Abstract
Background and Aims Traditional Chinese medicine (TCM) has been widely applied in chronic hepatitis B (CHB) supplementary treatment in China. Kidney yang deficiency syndrome (KYDS), one of the most common TCM syndromes of CHB, is more likely to progress to liver cirrhosis or hepatocellular carcinoma than other syndromes. Polymorphisms in the human leucocyte antigen- (HLA-) DQB1 and -DRB1 genes were reported to be associated with hepatitis B virus infection outcomes. Here, we investigated whether HLA-DQB1 and HLA-DRB1 are associated with the classification of CHB TCM syndromes. Methods We genotyped HLA-DQB1 and HLA-DRB1 alleles in a total of 105 subjects, including 74 CHB patients (28 KYDS and 46 non-KYDS) and 31 healthy individuals from Sichuan Province of Southwest China, by polymerase chain reaction sequence-based typing (PCR-SBT). Moreover, a meta-analysis was carried out for further verification. Results The proportion of patients with high HBV DNA load (≥2000 IU/ml) in the KYDS group is higher than that in the non-KYDS group (60.70% [17/28] vs. 28.30% [13/46]); P=0.01). The frequencies of HLA-DQB1∗02:01 (P=0.04) and HLA-DRB1∗03:01 (P=0.04) in the KYDS group were significantly increased compared to the non-KYDS group. The gene test and meta-analysis showed that HLA-DRB1∗08:03 confers susceptibility to CHB (odds ratio = 1.57). Conclusion We found an association between HLA-DRB1/DQB1 polymorphisms and KYDS of CHB. Moreover, KYDS patients of CHB are characteristic with high HBV DNA loads. These findings help to reveal the biological mechanism of KYDS in high risk of CHB progression and suggest a potential prognostic value for disease outcome evaluation.
Highlights
Lots of strategies have been applied [1], hepatitis B virus (HBV) infection is still a worldwide public health threat that causes considerable liver-related morbidity and mortality
All the enrolled patients should be diagnosed as CHB according to the guideline of prevention and treatment for chronic hepatitis B (2015 version) [19]: with positive HBsAg for more than six months, with persistent or intermittent elevation in ALT/ AST levels or liver biopsy showing chronic hepatitis, and with positive HBV DNA viral load. e diagnostic criteria of Kidney yang deficiency syndrome (KYDS) refer to Diagnostics of Traditional Chinese Medicine (2002 edition) [20] (Supplementary Table S1). e nonKYDS patients were those who diagnosed with the other type of Traditional Chinese medicine (TCM) syndromes
Discussion e persistence of HBV infection in CHB is due to the reservoir of HBV covalently closed circular DNA in the nucleus of infected hepatocytes, which serves as a template for viral transcription [30]
Summary
Lots of strategies have been applied [1], hepatitis B virus (HBV) infection is still a worldwide public health threat that causes considerable liver-related morbidity and mortality. It has been reported that patients of KYDS with CHB had a higher risk to progress to LC or HCC than the other syndromes [10]. CHB patients of KYDS possess lower levels of CD4+ T cells, IL-2, and IFN-c than the other TCM syndromes, while the levels of IL-6 and IL-10 in KYDS were higher [12]. Traditional Chinese medicine (TCM) has been widely applied in chronic hepatitis B (CHB) supplementary treatment in China. Kidney yang deficiency syndrome (KYDS), one of the most common TCM syndromes of CHB, is more likely to progress to liver cirrhosis or hepatocellular carcinoma than other syndromes. E proportion of patients with high HBV DNA load (≥2000 IU/ml) in the KYDS group is higher than that in the non-KYDS group (60.70% [17/28] vs 28.30% [13/46]); P 0.01). KYDS patients of CHB are characteristic with high HBV DNA loads
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