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Revealing the causal relationship between HBV and HCV infection and liver cirrhosis by Mendelian randomization
Ju-Cun Huang1, Yu-Wei Feng1, Kang Zhao1
1Liver Disease Department of Integrated Traditional Chinese and Western Medicine, Hubei No.3 People's Hospital of Jianghan University, Wuhan, China.
Insights
Mendelian randomization analysis reveals that hepatitis B virus (HBV) and hepatitis C virus (HCV) infections causally link to cirrhosis. Monitoring aspartate aminotransferase (AST) levels may indicate liver damage from chronic HBV.
Area of Science:
- Genetics and Hepatology
- Viral Hepatitis Research
- Biomarker Analysis
Background:
- Chronic viral hepatitis (HBV, HCV) and cirrhosis pose significant patient burdens.
- Liver biomarkers aid in assessing liver damage.
- Understanding causal links is crucial for disease management.
Purpose of the Study:
- To investigate causal relationships between HBV, HCV, liver biomarkers, and cirrhosis using Mendelian randomization (MR).
- To analyze the impact of viral hepatitis on liver biomarkers and cirrhosis development.
Main Methods:
- A bidirectional, multi-sample MR approach utilized GWAS data.
- Data from 351,885 HBV and 176,698 HCV samples were analyzed.
- R language and TwoSampleMR package employed inverse-variance weighting, weighted median, and MR-Egger methods.
Main Results:
- Cirrhosis showed a potential causal link with HBV infection (OR=1.253, p=0.019).
- HBV infection was associated with decreased AST levels (OR=0.972, p<0.01).
- HCV infection demonstrated a strong causal link with cirrhosis (OR=2.213, p<0.01).
- No significant pleiotropy or heterogeneity was detected.
Conclusions:
- A causal relationship exists between HBV and AST levels, useful for monitoring liver damage.
- HBV and HCV infections are causally linked to cirrhosis, the terminal stage of these infections.
- Managing viral hepatitis progression can reduce the risk of developing cirrhosis.
Background:
The chronic progression of viral hepatitis and the terminal stage of cirrhosis impose a long-term disease burden on patients. The assessment of liver damage can be facilitated through the measurement of liver biomarkers.
Objectives:
To conduct a comprehensive analysis of the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), liver biomarkers, and cirrhosis via Mendelian randomization (MR).
Material And Methods:
A bidirectional multi-sample MR approach was used to extract data from publicly available genome-wide association studies (GWAS) databases. Information on liver biomarkers and cirrhosis, along with data from 351,885 HBV samples containing 19,079,722 single nucleotide polymorphisms (SNPs) and 176,698 HCV samples comprising 12,454,320 SNPs, were aggregated. The TwoSampleMR 0.5.7 package in R language facilitated the bidirectional MR analysis, utilizing methods such as inverse-variance weighting, weighted median and MR-Egger to investigate the causal relationships between HBV, HCV, liver biomarkers, and cirrhosis.
Results:
The MR analysis revealed potential causal relationships between cirrhosis and HBV infection, indicating an increased probability of HBV as cirrhosis escalates (odds ratio (OR) = 1.253; 95% confidence interval (95% CI): 1.037-1.514; p = 0.019). Additionally, a potential causal link was observed between HBV and the level of aspartate aminotransferase (AST), with an increase in HBV leading to a gradual decrease in AST levels (OR = 0.972; 95% CI: 0.958-0.986; p < 0.01). A similar causal relationship was identified between HCV infection and cirrhosis, where the probability of cirrhosis significantly increases with rising HCV levels (OR = 2.213; 95% CI: 1.752-2.796; p < 0.01). The results demonstrated no pleiotropy or heterogeneity within the analysis.
Conclusions:
This research highlights a causal relationship between HBV and AST levels, suggesting that monitoring AST levels can indicate the extent of liver damage caused by chronic HBV infection. Additionally, causal connections were established between HBV, HCV and cirrhosis, emphasizing that cirrhosis represents the terminal stage of chronic HBV and HCV infections. By managing the progression of the disease, the risk of cirrhosis can be reduced.
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