Liver and intestine transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73604/1/j.1600-6135.2004.00400.x.pd

Failure of Fibrotic Liver Regeneration in Mice Is Linked to a Severe Fibrogenic Response Driven by Hepatic Progenitor Cell Activation

Failure of fibrotic liver to regenerate after resection limits therapeutic options and increases demand for liver transplantation, representing a significant clinical problem. The mechanism underlying regenerative failure in fibrosis is poorly understood. Seventy percent partial hepatectomy (PHx) was performed in C57Bl/6 mice with or without carbon tetrachloride (CCl4)-induced liver fibrosis. Liver function and regeneration was monitored at 1 to 14 days thereafter by assessing liver mass, alanine aminotransferase (ALT), mRNA expression, and histology. Progenitor (oval) cell mitogen tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and TWEAK-neutralizing antibody were used to manipulate progenitor cell proliferation in vivo. In fibrotic liver, hepatocytes failed to replicate efficiently after PHx. Fibrotic livers showed late (day 5) peak of serum ALT (3542 ± 355 IU/L compared to 93 ± 65 IU/L in nonfibrotic livers), which coincided with progenitor cell expansion, increase in profibrogenic gene expression and de novo collagen deposition. In fibrotic mice, inhibition of progenitor activation using TWEAK-neutralizing antibody after PHx resulted in strongly down-regulated profibrogenic mRNA, reduced serum ALT levels and improved regeneration. Failure of hepatocyte-mediated regeneration in fibrotic liver triggers activation of the progenitor (oval) cell compartment and a severe fibrogenic response. Inhibition of progenitor cell proliferation using anti-TWEAK antibody prevents fibrogenic response and augments fibrotic liver regeneration. Targeting the fibrogenic progenitor response represents a promising strategy to improve hepatectomy outcomes in patients with liver fibrosis

Impact of substance abuse on access to renal transplantation.

Abstract Background: With an ever-increasing demand for kidneys and limited supply pool, it is essential to understand the balance between utility and equity in transplant access. The goal of this project was to evaluate the association between recipient\u27s substance abuse and renal transplant access in patients with end-stage renal disease (ESRD). Methods: We used data from the United States Renal Data System. The primary variables of interest were abuse of alcohol, tobacco, or illicit drugs based on information from Centers for Medicare & Medicaid Services form 2728. We analyzed three outcomes in Cox model: (1) being placed on the waiting list for renal transplantation or transplanted (whichever occurred first); (2) first transplant in patients who were placed on the waiting list; and (3) graft loss or mortality after transplant. In addition, we performed subgroup analysis based on age, race, sex, diabetic status, and donor type. Results: We analyzed 1,077,699 patients (age of ESRD onset 62.9±15.5 years, 54.1% males, 64.2% white, and 29.7% African American). When compared with those with no substance abuse, abusing all three substances was associated with reduced transplant access (hazard ratio 0.39, P\u3c0.001 for wait listing/transplant; hazard ratio 0.67, P=0.019 for transplant). This trend was similar in most subgroups studied. Conclusion: We demonstrated that patients with ESRD abusing or dependent on tobacco, alcohol, or illicit drugs are less likely to be placed on the waiting list for kidney transplant; and once on the list are less likely to be transplanted. The possible utility justifications for such disparity and potential interventions are discussed

Increasing time delay from presentation until surgical referral for hepatobiliary malignancies

AbstractBackgroundStudies have shown that delayed treatment of several non-hepatobiliary (HB) malignancies is associated with adverse effects on disease progression and survival. Delayed treatment of HB malignancies has not been thoroughly investigated.MethodsWe performed a retrospective institutional review of patients referred to the Hepatobiliary Surgery Service at Beth Israel Deaconess Medical Center (BIDMC) for hepatobiliary malignancies from 2002 to 2008. Primary outcomes included the time delays (TD) in patient workup. Secondary outcomes were reasons for delay as well as disparities in TD based on demographic factors.ResultsMultivariate-adjusted linear regression showed a significant trend of increasing time from presentation until referral to a HB surgeon over the 7-year period (P= 0.001). There were no differences in TD by gender, age or education level. Multivariate-adjusted linear regression showed a significant trend of increasing number of imaging tests performed prior to referral [computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasound and endoscopic ultrasound (US/EUS)] (P < 0.001). Multivariate-adjusted linear regression in resectable patients showed a significant difference in overall length of survival in those with a TD1 > 30 days compared with those with a TD1 (TD from presentation until referral) <30 days (P= 0.042).ConclusionsDelays were associated with an increase in imaging studies and delays adversely affect survival in resected patients. Referring physicians are encouraged to expedite the evaluation and early referral of all patients to an HB surgeon for evaluation and treatment

Liver and intestine transplantation: summary analysis, 1994–2003

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72721/1/j.1600-6135.2005.00839.x.pd