Safety and efficacy of 48-week pegylated interferon- α-2b therapy in patients with hepatitis B virus-related compensated liver cirrhosis: a pilot observational study

Abstract

Background: Pegylated interferon-α (PEG-IFN-α) therapy could decrease hepatitis B surface antigen (HBsAg) and improve long-term prognosis of hepatitis B virus (HBV) infection. However, studies on safety and efficacy of PEG-IFN-α for patients with HBV-related cirrhosis are limited.

Methods: This was a single-center study. Fifty-four patients with HBV-related compensated cirrhosis were enrolled. All patients received subcutaneous injection of PEG-IFN-α-2b 180 μg per week for 48 weeks. The monotherapy of PEG-IFN-α-2b was used for treatment-naïve patients, while addition of PEG-IFN-α-2b to on-going nucleos(t)ide analogs (NAs) was used for NAs-experienced patients. Clinical symptoms, laboratory tests, examination indicators, and adverse events were collected at each observational time point.

Results: Forty-two patients achieved undetectable serum HBV DNA at 48 weeks post-therapy. HBsAg level was significantly reduced at 48 weeks post-therapy (227.2 IU/mL vs. 1,668 IU/mL; p < 0.001), especially in NAs-experienced patients (161.0 IU/mL vs. 1,207 IU/mL; p = 0.005). Three patients achieved HBsAg loss, and two of them obtained HBsAg seroconversion. There were no significant differences in liver stiffness measurement, thickness and length of spleen, or diameter of portal vein between baseline and 48 weeks post-therapy (p > 0.05). The aminotransferase levels were increased, while white blood cells, neutrophils, and platelets counts were decreased during PEG-IFN-α-2b therapy (p < 0.05), especially in treatment-naïve patients. Three patients discontinued PEG-IFN-α-2b therapy due to severe adverse events. No patients suffered with virological breakthrough or progressed to end-stage liver diseases during observational period.

Conclusion: A finite course of PEG-IFN-α-2b therapy was well-tolerated, and reduced HBsAg level without accelerating disease progression in patients with HBV-related compensated cirrhosis.

Clinical trial registration: This trial is a part of ZhuFeng Project (ClinicalTrials.gov, identifier NCT04035837).

Keywords: antiviral therapy; clinical cure; hepatitis B virus; liver cirrhosis; pegylated interferon-α.

Figure 1

Consolidation standards of reporting trails (CONSORT) flow diagram for this study.

Figure 2

Evolution of therapeutic response to pegylated interferon-α-2b over 48 weeks in all enrolled patients with hepatitis B virus-related compensated liver cirrhosis. (A) Changes of serum HBsAg level at different observational time points. The points indicate median, while the bars indicate interquartile range. Statistical analyses were performed using Kriskal-Wallis H test followed by Dunn’s multiple comparison test. (B) Change of liver stiffness measurement (LSM) at 48 weeks compared with baseline. (C) Change of thickness of spleen at 48 weeks compared with baseline. (D) Change of length of spleen at 48 weeks compared with baseline. (E) Change of diameter of portal vein at 48 weeks compared with baseline. The central lines indicate median or mean, the boxes indicate standard deviation or interquartile range, and the bars indicate the minimum to maximum range. Statistical analyses were performed using Mann–Whitney U test or Student’s t-test.

Figure 3

Evolution of therapeutic response to pegylated interferon-α-2b over 48 weeks in treatment-naïve group and nucleos(t)ide analogs (NAs)-experienced group. (A) Changes of serum HBsAg level at different observational time points in two groups. The black line indicates treatment-naïve group, while the red line indicates NAs-experienced group. The points indicate median, while the bars indicate interquartile range. Statistical analyses were performed using Kriskal-Wallis H test followed by Dunn’s multiple comparison test. (B) Change of liver stiffness measurement (LSM) at 48 weeks compared with baseline in two groups. (C) Change of thickness of spleen at 48 weeks compared with baseline in two groups. (D) Change of length of spleen at 48 weeks compared with baseline in two groups. (E) Change of diameter of portal vein at 48 weeks compared with baseline in two groups. The central lines indicate median or mean, the boxes indicate standard deviation or interquartile range, and the bars indicate the minimum to maximum range. Statistical analyses were performed using Mann–Whitney U test or Student’s t test. ^## p < 0.01 compared with baseline.

Figure 4

Evolution of liver function and blood routine test in response to pegylated interferon-α-2b over 48 weeks in all enrolled patients with hepatitis B virus-related compensated liver cirrhosis. Changes of (A) alanine aminotransferase (ALT) level, (B) aspartate aminotransferase (AST) level, (C) albumin level, (D) white blood cells (WBC) count, (E) neutrophils count, (F) platelets count, (G) hemoglobin (HGB) level at different observational time points. The points indicate median or mean, while the bars indicate interquartile range or standard deviation. Statistical analyses were performed using Kriskal-Wallis H test followed by Dunn’s multiple comparison test or one-way analysis of variance followed by Tukey test. ^#p < 0.05, ^##p < 0.01, ^###p < 0.001 compared with baseline.

Figure 5

Evolution of liver function and blood routine test in response to pegylated interferon-α-2b over 48 weeks in treatment-naïve group and nucleos(t)ide analogs (NAs)-experienced group. Changes of (A) alanine aminotransferase (ALT) level, (B) aspartate aminotransferase (AST) level, (C) albumin level, (D) white blood cells (WBC) count, (E) neutrophils count, (F) platelets count, (G) hemoglobin (HGB) level at different observational time points in two groups. The black line indicates treatment-naïve group, while the red line indicates NAs-experienced group. The points indicate median or mean, while the bars indicate interquartile range or standard deviation. Statistical analyses were performed using Kriskal-Wallis H test followed by Dunn’s multiple comparison test or one-way analysis of variance followed by Tukey test. ^#p < 0.05, ^##p < 0.01, ^###p < 0.001 compared with baseline. ^&p < 0.05 compared with NAs-experienced group in the same observational time point.