Intravenous Cidofovir Research Articles

Intravenous Immunoglobulin in BK Virus Nephropathy

The incidence of post transplant viral infections has increased with the use of more potent immunosuppressive regimens. Consequently, BK virus nephropathy (BKVN) has arisen as a significant cause of graft dysfunction and loss. Reduction of immunosuppression is the first line management of post-transplant viral infections. Other therapies such as intravenous immunoglobulin (IVIg), cidofovir, leflunomide and fluoroquinolones have been tried with varying degrees of success.

Urrets-Zavalia syndrome as a complication of ocular hypotonia due to intravenous cidofovir treatment

Sir, Cidofovir (HPMPC) is widely used for the treatment of CMV retinitis and is also effective against VZV and HSV.1 This treatment can be responsible for two ocular side effects: anterior uveitis and severe and prolonged ocular hypotony.1, 2 Ocular hypotony can be irreversible despite specific treatment with poor visual prognosis.1, 2 The suspected physio-pathogenic mechanism of this complication is a direct toxicity of cidofovir on the ciliary body.2, 3

BK Virus Encephalitis

To describe a case of BK virus encephalitis with attempted direct antiviral therapy, review the reported cases of BK virus in the central nervous system, and report the novel use of intravenous cimetidine in place of oral probenecid to minimize the toxicities of intravenous cidofovir. A 36-year-old male with acute myelomonocytic leukemia and subsequent myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplant. His course was complicated by severe graft-versus-host disease involving his skin and gastrointestinal tract. Five weeks after transplantation, he developed fever and confusion. Magnetic resonance imaging was suggestive of limbic encephalitis and cerebrospinal fluid tested positive for BK virus. Therapy with intravenous cidofovir was thought to be indicated. Although probenecid is commonly used to minimize the toxicities of cidofovir, the patient's severe graft-versus-host disease raised concerns about absorption of oral medications. Based on animal models and pharmacokinetic data, intravenous cimetidine was used in place of oral probenecid. Despite these therapies, the patient's mental status did not improve. He developed progressive organ system failure, and care was ultimately withdrawn. BK virus is increasingly described as a cause of encephalitis. The majority of reported cases have occurred in immunocompromised patients and have generally had a poor outcome. This case describes attempted antiviral therapy using cidofovir, the antiviral agent used most frequently in other syndromes due to BK virus. Intravenous cimetidine is a novel modality used to minimize ocular and renal toxicities frequently seen with cidofovir, and we believe this warrants further investigation. BK virus may be a cause of encephalitis in immunocompromised hosts, and cidofovir represents a possible treatment option. Intravenous cimetidine can be considered to minimize toxicities associated with cidofovir use in patients unable to tolerate or absorb oral probenecid.

Severe Necrotizing Adenovirus Tubulointerstitial Nephritis in a Kidney Transplant Recipient

Adenoviruses (AdV) are emerging pathogens with a prevalence of 11% viruria and 6.5% viremia in kidney transplant recipients. Although AdV infection is common, interstitial nephritis (ADVIN) is rare with only 13 biopsy proven cases reported in the literature. We report a case of severe ADVIN with characteristic histological features that includes severe necrotizing granulomatous lesion with widespread tubular basement membrane rupture and hyperchromatic smudgy intranuclear inclusions in the tubular epithelial cells. The patient was asymptomatic at presentation, and the high AdV viral load (quantitative PCR>2,000,000 copies/mL in the urine and 646,642 copies/mL in the serum) confirmed the diagnosis. The patient showed excellent response to a combination of immunosuppression reduction, intravenous cidofovir, and immunoglobulin therapy resulting in complete resolution of infection and recovery of allograft function. Awareness of characteristic biopsy findings may help to clinch the diagnosis early which is essential since the disseminated infection is associated with high mortality of 18% in kidney transplant recipients. Cidofovir is considered the agent of choice for AdV infection in immunocompromised despite lack of randomized trials, and the addition of intravenous immunoglobulin may aid in resolution of infection while help prevention of rejection.

Histopathologic Resolution of Adult Liver Transplantation Adenovirus Hepatitis With Cidofovir and Intravenous Immunoglobulin: A Case Report

Adenovirus (ADV) infections in adult solid organ transplant recipients, although rare, are associated with high mortality. There are no randomized controlled trials establishing the efficacy of specific treatment modalities. To our knowledge apparent response to treatment with combination therapy with intravenous cidofovir (CDV) and immunoglobulin (IVIG) has only been demonstrated in 2 adult renal transplant recipients in whom ADV was documented in body fluids only. We describe an adult liver transplant recipient diagnosed with ADV hepatitis based on positive immunohistochemical staining of a liver biopsy specimen, positive blood ADV DNA polymerase chain reaction (PCR), and treated with the combination of CDV and IVIG. We demonstrated both clearance of viremia and histopathologic resolution of the hepatitis despite the patient's fatal outcome. To our knowledge this is the only case documenting eradication of tissue-invasive ADV disease in any solid organ transplant recipient using CDV and IVIG. This case provides evidence to support the use of this drug combination, which has many potential toxicities that might discourage its use otherwise.

Pneumonitis post-haematopoeitic stem cell transplant – Cytopathology clinches diagnosis

BackgroundPrimary BK virus (BKV) infection is probably acquired by the respiratory route in childhood, and latent virus persists principally in the urinary tract. BKV reactivation is implicated in late onset haemorrhagic cystitis (HC) post Haematopoietic Stem Cell Transplant (HSCT). There is emerging evidence that BKV can cause life-threatening pneumonitis in immunocompromised individuals. ObjectivesTo describe the first known case of BKV pneumonitis in an adult HSCT recipient. Study design/ResultsA 19-year old male underwent an ABO–incompatible, volunteer unrelated donor allogeneic HSCT for high risk AML. The post-transplant period was complicated by moderate-severe cutaneous and gut acute graft-versus-host disease (aGVHD) and severe HC, attributable to BKV. Treatment encompassed intensification of immunosupression for aGVHD and weekly intravenous (IV) cidofovir (2.5mg/Kg) for BK viruria.He was readmitted with presumed septic shock and acute renal failure. After a transient improvement on broad spectrum antibacterials, he suffered significant respiratory deterioration. CT imaging revealed diffuse ‘ground-glass’ attenuation. Cytopathological assessment of a broncho-alveolar sample (BAL) was consistent with polyomavirus pneumonitis. No other cause was found to account for the respiratory deterioration. He did not respond to therapy and died of multi-organ failure. ConclusionsBKV is implicated in haemorrhagic cystitis in HSCT recipients but not routinely considered as a cause of pneumonitis. There are just 5 other cases in the literature, including 3 patients with AIDS. BKV should be considered as a possible cause of pneumonitis in HSCT recipients.

Intravesicular Cidofovir for the Treatment of Polyomavirus-Associated Hemorrhagic Cystitis

To review the literature regarding the use of intravesicular cidofovir in the treatment of polyomavirus-associated hemorrhagic cystitis. Searches of PubMed were conducted, with key search terms including intravesicular cidofovir, polyomavirus, BK virus, JC virus, and hemorrhagic cystitis. Limits were set to include human subjects. All articles identified were evaluated, and one was excluded due to being published only in the German language. All case studies/case series were included if patients received at least 1 dose of intravesicular cidofovir for treatment of cystitis. Polyomavirus-associated hemorrhagic cystitis is more common in immunocompromised patients, particularly those who have undergone stem cell transplantation. Early-onset cystitis is often due to chemotherapy agents, while cystitis that develops 10-14 days into therapy is often associated with infection with polyomavirus, such as BK virus. There is no standard of therapy for polyomavirus-associated cystitis other than hyperhydration and continuous bladder irrigation, and many different therapeutic agents have been used in this setting, with mixed results. One such agent, intravenous cidofovir, provides clinical improvement but carries a risk of renal failure. Intravesicular cidofovir has been reported in case reports/series to provide positive symptomatic improvement; however, it has not been universally found to decrease urine viral load. At this time, it appears that intravesicular cidofovir may be used as an option to provide symptomatic relief in patients with polyomavirus-associated hemorrhagic cystitis. However, it is not definitively known whether its use significantly decreases urine virus load in these patients. Larger clinical trials need to be conducted to fully understand the role of intravesicular cidofovir in this setting.

Cidofovir Therapy for Adenovirus Pneumonia in an AIDS Patient on HAART: A Case Report

Introduction: Adenovirus infections are associated with significant morbidity and mortality among immunocompromised hosts. Adenovirus pneumonia is a rare and often fatal disease in patients with AIDS. Case Report: We report a case of a 28-year-old woman with advanced HIV/AIDS, who developed pneumonia four weeks after initiation of highly active antiretroviral therapy (HAART). Despite empiric antibiotics, the patient developed worsening hypoxemia and progressive pneumonia on chest x-ray. Culture data from a bronchoalveolar lavage (BAL) was negative for bacteria, fungi, pneumocystis jirovecii, but was positive for adenovirus detected by PCR. After transfer to a tertiary care hospital intensive care unit, a repeat BAL confirmed the presence of adenovirus by immunohistochemical staining. Tissue samples sent for histopathology revealed smudge cells. Serum adenovirus viral load was 1.6 × 105 copies/mL. Intravenous cidofovir, 1 mg/kg/day, was initiated and scheduled three times a week. The patient exhibited remarkable improvement and was discharged to home in stable condition after four doses of cidofovir treatment. Discussion: Prior to our case, the few published accounts of HIV patients with adenovirus pneumonia treated with cidofovir have all resulted in death. Our case is distinct from these cases by the lack of concomitant pulmonary infection and the initiation of HAART prior to presentation. Conclusion: To our knowledge, we present the first case of adenovirus pneumonia in a patient with AIDS successfully treated with cidofovir. Our case suggests that limited and low dose cidofovir may be an efficacious approach to treat adenovirus pneumonia among HIV patients, especially those established on HAART.

An Outbreak of Adenovirus Type 7 in a Residential Facility for Severely Disabled Children

Adenoviruses cause a variety of clinical symptoms, involving the respiratory, gastrointestinal, urogenital, and neurologic systems. Only a few of the 55 known serotypes of adenovirus that affect humans can cause outbreaks of respiratory tract infection. To describe the characteristics and clinical manifestations of severe respiratory disease contracted by 8 physically and cognitively disabled children during a very short outbreak of adenovirus serotype 7 infection in a residential facility. The clinical, imaging, and laboratory findings of the patients who were hospitalized with severe respiratory symptoms were retrospectively reviewed. Molecular typing of the adenovirus was performed. During 10 days in February 2010, 8 severely disabled children, 9 months to 5 years of age (median 22.5 months), from the same residential facility, were hospitalized due to severe acute respiratory disease with hypoxemia. Four of them (50%) needed mechanical ventilation for 2 to 8 days and one developed multisystem failure, including acute renal failure. Adenovirus serotype 7 was detected in the respiratory specimens of all 8 children. Two patients were treated with intravenous cidofovir. All 8 patients survived and were discharged after hospitalization of 6 to 15 (median: 11.5) days. The epidemiologic investigation revealed that all the 8 affected children shared a playroom and a caregiver worked with them while suffering fever, sore throat, and conjunctivitis before the onset of the outbreak. Adenovirus type 7 may cause short outbreaks of infection in institutions, causing children to develop life-threatening disease. Early detection of pathogens causing respiratory infections in institutions, isolation, and other preventive precautions are advocated. Moreover, vaccination of health care providers in institutions with the currently available live, oral adenovirus vaccine for types 4 and 7 should be considered.

Intravenous cidofovir for resistant cutaneous warts in a patient with psoriasis treated with monoclonal antibodies

Human papilloma virus is a common and often distressing cutaneous disease. It can be therapeutically challenging, especially in immunocompromised patients. We report a case of recalcitrant cutaneous warts that resolved with intravenous cidofovir treatment. The patient was immunocompromised secondary to monoclonal antibody therapy for psoriasis.

Adenovirus Disease after Kidney Transplantation: Course of Infection and Outcome in Relation to Blood Viral Load and Immune Recovery

Information on the clinical spectrum and management of adenovirus infection after kidney transplantation is limited. From April 2007 to April 2010, 17 kidney transplant recipients were diagnosed with adenovirus disease. The median time to infection was 5 (range, 2-300) weeks after transplantation. Of the 17 patients, 13 (76.5%) presented early, within 3 months posttransplant, and four (23.5%) presented late, more than 3 months after transplant. Besides urinary tract, involvement of other organs was common (63.6%) among patients with adenovirus viremia. Despite reduction of immunosuppression, six patients subsequently had a rise in the level of blood viral load, mostly within a week after diagnosis. However, only three (27.3%) patients with early infection developed disease progression. Compared to the late infection group, patients with early infection had significantly lower absolute lymphocyte counts at week 1 (p = 0.01) and 3 (p = 0.002) after diagnosis. Four patients received intravenous cidofovir. At 6-month follow-up, 10 (90.9%) patients had reversible graft dysfunction. Only one (5.7%) died from bacterial sepsis. Adenovirus disease is a significant complication following kidney transplantation. Early case recognition with reduction of immunosuppression is critical. Serial blood adenovirus viral loads and assessment of lymphocyte recovery are also useful in monitoring the course of infection.

Efficacy of Intravenous Cidofovir in the Treatment of Giant Molluscum Contagiosum in a Patient With Human Immunodeficiency Virus

Molluscum contagiosum virus (MCV) is a DNA virus in the Poxviridae family that may cause extensive and voluminous lesions often resistant to topical therapies in patients with AIDS and other immunocompromised patients. We present a case of eruptive giant molluscum that caused remarkable deformity in a patient with AIDS. Intravenous (IV) cidofovir was used as therapy, resulting in dramatic improvement.

Acyclovir-resistant herpes simplex virus treated with intravenous foscarnet and topical cidofovir

Acyclovir-resistant herpes simplex virus treated with intravenous foscarnet and topical cidofovir

Drug-resistant herpes simplex virus in HIV infected patients

Herpes simplex virus type 2 (HSV2) infection is a major source of morbidity in human immunodeficiency virus (HIV)-infected patients, since reactivations - whether symptomatic or asymptomatic - are associated with increased HIV viral load and viral shedding. Acyclovir, valacyclovir and famcyclovir are indicated for the treatment of HSV2 in HIV patients. This class of drugs has been shown to enhance survival in HIV-infected individuals. However, with the emergence of drug-resistant strains of HSV2, the rates of resistance among HIV patients are almost ten-fold those in immunocompetent individuals, comparing 0.6% to 6%. These HSV2 infections tend to be more severe and to recur. More ominously, disease progression of HIV is promoted by concurrent infection with HSV2. Intravenous foscarnet and cidofovir may be used for acyclovir-resistant HSV; however, resistance to these drugs has been documented. Newer therapies such as the toll-like receptor agonist imiquimod and immunomodulating dipeptides offer promise for the treatment of HSV2 in HIV-infected individuals.

Eradication of disseminated adenovirus infection in a pediatric hematopoietic stem cell transplantation recipient using the novel antiviral agent CMX001

Adenovirus infection is a serious and often fatal complication in hematopoietic stem cell transplant patients. There are currently no FDA-approved therapies for adenovirus infection, with only anecdotal, off-label uses described for a variety of anti-viral agents or immune therapies. We report the first case of successful eradication of disseminated adenovirus infection by the novel antiviral agent CMX001 in a severely immunocompromised pediatric stem cell transplant recipient following failure to respond to intravenous cidofovir. Complete clinical and virologic response was documented; virologic and pharmacokinetic data are reported. CMX001 is a promising new oral antiviral agent under development for the prophylaxis and treatment of severe infections caused by double-stranded DNA viruses including adenovirus in immunocompromised patients.

Treatment of recurrent respiratory papillomatosis lung involvement by cidofovir infusion

Lung parenchyma involvement in recurrent respiratory papillomatosis (RRP) is rare, can be severe, and has variable outcomes. Although several reports have described the effects of different drugs (interferon alpha, indol-3-carbinol, cidofovir, etc.), there is no standard treatment for lung involvement in respiratory papillomatosis. We discuss herein the controversial effectiveness of cidofovir in light of a new observation of respiratory papillomatosis involving lung parenchyma. The reported case is one of rare pulmonary involvement in RRP and shows the effectiveness of intravenous cidofovir alone on symptoms, high-resolution computed tomography abnormalities, and pulmonary function tests. Aggravation after stopping cidofovir may also be interpreted as an indirect argument for the effectiveness of cidofovir in this case.

Low-dose cidofovir in the treatment of symptomatic BK virus infection in patients undergoing allogeneic hematopoietic stem cell transplantation: a retrospective analysis of an algorithmic approach

BK virus (BKV) reactivation occurs in 50% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Standardized antiviral management of BKV infection has not been established. In order to develop a uniform guideline, a treatment algorithm for the management of symptomatic BKV replication was implemented for our allo-HSCT population. This is a retrospective analysis of patients treated according to the protocol between January 2008 and January 2009. Eighteen patients developed symptomatic BKV replication a median of 43 days after allo-HSCT. All patients had BK viruria and 12 patients had BK viremia in addition to viruria. Patients with isolated viruria were treated with intravenous (IV) low-dose cidofovir (0.5-1mg/kg IV weekly) until symptom resolution. In patients with BK viremia, therapy was continued until virological clearance was achieved in the blood. Four patients also received intravesical instillation of cidofovir per physician discretion. Thirteen of 18 (72%) patients with viruria and 8 of 12 (75%) patients with viremia responded to treatment. Three patients developed transient renal dysfunction. Low-dose cidofovir is safe and effective in allo-HSCT recipients. In absence of randomized prospective data, an institutional algorithmic protocol removes variance in practice pattern and derives data that may be used for research and improved patient care.

Incorporation of ANTI-HHV-8 Agents as Targeted Therapy for the Treatment of HIV-Associated Primary Effusion Lymphoma.

Abstract 4768 BackgroundPrimary effusion lymphoma (PEL) is a non-Hodgkin lymphoma (NHL) which comprises 4% of all AIDS-related lymphomas. PEL has a predilection for body cavities, causing pleural and pericardial effusions and ascites, but may present as masses. EBV is present in PEL cells in 80% of cases, but HHV-8 infection in PEL cells is required for the diagnosis (dx). Historically, treatment encompassed approaches including intracavitary antiretroviral medications (ARV) or chemotherapeutic agents, single or multi-agent systemic chemotherapy, and systemic ARVs, but median survival in case series using these approaches was only 6 months (mo). Treatment with multi-agent chemotherapy and highly active ARV therapy (HAART) yields good outcome in other HIV-NHL with survival approaching that of the HIV-negative population, but gives unknown survival rates in PEL. Recent consideration has been given to targeted therapy directed against HHV-8 infection with antiviral agents, with encouraging outcomes reported in the literature, particularly the HHV-8 associated syndromes Kaposi Sarcoma (KS) and Multicentric Castleman's Disease. We report on 5 patients (pts) diagnosed with PEL and treated at St. Paul's Hospital, 2 of whom are receiving valganciclovir (VGCV) therapy directed against HHV-8 infection of PEL cells. MethodsWe conducted a retrospective review of pts with a tissue dx of PEL since 2004. PEL data was collected from the clinical charts and HIV-related data from the BC Centre for Excellence in HIV/AIDS (CFE) database. A literature search was performed to capture prior studies of anti-HHV-8 medications used to treat PEL. ResultsThe median age at PEL diagnosis was 60 (range 48-68) years (y); gender was: male, n=4; and female, n=1. 2 pts had a history of KS. The median CD4 count at PEL dx was 230 (50-560) cells/ml, 1 pt had a CD4 count of 50 cells/ml and all others were ≥210 cells/ml; median HIV viral load (VL; reported in 4) was 81 (35-176,600) copies/ml. The median time from HIV dx to PEL dx was 6 (0-21) y and from initiation of HAART to PEL dx 1 (0-11) y. Clinical PEL presentation was: pleural effusions, n=4; pericardial effusion, n=2; ascites, n=1; associated mass, n=1; mass without effusions, n=1. PEL treatment was: CHOP + HAART, n=2; CHOP + HAART + VGCV, n=1; HAART + VGCF, n=1; supportive care, n=1. 2 pts receiving CHOP and HAART are both in complete remission (CR) at 8 and 57 months (mo) from PEL dx. 2 pts diagnosed since December 2008 are receiving VGCV and HAART, and 1 of these pts is receiving CHOP with good tolerance (the other pt declined cytotoxic chemotherapy). Of 3 pts receiving CHOP, there was 1 episode of febrile neutropenia (FN) in 1 pt and 5 episodes of FN and 3 clinical infections in a second pt. The same pt had profound anemia and thrombocytopenia requiring transfusion support; this pt did not receive VGCV. 1 pt receiving VGCV with HAART and CHOP required G-CSF support but did not develop FN or clinical infection. 1 pt presented with a poor performance status, received supportive care only and died within one mo of PEL dx; all others are alive at 4, 8, 14 and 57 months from PEL dx. A literature review identified 2 reports of pts with PEL receiving systemic cidofovir (CDFV) directed against HHV-8. One pt with a CD4 count of 72 cells/ml and an HIV-VL of 75,000 copies/ml received unspecified systemic chemotherapy, HAART and intravenous (IV) CDFV followed by VGCV and is in CR at 68 mo from PEL dx. A second pt with a CD4 of 498 cells/ml (HIV-VL not reported) received HAART, IV cidofovir and interferon and is in CR at 28 mo. ConclusionsPEL treatment has focused on optimization of HIV control with HAART and lymphoma control with chemotherapy, however, antiviral medications as targeted therapy directed against HHV-8 infection of PEL cells may be used without undue toxicity and possibly with success. PEL generally involves latent HHV-8 infection, which is theoretically not susceptible to antiviral medications, but there are reports in the literature of encouraging results achieved by combining agents to induce lytic infection (including chemotherapeutic agents) with anti-herpes virus therapy. Our review indicates good tolerance of VGCV with HAART ± CHOP chemotherapy, and that with newer treatment approaches, pts may live longer than the 6 mo median survival previously reported. To our knowledge, our pts receiving VGCV are the third and fourth pts reported receiving anti-HHV-8 therapy as treatment for PEL. Disclosures:Off Label Use This presentation discusses the use of valganciclovir in the treatment of HHV-8 associated primary effusion lymphoma..

Cidofovir for BK Virus–Associated Hemorrhagic Cystitis: A Retrospective Study

BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P = .01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P = .001 and P = .001, respectively). Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.

Human herpesvirus 6 infections after liver transplantation

Human herpesvirus 6 (HHV-6) infections occur in > 95% of humans. Primary infection, which occurs in early childhood as an asymptomatic illness or manifested clinically as roseola infantum, leads to a state of subclinical viral persistence and latency. Reactivation of latent HHV-6 is common after liver transplantation, possibly induced and facilitated by allograft rejection and immunosuppressive therapy. Since the vast majority of humans harbor the virus in a latent state, HHV-6 infections after liver transplantation are believed to be mostly due to endogenous reactivation or superinfection (reactivation in the transplanted organ). In a minority of cases, however, primary HHV-6 infection may occur when an HHV-6 negative individual receives a liver allograft from an HHV-6 positive donor. The vast majority of documented HHV-6 infections after liver transplantation are asymptomatic. In a minority of cases, HHV-6 has been implicated as a cause of febrile illness with rash and myelosuppression, hepatitis, pneumonitis, and encephalitis after liver transplantation. In addition, HHV-6 has been associated with a variety of indirect effects such as allograft rejection, and increased predisposition and severity of other infections including cytomegalovirus (CMV), hepatitis C virus, and opportunistic fungi. Because of the uncommon nature of the clinical illnesses directly attributed to HHV-6, there is currently no recommended HHV-6-specific approach to prevention. However, ganciclovir and valganciclovir, which are primarily intended for the prevention of CMV disease, are also active against HHV-6 and may prevent its reactivation after transplantation. The treatment of established HHV-6 disease is usually with intravenous ganciclovir, cidofovir, or foscarnet, complemented by reduction in the degree of immunosuppression. This article reviews the current advances in the pathogenesis, clinical diagnosis, and therapeutic modalities against HHV6 in the setting of liver transplantation.