ABSTRACT
Objective To identify the predictive factors associated with hepatitis B surface antigen (HBsAg) loss in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients treated with pegylated interferon (PEG-IFNα-2a).Methods Seventy-two HBeAg positive CHB patients were treated with PEG-IFNa-2a 180 μg weekly for 48 weeks. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatitis B virus (HBV) DNA,HBeAg, and HBsAg were quantitatively detected every 3 months. The relationship between HBV DNA, HBeAg, and HBsAg levels at baseline, week 12, 24 of treatment and HBsAg loss was analyzed.The data were statistically assessed by Fisher's exact test,and receiver operating characteristic (ROC) curve. ResultsTotally 65 patients accomplished the therapy, and 7 (10.8％)patients achieved HBsAg loss. HBsAg loss at week 48 of treatment was associated with HBeAg level at week 12 of treatment (Fisher's exact test, P= 0. 023), HBeAg level at week 24 (Fisher's exact test, P=0. 004), and lower HBsAg levels (＜250 IU/mL) at week 12 and 24 of treatment (Fisher's exact test,P=0. 001 and 0.002, respectively). HBsAg loss was associated with HBV DNA negative ( ＜ 1000 copy/mL) at week 12 of treatment (Fisher's exact test, P = 0. 039), while not associated with HBV DNA negative at week 24 of treatment (Fisher's exact test, P=0. 130). ROC curve analysis revealed that the AUC was 0. 8584(P=0. 0021) of HBsAg level at week 12, 0. 9606(P=0. 001) of HBsAg level at week 24, and 0. 8350(P=0. 040) of HBeAg level at week 24. ConclusionLevels of HBsAg and HBeAg at week 24 of treatment might serve as effective factors to predict HBsAg loss in patients received PEG-IFN monotherapy.
ABSTRACT
Objective To investigate the association between hepatitis B virus (HBV)genotype, the mutations in HBV basic core gene promoter(BCP), pre C/C gene region and treatment response to interferon (IFN)α-1b. Methods Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients were treated with IFNα-Ib for 6 months and were followed up for 6 months after the end of treatment. Restriction Fragment Length Polymorphism (RFLP) was used for determining HBV genotype. HBV DNA was amplified by polymerase chain reaction (PCR) and analyzed for BCP and pre C/C gene region by sequencing. Measurement data were compared using t test and analysis of variance. Enumeration data were compared using chi-square test, Fisher exact probability test.Logistic regression analysis was utilized for multi-factor analysis. Results There were 39 patients who completed the treatment and follow up in this study. At the end of treatment, 16(41.0%) patients showed response to the IFNα-lb treatment. At the end of follow-up, four out of 16 patients who achieved on treatment response relapsed. Among 3a patients, 29 (74.4 %) were infected with genotype B and 10 (25. 6%) with genotype C. The treatment response rates were not significant different between the groups with different genotypes. The double mutation pattern (T1762/A1764) was found in eight (20. 5%) patients. The response rates to IFNα-lb treatment were not significant different between the group with and without double mutation pattern. A1896 mutation was detected in eight patients at baseline. Three of them became HBeAg negative at the end of treatment and returned to HBeAg positive during follow-up. The non-lyphocyte epitope mutations, L60V and I97L, were found in 15 patients (38. 5%) and 14 patients (35.9%), respectively. At the end of follow-up, the patients with 60V had a significantly lower HBeAg seroconversion rate and HBV DNA undetectable rate compared to the patients with 60L (Fisher exact probability test; P = 0.0126 and 0.0069,respectively). The HBV DNA undetectable rates in the patients with 97I were significantly lower than those in patients with 97L both at the end of treatment and the end of follow-up (Fisher exact probability test; P= 0.0484 and 0. 0024, respectively). Logistic regression analysis results showed that there was no association between the above viral mutations and the treatment response to IFNαlb. Conclusions There is no association between HBV genotype, BCP double mutation pattern and IFN-α treatment response. The non-lyphocyte epitope mutations, L60V and I97L, may have impact on IFN-α treatment response.