The systemic inflammatory response syndrome (SIRS) in acute liver failure (ALF), in which infection is common, has not been studied. In this study, SIRS components were recorded on admission and during episodes of infection, in 887 ALF patients admitted to a single center during an 11-year period. Overall, 504 (56.8%) patients manifested a SIRS during their illness, with a maximum of 1, 2, and 3 concurrent SIRS components in 166, 238, and 100 patients, respectively. In 353 (39.8%) patients who did not become infected, a SIRS on admission was associated with a more critical illness, subsequent worsening of encephalopathy, and death. Infected patients more often developed a SIRS and one of greater magnitude. The magnitude of the SIRS in 273 patients with bacterial infection correlated with mortality, being 16.7%, 28.4%, 41.2%, and 64.7% in patients with 0, 1, 2, and 3 maximum concurrent SIRS components, respectively. Similar correlations with mortality were seen for SIRS associated with fungal infection, bacteremia, and bacterial chest infection. Fifty-nine percent of patients with severe sepsis died, as did 98% of those with septic shock. A significant association was found between progressive encephalopathy and infection. Infected patients with progressive encephalopathy manifested more SIRS components than other infected patients. For patients with a SIRS, the proportions of infected and noninfected patients manifesting worsening encephalopathy were similar. In ALF, the SIRS, whether or not precipitated by infection, appears to be implicated in the progression of encephalopathy, reducing the chances of transplantation and conferring a poorer prognosis. (HEPATOLOGY 2000;32:734-739.)Definitions of sepsis include the components of the systemic inflammatory response syndrome (SIRS), 1 namely temperature greater than 38°C or less than 36°C; heart rate greater than 90 beats per minute; tachypnea greater than 20 breaths per minute or PaCO 2 less than 4.3 kPa; white cell count greater than 12 ϫ 10 9 /L or less than 4 ϫ 10 9 /L or the presence of greater than 10% immature neutrophils. The presence of 2 or more SIRS components when triggered by infection is termed sepsis. Severe sepsis is defined by a deterioration in the presence of hypotension, organ dysfunction, and hypoperfusion abnormalities, and the term septic shock is reserved for severe sepsis with hypotension despite fluid resuscitation. 1 The progression from SIRS through sepsis, severe sepsis to septic shock, is a continuum reflecting the inflammatory response to infection. During this process an increasing proportion of patients will develop the adult respiratory distress syndrome, disseminated intravascular coagulation, acute renal failure, and multiorgan dysfunction syndrome. 2

A prospective study of bacterial and fungal infections after liver transplantation in 284 adults was undertaken. One hundred seventy-five (62%) became infected; bacterial or fungal infections occurred in 159 (56%) and 36 (13%) patients, respectively. Gram-positive cocci, in particular Staphylococcus aureus and Enterococcus faecium, were the commonest bacterial pathogens, and bacteremia and wound infection were the most frequent bacterial infections. Acute rejection and prolonged admission were independent risk factors for bacterial infection; pretransplantation antibacterials had a protective effect. Fungal infection most frequently involved the urinary tract and chest; Candida albicans was the most common pathogen. Four independent variables predicted fungal infection: low pretransplantation hemoglobin, high pretransplantation bilirubin, return to surgery, and prolonged therapy with ciprofloxacin. Patients with acute liver failure were more prone to bacterial, but not fungal, infection. No associations were found between infections and duration of surgery. Bacterial, and to a lesser extent, fungal infections are important complications of liver transplantation. However, liver transplantation surgery per se may not be the major determinant of infection.

Hepatocyte transplantation has been investigated in patients with liver-based metabolic disorders and acute liver failure. We report the first use of hepatocyte transplantation in two brothers with severe inherited coagulation factor VII deficiency. Patient 1 received a total of 1.09x10(9) cryopreserved hepatocytes, and patient received 2.18x10(9) fresh and cryopreserved hepatocytes through a Hickman line inserted in the inferior mesenteric vein. Infusion of isolated human hepatocytes improved the coagulation defect and markedly decreased the requirement for exogenous recombinant factor VII (rFVIIa) to approximately 20% of that before cell transplantation. In both patients, episodes of line sepsis were associated with an increase in rFVIIa requirement. Six months posthepatocyte transplantation, higher rFVIIa doses were required, suggesting loss of transplanted hepatocyte function. Because of increasing problems with venous access and long-term uncertainty of the efficacy of hepatocyte transplantation, orthotopic liver transplantation was performed successfully in both cases.

To compare the efficacy of a selective parenteral and enteral antimicrobial regimen in patients with fulminant liver failure, we classified 104 patients on reaching grade II encephalopathy as infected or non-infected. Patients who were infected were randomly assigned to receive IV cefuroxime (group 1) or selective parenteral and enteral antimicrobial regimen (group 2). Noninfected patients were randomly selected to receive either selective parenteral and enteral antimicrobial regimen (group 3) or no initial antimicrobials until clinically indicated (group 4). The four groups were comparable regarding age, sex, cause of disease, coma grade, international normalization ratio, presence of kidney failure and indicators of poor prognosis on admission to the study. Clinical parameters such as white cell count, temperature or changes in the chest radiograph, which were used to stratify patients into those infected or not, were not good predictors of infection because early infection rates were similar in the two groups. Three patients died within 24 hr and were excluded from the analysis. We found 42 microbiologically confirmed infections: group 1, 6 of 21; group 2, 8 of 21; group 3, 9 of 28; and group 4, 19 of 31. A reduction in infection was seen between groups 3 and 4 (p < 0.05). Patients receiving the selective parenteral and enteral antimicrobial regimen (groups 2 and 3) had fewer infections than the control group (group 4) (p < 0.005). Groups receiving early antimicrobial therapy (groups 1, 2 and 3) had a lower incidence of infection compared with group 4 (p < 0.0005). Overall, 55.5% survived, with no significant difference between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

SummaryInvasive fungal disease (IFD) is difficult to diagnose. We investigated the incidence of IFD and risk factors using the revised European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG) definitions. Patients (N = 203) undergoing intensive therapy with expected neutropenia ≥10 d were recruited prospectively and followed for a median (range) of 556 (12-730) d. Baseline chest computerized tomography (CT) was performed pre-therapy. Twice-weekly surveillance with galactomannan (GM) was combined with targeted b-D-glucan (BDG) testing on patients with possible IFD or who were GM-positive. Tissue diagnosis was obtained whenever possible. The cumulative incidence of proven/probable IFD among the 202 evaluable cases after 2 years follow-up was 21%, including 14 proven and 30 probable IFDs. Using either GM or BDG as the sole biomarker (plus host and clinical evidence) the apparent overall incidence of proven/probable IFD was 11% and 16%, respectively. Combined GM/BDG detected all biopsy-proven mould IFD. Baseline CT abnormalities were found in 76/202 (38%) patients. Baseline CT abnormalities and Karnofsky score <90, monocytopenia >10 d and bacteraemia were independent risk factors associated with greater than twofold increased IFD risk. This combined diagnostic approach identified a high incidence of IFD and important risk factors in this cohort.

Tuberculosis after liver transplantation has a significant morbidity and mortality. Pretransplantation a personal and family history of tuberculosis must be sought, and screening of patients and their families should be considered. Standard regimens incorporating isoniazid and rifampin are effective, but regular monitoring of liver function is essential to detect drug-induced hepatotoxicity.

Solid-organ transplant recipients are at risk from various infectious diseases, many of which can be prevented by immunizations that could reduce morbidity and mortality. However, it is not uncommon for children requiring transplantation to have received inadequate or no immunizations pre-transplant. Every effort should be made to immunize transplant candidates early in the course of their disease according to recommended schedules prior to transplantation. It is also important to immunize their household contacts and healthcare workers. In this review, we summarize the major immunization issues for children undergoing transplantation, the data currently available on immunization safety and efficacy, and suggest immunization practices to reduce vaccine-preventable disease. There is a real need for a standardized approach to the administration and evaluation of immunizations in this group of patients.

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