Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients

The impact of cytomegalovirus (CMV) infection post-transplantation is in part influenced by the degree of immunosuppression. While mycophenolate mofetil (MMF) does not increase the overall incidence of CMV infection, we have questioned whether or not it increases its severity. Using a case control study design in which 29 renal transplant patients developed CMV disease [17 (59%) of which received azathioprine (AZA) and 12 (41%) received MMF], increases in the frequency of organ involvement with CMV (58 vs. 18%; p = 0.03) and in the number of organs involved with CMV were noted in the MMF versus the AZA group (2.0 vs. 1.0; p = 0.015). These results indicate that the increased immunosuppressive activity of MMF impacts the morbidity of CMV infection, thus warranting the use of effective anti-CMV preventive regimens while patients are treated with MMF.     

Effect of individualized therapy for AIDS patients with cytomegalovirus retinitis in intravitreal ganciclovir injections

The effect of intravitreal ganciclovir injection combined with intravenous infusion on acquired immune deficiency syndrome (AIDS) patients with cytomegalovirus retinitis (CMVR) was investigated. A total of 32 eyes in 23 AIDS patients diagnosed as CMVR from 2017 to 2018 were included in the retrospective study. All patients underwent induction therapy by using intravenous drip of the anti-cytomegalovirus (CMV) agent ganciclovir (5 mg/kg q12h) combined with intravitreal ganciclovir injection (3 mg/time, 2 times/wk). The visual acuity, fundus photographs, lesion location, and number of intravitreal injections were observed preoperatively and postoperatively. Totally 14 eyes were cured during induction therapy. The number of injections [4.13 (2 to 6)] in CMVR patients with peripherally fundus lesions were significantly lower than those with central lesions [4.89 (2 to 6)]. The individualized therapy of intravitreal ganciclovir injections for AIDS patients with CMVR can effectively reduce the numbers of intravitreal injections.     

更昔洛韦与病毒唑治疗小儿水痘的疗效比较

目的:探讨更昔洛韦与病毒唑治疗小儿水痘的临床疗效。方法:将120例水痘患儿随机分为两组,更昔洛韦 组、病毒唑组各60例。更昔洛韦组给予更昔洛韦5mg/(kg·d)静滴,每日1次治疗;病毒唑组给予病毒唑10mg/ (kg·d)静滴,每日1次治疗。两组均计数退热时间及皮疹结痂时间,同时观察药物的毒副作用。结果:更昔洛韦 组平均退热时间为(2.61±0.47)d,明显少于病毒唑组(3.7±0.38)d(P<0.05);皮疹结痂时间,更昔洛韦组为 (3.24±0.27)d,明显少于病毒唑组(4.3±0.31)d(P<0.05)。两组药物治疗过程中无明显毒副作用。结论:更昔 洛韦治疗小儿水痘疗效显著,明显优于病毒唑。     

Patterns of cytomegalovirus infection in simultaneous kidney–pancreas transplant recipients receiving tacrolimus, mycophenolate mofetil, and prednisone with ganciclovir prophylaxis

Abstract: Background: The impact of tacrolimus (TAC), mycophenolate mofetil (MMF) and steroid immunosuppression on cytomegalovirus (CMV) infection in combination with ganciclovir prophylaxis in simultaneous kidney–pancreas transplantation (SKPT) has not been well studied. Methods: A retrospective analysis was made of 75 SKPTs performed between 1 January 1996 and 7 January 1999. All patients received ganciclovir for 3 months, but CMV donor (D)+/ recipient (R)? patients received ganciclovir for 6 months. Results: 16/74 (22%) were CMV D+/R?, 25 (33%) D+/R+, 16 (22%) D?/R+, and 17 (23%) D?/R? (1 patient with unknown donor serology was excluded). The mean time to CMV infection was 198 days post‐transplant. The incidence of either CMV infection or tissue invasive CMV disease was 16/74 (22%), including 9 (12%) with CMV infection and 7 (10%) CMV disease. The one‐year patient, kidney, and pancreas graft survival rates were 91%, 89%, and 83%, respectively. The mean follow‐up was 29 months (minimum of 12 months). CMV infection was not associated with an increased incidence of graft failure or mortality. The D+/R? group had the highest incidence of CMV infection (44%) compared with the other serologic groups (17%, P=0.02). Concurrent CMV and rejection occurred more frequently in the D+/R? than the other serologic groups (25% vs. 7%, P=0.03). The D?/R? group had the best outcomes, with no CMV infection, improved kidney graft survival at the end of follow‐up (82% vs. 72%, P=0.04) and the highest event‐free survival (no CMV infection, rejection, or graft loss) when compared to the other groups (76% vs. 33%, P<0.01). Conclusions: Compared to previous studies, ganciclovir prophylaxis delayed the onset and reduced the severity of CMV infection in patients receiving TAC, MMF, and steroids. Despite ganciclovir prophylaxis, CMV seronegative patients receiving CMV D+ organs had worse outcomes than seronegative recipients receiving CMV D? organs.     

Cytomegalovirus maculopapular eruption in a kidney transplant patient

Abstract: Cytomegalovirus (CMV) is the most important viral agent in kidney transplantation. Clinical manifestations of CMV disease in transplantation include hepatitis, pneumonitis, pancreatitis, kidney allograft dysfunction, colitis, and meningoencephalitis. However, skin involvement is rare. We describe a severely compromised cadaveric‐kidney transplant recipient who developed renal failure, colonic ulcers, and a maculopapular rash accompanied by fever and malaise 4 months after transplantation. Only the skin biopsy was diagnostic and consistent with CMV disease. Intravenous ganciclovir administration resulted in clinical improvement of CMV‐induced skin lesions; kidney function normalized and the patient became asymptomatic after 14 days of ganciclovir therapy. Nephrologists should consider the diagnosis of CMV disease in the febrile immunosuppressed patient with skin involvement. Skin biopsy must be considered as a useful and safe procedure in patients with a rash to obtain a prompt diagnosis and efficiently treat this immunocompromised population.     

Ganciclovir‐resistant post‐transplant cytomegalovirus infection due to combined deletion mutation at codons 595‐596 of the UL97 gene

The development of antiviral‐resistant cytomegalovirus (CMV) infection complicates the management of transplant recipients. We describe the case of a 65‐year‐old male who developed CMV disease on valganciclovir prophylaxis (donor CMV IgG positive, recipient CMV IgG indeterminate) 30 days after combined liver–kidney transplantation for alcoholic cirrhosis and hepato‐renal syndrome. After an initial complete response to treatment dose oral valganciclovir, he developed recurrent CMV viraemia. Resistance testing revealed a UL97 mutation with in‐frame deletions of codons 595‐596. He was treated successfully with foscarnet and reduction in immunosuppression. This mutation has not been described previously and was suspected to confer ganciclovir resistance. Ganciclovir resistance occurs most commonly due to mutations in the UL97 or UL54 genes, which encode a protein kinase and a DNA polymerase, respectively. The UL97‐encoded protein kinase phosphorylates ganciclovir to ganciclovir triphosphate, which competitively inhibits viral replication. Mutations in the UL97 gene are typically point mutations or deletions. We describe a new mutation, del595‐596 in the CMV UL97 gene, occurring in the context of clinical treatment failure with standard and double‐dose ganciclovir, and successful virological control achieved with foscarnet. This mutation is likely to result in ganciclovir resistance, although recombinant phenotyping is required for confirmation.     

Prevention dof recurrent cytomegalovirus disease in renal and liver transplant recipients: effect of oral ganciclovir

Background: Although the primary treatment of symptomatic cytomegalovirus (CMV) disease in organ transplant recipients is successful in >90% of individuals, relapsing disease, particularly in those with primary infection, remains an important problem. Previously, we had observed that the rate of symptomatic recurrence was >60% in those with primary disease (seronegative for CMV prior to transplant), and approximately 20% in those who were seropositive prior to transplant. The present study was undertaken to determine whether a maintenance regimen of oral ganciclovir for 2–3 months added to the routine 14–21 days of intravenous ganciclovir would further prevent symptomatic CMV recurrence. Methods: From May 1995 until June 1998, all kidney and liver transplant recipients with confirmed tissue‐invasive CMV disease or CMV syndrome were treated with 14–21 days of intravenous ganciclovir (5 mg/kg b.i.d. with dose adjusted for renal dysfunction) followed by 2–3 months of oral ganciclovir (2 g daily). The incidence of recurrence of CMV disease and/or viremia during and after oral therapy was then determined over a mean follow‐up of 530.6 days. Results: Thirty‐seven patients, 19 kidney and 18 liver transplant recipients, were studied; 5 had biopsy‐proven tissue‐invasive disease (13.5) and 32 suffered a CMV syndrome (86.5). Twenty‐one of these patients (58.6) were seronegative for CMV prior to transplant and received an allograft from a seropositive donor (D+/R?). Overall, 10 patients (27.0) developed CMV recurrence. Eight of 21 patients who were D+/R? for CMV (38.1) developed recurrence as opposed to 2 of 16 patients with other serologic status (12.5) (P=0.14). Patients with recurrent CMV disease and/or viremia had a peak antigenemia assay titer during their initial CMV event of 319.2 positive cells/2 slides compared with 109.8 positive cells/2 slides for patients without recurrent CMV infection (P=0.14); the trend of having a higher peak antigenemia assay titer among patients who recurred occurred both in patients who were at risk of primary CMV infection (D+/R? for CMV) and in those who were not. Two patients developed recurrent infection with strains of CMV that were resistant to ganciclovir. Conclusions: This new therapeutic regimen of oral ganciclovir following intravenous ganciclovir slightly reduced the overall rate of recurrent CMV disease and/or viremia, but it still did not adequately prevent CMV recurrence in patients who are at risk of primary infection prior to transplant. Of particular concern, 2 patients with primary infection treated with this regimen developed ganciclovir‐resistant recurrent disease ( Note Presented in part at the American Society of Transplant Physicians Meeting, May 1999, Chicago, Illinois.
).     

Valganciclovir is an effective prophylaxis for cytomegalovirus disease in liver transplant recipients

Objectives:

Cytomegalovirus (CMV) infection is responsible for significant morbidity and mortality among solid organ transplant recipients. Prophylaxis using valganciclovir (VGCV) in orthotopic liver transplant (OLT) recipients is not approved by the Food and Drug Administration and its use is controversial. This study aimed to evaluate the effectiveness of VGCV in CMV prophylaxis in OLT recipients.

Methods:

We carried out a retrospective, single-centre study including all OLT procedures performed during 2005–2008. Patients with early death (at ≤30 days), without CMV serology or prophylaxis, or with follow-up of <1 year were excluded.

Results:

The overall incidence of CMV disease was 6% (n = 9). The ganciclovir (GCV) and VGCV groups had similar incidences of CMV disease (4.6% vs. 7.0%; P = 0.4) and similar distributions of disease presentation (CMV syndrome vs. tissue-invasive CMV; P = 0.4). Incidences of CMV infection, as well as disease presentation, were similar between the high-risk (CMV D+/R−) and non-high-risk groups (P = 0.16). Although acute cellular rejection occurred more frequently in patients who developed CMV disease (P = 0.005), overall survival in these patients did not differ from that in patients who did not develop CMV infection (P = 0.5).

Conclusions:

Valganciclovir is an effective antiviral for the prevention of CMV disease in liver transplant recipients. Our data support its use in high-risk OLT patients.     

更昔洛韦与阿昔洛韦治疗水痘临床疗效的对比研究

目的对比分析更昔洛韦与阿昔洛韦治疗水痘的临床疗效与安全性。方法选取2017年6月—2018年6月我院收治的110例水痘患者作为研究对象,按照随机数字表法分为阿昔洛韦组(阿昔组)与更昔洛韦组(更昔组),各55例。对比分析2组患者临床疗效,临床症状改善时间,不良反应发生情况及用药安全性等。结果治疗7d后,更昔组总有效率为96.36%,明显高于阿昔组的78.18%,差异有统计学意义(P<0.05);更昔组水痘-带状疱疹病毒转阴时间为(1.58±1.01)d,短于阿昔组的(2.92±1.06)d。此外,更昔组水疱结痂时间、退热时间、疼痛与瘙痒缓解时间也均短于阿昔组,差异均有统计学意义(P均<0.05);更昔组不良反应发生率为3.64%,低于阿昔组14.55%的不良反应发生率,差异有统计学意义(P<0.05)。结论在临床基础资料均衡的情况下,与阿昔洛韦相比,更昔洛韦治疗水痘临床总有效率更高,患者水疱结痂时间及临床症状改善时间均更短且治疗安全性更高,不良反应发生率低,具有临床推广价值。     

Interferon treatment with or without oral ganciclovir in HBeAg-negative chronic hepatitis B: a randomized study

The treatment of HBeAg-negative chronic hepatitis B with alpha interferon alone is unsatisfactory. We evaluated the efficacy of combined administration of interferon-a2a (IFN) with oral ganciclovir, a nucleoside analogue. Forty patients with hepatitis B virus (HBV)-DNA-positive/HBeAg-negative chronic hepatitis B, were randomized to receive 4.5 MU IFN thrice weekly, subcutaneously, alone or in combination with 3 g ganciclovir per os daily for 26 weeks and followed for 12 months after treatment. Mean serum HBV-DNA levels decreased by 4.0 log10 in the combination group (from 5 x 106 to 4.8 x 102 copies/ml) and by 2.2 log10 in the interferon group (from 8 x 106 to 4.8 x 104 copies/ml) by quantitative polymerase chain reaction (PCR). HBV-DNA became undetectable in 11 of 20 (55%) and in three of 20 (15%) patients in the two groups, respectively (P=0.02). The alanine aminotransferase levels became normal in all patients receiving combination therapy, compared to 75% of those in the interferon group. After cessation of therapy, HBV-DNA increased or reappeared in all patients with 85% also relapsing biochemically. One year after treatment, three patients in each group (15%) remained in sustained biochemical remission with very low serum HBV-DNA levels (median 15 700 copies/ml). We conclude that, in HBeAg-negative chronic hepatitis B, 6-month combination therapy with oral ganciclovir and IFN is associated with complete biochemical remission in all treated patients and a 4 log10 decrease in serum HBV-DNA levels. The end of treatment efficacy of this combination scheme is far super- ior to that of IFN monotherapy but sustained responses are few. Further studies are warranted to evaluate the efficacy of prolonged combination schemes with nucleoside analogues and IFN, compared to IFN monotherapy.