Multi-clustering study on the association between human leukocyte antigen-DP-DQ and hepatitis B virus-related hepatocellular carcinoma and cirrhosis in Viet Nam.

Human leukocyte antigen (HLA) class II molecules are cell surface receptor proteins found on antigen-presenting cells. Polymorphisms and mutations in the HLA gene can affect the immune system and the progression of hepatitis B. To study the relation between rs2856718 of HLA-DQ, rs3077, and rs9277535 of HLA-DP, hepatitis B virus (HBV)-related cirrhosis, and hepatocellular carcinoma (HCC). In this case-control study, the genotypes of these single nucleotide polymorphisms (SNPs) were screened in 315 healthy controls, 471 chronic hepatitis B patients, 250 patients with HBV-related liver cirrhosis, and 251 patients with HCC using TaqMan real-time PCR. We conducted Hardy-Weinberg equilibrium and linkage disequilibrium tests on the genotype distributions of rs2856718, rs3077, and rs9277535 before hierarchical clustering analysis to build the complex interaction between the markers in each patient group. The physical distance separating these SNPs was 29816 kB with the disequilibrium (D') values ranging from 0.07 to 0.34. The close linkage between rs3077 and rs9277535 was attributed to a distance of 21 kB. The D' value decreased from moderate in the healthy control group (D' = 0.50, P < 0.05) to weak in the hepatic disease group (D' < 0.3, P < 0.05). In a combination of the three variants rs2856718, rs3077, and rs9277535, the A allele decreased hepatic disease risk [A-A-A haplotype, risk ratio (RR) = 0.44 (0.14; 1.37), P < 0.05]. The G allele had the opposite effect [G-A/G-G haplotype, RR = 1.12 (1.02; 1.23), P < 0.05]. In liver cancer cases, the A-A-A/G haplotype increased the risk of HCC by 1.58 (P < 0.05). Rs9277535 affects liver fibrosis progression due to HBV infection, while rs3077 is associated with a risk of HBV-related HCC. The link between rs2856718, rs3077, and rs9277535 and disease risk was determined using a multi-clustering analysis.

Nguyen TT ，Ho TC ，Bui HTT ，Tran VK ，Nguyen TT ... -  《-》

Immune-checkpoint HLA-G gene polymorphisms, 3'-UTR types and their association with hepatocellular carcinoma and treatment response in Indian population.

Human leukocyte antigen-G (HLA-G) is a cancer-associated immune checkpoint protein implicated in tumor-driven immune escape mechanisms. This study was undertaken to determine genetic variations at the 3'-UTR of the HLA-G gene that may alter its expression, identify risk alleles and genotypes for their association with hepatocellular carcinoma (HCC), and treatment responses in the Indian population. Case-control genetic association study of HLA-G gene UTR polymorphisms with HCC and response to locoregional therapy (LRT). HCC cases (n = 100) and healthy controls (n = 110) were recruited for the genetic association study, of which 88 patients received LRT. Single nucleotide polymorphisms (SNPs) at the HLA-G 3'-UTR gene were genotyped by sequencing and PCR-RFLP. The genetic association of 14 SNPs with HCC and LRT responses was determined using population genetic approaches. Three of the 14 SNPs (rs1707, rs1710, and rs1063320) were found to be genetically associated with HCC risk and treatment responses. These three UTR SNPs are important for miRNA binding. We did not observe significant association of the most studied SNP, rs371194629 (INDEL, +2960), with HCC or treatment response. Serum sHLA-G levels were found to be significantly (p = 0.027) higher in HCC patients as compared to healthy controls. Highly prevalent UTR haplotypes in Indian HCC patients were UTR-4, -1, and -7 whereas in healthy controls it was UTR-3, and 15 as determined by a linkage disequilibrium (LD) plot using 8 SNPs. HLA-G SNPs are genetically associated with HCC and treatment response. Haplotypes associated with high levels of HLA-G expression are more prevalent in HCC than in healthy controls. Population genetic approaches were used to study HLA-G gene polymorphisms in the Indian population for its genetic association with HCC risk, treatment response and altered gene expression. Out of the 14 SNPs studied for HLA-G UTR, three were linked to HCC and response to locoregional therapy. Linkage disequilibrium and UTR haplotyping analysis show that the UTR-4 haplotype linked to high HLA-G levels, is more common in HCC patients, while the UTR-3 haplotype, linked to low HLA-G levels, is more common in healthy controls. This study is the first to look at the UTR types based on HLA-G gene polymorphisms of Indian HCC patients and their response to therapy.

Nadda N ，Yadav R ，Roy N ，Singh N ，Kumar S ，Paul SB ，Gamanagatti S ，Saraya A ，Shalimar ，Nayak B ... -  《Frontiers in Immunology》

The load of hepatitis B virus reduces the immune checkpoint inhibitors efficiency in hepatocellular carcinoma patients.

Chronic viral infection may lead to an immunosuppressive microenvironment, whereas the association between virus-related indicators and treatment response in hepatocellular carcinoma(HCC) patients undergoing immune checkpoint inhibitors(ICIs) therapy remains a topic of debate. We aim to investigate the influence of hepatitis virus on the ICI efficiency in HCC patients through a meta-analysis. We searched PubMed, Cochrane Library, Embase, and Web of Science until 14 July 2024 to identify cohort studies involving ICIs treatments in HCC patients. We extracted data from the literature related to hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, baseline HBV load, and antiviral therapy. Overall survival (OS) and progression-free survival (PFS) were considered as the primary endpoints, while objective response rate (ORR) was regarded as a secondary endpoint. We included 55 cohort studies published between 2019 and 2024, involving a patient population of 7180 individuals. Summarized hazard ratio (HR) comparing HBV infection with non-HBV infection in the context of ICIs therapy revealed no significant association between HBV infection and either mortality risk or progression risk with the pooled HR for OS of 1.04(95%CI: 0.93-1.16, P=0.483) and the pooled HR for PFS of 1.07(95%CI:0.96-1.20, P=0.342). HBV infected patients with HCC may have better tumor response than non-HBV infected patients receiving ICIs with the combined relative risk(RR) for ORR was 1.94 (95%CI: 1.12-3.38, P=0.002). High baseline HBV load is associated with poor survival outcomes in patients with HCC who receive ICIs with the pooled HR for OS was 1.74 (95%CI: 1.27-2.37, P=0.001), thereby antiviral therapy has the potential to significantly enhance prognostic outcomes with the pooled HR for OS was 0.24 (95% CI: 0.14-0.42 P<0.001) and the pooled HR for PFS was 0.54 (95% CI: 0.33-0.89 P=0.014). In individuals with HCC who received ICIs, there was no notable link found between HBV or HCV infection and prognosis. However, HBV infection showed a connection with improved tumor response. A higher initial HBV load is linked to worse survival results in HCC patients undergoing ICIs treatment and antiviral therapy can significantly improve its prognosis.

Ji Z ，Li J ，Zhang S ，Jia Y ，Zhang J ，Guo Z ... -  《Frontiers in Immunology》

Impacts of human leukocyte antigen DQ genetic polymorphisms and their interactions with hepatitis B virus mutations on the risks of viral persistence, liver cirrhosis, and hepatocellular carcinoma.

Human leukocyte antigen (HLA)-DQ genetic polymorphisms have been associated with chronic hepatitis B virus (HBV) outcomes. We aimed to determine impacts of HLA-DQ polymorphisms and their interactions with HBV mutations on the risks of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). rs2856718 (A>G) and rs9275319 (A>G) were genotyped in 1342 healthy controls, 327 HBV surface antigen (HBsAg) seroclearance subjects, 611 asymptomatic HBsAg carriers (ASCs), 1144 chronic hepatitis B (CHB) patients, 734 LC patients, and 1531 HCC patients using quantitative PCR. HBV mutations were detected by direct sequencing. Logistic regression analyses were utilized to assess the factors and/or multiplicative interactions significantly associated with liver diseases. rs9275319 variant genotypes were inversely associated with HBV persistence compared to HBV natural clearance subjects. rs2856718 variant genotypes significantly increased LC risk compared to ASCs plus CHB patients (GG vs. AA: odds ratio [OR], 1.52, 95% confidence interval [CI], 1.17-1.97 and AG+GG vs. AA: OR, 1.27; 95% CI, 1.04-1.54) and decreased HCC risk compared to HCC-free HBV-infected subjects (AG vs. AA: OR, 0.76; 95% CI, 0.65-0.89 and AG+GG vs. AA: OR, 0.78, 95% CI, 0.68-0.90). rs2856718 variant genotypes were significantly associated with an increased frequency of HBV A1726C mutation, a LC-risk, HCC-protective mutation, in genotype C. A rs9275319 variant genotype (GG) was significantly associated with an increased frequency of preS1 start codon mutation, an HCC-risk mutation, in genotype C. The interaction of rs2856718 AG+GG genotype with T1753V, a HCC-risk mutation, significantly reduced LC risk, with an OR of 0.26 (95% CI, 0.09-0.78); whereas the interaction of rs2856718 AG genotype with C1673T, a LC-risk mutation, significantly increased HCC risk, with an OR of 2.80 (95% CI, 1.02-7.66) in genotype C HBV-infected subjects. Conclusively, the HLA-DQ polymorphisms affect the risks of LC and HCC differently in chronic HBV-infected subjects, possibly via interacting with the HBV mutations.

Ji X ，Zhang Q ，Li B ，Du Y ，Yin J ，Liu W ，Zhang H ，Cao G ... -  《-》

Prevalence, Risk Factors, and Clinical Profiles of Hepatitis D Virus in Nigeria: A Systematic Review, 2009-2024.

Adepoju VA ，Udah DC ，Adnani QES 《Viruses-Basel》