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Although most iron in plasma is bound to transferrin, recent evidence suggests that the nontransferrin-bound fraction contributes to hepatic iron loading and toxicity seen in iron-overload disorders. Our studies of isolated perfused rat liver previously demonstrated saturable uptake of nontransferrin-bound iron that continues despite hepatic iron overload. To further characterize the mechanism of transport of this form of iron, we measured binding of 55Fe-labeled ferrous ascorbate to rat liver plasma membrane vesicles under varying conditions. Binding of 5 mumol/L iron by both basolateral and canalicular membranes was time-dependent and linear for the first 5 sec. Initial rate of binding of ferrous ascorbate to basolateral membrane vesicles was temperature dependent and increased by calcium but, in contrast to the perfused rat liver, was not inhibited by other divalent cations. Binding velocities by basolateral membrane vesicles were saturable at increasing iron concentration (Km = 33 mumol/L, Vmax = 16 pmol/mg protein/sec). Ferrous iron binding by canalicular membrane vesicles was also temperature dependent, but initial association rates were not saturable over the concentration range studied (2 to 20 mumol/L). We conclude that nontransferrin-bound iron associates with basolateral liver plasma membrane vesicles by a saturable mechanism sensitive to temperature and calcium and consistent with a membrane carrier. Other divalent cations do not inhibit membrane association but may compete for a subsequent cytosolic binding site.

Background: Steroid minimization regimens have become increasingly popular for kidney transplant recipients. We studied outcomes for liver transplant recipients with a regimen using rapid discontinuation of prednisone (RDP). Results: The study group consisted of 83 recipients transplanted between June 2004 and January 2006. Immunosuppression consisted of tacrolimus, MMF, and two doses of basiliximab with six d of steroids. Patients with underlying autoimmune disorders (PSC, autoimmune hepatitis) were not included as they were maintained on steroids. The control group consisted of 83 recipients transplanted between January 2002 and May 2004. Immunosuppression consisted of tacrolimus, MMF and steroids, with no antibody induction. Mean MELD score at time of transplant was significantly higher in the steroid free group vs. the control group (28 vs. 23, p = 0.02); mean donor age was also higher (42 vs. 37 yr, p = 0.02). Other characteristics including recipient age, cold ischemic time, donor source, and cause of liver disease were similar (p = ns). Mean length of follow-up was 16.1 months in the RDP group and 32 months in the control group; a minimum of six months follow up was present for all patients. Patient and graft survival rates were not statistically different in the two groups (p = ns). Biopsy proven rejection was low in both groups and not significantly different (at one yr post-transplant 11% in the RDP group vs. 12% in control, p = 0.53). Based on protocol biopsy data, histologic recurrence of hepatitis C was demonstrated in 56% of the control group hepatitis C positive recipients vs. 39% in the RDP group (p = 0.05). There was a significantly lower incidence of post-transplant diabetes (PTDM) in the RDP vs. control group (at 6 months post-transplant 12% vs. 32%, p = 0.004). Conclusions: Rapid discontinuation of prednisone in liver transplant recipients is not associated with an increased risk of rejection, and may be associated with lower morbidity, especially PTDM and hepatitis C recurrence.

Compliance with complex immunosuppressant drug therapies in transplant recipients might be improved with regimens that require less frequent dosing. A once-daily extended release (XL) formulation of tacrolimus has been developed that allows a 1:1 conversion from the twice-a-day tacrolimus (TAC) formulation and has a good exposure to trough concentration correlation. In an open-label, multicenter study, stable liver transplant recipients (n=69) were converted from twice-a-day TAC to XL once-daily in the morning, and were maintained for at least 2 years postconversion using the same therapeutic monitoring and patient care techniques employed with TAC. Two years after conversion, the incidence of biopsy-confirmed acute rejection was 5.8% (4 of 69); patient and graft survival was 98.6% (68 of 69). The safety profile of XL was consistent with that previously reported for TAC. Liver transplant recipients can be converted from twice-a-day TAC to once-daily XL and maintained for at least 2 years postconversion with neither unique efficacy nor safety concerns.

The number of liver transplants performed yearly has slowly and steadily increased over the last 10 years, reaching 6441 procedures in 2005. The number of living donor liver transplants performed rose steadily from 1996 to 2001, when it peaked at 519; since 2003 there have been approximately 320 such procedures performed each year. The continual increase in the size of the waiting list for a liver transplant, which peaked in 2001 at 14 897 patients, was interrupted in 2002 by the implementation of the allocation system based on the model for end-stage liver disease and pediatric end-stage liver disease (MELD/PELD). Activity in all areas of intestinal transplantation continues to increase. One-year patient and graft survival following intestine-alone transplantation now seem to be superior to outcomes following liver-intestine transplantation. Other topics covered here include the recent ‘Share 15’ component of the MELD allocation system; liver transplantation following donation after cardiac death; simultaneous liver-kidney transplantation and waiting list and post-transplant outcomes for both liver and intestine transplantation, broken out by a variety of clinical and demographic factors.

268 www.thelancet.com/infection Vol 15 March 2015 but similar to what has been described in other extrahepatic manifestations related to HEV infection. In all reported cases thus far, HEV RNA in the cryoprecipitate was not assessed. In view of the growing interest in HEV infection and prevention, especially in immunosuppressed patients, more studies are needed to further delineate the HEV extrahepatic manifestations and their immunopathogenesis.

Background Neoral is a microemulsion formulation of cyclosporine that has a better pharmacokinetic profile than the standard formulation (Sandimmune). To prove the safety of converting stable liver transplant patients from Sandimmune to Neoral, we conducted a prospective trial involving 54 patients. Method. The average time from transplantation to conversion was 48.5±21.6 months. Thirty of 54 patients (55%) required a dose reduction during the study for various reasons. Five of 30 patients had the first dose reduction because of increased levels of cyclosporine. Seven patients required more than one dose reduction. Results. Sixteen patients suffered serious adverse events. Six patients had a biopsy-proven rejection. Four of 6 patients had trough cyclosporine levels within 20% of baseline value immediately before developing rejection. Conclusion. Converting patients from the standard formulation to the microemulsion formulation of cyclosporine seems to expose stable patients to unnecessary risks.

Mycophenolate mofetil (MMF) used in a triple-drug regimen has been shown to decrease acute rejection rates, compared to a double-drug regimen. The impact of MMF on late acute rejection (LAR) episodes has not been well described. To investigate the risk of LAR (rejection ≥6 months post-transplantation) data from the Scientific Registry of Transplant Recipients (SRTR) were used. We studied adult primary liver transplant recipients transplanted between June 1, 1995, and April 30, 2004, with hepatitis C virus (HCV) (n = 3356), hepatitis B virus (HBV) (n = 550) or a nonviral (n = 5740) primary cause of liver disease who were recorded as receiving continuous 3-(MMF + Tacro + steroids) versus 2-drug (Tacro + steroids) therapy for at least 6 months immediately post transplantation. Kaplan–Meier analysis showed significantly lower LAR rates 4 years post-transplant in 3- versus 2-drug HCV, HBV and nonviral disease patients. Multivariate regression confirmed 3- versus 2-drug therapy to be associated with a decreased risk of LAR. Late graft survival was significantly lower at 4 years post-transplant for patients with LAR 6–12 months post-transplantation versus patients with early rejection (78.0% vs. 87.0%, p < 0.001) and no rejection (88.1%, p < 0.001). Three-drug versus 2-drug therapy for a minimum of 6 months may offer a better treatment strategy to avoid the consequences and expense of LAR episodes.

Background: We examined outcomes in recipients who underwent a liver transplant for HBV-induced liver disease and received a protocol for prophylaxis that did not use HBIG maintenance. Results: Between October 2002 and July 2005, a total of 14 liver transplant recipients were identified that met the study criteria. Mean recipient age was 47.6 yr; mean donor age was 37.2 yr. Category of transplant was as follows: cadaveric liver (n=10, 71%), cadaveric split-liver (n=2, 14%), and cadaveric liver–kidney (n=2, 14%). Liver disease was diagnosed at a mean of 7.3 yr before transplant; three (21%) had a coexisting hepatocellular cancer at the time of transplant. Pre-transplant, all 14 (100%) recipients were hepatitis B surface antigen (HBsAg) positive, and 11 (79%) were HBV DNA positive (mean viral load of 251.2 pg/mL). Three (21%) were E antigen positive, and one (7%) was D antigen positive. Pre-transplant, seven patients (50%) were on anti-viral therapy and there was documented diminution in viral loads after initiating anti-viral therapy in 3 cases. Three (21%) were hepatitis C virus (HCV) antigen positive and all had low-RNA titers. With mean follow-up of 14.1 months, all 14 patients are alive with a functioning graft. Mean ALT, AST and total bilirubin values are currently at 43.2, 32.2, and 0.84, respectively. One recipient remains HBsAg surface antigen positive post-transplant but has normal lab values. The remaining recipients have no evidence of HBV recurrence by serology and protocol biopsies. The regimen has been well tolerated without the need for drug reduction or discontinuation because of side-effects. Conclusion: Longer follow-up is needed, but this regimen may represent an alternative to chronic HBIG maintenance therapy.

The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C–positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 ± 50 days) than with tacrolimus (70 ± 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 μmol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline. Liver Transpl 12:1464–1472, 2006. © 2006 AASLD.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.

Immunosuppression is often incriminated for the increased risk of post-transplant malignancies. To examine whether triple- (MMF+Tacro+CS) versus dual-drug therapy (Tacro+CS) is associated with an increased incidence of malignancy, or death due to malignancy, data from a large registry of liver transplant recipients were analyzed. Data from adult primary liver recipients reported to the Scientific Registry of Transplant Recipients between June 1, 1995, and April 30, 2004, and recorded at transplant on triple-drug (n = 9180) or dual-drug (n = 10 099) therapy were included. Kaplan-Meier survival analysis showed no significant differences in death due to malignancy 4 years post-transplantation between the treatment groups. Multivariable analysis using Cox proportional hazard models confirmed no differences in risk of death due to malignancy between the groups (HR: 0.83, p = 0.107). Incidence of any post-transplant malignancy was also not significantly different. Older recipient age and cause of liver disease were significantly associated with an increased risk of malignancy-related death. These data utilizing relatively short follow-up suggest the addition of MMF to Tacro+CS at transplant is not associated with death due to malignancy, at least in the short term. Individual recipient factors appear to be important risk factors for malignancy-related death; elucidating these risk factors can assist in identifying who should be monitored most aggressively for post-transplant malignancies.

This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.

To evaluate the impact of mycophenolate mofetil (MMF) on long-term outcomes of tacrolimus and corticosteroids, we analyzed data reported to the Scientific Registry of Transplant Recipients for 11,670 adult patients (3463 with hepatitis C [HCV]) who underwent primary, single-organ, liver transplantation between 1995 and 2001. Patients who were discharged from the hospital on tacrolimus-based immunosuppression with (n = 4466; n = 1323 HCV) or without MMF (n = 7204; n = 2140 HCV) were included in the analysis. Recipients treated at discharge with MMF, tacrolimus, and corticosteroids had significantly increased patient survival (81.0% vs. 77.0% at 4 years, P < 0.0001) and graft survival (76.4% vs. 72.9%, P < 0.0001), and lower rates of acute rejection (29.0% vs. 33.4%, P < 0.001) as compared to recipients treated at discharge with tacrolimus and corticosteroids alone. A trend toward lower rates of death from infection was observed (6.1% at 4 years for MMF vs. 7.1% at 4 years for tacrolimus and corticosteroids, P = 0.0508), but this result did not reach statistical significance. In multiple regression analyses, MMF triple therapy at discharge was associated with a reduced risk of death (hazard ratio [HR] = 0.77, P < 0.001), graft loss (HR = 0.81, P < 0.001), acute rejection (HR = 0.89, P = 0.002), and death from infectious complications (HR = 0.80, P = 0.007). Outcomes were similar for the cohort with HCV.In conclusion, the addition of MMF at discharge to tacrolimus-based immunosuppression is associated with improved long-term outcomes after liver transplantation in patients with and without HCV.

Concern remains regarding the possibly higher risk to living liver donors of the right lobe (RL), as compared with the left lateral segment (LLS). We studied outcomes and responses to quality of life (QOL) surveys in the two groups. From 1997 to 2004, we performed 49 living donor liver transplants (LDLTs): 33 RL and 16 LLS. Notable differences included a higher proportion of female and unrelated donors in the RL group. A significantly larger liver mass was resected in RL (vs. LLS) donors: 720 (vs. 310) g, p = 0.01; RL donors also had greater blood loss (398 vs. 240 mL, p = 0.04) and operative times (7.2 vs. 5.7 h, p = 0.05). However, those findings did not translate into significant differences in donor morbidity. The complication rate was 12.5% in LLS donors and 9.1% in RL donors (p = ns). Per a QOL survey at 6 months postdonation, no significant differences were noted in SF-12 scores for the two groups. Recovery times were somewhat longer for RL donors. Mean time off work was 61.0 days for RL donors and 32.4 days for LLS donors (p = 0.004). RL donation is associated with greater operative stress for donors, but not necessarily with a more complicated recovery or differences in QOL.

Summary. We present the case of a 61-year-old man with severe haemophilia A and a high-titre factor VIII inhibitor who underwent successful orthotopic liver transplantation (OLT) for hepatocellular carcinoma. Postoperatively, a modest early anamnestic response to FVIII was followed by immunological tolerance to FVIII. This case illustrates the technical feasibility of OLT in some patients with high-titre inhibitors to FVIII, and suggests that immune tolerance may be induced by endogenously produced FVIII from the transplanted organ.

Once regarded as a last-resort therapy for patients with end-stage liver disease, liver transplantation has become a viable therapeutic option because of sweeping improvements in surgical techniques and the development of more powerful immunosuppressive agents. The addition of tacrolimus to the immunosuppression regimen represents a highly potent therapy and a powerful defense against acute rejection. In the decade since tacrolimus was approved for use in the United States, it has become a widely used immunosuppressant in the field of liver transplantation.

Key Points 1. Recurrent hepatitis C is an increasing problem post-transplantation. 2. It is difficult to determine histologically if alloimmunity, i.e., rejection, is also plays a role in posttransplantation hepatitis C. 3. Change in the degree of immunosuppression, rather than the absolute amount of immunosuppression, is bad for HCV-infected recipients. 4. Corticosteroid boluses are bad for HCV-infected recipients.

A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor. Our aim was to assess the capability of the Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver recipients according to their severity of liver disease and mortality risk on the OPTN liver waiting list.The MELD model predicts liver disease severity based on serum creatinine, serum total bilirubin, and INR and has been shown to be useful in predicting mortality in patients with compensated and decompensated cirrhosis. In this study, we prospectively applied the MELD score to estimate 3-month mortality to 3437 adult liver transplant candidates with chronic liver disease who were added to the OPTN waiting list at 2A or 2B status between November, 1999, and December, 2001.In this study cohort with chronic liver disease, 412 (12%) died during the 3-month follow-up period. Waiting list mortality increased directly in proportion to the listing MELD score. Patients having a MELD score9 experienced a 1.9% mortality, whereas patients having a MELD scoreor =40 had a mortality rate of 71.3%. Using the c-statistic with 3-month mortality as the end point, the area under the receiver operating characteristic (ROC) curve for the MELD score was 0.83 compared with 0.76 for the Child-Turcotte-Pugh (CTP) score (P0.001).These data suggest that the MELD score is able to accurately predict 3-month mortality among patients with chronic liver disease on the liver waiting list and can be applied for allocation of donor livers.

The initial enthusiasm for performing orthotopic liver transplantation (OLT) on patients with chronic hepatitis B virus (HBV) infectionwas tempered in the early 1990s by a high rate of recurrent infection, with the subsequent development of severe recurrent hepatitis frequently leading to loss of the allograft.1 In the absence of effective therapy, recurrent infection, defined as the appearance after OLT of detectable hepatitis B surface antigen (HBsAg) in serum, occurred in 70% to 90%2 of patients who were HBsAg positive preoperatively. Subsequent histological findings of hepatitis were seen in most patients, including the lesion termed fibrosing cholestatic hepatitis.3 This lesion is marked by overexpression of HBV proteins in hepatocytes, with cellular swelling and cholestasis, but only minimal inflammation. These observations suggested that HBV may be directly cytopathic in the post-OLT setting. Fortunately, most patients who clear HBsAg after OLT have a normal liver on histological studies and a benign clinical course.2 Patients at greatest risk for developing recurrent HBV infection are those with chronic HBV infection and, in particular, detectable HBV DNA or hepatitis B e antigen in serum before OLT.2,4 Patients at lower risk for reinfection include patients with acute HBV infection and those coinfected with hepatitis D virus, which appears to suppress HBV replication. A major breakthrough came when several studies showed that hepatitis B immune globulin (HGIg) administered intravenously in high doses during and after OLT could substantially reduce the risk for reinfection, leading to improved survival rates.2,5-8 Using HBIg alone to prevent recurrent HBV infection was most effective in those at lower risk for recurrent infection, i.e., patients with hepatitis D virus coinfection or acute hepatitis B or those who were HBV DNA negative in serum.2,5 However, intravenous administration of HBIg is costly, i.e., currently $74,320 for eight daily doses of HBIg during the first week post-OLT and monthly thereafter and approximately $45,000 per annum after year 1 (local data). When used alone, it may be required for life. Late breakthroughs also have occurred in patients who develop a variety of mutations in the HBV S gene.9 For these reasons, there is an extreme need for true antiviral agents that might inhibit viral replication and prevent HBV reinfection when used pre-OLT. Several nucleoside analogues have been shown to meet such criteria.8,10,11 The first such agent, lamivudine, has been shown to markedly decrease the rate of HBV reinfection after OLT, even when administered alone.10,12 Lamivudine is very well tolerated and much less expensive than HBIg. The major limitation to its use is the development of resistance through viral mutation at the YMDD locus of the polymerase molecule.10,13,14 Resistance develops in up to 30% of transplant recipients by 1 year. Moreover, severe recurrent disease has occurred in patients after the development of viral breakthrough.11,13 Because of the problem of viral mutation leading to viral escape with the use of both lamivudine and HBIg, many programs have combined the use of lamivudine with HBIg.7,15,16 Neither the optimal dosage and treatment interval nor the utility of measuring antibody to HBsAg titers to monitor therapy in this setting have been established. However, it appears that much lower doses of HBIg are required when combined with lamivudine, and the rate of acquired viral resistance is much lower. Several groups have published excellent results using relatively low-dose HBIg administered intramuscularly, which reduces both the cost and side effects of HBIg.With such regimens, the rate ofHBV infection is down to 5% or less.7,15 Newer agents with antiviral activity against HBV include adefovir and entecavir. These agents are attractive in that they have activity against the YMDD mutant variants of HBV.11,13 In the future, we likely will use combinations of antiviral agents with differing sites of action to prevent HBV reinfection after OLT. In this current era, a key question is whether one needs to continue HBIg therapy for life. As stated, the use of HBIg adds substantially to the cost of performing OLT on patients with hepatitis B and, when adminisFrom the Liver Transplantation Program, University of Minnesota, Minneapolis, MN. Address reprint requests to John R. Lake, MD, University of Minnesota, Department of Medicine, 420 Delaware St, Box 36, Minneapolis, MN 55455. Telephone: 612-625-0684; FAX: 612-625-5620; E-mail: lakex009@umn.edu Copyright © 2002 by the American Association for the Study of Liver Diseases 1527-6465/02/0810-1016$35.00/0 doi:10.1053/jlts.2002.35978

The shortage of cadaver donor livers has been most severe for adult patients. Split liver transplantation is one method to expand the donor pool, but to have a significant impact on the waiting list, it needs to be applied for 2 adult recipients. We split livers from 6 cadaver donors, and transplanted 12 adult recipients. All splits were performed in situ with transection through the midplane of the liver, resulting in a right lobe and a left lobe graft. Mean donor age was 19.7 years; mean donor weight was 79.1 kg. Mean recipient age was 41.5 years. Mean weight of right lobe recipients was 89 kg; left lobe recipients, 60 kg. All donors were hemodynamically stable and had normal liver function tests. Mean operative time for the procurement was 7.4 h. Average blood loss during the transection of the liver was 490 mL. Mean GW/ RW ratio for all recipients was 0.87%; right lobe recipients, 0.86%; and left lobe recipients, 0.88%. With mean follow-up of 9.3 months, patient and graft survival rates were both 83.3%. There were 2 deaths: 1 after hepatic artery thrombosis (HAT) and subsequent multiorgan failure; the other after HAT, a liver retransplant, and subsequent gram-negative sepsis. The remaining 10 recipients are doing well. We observed no cases of primary nonfunction. Other complications included bile leak and/or stenosis (n = 3), bleeding from the Roux loop (n = 1), bleeding after percutaneous biopsy (n = 1), and incisional hernia (n = 1). In conclusion, split liver transplantation, using 1 cadaver liver for 2 adult recipients, can be performed successfully. Crucial to success is proper donor and recipient selection.

Split-liver transplantation is becoming a useful technique to expand the donor pool. Whether the split should be performed in situ or ex situ is not clear. One potential disadvantage of in situ splits is that prolonged surgical time and increased blood loss may negatively affect the function of other solid organs (kidneys, pancreas, and heart) procured from the same donor. Therefore, we studied the function of other organs posttransplantation. Between September 1, 1999, and March 31, 2000, we performed six in situ splits at the University of Minnesota (Minneapolis, MN). These six splits yielded six right-lobe liver grafts and six left-lobe liver grafts, which were transplanted into 12 adult-size recipients. Other grafts obtained from these six donors were as follows: kidney (n = 11), heart (n = 4), lungs (n = 1), pancreas (n = 2), and kidney-pancreas (n = 1). We then analyzed posttransplantation function of these grafts and the postoperative course of transplant recipients. All six donors were hemodynamically stable at the time of procurement. Mean donor age was 19.7 years. Mean surgical time for the procurement was 7.4 hours, with an average blood loss of 490 mL during in situ splitting of the liver. The 12 liver grafts showed good initial function with no primary nonfunction. The other organs also showed good function. Of 11 kidney recipients, only 1 patient developed delayed graft function, which resolved within 4 days. In addition, 1 kidney was lost early because of severe acute rejection. For the 10 recipients with functioning kidneys, mean creatinine level at hospital discharge was 2.0 mg/dL, and mean creatinine level after an average 9-month follow-up was 1.3 mg/dL. Of the 4 heart transplant recipients, 3 patients had good graft function immediately posttransplantation, with an ejection fraction greater than 60%, minimal inotropic requirements, and no surgical complications. The fourth heart transplant recipient, a critically ill status 1 patient, had poor initial function and a prolonged intensive care unit stay. At hospital discharge, pancreas and pancreas-kidney transplant recipients were all insulin free, with good urine amylase levels, no surgical or infectious complications, and no evidence of significant pancreatitis posttransplantation. The kidney of the pancreas-kidney transplant recipient functioned immediately; creatinine level after 7 months of follow-up was 1.2 mg/dL. Despite increased surgical time and blood loss, in situ splitting of liver grafts can be accomplished in stable donors without significant negative effects on other organs.

A 54-year-old man first learned that he had liver disease 5 years ago. He was complaining of aches and pains when his wife noticed that his eyes had turned yellow. He presented to the emergency room and was referred to the transplant evaluation clinic. Liver transplantation evaluation confirmed that the patient was infected with hepatitis C virus (HCV) genotype 1a. The viral copy number was 1.4 million copies/mL HCV RNA. In addition to jaundice, he had ascites and mild encephalopathy. He had been married for 25 years with 2 children. In the past he worked in construction, but he had not been able to work for 2 years before his initial presentation because of chronic back pain. Before recognition of liver disease, his normal pattern was to drink 2-4 beers a day. He answered negatively to all 4 CAGE questions. He stopped all alcohol when he was given the advice to stop on account of liver disease. He had no reaction to stopping alcohol. He had a history of one conviction for driving while impaired 25 years ago. He went to drivers education classes to get his license back. He agreed that he had “experimented” with intravenous drugs when he was a teenager. He was also tattooed when he was 18. There is a history of probable alcoholism affecting his mother. Antiviral therapy was not attempted, and the patient was placed on the transplant waiting list. Four years ago, he underwent orthotopic liver transplantation. Histopathological examination of the explanted liver revealed micronodular cirrhosis without neoplasm. He received posttransplantation immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone. He had no episodes of acute cellular rejection. Fifteen months after the transplant, when his immunosuppression had been reduced to just tacrolimus, he was treated with pegylated interferon alfa-2a and ribavirin. He was unable to tolerate this because of depression and because of “feeling terrible.” It was stopped after 8 weeks. Two years ago, results of a percutaneous liver biopsy showed one core of hepatic tissue with 14 portal tracts. The portal tracts contained moderate inflammation, comprising mostly lymphocytes and plasma cells, with occasional eosinophils and neutrophils. A few nodular lymphoid aggregates were also seen. There was mild interface hepatitis. One to 3 necroinflammatory foci were found per lobule. Occasional ballooned hepatocytes and acidophil bodies were seen. The parenchyma was negative for marked steatosis, Mallory hyaline, cholestasis, alpha-1 antitrypsin-like globules, and iron deposits. A Trichrome-stained slide showed portoportal fibrous bridging with rare portocentral fibrous bridging. There was mild pericellular fibrosis. In summary, these histopathological appearances were characterized as chronic HCV, grade 2, stage III, with mild pericellular fibrosis. For the past year, his main problem has been recurrent persistent intractable ascites. He underwent a transjugular intrahepatic portosystemic shunt placement 3 months ago. He was admitted to the hospital 2 months ago with encephalopathy. He was treated with increased lactulose, and although the symptoms improved, they did not resolve completely.

This study was designed to determine the cause of posttransplantation hepatitis in patients undergoing transplantation for liver disease of nonviral cause; the role of acquired hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis G virus (HGV) in posttransplantation hepatitis; and the course of posttransplantation hepatitis of unknown cause. Two hundred forty-three patients underwent transplantation for nonviral liver diseases (mean age, 48 years; 103 men, 140 women). Serological and virological assays for HBV and HCV were performed pretransplantation to exclude preexisting infection and posttransplantation to investigate the cause of posttransplantation hepatitis. Histology was graded on all available biopsy specimens; posttransplantation hepatitis was assessable in 150 patients. Posttransplantation hepatitis was present in 29% (44 of 150) of the patients after a median follow-up of 47 months (range, 1 to 101 months). Actuarial survival was significantly lower in patients with posttransplantation hepatitis compared with patients without (71% v 89% at 5-year follow-up; P 5 .03). HCV and HBV were identified posttransplantation in 14% and 9% of patients with hepatitis, respectively. After the exclusion of HCV and HBV infection, 22% (33 of 150) of the patients had posttransplantation hepatitis of unknown cause. HGV was present in 58% of these patients, but HGV was equally prevalent in patients without posttransplantation hepatitis. When patients with HBV and HCV were excluded, there was no difference in survival between patients with posttransplantation hepatitis compared with patients without (P 5 .08, log-rank test). Posttransplantation hepatitis was present in approximately 30% of the patients undergoing transplantation for nonviral diseases, with a median follow-up of 47 months. Known hepatitis viruses (HBV, HCV) were present in one fourth of the patients with posttransplantation hepatitis; 22% (33 of 150) of the patients had hepatitis of unknown cause, suggesting that other, as yet undiscovered, hepatitis viruses may exist. Copyright r 1998 by the American Association for the Study of Liver Diseases

Hepatic allograft rejection remains an important problem following liver transplantation, and, indeed, complications related to the administration of immunosuppressive therapy remain a predominant cause of posttransplantation morbidity and mortality. The Liver Transplantation Database (LTD) was used to study a cohort of 762 consecutive adult liver transplantation recipients and determined the incidence, timing, and risk factors for acute rejection. We also evaluated the impact of histological severity of rejection on the need for additional immunosuppressive therapy and on patient and graft survival. Four hundred ninety (64%) of the 762 adult liver transplantation recipients developed at least one episode of rejection during a median follow-up period of 1,042 days (range, 336-1,896 days), most of which occurred during the first 6 weeks after transplantation. Multivariate analysis revealed that recipient age, serum creatinine, aspartate transaminase (AST) level, presence of edema, donor/recipient HLA-DR mismatch, cold ischemic time, and donor age were independently associated with the time to acute rejection. An interesting observation was that the histological severity of rejection was an important prognosticator: the use of antilymphocyte preparations was higher, and the time to death or retransplantation was shorter, for patients with severe rejection. Findings from this study will assist in decision-making for the use of immunosuppressive regimens and call into question whether complete elimination of all rejection or alloreactivity is a desirable goal in liver transplantation.

Obesity is a concern in the long-term management of patients following liver transplantation, yet the risk of obesity and the factors that influence its development have not been well defined. We evaluated posttransplantation weight change among a cohort of 774 adults who had their height and weight recorded before liver transplantation at three major centers. Obesity was defined as a body mass index (BMI) of at least 30 kg/m2. Weight at transplantation was adjusted by the amount of ascites removed. Mean BMI increased from 24.8 kg/m2 pretransplantation to 27.0 kg/m2 in the first posttransplantation year, to 28.1 kg/m2 in the second year, and very little with subsequent observation. Among 320 patients who were not obese before transplantation, 21.6% became obese within 2 years after transplantation. On evaluation of numerous potential donor and pretransplantation risk factors, greater recipient BMI, greater donor BMI, and being married were found to be predictors of subsequent obesity (P

The objective of this study was to analyze a series of patients with Enterococcus faecium infection following transjugular intrahepatic portosystemic shunts (TIPS) in order to define the risk factors, outcome, and role of treatment including hepatic transplantation. This study is a case series from a tertiary referral center for liver transplantation. The medical records of four patients referred to one teaching hospital in San Francisco between 1990 and 1995 for evaluation or management of Enterococcal infection following TIPS were reviewed. A review of the microbiology records of all 314 patients who underwent TIPS at that institution and a MEDLINE search were performed to assess whether any other cases existed. The effect of therapy on survival was assessed, in particular, the repeated use of TIPS and prolonged courses of antibiotics. All four patients had thrombosis of their TIPS at the time of diagnosis of enterococcal bacteremia. All were treated with prolonged courses of intravenous antibiotics. One patient had echocardiographic evidence of subacute bacterial endocarditis with chronic aortic insufficiency. In all cases, liver transplantation was contraindicated in the acute setting because of uncontrolled endovascular infection. Two of four patients survived; these were the only two patients who had had a successful repeat TIPS. Enterococcal bacteremia is a rare complication following TIPS but carries a high mortality. It usually occurs in the setting of technically difficult TIPS with shunt thrombosis. Management should be focused on long term antibiotics and attempts at reestablishment of portal decompression with another TIPS. Liver transplantation should not be considered until the infection is cleared. Prophylaxis for Enterococcus species should be considered in technically difficult or unsuccessful TIPS.

A multicenter, retrospective analysis of 623 liver transplant recipients was performed to define safe and effective cyclosporine doses and blood levels at various times after transplantation. Patient and graft survival were assessed as efficacy parameters, and serum creatinine and cholesterol levels as safety parameters. The mean daily cyclosporine dose was 12.1 mg/kg/d at 1 month posttransplantation and 5.5 mg/kg/d after 1 year. After 4 years, the mean cyclosporine dose was maintained at 4.0 mg/kg/d. Mean cyclosporine blood levels showed a similar trend. Patient and graft survival after 4 years of cyclosporine maintenance therapy were 72% and 67%, respectively. Both serum creatinine and cholesterol levels were stable over the study period, and neither correlated with cyclosporine dose. The cumulative incidence of biopsy-proven acute cellular rejection was 59% for early (6 months) episodes and 21% for late (or = 6 months) episodes. Patient and graft survival did not differ significantly between patients experiencing early or late acute rejection episodes and those who did using univariate analysis. The high patient and graft survival, low rejection rates, and lack of significant renal dysfunction or hypercholesterolemia suggest that the cyclosporine doses and blood levels described are safe and therapeutically effective.

Organ donors are a potential source of transmissible disease after transplantation. The aim of this study was to evaluate the risk of acquiring hepatitis B among transplantation recipients of livers from donors without serum hepatitis B surface antigen (HBsAg) but with antibody to hepatitis B core antigen (anti-HBc).The transplantation experience of four centers between 1989 and 1994 was reviewed. Recipients of livers from 674 donors were considered informative for hepatitis B virus transmission.Hepatitis B developed in 18 of 23 recipients of livers from anti-HBc-positive donors (78%) compared with only 3 of 651 recipients of anti-HBc-negative donor livers (0.5%) (P0.0001). HBsAg persisted in all recipients with donor-related hepatitis B. Liver histology showed chronic hepatitis of moderate severity in 2 of 13 recipients at 1 year and 5 of 8 recipients between 1.6 and 4.5 years from transplantation. Liver transplantation from an anti-HBc-positive donor was associated with decreased 4-year survival (adjusted mortality hazard ratio of 2.4; 95% confidence interval, 1.4-4.0).De novo posttransplantation hepatitis B infection occurs at a high rate in recipients of donors with anti-HBc. Transmission of hepatitis B through transplantation suggests that the virus may persist in the liver despite serological resolution of infection.

Objective: To evaluate the impact of surgical complications on length of stay and hospital charges after liver transplantation. Design: A retrospective economic evaluation of the outcomes during initial hospitalization after liver transplantation. Setting: University hospital treating referred patients. Patients: The study population was 109 patients undergoing 111 liver transplantations during fiscal year 1993. Main Outcome Measures: Hospital charges and length of stay during the initial hospitalization after liver transplantation. Multivariate regression methods were used to analyze the impact of surgical complications on costs. Results: Of the 111 transplantations, 30 (27%) had a surgical complication that required a return to the operating room during the initial hospitalization. The effect of a surgical complication was to increase the mean hospital charges (excluding physician charges) from $150 092 to $347 728 (difference of mean, $197 636; confidence interval of difference, $114 153 to $319 326). The median length of stay was 16 days for patients without complications and 45 days for those with complications. Univariate and multivariate models suggested that surgical complications had the greatest effect on length of stay and hospital charges among the factors studied. Complications tended to occur more frequently among patients with United Network for Organ Sharing (UNOS) status 1 (42% vs 22%), but this did not reach statistical significance ( P =.09). Conclusions: Surgical complications after liver transplantation have a marked impact on the cost of the procedure. The magnitude of this effect is greater than that of UNOS status, presence of rejection, or other demographic or clinical factors studied. Complications tend to occur in the most ill patients. Identifying strategies to reduce the risk of complications, particularly in patients with UNOS status 1, likely can reduce the cost of transplantation. Arch Surg. 1997;132:1098-1103

Background. A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. Methods. Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. Results. Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of ≤10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin >10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus ≤90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted >90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. Conclusions. Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

To examine the prevalence of hepatitis G virus (HGV) in end-stage liver disease of unknown cause and the role of HGV infection in posttransplantation hepatitis, we studied 46 patients undergoing liver transplantation (mean age, 50 years; M: F, 18:28) with cryptogenic cirrhosis. HGV RNA was detected by polymerase chain reaction (PCR) and was quantified by a branched DNA (bDNA) assay. The prevalence of HGV RNA was determined in samples collected before and after liver transplantation and was found to be 22% and 67%, respectively. We evaluated the prevalence of posttransplantation hepatitis in 25 patients, 16 of whom were HGV-positive and 9 were HGV-negative. The proportion of patients with hepatitis was not significantly different in the two groups (38% in HGV-positive and 22% in HGV-negative patients). The median histological scores were significantly higher in liver biopsies from patients with HGV infection than in those without HGV infection (2 [range, 0-14] and 1 [range, 0-3]; P = .01), but the histological scores were low overall. The duration of follow-up was similar in the two groups. HGV RNA levels were not correlated with the severity of liver disease based on histological score (r = −.08). Graft survival and patient survival were not significantly different. We concluded that liver disease was frequent (32%) after transplantation in patients with a pretransplantation diagnosis of cryptogenic cirrhosis, although the disease was generally mild. Although HGV RNA was demonstrable in the majority (67%) of patients after transplantation, there was no relationship between the presence of HGV RNA and the presence of posttransplantation liver disease. The finding of posttransplantation hepatitis in the absence of known viruses (A-G), suggests that other, as-yet-unidentified viruses may be important.

Currently, allocation and distribution of organs are the most controversial aspects of liver transplantation. The scarcity of deceased donor organs has forced transplant centers and patients listed for transplant to compete with other local programs and locally listed patients, respectively, for liver grafts. The requirements for an optimal organ allocation system are (1) evidence-based outcome measures, (2) justice and equity, (3) maximal utility and (4) transparency. Balancing justice and equity for all candidates and individual vs. societal utility for a scarce resource is one of the largest challenges. The change in the allocation system from a waiting time-based system to a risk-based system using the Model for End stage Liver Disease (MELD) score has lowered pretransplant mortality, without adversely impacting posttransplant survival despite increased severity of illness at the time of transplantation (1,2). This is a model of how data-driven policy changes can improve outcomes. In this issue of the American Journal of Transplantation, Merion et al. present a detailed analysis of the scientific registry of transplant recipients to determine the transplant benefit for various MELD scores using time-dependent Cox regression models (3). Transplant benefit was defined as the difference in the likelihood of 1-year survival if one undergoes a transplant at a given MELD score vs. remaining on the waiting list. There is an overall survival benefit of transplantation in the first year; however, the benefit varied markedly by MELD score. A significant survival benefit with transplantation was seen only for patients with high MELD scores (i.e. >18); the survival benefit continuing to increase as MELD score increased, with greatest survival benefit being achieved in those at the highest MELD scores. Conversely, there was increased mortality in the first year posttransplant compared to remaining on the waiting list for patients with lower MELD scores (

Hepatitis G virus (HGV) is transmissible by blood transfusion, but its role in chronic liver disease is unknown. The aim of this study was to determine the prevalence of HGV infection in patients infected with hepatitis C virus (HCV) undergoing transplantation and evaluate the effects of HGV coinfection on the course of posttransplantation HCV infection.One hundred twenty-four patients infected with HCV undergoing liver transplantation were studied. Serum samples were tested for HCV and HGV RNA; HCV RNA was quantitated by branched DNA assay, and HCV genotype was determined.The prevalence of pretransplantation and posttransplantation HGV infection was 24% and 28%, respectively. Pre-transplantation HGV infection was positively correlated with posttransplantation HGV infection (P0.001). Pretransplantation clinical features were not different in patients infected with HCV with and without HGV infection. Posttransplantation HCV RNA levels were not significantly different in patients with and without HGV coinfection, but HCV genotype 1b was more frequent in patients with HGV coinfection. There were no differences in the histological severity of posttransplantation liver disease, graft, and patient survival between patients with and without HGV infection.Although HGV coinfection is frequent in patients with end-stage HCV disease undergoing liver transplantation, there is no association between the presence of HGV coinfection and the severity of liver disease post-transplantation, graft, or patient survival.

Infection with hepatitis C virus (HCV) genotype 1b has been reported to be associated with more severe posttransplantation liver disease than infection with non-1b genotypes. To address this issue, we evaluated the outcome in 124 patients who underwent liver transplantation for chronic HCV infection. The HCV genotype and/or serotype responsible for infection was determined by four different methods. HCV RNA was detected in serum samples by polymerase chain reaction (PCR) amplification, and quantified by branched DNA assay. Disease severity was expressed as a histological score (which included grading of portal inflammation, lobular activity, fibrosis, and cytopathic changes). Median duration of histological follow-up was 25 months (range 1-75 months). Genotype was assignable in 112 (92.5%) patients. Genotypes responsible for infection were as follows: 1a = 32.2%, 1b = 27.3%, 2a = 7.4%, 2b = 8.3%, 3a = 14%, and mixed infection (more than one subtype) = 3.3%. Level of viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and total histological score were not significantly different in patients infected with type 1b compared with patients infected with other genotypes. While duration of histological follow-up was greater in patients infected with type lb versus other types (P = .02), by univariate and multivariate analysis neither HCV genotype (lb versus others), level of viremia nor duration of histological follow-up were associated with disease severity. Moreover, there was no significant difference in the actuarial graft survival in patients infected with type lb compared with that of patients infected with non-lb types (82% and 87% at 3 years, respectively). Reanalysis using HCV genotype 1 showed no association with disease severity, graft survival, and patient survival. We conclude that HCV genotype 1 and subtype 1b are not associated with disease severity or graft survival in liver transplantation recipients.

OBJECTIVE: Living-related liver transplantation (LRLT) has established efficacy in children. In a larger recipient, LRLT requires the use of a small graft because of limits on the donor hepatectomy. SUMMARY BACKGROUND DATA: The minimum graft weight required for successful transplantation has not been well established, although a characteristic pattern of graft dysfunction has been observed in our patients who receive small grafts. The authors present a clinicopathologic study of small liver grafts obtained from living donors. METHODS: Clinical and histologic data were reviewed for 25 patients receiving LRLT. In five older recipients (small group), the graft represented 50% or less of expected liver weight, whereas in 20 others (large group), the graft represented at least 60% of expected liver weight. A retrospective analysis of graft function was conducted by analyzing clinical parameters and histology. RESULTS: In the small group, 2 of 5 grafts (40%) were lost due to poor function, leading to one patient death (20% mortality), whereas in the large group, 2 of 20 grafts (10%) were lost due to arterial thrombosis without patient mortality. Early ischemic damage related to transplant was comparable with aspartate aminotransferase 203 +/- 23 (small group) and 290 +/- 120 (large group) at 24 hours (p = not significant). Early function was significantly decreased in the small group, with prothrombin time 18.2 +/- 2.2 seconds versus 14.8 +/- 1.6 seconds (large group) on day 3 (p = 0.034). All small group patients developed cholestasis with significantly increased total bilirubin levels at day 7 (16 +/- 5.2 mg% vs. 3.7 +/- 2.7 mg%; p = 0.021) and day 14 (12.0 +/- 7.4 vs. 1.8 +/- 0.7; p = 0.021) compared with the large group. Protocol biopsies in the small group revealed a diffuse ischemic pattern with cellular ballooning on day 7, which progressed to cholestasis in subsequent biopsies. Large group biopsies showed minimal ischemic changes. Three small group patients recovered with normal liver function by 12 weeks. CONCLUSIONS: Clinical recovery after a small-for-size transplant is characterized by significant functional impairment associated with paradoxical histologic changes typical of ischemia. These changes apparently are due to graft injury, which can only be the result of small graft size. These findings have significant implications for the extension of LRLT to adults.

To evaluate the effect of donor age on graft and patient outcome after liver transplantation an analysis of a large-scale cohort study was performed at three tertiary referral liver transplant centers. Between April 1990 and June 1994, 772 adults underwent an initial single-organ liver transplantation. The age of the donors averaged 35 years;193 (25%) were 50 or above, the age used to define "older" donors. Groups were compared for demographic, clinical, and biochemical features. Outcome was measured using results of biochemical tests after transplantation and by graft and patient survival. Compared with younger donors, older donors were more commonly women (59% vs. 33%:P < or = .001) and died of central nervous system causes (79% vs. 28%) as opposed to trauma (13% vs. 63%:P < or = .001). The recipients of the two groups of donor livers did not differ in important respects. However, intraoperatively, livers from older donors were more likely to be assessed as either "poor" or "fair" as opposed to "good" (17% vs. 4%:P < or = .001) by the harvesting surgeon and to have initial "poor" or "fair" bile production (29% vs. 18%:P < or = .001). During the first week postoperatively, the serum aminotransferase and bilirubin levels and prothrombin times were higher in recipients of older than those of younger donor livers. During follow-up, graft survival was less for recipients of older donor livers at 3 months (81% vs.91%:P = .0001) and at 1 (76% vs. 85%:P = .007) and 2 years (71% vs. 80%:P = .005); patient survival showed similar though less marked differences. This association of donor age and poorer graft survival persisted after adjusting for many variables using bivariate and multivariate analyses. Importantly, however, the association with poor graft survival was largely among recipients of older donor livers, the quality of which was assessed as fair or poor by the harvesting surgeon; recipients of older donor livers assessed as good had a retransplant-free survival similar to that of younger donor livers (87% vs. 91% at 3 months). Thus, use of older donor livers, the quality of which are judged to be good by the harvesting surgeon, is not associated with a decrease in patient or graft survival after liver transplantation. differences. This association of donor age and poorer graft survival persisted after adjusting for many variables using bivariate and multivariate analyses. Importantly, however, the association with poorer graft survival was largely among recipients of older donor livers, the quality of which was assessed as fair or poor by the harvesting surgeon; recipients of older donor livers, the quality of which was assessed as fair or poor by the harvesting surgeon; recipients of older donor livers assessed as good had a retransplant-free survival similar to that of younger donor livers (87% vs. 91% at 3 months). Thus, use of older donor livers, the quality of which are judged to be good by the harvesting surgeon, is not associated with a decrease in patient or graft survival after liver transplantation.