bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing strategies in diagnosis and management of hilar cholangiocarcinoma
Authors: Figueras Juan , Llado Laura , Valls Carlos , Serrano Teresa , Ramos Emilio , Fabregat Juan , Rafecas Antonio , Torras Jaume , Jaurrieta Eduardo
Published: March 2004

Hilar cholangiocarcinoma is one of the most difficult tumors to stage and treat. This study aims to evaluate (1) the best diagnostic imaging, (2) the usefulness of preoperative biliary drainage, (3) the resectability rate, and (4) the results of palliative treatments and surgical resection. Seventy-six patients with hilar cholangiocarcinoma with a mean age of 64 ± 11 years were treated at our institution from 1989 to 1999. Patients were studied preoperatively using ultrasound, computed tomography (CT), and percutaneous cholangiography or magnetic resonance cholangiography. Forty-eight patients (63%) underwent palliative treatment. Twenty-eight patients underwent surgical curative therapy; 20 resections and 8 orthotopic liver transplantations (OLTs). Percutaneous transhepatic cholangiography was performed in 18 of 28 patients (64%), and magnetic resonance cholangiography in 5 patients; both methods were equally effective in establishing tumoral invasion of the biliary ducts. Five patients did not undergo either diagnostic modality. Excluding the patients who underwent OLT, no significant differences were found in surgical mortality (1 v 2 patients) or postoperative morbidity (100% v 66%) for patients with and without preoperative biliary drainage. The postoperative mortality rate was 11% (3 of 28 patients). The overall resectability rate was 37%. Mean survival in the surgical and palliative groups was 35 and 6 months, respectively (P < .0001). Patients who underwent OLT had a better 5-year survival rate than those treated by tumor resection (36% v 21%; P = .02). Combined chemotherapy and radiotherapy apparently did not provide a significant survival benefit. Helical CT and magnetic resonance cholangiography are useful techniques to delineate tumor extent and rule out vascular invasion and lymph node or liver metastases. No clear conclusions regarding preoperative drainage can be drawn from this study. A high resectability rate (37%) is feasible with major hepatectomy.
Selection of donors and recipients for living donor liver transplantation
Authors: Trotter James F.
Published: March 2004

Key Points

1. Living donor liver transplantation (LDLT) is increasingly used for adults with end-stage liver disease.

2. Standards for acceptable rates of donor morbidity, and even mortality, must be evaluated in the context of recipient risk of dying while on the waiting list and outcome after transplantation.

3. Use of our current criteria in Colorado for selection of donors and recipients indicated that 15% of recipients could undergo LDLT.
Treatment options for other hepatic malignancies
Authors: O’Grady John G.
Published: March 2004

Key Points

1. Resection rates for cholangiocarcinoma (unrelated to primary sclerosing cholangitis) have increased to 54% to 79%, and the subsequent 5-year survival rates are 24% to 31%.

2. Multimodality approaches involving various combinations of chemotherapy, irradiation, and surgery increasingly are being used to treat cholangiocarcinoma.

3. The role of liver transplantation in the management of cholangiocarcinoma is limited by the perception that it is inappropriate to use scarce organs when 5-year survival rates are 25%.

4. Liver transplantation is an important intervention in patients with tumors that remain unresectable after chemotherapy. The role of liver transplantation in patients with extrahepatic disease that responds to chemotherapy is controversial. Careful timing of surgery is required to avoid secondary drug resistance.

5. Liver transplantation has been successfully applied to a range of rare hepatic malignancies, but small numbers preclude strong recommendations on the appropriateness of this practice.
Retransplantation for hepatitis C: Implications of different policies
Authors: Rosen Hugo R.
Published: March 2004

Key Points

1. Approximately 20% of hepatitis C virus (HCV)-positive liver transplant recipients develop evidence of allograft cirrhosis by year 5.

2. The prevalence of HCV infection in patients undergoing retransplantation has significantly increased since 1990.

3. Retransplantation for recurrent HCV is associated with poor long-term survival.

4. Preoperative hyperbilirubinemia (billirubin ≥5 mg/dL) and renal failure predict poor outcome after retransplantation.

5. Retransplantation is the only viable option for patients in whom allografts fail because of recurrent HCV disease.
Regional cerebral blood flow autoregulation in patients with fulminant hepatic failure
Authors: Larsen Fin Stolze , Strauss Gitte , Møller Kirsten , Hansen Bent Adel
Published: March 2004

The absence of cerebral blood flow autoregulation in patients with fulminant hepatic failure (FHF) implies that changes in arterial pressure directly influence cerebral perfusion. It is assumed that dilatation of cerebral arterioles is responsible for the impaired autoregulation. Recently, frontal blood flow was reported to be lower compared with other brain regions, indicating greater arteriolar tone and perhaps preserved regional cerebral autoregulation. In patients with severe FHF (6 women, 1 man; median age, 46 years; range, 18 to 55 years), we tested the hypothesis that perfusion in the anterior cerebral artery would be less affected by an increase in mean arterial pressure compared with the brain area supplied by the middle cerebral artery. Relative changes in cerebral perfusion were determined by transcranial Doppler-measured mean flow velocity (Vmean), and resistance was determined by pulsatility index in the anterior and middle cerebral arteries. Cerebral autoregulation was evaluated by concomitant measurements of mean arterial pressure and Vmean in the anterior and middle cerebral arteries during norepinephrine infusion. Baseline Vmean was lower in the brain area supplied by the anterior cerebral artery compared with the middle cerebral artery (median, 47 cm/s; range, 21 to 62 cm/s v 70 cm/s; range 43 to 119 cm/s, respectively; P < .05). Also, vascular resistance determined by pulsatility index was greater in the anterior than middle cerebral artery (median, 1.02; range 1.00 to 1.37 v 0.87; range 0.75 to 1.48; P < .01). When arterial pressure was increased from 84 mm Hg (range 57 to 95 mm Hg) to 115 mm Hg (range, 73 to 130 mm Hg) during norepinephrine infusion, Vmean remained unchanged in 2 patients in the anterior cerebral artery, whereas it increased in the middle cerebral artery in all 7 patients. In the remaining patients, Vmean increased approximately 25% in both the anterior and middle cerebral arteries. Thus, this study could only partially confirm the hypothesis that autoregulation is preserved in the brain regions supplied by the anterior cerebral artery in patients with FHF. Although the findings of this small study need to be further evaluated, one should consider that autoregulation may be impaired not only in the brain region supplied by the middle cerebral artery, but also in the area corresponding to the anterior cerebral artery.
Biliary anastomosis in living related liver transplantation using the right liver lobe: Techniques and complications
Authors: Testa Giuliano , Malagó Massimo , Valentín-Gamazo Camino , Lindell Gert , Broelsch Christoph E.
Published: March 2004

Since the introduction of adult-to-adult living donor liver transplantation using the right lobe of the liver, biliary problems have led the list of complications resulting in postoperative morbidity. We report our experience with the first 30 living donor liver transplantations performed in our institution from August 1998 to January 2000. Patients were 21 men and 9 women, with a mean age 45 ± 16 years. Mean recipient weight was 65.1 ± 17.9 kg, mean graft weight was 877 ± 146 g, and the mean graft-recipient weight ratio was 1.5 ± 0.6. Patient and graft survival rates were 83.3% and 80%, respectively. Biliary anastomosis was either an end-to-end hepaticocholedochostomy with a T-drain or hepaticojejunostomy. Mean follow-up was 217.4 ± 149.8 days. The overall complication rate was 26.6% (8 of 30 procedures) and was directly correlated to the type of anastomosis and number of bile ducts. Surgical revision was necessary in all cases. Biliary complications were not the primary cause of graft loss. Adult living donor liver transplantation using the right lobe is a successful procedure, with graft and patient survival similar to those in cadaver full-organ transplantation. Postoperative morbidity, mainly caused by biliary leak, was directly related to the number of ducts and type of anastomosis. With increasing experience, we have better defined our plane of transection on the hilar plate, with the goal of obtaining only 1 biliary duct for the anastomosis. We also improved our parenchymal transection technique, which resulted in a decreased incidence of leak at the cut-surface area.
Living donor liver transplantation in adults: Outcome in Japan
Authors: Todo Satoru , Furukawa Hiroyuki , Jin Maeng Bon , Shimamura Tsuyoshi
Published: March 2004

Key Points

1. Twenty centers in Japan performed 308 living donor liver transplants (LDLT) in adults.

2. Right lobe grafts were used in the minority of cases (27.1%); most had left lobe grafts (72.9%). Survival was not influenced by the type of graft.

3. There were no donor deaths (0%); 9.3% of donors experienced mild to moderate complications. Biliary complications were the most frequent.

4. Overall recipient survival was 72.4%.
Ethical issues surrounding adult-to-adult living donor liver transplantation
Authors: Shapiro Robyn S. , Adams Mark
Published: March 2004

Key Points

1. The ethical principle of utility is enhanced by living donor liver transplantation (LDLT). LDLT carries the potential to optimize efficient use of organs, minimize pretransplant morbidity and mortality, and increase availability of cadaveric organs.

2. The most serious ethical concerns in LDLT focus on the risks to the donor and relate to the principle of nonmaleficence—“do no harm”. Although exact risk remains uncertain, there is potential for significant donor morbidity and even mortality.

3. Careful consideration must be given to development of the best approach to obtaining truly informed consent.

4. Specific criteria for LDLT should be developed for transplant centers, donors, and recipients. Informed consent should be standardized.

5. A national registry for donors and recipients of LDLT is needed.
Living donor liver transplantation in adults: Outcome in Europe
Authors: Broelsch Christoph E. , Malagó Massimo , Testa Giuliano , Gamazo Camino Valentin
Published: March 2004

Key Points

1. Eleven European centers have performed 228 living donor liver transplants (LDLT): 105 in children and 123 in adults.

2. Right lobe donation was used in 111 of 123 adult cases (90%).

3. There was 1 donor death (˜0.8%), and 17.8% of donors experienced significant complications.

4. Eighty-six percent of recipients and 83% of grafts survived. Biliary complications occurred in 14.6%.
Confirmation of the role of the mayo risk score as a predictor of resource utilization after orthotopic liver transplantation for primary biliary cirrhosis
Authors: Gilroy Richard K. , Lynch Stephen V. , Strong Russell W. , Kerlin Paul , Balderson Glenda A. , Stuart Katherine A. , Crawford Darrell H.G.
Published: March 2004

Resource utilization is an important consideration when patients are selected for orthotopic liver transplantation (OLT). The Mayo Risk Score has been proposed to help predict optimum time for OLT. We assessed the relation between Mayo risk score, Child-Pugh score, and resource utilization and outcome after OLT for primary biliary cirrhosis. The mean Mayo risk score was greater in patients who died than in the survivors (8.6 ± 1.4 v 7.1 ± 1.8; P < .05). There was a positive correlation between Mayo risk score and the 4 resource variables studied (intraoperative blood requirements, time ventilated, and duration of intensive care unit and hospital stays). Patients with a Mayo risk score greater than 7.8 used almost twice the resources of patients with a risk score less than 7.8. A positive correlation also existed between Child-Pugh score and duration of hospital stay. The mean Child-Pugh score in patients who died was greater than that in survivors (10.7 ± 2.0 v 8.5 ± 2.8, P = .03). This study confirms that Mayo Risk score is an important predictor of resource utilization and outcome after OLT.
Expanding the use of transjugular intrahepatic portosystemic shunts for veno-occlusive disease
Authors: Rajvanshi Pankaj , McDonald George B.
Published: March 2004

Severe veno-occlusive disease (VOD) of the liver is a leading cause of mortality after bone marrow transplantation (BMT). Vascular and parenchymal injuries account for acute portal hypertension and liver failure is frequently present. We describe the results of transjugular intrahepatic portosystemic shunt (TIPS) for the management of VOD after BMT. TIPS was performed in 10 patients with histologically proven severe VOD. Portal hypertension was controlled by TIPS in all patients (mean hepatic venous pressure gradient before, 20 ± 11 vs 6 ± 5 mm Hg after TIPS, P < 0.01) without technical complications. Five patients with rapidly worsening VOD died within 10 days of TIPS without any improvement. The five remaining patients with less advanced disease showed improvement in various clinical and biological parameters. Four patients subsequently died. The lone survivor continues to do well with resolution of VOD 6 months after TIPS. TIPS can be performed safely and controls portal hypertension in VOD after BMT. Arguments from the present series and from eight previously reported cases favour earlier application of TIPS to obtain improved overall survival.
Clinical usefulness of Epstein-Barr viral load in solid-organ transplantation
Authors: Buteau Chantal , Paya Carlos V.
Published: March 2004

Epstein-Barr virus (EBV) DNA was quantitated in peripheral blood mononuclear cells (PBMC) from 25 healthy subjects, 105 asymptomatic solid-organ transplant (SOT) recipients, and 15 SOT recipients with symptomatic EBV infections by using a newly developed quantitative-PCR technique. Patients with symptomatic EBV infections had significantly higher (P < 0.001) median EBV DNA levels than asymptomatic SOT recipients and immunocompetent individuals. In SOT recipients, the positive predictive value of EBV DNA levels of > 1,000 genome equivalents (GE)/0.5 μg of total PBMC DNA was 64.7% for symptomatic EBV infection, while the negative predictive value was 96.1%. In 19 of 32 (59.3%) asymptomatic SOT recipients, EBV DNA levels were consistently below 1,000 GE for as long as 18 months, while 10 of 32 (31.2%) patients had 1,000 to 5,000 EBV GE at least once during follow-up. In a minority of patients (3 of 32; 9.3%), ≥ 5,000 GE could be detected at least once during follow-up. Reduction of immunosuppressive treatment decreased EBV DNA levels by ≥ 1 log10 unit in patients with symptomatic EBV infections. Quantification of EBV DNA is valuable for the diagnosis and monitoring of symptomatic EBV infections in SOT recipients.
High levels of hepatitis C virus RNA in native livers correlate with the development of cholestatic hepatitis in liver allografts and a poor outcome
Authors: Deshpande Vikram , Burd Eileen , Aardema Kay L. , Ma Chan K. , Moonka Dilip K. , Brown Kimberly A. , Abouljoud Marwan S. , Nakhleh Raouf E.
Published: March 2004

A subset of hepatitis C virus (HCV)-positive liver transplant recipients develop cholestatic hepatitis (CH). We investigated the role of pretransplantation disease activity (estimated by Knodell score and HCV RNA quantitation) in the native liver explant on the development of CH and graft and patient outcome. Eight patients with CH were identified among HCV-positive liver transplants and were compared with 20 consecutive patients with recurrent HCV hepatitis of noncholestatic type in liver transplants. We evaluated all 28 explanted native livers histologically using the Knodell scoring system. HCV viral load was measured in the native explant and 5 allograft explants from the CH group using Amplicor HCV RNA Monitor test. Six of 8 patients with CH had HCV RNA levels of 5,000 copies/μg of DNA or greater in the native liver explant, whereas only 1 of the control group had viral loads greater than this level. Greater HCV RNA levels correlated with worse graft and patient survival (P < .001). The 3-year survival rate in the CH group was 18% compared with 77% in the control group (P < .001). There was no difference in the primary immunosuppressive regimens used in the 2 groups. We conclude that (1) CH has a uniformly poor prognosis, (2) type of immunosuppressive therapy appears to have little influence on the development of CH, (3) high pretransplantation HCV RNA levels in the native explant may predict the development of CH, and (4) patients with high HCV RNA levels in the explanted native liver may be appropriate candidates for antiviral therapy to prevent the development of CH.
Rejection of pig liver xenografts in patients with liver failure: Implications for xenotransplantation
Authors: Tector Joseph A. , Berho Mariana , Fridell Jonathan A. , DiCarlo Antonio , Liu S. , Soderland Carl , Barkun Jeffrey S. , Metrakos Peter , Tchervenkov Jean I.
Published: March 2004

The pathophysiological state of rejection in liver xenotransplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig-to-human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xenoreactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b-9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure.
A novel approach in treating recurrent bilateral hepaticojejunostomy biliary strictures post-liver transplantation: Successful use of Simpson’s atherectomy device
Authors: Rajadhyaksha Amar , Kim Ducksoo , Chari Ravi , Frassica Joseph , Primack William , Katz Eliezer
Published: March 2004

Biliary complications occur in 6% to 34% of patients who undergo orthotopic liver transplantation. Strictures at the anastomosis site or elsewhere in the biliary tract are common. These strictures are amenable to interventional radiological and surgical procedures; however, retransplantation is sometimes an inevitable outcome. An 8-year-old boy received combined liver and kidney transplants May 31, 1998. Hepatic artery thrombosis was diagnosed postoperative day 1 and treated with revascularization. The choledochojejunostomy was revised twice and resulted in a high hepaticojejunostomy. Significant strictures on both the right and left hepatic ducts at the anastomosis site were unsuccessfully treated by multiple interventional radiological procedures. The option of retransplantation was seriously explored. Simpson’s atherectomy device was used in a novel approach February 24, 1999, and strictures on both ducts were successfully treated. At 1-year postprocedure, the patient has normal liver function with no evidence of recurrence of the strictures. Further experience with this novel technique is required to assess its role in treating biliary strictures post liver transplantation.
Use of transjugular intrahepatic portosystemic shunt as a bridge to liver transplantation in a patient with severe hepatopulmonary syndrome
Authors: Lasch Hugh M. , Fried Michael W. , Zacks Steven L. , Odell Pat , Johnson Mark W. , Gerber David A. , Sandhu Fatejeet S. , Fair Jeffrey H. , Shrestha Roshan
Published: March 2004

Hepatopulmonary syndrome (HPS) is defined by the presence of the triad of liver disease, arterial hypoxemia, and intrapulmonary vascular dilatation. The clinical implication of this disorder is impairment of gas exchange. Numerous reports in the literature show that this condition is reversible with orthotopic liver transplantation (OLT). However, patients with HPS often present with Pao2 levels that are quite low. OLT with a preoperative Pao2 less than 50 mm Hg is associated with unacceptably high mortality and morbidity. We report a case of severe HPS in which a transjugular intrahepatic portosystemic shunt was successfully used to improve oxygenation, thus allowing a successful elective OLT.
Tacrolimus conversion improves hyperlipidemic states in stable liver transplant recipients
Authors: Manzarbeitia Cosme , Reich David J. , Rothstein Kenneth D. , Braitman Leonard E. , Levin Scott , Munoz Santiago J.
Published: March 2004

With improvements in surgical technique and the advent of new and more effective immunosuppressive agents, survival rates in liver transplant recipients have dramatically improved. However, hyperlipidemia frequently develops in patients administered cyclosporine-based immunosuppression long-term, although it appears to occur less often with newer, tacrolimus-based regimens. We sought to determine whether an isolated change in the baseline immunosuppressive regimen (cyclosporine to tacrolimus) would improve hyperlipidemic states in these patients. Twenty-one long-term stable liver transplant recipients with hyperlipidemia, manifested by elevated cholesterol and/or triglyceride levels, were offered conversion to tacrolimus from cyclosporine A therapy. Lipid profiles were monitored at baseline (while on cyclosporine therapy) and at 1 and 3 months after conversion to tacrolimus therapy. There were no other medication manipulations. After conversion to tacrolimus therapy, mean cholesterol levels decreased from 251 to 202 mg/dL at 1 month (P < .001) and 194 mg/dL at 3 months (P < .001). Similarly, triglyceride levels decreased from 300 to 207 mg/dL by 1 month (P = .011) and 203 mg/dL by 3 months (P < .001). There was also a statistically significant decrease for very low-density lipoprotein levels at 3 months (P = .005) and low-density lipoprotein levels at 1 and 3 months (P = .013 and P = .014, respectively). High-density lipoprotein levels did not significantly change after conversion to tacrolimus therapy. Conversion was not accompanied by adverse side effects, and patients tolerated the change well. In conclusion, simple conversion from cyclosporine to tacrolimus-based immunosuppression therapy is safe and improves posttransplantation hyperlipidemia in a subgroup of liver transplant recipients.
Liver transplantation in patients with portal vein thrombosis
Authors: Manzanet Gerardo , Sanjuán Fernando , Orbis Paco , López Rafael , Moya Ángel , Juan Manuel , Vila Juanjo , Asensi Josep , Sendra Pedro , Ruíz José , Prieto Martín , Mir José
Published: March 2004

The aim of this study is to analyze the incidence, risk factors, management, and follow-up of patients with portal vein thrombosis (PVT) undergoing primary orthotopic liver transplantation (OLT). Four hundred fifteen OLTs were performed in 391 patients. In 62 patients, partial (group 1; n = 48) or complete (group 2; n = 14) PVT was found at the time of surgery. Portal flow was reestablished by venous thrombectomy. In this study, we compare 62 primary OLTs performed in patients with PVT at the time of OLT with a group of 329 primary OLTs performed in patients without PVT (group 3) and analyze the incidence of PVT, use of diagnostic methods, surgical management, and outcome. We found no significant differences among the 3 groups for length of surgery, cold and warm ischemic times, and postoperative stay in the intensive care unit. With the piggyback technique, groups 1 and 2 had greater blood losses and required more blood transfusions than group 3. The early reoperation rate was greater in group 2. The incidence of rethrombosis was 4.8% (group 1, 2%; group 2, 14.3%). Reexploration and thrombectomy (2 patients) and retransplantation (1 patient) had a 100% mortality rate. In particular, the mortality rate of patients with complete PVT with extension into the splanchnic veins is high (33%). Three-month and 4-year patient survival rates were statistically similar in the 3 groups. The presence of PVT at the time of OLT is not a contraindication for OLT. However, if PVT extends into the splanchnic veins, the outcome is guarded.
Domino split-liver transplantation from a living donor: Case reports of in situ and ex situ splitting
Authors: Inomata Yukihiro , Nakamura Taro , Uemoto Shinji , Tanaka Koichi , Wakabayashi Go , Shimazu Motohide
Published: March 2004

The liver from a patient with familial amyloid polyneuropathy (FAP) scheduled for living donor liver transplantation can be split and transplanted into 2 adult patients with end-stage liver disease. We have performed this procedure, called domino split transplantation, twice. The native liver was split in situ in 1 patient with FAP and ex situ in the other patient with FAP. The recipients of the livers from the patients with FAP and their living donors are doing well without serious complications. Of the 4 secondary recipients, 3 patients survived. Domino split-liver transplantation from a living donor thus appears to be a promising procedure for expansion of the donor pool.
Posttransplantation dialysis-associated infections: Morbidity and impact on outcome in liver transplant recipients
Authors: Singh Nina , Gayowski Timothy , Wagener Marilyn M.
Published: March 2004

The aim of this study is to assess the predictors, impact on infectious morbidity, and outcome of posttransplantation dialysis in liver transplant recipients and to compare the results with data from patients who did not require dialysis after transplantation. The study sample included 176 consecutive patients undergoing liver transplantation; the median follow-up was 4.3 years. All patients were administered tacrolimus as primary immunosuppression. Overall, 16% (28 of 176 patients) of the patients required dialysis after transplantation. Patients requiring dialysis had significantly greater pretransplantation creatinine levels (2.4 v 1.2 mg/dL; P = .009), were more likely to require pretransplantation dialysis (21% v 1%; P = .0001), and had a greater rate of biopsy-proven rejection episodes (50%, 14 of 28 episodes v 20%, 30 of 148 episodes; P = .0009) and longer posttransplantation intensive care unit lengths of stay (P = .0001). The incidence of infections (91% v 41%; P = .0001) and episodes of infection per patient (2.4 v 0.7 episodes; P = .0001) were significantly greater in patients undergoing dialysis compared with those not undergoing dialysis. There was no difference in the frequency of cytomegalovirus (CMV) infection or disease; however, bacterial infections (87% v 31%; P = .0001) and invasive fungal infections (39% v 7%; P = .0001) were significantly more likely to occur in patients requiring dialysis. In logistic regression, dialysis (P = .0006) and CMV infection (P = .007) were independent significant predictors of major infections. Overall survival (assessed by Kaplan-Meier probability) was less in patients undergoing dialysis compared with those not undergoing dialysis (P = .0001). Among dialyzed patients, only 10% of those who survived had an invasive fungal infection compared with 46% of those who died (P = .08); 5 of 6 patients died within 1 month of the fungal infection. The need for dialysis portended a grave outcome in liver transplant recipients and identified a subgroup of patients at a significantly greater risk for major infections, particularly fungal infections, after liver transplantation.
Hepatic involvement in hereditary hemorrhagic telangiectasia: An unusual indication for liver transplantation
Authors: Hillert Christian , Broering Dieter C. , Gundlach Matthias , Knoefel Wolfram T. , Izbicki Jakob R. , Rogiers Xavier
Published: March 2004

Hereditary hemorrhagic telangiectasia (HHT) is a vascular disease with multiple organ manifestations. Severe hepatic involvement is an unusal indication for liver transplantation. We report on a 39-year-old woman diagnosed with HHT and decompensation of the disease during her second pregnancy. After delivery, hemobilia occurred, followed by severe therapy-resistant cholangitis and progressive liver dysfunction. Because of progressive loss of liver function, orthotopic liver transplantation needed to be performed. The various aspects of liver involvement in Osler’s disease, diagnosis, and therapy are discussed.
Right hepatic lobectomy as a liver graft-saving procedure
Authors: Honoré Pierre , Detry Olivier , Hamoir Etienne , Defechereux Thierry , Detroz Bernard , Meurisse Michel , Jacquet Nicolas
Published: March 2004

Retransplantation is common after liver transplantation (LT). However, in the present era of organ shortages, every attempt to save the liver graft should be performed before considering retransplantation. We report our experience with right hepatic lobectomy (RHL) for liver graft salvage. In a retrospective series of 180 adult LTs, 4 patients underwent RHL (Couinaud’s segments V, VI, VII, VIII) in the post-LT period. In all cases, the procedure was performed without Pringle’s maneuver or mobilization of the left liver lobe to preserve its vascularization. Three liver graft recipients developed intrahepatic biliary strictures, mainly localized to the right lobe of the graft, and RHL was performed 14, 75, and 78 months after LT. These patients were alive at last follow-up without further episodes of cholangitis or retransplantation (mean follow-up, 38 months). The fourth patient developed early post-LT right liver necrosis with a functioning hepatic artery and underwent right lobectomy 48 hours after LT. He later developed cholangitis secondary to late hepatic artery thrombosis, requiring retransplantation after 18 months. We conclude that RHL can be considered a graft-saving option in selected liver transplant recipients with localized biliary strictures, with excellent patient and graft survival.
Recurrent autoimmune hepatitis after orthotopic liver transplantation
Authors: González-Koch Alvaro , Czaja Albert J. , Carpenter Herschel A. , Roberts Stuart K. , Charlton Michael R. , Porayko Michael K. , Rosen Charles B. , Wiesner Russell H.
Published: March 2004

To determine the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease were monitored after surgery in accordance with a surveillance protocol. Tacrolimus or cyclosporine plus prednisone were administered to each patient, and liver biopsy examinations were performed at least annually according to protocol. Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent disease was defined as the presence of lymphoplasmacytic infiltrates in liver tissue in the absence of other causes of allograft dysfunction. Autoimmune hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6 ± 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by surveillance liver biopsy assessment in 2 patients. Histological changes were mild, and there was no progression to cirrhosis during 4.9 ± 0.9 years of observation. Five-year patient (86% v 82%; P = .9) and graft (86% v 67%; P = .5) survival rates were not statistically different between patients with and without recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with than without recurrence (100% v 40%; P = .008) and healthy subjects (100% v 49%; P = .01). Recurrent disease was unrelated to donor HLA status. In conclusion, recurrence after transplantation for type 1 autoimmune hepatitis is common. Its mild manifestations and favorable prognosis may reflect early detection by a surveillance protocol and/or continuous corticosteroid treatment. HLA-DR3- or HLA-DR4-positive recipients are at risk for recurrence regardless of donor HLA status.
Evidence of serious graft damage induced by de novo hepatitis B virus infection after liver transplantation
Authors: Segovia Roberto , Sánchez-Fueyo Alberto , Rimola Antoni , Grande Luis , Bruguera Miquel , Costa Josep , Soguero Carolina , Uriz Juan
Published: March 2004

De novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is commonly believed to be a relatively benign condition, in contrast to post-OLT infection recurrence, considered a very aggressive complication. We reviewed the charts of 569 non-HBV-related OLTs performed at our institution and identified 19 patients (3%) with de novo HBV infection (appearance of hepatitis B surface antigen [HBsAg] after OLT). After a median follow-up of 25 months beyond the detection of HBsAg, 12 patients (63%) had developed serious HBV-related graft damage (cirrhosis in 6 patients, bridging chronic hepatitis in 4 patients, and fulminant hepatitis in 2 patients); 7 patients (37%) had lost their grafts; and 4 patients (21%) had died. All graft losses and deaths were related to de novo HBV infection. Similar rates of severe graft damage (62%), graft loss (38%), and death (33%) related to HBV infection were found in a concomitant series of 21 patients with recurrent HBV infection after OLT. Responses to antiviral therapy (interferon or lamivudine) were also similar in the 2 groups of patients. In 12 patients with de novo HBV infection, evidence of past HBV infection (positive serum antibody to hepatitis B core antigen and/or serum or liver tissue HBV DNA) were detected in the donor (7 patients) or recipient (5 patients). No differences were observed in the clinical course after stratification according to the attributed origin of de novo HBV infection. We conclude that de novo HBV infection after OLT is associated with high rates of morbidity and mortality, similar to those described for post-OLT HBV infection recurrence.
Interspecies differences in hepatic Ca2+-ATPase activity and the effect of cold preservation on porcine liver Ca2+-ATPase function
Authors: Janicki Piotr K. , Wise Paul E. , Belous Andrey E. , Pinson Wright C.
Published: March 2004

The accumulation of intracellular calcium ([Ca2+]i) caused by ischemia-reperfusion during liver transplantation has been implicated as a factor leading to primary graft nonfunction. Plasma membrane (PM) and endoplasmic reticulum (ER) Ca2+-adenosinetriphosphatases (ATPases) are the primary transporters that maintain [Ca2+]i homeostasis in the liver. We hypothesized that the porcine liver is better than the rat liver as a model for the study of human liver Ca2+-ATPase activity. We also hypothesized that cold preservation would depress Ca2+-ATPase activity in the porcine liver. Pig and rat livers were harvested, and human liver samples were obtained from surgical resection specimens. All were preserved with University of Wisconsin solution, and porcine livers were also preserved on ice for 2 to 18 hours. Ca2+-ATPase activity was measured after incubation with 45Ca2+ and adenosine triphosphate in the presence of specific Ca2+-ATPase inhibitors. Porcine PM and ER Ca2+-ATPase activities were 0.47 ± 0.03 and 1.57 ± 0.10 nmol of Ca2+/mg of protein/min, respectively. This was not significantly different from human liver, whereas rat liver was significantly greater at 2.60 ± 0.03 and 9.2 ± 0.9 nmol of Ca2+/mg of protein/min, respectively. We conclude that the Ca2+-ATPase activity in the pig liver is equivalent to that of human liver, and thus, the pig liver is a better model than the rat liver. Cold preservation studies showed a significant decrease in porcine hepatic PM Ca2+-ATPase activity after 4 hours of storage and near-total inhibition after 12 hours. Porcine hepatic ER Ca2+-ATPase activity showed a 45% decrease in activity by 12 hours and a 69% decrease by 18 hours. We conclude that cold ischemia at clinically relevant times depresses PM Ca2+-ATPase more than ER Ca2+-ATPase activity in pig liver homogenates.
Hepatic artery thrombosis after orthotopic liver transplantation: A review of nonsurgical causes
Authors: Pastacaldi Sabrina , Teixeira Rosangela , Montalto Paolo , Rolles Keith , Burroughs Andrew K.
Published: March 2004

Hepatic artery thrombosis (HAT) is one of the principal causes of morbidity and graft loss following liver transplantation. There are several risk factors for the development of HAT; technical aspects of the arterial anastomosis are important particularly for early thrombosis, but the improvement of surgical technique has lessened this problem. Apart from technical causes, other risk factors include a variety of conditions such as low donor/recipient age ratio, immunologic factors, clotting abnormalities, tobacco use, and infections. In particular, cytomegalovirus (CMV) infection of endothelial cells has been recently suggested as an infective cause of HAT, as it is known to be followed by a rapid procoagulant response. Thus, latent CMV in an allograft may become activated and promote or contribute to vascular thrombosis. This review evaluates these aspects, focusing on data relating CMV infection or viremia to HAT following liver transplantation.
Preliminary results of a liver allocation plan using a continuous medical severity score that de-emphasizes waiting time
Authors: Freeman Richard B. , Rohrer Richard J. , Katz Eliezer , Lewis David W. , Jenkins Roger , Cosimi Benedict A. , Delmonico Francis , Friedman Amy , Lorber Marc , O’Connor Kevin , Bradley James
Published: March 2004

Liver allocation remains problematic because current policy prioritizes status 2B or 3 patients by waiting time rather than medical urgency. On February 21, 2000, we implemented a variance to the United Network for Organ Sharing liver allocation policy that redefined status 2A by much more rigid, definable criteria and prioritized status 2B patients by using a continuous medical urgency score based on the Child-Turcotte-Pugh score and other medical conditions. In this system, waiting time is used only to differentiate status 2B candidates with equal medical urgency scores. Comparing the 6-month period (period 1; n = 67) before implementation of this system to the 6-month period after implementation (period 2; n = 75), there was a significant reduction in the number of transplantations performed for patients listed as status 2A (46.3% to 14.7%; P = .002) and an increase in the number of patients listed as status 2B who received transplants (44.8% to 70.7%; P = .10). Most dramatically, there was a 37.1% reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62 deaths in period 2 (P = .005), with the most significant reduction for patients removed from this list at status 2B (52 v 18 patients; P = .04). There were 3 postoperative deaths in each period, with only 1 graft lost in period 2. Status 2B patients with the greatest degree of medical urgency received transplants without multiple peer reviews requesting elevation to 2A status. We conclude that a continuous medical urgency score system allocates donor livers much more fairly to those in medical need and reduces waiting list mortality without sacrificing efficacy.
Liver transplantation in cirrhotic patients with diabetes mellitus: Midterm results, survival, and adverse events
Authors: Blanco José J. , Herrero Ignacio J. , Quiroga Jorge , Sangro Bruno , Gómez-Manero Noemí , Pardo Fernando , Cienfuegos Javier A. , Prieto Jesús
Published: March 2004

Liver cirrhosis is frequently associated with diabetes mellitus (DM), and this metabolic complication is also frequent after orthotopic liver transplantation (OLT). The aim of our study is to investigate which factors are associated with DM before and after OLT and their impact on post-OLT evolution. We evaluated the prevalence of DM among 115 liver transplant candidates with cirrhosis and assessed their evolution after OLT (median follow-up, 41 months). Sixteen candidates had DM requiring pharmacological therapy (group A), 45 candidates had DM controlled with diet (group B), and 54 candidates did not have DM (group C). One-year and 3-year actuarial survival rates were 100% and 100% for group A, 91% and 85% for group B, and 77% and 74% for group C, respectively (P < .03). Post-OLT DM was more frequent in group A. The incidence of other metabolic complications, major infections, rejection, and arterial hypertension; the need for hospitalization; and renal and graft function of patients in groups A, B, and C were similar. The only risk factor for DM 1 year after OLT on multivariate analysis was pre-OLT DM requiring pharmacological treatment. The incidence of complications, need for hospitalization, and renal and graft function 1 year after OLT for patients with post-OLT DM were similar to those of patients without post-OLT DM. In conclusion, patients with cirrhosis who have DM have a greater risk for post-OLT DM, but their midterm survival is not worse than the survival of those without DM.
Physical activity and health-related quality of life in liver transplant recipients
Authors: Painter Patricia , Krasnoff Joanne , Paul Steven M. , Ascher Nancy L.
Published: March 2004

The US Surgeon General’s Report on Physical Activity and Health recommends that people of all ages engage in regular physical activity, and that significant health benefits can be obtained through a moderate amount of physical activity. Physical activity appears to improve health-related quality of life (HRQOL) by enhancing physical functioning in persons compromised by poor health. The Medical Outcomes Study Short Form-36 (SF-36) Health Status Questionnaire was sent to all patients who were 5 years or more post-liver transplantation at the University of California at San Francisco. Additional questions related to coexisting medical conditions and participation in regular physical activity were included. SF-36 scale scores were compared between active and inactive patients. Regression analysis was also performed to determine the contributions of coexisting medical conditions and physical activity to the physical scales of the SF-36 questionnaire. Patients who participated in regular physical activity had significantly higher scores on all physical scales and the physical component scale (PCS). The regression model, which included age, sex, time posttransplantation, retransplantation, recurrence of hepatitis C, number of comorbid conditions, and physical activity participation showed that both the number of comorbid conditions and participation in physical activity were significant independent contributors to the physical functioning scale and PCS. This study indicates that physical activity is related to HRQOL after liver transplantation independent of other coexisting medical conditions.
Immune activation is required for the induction of liver allograft tolerance: Implications for immunosuppressive therapy
Authors: Bishop Alex G. , McCaughan Geoffrey W.
Published: March 2004

Liver transplants in many animal models are unusual because often they are not rejected even when transplanted across complete major histocompatibility complex barriers without immunosuppression. Their paradoxical behavior is even more obvious when the immune mechanism of acceptance is examined. Instead of acceptance resulting from a lack of immune response to the graft, the opposite occurs, and there is an unusual extensive increase in immune activation in acceptance compared with rejection. This abnormal extensive immune activation is driven by donor leukocytes transferred with the liver and results in death of the recipient cells that would normally reject the transplant. Some forms of immunosuppression inhibit this activation-associated liver transplant tolerance. The significance of these findings and possible means to design future treatment protocols for clinical transplantation that optimize management of liver transplant recipients are discussed.
Fitness testing of pediatric liver transplant recipients
Authors: Unnithan Viswanath B. , Veehof Suzanne H.E. , Rosenthal Philip , Mudge Christine , O’Brien Teresa H. , Painter Patricia
Published: March 2004

Liver transplantation is accepted as the standard management for end-stage liver disease in children. Pediatric heart and heart-lung transplant recipients have shown significantly diminished exercise capacities compared with age-matched, able-bodied, control subjects. The primary aim of this study is to compare the fitness levels of a group of pediatric liver transplant (LT) recipients (LT group, 20 boys, 9 girls; age, 8.9 ± 4.8 years; 56 ± 35 months posttransplantation) with a group of able-bodied control subjects (22 boys, 12 girls; age, 8.4 ± 3.8 years). The secondary aim is to compare the performance of the LT group against the Fitnessgram criterion standards. We assessed muscular endurance by means of a partial curl-up, flexibility by means of the back-saver sit and reach, and cardiorespiratory fitness by means of the progressive aerobic cardiovascular endurance run (PACER). The only significant (P < .05) difference between the 2 groups was the number of shuttles run in the PACER (control, 16.8 ± 9.8 v LT, 11.5 ± 8.4 shuttles). Other differences between the 2 groups were not significant. With regard to satisfying the Fitnessgram criterion standards, only 35% of the LT group achieved the standards for the partial curl-up, 88% of the LT group achieved the criterion standards for flexibility, and 0% achieved the standards for the PACER. These results indicate that the LT group has diminished exercise capacity. The origins of exercise limitations deserve further investigation.