The Serious Challenge of Occult Hepatitis B Virus Infection-Related Hepatocellular Carcinoma in China

Abstract

BackgroundIt is unknown how many people in China have chronic occult hepatitis B virus (HBV) infection (OBI) [chronic HBV infection with negative serum hepatitis B surface antigen (HBsAg) (N-HBsAg)]. Their clinical and virological characteristics, especially the correlation between the OBI and hepatocellular carcinoma (HCC), are still elusive and need to be investigated, including prevention, early diagnosis, and treatment strategies.Methods138 patients with HCC related to OBI were screened from 698 patients of HCC associated with HBV infection, their characteristics of epidemiology, clinical, biochemistry, virology, diagnostics, and therapeutics were analyzed retrospectively. Furthermore, the correlation between virological features and clinical features was investigated.ResultsIt was found that 19.8% (138/698) of patients with HBV-related HCC were OBI, of which 79.7% (110/138) were men, and 20.3% (28/138) were women. Most of the patients with OBI-related HCC were older men, and the median age was 63.2 years. In total 78.3% (108/138) of the patients had apparent right upper abdomen discomfort and/or pain and then sought medical examination, while 21.7% (30/138) of the patients were identified by health examination. A total of 10.9% (15/138) of the patients were admitted with chronic infection of HBV, and 2.2% (3/138) of the patients were admitted with a family history of hepatitis B. The alpha-fetoprotein (AFP) serum-positive rate was 39.1% (54/138). Tumor lesions >5.0 cm, with intrahepatic and/or extrahepatic metastasis, were found in 72.5% (100/138) of the patients. The diameter of the tumor in the Group of hepatitis B core antibody-positive [HBcAb(+)] and hepatitis B surface antibody-positive [HBsAb(+)] was 7.03 ± 3.76 cm, which was much smaller than 8.79 ± 4.96 cm in the Group of HBcAb(+) and HBsAb(−) (P = 0.035).ConclusionIt is estimated that at least 21 million OBI patients live in China. HBcAb(+) was not only the evidence of chronic HBV infection but also a dangerous mark for surface antigen-negative patients. A semi-annual or annual medical checkup is essential for all OBI patients to identify HCC as early as possible. The hypothesis underlying our analysis was that hepatitis B surface antibody would prevent the progress of HCC and facilitate the clearance of HBV in patients with OBI. Thereby, the hepatitis B vaccine could be used to prevent severe disease consequences.

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 ).…”

“…also found that serum anti-HBs titers were inversely proportional to the risk of HBV reactivation following re-positivity of the surface antigen ( 20 ). In a previous study of OBI patients, our team discovered that the average diameter of HCC in anti-HBs-positive patients was significantly smaller than that in anti-HBs-negative patients ( 11 ).…”

“…In local areas of China, the prevalence of OBI was 19.48% (640/3100 cases) in the young people without the hepatitis B vaccine and 4.70% (170/3615 cases) in that vaccinated with the hepatitis B vaccine ( 10 ). Our research team estimates at least 20 million OBI patients in China ( 11 ).…”

“…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 ).…”

“…Restoring the immune function of HBV-infected patients might eradicate the virus ( 6 ). Anti-HBs are known to be protective antibodies ( 17 ), capable of preventing reinfection and maintaining host immunosuppression against HBV ( 18 ), and our research team discovered that anti-HBs might also prevent HCC progression ( 11 ). It is proposed to treat OBI with a recombinant yeast-derived hepatitis B vaccine, observe immunological changes, and investigate its therapeutic potential.…”