Ethical dilemmas in patient selection for a new kidney transplant program in Guyana, South America.

INTRODUCTION: We describe ethical/moral issues in patient selection in a new living donor kidney transplant program in Guyana, South America. CASE REPORTS: Over 3 years, we screened 450 patients with chronic kidney disease among which 70 were suitable for kidney transplantation. There were five patients whose evaluations raised possible ethical dilemmas: one had nonadherence to dialysis; two of Guyanese origin living abroad wished to have the transplant performed in Guyana; a minor wished to donate to her mother; and another subject was considering commercialization of the transplant process. RESULTS: Since inception of the renal replacement program in 2008, we have completed 13 living kidney transplantations, 17 peritoneal dialysis placements, and 20 vascular access procedures. In the five patients wherein faced ethical dilemmas, three were rejected for consideration despite having living donors: one was nonadherent, the second excluded due to an attempt to commercialize the process, and the third, a minor who wished to donate to the mother. The other two patients were considered Guyanese ex-patriots acceptable for the program. DISCUSSION: The consequence of kidney failure in Guyana prior to introduction of renal replacement therapy was a virtual death sentence. These cases illustrate ethical dilemmas serving to throw into stark relief the implications of decisions made in a developing country versus those in a developing country.

Orthotopic liver transplantation for Wilson's disease: a single-center experience.

BACKGROUND: Wilson's disease is an inherited disorder of copper metabolism characterized by reduced biliary copper excretion, which results in copper accumulation in tissues with liver injury and failure. Orthotopic liver transplantation (OLT) can be lifesaving for patients with Wilson's disease who present with fulminant liver failure and for patients unresponsive to medical therapy. The aim of this study is to review our experience with OLT for patients with Wilson's disease. METHODS: Between 1988 and 2000, 21 OLTs were performed in 17 patients with Wilson's disease. Patient demographics, pre-OLT laboratory data, operative data, and early and late postoperative complications were reviewed retrospectively. One-year patient and graft survival was calculated. RESULTS: Eleven patients had fulminant Wilson's disease; in six patients the presentation was chronic. Mean patient age at presentation was 28 years (range 4-51 years); mean follow-up was 5.27 years (range 0.4-11.4 years). Neurologic features of Wilson's disease were not prominent preoperatively and did not develop post-OLT except in one patient who developed acute neuropsychiatric illness and seizure. Renal failure, present in 45% of patients with fulminant Wilson's disease, resolved post-OLT with supportive care. One-year patient and graft survivals were 87.5% and 62.5%, respectively. Fifteen survivors have remained well with normal liver function and no disease recurrence. CONCLUSION: Liver transplantation for hepatic complications of Wilson's disease cures and corrects the underlying metabolic defect and leads to long-term survival in patients who present with either acute or chronic liver disease. Acute renal failure develops frequently in patients with fulminant Wilsonian hepatitis and typically resolves postoperatively.

Liver transplantation for autoimmune hepatitis.

Publications about liver transplantation (LTX) for autoimmune hepatitis (AIH) have started to emerge, but many issues remain unresolved. We reviewed data on 32 patients transplanted for AIH to determine how pretransplantation and posttransplantation characteristics correlate with recipient outcome, including disease recurrence. Recipients were 37+/- 14 years old; 30 of 32 were women. Most had chronic disease (8 +/- 6 years); 25% had fulminant failure. The majority had ascites (91%), jaundice (88%), elevated prothrombin time (18 +/- 3 seconds), and hypoalbuminemia (2.7 +/- 0.6 g/dL). All had hypergammaglobulinemia (3.0 +/- 1.0 g/dL) and autoantibodies (72% antinuclear, 74% smooth muscle). Only one was HLA A1-B8-DR3 positive. Other autoimmune disorders affected 25% of patients; half improved after transplantation. Actuarial survival was 81% at 1 and 2 years posttransplantation. There was a high frequency of rejection (75% of recipients had 1.7 +/- 0.8 episodes), and 39% of rejections required OKT3. Among 24 recipients with long-term follow-up (27 +/- 14 months), histologically proven recurrent AIH occurred in 25%, 15 +/- 2 months posttransplantation; half (3 patients) required retransplantation 11 +/- 3 months after diagnosis. After retransplantation 2 of 3 patients had re-recurrence within 3 months; 1 received a third LTx. Recurrence occurred in 6 of 18 patients transplanted for chronic disease vs. 0 of 6 transplanted as fulminants (P = not significant [NS]). Patients with and without recurrence had similar rejection profiles. In summary, results of LTx for AIH are excellent. However, AIH patients have a high frequency of rejection and often require OKT3. Furthermore, severe recurrent AIH sometimes develops, particularly in chronic versus fulminant AIH patients and in those already retransplanted for recurrence. Multicenter studies could elucidate the best posttransplantation immunosuppressive regimens for AIH patients.

Risk factors for intra-abdominal infection after pancreas transplantation.

BACKGROUND: This study was designed to determine risk factors for intra-abdominal abscess after pancreas transplantation. METHODS: We performed a single-center retrospective review of all pancreas transplants from 1994 to 1999. Risk factors studied were donor age, body weight, body mass index, peak serum glucose, peak serum amylase, need for pressor agents, cause of death, cold ischemic preservation time, recipient age, type of dialysis, surgical technique, and peak recipient amylase. RESULTS: The 1-year graft survival rate was 90%. Of the 34 patients studied, there were 4 cases of peripancreatic abscess formation (12%). Elevated donor body weight (P <0.01), elevated body mass index (P <0.05), and the peak recipient serum amylase in the first postoperative week (P <0.01) were significant risk factors for the development of intra-abdominal infection. CONCLUSIONS: These data suggest that pancreas grafts from obese donors may be more susceptible to ischemia-reperfusion injury resulting in abscess formation.

Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients.

When tacrolimus side effects persist despite dose reduction, conversion to cyclosporine-based immunosuppression (CyA) is necessary. We characterized tacrolimus side effects that warranted discontinuation of the drug, and outcomes after conversion. Of 388 liver recipients who received tacrolimus as primary immunosuppression, 70 required conversion to CyA. We recorded indication for conversion, whether conversion was early or late after transplantation, tacrolimus dose and trough blood level at conversion, and incidence of rejection after conversion. Conversion was early in 29 patients (41.4%) and late in 41 (58.6%). Indications for early conversion were neurotoxicity (20), (insulin-dependent) diabetes mellitus (IDDM) (5), nephrotoxicity (3), gastrointestinal (GI) toxicity (6), and cardiomyopathy (1), and for late conversion were neurotoxicity (15), IDDM (12), nephrotoxicity (3), GI toxicity (5), hepatotoxicity (6), post-transplant lmphoproliferate disease (PTLD) (2), cardiomyopathy (1), hemolytic anemia (1), and pruritus (1). All early-conversion patients showed improvement/resolution of symptoms. Among late-conversion patients, 37 (90.2%) had improvement/resolution; in 4 (9.8%), adverse effects persisted. The overall rejection rate was 30%. Sixty-two patients (88.6%) are alive with functioning grafts 686 +/- 362 days (range, 154-1433 days) after conversion. When tacrolimus side effects are unresponsive to dose reduction, conversion to CyA can be accomplished safely, with no increased risk of rejection and excellent long-term outcome.

Retransplantation for late liver graft failure: predictors of mortality.

As patient survival after orthotopic liver transplantation (OLT) improves, late complications, including late graft failure, more commonly occur and retransplantation (re-OLT) is required more often. Survival after re-OLT is poorer than after primary OLT, and given the organ shortage, it is essential that we optimize our use of scarce donor livers. We sought to identify variables that predict poor outcome after late re-OLT. Among adults who underwent OLT between September 1989 and October 1997, we identified transplant recipients who survived greater than 6 months (n = 964) and analyzed those who required late re-OLT (>/=6 months after primary OLT). We recorded the indication for the initial OLT and interval from OLT to re-OLT. We also analyzed data collected at the time of re-OLT, including age, sex, indications for primary OLT and re-OLT, United Network for Organ Sharing status, preoperative laboratory values (white blood cells, platelets, hemoglobin, albumin, bilirubin, creatinine, and prothrombin time), Child-Pugh-Turcotte score, number of rejection episodes before re-OLT, and interval between OLT and re-OLT. In addition, we analyzed surgical factors (including procedure performed and use of packed red blood cells, fresh frozen plasma, and platelets), postoperative immunosuppression, and donor factors (age, ischemic time). Forty-eight patients (5%) underwent late re-OLT at a median of 557 days (range, 195 to 2,559 days) post-OLT. Survival rates after re-OLT at 90 days, 1 year, and 5 years were 71%, 60%, and 42%, respectively. Patients surviving 90 days or greater after re-OLT had an 85% chance of surviving to 1 year. Sepsis was the leading cause of death (15 of 25 deaths; 60%). Recipient age older than 50 years (P =.04), preoperative creatinine level greater than 2 mg/dL (P =.004), and use of intraoperative blood products (packed red blood cells, P =.001; fresh frozen plasma, P =.002; platelets, P =.004) had significant impacts on survival. Late re-OLT was associated with increased mortality. Careful patient selection, with particular attention to recipient age and renal function, may help improve results and optimize our use of scarce donor livers.

Long-term medical complications in patients surviving > or = 5 years after liver transplant.

BACKGROUND: Short-term outcomes of liver transplantation are well reported. Little is known, however, about long-term results in liver recipients surviving > or =5 years. We sought to analyze long-term complications in liver recipients surviving > or =5 years after transplant, to assess their medical condition and to compare findings to the general population. METHODS: We analyzed the chart and database records of all patients (n=139) who underwent liver transplantation at a major transplant center before January 1, 1991. Outcome measures included the presence of diabetes, hypertension, heart, renal or neurological disease, osteoporosis, incidence of de novo malignancy or fracture, or other pathology, body mass index, serum cholesterol and glucose, liver function, blood pressure, frequency of laboratory and clinic follow-up, current pharmacological regimen, and late rejection episodes. RESULTS: Ninety-six patients (70%) survived > or =5 years. Compared to numbers expected based on U.S. population rates, transplant recipients had significantly higher overall prevalences of hypertension (standardized prevalence ratio [SPR]=3.07, 95% confidence interval [CI], 2.35-3.93) and diabetes (SPR=5.99, 95% CI, 4.15-8.38), and higher incidences of de novo malignancy (standardized incidence ratio [SIR]=3.94, 95% CI, 2.09-6.73), non-Hodgkin's lymphoma (SIR=28.56, 95% CI, 7.68-73.11), non-melanoma skin cancer (estimated SIR> or =3.16) and fractures in women (SIR=2.05, 95% CI, 1.12-3.43). Forty-one of 87 (47.1%) patients were obese, and 23 patients (27.4%) had elevated serum cholesterol levels (> or =240 mg/dl, 6.22 mmol/L), compared to 33% and 19.5% of U.S. adults, respectively. Prevalences of heart or peptic ulcer disease were not significantly higher. CONCLUSIONS: Liver transplantation is being performed with excellent 5-year survival. Significant comorbidities exist, however, which appear to be related to long-term immunosuppression.

Transmission of factor VII deficiency through liver transplantation.

The liver is the primary site of synthesis for the majority of coagulation factors. There are published accounts of liver donor-to-recipient transmission of protein C deficiency with dysfibrinogenemia and factor XI deficiency. In this article, we report what we believe to be the first observation, of transmission of factor VII deficiency, a rare, autosomal recessive coagulation disorder, from an affected liver donor to a naive liver recipient. At 300 days after transplantation, the recipient remains with an isolated prolongation of the prothrombin time and a below-normal level of factor VII, and has had no bleeding complications.

Living related liver transplantation for acute liver failure in children.

The mortality rate among children with acute liver failure (ALF) on the waiting list for liver transplantation is high. We present our experience with living related donor liver transplantation (LRD-LT) in children who required urgent transplantation for ALF. Between December 1995 and July 1997, 6 children underwent LRD-LT for ALF. Cause of liver failure, recipient and donor demographics, clinical and laboratory data, surgical details, complications, and 6-month and 2-year graft and patient survival were recorded. Five boys and 1 girl received left lateral segment grafts from their parents. The mean age was 4 +/- 2.8 years (range, 1 to 9 years). ALF was caused by Wilson's disease in 1 patient and sickle cell intrahepatic cholestasis syndrome in 1 patient; in 4 patients, the cause was unknown. All patients had mental status changes; 2 were on life support. Mean pretransplantation liver function test values were: alanine aminotransferase, 972 +/- 565 U/L (normal, 1 to 53 U/L), total bilirubin, 31.3 +/- 12.4 mg/dL (normal, 0.1 to 1.2 mg/dL), prothrombin time, 34.3 +/- 12.4 seconds (normal, 10.8 to 13.3 seconds), international normalized ratio, 8.46 +/- 5.4 (normal < 2), and fibrinogen, 109 +/- 23.9 mg/dL (normal, 175 to 400 mg/dL). The donors were 5 mothers and 1 father. The mean donor age was 32.5 +/- 7.6 years (range, 19 to 40 years). No donor required blood transfusion, and no donor had any early or late postoperative complications. The donors' mean hospital length of stay was 5 days. In five cases, grafts were blood group-compatible; 1 child received a blood group-incompatible graft. All grafts functioned immediately. No patient had hepatic artery or portal vein thrombosis or biliary complications. The child who received a mismatched graft died of infection of the brain caused by Aspergillus spp at 22 days posttransplantation with a functioning graft. The child with ALF caused by sickle cell intrahepatic cholestasis syndrome developed outflow obstruction 3 months posttransplantation and required retransplantation; he eventually died of vascular complications related to his primary disease. Four children are alive at a mean follow-up of 27 months (range, 14 to 36 months). LRD-LT for children with ALF facilitates timely transplantation without drawing on cadaveric donor resources. The established safety record of LRD-LT made this option appealing to both physicians and parental donors.

Safe transplantation of blood type A2 livers to blood type O recipients.

BACKGROUND: Transplantation of blood type A subgroup 2 (A2) livers into non-A recipients has not been reported previously. A2 to O renal transplantation has been reported, with early results including some accelerated rejections and graft losses. This has led some to selectively offer A2 renal transplantation only for patients with low anti-A titers. Given the different clinical behavior of liver allografts to preformed antibody, we felt that such restriction was unnecessary. METHODS: We performed six cases of A2 to O liver transplantation with no augmented immunomodulation or restriction with regard to antibody titers. Clinical courses, anti-A titers, rejection rates, and graft and patient survival were evaluated. RESULTS: All six patients had high pretransplant anti-A titers (>1:8), and all six grafts functioned normally. There were nine rejections in the six patients, of which three were severe (steroid-resistant) and five were late (>90 days). No rejection was vascular, and no grafts were lost, with mean follow-up of 665 days. In one patient who had anti-A antibody measured at the time of rejection IGM titers increased from baseline. Currently all patients are home with normal function. CONCLUSIONS: We found that transplantation of blood group A2 livers into blood group O recipients is safe and can be performed without graft loss and without regard to anti-A titer level. The rate of acute cellular rejection is high in this small series, and a significant proportion of these events were late or required OKT-3. We did not rely on plasmapheresis or anti-A titer determinations. However, the potential for late rejection prompts us to consider the addition of a third immunosuppressive agent. The transplantation of A2 livers into O recipients can partially compensate for the more frequent use of O livers in recipients from other blood groups.

Selective decontamination of the digestive tract helps prevent bacterial infections in the early postoperative period after liver transplant.

UNLABELLED: In liver transplant (LTx) recipients, gut-associated bacterial and fungal organisms produce significant postoperative morbidity and mortality. We sought to assess the role of selective digestive decontamination (SDD) in preventing postoperative infections in a large single-center cohort of liver recipients transplanted under two non-simultaneous protocols. In 212 consecutive patients transplanted between 1/1/91 and 7/31/92, SDD (gentamicin 80 mg, polymyxin B 100 mg, nystatin suspension 10 mL) was employed, starting after induction of anesthesia and continued until POD 21 (SDD Group). In 157 consecutive patients transplanted between 1/1/93 and 12/31/93, SDD was not used (non-SDD Group). Both groups received IV vancomycin and cefotaxime prophylaxis. All culture-positive infections within the first 30 days post-LTx were recorded and classified as bacterial or fungal. Infection-related mortality (patients who died of infectious complications without any technical complication) was recorded. Groups did not differ in patient demographics, United Network for Organ Sharing (UNOS) status, use of veno-venous bypass, total/warm ischemia, or length of ICU stay. Infections developed in fewer SDD patients (56/212; 26%) than non-SDD patients (69/157; 44%) (p<0.001). The incidence of gram-negative infection was less in the SDD group (11% vs. 26%, p<0. 001) as was gram-positive infection (16% vs. 26%, p<0.001). Among patients who developed infection, there was no difference between groups in infections per patient. Primary graft non-function (PNF) developed in 20 SDD patients (7/20 had infections) and 8 non-SDD patients (6/8 had infections) (p=0.06). There were no differences in incidence of fungal infections or of infection-related mortality between groups. In the SDD group, there were fewer abdominal (p<0. 001), lung (p<0.001), wound (p<0.01), and urinary tract infections (p<0.05). CONCLUSION: Use of SDD in liver recipients early after transplant was associated with significantly fewer infections in the early postoperative period.

Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and constitutes 10% of primary liver malignancies. Surgery is the optimal therapy; the majority of the patients will require extensive resections that are associated with significant morbidity. METHODS: We retrospectively studied the records of 26 patients who underwent exploratory laparotomy for intrahepatic cholangiocarcinoma between June 1991 and December 1997 at the Mount Sinai Hospital. Patients with perihilar (Klatskin) tumors were excluded. All patients were considered resectable based on CT or MRI findings. Patients with positive margins or nodal invasion received adjuvant chemotherapy and radiation. RESULTS: Sixteen patients underwent 18 resections; in 10 patients the tumors were unresectable at laparotomy and only biopsy was performed. The mean age (62 versus 53 years) was significantly higher, and the mean total bilirubin level (0.71 versus 6.17 mg/dL) was significantly lower in the resected group (p=0.031 and 0.017, respectively). No patient with a total bilirubin over 1.2 mg/dL was found to be resectable. Median actuarial survivals were 42.9+/-8.9 months for resectable and 6.7+/-3.6 months for unresectable patients (p=0.005). Positive margins were associated with significantly shorter disease-free survival. But resected patients with positive margins survived significantly longer than those who were unresectable. Tumor size, presence of satellite nodules, and degree of tumor necrosis on histologic examination were significant predictors of outcomes. Survival among patients receiving adjuvant therapy was not significantly altered. CONCLUSIONS: We conclude that an aggressive surgical approach is warranted in patients with ICC because resection offers the only hope for longterm survival. Our findings emphasize the importance of achieving tumor-free margins. Noncurative resection offers a survival advantage over no resection. Histologic examination of resected specimens can help select patients with poor prognoses.

The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation.

Clinical recurrence of hepatitis C after liver transplantation can lead to cirrhosis, liver failure, and death. In patients undergoing liver transplantation for hepatitis C, we assessed the efficacy of interferon alfa-2b (IFN) in preventing recurrent hepatitis. We randomized 86 patients to either an IFN group (3 MU three times a week starting within 2 weeks after transplantation and continued for 1 year) or a control (no IFN) group. Recurrence, the primary end point, was diagnosed on biopsy performed at 1 year or for abnormal biochemistries. HCV RNA levels were measured by branched-chain DNA (bcDNA) assay and arbitrarily defined as low, moderate, or high (< 10 x 10(5), 10-100 x 10(5), or > 100 x 10(5) Eq/mL, respectively). Data on 30 IFN patients and 41 no-IFN patients who survived > or = 3 months were reviewed. Mean follow-up was 669 +/- 228 days for IFN patients and 594 +/- 254 days for no-IFN patients. IFN patients were less likely to develop recurrent hepatitis (8 IFN vs. 22 no-IFN patients, P = .017, log rank analysis). IFN and 1-month HCV RNA level were independent predictors of recurrence. IFN reduced the risk of recurrence by a factor of 0.4 (P = .04, Cox proportional hazards model); HCV RNA level > 100 x 10(5) Eq/mL at 1 month after transplantation increased the risk by a factor of 3.1 (P = .01). Low, moderate, and high viral levels at 1 and 3 months were associated with significantly different rates of recurrence in IFN patients (P = .05 at 1 month and P = .003 at 3 months) but not in untreated patients (P = .28 at 1 month and P = .25 at 3 months). In patients with two or more rejections, the risk of recurrence was increased by a factor of 2.17 (P = .05). On 47 1-year biopsies (24 IFN; 23 no IFN), piecemeal necrosis was more common in untreated patients (P < .02). One- and 2-year patient survival, respectively, was 96% and 96% with IFN and 91.2% and 87.2% without (P = NS). Prophylactic IFN reduced the incidence of recurrent hepatitis after transplant. Although IFN was most effective in patients with low HCV RNA levels, we also noted an effect in patients with moderate levels. IFN did not prevent viremia, suggesting that it may work through alternative mechanisms.

Liver transplant recipients are not at increased risk for nonlymphoid solid organ tumors.

BACKGROUND: Organ transplant recipients are at higher risk for developing lymphoid tumors, skin carcinomas, and sarcomas. Whether liver transplant recipients are at higher risk for developing more common cancers is unclear. METHODS: All patients with a history of malignancy prior to liver transplantation and those who developed malignancy, either de novo or recurrent, after transplantation were identified retrospectively. The following parameters were examined: age at diagnosis; indication for transplant; interval from transplant to tumor diagnosis; tumor treatment received; predisposing factors for the development of cancer; immunosuppression regimen, including the use of OKT3; number and treatment of rejection episodes; and survival. RESULTS: Of 888 patients, 29 (3.2%) had 31 previous malignancies; of these 29 patients, 4 developed a recurrence in the posttransplant period. Thirty-nine patients (4.3%) developed 43 de novo nonlymphoid malignancies. Alcoholic cirrhotic patients had a significantly higher incidence of de novo carcinomas. Except for skin carcinomas, tumors did not occur with greater frequency than in the general population, and recurrent tumors were not more aggressive than reported for that disease. One patient had an unrecognized renal cell carcinoma at the time of transplant that progressed rapidly; this patient died 64 days after transplantation. CONCLUSIONS: With current immunosuppressive regimens, liver transplant patients do not appear to be at an increased risk for developing nonlymphoid solid organ tumors. However, longer follow-up will be necessary to confirm these results.

Persistent hypersplenism early after liver transplant: the role of splenectomy.

BACKGROUND: Transient thrombocytopenia is common after liver transplantation, but persisting thrombocytopenia worsens the prognosis after transplant. METHODS: Two patients underwent splenectomy for persistent thrombocytopenia early after liver transplantation. The first patient had a platelet count of 17,000/mm3 on postoperative day (POD) 6; her hemoglobin and white blood cell counts were normal. Work-ups including bone marrow aspiration, Coombs test, and antiplatelet antibody test were negative. On POD 9, she had abdominal bleeding with a platelet count of 17,000/mm3 despite repeated platelet transfusions, and splenectomy was done. The second patient had a platelet count of 3000/mm3 on POD 14, white blood cell was 1600/mm3, and hemoglobin was 7.7 g/dl. Bone marrow biopsy revealed hypercellular marrow. Because his platelet count remained at 2000/mm3 despite empiric treatment with intravenous immune globulin and methylprednisolone, splenectomy was performed. RESULTS: The first patient's platelet count rose to 155,000/mm3 by POD 8. The second patient's platelet count reached 210,000/mm3 on POD 5. Neither patient has had an episode of thrombocytopenia at 36 and 32 months after splenectomy. CONCLUSIONS: Splenectomy can be used after liver transplantation for severe, persistent thrombocytopenic states that cannot be attributed to sepsis, intravascular coagulation, immunological causes, or drug effects.

Selective revascularization of hepatic artery thromboses after liver transplantation improves patient and graft survival.

BACKGROUND: Hepatic artery thrombosis (HAT) can be a devastating complication of orthotopic liver transplantation (OLT), but early diagnosis may allow successful revascularization and graft salvage. METHODS: We reviewed data on 1,026 liver transplants at our institution. For patients in whom HAT was diagnosed within 30 days after OLT, we recorded indications for ultrasonography and liver function tests at diagnosis, management of HAT, and graft and patient survival. RESULTS: Thirty-two patients (3.1%) developed HAT at 6.8+/-6.6 days (range, 1-29 days) after OLT. Twelve patients (37.5%) were asymptomatic at diagnosis. In 11 of these 12, HAT was diagnosed on routine duplex at 2.0+/-1.55 days after OLT; in the 12th patient, HAT was noted during re-exploration for unrelated bleeding on postoperative day 3. Eleven of 12 patients (91.6%) were revascularized; one patient (8.4%) received no treatment with no sequelae. Of the 11 who were revascularized, 9 (81.8%) had graft salvage and 2 (18.2%) received a second transplant, with one death. Twenty patients (62.5%) were symptomatic. In these 20, HAT was diagnosed at 9.85+/-6.93 days after OLT. Symptoms were: elevated liver function test results (serum glutamic oxaloacetic transaminase: 722+/-1792 U/ml, serum glutamic pyruvic transaminase: 678+/-963 U/ml, and bilirubin: 10.2+/-6.2 mg/dl) in 13 patients (65%); bile leak in 4 patients (20%), and sepsis in 3 (15%). Five of the 20 patients (25%) were revascularized; of these 5, 2 (40%) had graft salvage, 2 (40%) received a second transplant with 1 death, and 1 (20%) died of a liver abscess. Twelve symptomatic patients (60%) had immediate re-OLT; 10/12 are alive, 1 died of sepsis, and 1 died late of unrelated causes. Three symptomatic patients had no treatment; two died of biliary sepsis and one survived. Overall graft salvage was 83.3% in asymptomatic patients and 15% in patients with symptoms (P<0.001). Graft salvage in asymptomatic patients undergoing revascularization was 81.8%, versus 40% in symptomatic patients (P=NS). One-year patient survival was 91.7% in asymptomatic patients and 65% in symptomatic patients (with one late death excluded) (P=NS). CONCLUSIONS: Routine postoperative duplex ultrasonography should be performed early after liver transplantation. We believe that emergent revascularization of hepatic artery thrombosis in asymptomatic patients and retransplantation in symptomatic patients lead to improved graft salvage and patient survival with a relatively low incidence of late biliary complications.

Increased risk of early rejection correlates with recovery of CD3 cell count after liver transplant in patients receiving OKT3 induction.

BACKGROUND: We evaluated the utility of CD3 cell counts for monitoring OKT3 induction immunosuppression and for predicting early rejection in liver recipients. METHODS: In 32 adults in whom OKT3 and steroids were used to induce immunosuppression, CD3 cell subsets were labeled with CD3 (IgG1)-fluorescein isothiocyanate monoclonal antibody and assayed by flow cytometry before orthotopic liver transplantation and within 2-4 days, 5-7 days, and 8-10 days after transplantation. Trough OKT3 levels were measured at the same points in 10 patients. Early rejection (before postoperative [POD] day 21) was proven by elevated liver function tests and biopsy. Six patients were excluded for death, retransplantation, or early cessation of OKT3. RESULTS: Eight of 26 patients (30.8%) had early rejection and 18 (69.2%) had no early rejection. All had depletion of CD3 cells to <10.2% of baseline at POD 2-4. On POD 8-10, the mean CD3 count in rejectors was 213.31+/-184.98/mm3 vs. 22.71+/-32.42/mm3 in nonrejectors (P<0.001). By POD 8-10, five of eight (62.5%) patients who rejected had CD3 count recovery to >75% of baseline. No nonrejecting patient recovered to >26% of baseline (P<0.001). OKT3 levels did not correlate with CD3 recovery or rejection. CONCLUSIONS: The incidence of early rejection correlates strongly with recovery of CD3 counts by POD 10. Higher baseline CD3 counts do not predict early rejection.

Use of livers with microvesicular fat safely expands the donor pool.

BACKGROUND: The safety of transplanting livers with moderate to severe microvesicular steatosis is unknown. Livers that appear fatty are often abandoned at the donor hospital. We have recently used frozen-section biopsy to distinguish between microvesicular and macrovesicular steatosis. We present here our single-center experience with transplantation of 40 allografts with moderate or severe microvesicular steatosis. METHODS: We reviewed our data on 426 transplants and identified 40 cases in which the donor liver contained at least 30% microvesicular steatosis. Early graft function, patient and graft survival, and donor risk factors for steatosis were examined, and results in this cohort were compared with results in all other patients who received liver transplants at our center during the same time period. We also analyzed the reliability of donor frozen-section biopsies in quantitating microsteatosis. Persistence of steatosis was assessed on the basis of 1-year follow-up biopsies. RESULTS: The incidence of primary nonfunction and poor early graft function was 5% and 10%, respectively. One-year patient and graft survival rates were 80% and 72.5%, respectively. Donor obesity and traumatic death were commonly identified risk factors for microvesicular steatosis. Frozen-section biopsy was reliable for pretransplant decision-making about the use of potential grafts, and the steatosis had disappeared from the graft at 1 year in the majority of cases. CONCLUSIONS: Livers with even severe microvesicular steatosis can be reliably used for transplantation without the fear of high rates of primary nonfunction. There was a significant incidence of poor early graft function, but this did not affect outcome. Microsteatosis is usually associated with some underlying risk factor in the donor and is reversible, as demonstrated by follow-up biopsies after transplant.

Retransplantation for recurrent hepatitis C.

Recurrence of hepatitis C virus (HCV) after orthotopic liver transplant (OLT) may be mild or may lead to progressive liver disease requiring retransplantation (re-OLT). Results of re-OLT for hepatitis C are not well known. We analyzed outcomes in 14 patients retransplanted for recurrent hepatitis C. All had evidence of recurrent hepatitis on multiple biopsies. Polymerase chain reaction (PCR) was performed in blood or tissue samples from 12 patients when recurrence was suspected; all 12 were positive for HCV-RNA. Explants showed chronic hepatitis with bridging necrosis in 3 patients, hepatitis with transition to cirrhosis in 2, hepatitis and cirrhosis in 3, and cirrhosis alone in 2. In 2 patients, in whom immunosuppression had been withheld for 4 to 6 weeks, there was also evidence of chronic rejection. Four died of sepsis perioperatively (median, 32.5 days; range, 9-59); pre-OLT, 3 of 4 had renal failure, and 1 had fever with no obvious source of infection. Ten patients did well early after OLT and were discharged. One patient was readmitted 6 weeks after discharge and died of cytomegalovirus (CMV) infection 127 days after re-OLT. One patient with concomitant vanishing bile duct syndrome, probably due to chronic rejection, developed recurrent hepatitis and died of progressive liver failure 161 days after re-OLT. Eight patients are well at a median of 926 days (range, 315-1930) after re-OLT. Three have evidence of mild recurrent hepatitis on liver biopsy, one is overweight with severe steatosis on biopsy, and four have no evidence of recurrent hepatitis. Retransplantation for hepatitis C should be considered a viable option for patients who develop end-stage hepatic dysfunction secondary to recurrent disease and should be performed before development of infectious complications and renal insufficiency.