Time Of Transplant Evaluation Research Articles

Walking Ability and Brain Natriuretic Peptide Are Highly Predictive of Kidney Transplant Waiting List Removal.

Demographics, functional and frailty assessment' and biochemical data were retrospectively analyzed on 313 consecutive patients listed for kidney transplant. Troponin, brain natriuretic peptide, components of the Fried frailty metrics, pedometer activity, and treadmill ability were measured at the time of transplant evaluation and at subsequent re-evaluations. Cox proportional hazards models were used to identify factors associated with death or waiting list removal for medical reasons. Multivariate models were created to identify significant predictor sets. Among 249 patients removed while waitlisted, 19 (6.1%) died and 51 (16.3%) were removed for medical reasons. Mean follow-up duration was 2.3 y (±1.5 y). 417 sets of measurements were collected. Significant (P < 0.05) non-time-dependent variables associated with the composite outcome identified on univariate analysis included N-terminal probrain natriuretic peptide (BNP), treadmill ability, pedometer activity, diagnosis of diabetes and the Center of Epidemiological Studies Depression Scale question asking how many days per week could you not get going. Significant time-dependent factors included BNP, treadmill ability, Up and Go, pedometer activity, handgrip, 30 s chair sit-stand test, and age. The optimal time-dependent predictor set included BNP, treadmill ability, and patient age. Changes in functional and biochemical markers are predictive of kidney waitlist removal for death and medical reasons. BNP and measures of walking ability were of particular importance.

A CASE SERIES OF RAPID PROGRESSIVE FIBROTIC LUNG DISEASE AS A SEQUELA OF COVID-19 PNEUMONIA

A CASE SERIES OF RAPID PROGRESSIVE FIBROTIC LUNG DISEASE AS A SEQUELA OF COVID-19 PNEUMONIA

The Combined Roles of Race/Ethnicity and Substance Use in Predicting Likelihood of Kidney Transplantation.

Racial/ethnic minorities face known disparities in likelihood of kidney transplantation. These disparities may be exacerbated when coupled with ongoing substance use, a factor also reducing likelihood of transplantation. We examined whether race/ethnicity in combination with ongoing substance use predicted incidence of transplantation. Patients were enrolled between March 2010 and October 2012 at the time of transplant evaluation. Substance use data were retrieved from transplant evaluations. Following descriptive analyses, the primary multivariable analyses evaluated whether, relative to the referent group (White patients with no substance use), racial/ethnic minority patients using any substances at the time of evaluation were less likely to receive transplants by the end of study follow-up (August 2020). Among 1152 patients, 69% were non-Hispanic White, 23% non-Hispanic Black, and 8% Other racial/ethnic minorities. White, Black, and Other patients differed in percentages of current tobacco smoking (15%, 26%, and 18%, respectively; P = 0.002) and illicit substance use (3%, 8%, and 9%; P < 0.001) but not heavy alcohol consumption (2%, 4%, and 1%; P = 0.346). Black and Other minority patients using substances were each less likely to receive transplants than the referent group (hazard ratios ≤0.45, P ≤ 0.021). Neither White patients using substances nor racial/ethnic minority nonusers differed from the referent group in transplant rates. Additional analyses indicated that these effects reflected differences in waitlisting rates; once waitlisted, study groups did not differ in transplant rates. The combination of minority race/ethnicity and substance use may lead to unique disparities in likelihood of transplantation. To facilitate equity, strategies should be considered to remove any barriers to referral for and receipt of substance use care in racial/ethnic minorities.

Up to 50% of portal vein thrombosis remains undiagnosed until liver transplantation.

Impact of portal vein thrombosis (PVT) on the clinical course in liver transplant candidates remains unclear. This study aims to identify prevalence and risk factors for PVT, assess outcome after liver transplantation (LT) in patients with PVT and study the effect of anticoagulation. This single-center retrospective cohort study was performed from January 2006 until June 2016. Patients were stratified according to presence of PVT. Risk factors and outcome were assessed using logistic regression and survival analysis. Among 390 adults who underwent orthotopic LT, PVT occurred in 40 (10.3%). In, respectively, 10 (25%), 7 (17.5%), and 23 (57.5%) patients, PVT was identified at time of evaluation for transplantation, on the waiting list and during transplantation. A beneficial trend was present favoring the use of anticoagulation for PVT resolution (n=3/7 vs 0/9; p=.062). Patient and graft survival were similar between the groups after a median follow-up of 5years. However, 1-year patient survival was significantly lower (p=.031) in patients with PVT. Portal vein thrombosis occurred in 10% of patients awaiting LT was undiagnosed in 50% until moment of LT and had a deleterious effect on 1-year survival. Anticoagulation showed a beneficial trend on recanalization of PVT and survival rate.

Combined Heart-Kidney Transplant Versus Sequential Kidney Transplant in Heart Transplant Recipients

In patients with reduced kidney function there are no established guidelines to suggest combined heart-kidney transplant (HKTx) versus sequential kidney transplant (SKTx) using preoperative value of estimated glomerular filtration (eGFR). The United Network for Organ Sharing database was queried from 2000 to 2015 to evaluate survival of HKTx and SKTx population stratified by preoperative eGFR rate <45 mL/min. Aim of the study was to assess the eGFR rate that is most beneficial to perform a concomitant or a SKTx at time of transplant evaluation. In our analysis, patients who required SKTx are recipients that, after heart transplantation, developed or worsened kidney insufficiency due to calcineurin inhibitor nephrotoxicity. In recipients with eGFR <30 or dialysis, a total of 545 received HKTx and 80 received SKTx. The median waiting time between heart and kidney transplant in SKTx group was 6 years. The overall post-transplant survival was 81% and 80% and 75% and 59% at 5 and 1 years for the HKTx and SKTx groups, respectively (P = .04). In recipients with eGFR from 30 to 44, a total of 107 received HKTx and 112 received SKTx. The median waiting time between heart and kidney transplant in SKTx group was 4 years. Overall post-transplant survival showed no statistically significant differences in HKTx group (n=107) compared with SKTx group (n=112) and was 90% and 95% at 1 year and 74% and 52% at 5 years, respectively (P = .4) . To optimize organ and patient survival, eGFR value can be utilized to discern between HKTx versus SKTx in patients with decreased renal function at the time of heart transplantation. Patients with eGFR<30 or in dialysis presented better survival with HKTx, while both SKTx and HKTx are suitable for patients with eGFR between 30 and 45.

Transplant Rates and Outcomes of Young Acute Myeloid Leukemia (AML) Patients with Intermediate and Poor Risk Disease Referred to a Coordinated Acute Leukemia and Hematopoietic Stem Cell Transplant (HSCT) Program

▪Patients with intermediate and poor risk AML have unsatisfactory outcomes with conventional chemotherapy-based treatment. Allogeneic HSCT offers the best chance of long-term survival for patients who achieve complete remission (CR) and are eligible for such a procedure. There are several potential barriers to receiving an allogeneic HSCT, including but not limited to: achieving CR, timely referral to a transplant center, identifying a donor, and performing the HSCT prior to relapse or significant complications arising from induction and consolidation therapy. To better understand the outcomes of young, newly diagnosed non-favorable risk AML patients, we evaluated 271 consecutive adult patients (age ≤65 years) referred to our center between January of 2009 and July of 2017 for management. Patients were treated in an integrated acute leukemia and transplant management unit and it is our policy to offer intensive chemotherapy to all potentially eligible patients and HSCT to all transplant-eligible, non-favorable risk AML patients that achieve CR, with or without complete blood count recovery. Patient characteristics were as follows: Median age 55 (19, 65) years, male sex 50%, NCCN risk (intermediate 51%, poor 49%), FLT 3 ITD positive 15% and normal cytogenetics in 39%. Remission induction chemotherapy was given to 262patients with FLAG+/-IDA being the most commonly used regimen in 161 patients (61%) followed by 3+7 in 63 (24%)patients. Following induction, 211 (81%) achieved a CR1 after one (n=178), two (n=26) or three (n=7) courses of induction with a median follow up for survivors of 44.5 months. For patients with intermediate and poor risk NCCN categories, CR was achieved in 86% and 73% respectively. HSCT was performed on 146 (69%) patients (NCCN intermediate risk n=83, poor risk n=63): Myeloablative conditioning n=103 (71%), autologous (n=10), matched related donor (n=45), matched unrelated donor (n=51) and haploidentical mismatched related donor (n=40). Of the 65 patients in CR1 who did not receive HSCT, the reasons for not receiving HSCT were as follows: relapse prior to transplant (n=23), lack of psychosocial support (n=14), persistent active infection or organ dysfunction (n=16) at time of transplant evaluation, patient declined transplant (n=7) and poor performance status post induction (n=5). The 3 year estimates for OS and DFS were 50% and 44% respectively. Patients who received HSCT had a better 3 year OS and DFS of 59% and 52% compared to 27% and 27% for patients not receiving HSCT (p<0.001). In multivariate analysis, we analyzed factors associated with OS and DFS among patients in CR1 after induction. The variables considered were age at CR1 (≤49, 50-64, ≥65), gender, race (white, black), NCCN risk, induction regimen, cytogenetics at diagnosis (normal, abnormal), FISH at diagnosis (normal, abnormal), FLT3 ITD status, number of cycles to CR1 (1, ≥2), transplantation and year of CR1 (2008-2011, 2012-2014, 2015-2017). ). Transplantation was modelled as a time-dependent covariate where hazard of mortality for transplantation was only evaluated after transplantation was conducted. A forward stepwise algorithm was implemented and variables were selected if p values were less than 0.05. Factors associated with superior overall survival were age at CR1 (≤49 vs ≥60; HR 0.38, p<0.001), NCCN risk (intermediate vs poor HR 0.51, P<0.001), number of cycles to reach CR1 (1 vs ≥2, HR 0.58, p0.025) and receiving HSCT (Yes vs No, HR 0.71, p0.049). Factors associated with improved DFS were age at CR1 (≤49 vs ≥60 years, HR 0.45, p<0.001), NCCN risk (intermediate vs poor, HR0.53, p0.008) and receiving HSCT (yes vs no, HR 0.57, p0.006). This analysis shows that a timely coordinated approach of remission induction followed by HSCT in the majority of patients with non-favorable risk AML can lead to superior outcomes with more than half of the patients achieving long term survival. DisclosuresSolh:Amgen: Speakers Bureau; Celgene: Speakers Bureau; ADC Therapeutics: Research Funding.

Cardiac Troponin T Risk Stratification Model Predicts All-Cause Mortality Following Kidney Transplant

Background: We evaluated the role of increased cardiac troponin T (cTnT), vascular, and cardiac diseases in predicting 5 and 10-year all-cause mortality after kidney transplantation. Methods: We reviewed a cohort of 764 kidney transplant recipients and analyzed pertinent cardiovascular risk factors at the time of transplant evaluation. Proportional hazards regression analysis with bootstrapping method was utilized to provide a risk stratification score for mortality. Results: Mean age was 58.8 years (SD 12.1) and median follow-up was 7.0 years (range 1 day to 18.0 years). Fifty-four percent of patients (n = 415) had cTnT measured (median 0.02 ng/mL, range 0.01–4.91). Fifty-three percent (n = 407) had vascular disease, 59% (n = 448) had diabetes, and 44% (n = 336) had cardiac disease pre-transplant. Sixty percent (n = 460) required dialysis. Older age, increased cTnT, pre-transplant vascular and cardiac diseases predicted mortality in multivariate analysis. We derived 2 scoring systems with and without cTnT – the ACV and ACTV scores (age, cardiac disease, elevated cTnT, and vascular disease) – as predictors of mortality after kidney transplant. Point assignments were: age 60–69 years (1), age ≥70 years (2), cardiac disease (1), cTnT ≥0.04 ng/mL (1), and vascular disease (1). Both scoring systems significantly predicted mortality. The ACTV score better delineated risk stratification across score levels (0–2, 3–4, and 5 points). Conclusions: We developed a risk schema predictive of all-cause mortality after kidney transplant in a derivation cohort. The ACTV score, including an elevated cTnT, provided superior prediction compared to a scoring system without cTnT. Further studies to validate these findings are needed.

Low bone density and fractures before and after pediatric lung transplantation.

Children undergoing lung transplant are at risk for low bone mineral density (BMD) and fractures. The effect of lung transplantation on bone health in pediatric patients is unknown. We performed a retrospective chart review of all patients ages 2-21 years who underwent lung transplantation at our hospital from January 2000 to January 2015. 51 patients were studied. At the time of transplant evaluation, BMD Z-score was -2.2 ± 1.4, and 59% of patients had low BMD. BMD Z-score declined in the first year after treatment and returned to near-baseline by the third post-transplant year. Fractures occurred in 9 patients (18%) before and 15 patients (29%) after transplant. Bisphosphonate use was associated with improvement in BMD Z-score and lower mortality risk. Pediatric patients had a high prevalence of low BMD at the time of lung transplant evaluation. BMD Z-scores declined in the year after transplant and returned to the pre-transplant level by the third post-transplant year while remaining below normal levels. Fractures were common at sites associated with significant morbidity. These findings support efforts to optimize bone health before and after pediatric lung transplantation, and future studies are needed to evaluate the role of bisphosphonates in these patients.

Frailty and Transplantation.

Consequences of aging are gaining clinical relevance. In transplantation, aging and immunosenescence impact treatment and outcomes. The impact of aging, however, will critically depend on distinguishing healthy, chronological aging from biological aging that may result into frailty. Approximately 15% of individuals older than 65 years are frail, and it is expected that this condition will gain more clinical relevance with an expected increase to greater than 20% over the next 5 years. Clearly, frailty impacts various general aspects of health care and organ transplantation in particular including patient selection, waitlist management and treatment after transplantation. In general, frailty has been characterized by a compromised physiological reserve and an augmented vulnerability. In comparison to healthy aging, inflammatory markers and cytokines are increased in frail older adults. Thus, modifications of the immune response, in addition to physical limitations and changes of metabolism, are likely to impact outcomes after transplantation. Here, we provide a risk assessment of frailty at the time of transplant evaluation and review effects on outcomes and recovery after transplantation. Moreover, we summarize our current understanding of the pathophysiology of frailty and consequences on immune responses and metabolism.

Post-Traumatic Stress Symptoms in Pediatric Heart Transplant Recipients.

Traumatic experiences are not unusual in pediatric heart transplant (HT) recipients before and after transplantation. Post-traumatic stress symptoms (PTSS) present at the time of transplant evaluation and developing afterward occur with an unknown frequency. We sought to determine the burden of these symptoms in heart transplant patients. We reviewed 51 consecutive HTs between 2003-2007, including 40 primary transplants and 11 re-transplants. Symptoms were present in 17 of the 51 patients (34%) at the time of orthotopic heart transplantation evaluation. None met the criteria for full post traumatic stress disorder. Transplant complications were examined. Nineteen subjects of the total sample had rejection in the first year following transplant. Rejection rates in the first year was 41% for those with PTSS (7 of 17 patients) and 36% for those without (12 of 33 patients) (P=n.s). Of those patients presenting for a second heart transplant, 55% had PTSS at the time of transplant evaluation and/or the peritransplant period; whereas, (28%) undergoing a primary transplant had PTSS. In addition to symptoms resulting from the disease process leading to HT and other prior experiences, the HT itself seems to present a large psychiatric burden on patients. All patients need to be followed before and after HT for signs and symptoms related to PTSS. Future studies should be undertaken to determine if preventative detection and treatment of patients with these PTSS symptoms early can lead to better outcomes.

Abstract 599: Cardiovascular Risk Factors and Cardiovascular Events in Patients Undergoing Liver Transplantation

Introduction: Patients undergoing liver transplantation often have cardiovascular risk factors and may experience cardiovascular morbidity and mortality. Understanding the role of risk factors and the benefit of treatment is important for the careful selection of liver transplantation candidates to minimize post-transplant cardiac morbidity. We investigated the prevalence of cardiovascular risk factors and their association with cardiovascular events in liver transplantation patients. Methods: We studied 182 consecutive patients undergoing liver transplantation in our center between 1997 and 2011 to evaluate factors associated with new cardiovascular events after liver transplantation. Results: The cohort consisted of 179 men and 3 women with a mean age of 58.8 ± 6.2 years, model for end-stage liver disease (MELD) score of 17.4 ±7 at initial evaluation, and Framingham risk score of 9.0 ±5.1. In this cohort 15 ( 8.2%) patients were smokers, 48 (26.4%) had hypertension, 47 (25.8%) had diabetes mellitus, 35 (19.2%) had coronary artery disease, and 27 (14.8%) had dyslipidemia prior to their transplant surgery. After a median follow-up of 5.6 years, a total of 52 (28.6%) patients died and 6 (3.3%) died of cardiac causes. New coronary events and/or revascularization procedures post-transplant occurred in 22 (12%) patients. The pre-transplant variable associated with post-transplant cardiac events and/or revascularization was smoking status at the time of evaluation (P=0.01). Post-transplant factors associated with cardiac events included use of beta-blockers (P=0.01) or statins (P=0.01). Conclusion: Although cardiovascular risk factors and coronary disease are very common, cardiovascular events are relatively infrequent in patients undergoing liver transplantation. Smoking at time of transplant evaluation and post-transplant medical therapy with beta-blockers and statins are significantly associated with the occurrence of post-transplant cardiac events including revascularization.

Cytomegalovirus Infection and Cardiac Allograft Vasculopathy in Children

The relationship between viral infections, host immune responses, and long-term cardiac allograft outcomes is complex and not fully elucidated at this time.1 Children are exposed to many viruses, and young transplant recipients will often experience their primary infection for a given viral pathogen while under iatrogenic immunosuppression. Despite this, most viruses cause only mild clinical illness, and transplant recipients often clear infection in a fashion similar to that of their healthy (nonimmunocompromised) peers. Death or serious morbidity from acute viral infection, especially those caused by common respiratory and intestinal viruses, is very rare in children who have received heart transplants. Serious morbidity and mortality may, however, follow infection with human herpes viruses. Article p 1798 Human herpes virus infections occur in most children during the course of childhood, and the viruses persist in the body indefinitely. Many primary infections carry no symptoms, and the presence of prior infection is identified through evidence of seroconversion at the time of evaluation for transplantation. Symptomatic disease is more common when primary viral infection occurs in the immunocompromised host. Primary Epstein–Barr virus infection posttransplantation poses significant risk for the development of posttransplantation lymphoproliferative disorders.2 Cytomegalovirus (CMV) may also cause severe infection, especially if primary infection occurs in the early weeks or months after transplantation. This risk appears low, however, in the modern era.3 Prevention commonly involves early postoperative use of intravenous ganciclovir and/or oral administration of valganciclovir, with or without immunoglobulin preparations. The length of therapy varies widely between centers. Pretransplantation seropositive status for …

Hepatitis B vaccination in heart transplant candidates

Heart donor availability is limited. Various options have been proposed to expand the donor pool, including candidate vaccination to permit use of Hepatitis B (Hep B) positive donors. There are approximately 1.25 million carriers of the Hepatitis B virus in the United States. In order to include HepBsAg positive transplant donors, we initiated a protocol of routine vaccination against hepatitis B at the time of transplant evaluation. Seroconversion rates following vaccination in the general population are 95%, 90%, 85%, 70%, and 50% in the 20–29, 30–39, 40–49, 50–59, and over 59 year old age groups respectively. Seroconversion rates in patients with end-stage heart failure are not known.

Endovascular Exclusion of Saphenous Vein Graft Aneurysms Complicating Abdominal Aortic Aneurysm Repair

A 64-year-old man was referred for vascular evaluation before renal transplantation for ischemic nephropathy. In the past he had undergone bilateral renal artery revascularizations using saphenous vein. At the time of transplant evaluation, he was found to have bilateral aneurysms of the saphenous veins used to bypass his renal artery stenoses. He underwent successful endovascular exclusion of the aneurysms with 2 endovascular AneuRx extension cuffs. This case highlights both the versatility of endovascular treatments as well as the importance of a comprehensive vascular examination.

Decline in native renal function early after bladder-drained pancreas transplantation alone.

Pancreas transplant alone (PTA) has become accepted therapy for select nonuremic patients with type 1 diabetes mellitus. However, PTA may lead to significant complications including a decline in native renal function. This study examines trends in native renal function during the first posttransplant year in PTA recipients with a spectrum of pretransplant glomerular filtration rates (GFR). Renal function was studied in 23 recipients of bladder-drained PTA who underwent transplantation from April 1998 through September 2001. GFR was measured by corrected iothalamate clearance at the time of transplant evaluation and 1 year posttransplant and also calculated using the Cockcroft-Gault method at the transplant evaluation; at the day of transplantation; and at 1, 6, and 12 months posttransplant. Iothalamate clearance decreased in the first year in 96% of patients (22 of 23). The mean measured GFR decreased from 84 +/- 33 mL/min/1.73 m2 pretransplant to 52 +/- 26 mL/min/1.73 m2 at 1 year (P <0.001). Calculated creatinine clearance declined in the majority of patients at both 1 and 12 months after PTA, but some patients, including a few with low GFR, maintained stable renal function. Calculated GFR generally correlated well with measured GFR in most patients, with a few notable exceptions. One patient (baseline GFR, 42 mL/min/1.73 m2) developed renal failure in the first year after transplant and required kidney transplantation. Bladder-drained PTA results in a decline in native renal function in the majority of patients regardless of the pretransplant GFR. These data suggest the need for strategies to prevent or minimize the decline in renal function after PTA.

Excess risk of renal allograft loss associated with cigarette smoking.

Cigarette smoking contributes to a number of health-related problems, but its impact on renal transplant survival beyond accelerated patient death is unclear. We performed a cohort study of 645 adult renal allograft recipients from 1985 to 1995 to evaluate the relationship between smoking and graft outcome. Twenty-four percent of recipients (156/645) were smokers at the time of transplant evaluation. Of these, 90% continued to smoke after transplantation. Pretransplant smoking was significantly associated with reduced overall graft and death-censored graft survival. Patients who were smokers at the time of pretransplant evaluation had kidney graft survival of 84%, 65%, and 48% at 1, 5, and 10 years, respectively, compared with graft survival in nonsmokers of 88%, 78%, and 62% (P=0.007). Pretransplant smoking adversely affected death-censored graft survival in recipients of cadaveric (P=0.02) and of living donor kidneys (P=0.02). Reduced graft survival in pretransplant smokers could not be accounted for by differences in rejection (64% vs. 61%, P=0.35). In a multivariate analysis, pretransplant smoking was associated with a relative risk of 2.3 for graft loss. Among patients with a smoking history before transplantation, death-censored graft survival was significantly higher for those who quit smoking before transplant evaluation. Cigarette smoking before kidney transplantation contributes significantly to allograft loss. The effect of smoking on graft outcome is not explained by increases in rejection or patient death. Smoking cessation before renal transplantation has beneficial effects on graft survival. These effects should be emphasized to patients with end-stage renal disease who are considering renal transplantation.

Building Clinical Classifiers Using Incomplete Observations – A Neural Network Ensemble for Hepatoma Detection in Patients with Cirrhosis

One objective of liver transplant evaluation is to identify patients that harbor a hepatoma, but standard screening techniques are not sensitive enough. We trained neural network ensembles to predict the presence of hepatoma in patients with cirrhosis, based on information collected at the time of transplant evaluation. Network architecture and training were modified to handle missing observations. Three ensembles were trained: ensemble A using the subset with no missing observations (528 patients); ensemble B using the complete set, which included missing observations (853 patients); and ensemble C using the smaller subset, originally with complete data, but after a fixed number of observations were deleted (i.e., made "missing"). Ensemble performance on testing sets was very good. The areas under the ROC curves were 0.91, 0.89, and 0.90, for ensembles A, B, and C, respectively. Neural networks can successfully perform this classification task, and strategies can be developed that allow use of incomplete observations.

Early Liver Transplantation Is Indicated for Tyrosinemia Type I

SummaryLiver transplantation is now accepted as the treatment of choice for tyrosinemia type I (hereditary tyrosinemia). In an effort to determine whether any factors in these patients would aid in predicting optimal timing of the transplant procedure, we evaluated several clinical, biochemical, and radiographic parameters in five successive patients undergoing liver transplant for tyrosinemia type I at the University of Minnesota. All five patients evidenced prolonged periods of clinical and metabolic stability with dietary therapy and four of five remained stable at the time of evaluation for transplantation. Nevertheless, all five suffered significant and unexpected complications of tyrosinemia prior to the time of liver transplant. Four developed renal stones, two were in liver failure, and one developed a neurologic crisis that left him completely paralyzed. Hepatocellular carcinoma was found in one of the five at transplant. We could identify no clinical, biochemical, or radiographic study that was predictive of the likelihood of significant complications of the disorder. Survival from the transplant procedure itself was 100%. The inability to predict or prevent significant complications of tyrosinemia and the favorable outcome from transplantation lead us to recommend liver transplant for all patients with tyrosinemia type I by 12 months of age.

Early Liver Transplantation Is Indicated for Tyrosinemia Type I

Liver transplantation is now accepted as the treatment of choice for tyrosinemia type I (hereditary tyrosinemia). In an effort to determine whether any factors in these patients would aid in predicting optimal timing of the transplant procedure, we evaluated several clinical, biochemical, and radiographic parameters in five successive patients undergoing liver transplant for tyrosinemia type I at the University of Minnesota. All five patients evidenced prolonged periods of clinical and metabolic stability with dietary therapy and four of five remained stable at the time of evaluation for transplantation. Nevertheless, all five suffered significant and unexpected complications of tyrosinemia prior to the time of liver transplant. Four developed renal stones, two were in liver failure, and one developed a neurologic crisis that left him completely paralyzed. Hepatocellular carcinoma was found in one of the five at transplant. We could identify no clinical, biochemical, or radiographic study that was predictive of the likelihood of significant complications of the disorder. Survival from the transplant procedure itself was 100%. The inability to predict or prevent significant complications of tyrosinemia and the favorable outcome from transplantation lead us to recommend liver transplant for all patients with tyrosinemia type I by 12 months of age.