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，5mIU/(m2·次)，1次/2d，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，P Ⅲ P)、Ⅳ 型胶原(type Ⅳcollagen，CⅣ)];记录两组不良反应发生情况。采用t检验、x2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。
Clinical study on sequential therapy with recombinant human interferon-α2b and lamivudine in children with chronic hepatitis B in immune-tolerant phase
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/(m2·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(P Ⅲ P),and type Ⅳ collagen(C Ⅳ)]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 x2 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,P Ⅲ P,CⅣ decreased 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.
Hepatitis BImmune toleranceRecombinant human interferon α2bLamivudineChildren
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