The sK122R mutation of hepatitis B virus (HBV) is associated with occult HBV infection: Analysis of a large cohort of Chinese patients.

BACKGROUND: Occult HBV infection (OBI) is of great concern due to their complicated diagnosis and potential for public transmission. OBJECTIVE: The study aimed to determine the clinical prevalence of OBI and if viral immune escape-associated mutations contribute to the occurrence of OBI. STUDY DESIGN: A total of 91,037 HBV-infected patients with different related illnesses who were admitted to the Fifth Medical Center of Chinese PLA General Hospital from January 2005 to December 2017 were tested for OBI. Serum samples from 62 patients with OBI manifestations (OBI patients) and 124 matched non-OBI patients were sequenced for possible immune escape-associated mutations within the major hydrophilic region of HBV S protein. HBsAg and HBV DNA levels in representative viral strains were measured. RESULTS: Of the 91,037 tested patients, 487 (0.53 %) were negative for HBsAg but positive for HBV DNA and were defined as OBI patients. The prevalence in different illness categories varied. Immune escape-associated mutations were more frequently detected in OBI patients than in non-OBI patients (59.68 % vs. 35.48 %, P < 0.01), as did the coexistence of multiple mutations (43.55 % vs. 22.58 %, P < 0.01). Specifically, the prevalence rates of sT118 K, sK122R, and sV168A were increased in OBI patients. Strains with sK122R mutants (sK122R, sK122R + D144E, sK122R + C121R + D144E, and sK122R + F134L + D144E) from a follow-up OBI patient all showed significantly lower levels of HBsAg production than a wild-type strain. CONCLUSIONS: The study clarified the clinical prevalence of OBI, verified the influence of immune escape-associated mutations, and identified the role of the sK122R mutation in multiple OBI patients.