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Background & Aims: The effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited, due to inadequate risk stratification and suboptimal performance of current screening modalities. Methods: We developed a multicenter prospective cohort of patients with cirrhosis undergoing surveillance with MRI and applied global untargeted metabolomics to 612 longitudinal serum samples from 203 patients. Among them, 37 developed HCC during follow-up. Results: We identified 150 metabolites with significant abundance changes in samples collected prior to HCC (Cases) compared to samples from patients who did not develop HCC (Controls). Tauro-conjugated bile acids and gamma-glutamyl amino acids were increased, while acyl-cholines and deoxycholate derivatives were decreased. Seven amino acids including serine and alanine had strong associations with HCC risk, while strong protective effects were observed for N-acetylglycine and glycerophosphorylcholine. Machine learning using the 150 metabolites, age, gender, and PNPLA3 and TMS6SF2 single nucleotide polymorphisms, identified 15 variables giving optimal performance. Among them, N-acetylglycine had the highest AUC in discriminating Cases and Controls. When restricting Cases to samples collected within 1 year prior to HCC (Cases-12M), additional metabolites including microbiota-derived metabolites were identified. The combination of the top six variables identified by machine learning (alpha-fetoprotein, 6-bromotryptophan, N-acetylglycine, salicyluric glucuronide, testosterone sulfate and age) had good performance in discriminating Cases-12M from Controls (AUC 0.88, 95% CI 0.83-0.93). Finally, 23 metabolites distinguished Cases with LI-RADS-3 lesions from Controls with LI-RADS-3 lesions, with reduced abundance of acyl-cholines and glycerophosphorylcholine-related lysophospholipids in Cases. Conclusions: This study identified N-acetylglycine, amino acids, bile acids and choline-derived metabolites as biomarkers of HCC risk, and microbiota-derived metabolites as contributors to HCC development. Impact and implications: The effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited. There is an urgent need for improvement in risk stratification and new screening modalities, particularly blood biomarkers. Longitudinal collection of paired blood samples and MRI images from patients with cirrhosis is particularly valuable in assessing how early blood and imaging markers become positive during the period when lesions are observed to obtain a diagnosis of HCC. We generated a multicenter prospective cohort of patients with cirrhosis under surveillance with contrast MRI, applied untargeted metabolomics on 612 serum samples from 203 patients and identified metabolites associated with risk of HCC development. Such biomarkers may significantly improve early-stage HCC detection for patients with cirrhosis undergoing HCC surveillance, a critical step to increasing curative treatment opportunities and reducing mortality.
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Hepatic tuberculosis (TB) is an uncommon extrapulmonary manifestation of tuberculosis. Hepatic TB is more common in immunocompromised patients, such as those on immunosuppressive medications or those with a human immunodeficiency virus (HIV) infection. Primary hepatic TB is rare, and liver involvement is often secondary to spreading from the lymphatics, portal vein, or hepatic artery. We report a case of hepatic TB in a patient on adalimumab for ankylosing spondylitis (AS).
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Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. Results: During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59-64) years at OLT. Etiology associated with HCC was viral (N = 4) or Non-alcoholic steatohepatitis, NASH (N = 2). Tumor focality was multifocal (N = 4) and unifocal (N = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab (N = 4), nivolumab/ipilimumab (N = 1), and nivolumab as monotherapy (N = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. Conclusions: This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.
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Background: The COVID-19 pandemic has led to an increase in SARS-CoV-2-test positive potential organ donors. The benefits of life-saving liver transplantation (LT) must be balanced against the potential risk of donor-derived viral transmission. Although emerging evidence suggests that the use of COVID-19-positive donor organs may be safe, granular series thoroughly evaluating safety are still needed. Results of 29 consecutive LTs from COVID-19-positive donors at a single center are presented here. Methods: A retrospective cohort study of LT recipients between April 2020 and December 2022 was conducted. Differences between recipients of COVID-19-positive (nâ =â 29 total; 25 index, 4 redo) and COVID-19-negative (nâ =â 472 total; 454 index, 18 redo) deceased donor liver grafts were compared. Results: COVID-19-positive donors were significantly younger (Pâ =â 0.04) and had lower kidney donor profile indices (Pâ =â 0.04) than COVID-19-negative donors. Recipients of COVID-19-positive donor grafts were older (Pâ =â 0.04) but otherwise similar to recipients of negative donors. Donor SARS-CoV-2 infection status was not associated with a overall survival of recipients (hazard ratio, 1.11; 95% confidence interval, 0.24-5.04; Pâ =â 0.89). There were 3 deaths among recipients of liver grafts from COVID-19-positive donors. No death seemed virally mediated because there was no qualitative association with peri-LT antispike antibody titers, post-LT prophylaxis, or SARS-CoV-2 variants. Conclusions: The utilization of liver grafts from COVID-19-positive donors was not associated with a decreased overall survival of recipients. There was no suggestion of viral transmission from donor to recipient. The results from this large single-center study suggest that COVID-19-positive donors may be used safely to expand the deceased donor pool.
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BACKGROUND: Although Hispanic patients have high rates of end-stage liver disease and liver cancer, for which liver transplantation (LT) offers the best long-term outcomes, they are less likely to receive LT. Studies of end-stage renal disease patients and kidney transplant candidates have shown that targeted, culturally relevant interventions can increase the likelihood of Hispanic patients receiving kidney transplant. However, similar interventions remain largely unstudied in potential LT candidates. METHODS: Referrals to a single center in Texas with a large Hispanic patient population were compared before (01/2018-12/2019) and after (7/2021-6/2023) the implementation of a targeted outreach program. Patient progress toward LT, reasons for ineligibility, and differences in insurance were examined between the two eras. RESULTS: A greater proportion of Hispanic patients were referred for LT after the implementation of the outreach program (23.2% vs 26.2%, p = 0.004). Comparing the pre-outreach era to the post-outreach era, more Hispanic patients achieved waitlisting status (61 vs 78, respectively) and received a LT (971 vs 82, respectively). However, the proportion of Hispanic patients undergoing LT dropped from 30.2% to 20.3%. In the post-outreach era, half of the Hispanic patients were unable to get LT for financial reasons (112, 50.5%). CONCLUSIONS: A targeted outreach program for Hispanic patients with end-stage liver disease effectively increased the total number of Hispanic LT referrals and recipients. However, many of the patients who were referred were ineligible for LT, most frequently for financial reasons. These results highlight the need for additional research into the most effective ways to ameliorate financial barriers to LT in this high-need community.
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Hispánicos o Latinos , Trasplante de Hígado , Derivación y Consulta , Humanos , Femenino , Masculino , Persona de Mediana Edad , Texas , Adulto , Listas de Espera , Enfermedad Hepática en Estado Terminal/cirugía , AncianoRESUMEN
Background: Solid organ transplant (SOT) recipients are at risk of bloodstream infections (BSIs) with MDR organisms (MDROs). Objectives: To describe the epidemiology of BSI in the year after several types of SOT, as well as the prevalence of MDRO infections in this population. Methods: We conducted a single-centre, retrospective study of kidney, liver, heart, and multi-organ transplantation patients. We examined BSIs ≤1â year from SOT and classified MDRO phenotypes for Staphylococcus aureus, enterococci, Enterobacterales, Pseudomonas aeruginosa and Candida spp. We compared BSI characteristics between SOT types and determined risk factors for 90â day mortality. Results: We included 2293 patients [1251 (54.6%) kidney, 663 (28.9%) liver, 219 (9.6%) heart and 160 (7.0%) multi-organ transplant]. Overall, 8.5% of patients developed a BSI. BSIs were most common after multi-organ (23.1%) and liver (11.3%) transplantation (Pâ<â0.001). Among 196 patients with BSI, 323 unique isolates were recovered, 147 (45.5%) of which were MDROs. MDROs were most common after liver transplant (53.4%). The most frequent MDROs were VRE (69.8% of enterococci) and ESBL-producing and carbapenem-resistant Enterobacterales (29.2% and 27.2% of Enterobacterales, respectively). Mortality after BSI was 9.7%; VRE was independently associated with mortality (adjusted OR 6.0, 95% CI 1.7-21.3). Conclusions: BSI incidence after SOT was 8.5%, with a high proportion of MDROs (45.5%), especially after liver transplantation. These data, in conjunction with local antimicrobial resistance patterns and prescribing practices, may help guide empirical antimicrobial selection and stewardship practices after SOT.
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PURPOSE OF REVIEW: We review existing and newer strategies for treatment and surveillance of hepatocellular carcinoma (HCC) both pre and postliver transplantation. SUMMARY: HCC is rising in incidence and patients are often diagnosed at later stages. Consequently, there is a need for treatment strategies which include collaboration of multiple specialties. Combinations of locoregional, systemic, and surgical therapies are yielding better postliver transplantation (post-LT) outcomes for patients with HCC than previously seen. Tumor biology (tumor size, number, location, serum markers, response to therapy) can help identify patients who are at high risk for HCC recurrence posttransplantation and may expand transplant eligibility for some patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Incidencia , Recurrencia Local de NeoplasiaRESUMEN
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide and is associated with significant health care costs and burden. Management of HCC is guided based on the Barcelona Clinic Liver Cancer (BCLC) system and includes liver transplantation, surgical resection, and liver-directed and systemic therapies. In recent years, there have been significant advancements in understanding the immunogenicity of HCC and this has led to approval of different targeted agents as well as immunotherapy for advanced HCC. Tremelimumab is a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blocking antibody and has recently been approved in combination with durvalumab (a programmed death-ligand 1 [PDL1] inhibitor) as first-line therapy for advanced (Barcelona Clinic Liver Cancer Stage C) HCC. In this article, we review the different available systemic therapies for advanced HCC with special focus on the clinical utility of tremelimumab for the treatment of unresectable HCC.
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Following the Delphi consensus process, the term steatotic liver disease (SLD) was introduced to replace fatty liver disease, while the term metabolic dysfunction-associated steatotic liver disease (MASLD) emerged as the successor to the term nonalcoholic fatty liver disease (NAFLD).1 This revised nomenclature aims to enhance precision and mitigate negative connotations and potential stigmatization, while refining comprehension and disease categorization. Concurrently, a novel category was introduced to capture individuals whose alcohol consumption exceeded the previously defined thresholds of NAFLD but remained unclassified within the existing system. This category, termed MetALD, now delineates a spectrum of conditions and is defined as a daily intake of 20 to 50 g of alcohol (or weekly 140-350 g) for females and 30 to 60 g daily for males (or weekly 210-420 g).1 Within the MetALD spectrum, some individuals might predominantly exhibit MASLD characteristics, whereas others might be more inclined toward alcoholic liver disease (ALD).1 In the present study, we used a US nationally representative data set to calculate the prevalence of SLD and its subcategories in the United States.
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Small-for-size syndrome (SFSS) following living donor liver transplantation is a complication that can lead to devastating outcomes such as prolonged poor graft function and possibly graft loss. Because of the concern about the syndrome, some transplants of mismatched grafts may not be performed. Portal hyperperfusion of a small graft and hyperdynamic splanchnic circulation are recognized as main pathogenic factors for the syndrome. Management of established SFSS is guided by the severity of the presentation with the initial focus on pharmacological therapy to modulate portal flow and provide supportive care to the patient with the goal of facilitating graft regeneration and recovery. When medical management fails or condition progresses with impending dysfunction or even liver failure, interventional radiology (IR) and/or surgical interventions to reduce portal overperfusion should be considered. Although most patients have good outcomes with medical, IR, and/or surgical management that allow graft regeneration, the risk of graft loss increases dramatically in the setting of bilirubin >10 mg/dL and INR>1.6 on postoperative day 7 or isolated bilirubin >20 mg/dL on postoperative day 14. Retransplantation should be considered based on the overall clinical situation and the above postoperative laboratory parameters. The following recommendations focus on medical and IR/surgical management of SFSS as well as considerations and timing of retransplantation when other therapies fail.
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Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Donadores Vivos , Bilirrubina , Consenso , Laboratorios , SíndromeRESUMEN
Neuroendocrine tumors originate from neuroendocrine cells primarily located in the gastrointestinal tract. These tumors often metastasize to the liver. Primary hepatic neuroendocrine carcinomas are uncommon, and combined hepatocellular neuroendocrine carcinomas are exceedingly rare. There is a lack of data on the management of these rare tumors. Most cases have very poor prognosis secondary to aggressive behavior of the neuroendocrine tumor component. It is important for clinicians to be aware of this rare carcinoma to allow for early diagnosis and optimize potential treatment options.
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The success of solid organ transplant has steadily improved which has led to a unique set of post-transplant issues. The rates of de novo cancer in the solid organ transplant recipient population are higher than those in the general population. There is growing evidence that breast and gynecologic cancers may have a higher mortality rate in post-transplant patients. Cervical and vulvovaginal cancers specifically have a significantly higher mortality in this population. Despite this increased mortality risk, there is currently no consistent standard in screening and identifying these cancers in post-transplant patients. Breast, ovarian and endometrial cancers do not appear to have significantly increased incidence. However, the data on these cancers remains limited. Further studies are needed to determine if more aggressive screening strategies would be of benefit for these cancers. Here we review the cancer incidence, mortality risk and current screening methods associated with breast and gynecologic cancers in the post-solid organ transplant population.
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Background: Patients with cirrhosis have a high risk for morbidity and mortality in relation to abdominal surgery. Despite improvements in surgical techniques and intensive care, major abdominal surgery still remains a challenge. Major factors determining short- and long-term survival and perioperative complications in this patient population include severity of liver dysfunction, degree of portal hypertension (PHTN), and the presence of related complications such as ascites. Elective transjugular intrahepatic portosystemic shunt (TIPS) placement prior to surgery has been reported to improve perioperative outcomes, but available data is limited to case reports and small case series. We aimed to determine the impact of elective TIPS placement on perioperative outcomes after abdominal-pelvic surgeries in patients with cirrhosis. Methods: We performed a retrospective chart review of patients who underwent elective TIPS and compared these patients with a cohort of cirrhotic patients who underwent any abdominal surgeries without TIPS placement. The primary outcomes were mortality at 30 days and 1 year following surgery. Other post-operative outcomes compared between the two groups, included: blood loss, worsening ascites, wound leak, infections, encephalopathy, liver decompensation, and length of hospitalization. Results: Among 38 patients with cirrhosis who underwent abdominal surgery, 20 patients underwent pre-operative elective TIPS placement. Demographic characteristics of the two groups were comparable including age, gender, and body mass index (BMI). The median age was 62 years with a male predominance (62.5%). Both groups had similar etiologies of cirrhosis with hepatitis C virus (HCV) (34.2%) being most common. The most frequent indications for surgery were strangulated hernia (50%) in the TIPS group and acute cholecystitis (55.6%) in the non-TIPS group. Mean pre-TIPS hepato-venous portal gradient (HVPG) was 16.5 mmHg and mean post-TIPS HVPG was 7.0 mmHg. Mortality at 1 month was not statistically different between the groups (20% vs. 5.6%, respectively, P=0.19). The 1-year mortality was also not statistically different between the two groups (20% vs. 11.1%, P=0.36). Conclusions: We found no statistically significant difference in mortality or rate of post-operative complications between patients who received pre-operative TIPS and those who did not in our age-matched cohort.
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BACKGROUND: The need for liver retransplantation (reLT) has increased proportionally with greater numbers of liver transplants (LTs) performed, use of marginal donors, degree of recipient preoperative liver dysfunction, and longer survival after LT. However, outcomes following reLT have been historically regarded as poor. METHODS: To evaluate reLT in modern recipients, we retrospectively examined our single-center experience. Analysis included 1268 patients undergoing single LT and 68 patients undergoing reLT from January 2008 to December 2021. RESULTS: Pre-LT mechanical ventilation, body mass index at LT, donor-recipient ABO incompatibility, early acute rejection, and length of hospitalization were associated with increased risk of needing reLT following index transplant. Overall and graft survival outcomes in the reLT cohort were equivalent to those after single LT. Mortality after reLT was associated with Kidney Donor Profile Index, national organ sharing at reLT, and LT donor death by anoxia and blood urea nitrogen levels. Survival after reLT was independent of the interval between initial LT and reLT, intraoperative packed red blood cell use, cold ischemia time, and preoperative mechanical ventilation, all previously linked to worse outcomes. CONCLUSIONS: These data suggest that reLT is currently a safer option for patients with liver graft failure, with comparable outcomes to primary LT.
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Hepatopatías , Trasplante de Hígado , Humanos , Reoperación/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Trasplante de Hígado/efectos adversos , Supervivencia de InjertoRESUMEN
Background: Liver retransplantation (reLT) has historically had inferior survival relative to primary liver transplant (LT). To improve outcomes after reLT, researchers have identified factors predicting overall (OS) and/or graft survival (GS) after reLT. This systematic review and random effects meta-analysis sought to summarize this literature to elucidate the strongest independent predictors of post-reLT. Methods: A systematic review was conducted to identify manuscripts reporting factors affecting survival in multivariable Cox proportional hazards analyses. Papers with overlapping cohorts were excluded. Results: All 25 included studies were retrospective, and 15 (60%) were single-center studies. Patients on pre-transplant ventilation (HR, 3.11; 95% CI, 1.56-6.20; p = 0.001) and with high serum creatinine (HR, 1.46; 95% CI, 1.15-1.87; p = 0.002) had the highest mortality risk after reLT. Recipient age, Model for End-Stage Liver Disease score, donor age, and cold ischemia time >12â h also conferred a significant risk of post-reLT death (all p < 0.05). Factors affecting GS included donor age and retransplant interval (the time between LT and reLT; both p < 0.05). OS is significantly higher when the retransplant interval is ≤7 days relative to 8-30 days (p = 0.04). Conclusions: The meta-analysis was complicated by papers utilizing non-standardized cut-off values to group variables, which made between-study comparisons difficult. However, it did identify 7 variables that significantly impact survival after reLT, which could stimulate future research into improving post-reLT outcomes.
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INTRODUCTION: In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown. METHODS: Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use. RESULTS: A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years ( P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 ( P = 0.98), and follow-up after LT 2.3 vs 1.7 years ( P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%-96%) vs 86% (95% CI 66%-94%) and 85% (95% CI 79%-90%) vs 78% (95% CI 57%-89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61-4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07-2.94). DISCUSSION: Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT.
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Enfermedad Hepática en Estado Terminal , Várices Esofágicas y Gástricas , Hepatitis Alcohólica , Trasplante de Hígado , Humanos , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Hemorragia Gastrointestinal , Índice de Severidad de la Enfermedad , Hepatitis Alcohólica/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Malnutrition is a known risk factor for postoperative morbidity and mortality in patients awaiting liver transplantation (LT). Malnutrition is a potentially reversible risk factor, though there are no clear guidelines on the best mechanism for an improvement. It also remains unclear if preoperative nutritional interventions have benefits to post-transplant outcomes for transplant recipients. OBJECTIVES: Primary objective: To identify if preoperative optimization of nutritional status is associated with improved short-term outcomes after LT. SECONDARY OBJECTIVES: To determine if preoperative improvement of malnutrition improves short-term outcomes after LT, as well as if weight loss in obese patients affects short-term outcomes after LT. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. POSPERO Protocol ID: CRD42021237450 RESULTS: 3851 records were identified in searching the databases, 3843 records were excluded by not fulfilling eligibility criteria. Seven full-text articles were included for the final analysis of which three were randomized controlled trials, one was prospective observational studies, and three were retrospective observational studies. No appreciable difference in mortality, post-transplant complication rate was noted across the studies. Length of stay (LOS) was noted to be shorter in two observational studies of Vitamin D deficiency in liver transplant patients. CONCLUSIONS: We have made a weak recommendation supporting pre-transplant nutritional supplementation due to possible benefit in reducing LOS as well as the lack of harm (Quality of Evidence low | Grade of Recommendation; Weak). No effective conclusions were reached for the secondary objectives due to the conflicting evidence.
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Trasplante de Hígado , Estado Nutricional , Humanos , Estudios Retrospectivos , Obesidad , Estudios Observacionales como AsuntoRESUMEN
Malnutrition is a known risk factor for postoperative morbidity and mortality in patients awaiting liver transplantation (LT). Malnutrition is a potentially reversible risk factor, though there are no clear guidelines on the best mechanism for an improvement. It also remains unclear if preoperative nutritional interventions have benefits to post-transplant outcomes for transplant recipients. Primary objective: To identify if preoperative optimization of nutritional status is associated with improved short-term outcomes after LT. Secondary Objectives: To determine if preoperative improvement of malnutrition improves short-term outcomes after LT, as well as, if weight loss in obese patients affects short-term outcomes after LT. Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. POSPERO Protocol ID: CRD42021237450 3851 records were identified in searching the databases, 3843 records were excluded by not fulfilling eligibility criteria. Seven full-text articles were included for the final analysis of which three were randomized controlled trials, one was prospective observational studies, and three were retrospective observational studies. No appreciable difference in mortality, post-transplant complication rate was noted across the studies. Length of stay (LOS) was noted to be shorter in two observational studies of Vitamin D deficiency in liver transplant patients. We have made a weak recommendation supporting pre-transplant nutritional supplementation due to possible benefit in reducing LOS as well as the lack of harms (Quality of Evidence low | Grade of Recommendation; Weak). No effective conclusions were reached for the secondary objectives due to the conflicting evidence.
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Humanos , /tratamiento farmacológico , Trasplante de Hígado/normas , Desnutrición/prevención & control , Vitamina D/uso terapéuticoRESUMEN
BACKGROUND: Management of dual antiplatelet therapy (DAPT) in the perioperative setting is challenging, particularly in complex patient populations, such as those with underlying coagulopathy and/or recent percutaneous coronary interventions. METHODS: In this case series, we describe the perioperative use of cangrelor bridge therapy in two patients undergoing liver transplantation after recent coronary drug-eluting stent placement. OUTCOMES: In both patient cases, cangrelor use as a P2Y12 bridge at a dose of 0.75 µg/kg/min was safe and effective. Both patients were successfully switched back to their oral DAPT regimen post-operatively without additive bleeding or thrombotic complications. CONCLUSION: The use of cangrelor as bridge therapy in high-risk perioperative liver transplant patients appears to be a viable option when DAPT is warranted.
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Stents Liberadores de Fármacos , Trasplante de Hígado , Intervención Coronaria Percutánea , Adenosina Monofosfato/análogos & derivados , Quimioterapia Combinada , Humanos , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria , Resultado del TratamientoRESUMEN
Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in seven patients and were treated with systemic therapy and resection. The study population had a higher than expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.