| Objective(s):Hepatitis B virus (HBV) infection is a major public health problem and the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) worldwide. According to the global burden of Disease (GBD) study in 2015, there are more than 248 million chronic hepatitis B virus (CHBV) carriers worldwide (Mortality and Causes of Death,2015). Therefore, effective antiviral agents are urgently needed to treat or even halt the progression from chronic hepatitis to cirrhosis and HCC. Approved current therapeutic options for CHB include interferon alfa-2b, peginterferon alfa-2a(PEG-IFN-a) and five nucleos(t)ide analogues (NUCs), namely lamivudine (LAM), adefovir dipivoxil (ADV), telbivudine (LdT), entecavir (ETV), and tenofovir disoproxil fumarate (TDF). The primary aim of antiviral therapy for CHB is achieving alanine aminotransferase (ALT) normalization and durable suppression of serum HBV DNA to low or undetectable levels. CHB patients who have HBV DNA>500 copies/mL, elevated ALT level, and whether or not evidence of fibrosis should receive antiviral therapy regardless of their hepatitis B e antigen (HBeAg) status. Several international HBV management guidelines recommend PEG-IFN-a, ETV and TDF as the first-line treatments. However, NUCs cannot effectively eradicate covalently closed circular DNA (cccDNA) in HBV-infected hepatocytes; hence, viral replication may recur after cessation of NUCs treatment.Entecavir (ETV) are highly potent NUCs. However, the correlation between serum HBV DNA level (virological response) and HBeAg seroconversion after prolonged treatment with entecavir remains unclear and deserves further study.This paper makes a retrospective study to assess virological and serological response, as well as recuperation of hepatic function in patients treated with entacavir for 48 weeks in order to provide a scientific foundation for prevention and clinical treatment of hepatitis B.Methods:A total of 75 treatment-naive HBeAg-positive and HBeAg-negative CHB patients receiving at least 48 weeks of entecavir therapy aged 11-75 were enrolled in this study conducted from September 2014 to September 2015 by the outpatient service of the Department of Infectious Diseases, Kunming General Hospital of PLA Chengdu Command. They were divided into two groups based on their HBeAg status, i.e., HBeAg-positive patients (n=48) and HBeAg-negative patients (n=27). To evaluate the efficacy of entecavir therapy on HBeAg-positive patients and HBeAg-negative patients, retrospective analysis of HBV DNA, HBeAg, ALT, aspartate aminotransferase (AST), total bilirubin (TBIL), albumin, globulin, glomerular filtration rate (GFR) levels at week 4, week 12, week 24 and week 48 were performed. Patients with HBV DNA<500 copies/mL at week 24 were defined as complete virological response (CVR) group, and patients with HBV DNA>500 copies/ml and HBV DNA decrease> 2.0 log10 copies/mL at week 24 were defined as partial virological response (PVR) group. Statistical analysis were performed to investigate the the correlation between efficacy of ETV and age, sex, virological and serological response, as well as recuperation of hepatic and kidney function in patients after 48 weeks of ETV therapy. Results:The proportion of HBeAg-positive patients with HBV DNA< 500copies/mL after receiving entecavir 4,12,24 and 48 weeks are 0%,0%,34.2%and 60.5%, while the proportion of HBeAg-negative patients with HBV DNA< 500 copies/mL at week 4,12,24 and 48 are 0%,0%,23.5%, and 51.8%. One HBeAg-positive CHB patients achieved HBeAg seroconversion after 48 weeks treatment.71.4%(5/7) HBeAg-positive patients with PVR achieved normal ALT levels, while the normalization rate of HBeAg-positive patients with CVR is 65.9% (27/41), proving that ALT levels of HBeAg positive patients can be reduced greatly. Significant drop of AST levels can also be observed among HBeAg-positive patients. AST normalization rate of HBeAg-positive patients with PVR and CVR are 85.7% and 78.0%, respectively. Similar observations can be found among HBeAg-negative patients. Normalization rate of ALT and AST among HBeAg-negative patients are 66.7%(4/6) and 83.3%(5/6) in PVR patients, while 71.4%(15/21) and 66.7%(14/21) CVR patients proved normal ALT and AST levels, respectively.Conclusion:Clinical observations on enticavir therapy to 75 CHB patients indicate that, enticavir possesses rapid and potent antiviral activity with safety, on both HBeAg-positive and negative CHB patients. Entecavir for the initial treatment of patients with CHB rapid, potent antiviral activity and safety. Significant drop of HBV DNA levels is observed on both HBeAg-positive and negative CHB patients after 48 weeks enticavir treatment. One HBeAg-positive patient achieved seroconversion after treatment. HBeAg-positive patients with CVR showed lower HBeAg than HBeAg-positive patients with PVR. After receiving entecavir therapy for 48 weeks, ALT normalization rate of HBeAg-negative patient is slightly lower than that of HBeAg-positive patients, with no significant difference between two groups. The rate of achieving CVR at week 24 is higher among HBeAg-positive patients. For both HBeAg-positive and negative patients, the decrease of HBV DNA at week 12, ALT levels at week 12 and 24, and AST levels at week 12 and week 24 are related to achieving virological response (P< 0.05). No kidney function damage occurred to all 75 CHB patients after 48 enticavir treatment. |
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