The replication of beta-herpesviruses-cytomegalovirus (CMV), human herpesvirus (HHV)-6, and HHV-7-and their association with CMV disease and response to antiviral therapy were prospectively investigated in 33 liver transplant recipients not given antiviral prophylaxis. CMV, HHV-6, and HHV-7 DNA were detected within 8 weeks after transplantation in 70%, 33%, and 42% of the patients, respectively. The univariate association between CMV disease and the 3 beta-herpesviruses was more significant by virus load quantitation than by qualitative detection of DNA. This association with high levels of CMV, HHV-6, and HHV-7 (P<.001,.022, and.001, respectively) occurred mainly in CMV-seronegative recipients of transplants from CMV-seropositive donors. Antiviral therapy with ganciclovir (Gcv) reduced the load of CMV and HHV-6 and HHV-7. These results suggest that CMV disease in transplant recipients is related to the unique interaction of the 3 beta-herpesviruses and is ultimately reduced after intravenous Gcv treatment.

Summary Clostridium difficile colitis (CDC) remains a serious and common complication after liver transplantation (LT). Four hundred and sixty‐seven consecutive LTs in 402 individuals were performed between 1998 and 2001 at our center. Standard immunosuppression consisted of tacrolimus, mycophenolate, and steroids. CD toxins A and B were detected by using a rapid immunoassay or enzyme immunoassay. CDC was diagnosed in 32 patients (5–1999 days post‐LT), with 93.8% (30/32) of patients developing CDC during the first year post‐LT; three individuals had CDC more than 3 years post‐LT, one of which also had early CDC. All patients presented with abdominal pain and watery diarrhea. Patients who developed CDC within 1‐year post‐LT were significantly more likely to have a hemorrhagic, biliary, or infectious complication. Patients who developed CDC within 28 days post‐LT had a significantly higher model end‐stage liver disease score. Treatment consisted of fluid and electrolyte replacement and metronidazole and no patients developed toxic megacolon, required colonic resection, or died from CDC. CDC represents a potentially severe complication following LT. Most cases occur early post‐LT. Development of a hemorrhagic, biliary, or infectious complication is associated with the development of CDC.

These results suggest that HHV-6 seronegativity before transplantation is a valuable clinical marker that identifies patients at risk for developing fungal infection after transplantation.

The use of allografts from donors with hepatitis B core antibody in liver transplantation (LT) is associated with the risk of de novo hepatitis B virus (HBV) infection. Prophylaxis using hepatitis B Immune globulin (HBIg) and lamivudine alone or in combination has been reported. Yet, there are no standardized regimens and long-term efficacy is not known. We report a case of a patient who underwent LT for alcoholic liver disease who received an allograft from a donor with Hepatitis B core antibody. The patient had no previous exposure to HBV, was vaccinated against HBV, and had demonstrated Hepatitis B surface antibody present in serum before and 6 months after transplantation. Prophylaxis with short-term HBIg (1 week) and indefinite lamivudine was given. De novo HBV infection developed more than 3 years after LT with a lamivudineresistant polymerase mutant containing the rtM204I and rtl180L/M mutations. We reviewed the risk of de novo post-LT HBV infection in recipients of livers from hepatitis B core antibody positive donors. High risk were HBV naïve recipients, moderate risk recipients had isolated hepatitis B surface antibody (anti-HBs) or hepatitis B core antibody (anti-HBc), while low-risk recipients had both anti-HBs and anti-HBc. We reviewed prophylaxis protocols reported in the literature and made recommendations for management.

Antifungal prophylaxis has been proposed for liver transplant recipients at increased risk for invasive mold infection. Risk factors for invasive mold infection after liver transplantation were selected to divide recipients into 3 groups: (1) high risk-transplantation on hemodialysis or delay of hospital discharge beyond day 7 after transplantation because of allograft or renal insufficiency; (2) T he incidence of fungal infections reported after liver transplantation has ranged from 5% to 42%. 1-9 Candida species account for 62% to 91% of these infections, with case fatality rates of 10% to 75%; Aspergillus has been responsible for less than 10% of these infections, with case fatality rates as high as 80% to 100%. 5,10-13 Risk factors associated with invasive fungal infections after liver transplantation have included fulminant hepatic failure, increased operative time, increased operative transfusion requirements, class II human leukocyte antigen mismatch, posttransplantation abdominal surgery, symptomatic cytomegalovirus (CMV) infection, and preceding bacterial infections. 4,8 Risk factors associated with Candida infections tend to be those associated with surgical complications, whereas risk factors for Aspergillus infection tend to be associated with posttransplantation impairment of allograft and renal function. 14 Improvements in surgical and medical management of liver transplantation have been associated with decreasing rates of invasive candidiasis 15 ; indeed, without systemic antifungal prophylaxis, rates of less than 5% have been reported recently following liver transplantation. 15,16 However, these surgical and medical improvements have not been associated with a decrease in the frequency of invasive aspergillosis, 15 which has ranged from 1% to 6%. 7,17,18 Despite improvements in antifungal therapy, case-fatality rates of invasive Aspergillus infection after liver transplantation remain high at 33% to 60%, 17,19,20 and in some series, Aspergillus has been responsible for 16% of deaths after liver transplantation. 21 Aspergillus or other invasive mold infection developed in 3 liver transplant recipients during the first year of liver transplantation at Mayo Clinic in Jacksonville. An evaluation of these cases and a review of published experience led to the development of a clinical protocol that identified patients at increased risk for invasive mold infection and directed antifungal prophylaxis to the patients at highest risk. A retrospective assessment of the effectiveness of the risk stratification and of the Abbreviation: CMV, cytomegalovirus. From the

In a cohort of 43 liver transplant recipients who did not receive antiviral prophylaxis, qualitative and quantitative polymerase chain reactions (PCRs) from peripheral blood were prospectively compared to determine their value in the diagnosis of established cytomegalovirus (CMV) disease and for the early detection of CMV replication as a marker for preemptive antiviral therapy. Using a cutoff of 7000 copies of CMV DNA per sample, the specificity and positive predictive values of qualitative PCR for the diagnosis of established CMV disease increased from 33% to 89% and from 54% to 82%, respectively, without reducing the 100% sensitivity and negative predictive value. By contrast, quantification of viral load provided no additional advantage to qualitative PCR for the early diagnosis of CMV infection before development of disease.

Summary Bartonella henselae has not only been identified as the causative agent of cat scratch disease, but it is also associated with other significant infectious syndromes in the immunocompromized population. We describe two cases of B. henselae associated diseases in liver transplant recipients who both had contact with cats. The first recipient developed localized skin manifestation of bacillary angiomatosis in association with granulomatous hepatitis. He tested positive for Immunoglubulin G (IgG) antibodies against B. henselae. The second patient developed axillary lymphadenopathy, with biopsy showing necrotizing granulomatous inflammation and polymerase chain reaction studies were positive for B. henselae DNA. Her serology for bartonellosis showed a fourfold rise in antibody titers during her hospitalization. Both patients responded to treatment with Azithromycin in combination with Doxycycline. These were the only cases within a series of 467 consecutive liver transplants performed in 402 patients performed during a 4‐year period. Although bartonellosis is a rare infection in liver transplantation recipients, it should always be included in the differential diagnosis of patients presenting with fever, central nervous system (CNS) symptoms, skin lesions, lymphadenopathy, and hepatitis especially if prior contact with cats is reported.

HHV8 DNA sequences have recently been isolated from all types of Kaposi's sarcomas, and its association in the etiopathogenesis of this tumor has been established. However, little is known about the regulation of HHV8 replication in immunocompromised patients seropositive for this virus, and its impact on the development of Kaposi's sarcoma (KS). Through the study of a heart transplant patient who developed KS and in whom peripheral blood lymphocytes (PBLs) had been prospectively collected before and after transplantation, we have investigated the pathogenesis of HHV8. Our results indicate that (i) HHV8 can reactivate soon after transplantation; (ii) viral replication, as determined by quantification of HHV8 DNA load of PBLs, increases significantly after transplantation; and (iii) increased HHV8 DNA levels in PBLs are associated with the development of KS.