Reactivation of Occult Hepatitis B Virus Infection During Long-Term Entecavir Antiviral Therapy

Abstract

Up to now, it has not been clear whether occult hepatitis B virus (HBV) infection (OBI) can be treated with antiviral therapy whether OBI can develop drug resistance gene mutation or not. We report a middle-aged female patient with OBI who showed HBV reactivation (HBVr) during more than 3 years of intermittent entecavir (ETV) antiviral therapy: seropositive HBV surface antigen (HBsAg), increased e antigen (HBeAg), and repeatedly elevated serum HBV DNA. Genotype analysis showed that the patient was infected with HBV type B. Genetic sequencing of HBV showed the mutants of S143T, D144G, and G145R in the S gene region, and the mutant of site 1896 in the pre-Core region coexisted with the wild type (G1896A/G). No mutation was found in other HBV gene segments. Drug resistance gene analysis found RtL229W mutant, resistant to lamivudine but sensitive to ETV and other nucleoside analogs. This case of OBI provides us with the following clinical experiences: Firstly, it is necessary to detect HBV genotype, mutation, and drug-resistant genes at the initial diagnosis, which can be helpful for reasonable treatment. Secondly, identifying the risk factors and mechanisms associated with HBVr could help quantify the risk of HBVr and manage the clinical consequences. Thirdly, the OBI patients with hepatitis B e antigen-positive, HBV DNA > 1 × 103 IU/ml should be recommended regular and continuous antiviral therapy as soon as possible to prevent the occurrence of hepatocirrhosis and hepatocellular carcinoma (HCC).

The Investigation of Hepatitis B Vaccine Immune Responses in Occult Hepatitis B Virus-Infected Patients

“…Nearly two-thirds of OBI patients have varying degrees of liver fibrosis. A small number of OBI patients have an abnormal liver function and liver disease-related symptoms, indicating that OBI is not in a “healthy state.” From 12 to 36 weeks of observation, serum hepatitis B surface antigen and HBV DNA reactivation were found in two patients of Group B, which meant that HBV in the OBI state is not always stable or cleared, consistent with our previous findings ( 11 , 13 ).…”

“…OBI is a unique type of HBV infection that is currently circulating. Our research team and others have discovered that OBI can cause HBV reactivation, liver cirrhosis, and HCC ( 11 , 13 , 14 ).…”

False occult hepatitis B virus infection with negative HBsAg while positive HBeAg & overt DNA levels: Case report and literature review

“…If we use the criteria of Chinese CHB guidelines published in 2019, patients with HBV DNA positive (>20 IU/ml), and ALT sustained elevated (>ULN) are the Indications for antiviral therapy. Recently published case report maybe can give us some pointers [19], it reported an "OBI" with positive HBeAg and HBsAg-/HBV DNA+ (2.32 × 10 3 IU/ml) and received ETV treatment, 4 weeks after initiation of ETV treatment HBV DNA dropped below 100 IU/ml (Minimum detection value line) and maintained for 6 months. After that the patient spontaneously stopped taking ETV for 6 month and then the HBV DNA rebounded to 2.79 × 10 3 IU/ ml, the patient was encouraged to continue ETV treatment and achieve HBV DNA undetectable again.…”

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

“…Developing effective prevention strategies, including vaccination and anti-viral treatments, has significantly contributed to reducing the burden of HBV infection, although challenges remain, especially in regions with high prevalence rates. While advancements in anti-viral therapies have improved outcomes for many patients, the virus can persist in a latent state within the body, posing the risk of reactivation[ 4 , 5 ].…”