Complications In Liver Transplant Recipients Research Articles

A novel combination regimen for the treatment of refractory bacteremia due to multidrug-resistant Pseudomonas aeruginosa in a liver transplant recipient

Both bacteremia and biliary cast syndrome are serious post-transplant complications in liver transplant recipients. In the setting of increasing drug resistance in the current era, management of infections caused by multidrug-resistant (MDR) bacteria has proven challenging. We present a case of a liver transplant recipient who developed biliary cast syndrome and intractable MDR Pseudomonas bacteremia that failed to resolve with conventional antimicrobial therapy and which was finally controlled by a novel combination regimen of colistimethate, doripenem, and tobramycin. Future studies validating the clinical efficacy of this combination strategy are warranted.

T1556: Patient-Related Factors Influence Post-Endoscopic Retrograde Colangiography Complications in Liver Transplant Recipients

Complications of the biliary tract after liver transplantation (LT) are common and can be successfully managed with endoscopic retrograde cholangiography (ERC) in most cases. Although ERC may be associated with significant complications, specific risk factors in LT recipients have not been studied. The aim of this study was to examine specific risk factors for post-ERC complications in LT recipients.

Procalcitonin as a prognostic marker for infectious complications in liver transplant recipients in an intensive care unit

Clinically significant infections (CSIs) are life-threatening but difficult to diagnose after liver transplantation (LTx). This study investigates the value of procalcitonin (PCT) in addition to c-reactive protein (CRP) and the leukocyte count (LC) as a prognostic marker for CSIs in LTx recipients. The clinical course of 135 LTx recipients was prospectively studied. CSIs were defined as pulmonary, bloodstream, or intra-abdominal infections. Independent risk factors for CSIs were determined by Cox proportional hazard analysis. The concordance statistics (c-statistics) were used to assess the discrimination effect of PCT. Thirty recipients (22%) experienced a CSI. They had significantly higher peak PCT (27.2 versus 12.7 ng/mL, P = 0.014) and peak CRP (13.7 versus 9.9 mg/dL, P < 0.001) and a tendency toward a higher peak LC (19.3 versus 14.2 cells/nL, P = 0.051) in comparison with recipients without CSIs. Independent risk factors for CSIs were male sex [hazard ratio (HR) = 6.4], a body mass index (BMI) < 20 kg/m(2) (versus a BMI > 25 kg/m(2), HR = 13.8), acute liver failure as an indication for LTx (HR = 7.1), a cold ischemic time > 420 minutes (HR = 3.5), and peak CRP (HR = 1.1) but not peak PCT. The addition of peak PCT marginally improved the c-statistic from 0.815 to 0.827. In conclusion, although peak PCT differed significantly between recipients with and without CSIs, it was not an independent risk factor for CSIs and added little prognostic accuracy. Interestingly, the parameters peak CRP, male sex, low BMI, acute liver failure, and long cold ischemic time were independent risk factors for CSIs. They could serve as risk stratifiers directing medical therapy in clinical practice.

Clinical significance of HLA antibody detection in patients with biliary cast syndrome after liver transplantation

Objective To investigate the association of situation of HLA antibody with biliary cast syndrorne(BCS)in patients after liver transplantation and explore the role of HLA antibody in predicting BCS caused by immunization.Methods A total of 416 serum samples were collected at 8 time phases before and after liver transplantation from 52 patients.The 52 patients were divided into the BCS group(n=32)and NBCS group(n=20).The HLA-Ⅰ and HLA-Ⅱ antibodies in the serum samples were detected with ELISA.Meanwhile,ALT,AST,ALP,GGT,TB and DB were determined,Results The positive rate of HLA was significantly higher in the BCS group than in NBCS group (P<0.05).The recovery time of biliary complications were negatively correlated to the appearance time of HLA-Ⅱ antibody.Conclusion HLA-Ⅱ antibody can be dynamically monitored to help predict the biliary complications in liver transplantation recipients. Key words: Liver transplantation; HLA antibody; Biliary cast syndrome(BCS)

Estudio descriptivo de las complicaciones infecciosas en 109 receptores de trasplantes hepáticos consecutivos

Infectious disease is a common, serious complication in liver transplant recipients. The etiology of these infections undergoes changes related with technical advances, prophylaxis, and local epidemiology. Prospective study in patients who underwent liver transplantation from July 2003 to December 2005 at the Hospital Universitario Virgen del Rocío. An observational description of infections occurring during the first 2 years following transplantation was carried out. The incidence of infection was 1.32 episodes per patient over follow-up (443 +/- 248 days). The most frequent infections were surgical site (16%), cytomegalovirus (CMV) (14%), and urinary tract (11%). Etiologies included bacterial (64%), viral (31%), and fungal (5%) causes. The most common pathogens were CMV (21%), Escherichia coli (20%), among which, 40% were extended-spectrum beta-lactamase ESBL-producers, and Enterococcus spp. (11%). More than half the infectious episodes (58%) occurred in the first 4 months after transplantation. The 30-day mortality rate was 18%. In the group with infection, patient and graft survivals were 75% and 73% at the end of follow-up, and in the group without infection, survival was 80% in both cases (P=NS). The most common infectious syndromes following liver transplantation were surgical site infection, CMV infection, and urinary tract infection. Bacteria were the most commonly isolated microorganisms, and there was a high rate of ESBL-producing E. coli.

Neurologic Complications of Liver Transplantation in Pediatric Patients With the Hepatic Form of Wilson's Disease

The literature contains very little documentation on neurologic complications in liver transplant recipients for Wilson's disease. We retrospectively reviewed 17 consecutive cases of pediatric liver transplantation for the hepatic form of Wilson's disease to assess the types of neurologic complications that occurred, the incidence of those problems, and associated factors in this patient group. The patients were 12 boys and 5 girls; indications for liver transplantation were fulminant hepatic failure in 3 patients and chronic hepatic failure in 14 patients. Neurologic complications were observed in 10 of the 17 patients as 16 episodes. The most common neurologic complications were seizure (7 episodes in 6 patients) and sudden-onset headache (5 episodes in 4 patients). Tacrolimus was identified as the only possible cause of headache in 3 episodes. Encephalitis was the cause in 1 and intracranial hemorrhage was the cause in the other headache episode. We also noted 1 episode of tremor, 1 episode of acute dystonic reaction, 1 episode of diffuse encephalopathy, and 1 episode of common peroneal nerve palsy. Immunosuppressive agents were the primary cause of 12 of the 16 episodes of neurologic complications. Uremia with hypertension, compression of the right common peroneal nerve, encephalitis, and intracranial hemorrhages attributable to coagulopathy caused 1 neurologic episode each. Neurologic complications in patients with the hepatic form of Wilson's disease were frequent during the first 30 days after pediatric liver transplantation but did not affect survival. Transplantation teams should be aware of the high incidence of neurologic complications in pediatric patients with the hepatic form of Wilson's disease.

Gastrointestinal Complications in Liver Transplant Recipients: MITOS Study

Introduction Liver transplant recipients frequently suffer gastrointestinal (GI) complications but their prevalence and their influence on quality of life remain unknown. Objective The objective of this study was to asses the prevalence, impact on quality of life, and management of GI complications in liver transplant recipients. Patients and Methods This was an epidemiologic, cross-sectional, multicenter study. Four hundred seventeen liver recipients were recruited in 14 centers. A questionnaire was filled for every patient. Results The median age of the patients was 55 years. The median time since transplantation was 4.1 ± 4 years. Whereas 19.2% presented some GI disease before transplantation, 49.4% showed this type of complication after transplantation. Diarrhea was the most prevalent GI complication, and anorexia was the GI disorder that affected patients daily activities the most frequently. GI complications were more frequent among female patients, subjects with pretransplantation hiatal hernia, and those readmitted after transplantation. Of the patients with GI complications, 70.9% received pharmacological treatment (89.7% with gastric protectors). Immunosuppressive therapy was also modified because of GI complications. Immunosuppressive drug dose was reduced in 18.1%, transiently stopped in 3.4%, and definitively stopped in 3.4% of cases. The drug most frequently changed was mycophenolate mofetil: dose reduction, 23.6%; transient withdrawal, 5.7%; and definitive withdrawal, 6.6%. Conclusions The prevalence of GI complications in the liver transplant population was approximately 50%. GI complications showed a significant impact on the quality of life of the patients. They were related to female gender, to pretransplantation GI pathology, and posttransplantation hospital admission. These complications were frequently managed with pharmacological therapy or with changes in immunosuppressive therapy.

Possible therapeutic effect of lipid supplementation on neurological complications in liver transplant recipients

Neurological complications (NCs) represent a serious problem following liver transplantation and may develop either because of various peri-operative factors or the toxicity of immunosuppression. Although the causality assessment of NCs can be particularly difficult in the setting of organ transplantation, calcineurin inhibitors (CNIs) might influence NCs to a certain extent, regardless of the etiology. Therefore, minimizing the influence of CNIs could be a reasonable strategy for alleviating NCs. Based on our hypothesis that lipid supplementation prevents lipophilic CNIs from crossing the blood-brain barrier, soybean oil was administered to five liver transplant patients with NCs. In all of these patients, the neurological symptoms improved without discontinuing or reducing the dose of CNIs. Thus, lipid supplementation might be able to reduce the adverse neurological effects of CNIs.

Polymorphisms in the methylenetetrahydrofolate reductase gene are determinant for vascular complications after liver transplantation

The aim of this study was to evaluate the role of the C677T-MTHFR (methylenetetrahydrofolate reductase)-polymorphism (CC, CT and TT) for vascular complications in liver transplant recipients. Retrospective study. Hepatology-Transplantation-Unit, Johann Wolfgang Goethe-University, Frankfurt am Main. 48 liver transplant recipients were included, no dropouts. MTHFR polymorphism was detected by PCR amplification and digestion with Hinfl restriction enzyme. Vascular complications after liver transplantation were detected from the patients' records. The total serum homocysteine (HCY) was analyzed with high-pressure liquid chromatography. In the wild-type group (CC), the HCY levels were slightly high (14.0+/-1 micro M). Among the patients with the CT polymorphism, the HCY values were elevated (22.5+/-3 micro M). In the homozygous TT group, there was a significant increase (31.2+/-6 micro M, P<0.01) of the HCY values. The percentage of vascular complications was higher in the heterozygous CT (47%) and homozygous TT (62.5%) group compared with wild-type CC (21%). Patients with a homozygous TT genotype of the MTHFR polymorphism with a vascular complication had a highly significant elevated HCY level compared to the other genotype groups, both with and without any vascular complications (P<0.001). Recipients with an elevated HCY and the TT polymorphism have a higher probability of developing a vascular complication after transplantation (odds ratio: 4.3 and 11.0; 95% confidence interval: 1.15, 12.25 and 1.41, 85.24). The C677T polymorphism in the MTHFR gene and subsequent elevation of the total serum HCY is significantly associated with an increased incidence of vascular complications in liver transplant recipients.

Early Postoperative Response of Cytokines in Liver Transplant Recipients

We evaluated the early postoperative response of several cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) prior to liver transplantation (T 0) as well as 1, 6, and 12 hours and 1, 2, 3, 5, and 7 days afterward. Cytokine concentrations were correlated with serum levels of bilirubin as a predictor of postoperative complications. Cytokine levels were determined in plasma samples from 16 liver transplant recipients (13 men, 3 women) aged 43 to 61 years. IL-6 and IL-10 reached their maximum concentrations 1 hour after transplantation. Each increase in IL-6 correlated to a rise in IL-10. IL-2, IL-4, TNF-α, and IFN-γ had a particular time-course for each patient studied. Bilirubin fell to almost normal values but not in cases of postoperative complications, where IL-6 showed values four times higher compared to those of liver transplant recipients who did not show postoperative complications. IL-6 and IL-10 plasma concentrations and serum bilirubin level might be useful as a predictive factor of postoperative complications in liver transplant recipients.

Hyponatremia Impairs Early Posttransplantation Outcome in Patients With Cirrhosis Undergoing Liver Transplantation

Hyponatremia is associated with reduced survival in patients with cirrhosis awaiting liver transplantation. However, it is not known whether hyponatremia also represents a risk factor of poor outcome after transplantation. We aimed to assess the effects of hyponatremia at the time of transplantation on posttransplantation outcome in patients with cirrhosis. Two-hundred forty-one consecutive patients with cirrhosis submitted to liver transplantation during a 4-year period (January 2000-December 2003) were included in the study. The main end point was survival at 3 months after transplantation. Secondary end points were complications within the first month after transplantation. Patients with hyponatremia (serum sodium lower than 130 mEq/L) had a greater incidence of neurologic disorders, renal failure, and infectious complications than patients without hyponatremia (odds ratio; 4.6, 3.4 and 2.7, respectively) within the first month after transplantation. By contrast, hyponatremia was not associated with an increased incidence of severe intra-abdominal bleeding, acute rejection, or vascular and biliary complications. Hyponatremia was an independent predictive factor of early posttransplantation survival. Three-month survival of patients with hyponatremia was 84% compared with 95% of patients without hyponatremia (P < .05). Survival was similar after 3 months. In patients with cirrhosis, the presence of hyponatremia is associated with a high rate of neurologic disorders, infectious complications, and renal failure during the first month after transplantation and reduced 3-month survival. In cirrhosis, hyponatremia should be considered not only a risk factor of death before transplantation but also a risk factor of impaired early posttransplantation outcome.

Incidence and Management of Biliary Complications After Orthotopic Liver Transplantation: Ten Years’ Experience at King Fahad National Guard Hospital

Background Despite technical modifications and application of various surgical techniques, biliary tract complications remain a major source of morbidity after orthotopic liver transplantation. We sought to assess the incidence and management of biliary complications at a single liver transplant unit. Methods Among 184 consecutive deceased donor liver transplants performed between February 1994 and July 2004, 66 were female patients and 118 male patients of age range 2½ to 69 years. We retrospectively reviewed the data regarding biliary complications in liver transplant recipients, after 115 duct-to-duct anastomoses and 65 hepaticojejunostomy. We analyzed the incidence and type of biliary complications, management sequence, and success rate. We analyzed the correlation between the modality of biliary reconstruction and the type/incidence of biliary complications. Results Thirty-two patients developed biliary complications, giving an overall incidence of 17.4%. There was a higher incidence of complications among patients in the hepaticojejunostomy group (21.5%) than the duct-to-duct technique (15.1%). Bile leakage occurred in 12 patients, including eight successful cases (66.6%) of endoscopic stent insertion/radiological techniques and surgery in four cases (33.3%). Among the 12 patients with initial leaks, six developed a subsequent stricture (50%). There were 26 cases of biliary stricture, including 22 (84.6%) who were initially managed using nonsurgical techniques with a success rate of 59%. Conclusion Biliary complications remain an important cause of morbidity after orthotopic liver transplantation. They can usually be managed percutaneously or endoscopically; however, tight strictures and major leaks frequently required surgical intervention.

Multi-detector computed tomography angiography of the hepatic artery in liver transplant recipients

To evaluate the ability of multi-detector row computed tomography angiography (CTA) in detecting hepatic artery complications in the follow-up of liver transplant patients, performing volume-rendering as reconstruction technique. The anatomy of hepatic artery was studied in 27 liver transplant recipients with a four-row CT scanner using the following parameters: collimation, 1 mm; slice width, 1 mm; table feed, 6-8 mm/s; spiral reconstruction time, 0.5 s; reconstruction interval, 0.5 mm; mAs, 160; kVp, 120. Before the study, the patients received 1000 ml of water as oral contrast agent to produce negative contrast in the stomach and the small bowel. A non-ionic contrast medium was infused intravenously at a rate of 5 ml/s with a bolus tracking system. Volume-rendering of hepatic artery was performed with the 3D Virtuoso software. The celiac trunk, the hepatic artery, and the right and left hepatic arteries were successfully displayed in high detail in all patients. Side branches, including small collaterals, and hepatic artery anastomosis could also be readily visualized. Volume-rendered CTA detected six hepatic artery stenoses, two hepatic artery thromboses, and two intrahepatic pseudoaneurysms. In two cases, CT detected hepatic artery stenosis with a diameter reduction of less than 50%, while digital subtraction angiography showed a normal artery. Volume-rendered multi-detector CTA is a promising non-invasive technique, since it allows images of high quality to be generated with excellent anatomical visualization of the hepatic artery and its complications in liver transplant recipients.

Biliary complications in liver transplant recipients

Despite numerous advancements in the management of patients who have undergone cadaveric liver transplantation, biliary complications continue to challenge clinicians. Biliary leaks in the early postoperative period and strictures in the late postoperative period represent the two major posttransplant biliary complications. Intrahepatic and hilar strictures are particularly difficult to manage and frequently require retransplantation, which should not be delayed. Choledocholithiasis and the biliary cast syndrome are frequently associated with underlying biliary strictures, and endoscopic attempts at removal should precede surgical interventions. Sphincter of Oddi dysfunction is increasingly recognized despite unclear pathophysiology. Hemobilia is most commonly iatrogenic and requires a high suspicion and prompt intervention. Although the number of diagnostic and therapeutic options have increased, there is no consensus as to which is superior. In recent years there has been a trend toward nonsurgical interventions, in particular endoscopic approaches.

Sirolimus is not associated with a higher incidence of wound or hepatic artery complications in liver transplant recipients: Jeffrey C Dunkelberg, James F Trotter, Tracy Steinberg, Michael Wachs, Thomas Bak, Marcelo Kugelmas, Gregory T Everson, Igal Kam, University of Colorado Health Sciences Center, Denver, CO

Sirolimus is not associated with a higher incidence of wound or hepatic artery complications in liver transplant recipients: Jeffrey C Dunkelberg, James F Trotter, Tracy Steinberg, Michael Wachs, Thomas Bak, Marcelo Kugelmas, Gregory T Everson, Igal Kam, University of Colorado Health Sciences Center, Denver, CO

Interventional ultrasound: experience in 426 orthotopic liver transplantations

BackgroundThe purpose of this study was to analyze the role of interventional ultrasound in the treatment of nonvascular complications in liver transplant recipients. MethodsBetween August 1996 and May 2003, we performed 426 OLTs in 394 patients, 287 men (73%) and 107 women (27%), mean age of 50 ± 9.5 years (range 17 to 68.2). A total of 2556 diagnostic ultrasound examinations were performed, resulting in a mean of 5.9 per patient (range 2 to 21). The interventional maneuvers included: echo-guided biopsies; drainage of abdominal or thoracic effusions; drainage of abdominal, intrahepatic, or splenic collections; positioning of biliary drains; and use of the “rendezvous” technique. ResultsSix hundred seventy-seven echo-guided interventional maneuvers were performed in 394 OTL patients, comprising 417 (61.6%) biopsies and 260 (38.4%) therapeutic maneuvers. Eighty-one ascite drains were positioned (31.1%); in 73 cases, pleural effusions were drained (28.1%). Sixty-seven abdominal or intrahepatic collections were drained (25.8%), of which 36 (53.7%) were due to bilomas or biliary peritonitis, 15 (22.4%) hematomas, 4 (5.9%) hepatic abscesses, 11 (16.4%) infected abdominal collections, and 1 (1.5%) splenic abscess. Thirty-nine cases (15%) of biliary drainage were performed. In 33 cases (7.9%), the parenchymal biopsies were not diagnostic because of an inadequate specimen. The treatment success rate was 96.1%. No complications related to the therapeutic maneuvers were recorded, but there were 5 biopsy-related complications (1.2%). ConclusionsEcho-guided interventional maneuvers are safe, produce a high success rate, and represent an important option in the management of OLT patients.

De novo malignancies and liver transplantation

Introduction De novo tumors (DNTs) are the leading cause of late death among liver transplant recipients with an incidence of 5% to 15%, which is significantly greater than the general population. In this retrospective study, we compared this complication in liver transplant recipients to sex- and age-matched controls. Patients Among 410 patients who received liver allografts between March 1986 and December 2000, 32 (7.8%) developed a DNT. Epidermoid tumors were the most frequent histologic lineage. A complete response was observed in 19 patients (59.4%), a partial response in eight (25%), and no response in five (15%). Survival was lower among liver transplant recipients than controls, a difference that was statistically significant. Treatment consisted of surgery in 76.7%, radiotherapy in 16.7%, chemotherapy in 13.3%, and reduction of immunosuppression in 10%. Results The mean survival time in transplant patients of 122.97 months (95% CI; range 98–147 months) was significantly shorter than controls, 156.5 months (95% CI; range 141–171 months). About 50% of patients were smokers (active or ex-smokers), compared to 20.7% of controls ( P = .049). Significant differences were also found when the three subgroups (smokers, previous smokers, and nonsmokers) were analyzed separately ( P = .013). Patients were smokers (active or nonactive) among 45% of cases of skin tumors; 60% of hematological tumors; 71.4% of epidermoids; and 33% of sarcomas. Conclusions DNTs, a complication of long-term immunosuppression in patients after liver transplantation, most frequently presented as skin tumors and PTLD. Occurrence of a DNT was an adverse prognostic factor for survival. Smoking represents an independent risk factor for these tumors.

Conversion from calcineurin inhibitors to mycophenolate mofetil in liver transplant recipients with diabetes mellitus

Diabetes mellitus, a frequent metabolic complication in liver transplant recipients, may be produced by the diabetogenic effect of calcineurin inhibitors cyclosporine and tacrolimus. The aim of this study was to investigate the safety and metabolic effects of a gradual switch from cyclosporine or tacrolimus to mycophenolate mofetil among 12 diabetic liver transplant recipients. One patient was withdrawn from the study due to gastrointestinal side effects. Of the 11 remaining patients, cyclosporine or tacrolimus was completely withdrawn in five patients. Two patients developed suspected acute rejection episodes that were controlled by increasing the tacrolimus dosage. Glycosylated hemoglobin A 1C and C-peptide levels were significantly lower at 3 and 6 months after the initiation of mycophenolate mofetil ( P < .03 in all cases). Furthermore, urea and uric acid levels were significantly reduced after the change of treatment. In conclusion, a switch from cyclosporine/tacrolimus to mycophenolate mofetil may produce beneficial metabolic effects in diabetic liver transplant recipients, but poses a risk of graft rejection.

De novo malignancies in liver transplantation

Introduction De novo tumors (DNTs) are the leading cause of late death among liver transplant recipients with an incidence of 5% to 15%, which is significantly greater than the general population. In this retrospective study, we compared this complication in liver transplant recipients to sex- and age-matched controls.

Secondary Osteoporosis in Liver Transplant Recipients: a Longitudinal Study in Patients With and Without Cholestatic Liver Disease

Background: Metabolic bone disease is one of the major long-term complications in liver transplant recipients, but it remains unclear which patients are at highest risk for developing severe bone disease following transplantation. Methods: A total of 46 consecutive, adult patients with chronic liver disease accepted for a liver transplantation waiting list were prospectively included in the study. The patients were classified into two groups: group A—chronic cholestatic liver disease (n = 28), and group B—chronic non-cholestatic liver disease (n = 18). Bone mineral density (BMD) was measured at acceptance for the waiting list and at 3, 12 and 36 months following transplantation. Markers of bone turnover (serum-bone specific alkaline phosphatases (bALP), s-osteocalcin, s-l-collagen-C-terminal telopeptide (1-CTP) and urine N-terminal telopeptides u-Ntx) were measured at acceptance and at 3, 6, 12, 24 and 36 months following transplantation. BMD and markers of bone turnover were compared with similar values in a matched control group of 42 healthy individuals. Results: BMD decreased significantly during the early post-transplantation period (median bone loss femoral neck (FN) 3 months post-transplant 8.5%). BMD levels declined slightly from 3 to 12 months following transplantation and increased thereafter. The relative bone loss was greatest among group B patients (relative bone loss FN 3 months post-transplant: group A, 8% versus group B, 13%; P = 0.04). At 36 months, 8/17 group A and 2/9 group B patients had BMD levels that exceeded the pretransplant levels (P = 0.12). The early bone loss was positively correlated with an increase in resorption markers (s-1-CTP and u-Ntx). Group B had higher levels of both s-1-CTP and u-Ntx at 3 and 6 months post-transplant than group A patients (P = 0.03). Bone formation markers increased slowly from 6 months post-transplant and onwards. Relative bone loss was positively correlated to total glucocorticoid dose during the first 3 months post-transplant. There were no differences in BMD between patients receiving tacrolimus versus those receiving'cyclosporin A. Conclusion: Bone loss following liver transplantation is considerable in patients with both cholestatic and non-cholestatic liver disease, the first group has the poorest starting-point while the latter group has the greatest bone loss following transplantation. Bone loss is closely correlated with biochemical markers of bone resorption and total dose of glucocorticoids given post-transplant.