重组人干扰素α2b和拉米夫定序贯治疗用于乙肝免疫耐受期患儿的临床研究

Clinical study on sequential therapy with recombinant human interferon-α2b and lamivudine in children with chronic hepatitis B in immune-tolerant phase

目的观察重组人干扰素α2b(recombinant human interferon-α2b,rhIFN-α2b)和拉米夫定序贯治疗用于乙肝免疫耐受期患儿的效果。方法选择西安医学院第三附属医院2020年4月至2023年4月收治的96例乙肝免疫耐受期患儿为研究对象,按随机数字法分为研究组与对照组各48例。研究组男29例,女19例;年龄(7.54±1.36)岁;病程(2.25±0.54)年;有乙肝家族史28例。对照组男26例,女22例;年龄(7.63±1.41)岁;病程(2.44±0.51)年;有乙肝家族史26例。对照组口服拉米夫定片,0.1 g/次,1次/d,治疗24周。研究组采用rhIFN-α2b和拉米夫定序贯治疗:前4周单用rhIFN-α2b肌内或皮下注射,5 mIU/(m^(2)·次),1次/2 d,4周后加用拉米夫定,0.1 g/次,1次/d,持续治疗8周后停用rhIFN-α2b仅用拉米夫定,继续治疗12周。比较两组疗效;治疗4周、12周、24周后,记录两组乙肝病毒E抗原(hepatitis B virus E antigen,HBeAg)、乙肝病毒脱氧核糖核酸(hepatitis B virus DNA,HBV-DNA)转阴率和乙肝病毒E抗体(hepatitis B virus E antibody,HBeAb)转换率;治疗前及治疗24周后,比较两组肝功能[谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspertate aminotransferase,AST)、总胆红素(total bilirubin,TBil)]及肝纤维化指标[透明质酸(hyaluronic acid,HA)、层黏蛋白(laminin,LN)、Ⅲ型前胶原肽(type Ⅲ procollagen peptide,PⅢP)、Ⅳ型胶原(type Ⅳ collagen,CⅣ)];记录两组不良反应发生情况。采用t检验、χ^(2)检验进行统计学分析。结果研究组总有效率高于对照组[77.08%(37/48)比52.08%(25/48)](P<0.05)。治疗4周及12周后,研究组与对照组HBeAg、HBV-DNA转阴率比较差异均无统计学意义(均P>0.05),治疗24周后,研究组HBeAg、HBV-DNA转阴率均高于对照组(均P<0.05);两组治疗后不同时间点HBeAb转换率比较差异均无统计学意义(均P>0.05)。治疗24周后,两组ALT、AST、TBil均降低,且研究组[(39.16±7.51)U/L、(41.92±8.26)U/L、(15.13±4.29)μmol/L]均低于对照组[(47.38±8.02)U/L、(52.36±8.73)U/L、(18.67±4.86)μmol/L](均P<0.05)。治疗24周后,两组HA、LN、PⅢP、CⅣ均降低,且研究组[(113.57±30.16)μg/L、(96.41±29.05)μg/L、(78.14±20.96)μg/L、(90.26±26.31)μg/L]均低于对照组[(208.34±64.72)μg/L、(124.27±32.19)μg/L、(104.37±22.48)μg/L、(143.75±33.49)μg/L](均P<0.05)。两组不良反应发生率比较差异无统计学意义(P>0.05)。结论rhIFN-α2b和拉米夫定序贯治疗在乙肝免疫耐受期患儿中疗效确切,能有效减少病毒含量,阻止肝功能恶化及肝纤维化,且安全性较高。

Objective To observe the efficacy of sequential therapy with recombinant human interferon-α2b(rhIFN-α2b)and lamivudine in children with chronic hepatitis B in immune-tolerant phase.Methods A total of 96 children with chronic hepatitis B in immune-tolerant phase who were admitted to the Third Affiliated Hospital of Xi'an Medical University from April 2020 to April 2023 were selected as the study objects,and were divided into a study group and a control group with 48 cases in each group according to the random number method.There were 29 boys and 19 girls in the study group,aged(7.54±1.36)years;the course of disease was(2.25±0.54)years;there were 28 cases with family history of hepatitis B.There were 26 boys and 22 girls in the control group,aged(7.63±1.41)years;the course of disease was(2.44±0.51)years;there were 26 cases with family history of hepatitis B.The control group was treated with lamivudine tablets orally,0.1 g/time,once a day,for 24 weeks.The study group received sequential therapy with rhIFN-α2b and lamivudine:rhIFN-α2b was given by intramuscular or subcutaneous injection of 5 mIU/(m^(2)·time),once every 2 days for the first 4 weeks,and lamivudine was added at 0.1 g/time,once a day after 4 weeks;after continuous treatment for 8 weeks,rhIFN-α2b was discontinued and lamivudine was used only for 12 weeks.The efficacy of the two groups was compared.After 4,12,and 24 weeks of treatment,the negative conversion rates of hepatitis B virus E antigen(HBeAg)and hepatitis B virus DNA(HBV-DNA),and hepatitis B virus E antibody(HBeAb)conversion rate were recorded.The liver function[alanine aminotransferase(ALT),aspertate aminotransferase(AST),and total bilirubin(TBil)]and liver fibrosis indicators[hyaluronic acid(HA),laminin(LN),type Ⅲ procollagen peptide(PⅢP),and type Ⅳ collagen(CⅣ)]were compared between the two groups before treatment and 24 weeks after treatment.The incidences of adverse reactions in the two groups were recorded.t test and χ^(2) test were used for statistical analysis.Results The total effective rate of the study group was higher than that of the control group[77.08%(37/48)vs.52.08%(25/48)](P<0.05).After 4 and 12 weeks of treatment,there was no statistically significant difference in the negative conversion rate of HBeAg or HBV-DNA between the study group and the control group(all P>0.05);after 24 weeks of treatment,the negative conversion rates of HBeAg and HBV-DNA in the study group were higher than those in the control group(both P<0.05).There was no statistically significant difference in the HBeAb conversion rate between the two groups at different time points after treatment(all P>0.05).After 24 weeks of treatment,the levels of ALT,AST,and TBil decreased in both groups,and those in the study group[(39.16±7.51)U/L,(41.92±8.26)U/L,and(15.13±4.29)μmol/L]were lower than those in the control group[(47.38±8.02)U/L,(52.36±8.73)U/L,and(18.67±4.86)μmol/L](all P<0.05).After 24 weeks of treatment,the levels of HA,LN,PⅢP,CⅣdecreased in both groups,and those in the study group[(113.57±30.16)μg/L,(96.41±29.05)μg/L,(78.14±20.96)μg/L,and(90.26±26.31)μg/L]were lower than those in the control group[(208.34±64.72)μg/L,(124.27±32.19)μg/L,(104.37±22.48)μg/L,and(143.75±33.49)μg/L](all P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion The sequential therapy with rhIFN-α2b and lamivudine has clear efficacy in children with chronic hepatitis B in immune-tolerant phase,which can effectively reduce the virus content,prevent liver function deterioration and liver fibrosis,and has high safety.