Acute renal failure in the first 100 orthotopic liver transplant patients in Southern Iran

Postoperative acute renal failure is a frequent and serious medical complication following orthotopic liver transplant. Here, we report our experiences with liver transplant recipients who developed acute renal failure in the early period following orthotopic liver transplant. Among 100 liver transplants performed between April 1993 and January 2004, we retrospectively analyzed 91 patients (mean age, 29.9 +/- 14.0 years) who had undergone orthotopic liver transplant. The underlying causes of liver failure were cryptogenic liver cirrhosis (n=27), viral hepatitis (n= 21) (hepatitis-B-related liver cirrhosis [n=13], hepatitis-C-related liver cirrhosis [n=7], and hepatitis-B- and C-related liver cirrhosis [n=1]), autoimmune hepatitis (n=18), Wilson's disease (n=10), primary sclerosing cholangitis (n=8), biliary atresia (n=3), Budd-Chiari syndrome (n=2), and primary biliary cirrhosis (n=2). The immunosuppressive regimen included mycophenolate mofetil (azathioprine for 10 patients), cyclosporine, and steroids. Six patients received a combination of tacrolimus and steroids. Ten patients (10.9%) experienced acute renal failure, 7 (70%) were men, and none of them required renal replacement therapy and/or died. Four patients were diagnosed as having cryptogenic liver cirrhosis; 2 with hepatitis-C-related liver cirrhosis, 2 with autoimmune liver cirrhosis; 1 with primary biliary cirrhosis; and 1 hepatitis-B-related liver cirrhosis. Six patients were Child-Pugh's classification C, and the others were B. The rate of postoperative acute renal failure in our patients was relatively low when compared with other series, and our outcomes were good.     

Analysis of morbidity in liver transplant recipients following human albumin supplementation: a retrospective pilot study

OBJECTIVES: To assess incidence of morbidity (i.e., documented infection, acute renal failure, acute graft rejection, acute cardiovascular events, and hospital readmission rates) 6 months following liver transplantation using linear regression as a function of cumulative albumin dose. DESIGN: Retrospective chart review. SETTING: A 473-bed tertiary care teaching facility with a solid-organ transplantation center. PATIENTS: Forty liver transplant recipients examined from January 1 to December 31, 2003. MEASUREMENTS AND RESULTS: Data from 40 liver transplant recipients were collected. Mean albumin dose administered was 190.9 +/- 162.3 g. No statistical differences were identified in patients receiving less than 140 g (n=20) or more than 140 g (n=20) with respect to demographic data other than gender and ethnicity. The mean APACHE III (Acute Physiology and Chronic Health) score was 69.7 +/- 24.3. Approximately 70 episodes of morbidity and 23 readmissions were observed. Regardless of the APACHE III score, albumin was associated with increased overall morbidity and cardiovascular complications. Liver transplant recipients receiving more than 140 g had a longer hospital stay (14 vs. 8 days, P = .025) and intensive care unit stay (6 vs. 3 days, P = .051) than patients receiving 140 g or less. No correlation with risk of acute rejection was seen with albumin or tacrolimus. Conclusion-Albumin supplementation among liver transplant recipients was associated with a significant risk for cardiovascular complications and overall number of complications regardless of APACHE III score. Future prospective studies are needed to further define the potential risk for complications in this patient population.     

Quality of life after liver transplantation for acute hepatic failure.

Liver transplantation is now an accepted and successful therapy for both acute and cronic liver diseases. Whilst the study of health related quality of life (HRQoL) post-transplantation for chronic liver disease (CLD) has been well documented, there is little data measuring HRQoL following liver transplantation for acute liver failure (ALF), despite super urgent transplantation constituting 16.6% of al United Kingdom liver transplantation. Therefore, the aim of the present study was to document the HRQoL in patients who have received an emergency liver transplant for ALF. Data collection employed between method triangulation, using the Short Form 36 quality of life health questionnaire for both ALF (n=47) and CLD (n=49), and six semi-structured interviews. Only the qualitative element of the study is reported here. Phenomenological analysis of the semi-structured interviews identified four themes relating to the physical changes encountered (inactivity), physical recovery (health transition); changes made to the transplant recipients life styles (modification); and outlook. The majority of transplanted ALF transplant recipients' stated that they have a good quality of life, which was often comparable to their pretransplantation lifestyle. However, the initial recovery process was often difficult and was related to the physical changes instigated from their multi-organ failure and intensive care stay, which can present numerous physical and emotional challenges.     

Living donor liver transplantation for acute liver failure: a 10-year experience in a single center

BACKGROUND: Living donor liver transplantation has become an accepted treatment for various terminal liver diseases. STUDY DESIGN: Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed. RESULTS: Causes of liver failure included hepatitis B (n=12), hepatitis C (n=1), autoimmune hepatitis (n=2), Wilson's disease (n=3), and unknown causes (n=24). The graft types were: left lobe (n=33), right lobe (n=8), and lateral segment (n=1). The mean graft volume to standard liver volume ratios were 42.2+/-9.2% in left lobe grafts and 50.5+/-3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 +/-18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients. CONCLUSIONS: Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated.     

Long-term outcome of immunosuppression withdrawal after liver transplantation

Eighteen liver transplant recipients were followed up for 10 years after a trial of immunosuppression withdrawal. Three groups were identified according to the early outcome of complete (group A, n = 5), partial (group B, n = 9), and unsuccessful (group C, n = 4) withdrawal of immunosuppression. The indications for liver transplantation (LT) (August 1983-December 1988) were as follows: primary biliary cirrhosis (n = 3), primary sclerosing cholangitis (n = 3), Budd-Chiari syndrome (n = 3), acute liver failure (n = 3), hepatitis C virus (HCV) cirrhosis (n = 1), HCV and autoimmune hepatitis (n = 1), HCV and alcohol-related cirrhosis (n = 1), HCV and hepatocellular carcinoma (HCC) (n = 1), cystic fibrosis (n = 1), and liver metastases from testicular teratoma (n = 1). Immunosuppression was based on cyclosporine. All patients experienced 1 or more complications of prolonged immunosuppression (median, 7 years; range, 5-11). Thirteen patients (72%) are alive at a median interval of 17 years (range, 16-21) after LT. Of the 5 patients in group A, 2 currently have normal graft function with no rejection episodes, and 3 have restarted immunosuppression following late low-grade acute rejection (n = 1), retransplantation for chronic rejection (n = 1), and kidney transplantation (n = 1). Of the 9 patients in group B, 5 died. The deaths were due to ruptured arterial pseudoaneurysm following retransplantation, HCC recurrence, cardiac failure, renal failure, and posttransplant lymphoma at 5, 7, 7, 14, and 17 years after LT, respectively. All 4 patients in group C are alive on a full immunosuppressive regimen. Long-term follow-up of 18 LT recipients withdrawn from immunosuppression has shown that at a median of 17 years 10% of patients remain off all immunosuppression.     

Outcomes of liver transplantation for hepatitis B: a single-center study of 35 patients

BACKGROUND: Results of liver transplantation (LT) for hepatitis B (HBV) have improved in the past decade but recently drug resistance has been described, the clinical significance of which is unclear. The aims of this study were to evaluate outcomes of LT for HBV and describe the prevalence of drug resistance. METHODS: A retrospective chart analysis and review of the organ transplant database was performed to identify all patients transplanted for HBV between December 1982 and April 2004 who survived more than 3 months. RESULTS: Thirty-five patients were transplanted for HBV during this period: 27 men and 8 women. Median age at LT was 48.8 years (range 18.9 to 74.3). Four patients were transplanted for fulminant liver failure and 31 for decompensated cirrhosis. Intramuscular HBIG was administered to 8 patients and intravenous HBIG to 32 patients, data were unavailable for three patients. Lamivudine was prescribed for 18 patients (58%) pre-OLT and for 31 patients (88.6%) post-LT. Drug-resistant HBV developed in two patients (5.71%) receiving lamivudine and HBIG. Adefovir substitution resulted in improvement in liver function tests, in HBV DNA and in histology in both patients. Twenty-five patients are currently alive with and 1-year survival of 95% and a 5-year survival of 75%. Causes of death were respiratory failure (n = 3), metastatic cancer of unknown primary (n = 2), renal failure (n = 2), sepsis (n = 1), cerebrovascular accident (n = 1), and cerebral edema (n = 1). CONCLUSIONS: LT for HBV shows survival rates comparable to other liver transplant recipients. Lamivudine resistance was rare in this series but responded to adefovir substitution.     

Early-onset coronary artery disease after pediatric kidney transplantation: implicating the angiogenesis inhibitor, endostatin

Pediatric kidney transplant recipients have a higher rate of coronary artery disease (CAD) as adults. The angiogenesis inhibitor, endostatin, has been implicated in the development of atherosclerosis. Endostatin levels will vary between adult patients who received a kidney transplant as a child. We conducted a study in young adult patients who had undergone pediatric kidney (n = 12) or liver transplantation (n = 8). Coronary arterial calcification was measured using electron beam CT. Values were compared with age-matched control subjects from an epidemiologic database. Serum endostatin levels were measured using enzyme-linked immunosorbent assay. Risk factors for atherosclerosis were assessed. Kidney transplant recipients had a higher rate of CAD compared with liver transplant recipients (33 vs 0%, P = 0.03). Mean (± standard error of mean) serum endostatin levels were higher in kidney transplant recipients compared with liver transplant recipients (26 ± 7 vs 14 ± 3 ng/mL, P = 0.04) and control subjects (26 ± 7 vs 11 ± 1 ng/mL, P = 0.01). Pediatric kidney transplantation is associated with a higher rate of adult-onset CAD compared with liver transplantation. Endostatin levels were greater in kidney transplant recipients compared with liver transplant recipients and healthy control subjects. Endostatin may play a role in the development of atherosclerosis after kidney transplantation and may serve as a biomarker for atherosclerotic disease.     

Fatigue and physical function after orthotopic liver transplantation

Over the last two decades, orthotopic liver transplantation (OLT) has become an established treatment for acute and chronic liver failure. OLT impacts not only on survival, but also on health-related quality of life. This study was undertaken to describe the self-rated health of Danish liver transplant recipients, compare their self-rated health against that of the general population, and to investigate associations between sex, age, diagnosis, time after OLT, and postoperative physical function and fatigue. All adult surviving liver transplant recipients who underwent OLT in Copenhagen, Denmark, from 1990 to 1998 (n = 154) were contacted by mail and asked to complete a self-administered questionnaire. The questionnaire contained the 36-Item Short Form Health Survey, the Multidimensional Fatigue Inventory, the Hospital Anxiety and Depression Scale, and questions on marital status, education, and work. The response rate was 84.4% (n = 130). Liver transplant recipients reported poorer self-rated health than the general population in physical, but not in mental, health areas. One health aspect, fatigue, was investigated in great detail. This study found that liver transplant recipients experienced physical, rather than mental, fatigue. Diagnosis was found to be a predictor of postoperative physical function and fatigue because patients with an alcoholic or cryptogenic cirrhosis background had significantly poorer physical function and experienced more physical fatigue than liver transplant recipients with other diagnoses. Work status and survival time after OLT had significant effects on postoperative physical function and fatigue. Working and having undergone transplantation 4 to 5 years previously were associated with significantly better physical function and less physical fatigue than not working and having undergone transplantation 1 to 3 years previously. This study suggests that liver transplant recipients experience physical, rather than mental, impairment and fatigue and that diagnosis, work status, and survival time after OLT are associated with physical function and fatigue. (Liver Transpl 2002;8:251-259.)     

Outcome of renal transplantation subsequent to liver, heart, or lung transplantation

Renal dysfunction is a growing problem after liver, heart, or lung transplantation with the subsequent need for dialysis or renal transplantation. The aim of this study was to analyze the outcome after a subsequent kidney transplantation (secondary kidney transplantation) in liver, heart, or lung transplantation recipients. All secondary kidney transplantation patients from 1985 to 2006 were identified for the cause of kidney failure, time after initial transplantation, and current kidney function. One thousand two hundred three patient charts were reviewed including 22 (1.8%) secondary kidney transplantations: eight after lung, eight after heart, and six after liver transplantation. Renal failure was the result of perioperative renal failure (n = 3), toxic effects of cyclosporine (n = 16), a combination of cyclosporine nephrotoxicity and vascular ischemia (n = 3), or chronic renal failure due to polycystic kidney disease (n = 1). The median time after the initial organ transplantation was 114 months (range 30 to 241 months). The most recent median creatinine value was 103 micromol/L (82 to 704 micromol/L). Renal transplant rejection was noted in five patients: four in the lung transplant group, and one after heart transplantation. Three patients were deceased, one from secondary renal failure. One renal allograft was removed after renal artery thrombosis. In conclusion, there is sometimes a need for subsequent kidney transplantation after liver, heart, or lung transplantation. The outcome of renal transplantation subsequent to liver, heart, or lung transplantation is good with satisfactory renal function in this study population.     

Results of split liver transplantation in children

OBJECTIVE: To analyze the outcome of 80 consecutive pediatric split liver transplants performed at the authors' center between 1994 and 2000. SUMMARY BACKGROUND DATA: Split liver transplantation has become an accepted method of increasing the number of available grafts for pediatric liver transplant recipients. METHODS: The age of the patients at the time of transplantation ranged from 5 days to 16 years (median 3 years). Sixteen transplants were performed for acute liver failure and 64 for chronic liver failure. The ex situ splitting technique was used for all but four grafts. Fourteen livers were split for two pediatric recipients. Posttransplant follow-up ranged from 6 to 84 months (median 42 months). RESULTS: Overall patient survival at 6 months follow-up was 96.2%. Graft survival at six months was 93.7%. The Kaplan-Meier patient survival rates at 1 and 3 years were 93.5% and 88.1%, and the graft survival rates were 89.7% and 86.1%, respectively. Four patients required retransplantation. In the acute group (n = 16), the patient survival rates were 93.7% at 1 year and 76.4% at 3 years; there were three deaths due to posttransplant lymphoproliferative disease (PTLD), sepsis, and chronic rejection. In the chronic group (n = 64), the 1- and 3-year patient survival rates were 93.6% and 90.9%, respectively. There were six deaths in this group. Four patients died in the first year after the transplant due to intracranial bleeding, cerebral tumor recurrence, PTLD, and chronic rejection. There were two deaths at 3 years, one due to progressive renal failure secondary to cyclosporin toxicity and the other due to sepsis, portal hypertension, and recurrent bleeding. Vascular complications occurred in six (7.5%) patients and biliary complications in seven (8.7%). CONCLUSIONS: These results, which represent the experience of a single institution over the last 6 years, indicate that ex situ split liver transplantation can be performed in children with good overall outcome and acceptable morbidity.     

Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: Results from a double-blind randomized placebo-controlled trial

Basiliximab, a high-affinity chimeric monoclonal antibody, is effective in reducing acute rejection episodes in renal allograft recipients. We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients. Adult recipients of a primary cadaveric liver transplant were randomized to treatment, stratified by hepatitis C virus (HCV) seropositivity. Patients were administered 40 mg of basiliximab (n = 188) or placebo (n = 193) as two 20-mg bolus injections days 0 and 4, plus cyclosporine and steroids. Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point, including death or graft loss, and were assessed at 6 and 12 months and by HCV cohort. Because of differential efficacy responses between HCV-positive and HCV-negative cohorts, an additional analysis incorporating HCV recurrence as a component of treatment failure, termed problem-free transplant, was introduced. Safety and tolerability were monitored over the 12 months of the study. All 381 patients were assessable, and no meaningful differences in background characteristics were apparent between treatment groups. Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1% in the basiliximab group versus 43.5% in the placebo group. For death, graft loss, or first biopsy-confirmed acute rejection, rates were 44.1% versus 52.8%, respectively. The reduction in rejection episodes was concentrated in the HCV-negative cohort (14.5% relative to placebo; P = .034), with a much smaller difference (2.9%) in the HCV-positive cohort. For HCV-positive patients, problem-free transplant was shown at 12 months in 26.6% of the basiliximab group versus 11.6% in the placebo group (P = .020) and for all patients at 12 months in 39.7% of the basiliximab group versus 30.1% in the placebo group (P = .035). The incidence of infection and other adverse events was similar across the two treatment groups. There were 56 deaths (25 deaths, basiliximab group; 31 deaths, placebo group) over the 12-month study. The intravenous bolus injection was well tolerated. Immunoprophylaxis with 40 mg of basiliximab, in combination with cyclosporine and steroids, reduces the incidence of acute rejection episodes with no clinically relevant safety or tolerability concerns. The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant, incorporating recurrence as a component of treatment failure. (Liver Transpl 2002;8:132-142.)     

De novo malignancies after kidney and liver transplantations: experience on 582 consecutive cases

De novo malignancies after transplantation are a growing problem of solid organ transplant recipients, due to longer survival follow-up under chronic immunosuppression. The aim of this study was to analyze a population of 582 consecutive kidney (n = 382) and liver (n = 202) transplant recipients, who survived at least 12 months after transplantation, at a single transplant center for the development of de novo cancers. The incidence of de novo malignancies was 7% after both renal and liver transplantation. The median elapsed time from transplant to the diagnosis of de novo malignancy was 45 months (range 3 to 220) months for kidney and 37 months (range 12 to 101 months) for liver transplants. Skin cancers were the most common within renal recipients, while gastroenteric cancers were more frequently encountered in liver transplants. Oropharyngeal and upper digestive tract tumors were always associated with a history of chronic alcohol consumption in liver recipients. Liver transplant recipients treated for acute rejection had a worse cancer prognosis than patients without rejection 1- and 2-year survivals 83% and 63% versus 36% and 17% (P = .026). The estimated 1- and 2-year survival rates for all types of de novo malignancies were 79% and 66%, including 64% and 51% for solid organ tumors versus 89% and 89% for skin cancers and posttransplant lymphoproliferative disorder (PTLD) (P = .17) in renal transplants and 70% and 42%, including 57% and 28% for solid organ tumors versus 85% and 64% for skin cancers and PTLD (P = .43) in liver transplants respectively.     

ACE gene D/D genotype as a risk factor for chronic nephrotoxicity from calcineurin inhibitors in liver transplant recipients

BACKGROUND: Chronic renal failure (CRF) is a major cause of morbidity and mortality after orthotopic liver transplantation (OLTX) and is predominantly caused by calcineurin inhibitors (CI)-induced nephrotoxicity. The activation of the renin angiotensin system (RAS) has been implicated in the pathogenesis of chronic nephrotoxicity from CI. METHODS: We retrospectively investigated the genes coding for components of the RAS (ACE gene, Angiotensin II receptor 1 gene, Angiotensinogen gene) in 233 liver transplant recipients receiving Cyclosporine (CsA) or Tacrolimus (Tac) as maintenance immunosuppressant. All patients with serum creatinine (sCr) <1.0 mg/dL (n=143) before orthotopic liver transplantation (OLTX) were included in the final analysis. Patients were than categorized into two groups based upon their most recent postliver transplant sCr level: Group 1 (n=83) with sCr <1.5 mg/dL (mean 1.1+/-0.2) and group 2 (n=60) with sCr > or =1.5 mg/dL (mean 2.5+/-1.3) RESULTS: ACE D/D genotype was found in 57% of patients with sCr > or =1.5 mg/dL compared to 20% of patients with sCr <1.5 mg/dL (P<0.0001) CONCLUSIONS: Our analysis strongly suggests that liver transplant patients with ACE gene D/D genotype are at a significant higher risk of developing CI-induced chronic nephrotoxicity.     

亲属活体部分肝移植治疗肝豆状核变性手术适应征的探讨

目的:探讨亲属活体部分肝移植治疗肝豆状核变性手术适应证.方法:回顾性分析2001年1月至2007年2月37例接受亲属活体部分肝移植治疗的肝豆状核变性患者的临床资料.其中男性16例,女性21例,年龄7～21岁,中位年龄11岁.临床诊断包括:急性肝功能衰竭3例,慢性肝功能衰竭失代偿32例(其中伴有神经系统功能障碍13例),慢性肝功能衰竭代偿但伴有严重神经系统功能障碍2例.术前15例神经系统功能障碍患者的评分为(15.9±4.3)分.随访20～93个月,平均(48.1±27.6)个月.结果:本组37例患者获得随访,随访率100%.患者及移植物的1、3、5年存活率分别为91.9%、83.8%、75.7%和86.5%、78.4%、75.7%.供受者外科并发症包括:2例供者术后发生肝断而胆漏,经引流后治愈;3例受者发生血管并发症,其中2例为肝动脉栓塞,再次急诊行尸体肝移植后治愈;另1例为肝静脉吻合口狭窄,行介入球囊扩张治疗后治愈.神经系统功能障碍患者移植术后症状明显缓解,术后6、12、18、24和30个月评分分别为:[(17.5±3.7)分,n=13]、[(21.0±4.3)分,n=12]、[(23.9±3.9)分,n=10]、[(26.6±2.2)分,n=10]和[(28.1±1.9)分,n=7].结论:急性肝功能衰竭、慢性肝功能衰竭失代偿伴有(或不伴有)神经系统功能障碍均是亲属活体部分肝移植的手术适应证.对伴有严重神经系统功能障碍但肝功能相对稳定的患者,如内科治疗无效,仍可考虑行亲属活体部分肝移植.     

Topical testosterone treatment for chronic allograft failure in liver transplant recipients with recurrent hepatitis C virus

INTRODUCTION: Liver transplant recipients with allograft failure due to recurrent hepatitis C virus (HCV) infection often develop marked muscle wasting and ascites prior to death and are denied repeat liver transplantation. We sought to determine whether topical testosterone therapy is associated with improved muscle mass and survival in patients with chronic allograft failure post-liver transplant. METHODS: We performed a retrospective review of liver transplant recipients with chronic allograft failure. Group 1 patients were treated for >6 months with testosterone gel 1%; group 2 patients were untreated. RESULTS: Fourteen patients were identified with stage 3 or 4 fibrosis, muscle wasting, and allograft failure due to recurrent HCV. Group 1 (n=9) patients had statistically significant improvement in albumin, testosterone, muscle strength, well-being, and MELD/CTP scores, while there was no improvement seen for any of these parameters in group 2 (n=5). There were no deaths in group 1, while four of five patients in group 2 died on average 84 days posttransplant. Adverse effects of testosterone treatment included lower extremity edema (which resolved upon dose adjustment), hypertension, and pruritus. CONCLUSIONS: Topical testosterone gel appears to increase muscle strength, stimulate albumin synthesis, and improve survival in patients with allograft failure post-liver transplant.     

Prospective interventional study to evaluate the efficacy and safety of liposomal amphotericin B as prophylaxis of fungal infections in high-risk liver transplant recipients

INTRODUCTION: Invasive fungal infections are a life-threatening complication in transplant recipients. The prevalence of fungal infection after orthotopic liver transplantation (OLT) is 5% to 42%. The most common isolated pathogens are Candida and Aspergillus species. High-risk liver transplant recipients are more susceptible to the development of invasive fungal infections, with prevalence >40% and mortality rates of 78% to 100%. The strategy for fungal prophylaxis in this population has not been defined. PATIENTS AND METHODS: Among 100 consecutive OLT followed for 28 months, 21 recipients (15 men, overall mean age of 48.5 years, range 23-65 years) were considered to be high risk for the development of fungal infections when they presented at least one of the following criteria: acute liver failure, assisted ventilation >7 days, retransplantation, relaparotomy, antibiotic therapy >14 days, transfusion requirements >20 red blood cells units, and/or biliary leakage. This group received intravenous liposomal amphotericin B (1 mg/kg/d for 7-10 days). RESULTS: One-year survival in the high-risk group was 80%. Prevalence of invasive fungal infection was 9.5%. No Candida infection was observed. Two patients developed Aspergillus infection: an abdominal aspergillosis treated with percutaneous drainage and liposomal amphotericin B (5 mg/kg/d) showed a favorable clinical outcome. The other patient who developed brain aspergillosis died 25 days after OLT. Adverse events related to the drug were hypokalemia (n = 2), back pain (n = 3), and renal dysfunction (n = 2). None of these events required withdrawal of the prophylaxis regimen. CONCLUSION: In our series, prophylaxis with liposomal amphotericin B in high-risk liver graft recipients showed a low rate of severe fungal infections. More studies are needed in order to determine the highest risk population and the best drug dosage.     

A retrospective analysis of the use of caspofungin in recipients of liver transplant with a modified high index of suspicion for fungal infection. A critical review of mortality,acute cellular rejection,infections, and changes in the liver function tests while on caspofungin

Doria C, Bodzin AS, Vaccino S, Daskalakis C, Krawitz S, Ramirez CB. A retrospective analysis of the use of caspofungin in recipients of liver transplant with a modified high index of suspicion for fungal infection. A critical review of mortality, acute cellular rejection, infections, and changes in the liver function tests while on caspofungin.
Clin Transplant 2011: 25: 569–575. © 2010 John Wiley & Sons A/S. Abstract: This study is a retrospective analysis of death, adverse events (AE), fungal infections, and hepatic function among recipients of liver transplantation at high risk of fungal infection who received prophylactic treatment with caspofungin. After reviewing data of 105 patients who had received isolated liver transplant between January 2003 and April 2007, we identified and analyzed 82 high‐risk patients. Post‐transplant patients at high risk for fungal infection are commonly defined by the presence of at least one of the following: (i) re‐transplantation; (ii) re‐operation; (iii) renal dysfunction. However, in our practice, patients are also considered at high risk for developing fungal infections if they present with the following: (iv) fever of unknown origin; (v) hypothermia; (vi) positive random culture for fungus at the time of transplant (bile and/or ascites); (vii) sepsis; (viii) use of vasopressors; (ix) re‐intubation, during the first hospitalization after liver transplant; (x) prolonged intubation (>24 h), and (xi) acute respiratory distress syndrome, until negative fungal cultures are obtained. Exact conditional logistic regression was used to compare the risk of death, AEs, and fungal infections between patients who received caspofungin, other antifungal drugs, and no antifungal drugs. Analyses were then performed with SAS 9.1 (SAS Institute Inc., Cary, NC, USA). Patients were between 27 and 72 yr old (mean = 55), with two‐thirds male and three‐quarters Caucasian. Sixteen patients received caspofungin (11 preventively), and 32 received other antifungal (26 preventively). There were no proven fungal infections among the patients who received caspofungin, three infections among patients who received other antifungal (3/26 = 12%), and 14 infections among patients who were not preventively treated (14/45 = 31%). These infection rates were significantly different across the three groups (p = 0.029), with caspofungin and other antifungal preventive treatment comparable (p = 0.540), and both better than no preventive treatment at all (OR = 0.15, p = 0.049, for caspofungin versus no preventive treatment; OR = 0.29, p = 0.085, for other antifungal versus no preventive treatment). Caspofungin appears to be an effective preventive agent against fungal infections when used in recipients of liver transplant designated as high risk for fungal infection. Usage of caspofungin in these patients does not carry an apparent increase in risk of death or acute cellular rejection, although we observed a significantly higher risk of AEs, especially acute renal failure (p = 0.001), in patients who received this agent.     

Relationship between immunosuppression and osteoporosis in an outpatient liver transplant clinic

BACKGROUND: The aim of this study is to determine the relationship between immunosuppression, disease state, and osteoporosis in an outpatient liver transplant clinic. METHODS: All liver transplant recipients visiting an outpatient transplant clinic received bone density scanning with a dual-energy X-ray absorptiometry (DEXA) device of the calcaneal bone after completing a questionnaire assessing risk and medications currently being used. RESULTS: Of the 137 liver transplant (OLT) recipients completing questionnaires and receiving DEXA screening, patients with low bone density (n = 50) were older (56.6 +/- 12.7 years vs 50.2 +/- 10.1 years; P = .02) compared with normal density patients (n = 87) and were predominately female (64.0% vs 35.6%; P = .01). Based on disease state, patients with cholestatic liver failure had lower bone calcaneal area (17.3 +/- 1.3 cm2 vs 18.9 +/- 1.57 cm2; P < .01). Patients taking tacrolimus (n = 112), as compared with cyclosporine (n = 25), had a tendency toward fewer findings of low bone density (37.5% [42 of 112] vs 56.0% [14 of 25]; P = .08) but had more risk factors (3.1 +/- 1.2 vs 2.1 +/- 0.8; P = .001) and a higher prednisone dose (4.4 +/- 5.9 mg/d vs 2.1 +/- 3.8 mg/d; P = .026). For patients weaned from prednisone, the tacrolimus patients were less likely to have low bone density (36.2% vs 68.8%; P = .02). Mycophenolate mofetil did not influence bone density or area measured. CONCLUSIONS: After liver transplantation, patients taking cyclosporine were more likely to have low bone density compared with those taking tacrolimus.     

Outcomes of liver transplantation for acute fatty liver disease of pregnancy

Acute fatty liver of pregnancy (AFLP) often resolves after pregnancy delivery but can progress to acute liver failure necessitating liver transplantation. We performed a retrospective review of the national Scientific Registry of Transplant Recipients (SRTR) data to identify all women in the United States undergoing liver transplantation (LT) for acute liver failure (ALF) from AFLP from 1991 to 2015, and compared to outcomes in women of childbearing age undergoing transplant for ALF from acetaminophen and ALF from other etiologies. Women with AFLP were likely to be on life support at time of LT and had high rates of renal dysfunction (median Cr 2.1, IQR 1.2‐2.3), and hyperbilirubinemia (median bilirubin 17.1, IQR 11.0, 19.9). Although their early and late LT survival outcomes were comparable to the other indications for LT, cumulative 5‐year graft survival was numerically lower among AFLP patients (54%, 95% CI, 27‐76) compared to APAP (70%, 95% CI, 63‐77) and “Other ALF” (76%, 95% CI, 72‐80) groups. In conclusion, although AFLP is a rare indication for LT, AFLP patients were as sick or sicker than other women of childbearing age undergoing LT for ALF. Worsened graft survival may be related to higher rates of rejection in the AFLP group.