Intra-host diversity of drug-resistant cytomegalovirus: A case report of cytomegalovirus infection after allogeneic hematopoietic cell transplantation.

Cytomegalovirus (CMV) is a major infectious agent causing severe complications in allogeneic hematopoietic cell transplantation (HCT) recipients, thereby warranting the need for aggressive preemptive or targeted antiviral therapy. However, prolonged or repeated use of antiviral agents, such as ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), can result in drug-resistant CMV infection, posing challenges to successful outcomes. Here, we report a case of a patient with acute myeloid leukemia and drug-resistant CMV infection who presented with persistent CMV DNAemia, colitis, pneumonia, and encephalitis. An intra-host diversity of UL97 and UL54 mutations were detected through the genotypic resistance testing conducted on two blood samples (D+199 and D+224) and a cerebrospinal fluid (CSF) specimen (D+260) collected from the patient. UL97 L595W/L595F and L595W mutations were detected in the blood and CSF samples, respectively, that conferred GCV resistance. UL54 F412L mutation detected in all three samples conferred GCV/CDV resistance. However, the V787L mutation of UL54, conferring GCV/FOS resistance, was observed only in the D+224 blood sample. Despite combination therapy with FOS and high dose GCV and adjunctive therapy with leflunomide, the patient died from CMV infection and multiple organ failure on D+279. Further data on resistant mutations and intra-host diversity of CMV should be accumulated to elucidate the antiviral resistance and related outcomes.

Activity of curcumin against human cytomegalovirus infection in vitro / 生物医学工程学杂志

This study aimed to investigate the effect of curcumin (Cur) against human cytomegalovirus (HCMV) in vitro. Human embryonic lung fibroblasts were cultured in vitro. The tetrazolium salt (MTS) method was used to detect the effects of Cur on cell viability. The cells were divided into control group, HCMV group, HCMV + (PFA) group and HCMV + Cur group in this study. The cytopathic effect (CPE) of each group was observed by plaque test, then the copy number of HCMV DNA in each group was detected by quantitative polymerase chain reaction (qPCR), and the expression of HCMV proteins in different sequence was detected by Western blot. The results showed that when the concentration of Cur was not higher than 15 μmol/L, there was no significant change in cell growth and viability in the Cur group compared with the control group (P>0.05). After the cells were infected by HCMV for 5 d, the cells began to show CPE, and the number of plaques increased with time. Pretreatment with Cur significantly reduced CPE in a dose-dependent manner. After the cells were infected by HCMV, the DNA copy number and protein expression gradually increased in a time-dependent manner. Pretreatment with Cur significantly inhibited HCMV DNA copies and downregulate HCMV protein expression levels in a concentration-dependent manner, and the difference was statistically significant (P<0.05). In conclusion, Cur may exert anti-HCMV activity by inhibiting the replication of HCMV DNA and down-regulating the expression levels of different sequence proteins of HCMV. This study provides a new experimental basis for the development of anti-HCMV infectious drugs.

Multiple thrombosis associated with Cytomegalovirus enterocolitis in an immunocompetent patient: a case report.

BACKGROUND: Cytomegalovirus (CMV) is reported to have thrombogenic characteristics that activate factor X in vitro and stimulate the production of factor VIII and von Willebrand factor (vWF). Thrombosis associated with CMV infection is prevalent among immunocompromised patients and predominantly presents as a solitary large thrombus in the deep vein, pulmonary artery, splanchnic arteriovenous ducts, or other similar sites. Multiple thrombi, however, are rarely observed in such cases. Here, we report about an immunocompetent man with multiple microthrombi associated with CMV infection. CASE PRESENTATION: A 72-year-old Japanese man who complained of abdominal pain was hospitalized with multiple colonic stenosis. He was later diagnosed with CMV enterocolitis and treated with ganciclover from Day 27 post-admission. During hospitalization, the patient developed thrombi in his fingers. He was initially treated with anticoagulant therapy (rivaroxaban); however, the therapy was discontinued owing to a prolonged activated thromboplastin time and an elevated international normalized ratio of prothrombin time. Instead, vitamin K and fresh-frozen plasma were administered. Nevertheless, his coagulation profile remained abnormal. Eventually, he developed colonic perforation and had to undergo emergency surgery. An intraoperative specimen showed several microthrombi in the middle and small arteriovenous ducts of his small and large intestines. The patient's coagulopathy improved preoperatively, and his overall condition improved postoperatively. Since the activation of ADAMTS13 was reduced remarkably, the thrombotic tendency was determined to be a thrombotic microangiopathy-like condition owing to increased vWF. We could not attribute the coagulopathy to any other cause except CMV infection; therefore, we concluded that this was a case of multiple thrombosis associated with CMV. CONCLUSIONS: We present an extremely rare case of a patient with multiple thrombotic microangiopathy-like microthrombosis caused by CMV infection. Our findings suggest that CMV infection may be considered as a differential diagnosis for immunocompetent individuals who present with thrombosis of unspecified cause.

Clinical significance of post-treatment viral load of cytomegalovirus in patients with hematologic malignancies.

OBJECTIVES: Patients with hematologic diseases were at high risk for cytomegalovirus (CMV) diseases. In the present study, we compare various prognostic factors during CMV viremia, with specific emphasis on the relationship between viremia eradication and the long-term prognosis of patients after each episode. METHODS: Adult patients with hematologic diseases who had a detectable CMV viral load (VL) (equal to or above 150 copies/mL) were included in the study. Medical records were reviewed for demographic data including age, sex, hematologic and other underlying diseases, status of stem cell transplantation, antiviral medication, serum CMV viral load before and after antiviral treatment. RESULTS: A total of 101 episodes of CMV viremia occurred in patients with hematologic diseases. Comparison of various prognostic factors revealed non-survivors more frequently suffered from pneumonia and concomitant bacterial or fungal infections, had less frequently undergone hematopoietic stem cell transplantation (HSCT), and had higher peak VLs during viremic episodes. After antiviral therapy, eradication of viremia was much less frequently achieved in non-survivors. The Kaplan-Meier curves revealed that patients with detectable end-treatment VL had lower survival rates even if the antivirals were administered for more than 21 days. In a multivariate Cox proportional-hazard model, a detectable VL at the end of antiviral therapy independently predicted mortality within 180 days. CONCLUSIONS: In patients with hematologic diseases suffering CMV viremia, failure to eradicate viremia after antiviral therapy indicates a higher chance of mortality and can be regarded as a useful indicator in evaluating the patient's long-term prognosis.

Recommended foscarnet dose is not associated with improved outcomes in cytomegalovirus salvage therapy.

BACKGROUND: Cytomegalovirus (CMV) infection causes significant morbidity and mortality in transplant recipients. Ganciclovir and valganciclovir have proven efficacy but are limited by resistance and toxicity, whereas foscarnet typically retains activity when CMV has become resistant to other antivirals. Foscarnet dosing used in practice may be discordant with what is recommended in product labeling, as the result of an unconventional dosing nomogram or prescriber preference; however, it is unknown how discordant foscarnet dosing affects outcomes. OBJECTIVE: Our purpose was to characterize the relationship between initial foscarnet dosing intensity (relative to product labeling) and key effectiveness and safety endpoints. STUDY DESIGN: This single-center, retrospective study included immunosuppressed adults with CMV viremia who received foscarnet between January 2012-July 2017. Subjects were divided into low dose (LD) and non-low dose (NLD) groups, according to foscarnet dose intensity. The primary endpoint was time-to-CMV eradication. Secondary endpoints included time-to-CMV clearance, acute kidney injury, hematologic toxicity, and mortality. RESULTS: Of 87 subjects, 38 met inclusion. Primary immunosuppression reasons were solid organ (63%) or hematopoietic cell transplant (29%). Seventeen and 21 subjects were in the LD and NLD groups, respectively. Median time-to-CMV eradication was 17 days (LD group) versus 13 days (NLD group), p = 0.823. Median time-to-CMV clearance was also non-significant (p = 0.505). There was no association between initial foscarnet dosing intensity and acute kidney injury, hematologic toxicity, or mortality (24% in both groups). CONCLUSIONS: These findings suggest outcomes may be sensitive to other factors and underscore the need for further studies to improve understanding of foscarnet dosing in immunosuppressed patients.

Inhibition of Cytomegalovirus Replication with Extended-Half-Life Synthetic Ozonides.

Artesunate (AS), a semisynthetic artemisinin approved for malaria therapy, inhibits human cytomegalovirus (HCMV) replication in vitro, but therapeutic success in humans has been variable. We hypothesized that the short in vivo half-life of AS may contribute to the different treatment outcomes. We tested novel synthetic ozonides with longer half-lives against HCMV in vitro and mouse cytomegalovirus (MCMV) in vivo Screening of the activities of four ozonides against a pp28-luciferase-expressing HCMV Towne recombinant identified OZ418 to have the best selectivity; its effective concentration inhibiting viral growth by 50% (EC50) was 9.8 ± 0.2 µM, and cytotoxicity in noninfected human fibroblasts (the concentration inhibiting cell growth by 50% [CC50]) was 128.1 ± 8.0 µM. In plaque reduction assays, OZ418 inhibited HCMV TB40 in a concentration-dependent manner as well as a ganciclovir (GCV)-resistant HCMV isolate. The combination of OZ418 and GCV was synergistic in HCMV inhibition in vitro Virus inhibition by OZ418 occurred at an early stage and was dependent on the cell density at the time of infection. OZ418 treatment reversed HCMV-mediated cell cycle progression and correlated with the reduction of HCMV-induced expression of pRb, E2F1, and cyclin-dependent kinases 1, 2, 4, and 6. In an MCMV model, once-daily oral administration of OZ418 had significantly improved efficacy against MCMV compared to that of twice-daily oral AS. A parallel pharmacokinetic study with a single oral dose of OZ418 or AS showed a prolonged plasma half-life and higher unbound concentrations of OZ418 than unbound concentrations of AS. In summary, ozonides are proposed to be potential therapeutics, alone or in combination with GCV, for HCMV infection in humans.

Cyclophilin A as a target in the treatment of cytomegalovirus infections.

BACKGROUND: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity. METHODS: Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins. RESULTS: Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug. CONCLUSION: Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.

In vitro toxicity and efficacy of verdinexor, an exportin 1 inhibitor, on opportunistic viruses affecting immunocompromised individuals.

Infection of immunocompromised individuals with normally benign opportunistic viruses is a major health burden globally. Infections with viruses such as Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), Kaposi's sarcoma virus (KSHV), adenoviruses (AdV), BK virus (BKPyV), John Cunningham virus (JCPyV), and human papillomavirus (HPV) are significant concerns for the immunocompromised, including when these viruses exist as a co-infection with human immunodeficiency virus (HIV). These viral infections are more complicated in patients with a weakened immune system, and often manifest as malignancies resulting in significant morbidity and mortality. Vaccination is not an attractive option for these immune compromised individuals due to defects in their adaptive immune response. Verdinexor is part of a novel class of small molecules known as SINE (Selective Inhibitor of Nuclear Export) compounds. These small molecules demonstrate specificity for the nuclear export protein XPO1, to which they bind and block function, resulting in sequestration of XPO1-dependent proteins in the nucleus of the cell. In antiviral screening, verdinexor demonstrated varying levels of efficacy against all of the aforementioned viruses including previously with HIV. Studies by other labs have discussed likely mechanisms of action for verdinexor (ie. XPO1-dependence) against each virus. GLP toxicology studies suggest that anti-viral activity can be achieved at a tolerable dose range, based on the safety profile of a previous phase 1 clinical trial of verdinexor in healthy human volunteers. Taken together, these results indicate verdinexor has the potential to be a broad spectrum antiviral for immunocompromised subjects for which vaccination is a poor option.

Resistant Cytomegalovirus Infection After Renal Transplantation: Literature Review.

BACKGROUND: Resistant cytomegalovirus (R-CMV) is an emerging problem in the renal transplantation population. The most frequent CMVs are high-resistance mutations (UL97 gene). METHODS: We describe our experience in management of R-CMV after renal transplant at our center (2012-2016). RESULTS: We encountered 3 cases of R-CMV infection after renal transplant (all primary infections). All 3 patients received induction therapy with corticosteroids, tacrolimus, and mycophenolate mofetil. The first patient (basiliximab induction, preemptive CMV) developed CMV replication on day +53, which responded poorly both to standard-dose valganciclovir (vGCV) and high-dose ganciclovir (GCV) (creatinine clearance [CrCl] >70 mL/min; vGCV 900 mg twice daily for 50 days and GCV 7.5 mg/kg twice daily for 8 days). Hematologic toxicity occurred. The R-CMV test was positive and foscarnet (FOS) was initiated (90 mg/kg twice daily for 21 days). The second patient presented CMV infection (day +30, thymoglobulin induction, CMV prophylaxis), which was not controlled with the high dose (CrCl 23 mL/min; GCV 3.5 mg/kg twice daily and vGCV 900 mg twice daily), resulting in severe neutropenia. R-CMV was detected and FOS initiated (FOS 50 mg/kg twice daily for 7 days and 50 mg/kg every 2 days for 13 days). The third patient's infection occurred on day +22 (basiliximab induction, preemptive CMV). Standard-dose vGCV was uneffective (CrCl >70 mL/min, vGCV 900 mg twice daily) and it did not respond to the high dose (GCV 7.5 mg/kg twice daily and vGCV 2700 mg/d). Moderate hematologic toxicity occurred. R-CMV was diagnosed and FOS treatment begun (FOS 70 mg/kg per day for 2 weeks). CONCLUSIONS: Resistant CMV infection may be severe due to viral infection and side effects of high-dose antiviral treatment. We presented 3 cases requiring the use of FOS in the absence of response or toxic effects from the usual treatment, with an optimal sustained response (temporary in case 2) and without serious side effects.

Síndrome extrapiramidal con corea generalizada como forma de presentación atípica de leucoencefalopatía multifocal progresiva / Extrapyramidal syndrome with generalized chorea as an atypical presentation of progressive multifocal leukoencephalopathy

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High-dose Valganciclovir Treatment for Resistant Cytomegalovirus Colitis due to UL97 and UL54 Mutations.

We report the first case of a ganciclovir-resistant cytomegalovirus (CMV) involving the gastrointestinal tract that was successfully treated with high-dose valganciclovir. A kidney transplant recipient developed drug-resistant CMV colitis which was initially treated with valganciclovir, but his CMV was found to have major resistance to ganciclovir and cidofovir due to UL97 and UL54 mutations. The patient was switched to intravenous foscarnet 40 mg/kg given every twelve hours. However, foscarnet had to be discontinued after 4 days of treatment due to acute kidney injury. Patient was restarted on valganciclovir at a higher target dose of 1800 mg twice a day based on the creatinine clearance. CMV became undetectable 2 weeks after valganciclovir treatment was completed. High-dose valganciclovir along with immune suppression reduction may be a treatment option for CMV colitis with ganciclovir resistance due to dual UL97 and UL54 gene mutations.

Enzyme-Linked Immunospot Assay as a Complementary Method to Assess and Monitor Cytomegalovirus Infection in Kidney Transplant Recipients on Pre-emptive Antiviral Therapy: A Single-Center Experience.

BACKGROUND: Cytomegalovirus (CMV) disease represents a major cause of post-transplantation morbidity and mortality. To estimate the risk of infection and monitor response to antiviral therapy, current guidelines suggest combination of viral load monitoring with direct assessment of CMV-specific immune response. We used enzyme-linked immunospot (ELISpot) for the evaluation of CMV-specific T-cell response in kidney transplant recipients with CMV viremia and investigated how information gained could help manage CMV infection. METHODS: Seventeen patients on pre-emptive antiviral therapy and CMV quantitative polymerase chain reaction (qPCR) ≥500 copies/mL (first episode after transplantation) were assessed using ELISpot and divided into Weak (9 patients with baseline ELISpot <25 spot-forming colonies [SFCs]/200,000 peripheral blood mononuclear cells [PBMCs]) and Strong Responders (8 patients with baseline ELISpot ≥25 SFCs/200,000 PBMCs). CMV-specific T-cell response, infection severity, viral load, and antiviral therapy were prospectively recorded and compared between groups at 1, 2, and 24 months of follow-up. RESULTS: Demographic and transplant characteristics of Weak and Strong Responders were similar. No episodes of CMV disease were observed. Weak Responders were more likely to experience CMV syndrome (56% vs 36.5%) and late virus reactivation (56% vs 25%) than Strong Responders. Weak Responders showed higher baseline median viral loads (19,700 vs 9265 copies/mL) and needed antiviral therapy for longer (179 vs 59.5 days). T-cell response showed 2 main patterns: early and delayed. CONCLUSIONS: ELISpot provides prognostic information about infection severity, risk of late reactivation, and response to therapy. Randomized trials, evaluating the need for antiviral therapy in kidney transplant recipients with asymptomatic infection and effective virus-specific T-cell immune response, are warranted.

Epidemiology and Outcome of Ganciclovir-Resistant Cytomegalovirus Infection After Solid Organ Transplantation: A Single Transplant Center Experience in Thailand.

BACKGROUND: Data on drug-resistant cytomegalovirus (CMV) infection in solid organ transplantation (SOT) are not often reported from resource-limited settings. We aimed to investigate the epidemiology and outcomes of this infection in SOT recipients at our institution. METHODS: This was a retrospective study conducted from January 2012 to May 2015. We included all SOT recipients who were suspected for drug-resistant CMV infection. Genotypic assay for UL97 gene mutation was analyzed by real-time polymerase chain reaction. Patients were reviewed for demographic data, clinical presentation, virologic data, treatment, and outcomes. RESULTS: The population consisted of 18 (12 kidney, 6 liver) SOT recipients with a median age of 20 years (interquartile range [IQR], 1-49); 44% were male. Anti-CMV resistance testing was analyzed at a median time of 23 days (IQR, 14-33) after initiation of anti-CMV therapy with a median CMV load of log 3.79 copies/mL (IQR, 3.37-4.58). During a median period of 2 years (IQR, 1-3), 6 SOT recipients were identified with UL97 gene mutation in codon 460, conferring ganciclovir (GCV) resistance. Patients with UL97 gene mutation had a longer mean duration of CMV DNAemia compared with those without mutation (263 vs 107 days; P = .04). All patients received high-dose GCV. Two patients received foscarnet and cidofovir. Two patients died (non-CMV-related), and 4 patients developed opportunistic infections other than CMV. CONCLUSIONS: GCV-resistant CMV infection in SOT recipients is an emerging clinical problem in resource-limited country. Those with UL97 mutation CMV infection have prolonged duration of CMV DNAemia. Clinicians should be aware of this condition when caring for SOT recipients.

Adjuvant and salvage therapy with leflunomide for recalcitrant cytomegalovirus infections in hematopoietic cell transplantation recipients: A case series.

Cytomegalovirus (CMV) reactivation is a clinically significant complication in hematopoietic stem cell transplant (HCT) recipients. Alternative therapy for multidrug-resistant CMV is limited and often fails. Leflunomide has been used to treat resistant CMV infections, however, data on efficacy, safety, and guidance for therapeutic drug level monitoring are lacking. In this report, we describe 3 HCT recipients with multi-drug resistant CMV infections who received leflunomide as adjuvant and salvage therapy. The therapeutic effect of leflunomide as an anti-CMV agent based on virologic responses and therapeutic drug monitoring were evaluated.

[Systemic cytomegalovirus infection: changes in serum calcium and magnesium levels with foscarnet treatment]. / Infección sistémica por citomegalovirus: influencia del tratamiento con foscarnet en los niveles plasmáticos de calcio y magnesio.

Cytomegalovirus infection is common in cardiac transplant patients. Foscarnet is used, with limited evidence, as second-line treatment after ganciclovir failure in these patients. We describe the case of a paediatric cardiac transplant patient who developed electrolyte disturbances during foscarnet treatment for cytomegalovirus infection. The infection resolved after 6 weeks of treatment. Low ionized calcium and magnesium levels were observed during the drug infusion, which were treated with supplements. The serum levels reverted to normal after drug withdrawal.

Protective effect of curcumin against cytomegalovirus infection in Balb/c mice.

Curcumin has been found to suppress the activity of human cytomegalovirus (HCMV) in vitro, whereas its protective effects against HCMV infection in vivo remain unclear. In this study, we aimed to investigate the protective effects of curcumin against HCMV infection in Balb/c mice. Mice were randomly divided into the control, model, model+ganciclovir (positive control), and model+high-dose, model+middle-dose, and model+low-dose curcumin groups. In the model groups, each mouse was given HCMV by tail injection intravenously. Positive control animals were given ganciclovir. Animals in the curcumin treatment groups were given different concentrations of curcumin. The anti-HCMV activities of ganciclovir and curcumin were assessed by serological examination and pathology. Ganciclovir and curcumin treatment reduced the HCMV IgM level and HCMV DNA load; decreased the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), and lactate dehydrogenase (LDH) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) generation in infected mice. These treatments also suppressed malondialdehyde (MDA) content and upregulated superoxide dismutase (SOD) and glutathione (GSH) levels. In addition, both treatments prevented pathological changes of the lung, kidney, liver, and heart tissues in infected mice. Our findings indicate that curcumin protected Balb/c mice against HCMV infection possibly by its anti-inflammatory and antioxidant effects.

[POSITIVE EFFECTS OF MODERN IMMUNOCORRECTION ACCORDING TO THE ANALYSIS OF CYTOKINES AND SLPI IN PATIENTS WITH PYELONEPHRITIS].

The peculiarities of cytokines as compounds of immunogenesis are shown in the patients having acute (A) and chronic (Ch) pyelonephritis (PN). The combination of antibacterial therapy with Nukleinat and Galavit promotes the positive changes of cytokin-producing ability of immunocompetent cells and decrease in the level of proinflammation cytokines in blood and urine, secretory leucocyte protease inhibitor (SLPI) in urine. In children with PN and adult patients with diagnostically elevated titres of antibodies (IgG) to Herpes simplex virus, Cytomegalovirus are shown the positive effects of Kanephron® H and Proteflazidum, accordingly. Clinico-immunological effects of immunomodulators testify to the expediency of this usage in complex therapy with the aim to modulate the cytokine link of immunity for improvement of the effective treatment in APN and the protection against aggravation of kidney functioning in ChPN.

Maribavir use in practice for cytomegalovirus infection in French transplantation centers.

Maribavir (MBV), a UL97 inhibitor, shows good oral bioavailability, low host cell toxicity, and theoretical benefits to inhibit cross-resistant viruses. We herein examined clinical and virological outcomes of 12 patients, including 3 bone marrow recipients and 9 organ recipients infected with resistant cytomegalovirus (CMV) and treated with MBV during 2011-2012. All received at least 800-mg daily doses. They had developed clinical (12/12) and/or virological (11/12) resistance to CMV infection. Based on a decrease of viral load in blood >1.5 log copies/mL half of them responded to MBV treatment. The individual changes varied from a rapid decrease in viral load (n = 4) to no response (n = 3) with some late response slowly decreasing viremia (n = 3). In 2 cases MBV was used as secondary prophylaxis. No clear parameter emerged as a clinical surrogate for nonresponse to MBV. These results contrast with the lack of efficacy in phase III trials of MBV prophylaxis among stem cell recipients, which were possibly due to low doses or inadequate timing of drug initiation in the study. Additional clinical and surrogate laboratory markers are needed to determine antiviral responses to guide MBV use. Dosage ranging studies might benefit future MBV use.

Clinical study on treatment of infantile cytomegalovirus hepatitis with integrated Chinese and Western medicine.

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) in treating infantile cytomegalovirus hepatitis (ICH). METHODS: A total of 100 infant ICH patients were randomly assigned to two groups, 60 in the treatment group and 40 in the control group. Ganciclovir was administered to all patients via intravenous dripping at dose of 5 mg/kg every 12 h for 2 weeks, followed by 5 mg/kg once a day for 5 days every week; the whole treatment course lasted 8 weeks. Besides, the patients in the treatment group were treated with CM of Qinggan Lidan Decoction (, QLD) during icteric stage, and Yigan Jiangmei Decoction (, YJD) in non-icteric hyper-aminotransferase stage by oral medication, while for those in the control group, glucurolactone 50 mg was given three times per day. The efficacy of treatment was evaluated at the ends of 2nd, 4th and 8th weeks, respectively. And a follow-up study was carried out for 6-24 months. RESULTS: The total effective rate was 95.0% (57/60) in the treatment group and 77.5% (31/40) in the control group; the overall curative effect in the former was superior to that in the later, showing a significant difference (P=0.021). Cholestasis and liver function were improved in both groups, and the effect of reducing serum bilirubin level in the treatment group was more rapid and extensive than that in the control group, which could reduce the post-hepatitis cirrhotic risk caused by long-term cholestasis and liver cell damage. CONCLUSION: The therapeutic efficacy of integrated CM and Western medical drug therapy, by using QLD during icteric stage and YJD in nonicteric hyper-aminotransferase stage, was significantly higher than that of routine Western medical treatment alone; it was an ideal project for the treatment of infantile cytomegalovirus hepatitis.

Presumed cytomegalovirus-associated retrobulbar optic neuritis in a patient after allogeneic stem cell transplantation.

A case of cytomegalovirus (CMV)-associated bilateral retrobulbar optic neuritis (ON) following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is reported. Abrupt onset of bilateral decreased vision occurred in a 33-year-old man 7 months after haplo-HSCT. His cerebrospinal fluid (CSF) demonstrated pleocytosis with an absence of leukemic cells. CMV DNA was detected in his blood and CSF sample. Neither encephalopathy nor retinopathy was found in this patient. He was diagnosed with bilateral retrobulbar ON. Although he was given enough antiviral treatment against CMV and immunosuppression with high-dose methylprednisolone, the patient's vision showed no improvement, and he has almost total bilateral blindness. This is the first report, to our knowledge, of CMV-associated bilateral retrobulbar ON in allogeneic stem cell transplantation.