Natural history of hepatitis C virus infection in multitransfused hemophiliacs: effect of coinfection with human immunodeficiency virus. The Multicenter Hemophilia Cohort Study.

The objective of this prospective cohort study was to describe the natural history of hepatitis C virus (HCV) infection and the effect of human immunodeficiency virus (HIV) on the clinical manifestations of HCV liver disease. Two hundred twenty-three hemophiliacs were followed in a comprehensive care setting with periodic clinical and laboratory evaluations. Dates of HIV seroconversion were determined retrospectively from frozen sera. HCV assays were performed by a "second generation" four-antigen recombinant immunoblot assay (RIBA 2). Liver failure was found after a latency period of 10 to 20 years in 9% of multitransfused HCV-positive/HIV-positive adult hemophiliacs without an AIDS-defining opportunistic infection or malignancy. Lymphocytopenia, decreased CD4 counts, and, possibly, thrombocytopenia were associated with liver failure which appeared to be accelerated by HIV disease and its treatment. This form of severe liver disease is being seen with increasing frequency among multi-transfused persons with hemophilia who are coinfected with HCV and HIV.

Factors predictive of death among HIV-uninfected persons with haemophilia and other congenital coagulation disorders.

Historically, the leading cause of death among persons with haemophilia and other congenital coagulation disorders was uncontrolled bleeding. Mortality was associated with severe deficiency of coagulation factors VIII or IX and especially with high-titre antifactor neutralizing antibodies (inhibitors). The catastrophic contamination of plasma donor pools with human immunodeficiency virus (HIV) resulted in acquired immunodeficiency syndrome replacing haemorrhage as the leading cause of death among persons with haemophilia. Rather little has been written, however, about mortality among those not infected with HIV. The objective of this study was to identify conditions associated with all-cause mortality among HIV-uninfected patients who were followed for a mean of 8.8 years in the Multicentre Hemophilia Cohort Study. Among the 364 children (mean age 8 years), there were four deaths; two related to cancer, one to trauma, and the fourth to haemorrhage, end-stage liver disease and sepsis. Among the 387 HIV-uninfected adults (mean age 35 years) there were 29 deaths, with haemorrhage the leading cause of death, followed by hepatic, stroke and cancer deaths. Prognostic factors for all-cause mortality among the adults included haemophilia Type A with neutralizing antibodies [age-adjusted relative rate (RR) 3.1, 95% confidence interval (CI) 1.4-6.9] and serologic evidence of both hepatitis B and C virus (RR 4.1, 95% CI 0.97-17.6). Although hepatitis C viral load was slightly lower in patients with hepatitis B virus surface antigenaemia, it was unrelated to vital status. We conclude that causes of death and prognostic factors for current HIV-uninfected haemophilia patients are similar to those noted before the HIV epidemic. Better understanding, prevention and control of neutralizing antibodies and hepatitis infections may substantially improve longevity for people with haemophilia.

Prognostic factors for all-cause mortality among hemophiliacs infected with human immunodeficiency virus.

To identify the prognostic significance of hemophilia- and virus-related factors, the authors undertook a survival analysis among 644 human immunodeficiency virus (HIV)-infected subjects enrolled in the Multicenter Hemophilia Cohort Study between 1985 and 1993. Acquired immunodeficiency syndrome (AIDS) was the leading cause of death, followed by hemorrhage and hepatic disease. Adverse prognostic factors included older age and CD4-positive lymphocyte values below 14 percent either at entry (age-adjusted mortality rate ratio (RR) = 6.4, 95% confidence interval (CI) 3.4-12.1) or after entry (time-dependent RR = 4.2, 95% CI 2.6-6.7); indeterminate antibody responses to hepatitis C virus (RR = 3.0, 95% CI 1.8-5.0); and inhibitory antibodies to factor VIII concentrates (RR = 1.8, 95% CI 1.1-3.1). Indeterminate hepatitis C virus status was associated with mortality from hepatic disease but not with AIDS mortality. Factors that were not prognostic included duration of HIV infection, hepatitis B virus infection, and other hemophilia variables. These findings suggest that fatal liver disease among coinfected subjects with an indeterminate hepatitis C virus status is probably related to an insufficient humoral response secondary to HIV immune dysfunction and that the risk of death among HIV-infected subjects is best evaluated with age and duration of low CD4 percentage.

Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization. The Multicenter Study of Perioperative Ischemia Research Group.

BACKGROUND: Acute changes in renal function after elective coronary bypass surgery are incompletely characterized and represent a challenging clinical problem. OBJECTIVE: To determine the incidence and characteristics of postoperative renal dysfunction and failure, perioperative predictors of dysfunction, and the effect of renal dysfunction and failure on in-hospital resource utilization and patient disposition after discharge. DESIGN: Prospective, observational, multicenter study. SETTING: 24 university hospitals. PATIENTS: 2222 patients having myocardial revascularization with or without concurrent valvular surgery. MEASUREMENTS: Prospective histories, physical examinations, and electrocardiographic and laboratory studies. The main outcome measure was renal dysfunction (defined as a postoperative serum creatinine level > or = 177 mumol/L with a preoperative-to-postoperative increase > or = 62 mumol/L). RESULTS: 171 patients (7.7%) had postoperative renal dysfunction; 30 of these (1.4% overall) had oliguric renal failure that required dialysis. In-hospital mortality, length of stay in the intensive care unit, and hospitalization were significantly increased in patients who had renal failure and those who had renal dysfunction compared with those who had neither (mortality: 63%, 19%, and 0.9%; intensive care unit stay: 14.9 days, 6.5 days, and 3.1 days; hospitalization: 28.8 days, 18.2 days, and 10.6 days, respectively). Patients with renal dysfunction were three times as likely to be discharged to an extended-care facility. Multivariable analysis identified five independent preoperative predictors of renal dysfunction: age 70 to 79 years (relative risk [RR], 1.6 [95% CI, 1.1 to 2.3]) or age 80 to 95 years (RR, 3.5 [CI, 1.9 to 6.3]); congestive heart failure (RR, 1.8 [CI, 1.3 to 2.6]); previous myocardial revascularization (RR, 1.8 [CI, 1.2 to 2.7]); type 1 diabetes mellitus (RR, 1.8 [CI, 1.1 to 3.0]) or preoperative serum glucose levels exceeding 16.6 mmol/L (RR, 3.7 [CI, 1.7 to 7.8]); and preoperative serum creatinine levels of 124 to 177 mumol/L (RR, 2.3 [CI, 1.6 to 3.4]). Independent perioperative factors that exacerbated risk were cardiopulmonary bypass lasting 3 or mor hours and three measures of ventricular dysfunction. CONCLUSIONS: Many patients having elective myocardial revascularization develop postoperative renal dysfunction and failure, which are associated with prolonged intensive care unit and hospital stays, significant increases in mortality, and greater need for specialized long-term care. Resources should be redirected to mitigate renal injury in high-risk patients.

Factors influencing serum neopterin and beta 2-microglobulin levels in a healthy diverse population.

Sera and questionnaire data from a population-based random sample of healthy adults was used to evaluate factors influencing neopterin and beta 2-microglobulin (beta 2m) values. Both neopterin and beta 2m levels increased with age and were higher among white than blacks (mean values for whites and blacks: neopterin, 5.06 vs 4.49 nmol/L; beta 2m, 1.36 vs 1.28 mg/L). Gender differences were noted for beta 2m but not neopterin values (beta 2m males vs females: 1.37 vs 1.29 mg/L). Neopterin values were lower among current smokers than among nonsmokers (4.32 vs 5.16 nmol/L) and were higher among users of antihistamines (5.46 among users vs 4.65 nmol/L among nonusers). Neopterin and beta 2m were correlated in this healthy adult population (adjusted r = 0.53, P = 0.001), yet no other interrelationships with numerous biologic markers except between beta 2m and serum-soluble interleukin-2 receptor levels (adjusted r = .41, P = 0.05) were observed. These findings provide important baseline information to consider before planning or evaluating studies utilizing neopterin or beta 2m levels.