Prediction of long-term outcomes in patients with chronic hepatitis D infection by quantitative HBcrAg/anti-HBc IgG ratio

BACKGROUND: Chronic hepatitis D virus (HDV) infection causes the most severe form of viral hepatitis. While HDV usually dominates over hepatitis B virus (HBV), several evidence support HBV role in determining HDV pathogenicity. We investigated the clinical value of novel HBV biomarkers for the prediction of long-term outcomes in patients with chronic hepatitis D (CHD).METHODS: Serum samples from CHD patients (N.=82; median age 51, 43-59 years; males, N.=58 [70.7%]) were retrospectively evaluated at baseline for hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and quantitative antibodies to hepatitis B core antigen (anti-HBc IgG) class IgG (Lumipulse® G600II; Fujirebio, Tokyo, Japan). An in-house RT-qPCR assay was used to quantify HDV RNA.RESULTS: Median patients’ follow-up (FU) was 8 (4-13) years. At baseline, HDV RNA was detectable in 72 (87.8%), with a median value of 5.28 (3.62-6.02) Log IU/mL. Median serum HBsAg, HBcrAg, and anti-HBc IgG values were 3.76 (3.13-4.01) Log IU/mL, 3.7 (2.8-4.6) Log U/mL, and 2.59 (2.18-3.02) Log IU/mL, respectively. During the FU, liver related events (LREs) occurred in 42 (51.2%) patients; 24 (29.3%) patients developed hepatocellular carcinoma (HCC) while 18 (22.0%) developed ascites. A total of 22 (26.8%) patients underwent liver transplant, while 13 (15.9%) died. HBcrAg was associated to mortality (adjusted hazard ratio [aHR]=1.62, P=0.032), while HBcrAg/anti-HBc IgG ratio resulted associated to an increased risk of HCC (aHR=2.75, P=0.007), LREs (aHR=2.01, P=0.013), and mortality (aHR=3.82, P=0.005).CONCLUSIONS: The measurement of HBcrAg and quantitative anti-HBc IgG may represent a valuable tool for risk stratification in patients with CHD.