From:  HLA-KIRs interactions in modulating natural killer cell responses against viral hepatitis: a concise review

 Impact of HLA-KIR combinations on HBV and HCV outcomes: a global perspective.

ReferencesYearPopulationFindings
Lu et al. [95]2008CHB Chinese patientsLower and higher frequencies of A and B haplotypes in patients with HBV, respectively
Gao et al. [98]2010HBV Chinese patientsThe homozygosity of KIR2DL3/HLA-C1 has a protective role against HBV
Pan et al. [100]2011HBV Chinese patientsIncreased risk of developing HCC following viral hepatitis through homozygous genotype for HLA-C group 1, HLA-Bw480I, and a combined pattern of KIR2DS4/1D
Moralès et al. [99]2012-HLA-Bw480I allele inhibits NK cells more effectively than HLA-Bw480T via stronger binding affinity for KIR3DL1
De Re et al. [108]2015CHC Italian patientsThe KIR2DS3 gene is related to the progression of HCV-related liver disease
Buchanan et al. [114]2015--KIR2DS3 promotes chronic infection and rapid progression
Di Bona et al. [103]2017CHB Italian patientsKIR2DL3 is protective in controlling HBV infection
Shah-Hosseini et al. [105]2017HBV Iranian patientsRecovered individuals had higher frequencies of KIR2DL5A, KIR2DS1, KIR3DS1 alleles, and specific KIR3DS1 genotypes
Yindom et al. [117]2017Gambian HCC and Cirrhosis patientsPatients with HBV carrying the KIR3DS1 allele are HBe antigen-positive and exhibit high viral loads
Li et al. [116]2017CHB Chinese patientsA direct relationship between the KIR3DS1/HLA-BBw4-80Ile gene combination and favorable response to IFN-α therapy
Podhorzer et al. [115]2017Argentine HCV cohortsNK receptor alterations accompany KIR2DS3 positivity
Zhuang et al. [113]2018Chinese HBeAg-positive cohortsKIR2DS3 carriage reduced entecavir response; impaired NK activation reduces antiviral efficacy
Djigma et al. [121]2020West African Cohort (Burkina Faso)A and B KIR haplotypes were associated with protection against HBV chronic infection evolution to cirrhosis and/or HCC
Auer et al. [106]2020HBV Vietnamese patientsKIR2DS4 allele is linked to chronic infection, whereas the combinations KIR2DL2/HLA-C1 and KIR2DL3/HLA-C1 lower the risk of CHB
Ursu et al. [96]2020CHC Romanian patientsAssociations between the KIR2DL3, KIR2DL5, KIR3DL3, KIR2DP1, KIR3DP1, and KIR2DS4 norm allele and an increased genetic predisposition to CHC
Joshita et al. [102]2021HBV Japanese patientsA direct association between the presence of the KIR2DS3 allele and HBV-related HCC
Varbanova et al. [104]2021HBV Bulgarian patientsA direct association between the presence of the KIR3DL1*004 allele and the development of CHB
Umemura et al. [109]2021HCV cirrhotic Japanese patientsKIR3DL1/HLA-Bw4 combination correlates with the progression of disease to HCC
Ursu et al. [31]2021CHC Romanian patientsElevated AST, ALT, and GGT levels in patients with the KIR2DL2/KIR2DL2-C1C1 genotype
Legaz et al. [101]2024Spanish man with alcoholic cirrhosisThe KIR2DL2/C2C2 combination plays a role in determining the genetic susceptibility of patients with alcoholic cirrhosis to viral hepatitis infections
Ryan et al. [110]2024HCV American patientsKIR2DL1/HLA-C2 and KIR3DL1/Bw4 combinations are associated with an increased risk of HCC
Martín-Sierra et al. [122]2024HCV Spanish patientsNo association found between HLA-KIR combinations and seroconversion following virus exposure in patients with HCV

ALT: alanine transaminase; AST: aspartate transferase; CHB: chronic hepatitis B; CHC: chronic hepatitis C; HBeAg: hepatitis B e antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HLA: human leukocyte antigen; IFN: interferon; KIR: killer immunoglobulin-like receptor; NK: natural killer; GGT: gamma-glutamyl transferase.