Male Liver Transplant Recipient Research Articles

Impact of sex on the outcomes of deceased donor liver transplantation.

Data examining the impact of sex on liver transplant (LT) outcomes are limited. It is clear that further research into sex-related differences in transplant patients is necessary to identify areas for improvement. Elucidation of these differences may help to identify specific areas of focus to improve on the organ matching process, as well as the peri- and post-operative care of these patients. To utilize data from a high-volume Eurotransplant center to compare characteristics of male and female patients undergoing liver transplant and assess asso ciation between sex-specific variables with short- and long-term post-transplant outcomes. A retrospective review of the University of Essen's transplant database was performed with collection of baseline patient characteristics, transplant-related data, and short-term outcomes. Comparisons of these data were made with Shapiro-Wilk, Mann-Whitney U, χ2 and Bonferroni tests applied where app ropriate. A P value of < 0.05 was accepted as statistically significant. Of the total 779 LT recipients, 261 (33.5%) were female. Female patients suffered higher incidences of acute liver failure and lower incidences of alcohol-related or viremic liver disease (P = 0.001). Female patients were more likely to have received an organ from a female donor with a higher donor risk index score, and as a high urgency offer (all P < 0.05). Baseline characteristics of male and female recipients were also significantly different. In multivariate hazard regression analysis, recipient lab-Model for End-Stage Liver Disease score and donor cause of death were associated with long-term outcomes in females. Pre-operative diagnosis of hepatocellular carcinoma, age at time of listing, duration of surgery, and units transfused during surgery, were associated with long-term outcomes in males. Severity of complications was associated with long-term outcomes in both groups. Overall survival was similar in both males and females; however, when stratified by age, females < 50 years of age had the best survival. Female and male LT recipients have different baseline and transplant-related characteristics, with sex-specific variables which are associated with long-term outcomes. Female recipients < 50 years of age demonstrated the best long-term outcomes. Pre- and post-transplant practices should be individualized based on sex-specific variables to optimize long-term outcomes.

Unsupervised Exercise Intervention vs. Adherence to a Mediterranean Diet Alone: The Role of Bioelectrical Impedance Vector Analysis and Cardiovascular Performance in Liver-Transplanted Recipients.

(1) Background: Cardiovascular disease is one of the leading causes of mortality after liver transplantation. Body composition and cardiovascular performance assessment represent a potential approach for modulating lifestyle correction and proper follow-up in chronic disease patients. This study aimed to verify the additional role of an unsupervised physical activity program in a sample of male liver transplant recipients who follow the Mediterranean diet. (2) Methods: Thirty-three male liver transplant recipients were enrolled. Sixteen subjects followed a moderate-intensity home exercise program in addition to nutritional support, and seventeen received advice on the Mediterranean diet. After six months, bioelectrical vector impedance analysis (BIVA) and cardiopulmonary exercise testing (CPET) were performed. (3) Results: No differences in CPET (VO2 peak: exercise 21.4 ± 4.1 vs. diet 23.5 ± 6.5 mL/kg/min; p = 0.283) and BIVA (Z/H: exercise 288.3 ± 33.9 vs. diet 310.5 ± 34.2 Ω/m; p = 0.071) were found. Furthermore, the BIVA values of resistance correlate with the submaximal performance of the Ve/VCO2 slope (R = 0.509; p < 0.05) and phase angle with the maximal effort of the VO2 peak (R = 0.557; p < 0.05). (4) Conclusions: Unsupervised physical exercise alone for six months does not substantially modify liver transplant recipients' cardiovascular performance and hydration status, despite their adherence to a Mediterranean diet. The body composition analysis is useful to stratify the risk profile, and it is potentially associated with better outcomes in transplanted subjects.

Reduced upper limb lean mass on dual energy X-ray absorptiometry predicts adverse outcomes in male liver transplant recipients.

BACKGROUNDPre-transplant muscle wasting measured by computed tomography has been associated with adverse clinical outcomes after liver transplantation including increased rates of sepsis and hospitalisation days. Upper limb lean mass (LM) measured by dual-energy X-ray absorptiometry (DEXA) was recently identified as a novel predictor of sarcopenia-associated mortality in men waitlisted for transplantation.AIMTo investigate the use of DEXA LM in predicting gender-stratified early post-transplant outcomes.METHODSLiver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were included. Endpoints included post-transplant mortality and graft failure, bacterial infections, acute cellular rejection (ACR) and intensive care and total hospital length of stay.RESULTSFour hundred and sixty-nine patients met inclusion criteria of which 338 were male (72%). Median age was 55.0 years (interquartile range 47.4, 59.7) and model for end-stage liver disease (MELD) score 16. Median time from assessment to transplantation was 7 mo (3.5, 12). Upper limb LM was inversely associated with bacterial infections at 180 d post-transplant (hazard ratio = 0.42; 95% confidence interval: 0.20-0.89; P = 0.024) in males only. There was a negative correlation between upper limb LM and intensive care (τb = -0.090, P = 0.015) and total hospital length of stay (τb = -0.10, P = 0.0078) in men. In women, neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of stay. Body composition parameters, MELD and age were not associated with 90-d mortality or graft failure in either gender. There were no significant predictors of early ACR.CONCLUSIONSarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with cirrhosis. DEXA upper limb LM provides a novel measure of muscle wasting that has prognostic value in this cohort. The lack of association in women requires further investigation.

Delayed Neutropenia in Heart Transplant Recipients Following COVID-19 Diagnosis

Introduction`Neutropenia is observed after heart transplantation due to medication effects and viral infections. SARS-CoV-2 infection, which causes Covid-19 illness, can uncommonly cause neutropenia in non-transplant recipients. Delayed neutropenia following SARS-CoV-2 infection in heart transplant recipients (HTRs) has not been described.Case ReportCase 1: A 45 year old male combined heart and liver transplant recipient was diagnosed with Covid-19 17 months after transplant. Neutropenia had been noted six months after transplant in the setting of valganciclovir and mycophenolate mofetil (MMF) use, which resolved with discontinuation of those medications. At the time of his Covid-19 diagnosis, his immunosuppression regimen included tacrolimus with a target level 8-10 ng/mL and prednisone 5 mg once daily, and he had an asymptomatic course. His absolute neutrophil count (ANC) four weeks prior to Covid-19 diagnosis was 1,690/uL. The ANC obtained nine weeks after Covid-19 diagnosis was 890/uL. Testing for cytomegalovirus was negative and no neutrophil-depleting medications were identified. He received two doses of granulocyte colony stimulating factor (G-CSF). The subsequent ANC two days after the second dose was 3,600/uL. Case 2: A 66 year old male HTR was diagnosed with Covid-19 31 months after transplant. His symptoms included fever, cough, and diarrhea and he was admitted for inpatient care. Immunosuppression at the time of diagnosis included tacrolimus with a target level of 8-10 ng/mL and MMF 1000 mg twice daily, which was later decreased to 500 mg twice daily. The ANC nadir during his acute illness was 1310/uL. Six weeks after Covid-19 diagnosis, his ANC was 420/uL. Testing for cytomegalovirus was negative. The patient required a total of six doses of G-CSF over six weeks due to persistent neutropenia. MMF was discontinued. He was referred to a hematologist for persistent neutropenia. A bone marrow biopsy showed normal neutrophil production, and increased peripheral neutrophil consumption was hypothesized.SummaryAcute viral infections including SARS-CoV-2 can cause neutropenia, but delayed neutropenia is rare and has not been described in HTRs. Careful monitoring of the complete blood count (with differential) may be useful in this population following a Covid-19 diagnosis. Modulation of immunosuppression and G-CSF administration can support neutrophil recovery.

Effect of Jejunal Administration on Tacrolimus Trough Concentrations in a Pediatric Liver Transplant Recipient.

Maintenance immunosuppression regimens containing calcineurin inhibitors, specifically tacrolimus, are standard of care for rejection prevention in pediatric liver transplantation. Challenges with tacrolimus administration are common with pediatric patients, and guidance for non-oral, enteral administration of tacrolimus is limited. We report the case of an 11-year-old male orthotopic liver transplant recipient with a history of malnutrition requiring a jejunostomy tube (J-tube) for enteral nutrition and medication administration post-transplantation. Tacrolimus was initially given orally, and then transitioned to J-tube administration for 10 days. Tacrolimus trough concentrations declined significantly following conversion to J-tube administration and remained subtherapeutic despite a 3-fold dose increase. Once transitioned back to the oral route, trough concentrations became supratherapeutic requiring dose reductions until goal concentrations were achieved. This case demonstrates reduced bioavailability and need for increased dosing, when tacrolimus is administered through a J-tube.

Neuroinvasive chikungunya in a liver transplant recipient

The influence of chronic immunosuppression on the course of chikungunya virus (CHIKV) infection in recipients of solid organ transplantation (SOT) is still unsettled. Scarce data suggest that the course of CHIKV infection is generally benign in this population. In addition, the occurrence of severe atypical manifestations associated with CHIKV has not been well documented among SOT recipients. In this report, we describe a 64-year-old male liver transplant recipient who was admitted with fever, headache, arthralgia, left palpebral ptosis, mydriasis, and right hemiparesis. Cranial magnetic resonance imaging did not reveal any alteration suggestive of acute infection. Nevertheless, CHIKV was detected in the cerebrospinal fluid (CSF) with a real-time reverse transcriptase assay. Other PCR assays carried out in CSF were negative for HSV-1 and 2, cytomegalovirus, dengue virus (DENV), and Zika virus (ZIKV). CHIKV viremia was also detected while PCR assays for ZIKV and DENV in the blood were negative. ZIKV viruria was simultaneously present in this case. All neurologic manifestations waned within 2weeks after the onset. This report shows that chikungunya must be considered in the differential diagnosis of acute neurologic disease in SOT recipients who live in or have recently traveled to endemic areas.

A retrospective cohort study of preoperative lipid indices and their impact on new-onset diabetes after liver transplantation.

BackgroundThe correlation between preoperative lipid profiles and new‐onset diabetes after transplantation (NODAT) remains relatively unexplored in liver transplant recipients (LTRs). Thus, we aimed to investigate the preoperative lipid profiles in Chinese LTRs and evaluate the different influences of preoperative total cholesterol, total triglycerides (TG), high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol on the development of NODAT in both sexes.MethodsA total of 767 Chinese LTRs from Zhongshan Hospital were retrospectively evaluated. NODAT was defined according to the American Diabetes Association guidelines; the relationship between each preoperative lipid index and NODAT development was analyzed separately in men and women.ResultsPretransplant hypotriglyceridemia was observed in 35.72% of the total LTRs. In men, only the preoperative TG level was significantly associated with incident NODAT after adjusting for potential confounders (hazard ratio 1.37, 95% confidence interval 1.13‐1.66, P = .001). There was a nonlinear relationship between the preoperative TG level and NODAT risk. The risk of NODAT significantly increased with preoperative a TG level above 0.54 mmol/L (log‐likelihood ratio test, P = .043). In women, no significant association was observed.ConclusionAmong male LTRs, a higher preoperative TG level, even at a low level within the normal range, was significantly and nonlinearly associated with an increased risk of NODAT.

Prospective Study on Sexual Dysfunction in Male Chinese Liver Transplant Recipients.

In patients with end-stage liver disease, hypogonadism and erectile dysfunction are often seen. This study was to determine the incidence of erectile dysfunction before and after liver transplantation (LT) with correlation to change in sex hormone levels from a Chinese cohort. This prospective longitudinal study was registered with The University of Hong Kong Clinical Trials Centre (HKUCTR-1563). The Institutional Review Board approval number is UW-12-273. The study period was from January 2012 to December 2016. Adult male patients with end-stage liver disease enlisted for LT were recruited on informed written consent. All recruited patients were to complete a cross-sectional cohort questionnaire—International Index of Erectile Function, version 5 (IIEF5)—and to receive serum sex hormone checks before and after LT. Twenty-eight patients who underwent LT were included in the analysis. The included patients had significantly reduced prolactin (p < .001) and 17-beta-estradiol (p = .024) after LT. There was also a significant drop of IIEF5 score at 1 month after LT, but the score returned to pre-LT level at 6 months. This study demonstrated that there was improvement in sex hormone levels after LT, namely, normalization of estradiol level and lowering of prolactin and progesterone levels. However, improvement in sex hormone levels did not translate into improvement of erectile dysfunction.

Higher Risk of Posttransplant Liver Graft Failure in Male Recipients of Female Donor Grafts Might Not Be Due to Anastomotic Size Disparity.

Posttransplant liver graft failure occurs most often in male recipients of livers from female donors. The respective role of donor sex itself and the size disparity in graft vessels/bile ducts according to donor sex are unclear. Thus, we aimed to evaluate the importance of donor sex with adjustment for anastomotic size disparity between female and male donor grafts. A total of 309 male patients without hepatic tumors who underwent living donor liver transplantation were analyzed (109 female donors and 200 male donors). The primary outcome was posttransplant graft failure (ie, retransplantation or death). Survival analysis was performed using the Cox model. Analyzed anastomosis-related factors comprised graft weight, number and size of hepatic vessels/bile ducts, and anastomosis techniques. Graft failure probabilities at 1, 6, 12, 24, and 60 months posttransplantation were 9.1%, 19.5%, 20.2%, 23.0%, and 27.0%, respectively, with female donors and 2.0%, 5.5%, 8.1%, 10.1%, and 13.5% with male donors (hazards ratio [HR], 2.29; 95% confidence interval [CI], 1.35-3.88; P = 0.002). Multivariable analysis confirmed the significance of donor sex (HR, 2.30; 95% CI, 1.14-4.67; P = 0.021) after adjustment for anastomosis-related factors. All analyzed anastomosis-related factors showed no significant association with graft failure, although size of the graft hepatic artery showed marginal significance (HR, 0.50; 95% CI, 0.25-1.01; P = 0.053). The significance of donor sex was lost when donor was older than 36 to 40 years (age of poor ovarian reserve and the end of female fertility). Our institutional pediatric recipient cohort validated the inferiority of female-to-male donation. Donor sex appears to be an independent factor modulating graft failure risk in male liver transplant recipients.

Prospective Trial on Sexual Dysfunction in Male Chinese Liver Transplant Recipients

Prospective Trial on Sexual Dysfunction in Male Chinese Liver Transplant Recipients

Rhabdomyolysis as a Clinical Manifestation of Association With Ciprofibrate, Sirolimus, Cyclosporine, and Pegylated Interferon-α in Liver-Transplanted Patients: A Case Report and Literature Review

BackgroundRhabdomyolysis is a syndrome characterized by impaired metabolic integrity of myocytes, causing the release of intracellular constituents into the circulation, and can be a serious side effect of drug intake. Case ReportThis report describes a unique case of rabdomyolysis secondary in which ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-α in a liver transplant patient was used. A 47-year-old male liver transplant recipient in 2009, who had hepatitis C and incidental hepatocellular carcinoma, underwent immunosuppressive therapy (cyclosporine and sirolimus). The patient is currently in treatment for viral recurrence with pegylated interferon-α and ribavirin; he had a history of hypertriglyceridemia treated with ciprofibrate. He had development of severe and generalized myalgia and fever after the eighth application of pegylated interferon-α and increasing doses of cyclosporine. Laboratorial tests showed acute renal failure and significant increase in creatine kinase. Rhabdomyolysis secondary to interaction of fibrate-cyclosporine–pegylated interferon-α was postulated. ConclusionsMedical professionals should be aware of possible drug interactions and should monitor patients receiving these drugs.

Successful management of splenic artery steal syndrome with hepatic artery stenosis in an orthotopic liver transplant recipient

Splenic artery steal syndrome is an uncommon but serious complication of orthotopic liver transplantation. We report a case of splenic artery steal syndrome with hepatic artery stenosis in a 65-year-old male liver transplant recipient who was successfully managed by hepatic artery stenting and splenic artery embolization in a single procedure. A 65-year-old man underwent orthotopic liver transplantation due to alcoholic cirrhosis using a piggyback technique. Relevant parameters were measured. The splenic blood flow was apparently reduced and arterial perfusion of the graft was restored. The patient was still in good condition after 4 months of follow-up. The success of this strategy indicates that the patency of the hepatic artery should be maintained and the splenic artery should be embolized to assure sufficient blood supply of the graft.

A mixed infection of Leuconostoc lactis and vancomycin-resistant Enterococcus in a liver transplant recipient

Bacterial infection in patients who have undergone liver transplantation is a major complication of the procedure. Leuconostoc spp. are important pathogenic bacteria in individuals with poor immune function, especially transplant patients. In this report, we describe the case of a 45-year-old Asian male liver transplant recipient who was initially preliminarily diagnosed with infection with Leuconostoc pseudomesenteroides by using the microbial tests of the VITEK 2 system and the aesculin hydrolysis test, and with vancomycin-resistant Enterococcus. Subsequently, the Leuconostoc isolate was identified as Leuconostoc lactis by 16S rRNA gene partial sequencing. In this paper, we discuss our identification of L. lactis based on physiological characteristics and molecular methodology. Accurate identification of these infections is important for the outcome; use of 16S rRNA gene sequence analysis offers a rapid and precise diagnostic approach. Administration of the drug linezolid may be useful for the treatment of both Leuconostoc spp. and vancomycin-resistant Enterococcus infections. We suggest that clinical analysts should use molecular methods in addition to biochemical tests in order to identify Leuconostoc at the species level more accurately.

Treatment of hepatitis C recurrence is less successful in female than in male liver transplant recipients

It has been recently suggested that the risk of graft loss after liver transplantation (LT) may increase in female HCV patients. The aim of the study was to examine gender differences in HCV therapy tolerance and outcome in LT patients treated for HCV recurrence. A retrospective study was conducted on liver recipients with HCV recurrence, who were given antiviral therapy from 2001 to 2009 in 12 transplant centers in Italy. Sustained virological response (SVR), adherence-to-therapy, and side effects were evaluated. A multivariate logistic regression model was used after adjusting for possible confounders. The data regarding 342 treated patients were analyzed. SVR was reported in 38.8% of patients. At baseline, male and female did not differ in HCV viral load, histology, or rate of diabetes. SVR was lower in females than in males (29.5% vs. 42.1%; P=0.03). Adherence-to-therapy was also lower in females than in males 43.4% vs. 23.8%; P=0.001); anemia was the main reason for lower adherence. In a multivariate analysis in patients Genotype1, female gender (P<0.04), early virological response (P<0.0001), and adherence to therapy (P<0.0001) were independent predictors for SVR. In conclusion, female gender represents an independent negative prognostic factor for the outcome of HCV antiviral therapy after LT.

Preoperative Natriuretic Peptide-B Values and Ascites in Male Liver Transplant Recipients

Plasma preoperative values of natriuretic B peptide (pro-BNP) were correlated with ascites in men experiencing hepatic cirrhosis due to different etiologies on the active waiting list for liver transplantation. The study was performed in 54 male recipients of a liver transplant. Written informed consent was obtained from the patients or their relatives, and the study protocol was approved by our local Clinical Research (Ethics) Committee. Male patients were classified into two groups: group 1 included patients with alcoholic hepatic cirrhosis ( n = 30) distributed as 19 men with no ascites, four with nonrefractory ascites, and seven with refractory ascites; group 2 included cases of viral hepatitis cirrhosis ( n = 24) distributed as 13 men with no ascites, nine with non-refractory ascites, and two with refractory ascites. A group of six healthy male volunteers was used to establish normal (basal) values of pro-BNP and left auricular diameter (LAD). Pro-BNP values were determined in plasma samples by an electrochemiluminiscence immunoassay. Pro-BNP plasma levels in patients with alcoholic cirrhosis were threefold greater among patients with no ascites or no refractory ascites compared with healthy men, whereas pro-BNP values were fivefold enhanced among alcoholic patients with refractory ascites. The viral hepatitis cirrhosis group showed pro-BNP plasma values 1.5-fold enhanced in men with no ascites, whereas pro-BNP reached fivefold with either nonrefractory or refractory ascites. The enhanced pro-BNP plasma levels indicated advanced hepatic degradation, seemingly related to the presence of refractory ascites associated with cirrhosis.

Elevated Incidence of Fractures in Solid-Organ Transplant Recipients on Glucocorticoid-Sparing Immunosuppressive Regimens

This study was conducted to assess the occurrence of fractures in solid-organ transplant recipients. Methods. Medical record review and surveys were performed. Patients received less than 6 months of glucocorticoids. Results. Of 351 transplant patients, 175 patients provided fracture information, with 48 (27.4%) having fractured since transplant (2–6 years). Transplants included 19 kidney/liver (50% male), 47 kidney/pancreas (53% male), 92 liver (65% male), and 17 pancreas transplants (41% male). Age at transplant was 50.8 ± 10.3 years. Fractures were equally seen across both genders and transplant types. Calcium supplementation (n = 94) and bisphosphonate therapy (n = 52) were observed, and an association with a lower risk of fractures was noted for bisphosphonate users (OR = 0.45 95% C.I. 0.24, 0.85). Fracture location included 8 (16.7%) foot, 12 (25.0%) vertebral, 3 (6.3%) hand, 2 (4.2%) humerus, 5 (10.4%) wrist, 10 (20.8%) fractures at other sites, and 7 (14.6%) multiple fractures. The estimated relative risk of fracture was nearly seventeen-times higher in male liver transplant recipients ages 45–64 years compared with the general male population, and comparable to fracture rates on conventional immunosuppressant regimens. Conclusion. We identify a high frequency of fractures in transplant recipients despite limited glucocorticoid use.

Hepatic involvement in a liver transplant recipient with disseminated cryptococcosis

Cryptococcosis occurs primarily in immunocompromised patients such as organ transplant recipients. Central nervous system and pulmonary infections are documented most frequently; hepatic involvement is rarely reported. We report a case of early hepatic cryptococcosis in a 54-year-old male liver transplant recipient. Two weeks after orthotopic liver transplant, he was readmitted with fever, malaise, diarrhea, and progressive pulmonary infiltrates. On admission, liver-associated enzymes were decreased from those at discharge after transplantation. Blood and bronchoalveolar lavage cultures were positive for Cryptococcus neoformans. Despite treatment with amphotericin B and flucytosine, the patient developed both marked cholestasis and transaminase elevation. A liver biopsy performed 22 days after admission revealed numerous yeast-like organisms in hepatic sinusoids consistent with C. neoformans. Despite treatment, the patient died 55 days after admission and 66 days after transplantation. Our case illustrates hepatic involvement of cryptococcal infection within the first month following transplantation.

Benign Transient Hyperphosphatasemia Associated With Epstein-Barr Virus Enteritis in a Pediatric Liver Transplant Patient: A Case Report

Transient hyperphosphatasemia was found in a 3-year-old male liver transplant recipient. The condition was associated with diarrheal disease due to the Epstein-Barr virus (EBV). Immunosuppression was tapered and valganciclovir prescribed for 3 months, after which the diarrhea resolved and the EBV polymerase chain reaction assays became negative. After 6 months, alkaline phosphatase levels normalized. Isolated elevation of alkaline phosphatase in conjunction with enteric infection is a rare condition. No further diagnostic or therapeutic interventions except treatment of the underlying infection are needed, as this has been shown to be a benign, transient condition.

Donor‐transmitted toxoplasmosis in liver transplant recipients: a case report and literature review

Transmission of toxoplasmosis via liver transplantation is extremely uncommon. Here we report the case of a 52-year-old male liver transplant recipient who on day 32 post transplant developed pneumonia followed by respiratory failure. Donor-transmitted toxoplasmosis was confirmed as the etiology by both serologic and molecular testing. We also review all previously published cases of toxoplasmosis in the English-language adult liver transplant literature.

Merkel Cell Carcinoma in a Liver Transplant Patient

Merkel cell carcinoma (MCC) is an aggressive tumor, the incidence of which is seemingly increased in immunocompromised patients. We report on a new case of MCC occurring in a 69-year-old male liver transplant recipient 6.5 years after transplantation. The outcome was marked by early skin and lymph node relapses treated by radiotherapy alone, and the patient ultimately died 30 months after first diagnosis. Together with data from the literature, this case emphasizes the importance of early diagnosis and adequate management of this aggressive disease for which wide initial surgical excision, accurate staging, and close follow-up are of critical importance to outcome, especially in this setting of immunosuppressive treatment, which is usually associated with a higher rate of recurrence.