Project HELP: a study protocol to pilot test a shared decision-making tool about treatment options for patients with hepatitis C and chronic kidney disease.

BACKGROUND: Recent advances in treatment have given patients with chronic kidney disease (CKD) access to safer and more effective medications to treat comorbid hepatitis C virus (HCV) infection. Given the variety and complexity of treatment options that depend on patients' clinical characteristics and personal preferences, education and decision support are needed to prepare patients better to discuss treatment options with their clinicians. METHODS: Drawing on International Patient Decision Aids Standards guidelines, literature reviews, and guidance from a diverse expert advisory group of nephrologists, hepatologists, and patients, we will develop and test a HCV and CKD decision support tool. Named Project HELP (Helping Empower Liver and kidney Patients), this tool will support patients with HCV and CKD during decisions about whether, when, and how to treat each illness. The tool will (1) explain information using plain language and graphics; (2) provide a step-by-step process for thinking about treating HCV and CKD; (3) tailor relevant information to each user by asking about the individual's stage of CKD, stage of fibrosis, prior treatment, and comorbidities; (4) assess user knowledge and values for treatment choices; and (5) help individuals use and consider information appropriate to their values and needs to discuss with a clinician. A pilot study including 70 individuals will evaluate the tool's efficacy, usability, and likelihood of using it in clinical practice. Eligibility criteria will include individuals who understand and read English, who are at least 18 years old, have a diagnosis of HCV (any genotype) and CKD (any stage), and are considering treatment options. DISCUSSION: This study can identify particular characteristics of individuals or groups that might experience challenges initiating treatment for HCV in the CKD population. This tool could provide a resource to facilitate patient-clinician discussions regarding HCV and CKD treatment options.

Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management.

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

Reproducibility of glucose, fatty acid and VLDL kinetics and multi-organ insulin sensitivity in obese subjects with non-alcoholic fatty liver disease.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities in basal glucose and free fatty acid (FFA) metabolism, multi-organ insulin resistance and alterations in lipoprotein kinetics. These metabolic outcomes can be evaluated in vivo by using stable isotopically labeled tracer methods. An understanding of the reproducibility of these measures is necessary to ensure adequate statistical power in studies designed to evaluate metabolic function in subjects with NAFLD. METHODS: We determined the degree of intra-individual variability of skeletal muscle, adipose tissue, and hepatic insulin sensitivity and basal plasma glucose, FFA, and very-low-density lipoprotein triglyceride and apolipoprotein B-100 (apoB-100) kinetics in eight obese subjects with NAFLD (age: 44 ± 3 years; body mass index: 38.2 ± 1.7 kg m(-2); intrahepatic triglyceride content: 24.5 ± 3.9%), by using the hyperinsulinemic-euglycemic clamp technique and stable isotope-labeled tracer methods and mathematical modeling on two separate occasions ∼2 months apart. RESULTS: The intra-individual variability (coefficient of variation) ranged from 6% for basal glucose production to 21% for insulin-stimulated glucose disposal (percentage increase from basal). We estimated that a 25% difference in any outcome measure can be detected with a sample size of ≤ 8 subjects for paired studies and ≤ 15 subjects per group for unpaired studies, assuming an α value of 0.05 and a ß value of 0.20 (that is, 80% power). CONCLUSION: These results demonstrate that only a small number of subjects are needed to detect clinically relevant effects in insulin sensitivity and hepatic lipoprotein metabolism in obese subjects with NAFLD, and will be useful to determine appropriate sample size for future metabolic studies.

Long-term management of the liver transplant patient: recommendations for the primary care doctor.

No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient.

A yeast artificial chromosome contig from human chromosome 14q24 spanning the Alzheimer's disease locus AD3.

Familial Alzheimer's disease has been previously linked to three genetic loci on chromosomes 21, 19 and 14. The AD3 locus on chromosome 14 has not been cloned and the molecular defect in chromosome 14-linked AD3 families has yet to be identified. Genetic linkage analysis has placed the AD3 locus in band 14q24 between the dinucleotide markers D14S61 and D14S289, a genetic distance of approximately 6.4 cM. We have constructed a yeast artificial chromosome (YAC) contig that covers the entire minimal region, encompassing all genetic markers that are non-recombinant for the disease in AD3-linked families. This contig, constructed by using a combination of YAC end sequence walking and sequence-tagged site (STS) mapping, consists of 63 YACs from three different libraries. The AD3 contig contains 12 polymorphic dinucleotide repeat markers from D14S61 to D14S251, as well as an additional 43 non-polymorphic STSs. This contiguous physical map of the region will allow the physical distances between the markers to be determined, as well as providing a framework for the identification of candidate genes.