更昔洛韦联合腺苷蛋氨酸治疗巨细胞病毒性肝炎患儿的临床疗效

正新生儿极易发生婴儿巨细胞病毒性肝炎(Infant cytomegalovirus hepatitis,ICH),严重影响小儿生长发育~([1-2])。更昔洛韦(Ganciclovir,GCV)为国内外广泛使用的一线抗血清巨细胞病毒(CMV)药物,但更昔洛韦治疗巨细胞病毒感染疗程较长、费用贵、疗效不确切,且具有骨髓抑制等不良反应~([3])。腺苷蛋氨酸能促进胆汁的排泄,抗氧化及解毒作用,减轻肝内胆汁淤     

人巨细胞病毒致肝炎综合征婴儿治疗前后外周血miR-NA水平变化及意义

目的探讨人巨细胞病毒致肝炎综合征婴儿治疗前后外周血miRNA水平变化及意义。方法选取桂林市妇幼保健院新生儿科2013年12月-2014年12月收治的人巨细胞病毒致肝炎综合征婴儿30例设为观察组,并选择30名健康婴儿设为对照组。结果治疗前,观察组的各项miRNA表达水平均显著高于对照组,差异有统计学意义(P0.05);治疗后,观察组中更昔洛韦敏感组的hsa-miR-433与更昔洛韦不敏感组比较,差异无统计学意义(P0.05),但hsa-miR-92、hsa-miR-96、hsa-miR-183差异均有统计学意义(P0.05);观察组中更昔洛韦不敏感组的hsa-miR-433、hsa-miR-96较治疗前均显著下降(P0.05);hsa-miR-92、hsa-miR-183较治疗前差异均无统计学意义(P0.05)。而更昔洛韦敏感组的hsa-miR-183较治疗前显著上升,hsa-miR-433较治疗前显著下降(P0.05);hsa-miR-92、hsa-miR-96较治疗前差异无统计学意义(P0.05)。结论人巨细胞病毒致肝炎综合征婴儿治疗前后外周血miRNA水平出现变化,miRNA对肝炎综合征婴儿的临床治疗具有一定的指导意义。     

更昔洛韦联合双歧杆菌三联活菌治疗小儿巨细胞病毒感染性肝炎的有效性和安全性分析

目的更昔洛韦联合双歧杆菌三联活菌治疗小儿巨细胞病毒感染性肝炎的有效性和安全性。方法选取2014年12月—2017年12月在我院诊治的巨细胞病毒感染性肝炎患儿98例,根据患儿入院先后顺序分为两组,对照组给予更昔洛韦进行治疗,观察组在对照组的基础上联合双歧杆菌三联活菌进行治疗。比较两组患儿的临床治疗效果、肝功能相关指标及其恢复至正常时间、CMV-DNA和CMV-IgM的转阴率及不良反应发生率。结果观察组的临床总有效率为89.58%,对照组为72.00%,观察组显著高于对照组(P0.05);治疗前两组肝功能相关指标丙氨酸氨基转移酶(ALT)、血清总胆红素(TBil)和胆汁酸(TBA)相比无统计学差异(P0.05),治疗后两组的ALT、TBil和TBA水平均显著下降,观察著显著低于对照组(P0.05),但在正常范围内;观察组患儿肝功能相关指标恢复正常时间均显著短于对照组(P0.05);观察组患儿的CMV-DNA和CMV-IgM的转阴率显著高于对照组(P0.05),两组不良反应发生率相比无统计学差异(P0.05)。结论采用更昔洛韦联合双歧杆菌三联活菌治疗小儿巨细胞病毒感染性肝炎临床效果更好,肝功能相关指标恢复快,CMV-DNA和CMV-IgM转阴率高,且不增加患儿的不良反应发生率,值得临床借鉴。     

短程间歇更昔洛韦治疗婴儿巨细胞病毒肝炎临床疗效观察

目的 观察短期更昔洛韦间歇治疗婴儿巨细胞病毒(CMV)肝炎的临床疗效.方法 回顾性分析短程、间歇更昔洛韦治疗婴儿CMV肝炎的疗效,观察治疗组85例和对照组37例治疗前、后肝功能(TBil、直接胆红素、ALT、AST、γ-GT)的变化和治疗过程中更昔洛韦的不良反应.计量资料采用方差分析,计数资料采用卡方检验.结果 短程更昔洛韦治疗后,治疗组TBil从(109.1±77.8)μmol/L降至(62.9±68.1)μmol/L(F=15.34,P<0.01),ALT从(160.2±395.3)U/L降至(68.1±56.0)U/L(F=4.73,P<0.05);对照组TBil从(94.9±47.4)μmol/L降至(49.2±31.5)μmol/L(F=14.80,P<0.01),但ALT从(131.6±206.2)U/L降至(55.3±31.2)U/L(F=3.50,P=0.067).治疗组再次入院率为10.6%,明显低于对照组的21.6%.仅1例(0.8%)患儿间歇更昔洛韦治疗3次,最长住院日6周.结论 短程、间歇更昔洛韦可能更适用于治疗婴儿CMV肝炎,未见明显药物不良反应,可减少住院日.     

中药直肠滴入联合西药对婴儿肝炎综合征患儿血生化指标的影响

目的:观察肝炎综合征经验方汤剂直肠滴入联合西药治疗淤胆型婴儿肝炎综合征的临床疗效及对患儿相关指标的影响.方法:经诊治淤胆型婴儿肝炎综合征患者83例,采用随机数字表法分为治疗组42例和对照组41例,对照组患者给予西医常规治疗方案,治疗组在对照组基础上给予中药直肠滴入,每个疗程2 wk,2组均进行3个疗程,观察临床疗效、血生化指标包括血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、血清总胆汁酸(total bile acids,TBA)、碱性磷酸酶(alkaline phosphatase,ALP)、总胆红素(total bilirubin,TBIL)、直接胆红素(direct bilirubin,DBIL)、谷氨酰转肽酶(gammaglutamyl transpeptidase,GGT)及CMV-Ig M转阴率,肝脏大小等情况.结果:治疗组CMV-Ig M转阴率、总有效率明显高于对照组(P0.05).两组ALT、TBA、ALP、TBIL、DBIL及GGT均较治疗前明显降低(P0.05),且治疗组较对照组下降水平更为显著,具有显著性差异(P0.05).两组肝脏较治疗前明显缩小(P0.05),治疗后组间比较具有统计学意义(P0.05).治疗组黄疸消退时间明显短于对照组,具有显著性差异(P0.05).结论:肝炎综合征经验方汤剂直肠滴入联合西药常规治疗降低婴儿肝炎综合征淤胆型患者的ALT、TBA、ALP、TBIL、DBIL及GGT水平,提高巨细胞病毒感染抗-CMVAg M阴转率.     

病毒性肝炎——总论

老年肝病患52例并发败血症及感染性休克的临床分析，板茵汤治疗肝炎60例，更昔洛韦治疗婴儿巨细胞病毒性肝炎疗效观察，肝炎病毒诱导的抗β1肾上腺素能受体抗体致钙电流和胞内钙增加的研究，茵栀黄注射液联合丙谷胺治疗肝细胞性黄疸疗效观察，肝病患血清酸性α-醋酸萘酯酶及其同工酶的变化，更昔洛韦治疗新生儿巨细胞病毒肝炎的疗效评价。     

更昔洛韦治疗巨细胞病毒性肝炎12例观察

婴儿巨细胞病毒(Cytomegatovirus，CMV)性肝炎，为新生儿CMV性肝炎的延续，亦可为生后获得性感染所致，起病缓慢而隐匿。临床上以阻塞性黄疸，肝脾肿大，肝功能受损为特征。近2年来我们应用更昔洛韦治疗CMV性肝炎12例，疗效满意。现报告如下。     

病毒性肝炎：总论

可溶性CD40在肝病患者血清中的表达及其临床意义，儿童病毒性肝炎87例临床分析，更昔洛韦治疗婴儿巨细胞病毒性肝炎30例，134例自身免疫性肝病患者自身抗体的分析，自身免疫性肝炎临床、免疫学及病理学特征分析142例。     

病毒性肝炎——总论

不同类型肝炎患血清HA HPCⅢ LN IV-C水平的比较；血清前白蛋白、胆碱酯酶与肝组织病理损害的相关性研究；肝病患 110例血清甲状腺相关物质的检测及临床意义；病毒性肝炎合并晚期妊娠的观察及护理；更昔洛韦治疗婴儿巨细胞病毒性肝炎临床观察。     

更昔洛韦联合茵栀黄治疗婴儿巨细胞病毒性肝炎初步研究

目的探讨更昔洛韦联合茵栀黄口服液治疗婴儿巨细胞病毒性肝炎的临床效果。方法2015年1月~2016年12月我院门诊和病房收治的的巨细胞病毒性肝炎患儿76例,采用随机数字表法将其随机分为对照组38例和观察组38例。给予对照组患儿更昔洛韦静脉滴注,观察组患儿在对照组治疗的基础上给予茵栀黄口服液口服。采用ELISA法检测血清TNF-α和IFN-γ,采用荧光定量PCR法检测血清CMV DNA载量。结果在治疗2 w末,观察组患儿血清ALT、AST、TBIL、TBA水平分别为（24.1±9.1）U/L、（24.6±10.3）U/L、（3.7±1.4）μmol/L、（24.3±8.6）μmol/L,均显著低于对照组的（58.3±18.6）U/L、（58.3±26.9）U/L、（28.6±13.7）μmol/L、（38.5±15.4）μmol/L（P<0.05）;血清TNF-α水平为（30.4±7.1）pg/ml,显著低于对照组的（35.3±7.5）pg/ml（P<0.05）;观察组和对照组患儿血清IFN-γ水平分别为（40.7±8.3）pg/ml和（39.3±7.9）pg/ml,差异无统计学意义（P>0.05）;观察组患儿血清CMV DNA转阴率为100.0%,对照组为97.4%,两组差异无统计学意义（P>0.05）。结论更昔洛韦联合茵栀黄口服液治疗婴儿巨细胞病毒性肝炎,在保护肝功能、降黄、利胆、病毒转阴和调节机体免疫功能方面效果显著。     

Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation

The present study compared foscarnet with ganciclovir for preemptive therapy of cytomegalovirus (CMV) infection after allogeneic blood or marrow stem cell transplantation (SCT). Patients with CMV infection, as detected by weekly antigenemia or polymerase chain reaction (PCR) in blood leukocytes, were randomized to intravenous therapy for 2 weeks with either foscarnet at 60 mg/kg or ganciclovir at 5 mg/kg administered every 12 hours; if CMV infection remained detectable, patients received an additional 2 weeks of intravenous foscarnet at 90 mg/kg or ganciclovir at 6 mg/kg given once daily for 5 days per week, after which therapy was stopped. Primary efficacy endpoint was the occurrence of CMV disease or death from any cause within 180 days after SCT. A total of 213 patients were treated with either foscarnet (n = 110) or ganciclovir (n = 103). Kaplan-Meier estimates of event-free survival within 180 days after SCT were similar in the 2 treatment groups (P =.6). During study treatment, severe neutropenia (< 0.5 x 10(9)/L) occurred in 11 (11%) patients on ganciclovir versus 4 (4%) patients on foscarnet (P =.04), and impaired renal function was observed in 5 (5%) patients on foscarnet versus 2 (2%) patients on ganciclovir (P =.4). Neutropenia or thrombocytopenia required discontinuation of ganciclovir in 6 (6%) patients but in no foscarnet-treated patient (P =.03). After allogeneic SCT, preemptive therapy of CMV infection with foscarnet shows similar efficacy as with ganciclovir, but is associated with a lower proportion of patients who develop severe neutropenia and who require discontinuation of antiviral therapy due to hematotoxicity.     

更昔洛韦联合思密达治疗轮状病毒肠炎56例效果分析

将收治的轮状病毒肠炎婴幼儿120例随机分为2组,对照组64例,使用更昔洛韦5～10mg/(kg·d)静脉滴注;观察组56例,更昔洛韦5～10 mg/(kg·d)静脉滴注,同时口服思密达,每次1/3包,3次/d。治疗后,对照组和观察组总有效率分别为62.50%(40/64)和89.29%(50/56),差异有统计学意义(P<0.05)。表明更昔洛韦联合思密达治疗婴幼儿轮状病毒肠炎疗效显著,值得推广。     

Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients

The efficacy and safety of oral valganciclovir was compared to ganciclovir i.v. in pre-emptive treatment of cytomegalovirus (CMV) in T-cell-depleted allogeneic stem cell transplant (allo-SCT) recipients. A therapeutic guideline was developed to allow the safe application of valganciclovir in allo-SCT recipients requiring CMV therapy. In total, 107 consecutive transplant recipients were evaluated. Cytomegalovirus DNA load in plasma was monitored longitudinally; details on antiviral therapy and treatment responses were analyzed retrospectively. Fifty-seven CMV treatment episodes were recorded in 34 patients: 20 with valganciclovir (900 mg twice-daily) and 37 with ganciclovir (5 mg/kg twice-daily). Median CMV DNA load reduction was 0.079 and 0.069 log10 copies/ml/day in the ganciclovir and valganciclovir group, respectively. Good response on CMV DNA load (reduction below 3.0 log10 copies/ml) was observed in 75.7% of ganciclovir and 80.0% of valganciclovir treatment episodes. Severe adverse effects were not observed and CMV-related disease did not occur. However, the percentage of patients receiving erythrocyte transfusion was higher in the group of patients receiving ganciclovir as compared to valganciclovir (41 versus 20%, P=0.116). In conclusion, pre-emptive treatment with valganciclovir and ganciclovir, led to similar reduction of CMV DNA load. Oral valganciclovir is an attractive and safe alternative for pre-emptive CMV treatment in T-cell-depleted allo-SCT recipients.     

Randomized clinical trial of ganciclovir vs acyclovir for prevention of cytomegalovirus antigenemia after allogeneic transplantation

Cytomegalovirus (CMV) disease remains a major cause of morbidity following allogeneic stem cell transplantation (SCT). In a prospective randomized trial, we tested prophylactic therapy with ganciclovir or acyclovir for patients at high risk of disease. Ninety-one CMV seropositive recipients of related (n = 53) and unrelated (n = 38) donor transplants were enrolled. All patients received intravenous (i.v.) ganciclovir 5 mg/kg every 12 h days -7 to -2, followed by acyclovir 10 mg/kg i.v. every 8 h from day -1 until neutrophil engraftment. Patients were then randomly assigned to either ganciclovir (n = 45) or acyclovir (n = 46) until day 100 post transplant. Any degree of antigenemia was treated with ganciclovir 5 mg/kg i.v. twice a day for 2 weeks, followed by 5 mg/kg i.v. each weekday for 6 weeks. At day 100, the cumulative incidence of antigenemia was 31% (95% CI 17-45%) for ganciclovir and 41% (95% CI 26-56%) (P = 0.22) for acyclovir prophylaxis, respectively. The assigned prophylaxis cohort did not predict for CMV antigenemia. The cumulative incidence of CMV disease at 12 months was 13% (95% CI 3-23%) and 17% (95% CI 6-28%) (P = 0.59) for the ganciclovir- and acyclovir-treated groups, respectively. An absolute neutrophil count (ANC) 相似文献   

Perinatal Cytomegalovirus Hepatitis in Saudi Infants: A Case Series

Background/Aim:

Cytomegalovirus (CMV) is the most common congenital viral infection, occurring in 0.4%–2.3% of all live births. The clinical manifestations of CMV are multiorgan involvement. Currently, the numbers of studies of hepatic CMV infection in immunocompetent infants are insufficient and little information exists in the medical literature about the hepatic manifestations and complications of CMV.

Patients and Methods:

Nine infants diagnosed with hepatic CMV infection were included in the study. The diagnosis was based on the presence of IgM anti-CMV antibodies titer in serum and detection of CMV-DNA in blood. The authors identified clinical characteristics, biochemical characteristics, immunologic markers, and the outcome of hepatic CMV with or without treatment.

Results:

Jaundice was the most common clinical feature of CMV infection in infancy (100%). Hepatic abnormalities in the form of cholestasis (defined as a serum conjugated bilirubin concentration greater than 17.1 μmol/L or greater than 20% of the total serum bilirubin) were found in all patients (100%), hepatitis (77%), hypoalbuminemia (55%), elevated alkaline phosphatase, and gamma-glutamyltransferase (77%). Other findings showed hepatosplenomegaly (44%), thrombocytopenia (22%) and low birth weight (11%) The treatment of hepatic CMV infection was indicated in 66% and was not indicated in 33%. Both of them had resolved cholestasis and hepatitis.

Conclusion:

Jaundice and cholestasis were the most common clinical features of hepatic CMV infections. Hepatic CMV infection in young infants is often a self-limited illness that does not require antiviral therapy. Most of the patients with hepatic CMV infection had a favorable outcome.     

Prevention of primary cytomegalovirus disease in organ transplant recipients with oral ganciclovir or oral acyclovir prophylaxis

Background: Optimal prophylaxis against cytomegalovirus (CMV) disease for organ transplant patients at risk for primary infection (donor seropositive, recipient seronegative, D+R?) remains to be determined. We hypothesized that prolonged oral ganciclovir therapy following intravenous therapy would provide increased protection. Methods: A total of 155 evaluable D+R? organ transplant recipients from 13 transplant centers were entered into the study: all received intravenous ganciclovir (5 mg/kg/day) for 5–10 days and then either oral acyclovir (400 mg tid) or oral ganciclovir (1 g tid) for an additional 12 weeks. Patients were assigned to their treatment groups at a central randomization site, with a separate randomization scheme for each of the organs transplanted (kidney, heart, or liver). In the case of kidney transplants, the patients were stratified according to source of the kidney (living related vs. cadaveric donor). The primary endpoint was the incidence of CMV disease in the first six months post‐transplant. Results: Treatment with oral ganciclovir was associated with a significant decrease in the incidence of symptomatic disease or viremia when compared with the oral acyclovir group (32% vs. 50%, P<0.05). This difference was most marked in terms of tissue invasive disease: only 3 of 15 symptomatic patients in the ganciclovir group vs. 10 of 21 in the acyclovir group developed tissue‐invasive infection (P<0.05). There was a significant difference in the time to CMV disease or viremia in the two groups: mean time 212±17 days post‐transplant for the acyclovir group vs. 291±13 days for the ganciclovir group (P<0.001). The incidence of allograft rejection was 34% in the ganciclovir group and 46% in the acyclovir group (P=NS). Leukopenia was more common in the ganciclovir group (P<0.05), but in no case did it require drug discontinuation. Ganciclovir resistance did not develop in this study. Conclusion: Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease.     

Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection

PCR-based preemptive therapy with ganciclovir has been shown to reduce the incidence of CMV disease after BMT. Failures of this treatment strategy are CMV disease and secondary non-viral infections. Eighty-six consecutive patients at high risk for CMV disease who received PCR-based preemptive therapy with ganciclovir were assessed for treatment failures and possible risk factors. Ganciclovir was initiated in 57 of 86 patients (66%). Only 28 of 86 (32%) patients received 4 or more weeks of ganciclovir. Recurrence of CMV infection after successful treatment was more frequent among recipients of a BMT from an unrelated compared to a sibling donor (P = 0.004). Three (3.5%) patients developed non-fatal early onset CMV disease and seven of 68 (10.3 %) late onset CMV disease (>100 days post transplant). Risk factors for late onset CMV disease were cGVHD (P = 0.0017) and duration of prior antiviral therapy >4 weeks (P = 0. 0073). The incidence of secondary non-viral infections was 28% with the duration of antiviral treatment being a significant risk factor for secondary bacterial (P = 0.0045) and invasive fungal infections (P = 0.006). Thus, PCR-based preemptive treatment with ganciclovir reduces early onset CMV disease, but the duration of antiviral therapy prior to day +100 is a significant risk factor for late onset CMV disease as well as secondary non-viral infections.     

Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan

AIM： TO investigate active cytomegalovirus （CMV） infection following the cydosporine A （CyA） treatment of steroid-refractory ulcerative colitis （UC）. METHODS： Twenty-three patients with severe UC not responding to steroid therapy （male 14, and female 9） enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA （average 4 mg/kg per day） for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology （IgM antibody by ELISA）, quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin （HE）-stained colonic biopsies. CMV infection was indicated by positive results in any test. RESULTS： No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV （IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%）. There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection （83.3%） required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. CONCLUSION： Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immunosuppressive therapy.     

单倍体骨髓移植后巨细胞病毒感染的防治

目的:研究单倍型骨髓移植后,巨细胞病毒(CMV)感染的预防策略及发病情况。方法:98例单倍型骨髓移植患者,62例及1例CMVpp65阳性供者,接受更昔若韦预防治疗,受者5 mg／kg,2次／d,移植前-9 d～-2 d,31例移植后出现CMV抗原血症阳性患者,其中18／60例预防组,13／35例非预防组阳性病例,接受更昔若韦5 mg／kg,2次／d×2周,后改为5 mg／kg,1次／d,到CMVpp65转阴。移植后CMVpp65每周检测1次。结果:预防组18／60例移植后出现CMV抗原血症阳性,出现中位时间56(25～84)d。非预防组13／35例CMVpp65阳性,中位时间52(19～75)d,前者1例患者(1．6％)发展为CMV结肠炎,后者4例(11．4％),2例CMV肺炎,1例CMV结肠炎,1例CMV脑炎。结论:单倍型骨髓移植后,用CMVpp65检测CMV抗原血症是一种简便,可靠的方法。低剂量短疗程,静脉注射更昔若韦提前预防CMV病可能是一种有效的方法。