Comparison of pegylated interferon monotherapy and de novo pegylated interferon plus tenofovir combination therapy in patients with chronic hepatitis B

Abstract

Background and aim: We aimed to evaluate the effectiveness of pegylated interferon (Peg-IFN) monotherapy (IFN group) and combination therapy with tenofovir (TDF) and Peg-IFN (IFN+TDF group) in chronic hepatitis B (CHB) patients. Patients and methods: Data of 143 CHB patients were analyzed in this study. All patients enrolled received liver biopsy. Virologic responses were defined as hepatitis B virus (HBV) DNA <100 IU/mL, biochemical responses were defined as normalization of alanine aminotransferse (ALT) levels, and HBeAg serological response was defined as HBeAg loss or HBeAg seroconversion to HBeAb. HBsAg serological response was defined as HBsAg loss or HBsAg seroconversion to HBsAb. Results: We observed that a total of 16.7% (11/66) and 33.8% (26/77) patients in IFN and IFN+TDF group achieved complete viral suppression after 48 weeks treatment (P=0.02). Although HBeAg levels in CHB patients in the IFN+TDF group decreased more rapidly during the 48-week treatment, we did not observe significant differences in HBeAg serological loss or seroconversion rates between the two groups at 24 and 48 weeks. HBsAg loss was observed in 13.0% (10/77) of CHB patients in the IFN+TDF group at 48 weeks, compared with only 3% (2/66) patients in the IFN group (P=0.032). No significant difference was observed in HBsAg seroconversion rate between the two groups during 48-week treatment. The biochemical response rate was also significantly higher in the IFN+TDF group than that in the IFN group at week 48 (P=0.015). Multivariate logistic analysis showed that IFN+TDF treatment (OR=4.41, P=0.003), severe baseline hepatic inflammation (OR=4.16, P<0.001), and lower baseline serum HBV DNA levels (OR=0.98, P=0.03) were strong predictors for the virological response. Younger age (OR=0.89, P=0.01), higher baseline ALT level (OR=1.01, P=0.038), and lower baseline HBeAg level (OR=0.99, P=0.008) were independent predictors for HBeAg sero-response after 48 weeks treatment. While only severe liver fibrosis (OR=1.69, P=0.028) and lower baseline HBsAg level (OR=0.22, P=0.005) were independent factors associated with HBsAg sero-response after 48 weeks treatment. Conclusion: Peg-IFN combined with TDF may increase the virological response rate, biochemical response rate, and HBsAg loss rate in patients with CHB infection. The combination treatment is more suitable for those patients who are likely to respond to the treatment.

Keywords: hepatitis B; pegylated interferon; tenofovir; virological response.

Figure S1

Flow chart of the study. Abbreviations: CHB, chronic hepatitis B virus; HCV, hepatitis C virus; Peg-IFN, pegylated interferon; TDF, tenofovir.

Figure 1

Change of HBV DNA viral load and proportion of patients with virological response at week 24 and week 48. (A) Significant rapid decreases of DNA loads were observed in IFN+TDF groups at week 12 (3.78±2.31 vs 2.47±1.87 log₁₀ IU/mL in IFN group and IFN+TDF group, P<0.001), week 24 (2.43±1.64 vs 1.82±1.56 log₁₀ IU/mL, P=0.024), and week 48 (1.80±1.90 vs 1.22±1.23 log₁₀ IU/mL, P=0.029), respectively. (B) A total of 10.6% (7/66) and 23.4% (18/77) patients in IFN group and IFN+TDF group achieved complete viral response, respectively (P=0.045). At week 48, 16.7% (11/66) and 33.8% (26/77) patients in IFN and IFN+TDF group achieved complete viral suppression, respectively (P=0.020). Abbreviations: HBV, hepatitis B virus; IFN, interferon; TDF, tenofovir.

Figure 2

Change of serum HBeAg level and proportion of patients with HBeAg sero-response. HBeAg levels in CHB patients in the IFN+TDF group decreased more rapidly during the 48-week treatment (A), we did not observe significant differences in HBeAg serological loss or seroconversion rates between the two groups at weeks 24 and 48 (B and C). Abbreviations: CHB, chronic hepatitis B; IFN, interferon; TDF, tenofovir.

Figure 3

Change of serum HBsAg level and proportion of HBsAg sero-response. HBsAg level in the IFN+TDF group was significantly lower than that in the IFN group at 12 weeks, 24 weeks, and 48 weeks (A). HBsAg loss was observed in 13.0% (10/77) of CHB patients in the IFN+TDF group at week 48, compared with only 3% (2/66) patients in the IFN group (B). No significant difference was observed in HBsAg seroconversion rate between the two groups during 48-weeks treatment (C). Abbreviations: HBsAg, hepatitis B surface antigen; CHB, chronic hepatitis B; IFN, interferon; TDF, tenofovir.

Figure 4

Change of serum ALT level and proportion of biochemical response. ALT level in CHB patients in the IFN+TDF group was significantly lower than that in the IFN group at week 48 (A). The biochemical response rate was also significantly higher in the IFN+TDF group than that in the IFN group at week 48 (B). Abbreviations: ALT, alanine aminotransferse; CHB, chronic hepatitis B; IFN, interferon; TDF, tenofovir.