中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2014年
4期
272-276
,共5页
免疫抑制剂%肝炎病毒,乙型%再激活%肝功能衰竭,暴发性
免疫抑製劑%肝炎病毒,乙型%再激活%肝功能衰竭,暴髮性
면역억제제%간염병독,을형%재격활%간공능쇠갈,폭발성
Immunosuppressor%Hepatitis B virus%Reactivation%Fulminant hepatic failure
目的 了解糖皮质激素激活乙型肝炎病毒(HBV)复制致肝衰竭患者的临床特点,诊治经验及预后,探讨其发病机制.为临床决策提供参考. 方法 对我院收治的7例乙型肝炎应用糖皮质激素后HBV复制激活并致肝衰竭的病例资料进行回顾性分析.留取其中一例无细菌感染征象患者血清,以不同浓度培养HepG2.2.15细胞和HepG2细胞48 ～ 72 h,四甲基偶氮唑盐(MTT)法及Hochester33342染色检测细胞增殖抑制及凋亡情况,抑制率数值的比较采用t检验. 结果 (1)临床资料:7例乙型肝炎患者,男性6例,女性1例,年龄35 ～ 67岁.在使用糖皮质激素前肝功能均正常.其中5例为HBsAg、抗-HBe、抗-HBc阳性,1例为HBsAg、抗-HBc阳性,1例为抗-HBs、抗-HBe、抗-HBc阳性.使用糖皮质激素治疗的原发病为:肾病综合征2例,多囊肾并慢性肾炎1例,肾移植1例,淋巴瘤1例,原发性血小板减少性紫癜1例,脉管炎1例.从使用糖皮质激素到肝衰竭症状出现时间为4～11个月.HBV标志物转换:其中HBeAg转阳性者4例,包括1例原抗-HBs、抗-HBe、抗-HBc阳性者转为HBsAg、HBeAg、抗-HBc阳性.HBV DNA载量变化:使用糖皮质激素前检测HBV DNA低于检测下限4例,1例为1.24×103 IU/ml,2例未测.肝功能衰竭症状出现后,7例均进行HBV DNA检测,为5.75×107 IU/ml～ 1.34×109 IU/ml.抗病毒治疗:使用拉米夫定3例,100 mg/d;恩替卡韦4例,3例0.5 mg/d,1例多囊肾并慢性肾炎及尿毒症患者0.05 mg/d;均予常规护肝,血浆白蛋白支持及血浆置换治疗.7例患者均死亡.从肝病症状发作到死亡时间24 ～ 47 d.(2) MTT实验显示肝衰竭患者血清对HepG2.2.15细胞和HepG2细胞均有抑制增殖效应,并呈现剂量依赖效应;肝衰竭患者血清对HepG2.2.15细胞的增殖抑制效应显著强于HepG2细胞.(3) Hochester33342染色显示肝衰竭患者血清导致HepG2.2.15细胞凋亡显著强于HepG2细胞. 结论 乙型肝炎患者进行糖皮质激素治疗会激活HBV复制并导致肝功能衰竭,补救性抗病毒治疗效果不佳,病死率高.对于HBsAg阳性患者使用糖皮质激素前应予常规进行预防性抗病毒治疗.HBV复制导致肝细胞在肝衰竭发生时更容易发生细胞凋亡和增殖抑制,这可能是HBV再激活肝衰竭程度较重的机制之一.
目的 瞭解糖皮質激素激活乙型肝炎病毒(HBV)複製緻肝衰竭患者的臨床特點,診治經驗及預後,探討其髮病機製.為臨床決策提供參攷. 方法 對我院收治的7例乙型肝炎應用糖皮質激素後HBV複製激活併緻肝衰竭的病例資料進行迴顧性分析.留取其中一例無細菌感染徵象患者血清,以不同濃度培養HepG2.2.15細胞和HepG2細胞48 ～ 72 h,四甲基偶氮唑鹽(MTT)法及Hochester33342染色檢測細胞增殖抑製及凋亡情況,抑製率數值的比較採用t檢驗. 結果 (1)臨床資料:7例乙型肝炎患者,男性6例,女性1例,年齡35 ～ 67歲.在使用糖皮質激素前肝功能均正常.其中5例為HBsAg、抗-HBe、抗-HBc暘性,1例為HBsAg、抗-HBc暘性,1例為抗-HBs、抗-HBe、抗-HBc暘性.使用糖皮質激素治療的原髮病為:腎病綜閤徵2例,多囊腎併慢性腎炎1例,腎移植1例,淋巴瘤1例,原髮性血小闆減少性紫癜1例,脈管炎1例.從使用糖皮質激素到肝衰竭癥狀齣現時間為4～11箇月.HBV標誌物轉換:其中HBeAg轉暘性者4例,包括1例原抗-HBs、抗-HBe、抗-HBc暘性者轉為HBsAg、HBeAg、抗-HBc暘性.HBV DNA載量變化:使用糖皮質激素前檢測HBV DNA低于檢測下限4例,1例為1.24×103 IU/ml,2例未測.肝功能衰竭癥狀齣現後,7例均進行HBV DNA檢測,為5.75×107 IU/ml～ 1.34×109 IU/ml.抗病毒治療:使用拉米伕定3例,100 mg/d;恩替卡韋4例,3例0.5 mg/d,1例多囊腎併慢性腎炎及尿毒癥患者0.05 mg/d;均予常規護肝,血漿白蛋白支持及血漿置換治療.7例患者均死亡.從肝病癥狀髮作到死亡時間24 ～ 47 d.(2) MTT實驗顯示肝衰竭患者血清對HepG2.2.15細胞和HepG2細胞均有抑製增殖效應,併呈現劑量依賴效應;肝衰竭患者血清對HepG2.2.15細胞的增殖抑製效應顯著彊于HepG2細胞.(3) Hochester33342染色顯示肝衰竭患者血清導緻HepG2.2.15細胞凋亡顯著彊于HepG2細胞. 結論 乙型肝炎患者進行糖皮質激素治療會激活HBV複製併導緻肝功能衰竭,補救性抗病毒治療效果不佳,病死率高.對于HBsAg暘性患者使用糖皮質激素前應予常規進行預防性抗病毒治療.HBV複製導緻肝細胞在肝衰竭髮生時更容易髮生細胞凋亡和增殖抑製,這可能是HBV再激活肝衰竭程度較重的機製之一.
목적 료해당피질격소격활을형간염병독(HBV)복제치간쇠갈환자적림상특점,진치경험급예후,탐토기발병궤제.위림상결책제공삼고. 방법 대아원수치적7례을형간염응용당피질격소후HBV복제격활병치간쇠갈적병례자료진행회고성분석.류취기중일례무세균감염정상환자혈청,이불동농도배양HepG2.2.15세포화HepG2세포48 ～ 72 h,사갑기우담서염(MTT)법급Hochester33342염색검측세포증식억제급조망정황,억제솔수치적비교채용t검험. 결과 (1)림상자료:7례을형간염환자,남성6례,녀성1례,년령35 ～ 67세.재사용당피질격소전간공능균정상.기중5례위HBsAg、항-HBe、항-HBc양성,1례위HBsAg、항-HBc양성,1례위항-HBs、항-HBe、항-HBc양성.사용당피질격소치료적원발병위:신병종합정2례,다낭신병만성신염1례,신이식1례,림파류1례,원발성혈소판감소성자전1례,맥관염1례.종사용당피질격소도간쇠갈증상출현시간위4～11개월.HBV표지물전환:기중HBeAg전양성자4례,포괄1례원항-HBs、항-HBe、항-HBc양성자전위HBsAg、HBeAg、항-HBc양성.HBV DNA재량변화:사용당피질격소전검측HBV DNA저우검측하한4례,1례위1.24×103 IU/ml,2례미측.간공능쇠갈증상출현후,7례균진행HBV DNA검측,위5.75×107 IU/ml～ 1.34×109 IU/ml.항병독치료:사용랍미부정3례,100 mg/d;은체잡위4례,3례0.5 mg/d,1례다낭신병만성신염급뇨독증환자0.05 mg/d;균여상규호간,혈장백단백지지급혈장치환치료.7례환자균사망.종간병증상발작도사망시간24 ～ 47 d.(2) MTT실험현시간쇠갈환자혈청대HepG2.2.15세포화HepG2세포균유억제증식효응,병정현제량의뢰효응;간쇠갈환자혈청대HepG2.2.15세포적증식억제효응현저강우HepG2세포.(3) Hochester33342염색현시간쇠갈환자혈청도치HepG2.2.15세포조망현저강우HepG2세포. 결론 을형간염환자진행당피질격소치료회격활HBV복제병도치간공능쇠갈,보구성항병독치료효과불가,병사솔고.대우HBsAg양성환자사용당피질격소전응여상규진행예방성항병독치료.HBV복제도치간세포재간쇠갈발생시경용역발생세포조망화증식억제,저가능시HBV재격활간쇠갈정도교중적궤제지일.
Objective To investigate the clinical features and mechanisms of hepatitis B virus (HBV)reactivation induced by chemotherapy or immunosuppressive therapy and subsequent fulminant hepatic failure (FHF) in patients with autoimmune diseases.Methods Seven cases of FHF related to HBV reactivation were retrospectively assessed.All patients had been confirmed as hepatitis B e antigen (HBeAg) seronegative and had undergone glucocorticoid-based therapy to manage primary diseases,including nephrotic syndrome (2 cases),polycystic kidney disease combined with chronic nephritis (1 case),conditions following kidney transplantation (1 case),lymphadenoma (1 case),idiopathic thrombocytopenic purpura (1 case),and angitis (1 case).Levels of sero-markers of HBV and HBV DNA were recorded.Serum samples from patients were respectively applied to HepG2.2.15 and HepG2 cell lines in order to investigate the effects on cell proliferation (by MTT assay) and apoptosis (by Hoechst 33342 staining assay).Intergroup differences were statistically assessed by the t-test.Results For all patients,the initial clinical signs of hepatic failure emerged at 4 to 11 months after receipt of the glucocorticoid treatment.At the time of hepatic failure,HBeAg seropositivity was detected in 4 patients,including one patient who also showed seropositivity for the hepatitis B surface antibody (HBsAb).All 7 patients showed high levels of HBV DNA when the hepatitis condition flared.Neither remedial antiviral treatments nor internal medicine comprehensive treatments,including therapeutic plasma exchange,were effective in any of these cases.The duration from clinical signs onset to death ranged from 24 to 47 days.Treatment of HepG2.2.15 and HepG2 cells with serum samples from patients with FHF showed a dosage-effect relationship of the serum concentration on the cellular proliferation inhibition rate,with the serum of patients with FHF having more severe inhibiting effects on the HepG2.2.15 cells than on the HepG2 cells.The HepG2.2.15 cells showed a greater tendency towards apoptosis upon treatment with serum samples from patients with FHF,compared to the HepG2 cells.Conclusion HBV reactivation induced by chemotherapy or immunosuppressive therapy is a problem currently encountered in the management of malignancies or rheumatic autoimmune disease patients.It is critical to verify HBV status prior to initiation of these treatment strategies so that appropriate antiviral prophylaxis may be administered,so as to reduce the risk of HBV reactivation and subsequent repression of cell proliferation and apoptosis that can promote development of FHF and increase a patient's risk of death.
