Split liver network: a collaborative internet-based scenario to expand the organ pool.

BACKGROUND: Split liver transplantation (SLT) has become a crucial option to maximize the liver pool, while organ procurement organizations (OPOs) usually allocate whole livers to single centers. In 2003, Italian Ministry of Health funded the Innovative Strategies to Expand Cadaveric Donor Pool for Liver Transplantation project with the goal to establish sharing criteria for SLT for two adults (SLT A/A), involving Italian transplantation centers, the North Italy Transplant OPO, and the Italian National Transplant Center. METHODS: SITF group defined donor/recipient inclusion criteria, setting minimum graft/recipient weight ratio (GRWR) at 1.2%. Donors and recipients on waiting list were shared on an Internet secured Web-based application (Split Liver Network [SLN]). SLN performs real-time matches between the registered donor and all patients on the bases of GRWR, displaying a size-based list of matched donor/patients, figuring hemiliver allocation once the whole organ is referred to a specific center. RESULTS: In the 2005 period, 47 donors and 124 patients were entered by nine centers, and six hemiliver allocations for three SLT A/A procedures were performed. By retrospective simulation of 32 donors and 613 recipients in the Nord Italia Transplant area, matchable recipients were available for all donors, while blood group frequency seemed a determining factor, more than donor body weight. COMMENTS: SLN hemiliver allocation might increase matching possibilities, offering a timely transplant for recipients of rare group, small-size, or in need of short wait. Our experience suggests that such an environment may be helpful to share a macroregional pool of liver recipients and to optimize SLT.

Risk of transmission of hepatitis B virus from anti-HBC positive cadaveric organ donors: a collaborative study.

Organ donors with a serologic profile of recovered (HBsAg negative and/or anti-HBc IgG positive) hepatitis B virus infection (HBV) have been reported to transmit HBV to recipients. In Italy, up until 2002, anti-HBc determination was not mandatory. We retrospectively evaluated the incidence of HBV transmission among recipients transplanted with organs from anti-HBc positive donors from 1997 to 1999. Anti-HBc was screened in 886 available sera among 964 HBsAg and anti-HCV negative donors. HBV transmission was evaluated in 325 kidney, liver, and heart recipients according to their pretransplant HBV serum profile. Of 210 anti-HBc positive donors, 185 were anti-HBc positive/anti-HBs positive and 25 anti-HBc positive/anti-HBs negative with a prevalence of 20.8% and 2.8%, respectively. One hundred seven sera (51%) were collected from donors after transfusion of blood components, the remainder were either before transfusion or from nontransfused donors. The 210 anti-HBc positive subjects donated 356 kidneys, 117 livers and 117 hearts, among whom follow-up is presently available for 251 kidney, 61 liver, and 25 heart recipients. No HBV transmission was observed independent of the recipient immunological profile among the kidney or heart recipients. In liver recipients, no transmission was reported in recovered or vaccinated patients, while a high incidence (43%) of de novo hepatitis was observed among naive patients. In conclusion, there does not seem to be a risk of transmitting HBV through anti-HBc positive transplants in heart and kidney recipients; only naive liver recipients are at high risk of HBV infection.

Red blood cell antioxidant and iron status in alcoholic and nonalcoholic cirrhosis.

BACKGROUND: Iron overload has been reported in alcoholic liver cirrhosis but it remains to be established whether iron is involved in inducing oxidative damage to erythrocytes in alcoholic cirrhosis. The aim of this study was to assess oxidative damage and red cell indicators of antioxidant defences in alcoholics with mild-to-severe liver cirrhosis, taking into account the iron status. MATERIALS AND METHODS: Twenty-nine patients with alcoholic liver cirrhosis (AC) and 27 with nonalcoholic cirrhosis (NAC) were studied. Serum lipid peroxides (LPO) were assayed by a colourimetric method. Serum-free malonyldialdehyde (MDA) was assayed by selected ion monitoring in positive chemical ionization; serum 4-hydroxy-2(E)-nonenal (4-HNE) was determined by a colorimetric method. Reduced (GSH) and oxidized glutathione (GSSG), adenine and pyridine cofactors were assayed in whole blood extracts by HPLC. Hexose-monophosphate shunt (HMPS), glycolytic pathway (EMP) and antioxidant enzyme activities were determined by standard methods. Iron status was evaluated by standard clinical chemistry and by histological grading of liver iron. Nontransferrin-bound iron (NTBI) was measured in serum by HPLC. RESULTS: GSH progressively decreased with increasing severity of liver involvement in AC and NAC. MDA, 4-HNE and NTBI were significantly higher in AC serum. Stimulation of red cell HMPS and reducing potential, in terms of NADPH production, were more pronounced in AC. CONCLUSIONS: These results suggest that NTBI is more important than the decrease of antioxidant defences in inducing lipid peroxidation. NTBI may play a catalytic role in free radical reactions in the presence of cellular reductants such as NADPH.

Non-transferrin-bound iron in alcohol abusers.

BACKGROUND: Non-transferrin-bound iron, a low-molecular-weight iron complex capable of initiating free radical formation and lipid peroxidation, has been detected in the serum of animals experimentally fed with alcohol, but no data have been reported in alcohol abusers. The purpose of this study was to evaluate whether non-transferrin-bound iron is present in chronic alcohol abusers with liver involvement and whether alcohol plays any part in its appearance. METHODS: We measured non-transferrin-bound iron in a cohort of chronic alcohol abusers with and without liver cirrhosis at presentation, when 43 were active abusers and 33 were abstainers, and in a smaller group during a follow-up period. RESULTS: At presentation, non-transferrin-bound iron was detectable in 83.7% of active abusers but only in 21.2% of abstainers, and within the group of abusers, patients with cirrhosis had significantly higher non-transferrin-bound iron than patients without. Non-transferrin-bound iron was present not only in patients with transferrin saturation >45% but also in those with transferrin saturation < or =45%. Multiple regression analyses revealed that only alcohol intake and total bilirubin were associated independently with non-transferrin-bound iron values. Longitudinal study confirmed the data of the cross-sectional study. CONCLUSIONS: Non-transferrin-bound iron could have a role in initiating or promoting alcohol-induced liver damage.

Carbohydrate-deficient transferrin, a sensitive marker of chronic alcohol abuse, is highly influenced by body iron.

Carbohydrate-deficient transferrin (CDT), a microheterogeneous form of serum transferrin (Tf), has been proposed as the most reliable marker of chronic alcohol consumption, although unexplained false-positive and -negative results have been reported. We investigated whether body iron influenced CDT serum levels by studying alcohol abusers with or without iron overload and nonabusers with iron deficiency or iron overload caused by genetic hemochromatosis (GH). In alcohol abusers, CDT was significantly lower in the presence of iron overload than in the absence (24.6 +/- 16.5 U/L vs. 33.3 +/- 11.7 U/L; P <.01), with false-negative results almost exclusively in patients with iron overload. Similarly, in nonabusers with GH, CDT was lower than in normal controls (9.6 +/- 2. 2 U/L vs. 15.7 +/- 3.3 U/L; P <.0001), whereas, patients with iron deficiency anemia had significantly higher levels than controls (28. 1 +/- 5.8 U/L vs. 15.7 +/- 3.3 U/L; P <.0001). In nonabusers, iron supplementation therapy significantly decreased CDT levels in patients with iron deficiency anemia (33.7 +/- 6.6 U/L vs. 21.7 +/- 5.2 U/L; P =.0007), while iron-depletion treatment significantly increased CDT levels in patients with GH (9.7 +/- 2.0 U/L vs. 14.7 +/- 4.0 U/L; P =.001). Alcohol abusers had a significant relationship between liver iron concentration (LIC) and the reciprocal of CDT (r =.65; P <.0001), while in nonabusers, there was a significant correlation between Tf and CDT (r =.72; P <.0001). In conclusion, CDT serum levels are markedly affected by the patient's iron status, with iron overload reducing its sensitivity in alcohol abusers and iron deficiency its specificity in nonabusers. CDT can be considered a reliable marker of alcohol abuse only when iron stores are normal.

Binding and suppressive activity of human recombinant ferritins on erythroid cells.

We studied the relation between ferritin cellular binding and suppressive activity of recombinant H- and L-ferritin on human erythroid cells at different proliferation/differentiation phases. L-ferritin failed to show any suppressive activity or detectable binding to erythroblasts at any stage of maturation. In contrast, H-ferritin demonstrated binding to erythroblasts derived from peripheral BFU-E cells which increased steadily between 7-14 days of culture up to 15,000 molecules per cell. Reticulocytes and erythrocytes failed to bind either L- or H-ferritin. H-ferritin suppressed BFU-E colony formation and reduced K562 cell proliferation at nanomolar concentrations. This suggests that the expression of H-ferritin binding sites is modulated by cellular proliferation and differentiation, that cells expressing H-ferritin binding sites are sensitive to ferritin suppressive activity and that a causal relation exists between ferritin cellular binding and suppressive activity.

Effect of estrogens and progesterone on human peripheral erythroid burst-forming unit (BFU-E) growth.

Variations in the number of peripheral burst-forming unit--erythroid (BFU-E) of healthy women were observed during a prolonged period of observation. These differences were related to different phases of the menstrual cycle. A peak in the number of BFU-E occurred on day 14 of the cycle corresponding to the serum 17-beta-estradiol peak. The effect of estrogens and progesterone on the in vitro growth of peripheral BFU-E of healthy women was assayed. Estrogens demonstrated a stimulatory and progesterone an inhibitory effect in total lymphomonocyte cultures, whereas neither hormone had an effect in monocyte-depleted cultures. Prostaglandin E1 (PGE1) which is known to be secreted by monocytes, stimulated the in vitro growth of peripheral BFU-E. These data suggest that estrogens and progesterone could have a role in the in vitro growth of peripheral BFU-E, probably mediated by monocytes.