Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C-related cirrhosis is the major indication for liver transplantation (LT). This disease recurs histologically in nearly all the HCV-infected patients during the first postoperative year. Chronic hepatitis C evolves to cirrhosis in 20% of the cases within 5 years after LT. However, the 5-year survival for a HCV-infected recipient is still comparable to that of a patient grafted for another indication; it will become worse later. High viremia after LT is associated with a more severe liver recurrent disease. The influence of viral genotype remains controversial. The impact of the type of immunosuppression on HCV recurrence is unclear. Steroids, that increase viremia, might have a deleterious effect on the outcome of chronic HCV-disease after LT. Antiviral combined therapy (Interferon + Ribavirin) soon after transplantation, before disease recurrence, is probably the best treatment at the present time; this remains still unproven. Retransplantation for HCV recurrent cirrhosis allows a 60% survival at 1 year.
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PMID:Hepatitis C recurrence after liver transplantation. 1069 75

HIV infections are zoonoses occurring in communities that hunt chimpanzees (HIV 1) and sooty mangabeys (HIV 2) in the forests of equatorial and West Africa respectively. Most cross species transmission to man probably fizzles out, but the transmission of HIV 1 type M around 1930 eventually resulted in a pandemic that has spread around the world. HIV 2 types A and B have caused epidemics in West Africa. HIV infections are characterised by three phases (i) an initial, primary infective phase with rising viraemia, asymptomatic and silent, lasting for some 10 weeks, (ii) a long quiescent phase with the viraemia and illness mostly held in check by the immune response and lasting some 10 years in HIV 1 and 20 years or so in HIV 2 and (iii) a terminal third phase lasting some 10 months with rising viraemia, falling CD4 levels and multiple opportunistic infections recognised in a community by the onset of a florid AIDS epidemic. The silent primary epidemic reached Nairobi around 1980, with the florid secondary AIDS epidemic peaking here around 1992 and overwhelming the hospitals and other health services. The introduction of highly active antiretroviral therapy (HAART) has dramatically improved the prognosis for individual patients with AIDS, but it has been education and a changing attitude to condoms that has led to a progressive fall in incidence, so that the worst of the epidemic may now be over. Modifying the immunological response during the quiescent phase with the hope of prolonging this phase indefinitely may be the way forward for those who are already infected. Steroids have been shown to have a possible role here rather than anti-retroviral drugs (ARVs) which are not curative and prone to the development of drug resistance. Limited personal experience suggests that steroids may also have a role in salvaging critically ill AIDS patients, who need to be treated as emergencies. With an educated public and attention to alternative routes of infection such as blood transfusion, the epidemic should be increasingly contained during the next 25 years, and may even fizzle out.
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PMID:HIV/AIDS: the first 25 years--a view from Nairobi. 1881 26

Tacrolimus is metabolized by CYP3A4 and CYP3A5 enzymes. Patients expressing CYP3A5 (in Caucasian patients about 15% of the population but more frequent in African Americans and Asians) have a dose requirement that is around 50% higher than non-expressers to reach the target concentration. CYP3A5 expressers can be considered fast metabolizers. The trough concentration/dose (C0/D) ratio of tacrolimus has recently been proposed as a prognostic marker for poor outcome after kidney transplantation. Patients with a low C0/D ratio (also referred to as fast metabolizers) seem to have more tacrolimus-related nephrotoxicity, more BK-viremia, and a lower graft survival. At first sight, the expression of CYP3A5 and a low C0/D ratio seem to be overlapping factors, both pointing towards patients in whom a higher tacrolimus dose is needed to reach the tacrolimus target concentration. However, there are important differences, and these differences may explain why the impact of the C0/D ratio on long term outcome is stronger than for CYP3A5 genotype status. Patients with a low C0/D ratio require a high tacrolimus dose and are exposed to high tacrolimus peak concentrations. The higher peak exposure to tacrolimus (and/or its metabolites) may explain the higher incidence of nephrotoxicity, BK-viremia and graft loss. A potential confounder is the concurrent maintenance treatment of corticosteroids, as steroids are sometimes continued in patients at high immunological risk. Steroids induce the metabolism of tacrolimus via pregnane X receptor mediated increased CYP3A4 expression, resulting in lower tacrolimus C0/D ratio in high risk patients. Also non-adherence may result in lower C0/D ratio which is also associated with poor outcome. The C0/D ratio of tacrolimus does seem to identify a group of patients with increased risk of poor outcome after kidney transplantation. Our recommendation is to monitor tacrolimus peak concentrations in these patients, and if these are high then target slightly lower pre-dose concentrations. Another possibility would be to switch to a prolonged release formulation or to dose the drug more frequently, in smaller doses, to avoid high peak concentrations.
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PMID:The Clinical Impact of the C0/D Ratio and the CYP3A5 Genotype on Outcome in Tacrolimus Treated Kidney Transplant Recipients. 3284 56