Genotypes and Hot Spot Mutations of Hepatitis B Virus in Northwest Chinese Population and Its Correlation with Diseases Progression

Abstract

Hepatitis B virus (HBV) infection is a critical incentive for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Different genotypes and genome mutations of HBV have been found to be related to the progression of these liver diseases. However, their clinical significance is still under debate. The objective of this study was to determine the association of HBV genotypes and hot spot mutations in the reverse transcriptase (RT) and basal core promoter-precore (BCP-PreC) region with HBV-infected diseases in a northwest Chinese population. HBV genotyping and DNA sequencing were performed in samples of 980 patients. Appropriate statistical methods were adopted to assess HBV genetic features and its clinical association. It was found that the prevalent HBV genotype in northwestern Chinese patients was HBV/C (61.33%), followed by HBV/B (36.63%). In RT region, in addition to the reported nucleoside analogue- (NA-) resistance missense mutations, new silent mutations at rt169 and rt180 were found to raise the risk of HCC in patients with HBV/C. And the heterozygous mutation status of rt169/rt180 was associated with the increased risk of both HCC and NA resistance (OR > 1, P < 0.01) regardless of HBV genotypes. In BCP-PreC region, multiple mutations and combinations, especially at nt 1762/1764 and nt 1896/1899, were characterized to be the causes of spurious HBeAg negativity and liver function injury, as well as the risk factors for HCC progression (P < 0.01). Additionally, a novel mutation at nt1799G>C was likely found to increase the risk of HCC in patients with HBV/B. These findings revealed an association between HBV genotypes and HBV genetic mutations in RT and BCP-PreC region and progression of hepatitis B. It would be helpful for risk evaluation and diagnostic improvement based on these genetic features.

A CRISPR-Cas12b–Based Platform for Ultrasensitive, Rapid, and Highly Specific Detection of Hepatitis B Virus Genotypes B and C in Clinical Application

“…In clinical practice, the genotype characteristic is essential for finding the severity of HBV infection and response to antiviral therapy in hepatitis B patients (Wang et al, 2015;Zhao et al, 2010). China has a high incidence of HBV, and genotypes B and C were identified as the most common agents (more than 95%) (Lin and Kao, 2011;Wang et al, 2019;Su et al, 2020). HBV genotype C causes more severe liver fibrosis, which more easily progresses to hepatocellular carcinoma, than genotype B infection (Zhao et al, 2010).…”

Hepatitis B Virus: From Diagnosis to Treatment

“…To date, ten genotypes of HBV, A to J, and more than 40 sub-genotypes that differ > 8% and 4-8% nucleotide divergence in the genome, respectively, have been identified (Al-Sadeq et al 2019). Different genotypes and sub-genotypes show different geographical distribution and are correlated with persistence of viral load, risk of developing cirrhosis, HBsAg seroclearance, antiviral therapy response, and prognosis due to the presence of mutations (Paudel and Suvedi 2019;Wang et al 2019). It has been known that patients infected with HBV genotype A are more likely to develop CHB infection than patients infected with genotype B, associated with the development of antiviral resistance or genotype C, associated with acute hepatitis (EASL 2017;Wang et al 2019).…”

“…Different genotypes and sub-genotypes show different geographical distribution and are correlated with persistence of viral load, risk of developing cirrhosis, HBsAg seroclearance, antiviral therapy response, and prognosis due to the presence of mutations (Paudel and Suvedi 2019;Wang et al 2019). It has been known that patients infected with HBV genotype A are more likely to develop CHB infection than patients infected with genotype B, associated with the development of antiviral resistance or genotype C, associated with acute hepatitis (EASL 2017;Wang et al 2019). HBV genotyping is not required for initial diagnosis; however, genome sequencing for evaluation of HBV genotypes and drug resistance mutations are useful parameters for patients at risk of developing HCC in order to monitor an efficient therapy (EASL 2017).…”

“…HBV, is a partially double-stranded DNA virus of 3.2 kilobases, and it transforms from pregenomic ribo-nucleic acid (RNA) to DNA by reverse transcription during its life cycle. The genome consists of an outer lipid envelope and inner nucleocapsid core encoded by four overlapping open reading frames, named C, X, P, and S (McNaughton et al 2019;Wang et al 2019). Although it is known as a virus with high replication ability, due to the absence of the proofreading reverse transcriptase enzyme, the naturally occurring mutations may arise in different genome regions.…”

Detection of Hepatitis B Virus M204V Mutation Quantitatively via Real-time PCR

“…The occurrence of drug resistance may lead to recurrence of hepatitis, and even cause progression of the disease, including virological breakthroughs, biochemical rebounds, hepatitis condition aggravation, and even hepatic failure. 4 , 5 Long-term drug resistance monitoring of patients with CHB who are taking LAM showed the proportion of hepatitis recurrence increased significantly compared to patients without drug resistance; in addition, the incidence of compensation cirrhosis was increased in patients with long-term drug resistance. 6 , 7 Not only for its impact on hepatitis, the occurrence of drug resistance will also lead to an increase in the incidence of hepatitis B-related liver cancer.…”