healthy from HCV + HCC group.

Conclusion: HMGB1 and SEPP1 are involved in pathogenesis of HCV and HCV induced HCC. Both of them could serve as predictive biomarkers for HCC in HCV patients.

Keywords: DAAs; HCV; HMGB1; Hepatocellular carcinoma; SEPP1.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / pathology*
  • Case-Control Studies
  • Female
  • HMGB1 Protein / blood*
  • Hepatitis C / drug therapy*
  • Hepatitis C / metabolism*
  • Humans
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Selenoprotein P / blood*

Substances

  • Antiviral Agents
  • Biomarkers, Tumor
  • HMGB1 Protein
  • HMGB1 protein, human
  • SELENOP protein, human
  • Selenoprotein P