bluuebunny/crossref_metadata_2025 huggingface dataset:
Body mass index as a predictor of hepatic steatosis in living liver donors
Authors: Rinella Mary E. , Alonso Estella , Rao Sambasiva , Whitington Peter , Fryer Jonathan , Abecassis Michael , Superina Riccardo , Flamm Steven L. , Blei Andres T.
Published: August 2002

Evaluation of the living donor for liver transplantation is a complex process involving such invasive studies as liver biopsy and angiography. It is important to establish the likelihood and extent of hepatic steatosis in living donors by clinical, imaging, and biochemical parameters to avoid performing a liver biopsy, if possible. In this study, the predictive value of body mass index (BMI), liver chemistry tests, and imaging studies was compared with liver histological examination in 33 potential living donors. Patients were grouped and compared based on their BMI (<25, 25 to 28, >28). No patient with a BMI less than 25 had hepatic steatosis. Of patients with a BMI of 25 to 28, steatosis was found on biopsy in 3 of 9 patients. Thirteen of 17 patients (76%) with a BMI greater than 28 had hepatic steatosis on liver biopsy. There was a significant correlation between BMI and overall grade of steatosis (R = 0.49). All subjects with steatosis detected on magnetic resonance imaging (MRI) or computed tomography (CT) had steatosis on biopsy, and all but 2 such patients had greater than 10% steatosis on biopsy. Conversely, 30% of patients in the MRI group and 24% of patients in the CT group failed to show hepatic steatosis when it was present on biopsy. Thus, it appears that liver biopsy could be avoided in subjects with a normal BMI and absence of risk factors. Individuals with a high BMI should undergo liver biopsy because biochemical and imaging data are currently inadequate to determine the extent of steatosis. Future studies should aim at improving the sensitivity of imaging techniques in the diagnosis of steatosis.
Dyslipidemia during sirolimus therapy in liver transplant recipients occurs with concomitant cyclosporine but not tacrolimus
Authors: Trotter James F. , Wachs Michael E. , Trouillot Thomas E. , Bak Thomas , Kugelmas Marcelo , Kam Igal , Everson Gregory
Published: August 2002

Since its approval as an immunosuppressive agent in renal transplantation, sirolimus (RAPA) recently has been used in the primary immunosuppression regimen at several liver transplant centers. One of the major side effects of RAPA is hypercholesterolemia, which is reported in up to 44% of patients. We describe our experience in 57 primary liver transplant recipients treated with RAPA and either cyclosporine A (CSA) or tacrolimus (TAC). We report the incidence and severity of hypercholesterolemia using a prednisone-free immunosuppressive regimen. Between January 2000 and September 2000, a total of 57 patients underwent transplantation at the University of Colorado Health Sciences Center (Denver, CO) with RAPA and either CSA or TAC. The initial 10 patients who underwent transplantation under this protocol were not administered corticosteroids, and the subsequent 47 patients were administered only 3 doses of methylprednisolone days 0, 1, and 2 postoperatively (1, 0.5, and 0.5 g, respectively). Total fasting cholesterol, high-density cholesterol, low-density cholesterol, and triglyceride levels were measured at monthly intervals. Mean serum cholesterol level was significantly greater in CSA patients (200 mg/dL) compared with TAC patients (158 mg/dL; P = .0003). Serum triglyceride levels were more than 2-fold greater with CSA (292 mg/dL) compared with TAC (134 mg/dL; P = .002). Hypercholesterolemia (cholesterol > 240 mg/dL) was present in 10 of 57 patients (18%) and was significantly more common in CSA-treated patients (8 of 27 patients; 30%) compared with TAC-treated patients (2 of 30 patients; 6%; P < .05). Hypertriglyceridemia (serum triglyceride > 300 mg/dL) was present in 10 of 57 patients (18%) and was significantly more common in CSA-treated patients (9 of 27 patients; 33%) compared with TAC-treated patients (1 of 30 patients; 3%; P < .05). We conclude that (1) concomitant use of TAC with RAPA reduces the prevalence and severity of posttransplantation dyslipidemia, and (2) these findings have important implications in the prevention of complications of hypercholesterolemia in liver transplant recipients.
Beneficial effects of converting liver transplant recipients from cyclosporine to tacrolimus on blood pressure, serum lipids, and weight
Authors: Neal David A.J. , Gimson Alexander E.S. , Gibbs Paul , Alexander Graeme J.M.
Published: August 2002

Hypertension and hyperlipidemia are more prevalent after liver transplantation with cyclosporine as the primary immunosuppressive agent compared with tacrolimus. To determine whether blood pressure, serum lipid level, or weight improves when patients switch immunosuppression therapy, we retrospectively studied 26 liver transplant recipients with stable graft function who had been converted from cyclosporine to tacrolimus therapy with a median follow-up of 8 months. One of the 26 patients developed pruritus necessitating withdrawal of tacrolimus. The results therefore concern the remaining 25 patients. With the exception of a small decrease in bilirubin level (P <.05), there was no difference in graft or renal function after conversion. Mean systolic blood pressure decreased from 158 ± 25 to 148 ± 22 mm Hg over a mean of 8 ± 3 months after conversion to tacrolimus (P = .015), whereas mean serum cholesterol level decreased from 5.3 ± 0.9 to 4.9 ± 0.9 mmol/L (P = .01). Sixty-eight percent of the patients lost weight, from a mean of 79.4 ± 22.6 to 76.1 ± 20.1 kg, in the 11 months after switching to tacrolimus therapy (P = .024). Serum triglyceride and blood glucose levels did not change, and no patient developed diabetes mellitus after conversion. These results indicate that switching from cyclosporine to tacrolimus can reduce blood pressure, serum cholesterol level, and weight after liver transplantation.
Right hepatic lobe donation for living donor liver transplantation: Impact on donor quality of life
Authors: Trotter James F. , Talamantes Michael , McClure Mary , Wachs Michael , Bak Thomas , Trouillot Thomas , Kugelmas Marcelo , Everson Gregory T. , Kam Igal
Published: August 2002

Adult right hepatic lobe living donor liver transplantation (LDLT) has rapidly gained widespread acceptance as an effective procedure for selected patients with end-stage liver disease. However, there are currently no published data on the effect of this procedure on the quality of life of donors. We report the results of a survey of our living liver transplant donors to determine the effect of right hepatic lobe donation on quality of life. We have performed 30 LDLTs since 1997; 24 of these have a follow-up of 4 months or longer. In August 2000, these patients were sent a questionnaire (including a Medical Outcomes Study 36-Item Short-Form Survey) regarding psychosocial outcomes and symptoms after surgery. Major complications occurred in 4 of 24 patients (16%), and minor complications, in 4 of 24 patients (16%). Complete recovery occurred in 75% of patients at a mean time of 3.4 months. Ninety-six percent of patients returned to the same predonation job after a mean time of 2.4 months, and 66% of patients required a period of light-duty work for a mean of 2.8 months before returning to full-duty work. A change in body image was reported in 42% of patients, and 71% reported mild ongoing symptoms (primarily abdominal discomfort) that they related to the donor surgery for which 29% sought evaluation by a physician. The donor’s relationship with the recipient was the same or better in 96% of donors, and the relationship with the donor’s significant other was the same or better in 88% of donors. Mean out-of-pocket expenses incurred by donors were $3,660. Sixty-three percent of donors reported experiencing more pain than anticipated. All patients would donate again if necessary, and 96% benefited from the donor experience. In conclusion, (1) all our donors are alive and well after donation; (2) almost all donors were able to return to predonation employment status within a few months; (3) most donors have mild persistent abdominal symptoms, and some donors had a change in body image that they attribute to the donor surgery; and (4) this information should be provided to potential donors so they may better understand the impact of donor surgery.
Analysis of causes of death in liver transplant recipients who survived more than 3 years
Authors: Pruthi Jatinder , Medkiff Katherine A. , Esrason Karl T. , Donovan John A. , Yoshida Eric M. , Erb Siegfried R. , Steinbrecher Urs P. , Fong Tse-Ling
Published: August 2002

Few studies have examined causes of death in long-term survivors of orthotopic liver transplantation (OLT). We reviewed causes of death among 299 adult liver transplant recipients who survived more than 3 years after OLT at 2 centers. Thirty-eight of the 299 patients subsequently died. Nonhepatic causes accounted for 22 of 38 late deaths (58%). Death caused by malignancies occurred in 9 patients between 3.3 and 8.0 years after OLT. Eight patients died of cardiovascular complications. The 6 patients who died of myocardial infarction had risk factors for coronary artery disease. Hepatic failure caused by recurrent liver disease or chronic rejection accounted for 16 of 38 late deaths (42%). These 16 patients were younger than patients who died of nonhepatic complications (mean ages, 50.7 v 62.1 years; P = .001). However, the mean interval between OLT and death was similar among patients who died of nonhepatic versus hepatic causes. Nine patients had recurrent liver disease leading to death, and 8 of 9 patients had recurrent chronic hepatitis C virus (HCV) infection. Chronic rejection resulting in graft failure and death occurred in 7 patients. In summary, de novo malignancies and cardiovascular complications accounted for more than half the late deaths. Patients who died of nonhepatic causes were significantly older than patients who died of hepatic causes. Chronic rejection and recurrent HCV infection accounted for the majority of hepatic causes of death. With longer follow-up, graft failure resulting from recurrent HCV infection will become the major cause of death in late survivors.
Transplantation of hepatitis C-positive livers in hepatitis C-positive patients is equivalent to transplanting hepatitis C-negative livers
Authors: Marroquin Carlos E. , Marino Gustavo , Kuo Paul C. , Plotkin Jeffrey S. , Rustgi Vinod K. , Lu Amy D. , Edwards Erick , Taranto Sarah , Johnson Lynt B.
Published: August 2002

A significant number of patients with end-stage liver disease secondary to hepatitis C die of disease-related complications. Liver transplantation offers the only effective alternative. Unfortunately, organ demand exceeds supply. Consequently, some transplant centers have used hepatitis C virus-positive (HCV+) donor livers for HCV+ recipients. This study reviews the clinical outcome of a large series of HCV+ recipients of HCV+ liver allografts and compares their course with that of HCV+ recipients of HCV-negative (HCV−) allografts. The United Network for Organ Sharing Scientific Registry was reviewed for the period from April 1, 1994, to June 30, 1997. All HCV+ transplant recipients were analyzed. Two groups were identified: a group of HCV+ recipients of HCV+ donor livers (n = 96), and a group of HCV+ recipients of HCV− donor livers (n = 2,827). A multivariate logistic regression model was used to determine the odds of graft failure and patient mortality, and unadjusted graft and patient survival were determined using the Kaplan-Meier method. There were no differences in demographic criteria between the groups. A greater percentage of patients with hepatocellular carcinoma received an HCV+ allograft (8.3% v 3.1%; P = .01). Patient survival showed a significant difference for the HCV+ group compared with the HCV− group (90% v 77%; P = .01). Blood type group A, group B, group O incompatibility was significant, with 4.2% incompatibility in the HCV+ group and only 1.3% in the HCV− group (P = .04). Donor hepatitis C status does not impact on graft or patient survival after liver transplantation for HCV+ recipients. Their survival was equivalent, if not better, compared with the control group. Using HCV+ donor livers for transplantation in HCV+ recipients safely and effectively expands the organ donor pool.
Histological recurrence and progression of hepatitis C after orthotopic liver transplantation: Influence of immunosuppressive regimens
Authors: Hunt John , Gordon Fredric D. , Lewis David W. , Pomfret Elizabeth , Pomposelli James J. , Jenkins Roger L. , Khettry Urmila
Published: August 2002

Post-orthotopic liver transplantation (OLT) recurrence of hepatitis C is virtually universal, but histological progression of disease is not. This study examines long-term clinical and liver histological features at and after OLT to elucidate factors predictive of hepatitis C recurrence and progression after OLT. A blinded retrospective review of clinical, serological, and histopathologic features of 65 patients who underwent OLT for hepatitis C and Non A Non B hepatitis was conducted. Histological findings of recurrent hepatitis C and progression (fibrosis, ≥ grade 2 by last follow-up) were correlated with clinical parameters. Histological recurrence of hepatitis C was seen in 43 of 65 patients, with progression in 19 patients. Histological findings in the native liver and post-OLT biopsy specimen at the time of recurrence showed no correlation with hepatitis C recurrence and progression. Patients treated with azathioprine (AZA)-containing immunosuppressive regimens experienced less recurrence (6 of 17 v 37 of 48 patients; P < .005) and progression (1 of 17 v 18 of 48 patients; P = .014) than those without AZA as part of their immunosuppressive regimen. No difference was seen between patients treated with cyclosporine versus those administered FK506 (P > .05). Histological recurrence of hepatitis C after OLT is seen in 66% of patients with progressive disease and 29% of all patients. The grade of inflammation in the native liver at the time of OLT and time of recurrence is not predictive of progression. AZA-containing regimens reduce histological recurrence and progression of hepatitis C in post-OLT patients.
Trends in expenditures for Medicare liver transplant recipients
Authors: Best Jennie H. , Veenstra David L. , Geppert Jeffrey
Published: August 2002

Liver transplantation, a resource-intensive medical procedure, is under particular scrutiny in the current era of cost containment. There have been significant changes in treatment protocols over the past decade; however, information is limited on how these changes have affected the economics of liver transplantation. This study examines a time series from 1993 to 1999 in Medicare expenditures for liver transplantation. We estimated total first- and second-year expenditures, as well as expenditures 90 days pretransplantation. These expenditures included inpatient, outpatient, physician, home health, and hospice care; immunosuppression expenditures were not estimated. Average first-year expenditures (in year 2000 dollars) for liver transplantation, excluding immunosuppressives, decreased from $201,677 in 1993 to $143,363 in 1998. Inpatient costs accounted for the majority of total expenditures, decreasing from $179,306 in 1993 to $120,445 in 1998. Total days of hospitalization decreased from 56.7 days in 1993 to 42.2 days in 1998. The majority of hospitalization occurred during the first 90 days posttransplantation, but decreased from 44.4 days in 1993 to 29.4 days in 1999. Substantial cost reductions over this period were a result of reduced hospitalization and occurred while survival rates gradually improved.
Recurrent hepatitis C after liver transplantation: A nonrandomized trial of interferon alfa alone versus interferon alfa and ribavirin
Authors: Ahmad Jawad , Dodson Forrest S. , Demetris Jake A. , Fung John J. , Shakil Obaid A.
Published: August 2002

Liver transplant recipients with recurrent hepatitis C virus (HCV) infection often have histological hepatitis, and in some patients, graft failure develops. The aim of this nonrandomized study is to determine the efficacy and tolerability of interferon alfa (IFN alfa) alone and IFN alfa and ribavirin combination therapy in such patients. Forty transplant recipients with recurrent hepatitis were initiated on therapy with IFN alfa-2b at 3 million units (MU) three times weekly for 1 month followed by 5 MU three times weekly for 5 months. Twenty patients were administered IFN alfa-2b, 3 MU three times weekly for 1 month followed by 5 MU three times weekly for 11 months, and ribavirin, 600 mg, twice daily orally for 12 months concurrently. The primary end point was sustained clearance of serum HCV RNA, and secondary end points were serum alanine aminotransferase (ALT) level normalization and histological improvement. Thirty patients completed 6 months of IFN-alfa monotherapy and 15 patients completed 12 months of IFN alfa and ribavirin combination therapy. End-of-treatment biochemical responses were similar in the two groups (IFN alfa, 20% v combination therapy, 25%); however, viral clearance was greater in the combination-therapy group (40% v 15%; P = .04). Six months after the completion of therapy, only 1 patient (2.5%) in the IFN-alfa group and 4 patients (20%) in the combination-therapy group were HCV RNA negative (P = .03). Serum ALT and HCV RNA levels declined significantly in both groups during therapy. There was no improvement in inflammatory grade, and fibrosis score was worse in both groups. Ten patients (25%) in the IFN-alfa group and 5 patients (20%) in the combination-therapy group withdrew because of adverse effects. We conclude that in liver allograft recipients with recurrent hepatitis C, combination therapy with IFN alfa and ribavirin is more efficacious than treatment with IFN alfa alone. However, the efficacy is limited by tolerability.
Ethical considerations and rationale of adult-to-adult living donor liver transplantation
Authors: Malagó Massimo , Testa Giuliano , Marcos Amadeo , Fung John J. , Siegler Mark , Cronin David C. , Broelsch Christoph E.
Published: August 2002

Adult-to-adult living donor liver transplantation (ALDLT) is a reality; shortly after its introduction into clinical practice, it is being performed in approximately 50 centers throughout the United States and Europe. The quick development of ALDLT and some deaths among donors repropose old ethical dilemmas and confront the transplant community with new urgent problems. To minimize risks for recipients and, especially, donors, two key questions are addressed: (1) who can or should perform the procedure, and (2) what patient should undergo the procedure. The high risks taken by live donors undergoing a hemihepatectomy seem to be justified by the steadily increasing mortality of adult recipients waiting for transplantation. A comprehensive consent procedure is at the base of responsible decision making for both donors and recipients. In adherence to basic medical criteria, the autonomy of decision of donors and recipients may allow the extension of indications to patients not suitable to undergo transplantation with cadaveric grafts. The broadening of indications is appropriate only in centers with adequate experience and proven expertise in ALDLT. The medical community faces the duty of regulating ALDLT before external influences force undesired policy changes, particularly if not based on medical grounds. Individual centers and patients are ultimately responsible for the correct use of LDLT.
Long-term immunosuppression and drug interactions
Authors: Levy Gary A.
Published: August 2002

Key Points
De novo tumors after liver transplantation: A single-institution experience
Authors: Sanchez Edmund Q. , Marubashi Shigeru , Jung Ghapjoong , Levy Marlon F. , Goldstein Robert M. , Molmenti Ernesto P. , Fasola Carlos G. , Gonwa Thomas A. , Jennings Linda W. , Brooks Barbara K. , Klintmalm Goran B.
Published: August 2002

The aims of this analysis are to characterize the incidence and types of malignancies and tumor-specific mortality in our institution. Retransplantation, rejection episodes, and OKT3 use were evaluated. Our single-institution prospective database of 1,570 liver transplantations in 1,421 patients was analyzed. Data were statistically analyzed regarding sex, age at transplantation, time from transplantation to diagnosis of tumor, tumor type, and follow-up time. One hundred twenty-five patients (8.8%) developed de novo tumors; 69 patients were men, 56 patients were women. Seventeen patients received more than one allograft. De novo tumors were as follows: skin, 41; lymphomas, 35; lung, 11; colon, 6; anal, 2; rectal, 1; breast, 7; thyroid, 3; oropharyngeal squamous cell, 3; metastatic without primary tumor identified, 4; renal cell, 3; Kaposi’s sarcoma, 1; angiosarcoma, 1; uterine, 1; ovarian, 1; pituitary, 1; pancreatic, 2; cholangiocarcinoma, 1; and esophageal, 1. These tumors developed in a statistically significant chronological sequence. Lung cancers and lymphomas showed shorter mean survival times, as well as greater mortality. OKT3 use and rejection did not show significance in tumor development. De novo tumors post-liver transplantation affected our population in a distribution similar to that of the general nontransplantation population. Intense short courses of immunosuppression for rejection were not as important as chronic immunosuppression in the development of tumors. The risk for development was not enough to preclude transplantation. We found that tumors developed in chronological fashion. Therefore, directed surveillance, patient education, and early detection may facilitate earlier treatment.
Safe donor hepatectomy for living related liver transplantation
Authors: Sugawara Yasuhiko , Makuuchi Masatoshi , Takayama Tadatoshi , Imamura Hiroshi , Kaneko Junichi , Ohkubo Takao
Published: August 2002

Minimizing the risk of donor hepatectomy while preserving graft viability is an important concern in living related liver transplantation. This report describes clinical outcomes for living donor hepatectomy with reference to the type of hepatectomy. Donor hepatectomy was performed in 130 consecutive living donors. They were divided into three groups: left lateral or extended left lateral segmentectomy (group S; n = 50), left hepatectomy with or without caudate lobe or right lateral resection (group L; n = 64), and right hepatectomy (group R; n = 16). Intraoperative and postoperative data were examined and compared among the groups. No critical complications were observed in any group. However, there were differences in donor age, surgical and ischemia times, volume of blood loss, graft weight, and aspartate aminotransferase level elevation among the groups. Livers showed a substantial increase in volume, tending to the standard liver volume 1 month after surgery. Regardless of the extent of donor hepatectomy, serious complications did not occur after surgery. Surgical risk for a living donor is minimal if the operation is performed by experienced surgeons using present procedures.
A concise update on the status of liver transplantation for hepatitis B virus: The challenges in 2002
Authors: Vargas Hugo E. , Dodson Forrest S. , Rakela Jorge
Published: August 2002

Significant improvements in both patient and graft survival after orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related liver failure have been made during the last decade. Recurrence of HBV infection has decreased, even in high-risk patients. Despite ongoing progress, challenges remain for the next millennium, including the determination of cost-effective dosing strategies, treatment of HBV infection in liver transplant recipients, and ramifications of the use of new antiviral agents, specifically, the appearance of resistant strains. This review summarizes the relevant history of OLT for chronic viral hepatitis B, details accepted preventive and therapeutic treatments, and discusses ongoing experimental trials. Emphasis also is placed on new approaches in transplantation as they impact on the care of HBV-infected patients.
Tacrolimus dosing requirements and concentrations in adult living donor liver transplant recipients
Authors: Taber David J. , Dupuis Robert E. , Fann Amy L. , Andreoni Kenneth A. , Gerber David A. , Fair Jeffrey H. , Johnson Mark W. , Shrestha Roshan
Published: August 2002

Living donor liver transplantation in adult recipients is becoming increasingly common. The liver metabolizes most drugs, including immunosuppressive agents. Right-lobe grafts used in adult living donor liver transplantation consist of only 50% to 60% of the total liver. The purpose of this study is to determine whether there is a difference between tacrolimus doses and concentrations in patients who received a partial liver transplant from a living donor (LRD) versus those who received a whole-liver transplant from a cadaveric donor (CAD). Thirteen LRD recipients and 13 CAD recipients who underwent transplantation between April 1998 and July 2000 were included in this analysis. A CAD control group matched for age, sex, and race was used for comparison. Tacrolimus doses and concentrations were analyzed weekly for the first 4 weeks, then monthly for 6 months posttransplantation. There was no difference in acute rejection rates, renal and liver function test results, or number of potentially interacting medications administered between groups. LRD recipients required significantly lower doses of tacrolimus compared with CAD recipients at 2 weeks (0.058 v 0.110 mg/kg/d; P < .01), 3 weeks (0.068 v 0.123 mg/kg/d; P < .02), 4 weeks (0.086 v 0.141 mg/kg/d; P < .02), 2 months (0.097 v 0.141 mg/kg/d; P < .03), and 3 months (0.099 v 0.138 mg/kg/d; P < .03). Tacrolimus 12-hour trough concentrations were similar between groups at all times except for 2 weeks posttransplantation, when LRD recipients’ concentrations were significantly greater than those of CAD recipients (12.4 v 9.5 ng/mL; P < .03). In addition, in the first month posttransplantation, LRD recipients were more likely to have greater concentrations of tacrolimus (>15 ng/mL; 22.1% v 9.2%; P < .01). In conclusion, LRD recipients have significantly decreased tacrolimus dosing requirements compared with CAD recipients during the first 3 months posttransplantation despite having similar tacrolimus concentrations.
Post-liver transplantation diabetes mellitus: An association with hepatitis C
Authors: AlDosary Ahmad A. , Ramji Alnoor S. , Elliott Thomas G. , Sirrs Sandra M. , Thompson David M. , Erb Siegfried R. , Steinbrecher Urs P. , Yoshida Eric M.
Published: August 2002

A retrospective study was performed on all liver transplant recipients from British Columbia from 1989 to March 2000 to determine the prevalence and predictive factors of diabetes mellitus (DM) post-liver transplantation. DM was defined as hyperglycemia requiring treatment with insulin or oral hypoglycemic agents. Patient characteristics, cause of liver disease at transplantation, and immunosuppression regimen were considered. Both univariate and multiple logistic regression analyses were performed. Posttransplantation DM (PTDM) occurred in 43 of 177 transplant recipients (24%). Of these, 13 transplant recipients had DM pretransplantation, whereas 30 patients developed de novo PTDM. The majority of patients were treated with insulin (80%). In univariate analysis, transplantation for hepatitis C virus (HCV) liver disease was associated with a greater incidence of PTDM (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.46 to 6.23) and de novo PTDM (OR, 5.20; 95% CI, 2.25 to 11.99). Patients administered tacrolimus had a greater incidence of PTDM (OR, 2.04; 95% CI, 1.01 to 4.13), and there was a trend toward increased PTDM in older patients (mean age, 49 years). Recipient sex, steroid dosage, and acute rejection were not predictive of PTDM. The incidence of graft loss and death rates were similar between the two groups. On logistic regression, HCV was the only independent predictor of PTDM (OR, 4.12; 95% CI, 1.91 to 8.90) and de novo PTDM (OR, 6.02; 95% CI, 2.55 to 14.20). In conclusion, DM post-liver transplantation is a common occurrence and is associated with HCV.
Fate of hepatocyte and sinusoidal lining cell function and kinetics after extended cold preservation and transplantation of the rat liver
Authors: Miyagawa Yusuke , Imamura Hiroshi , Soeda Junpei , Matsunaga Kotaro , Mochida Satoshi , Fujiwara Kenji , Matsuyama Yutaka , Kawasaki Seiji
Published: August 2002

We investigated the chronological profile of graft damage and recovery after liver cold ischemia-reperfusion (I/R) injury, with particular attention to the role of apoptosis on hepatocyte and sinusoidal endothelial cell (SEC) damage. Male Lewis rats underwent rearterialized orthotopic liver transplantation using grafts subjected to a short (University of Wisconsin [UW] solution for 1 hour [UW1h]) and prolonged period (UW16h) of cold preservation. Experiments were performed immediately after preservation and 4 hours, 24 hours, 3 days, and 7 days after reperfusion. At each time, graft function, incidence of apoptotic cells, expression of the epitope recognized by a monoclonal antibody specific to rat SECs (SE-1), and incidence of proliferating cells were estimated. In the UW16h group, the proportion of apoptotic SECs was markedly elevated at 4 hours. The incidence of hepatocyte apoptosis was very low, although massive hepatocyte necrosis was evident at 24 hours. The incidence of proliferating hepatocytes and SECs peaked at 3 days, then returned to normal by 7 days. SE-1 expression was reduced immediately after preservation, followed by a marked reduction at 4 and 24 hours after reperfusion, and expression returned to normal by 7 days. Although SEC apoptosis was induced in the early phase of cold I/R injury, hepatocyte damage developed without the occurrence of apoptosis. Regeneration of both hepatocytes and SECs after cold I/R injury peaked at 3 days and was complete by 7 days, whereas functional recovery of these cell populations was complete 3 days after reperfusion.
Is it cost-effective to treat recurrent hepatitis C infection in orthotopic liver transplantation patients?
Authors: Saab Sammy , Ly David , Han Steven B. , Lin Robert K. , Rojter Sergio E. , Ghobrial Mark R. , Busuttil Ronald W.
Published: August 2002

Hepatitis C virus (HCV) recurs in the allograft almost universally after orthotopic liver transplantation (OLT), with a variable course ranging from mild hepatitis to frank cirrhosis. The uncertain prognosis after OLT has lead to widely increased use of antiviral therapy in the post-OLT setting. We compared two scenarios (antiviral therapy versus no antiviral therapy) using a Markov-based decision analytic model to simulate costs and health outcomes for recurrent HCV in three age and sex cohorts of post-OLT patients. Efficacy outcomes included total costs, cases of cirrhosis prevented, cases of death prevented, life-years gained, and cost per life-year saved. One-way sensitivity analyses were performed for sustained viral response; annual drug cost, discount rate, compliance, cirrhosis rate, decompensation rate, and cost of dying. Two-way sensitivity analyses were performed to compare effects of (1) changing sustained viral response and antiviral therapy costs, and (2) changing the sustained viral response and cirrhosis rate. The incremental cost-effectiveness ratio for the reference patient cohort of 1,000 men aged 55 years was $29,100 per life-year saved. The model was sensitive to drug costs, cirrhosis rate, and sustained viral response. The two-way sensitivity analysis showed that antiviral therapy remained cost-effective even if drug costs increased, as long as these increases were associated with higher sustained viral responses. The cost-effectiveness ratio also was sensitive to age and sex of cohort. The decision to treat HCV after OLT with antiviral therapy usually is based on many considerations. Such treatment can be cost-effective if baseline assumptions are met. Our model was sensitive to antiviral drug costs, cirrhosis rate, and sustained viral response. Patients with a progressive course of recurrent HCV are likely to have the greatest gain from antiviral therapy.
Right-liver living donor transplantation for decompensated end-stage liver disease
Authors: Testa Giuliano , Malagó Massimo , Nadalin Silvio , Hertl Martin , Lang Hauke , Frilling Andrea , Broelsch Christoph E.
Published: August 2002

Adult-to-adult living donor liver transplantation (LDLT) for patients with decompensated end-stage liver disease (DELD) is controversial. Nevertheless, these patients are most in need of a timely liver transplant. We present the results of 7 patients who underwent transplantation with this procedure and discuss the rationale for its possible broader application. Seven of 51 patients who underwent right LDLT (segments 5 to 8) between August 1998 and April 2001 had DELD, defined as Child-Pugh-Turcotte score greater than 13 or Model for End-Stage Liver Disease score greater than 30. All patients also were listed for cadaveric liver transplantation. Mean age of the 7 transplant recipients was 54 years (range, 44 to 63 years). Three patients had ethyltoxic cirrhosis; 2 patients, hepatitis C; 1 patient, hepatitis B; and 1 patient, autoimmune hepatitis cirrhosis. The average intensive care unit stay was 23 days (range, 3 to 88 days), and average hospital stay was 77 days (range, 27 to 132 days). Three patients are alive 31, 21, and 17 months after LDLT. At a mean follow-up of 15.1 ± 10 months, patient and graft survival rates are 43%. Four transplant recipients died day 30, 60, 117, and 180 after transplantation. Three of the seven donors (43%) experienced a complication. At present, all donors are well and have returned to their normal activities. No donors had regrets about the procedure, and all donors stated that they would donate again if presented with the same decision. In conclusion, with the lack of other therapeutic options, LDLT represents a timely and effective alternative to cadaveric liver transplantation. Better outcome is foreseeable with a decrease in posttransplantation complications and more experience in predicting survival of these critical patients.
Evidence of differential risk for posttransplantation malignancy based on pretransplantation cause in patients undergoing liver transplantation
Authors: Saigal Sanjiv , Norris Suzanne , Muiesan Paolo , Rela Mohamed , Heaton Nigel , O’Grady John
Published: August 2002

Organ transplant recipients are considered to be at greater risk for developing malignancy because of the prolonged immunosuppression associated with organ grafting. The purpose of this study is to determine risk factors, clinical characteristics, and outcomes of de novo nonlymphoid malignancies after liver transplantation from a large single-center series. All patients undergoing liver transplantation at the King’s College Hospital (London, UK) between January 1988 and December 1999 were analyzed retrospectively for the development of de novo malignancy in the posttransplantation period. Records were evaluated for age at diagnosis of malignancy, cause of liver disease, interval from transplantation to diagnosis of malignancy, predisposing factors for the development of cancer, immunosuppression regimen, treatment of malignancy, rejection episodes, and patient survival. Of 1,140 patients undergoing 1,271 liver transplantations, 30 patients (2.6%) developed de novo nonlymphoid malignancy after transplantation. Skin cancers were the most common (n = 13), followed by oropharyngeal carcinoma (n = 2), bladder carcinoma (n = 2), acute leukemia (n = 2), breast carcinoma (n = 2), and various other malignancies (n = 9). The mean time of presentation of the malignancy after transplantation was 45.1 ± 32 months (range, 6 to 133 months), and mean age at diagnosis of malignancy was 55 years (range, 34 to 71 years). The incidence of de novo malignancy was significantly greater in patients who underwent transplantation for alcoholic liver disease compared with other groups (P < .001). Although the incidence of de novo nonlymphoid malignancy after liver transplantation is low, patients who underwent transplantation for alcoholic cirrhosis appear to have an increased risk for developing posttransplantation malignancy.
Safe use of livers from donors with positive hepatitis B core antibody
Authors: Manzarbeitia Cosme , Reich David J. , Ortiz Jorge A. , Rothstein Kenneth D. , Araya Victor R. , Munoz Santiago J.
Published: August 2002

Thirty-five patients received liver transplants using liver donors who had positive test results for the hepatitis B core antibody (HBcAb). In the same time frame, 195 patients received HBcAb-negative liver donors. Mean follow up for patients receiving HBcAb-positive donors was 25 months. All patients receiving HBcAb-positive donors were monitored for recurrence of hepatitis B (HBV) with HBV DNA assays. There was no de novo HBV in recipients of HBcAb-negative grafts. In the group of patients receiving HBcAb-positive donors, 4 of 35 patients died within 3 months after transplant with no evidence of HBV recurrence at time of death. Four patients were transplanted for HBV-related disease and were postoperatively placed on lamivudine and hepatitis B immune globulin (HBIG). HBV recurrence was seen in one of these patients. Of the remaining 27 patients, three of three mismatched patients (HBcAb-positive donor to HBcAb-negative recipient) developed de novo HBV (100%). Of 24 matched patients (HBcAb-positive donor to HBcAb-positive recipient), only two (7%) developed recurrent HBV allograft reinfection. All de novo and recurrent HBV infections were successfully managed with HBIG and lamivudine therapy. Survival for this subgroup of patients receiving HBcAb-positive donors for non-HBV-related liver disease was 100%. We conclude that the judicious use of HBcAb-positive donors is reasonably safe and associated with low morbidity and mortality, with the appropriate follow-up protocols. Additionally, lamivudine use can be reserved for those cases with de novo or recurrent HBV in the liver allograft, or, selectively, as prophylaxis in those recipients patients who are naïve to HBV and receive an HBcAb-positive donor.
Role of gender and race mismatch and graft failure in patients undergoing liver transplantation
Authors: Rustgi Vinod K. , Marino Gustavo , Halpern Michael T. , Johnson Lynt B. , Umana Walter O. , Tolleris Christine
Published: August 2002

Previous data have suggested an increased risk of graft failure in male recipients of female livers, and in nonwhite recipients of orthotopic liver transplantation. United Network for Organ Sharing records of liver transplantations from 1992 through 2000 with at least one follow-up visit were reviewed. Analysis of these data was performed with proportional hazards regression, controlling for follow-up time, age, gender, ethnicity, number of comorbidities, functional status at time of transplant, and status 1 designation. Separate analyses comparing transplants among whites and blacks only and matched versus mismatched transplants for male and female recipients were performed. The results revealed that gender-mismatched patients (n = 13,992) had a higher likelihood of graft failure when compared with gender matched transplants (n = 18,522) (12.2% versus 11.3% respectively, P = .013). After controlling for the above potential confounders, gender-mismatched patients were found to have a 6.9% increase in likelihood of graft failure, (P = .042). Female recipients receiving male organs had no significant change in the risk of graft failure (11.5%; P = .368). A worse outcome was found in male recipients receiving female organs (12.9%; P = .0003). Graft failure rate among patients with donors matched by race (white to white or nonwhite to nonwhite; n = 21,818) was 11.6% versus 11.9%, and among unmatched patients (n = 10,697), the difference was not significant (P = .33). Multivariate regression analysis controlling for potential confounders confirmed that this difference was not significant (P = .21). Mismatch between black donors and white recipients was found to increase the risk of liver graft failure (27.4%, P = < .0001), independently of gender, number of comorbidities, and functional status at time of transplant.
Autoimmune hepatitis after liver transplantation and other lessons of self-intolerance
Authors: Czaja Albert J.
Published: August 2002

Autoimmune hepatitis has been described as recurrent or de novo disease after transplantation. The legitimacy of these diagnoses and the bases for their occurrence are unknown. To better understand these aspects of allograft dysfunction, the purported pathogenic mechanisms of classical autoimmune hepatitis were reviewed and extrapolated to recurrent and de novo disease after transplantation. Loss of self-tolerance may relate to defects in the negative selection of autoreactive immunocytes and the clonal expansion of promiscuous lymphocytes that are cross-reactive to homologous antigens (molecular mimicry). Repopulation of the allograft with recipient antigen-presenting cells and the presence of primed promiscuous cytotoxic T cells within the recipient are likely factors for recurrent disease. Targets may be the same peptides that triggered the original disease, donor-derived class II antigens of the major histocompatibility complex, or homologous antigens associated with unidentified hepatotrophic viruses. De novo disease is probably due to similar mechanisms, but its predilection for children suggests that thymic dysfunction associated with cyclosporine treatment may be a factor. Corticosteroid therapy is effective in each condition. In conclusion, recurrent and de novo autoimmune hepatitis after transplantation are examples of self-intolerance. The mechanisms that perturb immunologic homeostasis in this human model of the classical disease must be studied more rigorously.
Living donor liver transplantation for giant hepatic hemangioma with Kasabach-Merritt syndrome with a posterior segment graft
Authors: Kumashiro Yuji , Kasahara Mureo , Nomoto Kazuhiro , Kawai Masaru , Sasaki Katsuya , Kiuchi Tetsuya , Tanaka Koichi
Published: August 2002

We present a case of a giant hepatic hemangioma with Kasabach-Merritt syndrome, which was cured by living donor liver transplantation. A 48-year-old woman complained of abdominal fullness and appetite loss. The laboratory data showed disseminated intravascular coagulation and a morphologic evaluation revealed a giant hepatic hemangioma involving both lobes of the liver. Living donor liver transplantation was indicated for Kasabach-Merritt syndrome and an unresectable liver tumor. A posterior segment graft was used because the remnant liver volume of the donor might have been too small to sustain the liver function of the donor. The postoperative course was uneventful, and the recipient was discharged from hospital on day 15 after the transplantation without complications.
Treatment of posttransplantation recurrence of hepatitis C with interferon and ribavirin: Lessons on tolerability and efficacy
Authors: Narayanan Menon Kozhikode V. , Poterucha John J. , El-Amin Omer M. , Burgart Lawrence J. , Kremers Walter K. , Rosen Charles B. , Wiesner Russell H. , Charlton Michael
Published: August 2002

Recurrence of hepatitis C virus (HCV) infection after orthotopic liver transplantation is a major cause of graft failure. The aim of our study was to determine the safety, efficacy, and tolerability of combination therapy with interferon and ribavirin in the treatment of recurrent hepatitis after liver transplantation. Twenty-six patients (18 men) with histologically established HCV recurrence after liver transplantation for cirrhosis secondary to chronic HCV infection were treated with a combination of interferon alfa-2b (3 million units three times weekly) and ribavirin (800 to 1,000 mg/d). Dosage modifications were according to a standard protocol incorporating laboratory values and clinical side effects. Fifty percent of patients completed 1 year or more of therapy. On an intention-to-treat basis, nine patients (35%) showed an end-of-treatment virological response. Six of these nine patients completed greater than 6 additional months of follow-up, and all have had sustained virological responses. A histological response (decrease in histological activity index ≥ 2) was seen in 75% of virological responders and 67% of nonresponders. Adverse events requiring dose modification or cessation of therapy occurred in 66% of patients. Adjuvant therapies used to support hemoglobin levels included erythropoietin and red blood cell transfusions. There were no independent pretreatment predictors of a virological response, perhaps because of the small sample size. Combination therapy with interferon and ribavirin may be beneficial in patients with recurrent HCV after liver transplantation. The majority of patients require dose modifications because of side effects. Histological response is common in virological nonresponders. (Liver Transpl 2002;8:623-629.)
Predicting the decrease of conjugated bilirubin with extracorporeal albumin dialysis MARS using the predialysis molar ratio of conjugated bilirubin to albumin
Authors: Lee Kang-Hoe , Wendon Julia , Lee Margaret , Da Costa Maureen , Lim Seng-Gee , Tan Kai-Chah
Published: August 2002

Extracorporeal albumin dialysis with the molecular adsorbent recirculating system (MARS) machine is a new supportive intervention for patients with liver failure. It removes bilirubin and other albumin-bound toxins from the patient and has been shown by preliminary studies of liver failure patients to be beneficial. Our study examines the ability of predialysis molar ratio of bilirubin to albumin to predict the decrease of bilirubin by MARS. We had 5 patients and results from 29 treatments. The results showed a significant correlation between the predialysis molar ratio of bilirubin (total and conjugated) to albumin to the reduction in bilirubin (total and conjugated): R2 = 0.27 and 0.62 respectively, P < .005 for both. There was no significant correlation with the predialysis molar ratio of unconjugated bilirubin to albumin to the reduction in unconjugated bilirubin. The ratio of change in total bilirubin (μmol/L) to the predialysis molar ratio of total bilirubin to albumin and the ratio of change in conjugated bilirubin (μmol/L) to the predialysis molar ratio of conjugated bilirubin to albumin were 6.2 (± 4.2) and 10.8 (± 4.3), respectively (mean (± SD)). The results enable us to predict the likely reduction in bilirubin (especially conjugated) after each MARS treatment and also suggest to us that albumin infusion before MARS treatment may reduce the efficacy of bilirubin removal. Whether this ratio applies to other albumin-bound toxins remains open for investigation.
Cure of gastric antral vascular ectasia by liver transplantation despite persistent portal hypertension: A clue for pathogenesis
Authors: Vincent Catherine , Pomier-Layrargues Gilles , Dagenais Michel , Lapointe Réal , Létourneau Richard , Roy André , Paré Pierre , Huet Michel P.
Published: August 2002

Gastric antral vascular ectasia (GAVE) is a rare cause of chronic bleeding in cirrhotic patients. It has been suggested that these gastric lesions might be related to portal hypertension, hepatic insufficiency, or both parameters. We report two cases of cirrhotic patients in whom GAVE was the source of recurrent bleeding. These patients also had complete portal vein thrombosis. Liver transplantation was performed and an end-to-end cavoportal anastomosis was performed, leaving patients with persistent portal hypertension after surgery. We observed complete disappearance of the antral lesions several weeks after transplantation, which shows that the GAVE is not related to portal hypertension but is rather a direct consequence of liver failure. Possible pathophysiologic mechanisms are discussed.