Sonographic diagnosis and outcome of hepatic artery thrombosis after orthotopic liver transplantation in adults.

OBJECTIVE: The objective of our study was to determine the timing and frequency of symptomatic hepatic artery thrombosis in an adult orthotopic liver transplant population, the sensitivity of Doppler sonography for this diagnosis, and the clinical and sonography outcomes in this population. MATERIALS AND METHODS: The subjects included all adult recipients with orthotopic liver transplants during a 10.5-year period. A retrospective review of all cases of hepatic artery thrombosis detected on angiography or at surgery was correlated with sonography findings at diagnosis. Clinical and sonography outcomes were recorded. Patients were divided into early (< 1 week) and late hepatic artery thrombosis groups. Hepatic artery thrombosis was considered primary or secondary due to treatment of other hepatic artery complications. RESULTS: Of 522 transplants, 25 (4.8%) developed hepatic artery thrombosis that was primary in 18 (3.5%), with five early (1.0%) and 13 late (2.5%), and secondary in seven (1.3%). Sensitivities of sonography compared with angiography were 100% for detection of early hepatic artery thrombosis and 72.7% for late hepatic artery thrombosis. Seventeen patients (68%) with an episode of hepatic artery thrombosis are currently alive, 11 of whom have irreversible hepatic artery thrombosis; in 10 of the 11 cases, sonography showed that collateral arterial flow had developed. The mean survival was 51.4 months in the patients with irreversible hepatic artery thrombosis, eight of whom had documented biliary or septic complications (or both). CONCLUSION: Hepatic artery thrombosis is uncommon after liver transplantation in adults. Sonography is extremely sensitive for the detection of hepatic artery thrombosis in symptomatic patients during the immediate postoperative period. Sonography becomes less sensitive as the interval between transplantation and diagnosis of hepatic artery thrombosis increases due to collateral arterial flow. Patients with irreversible hepatic artery thrombosis typically develop interval arterial collaterals that can be seen on sonography. Biliary and septic complications are common but usually are self-limited.

Six year disease free survival after liver transplantation in a patient with T3 gallbladder carcinoma: case presentation and review of the literature.

BACKGROUND: The incidence of gallbladder carcinoma in cirrhotics is unknown. Known risk factors are primary sclerosing cholangitis and polypoid masses. CASE PRESENTATION: A sixty year old with primary sclerosing cholangitis, cirrhosis, and gallbladder polyps underwent liver transplantation. A polypoid lesion measuring 1.5 x 0.5 cm was found on the fundus of the gallbladder. Histological examination revealed moderately differentiated adenocarcinoma with full thickness penetration of the gallbladder encroaching liver parenchyma. Angiolymphatic invasion was noted. The lymph nodes, the cystic duct and the common duct were free of tumor (T3N0M0). Extensive evaluation did not demonstrate metastasis. No chemotherapy was given. He is currently six years post procedure and free of disease. CONCLUSION: "Incidentally" discovered stage IIA gallbladder carcinoma may not negatively affect long term survival after liver transplantation.

Posttransplant lymphoproliferative disease presenting as adrenal insufficiency: case report.

This is the first reported case of lymphoproliferative disease presenting with adrenal insufficiency after liver transplantation. A 38-year-old white man was admitted 8 months after transplantation for cryptogenic cirrhosis with fever (38-39 degrees C), chills, cough, and dyspnea. His blood pressure was 100/70 mm Hg, there was pallor of the conjunctiva, and a lymph node was palpable in the left groin. Laboratory analyses revealed the following values: serum sodium concentration (112 mmol/L), potassium (5.4 mmol/L), hemoglobin (7.8 g/L), white blood cell count (7.7 x 10(9)/L), glucose 3.9 (mmol/L), and mildly elevated liver functions. Abdominal ultrasound showed multiple hypoechoic solid-appearing lesions throughout the liver and spleen. Results of a biopsy specimen of the groin node confirmed polymorphic B-cell lymphoma. A negative Epstein- Barr virus screen before transplant became positive. The patient's fever increased to 40 degrees C. He subsequently developed sepsis and later, multiple organ failure. Autopsy confirmed extensive abdominal disease. The adrenal glands had been completely replaced by the tumor. Primary Epstein-Barr virus infection is associated with posttransplant lymphoproliferative disease. Replacement of the adrenal glands with a tumor produces a clinical picture of adrenal insufficiency.

Extended survival by urgent liver retransplantation after using a first graft with metastasis from initially unrecognized donor sarcoma.

A 58-year-old man underwent orthotopic liver transplantation for polycystic liver disease. Shortly after the procedure, it was discovered that the donor harbored a sarcoma of the aortic arch that had metastasized to the spleen, and bilateral renal cell carcinomas. The two sole organ recipients, our liver recipient and a lung recipient at another institution, were both listed for urgent retransplantation, which they received from the same second donor. The liver explant contained metastatic sarcoma. Twenty-four months survival following lung retransplantation has been previously reported. We report the 76-month disease-free survival in the liver recipient.

A multicenter evaluation of utility of chest computed tomography and bone scans in liver transplant candidates with stages I and II hepatoma.

OBJECTIVE: To determine utility of practice of chest computed tomography (CCT) and bone scan (BS) in patients with early-stage hepatoma evaluated for transplantation (LT). SUMMARY BACKGROUND DATA: Consensus-based policy mandates routine CCT and BS in LT candidates with hepatoma. No data exist either to support or refute this policy. METHODS: From January 1999 to December 2002, stages I and II hepatoma patients evaluated at 4 centers were included. Scan interpretation was positive, indeterminate, or negative. Outcomes of evaluation and transplantation were compared between groups based on scans. Total charges incurred were derived from mean of charges at the centers. RESULTS: One hundred seventeen stages I and II patients were evaluated. None had positive scans, 78 had negative, 29 had at least 1 indeterminate, and 10 did not have 1 or both scans. Twelve patients were declined listing, 6 from progression of hepatoma but none from CCT or BS findings. Two listed patients were delisted for progression of the hepatoma. Proportion of patients listed, transplanted, clinical and pathologic stage of hepatoma, and recurrence after LT were similar in groups with negative and indeterminate scans. Indeterminate scans led to 6 invasive procedures, 1 patient died of complications of a mediastinal biopsy, and none of the 6 showed metastases. Charges of $2933 were generated per patient evaluated. CONCLUSIONS: Positive yield of routine CCT and BS in patients with hepatoma is very low despite substantial charges and potential complications. CCT and BS performed only when clinically indicated will be a more cost-effective and safer approach.

Successful re-use of liver allografts: three case reports and a review of the UNOS database.

The donor organ shortage has compelled transplant centers to use organs from non-traditional sources. One example is the re-use of a previously transplanted organ, such as a kidney or liver. We report three cases detailing the successful re-use of liver allografts. In all three cases, the index recipient was declared brain-dead very soon post-transplant, but was felt to have a well-functioning liver graft. Important points in these cases were to ensure that the liver graft was functioning well in the index recipient, that it appeared normal per biopsy examination, and that ischemic time was kept very short at the time of the second transplant. We queried the United Network for Organ Sharing (UNOS) database for similar cases, and found 11 such cases, which we briefly describe herein.

Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials.

There is currently no effective treatment for recurrent hepatitis C after orthotopic liver transplantation (OLT). We therefore performed two randomized, controlled trials--a prophylaxis trial and a treatment trial--to evaluate the safety and efficacy of peginterferon alfa-2a in patients who had undergone OLT. The prophylaxis trial enrolled 54 patients within 3 weeks after OLT, and the treatment trial enrolled 67 patients 6 to 60 months after OLT. In each trial, patients were randomized to treatment with once weekly injections of 180 microg peginterferon alfa-2a or no antiviral treatment for 48 weeks and were followed up for 24 weeks thereafter. Peginterferon alfa-2a treated patients had significantly lower hepatitis C virus RNA levels and more favorable changes in hepatic histological features compared with untreated controls. However, only 2 treated patients in the prophylaxis trial (8%) and 3 in the treatment trial (12%) achieved a sustained virological response. In the prophylaxis trial, 8 patients (31%) in the peginterferon alfa-2a group and 9 (32%) in the untreated group were withdrawn prematurely; whereas in the treatment trial, 10 patients (30%) in the peginterferon alfa-2a group and 6 (19%) in the untreated group were withdrawn prematurely. The incidence of acute rejection was similar in the treated and untreated groups in both the prophylaxis (12% vs. 21%; P = .5) and treatment (12% vs. 0%; P = .1) trials. In conclusion, peginterferon alfa-2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post-OLT setting. Randomized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT.

Inducible left ventricular outflow tract gradient during dobutamine stress echocardiography: an association with intraoperative hypotension but not a contraindication to liver transplantation.

BACKGROUND: Dobutamine stress echocardiography (DSE) is frequently used in the evaluation of cardiac risk prior to orthotopic liver transplantation (OLT). In the general cardiac population, an inducible left ventricular outflow tract gradient (LVOT Delta) during DSE has variable prognostic importance. The purpose of this study was to determine the prevalence and clinical significance of LVOT Delta in patients undergoing OLT during DSE. METHODS: Consecutive medical records of 106 patients who had undergone OLT at our institution from January 1997 until January 2002 were retrospectively analyzed and divided into two groups based on the presence (Group I, LVOT Delta >36 mmHg) or absence (Group II, LVOT Delta< or = 36 mmHg) of a significant LVOT Delta measured during DSE. We determined any outcome differences between these two groups with regard to intraoperative hypotension, cardiac mortality, length of hospital stay, graft function, and renal function post-OLT. RESULTS: Forty-six patients had an LVOT Delta > 36 mmHg (Group I) and 60 patients had LVOT Delta< or = 36 mmHg (Group II). Baseline demographics were similar in both groups. There was no significant overall difference in cardiac mortality between Group I versus Group II patients (0 versus 1 patient, respectively, P=0.57). Intraoperative hypotension occurred in 4 patients in Group I versus 0 patient in Group II (P=0.03). Length of stay, graft function, and postoperative renal function were similar in both groups. CONCLUSION: A significant LVOT Delta >36 mmHg is a frequent finding occurring in 46/106 (43%) of patients who have DSE pre-OLT. Intraoperative hypotension is associated with patients having an LVOT Delta. However, post-OLT patients with significant LVOT Delta have a similar in-hospital outcome compared to patients without significant LVOT Delta.

Long-term outcome of controlled, non-heart-beating donor liver transplantation.

BACKGROUND: Previous reports have established the feasibility of using livers from controlled, non-heart-beating donors (CNHBD) with good immediate graft function. This has been largely borne out of necessity because of the donor shortage. METHODS: Retrospective database review for the last 7 years (1995-2002), encompassing 19 patients receiving CNHBD, with follow-up period of 1,000 +/- 694 days, median 762 days. Detailed review of recipient characteristics, operative and clinical course, immunosuppression, complications, survival rates, and comparison with the results obtained in patients receiving transplants of allografts procured in standard fashion, from heart-beating donors RESULTS: Kaplan-Meier patient survival rates were 100%, 89.5%, and 83.5% at 30 days, 1, and 2 years, respectively, which is not different from recipients of livers procured from heart-beating cadaveric donors (P=0.74, log-rank test). Five patients died at a mean follow-up time of 492 (range 46-1,103) days. The causes of death were related to secondary sclerosing cholangitis (n=1), cardiac failure (n=1), and sepsis (n=3). Two (10.5%) recipients underwent retransplantation, one for primary graft nonfunction and one because of biliary cast syndrome with cholangitis. Significant preservation damage (ALT>2,000) developed in five patients, but this did not affect survival. The incidence of vascular (15.6% vs. 9.6%, P=0.34) and biliary complications (10.55 vs. 13.8%, P=0.68) was no different than for those recipients receiving standard cadaveric donors. CONCLUSIONS: CNHBD safely expands the donor pool with similar long-term results as those obtained in patients receiving organs from brain-dead donors under standard procurement techniques.

Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database.

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PortoPH) are pulmonary vascular consequences of advanced liver disease associated with significant mortality after orthotopic liver transplantation (OLT). Data from 10 liver transplant centers were collected from 1996 to 2001 that characterized the outcome of patients with either HPS (n = 40) or PortoPH (n = 66) referred for OLT. Key variables (PaO2 for HPS, mean pulmonary artery pressure [MPAP], pulmonary vascular resistance [PVR], and cardiac output [CO] for PortoPH) were analyzed with respect to 3 definitive outcomes (those denied OLT, transplant hospitalization survivors, and transplant hospitalization nonsurvivors). OLT was denied in 8 of 40 patients (20%) with HPS and 30 of 66 patients (45%) with PortoPH. Patients with HPS who were denied OLT had significantly worse PaO2 compared with patients who underwent transplantation (47 vs. 52 mm Hg, P <.005). Transplant hospitalization survival was associated with higher pre-OLT PaO2 (55 vs. 37 mm Hg; P <.005). MPAP was significantly higher (53 vs. 45 mm Hg; P <.015) and PVR was significantly worse (614 vs. 335 dynes. s. cm(-5); P <.05) in patients with PortoPH who were denied OLT compared with patients who underwent transplantation. Transplant hospitalization mortality was 16% (5/32) in patients with HPS and 36% (13/36) in patients with PortoPH. All of the deaths in patients with PortoPH occurred within 18 days of OLT; 5 of the 13 deaths in patients with PortoPH occurred intraoperatively. We concluded that patients with HPS (based on a combination of low PaO2 and nonpulmonary factors) and patients with PortoPH (based on pulmonary hemodynamics) were frequently denied OLT because of pre-OLT test results and comorbidities. For patients who subsequently underwent OLT, transplant hospitalization mortality remained significant for both those with HPS (16%) and PortoPH (36%).

Liver transplantation using an organ donor with HELLP syndrome.

BACKGROUND: The shortage of organs for liver transplantation has forced transplant centers to expand the donor pool by using donors traditionally labeled as marginal. One such example is liver transplantation using a donor with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), a disorder of late pregnancy that involves the liver as one of the target organs. METHODS: Two patients who died from complications of HELLP syndrome were evaluated for attempted multi-organ procurement. Donor characteristics, gross and microscopic liver findings, and procurement and transplant outcomes were reviewed. RESULTS: One of the liver allografts was successfully transplanted; the other was not procured because of poor macroscopic appearance. CONCLUSION: It is possible to successfully transplant the liver from a donor that succumbs to HELLP syndrome, provided there is adequate recovery of liver function before procurement.

Fungal infections in solid organ transplant patients.

BACKGROUND: Solid organ transplantation is becoming increasingly more common in the treatment of end-stage organ failure. Opportunistic fungal infections are a frequent life-threatening complication of transplantation. MATERIALS AND METHODS: In this article, a review of the infections in the different organ transplant recipients is presented. RESULTS: The incidence of fungal infections in organ transplant patients ranges from 2% to 50% depending on the type of organ transplanted, kidney recipients being the least frequent and liver recipients having the highest rate of infection. New antifungal medications and immunosuppressants have changed the spectrum of fungal treatment and prevention. CONCLUSION: Prompt recognition and treatment of infection is imperative for successful therapy. Further advancements in early detection and the development of less toxic medications will lead to refinements in the treatment of fungal infections.

Combined liver and pancreas procurement from a controlled non-heart-beating donor with aberrant hepatic arterial anatomy.

BACKGROUND: The critical shortage of transplantable organs has resulted in the use of extended donors, including non-heart-beating donors (NHBDs). Combined procurement of both a whole pancreas and a liver from a single cadaver is always anatomically feasible. However, when aberrant vasculature is present, the potential for vascular injury increases. Because the rapid flush technique is used in NHBD procurement, the inability to palpate arterial pulsation may also increase the chance of vascular damage. METHODS: We report a case of a successful combined procurement of hepatic, pancreatic, and renal grafts from a controlled NHBD with right replaced and left accessory hepatic arteries. RESULT: The liver and the pancreas were successfully transplanted to two different recipients in two different institutions without any complications. All grafts are functioning well at 14 months of follow-up. CONCLUSION: Safe procurement of both the liver and pancreas is possible from certain controlled NHBDs, even with aberrant anatomy.

Liver transplantation for patients on methadone maintenance.

Most transplant programs require abstinence of at least 6 months from alcohol and illicit drugs before orthotopic liver transplantation (OLT). However, there are no published data regarding OLT outcomes in patients who are currently on methadone maintenance treatment (MMT) as part of the treatment of their heroin addiction at the time of OLT. The objective of this study is to evaluate our experience regarding the outcome of OLT in patients with end-stage liver disease (ESLD) who were on MMT at the time of OLT. Between March 1993 and May 1999, a total of 185 patients with ESLD underwent OLT at our center. Five transplant recipients (2.7%) had a history of heroin abuse and had undergone drug and alcohol rehabilitation, but could not be weaned off methadone. Pre-OLT status, drug history, perioperative course, compliance with medical therapy, post-OLT follow-up, and patient and allograft survival were analyzed in detail in these patients. All patients on MMT underwent uneventful OLTs. Their compliance with medications and follow-up was excellent. One patient was weaned completely off methadone after OLT. Post-OLT mean hospital stay in this group was 43 +/- 25 days. Although the number of patients was small, long-term outcome of liver transplant recipients on MMT appears similar to that of patients not on MMT who underwent OLT during this period. Our results suggest cirrhotic patients on MMT should be considered for OLT if they meet the same psychosocial requirements as patients with alcohol abuse. Furthermore, it is not necessary for patients to be weaned off methadone before OLT.

Cigarette smoking is associated with an increased incidence of vascular complications after liver transplantation.

Hepatic artery thrombosis (HAT) and other vascular complications are significant causes of morbidity after liver transplantation. Although cigarette smoking increases the risk of vascular complications after renal transplantation, its impact after liver transplantation remains unknown. Between May 1995 and April 2001, 288 liver transplantations were performed in 263 patients. Vascular complications developed in 39 patients (13.5%) (arterial complications, 28 patients [9.7%]; venous complications, 11 patients [3.8%]). Patient demographics, comorbid illnesses, and risk factors were analyzed using the Mann-Whitney U test, Chi-squared test, and Fisher's exact test. In patients with a history of cigarette smoking, incidence of vascular complications was higher than in those without history of cigarette smoking (17.8% v 8%, P =.02). Having quit cigarette smoking 2 years before liver transplantation reduced the incidence of vascular complications by 58.6% (24.4% v 11.8%, P =.04). The incidence of arterial complications was also higher in patients with a history of cigarette smoking compared with those without such history (13.5% v 4.8%, P =.015). Cigarette smoking cessation for 2 years also reduced the risk of arterial complications by 77.6% (21.8% v 5.9%, P =.005). However, the incidence of venous complications was not associated with cigarette smoking. Furthermore, there was no significant association between development of vascular complications and all other characteristics studied. Cigarette smoking is associated with a higher risk for developing vascular complications, especially arterial complications after liver transplantation. Cigarette smoking cessation at least 2 years before liver transplantation can significantly reduce the risk for vascular complications. Cigarette smoking cessation should be an essential requirement for liver transplantation candidates to decrease the morbidity arising from vascular complication after liver transplantation.

Safe use of livers from donors with positive hepatitis B core antibody.

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.