Carriage of the Laboratory of Genetics and Physiology Protein 2 Q425R Variant Reduces Liver Disease Severity in European Patients With Chronic Hepatitis Delta

Introduction: Laboratory of genetics and physiology protein 2 (LGP2) Q425R variant enhances interferon-mediated antiviral responses in chronic hepatitis delta (CHD) in vitro. This study aimed to evaluate the association between the LGP2 Q425R variant and liver disease severity in untreated CHD patients. Methods: In total, 192 patients with CHD were studied. LGP2 rs2074158 T>C genotyping was performed to identify the LGP2 wild-type (WT, TT genotype) and Q425R (CC/CT genotypes) variants. Liver fibrosis was evaluated by histology or liver stiffness measurement (LSM). Cirrhosis was defined by LSM > 12 kPa, and portal hypertension by thrombocytopenia. Associations between LGP2 WT and Q425R variants and clinical parameters were assessed using multivariate logistic regression analysis. Results: LGP2 WT and Q425R were detected in 68.2% and 31.8% of the patients, respectively. Q425R carriers showed a lower prevalence of cirrhosis (60.7% vs. 76.3%, p = 0.025) and higher platelet (PLT) counts (152 vs. 116 × 103/μL, p = 0.022). Q425R carriage (p = 0.003), younger age (p = 0.004), and lower serum bile acid levels (p = 0.029) were independently associated with lower cirrhosis rates. Q425R prevalence progressively decreased from 50% to 41% in patients with LSM values ≤ 6.2 kPa and > 6.2 ≤ 12 kPa and from 33.3% to 29.3% to 24.5% to 18.8% in cirrhotic patients with PLT ≥ 150, ≥ 100 < 150, ≥ 50 < 100 and < 50 × 109/L, respectively, (p = 0.011). Conclusions: The LGP2 Q425R variant is independently associated with a reduced risk of cirrhosis in European untreated patients with CHD. These results confirm in vivo that enhanced host innate immune responses modulate the natural history of CHD in vivo.