mycophenolic-acid and Hepatitis--Viral--Human

As newer immunosuppressive regimens have steadily reduced the incidence of acute rejection and have extended the life expectancy of allograft recipients, posttransplant malignancy has become an important cause of mortality. In fact, it is expected that cancer will surpass cardiovascular complications as the leading cause of death in transplant patients within the next 2 decades. An understanding of the underlying pathobiology and how to minimize cancer risks in transplant recipients are essential. The etiology of posttransplant malignancy is believed to be multifactorial and likely involves impaired immunosurveillance of neoplastic cells as well as depressed antiviral immune activity with a number of common posttransplant malignancies being viral-related. Although calcineurin inhibitors and azathioprine have been linked with posttransplant malignancies, newer agents such as mycophenolate mofetil and sirolimus have not and indeed may have antitumor properties. Long-term data are needed to determine if the use of these agents will ultimately lower the mortality due to malignancy for transplant recipients.

Topics: Azathioprine; Calcineurin Inhibitors; Carcinoma, Hepatocellular; Cyclosporine; Hepatitis, Viral, Human; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lymphoproliferative Disorders; Mycophenolic Acid; Neoplasms; Sirolimus; Skin Neoplasms; Tacrolimus; Transplantation Immunology; Transplantation, Homologous

In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for sepsis associated with immunosuppressive medications that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis.. The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee.. The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591.. Immunosuppressed patients, by definition, are susceptible to a wider spectrum of infectious agents than immunologically normal patients and, thus, require a broader spectrum antimicrobial regimen when they present with sepsis or septic shock. Special expertise managing immunosuppressed patient populations is needed to predict and establish the correct diagnosis and to choose appropriate empiric and specific agents and maximize the likelihood that patients will survive these microbial challenges.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antibodies, Monoclonal; Antifungal Agents; Antiviral Agents; Aspergillosis; Candidiasis; Consensus Development Conferences as Topic; Evidence-Based Medicine; Hepatitis, Viral, Human; Humans; Immune Tolerance; Immunocompromised Host; Immunophilins; Immunosuppressive Agents; Mycophenolic Acid; Pneumonia; Practice Guidelines as Topic; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

Topics: Acute Disease; Antiviral Agents; Azathioprine; Bile Duct Diseases; Bile Ducts, Intrahepatic; Cytokines; Cytomegalovirus Infections; Drug Therapy, Combination; gamma-Globulins; Ganciclovir; Graft Rejection; Heart Transplantation; Hepatitis, Viral, Human; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Middle Aged; Models, Biological; Mycophenolic Acid; Postoperative Complications; Ursodeoxycholic Acid

The impact of cytomegalovirus (CMV) infection post-transplantation is in part influenced by the degree of immunosuppression. While mycophenolate mofetil (MMF) does not increase the overall incidence of CMV infection, we have questioned whether or not it increases its severity. Using a case control study design in which 29 renal transplant patients developed CMV disease [17 (59%) of which received azathioprine (AZA) and 12 (41%) received MMF], increases in the frequency of organ involvement with CMV (58 vs. 18%; p = 0.03) and in the number of organs involved with CMV were noted in the MMF versus the AZA group (2.0 vs. 1.0; p = 0.015). These results indicate that the increased immunosuppressive activity of MMF impacts the morbidity of CMV infection, thus warranting the use of effective anti-CMV preventive regimens while patients are treated with MMF.

Topics: Acyclovir; Adult; Antiviral Agents; Azathioprine; Case-Control Studies; Cohort Studies; Cytomegalovirus Infections; Enteritis; Female; Ganciclovir; Hepatitis, Viral, Human; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Mycophenolic Acid; Pneumonia, Viral; Risk Factors; Severity of Illness Index