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Differential expression of haptoglobin isoforms in chronic active hepatitis, cirrhosis and HCC related to HBV
Jamal Sarvari1, Zahra Mojtahedi, Yasuhiro Kuramitsu
1Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran.
Insights
Researchers identified key serum proteins that change with hepatitis B virus (HBV) complications like chronic active hepatitis (CAH), cirrhosis, and hepatocellular carcinoma (HCC). Haptoglobin isoforms showed significant differences, potentially serving as biomarkers for these liver diseases.
Area of Science:
- Hepatology
- Proteomics
- Biomarker Discovery
Background:
- Hepatitis B virus (HBV) infection can lead to severe liver complications including chronic active hepatitis (CAH), liver cirrhosis, and hepatocellular carcinoma (HCC).
- Identifying specific biomarkers is crucial for early diagnosis, prognosis assessment, and guiding treatment strategies for HBV-related liver diseases.
Purpose of the Study:
- To identify differentially expressed serum proteins in patients with HBV infection across different stages of liver disease: CAH, cirrhosis, and HCC.
- To explore the potential of these identified proteins as diagnostic or prognostic biomarkers for HBV-induced liver complications.
Main Methods:
- Serum samples from patients with HBV-related CAH, cirrhosis, HCC, and healthy controls were analyzed.
- Proteomic analysis was performed using two-dimensional polyacrylamide gel electrophoresis (2DE) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS).
- Statistical analysis was applied to identify differentially expressed protein spots (≥1.5-fold change, p<0.05).
Main Results:
- A total of 54 differentially expressed protein spots were detected, with 35 identified by LC-MS/MS, corresponding to 13 unique proteins.
- Key identified proteins include haptoglobin (α-2 and β isoforms), retinol-binding protein, transthyretin, ficolin, leucine-rich-α-2-glycoprotein, α-1-antitrypsin, and clusterin.
- Notably, haptoglobin α-2 isoforms were significantly increased in HCC patients compared to cirrhosis patients, while a significant decrease was observed in cirrhosis patients.
Conclusions:
- The study successfully identified several differentially expressed serum proteins associated with HBV-related liver complications.
- Haptoglobin α-2 isoforms show promise as potential biomarkers, with distinct expression patterns differentiating HCC from cirrhosis.
- These findings contribute to the understanding of HBV pathogenesis and may aid in developing novel diagnostic and prognostic tools.
Abstract:
The three main complications of hepatitis B virus (HBV) infection are chronic active hepatitis (CAH), liver cirrhosis, and hepatocellular carcinoma (HCC). The aim of this study was to identify differentially expressed serum proteins among the three liver complications in patients with HBV infection. Differentially expressed proteins have been shown to be potential biomarkers for disease diagnosis, prognosis and therapy guidance. Two-dimensional polyacrylamid gel electrophoresis (2DE) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on sera from CAH, cirrhosis and HCC patients with HBV infection, as well as those obtained from healthy individuals. Of 54 differentially expressed (≥1.5-fold and p<0.05) protein spots, 35 spots were identified by LC-MS/MS. The identified spots correlated to 13 proteins. The proteins included haptoglobolin α-2 and β isoforms, haptoglobin cleaved β isoforms, retinol-binding protein, transthyretin, ficolin, leucine-rich-α-2-glycoprotein, α-1-antitrypsin and clusterin. Of particular interest is the significant increase of haptoglobin α-2 isoforms in HCC patients compared to cirrhosis ones. In contrast, a significant decrease of the isoforms was noted among cirrhosis patients.
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