Predictive role of serum HBsAg and HBcrAg kinetics in patients with HBeAg-negative chronic hepatitis B receiving pegylated interferon-based therapy.

OBJECTIVES: To investigate the role of serum hepatitis B core-related antigen (HBcrAg) kinetics in predicting long-term outcome of pegylated interferon (PEG-IFN)-based therapy in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). METHODS: A total of 121 Thai patients with HBeAg-negative CHB recruited from a previous randomized trial of 48-week PEG-IFN alone or combined with entecavir were enrolled. Hepatitis B surface antigen (HBsAg) and HBcrAg levels were serially examined. Paired biopsy samples taken at baseline and after treatment were assessed for intrahepatic covalently closed circular DNA (cccDNA). RESULTS: Persistent virologic remission (PVR, defined by persistent hepatitis B virus (HBV) DNA <2000 IU/mL) and HBsAg clearance at 3 years after treatment were 29% (35/121) and 9% (11/121) respectively. Baseline HBcrAg correlated with HBV DNA and cccDNA but not with HBsAg. Baseline HBsAg, as well as HBsAg and HBcrAg, declines were associated with PVR, while HBsAg decline was predictive of HBsAg clearance. High baseline antigen levels (HBsAg ≥3.4 log10 IU/mL plus HBcrAg ≥3.7 log10 U/mL) yielded high negative predictive values of PVR (45/50, 90%) and HBsAg clearance (50/50, 100%). At week 12, declines of HBsAg, HBcrAg and both antigens combined of <0.5 log10 yielded negative predictive values for PVR of 90% (71/79), 82% (61/74) and 96% (48/50) respectively. CONCLUSIONS: Quantitative HBcrAg was significantly associated with cccDNA in HBeAg-negative CHB. This novel antigen, together with HBsAg, could identify patients with low probability of PVR and HBsAg clearance in long-term follow-up.

Peg-interferon and ribavirin treatment in HIV/HCV co-infected patients in Thailand: efficacy, safety and pharmacokinetics.

OBJECTIVE: In Thailand, 7.2% of HIV patients are co-infected with hepatitis C virus (HCV), and these patients are treated with peg-interferon + ribavirin (PR) for their HCV infection. This study evaluates efficacy and safety of PR treatment and pharmacokinetics of ribavirin in this population. METHODS: HIV/HCV co-infected Thai patients were treated with PR for 24 or 48 weeks. Sustained virological response 24 weeks after the end of treatment (SVR24) was used to describe efficacy. (laboratory) safety parameters and ribavirin plasma concentrations were evaluated during study visits. Ribavirin concentrations were compared with t-tests for patients with and without anaemia (haemoglobin <10 g/dl) and SVR24. RESULTS: A total of 101 HIV/HCV co-infected patients were included; 88% were male (n = 88), and 46% were infected with genotype 3. The median (IQR) start dose was 14.28 mg/kg/day. SVR24 rate was 56%. All patients reported at least one (serious) adverse event, of which 28% of patients developed anaemia. Seven patients discontinued treatment due to toxicity issues. Geometric mean (IQR) ribavirin concentration was 1.81 (1.42-2.32) mg/l at week 8 of treatment. At week 8, patients with and without anaemia and SVR had ribavirin concentrations of 2.29 and 1.63 mg/l and 1.91 and 1.74 mg/l, respectively. CONCLUSIONS: PR treatment has comparable response rates and toxicity profile in Thai HIV/HCV co-infected patients as in Western HIV/HCV patients. However, ribavirin plasma concentrations were comparable with previously published studies in HIV/HCV co-infected patients, but both, just as SVR rate, were lower than in mono-infected patients.

A randomized clinical trial of peginterferon alpha-2b with or without entecavir in patients with HBeAg-negative chronic hepatitis B: Role of host and viral factors associated with treatment response.

Combining peginterferon (PEG-IFN) and a potent nucleoside/nucleotide analogue might improve treatment response in patients with chronic hepatitis B (CHB). The aims of this study were to compare the efficacy of PEG-IFN alpha-2b with or without entecavir in HBeAg-negative CHB and to investigate predictors of response. A total of 126 treatment-naïve patients were randomly assigned to receive monotherapy (n = 63) or combination therapy (n = 63) for 48 weeks. Virological response (VR) was defined as HBV DNA level <2000 IU/mL at week 96. Baseline factors including polymorphisms in the IFNL3 (rs12979860) and HLA-DPA1 (rs3077) genes and on-treatment viral kinetics were determined. At week 48, rates of undetectable HBV DNA were lower in the monotherapy than combination groups, but rates of HBsAg clearance and decline were comparable. At week 96, there was no difference between the corresponding groups regarding virological response (41.3% vs 38.1%, P = 0.856), HBsAg clearance (9.5% vs 4.8%, P = 0.491) and HBsAg decline. Baseline HBsAg level [odds ratio (OR): 3.14 (1.34-7.69), P = 0.012] and rs3077 polymorphism [OR: 2.78 (1.27-6.11), P = 0.011] were independent predictors of response. Patients carried GG genotype of rs3077 with low baseline HBV (<1000 IU/mL) had high probability of achieving VR (76.5%) and HBsAg clearance (29.4%). None of the patients without decrease in HBsAg combined with <2 log10 HBV DNA decline at week 12 achieved a virological response. In conclusion, the combination therapy lead to greater on-treatment HBV DNA suppression but did not improve virological response and HBsAg clearance/decline over monotherapy. Host and viral factors could help optimize decision-making at baseline and during PEG-IFN-based therapy.