Abstract

      Background and objective: Hepatitis B virus (HBV) is a DNA virus with high tendency toward hepatic tissue. There are currently about 3 million HBV-infected people and 350 to 400 million chronic carriers of this virus in the world. X protein plays a role in the over-expression of oncogenes, carcinogenicity of liver cells and overlaps with the basal core promoter of the virus. Mutations at specific nucleotides of this region increase viral replication and liver disease progression. The aim of this study was to investigate the frequency of mutations at nucleotides 1762, 1764 and 1766 of HBV X gene in patients with chronic hepatitis B and hepatitis B-related cirrhosis.

      Methods: In this study, 102 patients including 68 chronic hepatitis patients and 34 patients with hepatitis B-related cirrhosis were enrolled. After DNA extraction, HBV X gene was amplified and sequenced using Semi Nested-PCR. Obtained gene sequences were compared with the standard sequence of HBV virus X gene available in the gene bank (Okamoto AB033559). Then, the mutations in the gene X of HBV were identified.

      Results: Comparison of the standard sequence with sequences obtained from patients showed the presence of A1762T / G1764A mutation in 12 chronic (17.64%) and 13 cirrhotic (38.23%) patients. Also, C1766G / G1764T mutations were found in 8.23% of chronic patients and 17.64% of cirrhotic patients.

      Conclusion: A1762T / G1764A mutations in the overlapping region of the basal core promoter with gene X C-terminal may lead to liver disease progression from chronic hepatitis to cirrhosis, by changing the amino acid sequence of the X protein.

    

ABSTRACT
       Background and Objective: MiRNAs are small RNAs that are expressed in most eukaryotes, and can regulate gene expression by attaching to the 3’ end of target mRNA. MicroRNA-101 (miR-101) post-transcriptional regulation is important for host-virus interactions. In addition, miR-101 has a tumor suppressive role in liver cancer and metastasis, and induces apoptosis in tumor cells. We examined miR-101 expression in patients with chronic hepatitis B, hepatitis B virus (HBV)-associated cirrhosis and healthy individuals.
       Methods: The study was performed on 108 whole blood samples (36 samples from each group) collected in EDTA tubes. RNA was extraction by RNX-plus kit according to the manufacturer’s protocol. Finally, miRNA expression was evaluated using relative real time PCR.
         Results: A 2.4-fold increase was observed in miR-101 expression in patients with chronic hepatitis B, while there was a 3.5-fold increase in miR-101 expression in patients with HBV-associated cirrhosis compared with healthy controls (P=0.003). MiR-101 overexpression in patients with HBV-associated cirrhosis was more notable that in patients with chronic hepatitis B.
         Conclusion: According to the results, evaluating miR-101 expression may predict disease progression from chronic hepatitis B to HBV-associated cirrhosis.
         Keywords: MicroRNAs, Chronic Hepatitis B, Liver Cirrhosis, MiR-101.