Laboratory test results after living liver donation in the adult-to-adult living donor liver transplantation cohort study

Information on the long-term health of living liver donors is incomplete. Because changes in standard laboratory tests may reflect the underlying health of donors, results before and after donation were examined in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). A2ALL followed 487 living liver donors who donated at 9 US transplant centers between 1998 and 2009. The aminotransferase [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and alkaline phosphatase (AP) activities, bilirubin, international normalized ratio (INR), albumin, white blood cell count (WBC), hemoglobin (HGB), platelet count, ferritin, serum creatinine (SCR), and blood urea nitrogen (BUN) were measured at the evaluation and after donation (1 week, 1 month, 3 months, 1 year, and yearly thereafter). Repeated measures models were used to estimate median laboratory values at each time point and to test for differences between values at the evaluation (baseline) and postdonation time points. Platelet counts were significantly decreased at every time point in comparison with the baseline, and at 3 years, they were 19% lower. Approximately 10% of donors had a platelet count < 150 × 1000/mm 3 2 to 3 years post-donation. Donors with a platelet count ≤ 150 × 1000/mm 3 at 1 year had significantly lower mean platelet counts (189 ± 32 × 1000/mm 3 ) versus the remainder of the cohort (267 ± 56 × 1000/mm 3 , P < 0.0001) at the evaluation. Statistically significant differences compared to the evaluation values were noted for AST, AP, INR, and albumin through the first year, although most measurements were in the normal range. The median values for WBC, HGB, ferritin, albumin, SCR, BUN, and INR were not substantially outside the normal range at any time point. In conclusion, after 3 months, most laboratory values return to normal among right hepatic lobe liver donors, with a slower return to baseline levels for AST, AP, INR, and albumin. Persistently decreased platelet counts warrant further investigation. Liver Transpl, 2011. © 2011 AASLD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83476/1/22246_ftp.pd

Household crowding, social mixing patterns and respiratory symptoms in seven countries of the African meningitis belt.

OBJECTIVES: To describe the variation in household crowding and social mixing patterns in the African meningitis belt and to assess any association with self-reported recent respiratory symptoms. METHODS: In 2010, the African Meningococcal Carriage Consortium (MenAfriCar) conducted cross-sectional surveys in urban and rural areas of seven countries. The number of household members, rooms per household, attendance at social gatherings and meeting places were recorded. Associations with self-reported recent respiratory symptoms were analysed by univariate and multivariate regression models. RESULTS: The geometric mean people per room ranged from 1.9 to 2.8 between Ghana and Ethiopia respectively. Attendance at different types of social gatherings was variable by country, ranging from 0.5 to 1.5 per week. Those who attended 3 or more different types of social gatherings a week (frequent mixers) were more likely to be older, male (OR 1.27, p<0.001) and live in urban areas (OR 1.45, p<0.001). Frequent mixing and young age, but not increased household crowding, were associated with higher odds of self-reported respiratory symptoms (aOR 2.2, p<0.001 and OR 2.8, p<0.001 respectively). A limitation is that we did not measure school and workplace attendance. CONCLUSION: There are substantial variations in household crowding and social mixing patterns across the African meningitis belt. This study finds a clear association between age, increased social mixing and respiratory symptoms. It lays the foundation for designing and implementing more detailed studies of social contact patterns in this region

Recipient Morbidity After Living and Deceased Donor Liver Transplantation: Findings from the A2ALL Retrospective Cohort Study †

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72284/1/j.1600-6143.2008.02440.x.pd

Health-related quality of life and survival in liver transplant candidates.

Health-related quality of life (HRQOL) is an important measure of the effects of chronic liver disease in affected patients that helps guide interventions to improve well-being. However, the relationship between HRQOL and survival in liver transplant candidates remains unclear. We examined whether the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the Short Form 36 (SF-36) Health Survey were associated with survival in liver transplant candidates. We administered the SF-36 questionnaire (version 2.0) to patients in the Pulmonary Vascular Complications of Liver Disease study, a multicenter prospective cohort of patients evaluated for liver transplantation in 7 academic centers in the United States between 2003 and 2006. Cox proportional hazards models were used with death as the primary outcome and adjustment for liver transplantation as a time-varying covariate. The mean age of the 252 participants was 54 +/- 10 years, 64% were male, and 94% were white. During the 422 person years of follow-up, 147 patients (58%) were listed, 75 patients (30%) underwent transplantation, 49 patients (19%) died, and 3 patients were lost to follow-up. Lower baseline PCS scores were associated with an increased mortality rate despite adjustments for age, gender, Model for End-Stage Liver Disease score, and liver transplantation (P for the trend = 0.0001). The MCS score was not associated with mortality (P for the trend = 0.53). In conclusion, PCS significantly predicts survival in liver transplant candidates, and interventions directed toward improving the physical status may be helpful in improving outcomes in liver transplant candidates

A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis

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Water maser emission and the parsec-scale jet in NGC 3079

We have conducted VLBI observations of water maser and radio continuum emission in the nucleus of NGC 3079. The 22 GHz maser emission arises in compact clumps, distributed along an axis that is aligned with the major axis of the galactic disk. The velocities of the masers are consistent with their lying in the inner parsec of a molecular disk rotating in the same sense as the rest of the galaxy. However, the velocity field has a significant non-rotational component, which may indicate supersonic turbulence. The bright maser emission is not coincident with any detected compact 22 GHz continuum source, suggesting the high apparent luminosity of the maser may not due to beamed amplification of continuum emission. We observed two compact continuum sources that have inverted spectra between 5 and 8 GHz, and steep spectra between 8 and 22 GHz. NGC 3079 may be a nearby, low-luminosity example of the class of compact symmetric gigahertz-peaked spectrum (GPS) radio sources. We detected a third continuum component that lies along the same axis as the other two, strongly suggesting that this galaxy possesses a nuclear jet. Faint maser emission was detected near this axis, which may indicate a second population of masers associated with the jet.Comment: 31 pages, includes 8 figures. To appear in ApJ, Vol 495, 10 March 1998. Full-resolution figures and color plate available at http://cfa-www.harvard.edu/~trotter/ngc3079.htm

Severe Psychiatric Problems in Right Hepatic Lobe Donors for Living Donor Liver Transplantation

The morbidity and mortality from donation of a right hepatic lobe for living donor liver transplantation (LDLT) is an important issue for this procedure. We report the prevalence of severe psychiatric postoperative complications from the Adult-to-Adult Living Donor Liver Transplantation Cohort study (A2ALL), which was established to define the risks and benefits of LDLT for donors and recipients

Outcomes of donor evaluation in adult-to-adult living donor liver transplantation

The purpose of donor evaluation for adult-to-adult living donor liver transplantation (LDLT) is to discover medical conditions that could increase the donor postoperative risk of complications and to determine whether the donor can yield a suitable graft for the recipient. We report the outcomes of LDLT donor candidates evaluated in a large multicenter study of LDLT. The records of all donor candidates and their respective recipients between 1998 and 2003 were reviewed as part of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). The outcomes of the evaluation were recorded along with demographic data on the donors and recipients. Of the 1011 donor candidates evaluated, 405 (40%) were accepted for donation. The donor characteristics associated with acceptance (P < 0.05) were younger age, lower body mass index, and biological or spousal relationship to the recipient. Recipient characteristics associated with donor acceptance were younger age, lower Model for End-stage Liver Disease score, and shorter time from listing to first donor evaluation. Other predictors of donor acceptance included earlier year of evaluation and transplant center

Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis

BACKGROUND &amp; AIMS: Obeticholic acid (OCA) is a first-in-class farnesoid X receptor agonist and antifibrotic agent in development for the treatment of pre-cirrhotic liver fibrosis due to non-alcoholic steatohepatitis (NASH). We aimed to validate the original 18-month liver biopsy analysis from the phase III REGENERATE trial of OCA for the treatment of NASH with a consensus panel analysis, provide additional histology data in a larger population, and evaluate safety from &gt;8,000 total patient-years' exposure with nearly 1,000 participants receiving study drug for &gt;4 years.METHODS: Digitized whole-slide images were evaluated independently by panels of three pathologists using the NASH Clinical Research Network scoring system. Primary endpoints were (1) ≥1 stage improvement in fibrosis with no worsening of NASH or (2) NASH resolution with no worsening of fibrosis. Safety was assessed by laboratory values and adverse events.RESULTS: Prespecified efficacy analyses included 931 participants. The proportion of participants achieving a ≥1 stage improvement in fibrosis with no worsening of NASH was 22.4% for OCA 25 mg vs. 9.6% for placebo (p &lt;0.0001). More participants receiving OCA 25 mg vs. placebo achieved NASH resolution with no worsening of fibrosis (6.5% vs. 3.5%, respectively; p = 0.093). Histology data in a larger population of 1,607 participants supported these results. Safety data included 2,477 participants. The incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and deaths was not substantively different across treatment groups. Pruritus was the most common TEAE. Rates of adjudicated hepatic, renal, and cardiovascular events were low and similar across treatment groups.CONCLUSIONS: These results confirm the antifibrotic effect of OCA 25 mg. OCA was generally well tolerated over long-term dosing. These data support a positive benefit:risk profile in patients with pre-cirrhotic liver fibrosis due to NASH.IMPACT AND IMPLICATIONS: Patients with non-alcoholic steatohepatitis (NASH) often have liver scarring (fibrosis), which causes an increased risk of liver-related illness and death. Preventing progression of fibrosis to cirrhosis or reversing fibrosis are the main goals of drug development for NASH. In this clinical trial of obeticholic acid (OCA) in patients with NASH (REGENERATE), we reaffirmed our previous results demonstrating that OCA was superior to placebo in improving fibrosis using a more rigorous consensus panel analysis of liver biopsies taken at month 18. We also showed that OCA treatment resulted in dose-dependent reductions of serum liver biochemistries and liver stiffness measurements compared with placebo, even in participants in whom histologic fibrosis did not change at 18 months, providing evidence that the benefit of OCA extends beyond what is captured by the ordinal NASH CRN scoring system. OCA was well tolerated with a favorable safety profile supporting a positive benefit: risk profile in patients with pre-cirrhotic liver fibrosis due to NASH.</p