Increased expression of long non-coding RNA FIRRE promotes hepatocellular carcinoma by HuR-CyclinD1 axis signaling.

There is a critical need to understand the disease processes and identify improved therapeutic strategies for hepatocellular carcinoma (HCC). The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. The aim of this study was to identify a lncRNA as a potential biomarker of HCC and investigate the mechanisms by which the lncRNA promotes HCC progression using human cell lines and in vivo. Using RNA-Seq analysis, we found that lncRNA FIRRE was significantly upregulated in hepatitis C virus (HCV) associated liver tissue and identified that lncRNA FIRRE is significantly upregulated in HCV-associated HCC compared to adjacent non-tumor liver tissue. Further, we observed that FIRRE is significantly upregulated in HCC specimens with other etiologies, suggesting this lncRNA has the potential to serve as an additional biomarker for HCC. Overexpression of FIRRE in hepatocytes induced cell proliferation, colony formation, and xenograft tumor formation as compared to vector-transfected control cells. Using RNA pull-down proteomics, we identified HuR as an interacting partner of FIRRE. We further showed that the FIRRE-HuR axis regulates cyclin D1 expression. Our mechanistic investigation uncovered that FIRRE is associated with an RNA-binding protein HuR for enhancing hepatocyte growth. Together, these findings provide molecular insights into the role of FIRRE in HCC progression.

Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis c infected donors to hepatitis c naïve recipients: A large single center experience.

BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.

The Effect of a Merit Point Incentive System on the Willingness to Donate Organs.

PURPOSE: Although over 90% of the population of the United States supports organ donation, only 60% of the population is registered as donors. Currently, there is a need for a nonmonetary incentive that will improve willingness to donate. We assessed the young adult population's perspective on their willingness to donate organs when merit points are granted to their family members to prioritize their potential transplant if needed. METHODS: We administered a Qualtrics survey from March 2022 to September 2022 to the undergraduate students volunteering to participate at Saint Louis University, which comprised 10 questions that addressed the attitudes of participants regarding the effects of various factors, including the type of donation and the presence of merit points (vouchers granted to self or a family member to facilitate a potential transplant if needed), on participant's willingness to donate an organ while alive or after death. The responses were analyzed by using SAS software (SAS Institute). RESULTS: A total of 572 participants completed the survey. Overall, only 6.5% of surveyed students were unwilling to donate after death. The willingness to donate while alive to a family member was significantly higher than donating to a stranger (95.8% vs 71.2%, P < .0001). When merit points were added, the unwillingness to donate significantly decreased from 6.5% to 3.8%. However, this change was observed only when the merit points were given to a family member and not to self. When merit points were granted, unwillingness to provide a living donation to a stranger decreased from 28.8% to 16.4% (P < .0001). CONCLUSIONS: Merit points to first-degree family members improve students' expressed willingness to donate organs after death; however, self-merit points did not decrease the rate of "unwillingness to donate after death." When living donation is assessed, offering merit points appears to decrease the "unwillingness to donate to strangers." The adoption of a merit point system in the United States may increase the rates of organ donation.

Normothermic ex vivo perfusion of deceased donor kidneys and its clinical potential in kidney transplantation outcomes.

In recent years, normothermic machine perfusion (NMP) has emerged in conversation surrounding organ preservation and transplantation techniques with the goal of improving patient and clinical outcomes. This is in great attempt to address the rate of non-utilization and the shortage of available organs in kidney transplantation. This focus in mind, normothermic perfusion presents itself as a potential tool to mimic physiological conditions and improve current preservation methods, such as static cold storage. This review serves to improve understanding of the observed connection between the consequences of ischemia and reperfusion injury and traditional preservation techniques as well as how renal NMP may mitigate these issues. Previous studies suggest that reducing time in static cold storage methods by promoting the normothermic perfusion model results in decreased delayed graft function and post-transplant complications. This review also aims to present the immense clinical potential NMP has on future kidney transplantation success and what this means for the fields of nephrology and transplantation. While great strides have been made to evaluate normothermic perfusion's impact on kidney graft viability and transplant success, future research into unified protocol, clinically relevant biomarkers, cost-utility analysis, and use with associated therapeutic and imaging modalities is paramount.

Hepatic Adrenal Rest Tumors Mimicking Hepatocellular Carcinoma: A Case Report and Review of the Literature.

Adrenal rest tumors are rare collections of aberrantly located adrenocortical tissue. They are most commonly found in the kidneys, and hepatic involvement is rare with few published case reports. When located in the liver, imaging findings are frequently indistinguishable from hepatocellular carcinoma (HCC), but when resected, histologic examination shows adrenocortical tissue. Here, we present a patient with a history of nonalcoholic steatohepatitis with advanced fibrosis who was identified as having HCC by cross-sectional imaging but was found to have a hepatic adrenal rest tumor (HART) after resection. HARTs can share imaging characteristics with HCC, and this alternative diagnosis should be considered, especially for hepatic segment VII lesions.

Novel Therapeutic Approaches for Mitigating Complications in Short Bowel Syndrome.

Short bowel syndrome (SBS) is a particularly serious condition in which the small intestine does not absorb sufficient nutrients for biological needs, resulting in severe illness and potentially death if not treated. Given the important role of the gut in many signaling cascades throughout the body, SBS results in disruption of many pathways and imbalances in various hormones. Due to the inability to meet sufficient nutritional needs, an intravenous form of nutrition, total parental nutrition (TPN), is administered. However, TPN presents difficulties such as severe liver injury and altered signaling secondary to the continued lack of luminal contents. This manuscript aims to summarize relevant studies into the systemic effects of TPN on systems such as the gut-brain, gut-lung, and gut-liver axis, as well as present novel therapeutics currently under use or investigation as mitigation strategies for TPN induced injury.

Intraoperative Doppler Ultrasound for Detection of Early Postoperative Vascular Complications in Orthotopic Liver Transplants.

Liver transplantation is currently the only curative treatment for patients with end-stage liver disease. However, liver transplantation can be associated with catastrophic complications in the early postoperative setting, including hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT). Postoperative complications are associated with hepatic artery resistive index (RI) < 6, systolic acceleration time (SAT) > 0.08 seconds and peak systolic velocity (PSV) > 200 cm/s on doppler ultrasound (DUS). DUS is also used in an intraoperative setting to assess patency and early complications prior to the end of the operative period, allowing for early correction. This literature review evaluates the prevalence of DUS use in intraoperative settings to identify transplant complications. A lack of consistency and minimal knowledge of intraoperative DUS warrants additional research into its usage and standardization.

Ehrlichiosis in a Recent Liver Transplant Recipient Leading to Multiorgan Failure.

Ehrlichia infection has a broad spectrum of diseases ranging from asymptomatic to fatal. While Ehrlichia often presents as a mild form of the disease in immunocompetent patients, immunosuppressed patients are at increased risk for a more virulent and potentially fatal infection. Our liver transplant patient presented with fever, persistent headaches, and negative Ehrlichia antibodies. Empiric antibiotic therapy was started and along with knowledge of prior tick infection, doxycycline was added. Subsequent positive PCR and observation of Ehrlichia chaffeensis in peripheral blood smear confirmed the diagnosis. The patient did recover from infection but not before it manifested in hepatic, renal, and pulmonary involvement. Therefore, a high level of suspicion is necessary for early detection and treatment initiation to prevent a devastating progression of the disease in immunosuppressed patients.

Novel NMP split liver model recapitulates human IRI and demonstrates ferroptosis modulators as a new therapeutic strategy.

BACKGROUND: Almost 9%of deceased donor livers are discarded as marginal donor livers (MDL) due to concern of severe ischemia reperfusion injury (IRI). Emerging data supports ferroptosis (iron regulated hepatocellular death) as an IRI driver, however lack of robust preclinical model limits therapeutic testing. In this manuscript we describe the development of a novel rigorous internal control system utilizing normothermic perfusion of split livers to test ferroptosis regulators modulating IRI. METHODS: Upon institutional approval, split human MDLs were placed on our normothermic perfusion machine, Perfusion Regulated Organ Therapeutics with Enhanced Controlled Testing (PROTECT), pumping arterial and portal blood. Experiment 1 compared right (UR) and left (UL) lobes to validate PROTECT. Experiment 2 assessed ferroptosis regulator Deferoxamine in Deferoxamine Agent Treated (DMAT) vs. No Agent Internal Control (NAIC) lobes. Liver serology, histology, and ferroptosis genes were assessed. RESULTS: Successful MDL perfusion validated PROTECT with no ALT or AST difference between UR and UL (∆ALT UR: 235, ∆ALT UL: 212; ∆AST UR: 576, ∆AST UL: 389). Liver injury markers increased in NAIC vs. DMAT (∆ALT NAIC: 586, ∆ALT DMAT: -405; ∆AST NAIC: 617, ∆AST DMAT: -380). UR and UL had similar expression of ferroptosis regulators RPL8,HO-1 and HIFα. Significantly decreased intrahepatic iron (p = .038), HO-1 and HIFα in DMAT (HO-1 NAIC: 6.93, HO-1 DMAT: 2.74; HIFαNAIC: 8.67, HIFαDMAT: 2.60)and no hepatocellular necrosis or immunohistochemical staining (Ki67/Cytokeratin-7) differences were noted. CONCLUSION: PROTECT demonstrates the therapeutic utility of a novel normothermic perfusion split liver system for drug discovery and rapid translatability of therapeutics, driving a paradigm change in organ recovery and transplant medicine. Our study using human livers, provides preliminary proof of concept for the novel role of ferroptosis regulators in driving IRI.

Cryoablation for Renal Cell Carcinoma Prior to Liver Transplantation: A Case Report.

Extrahepatic malignancies are a relatively rare incidental finding during liver transplant work-up that provides a significant barrier to continued transplant evaluation and requires treatment to limit the risk of recurrence. There have only been 11 previously reported cases of pre-liver transplant renal cell carcinoma (RCC), of which all underwent partial or radical nephrectomy. Percutaneous cryoablation therapy has been gaining acceptance as a curative treatment alternative for RCC and is a new therapeutic standard for patients who are poor candidates for surgical resection. Recent studies have demonstrated the safety and efficacy of cryoablation for RCC in native kidneys and in solid masses in kidney allografts, but there is no data on the efficacy or recurrence of RCC when cryoablation is used for the treatment of RCC in a native kidney prior to solid organ transplantation. The patient underwent percutaneous cryoablation therapy of a T1a RCC of the native kidney 10 months prior to orthotopic liver transplant (OLT) without subsequent partial or radical nephrectomy. At seven years post-ablation therapy, the patient has no evidence of tumor recurrence despite immunosuppressive therapy post-transplantation. Cryoablation is potentially a safe and highly effective means of treating RCC in patients who are not candidates for nephrectomy secondary to complications associated with end-stage liver disease. In our case, the patient was treated with cryoablation and received standard post-transplant immunosuppression without recurrence of RCC at seven years. More studies are needed to determine inclusion and exclusion criteria for cryoablation and to confirm long-term efficacy as well as a strategy for duration and frequency of surveillance in these patients.

Clinician and patient attitudes toward use of organs from hepatitis C viremic donors and their impact on acceptance: A contemporary review.

BACKGROUND: The use of Hepatitis C (HCV) NAT positive allografts remains unusual and is clustered at few centers. We conducted a contemporary literature review to assess whether patient and clinician attitudes toward viremic organs impact acceptance. METHODS: Databases including PubMed, MEDLINE, and SCOPUS databases were reviewed to identify studies focused on evaluating patient and provider perceptions of HCV NAT positive organ use within the DAA era (January 2015-April 2021). Search included MeSH terms related to Hepatitis C, transplantation, and patient and clinician attitudes. Two investigators extracted study characteristics including information on willingness to accept viremic organs, HCV-specific outcomes knowledge, HCV-specific concerns, and factors that contributed to acceptance or non-acceptance. RESULTS: Eight studies met all inclusion criteria. These included three pretransplant patient-directed studies, two post-transplant patient-directed studies, one pre- and post-transplant patient-directed study, and two clinician-directed studies. Common themes identified were concerns regarding HCV cure rates, viremic organ quality, DAA cost, stigma, and the possibility of HCV transmission to household members. The perception of decreased waitlist time was associated with viremic organ acceptance. Physician trust played a mixed role in acceptance patterns. CONCLUSIONS: Knowledge of high cure rates, shorter waitlist times, and higher organ quality appear to have the highest impact on organ acceptance.

Recurrent Perihepatic Abscesses Arising from a Gastric Remnant Leak: Delayed Complication of a Revision Roux-en-Y Gastric Bypass.

Roux-en-Y gastric bypass is a procedure commonly used for weight loss associated with improved outcomes and decreased complications when compared to some counterparts. The procedure involves restriction of the stomach that is achieved by creation of a gastric pouch and bypass of the duodenum and a portion of the jejunum to aid in restrictive and malabsorptive weight loss. While many complications, both early and late, have been described following the procedure, recurrent perihepatic abscess has not been described in the literature. We present a case of a 66-year-old woman with recurrent extrahepatic abscesses following revision of a Roux-en-Y gastric bypass.

Treatment of Hepatitis C Post-Liver Transplantation Could Mitigate Discard Rates of Hepatitis C-Positive Deceased Donor Livers and Expand the Donor Pool.

BACKGROUND: Prior to 2014, treatment for hepatitis C was limited. However, the subsequent introduction of direct acting antiviral medications (DAA) against hepatitis C led to improvements in morbidity and better medication tolerance. DAA therapy allowed for an increase in treatment rates of hepatitis C in patients on the liver transplant waiting list. With the popularization of DAA, there became a growing concern about the utility of hepatitis C-positive (HCV+) deceased liver donors, especially after treating HCV+ potential recipients on the transplant waiting list. METHODS: This is a retrospective, observational study using Mid-America Transplant Services (MTS) database from 2008 to 2017. Comparison was made before the widespread use of DAAs 2008-2013 (pre-DAA) against their common practice use 2014-2017 (post-DAA). All deceased liver donors with HCV antibody or nucleic acid positive results were evaluated. RESULTS: Between 2008 and 2017, 96 deceased liver donors were positive for HCV. In the pre-DAA era, 47 deceased liver donors were positive for HCV, of which 32 (68.1%) were transplanted and 15 (31.9%) were discarded. In the post-DAA era, a total of 49 HCV+ organs were identified, out of which 43 (87.8%) livers were transplanted and 6 (12.2%) were discarded. Discard rate was significantly higher in the pre-DAA population (31.9% vs. 12.2%, p = 0.026). Secondary analysis showed a distinct trend towards increased regional sharing and utilization of HCV+ donors. CONCLUSION: In order to reduce discard rates of HCV+ patients, our data suggest that transplant centers could potentially delay HCV treatment in patients on the transplant waitlist.

A Unique Presentation of Bouveret's Syndrome: Two Large Gallstones Obstructing Both the Gastric Outlet and the Common Bile Duct Simultaneously.

Bouveret's syndrome refers to a gastric outlet obstruction secondary to impaction of a gallstone in the pylorus or proximal duodenum. Thus, it can be considered a very proximal form of gallstone ileus and is infrequent. We describe such a unique case that a female patient presents with Bouveret's syndrome and concomitant common bile duct obstruction by a second gallstone. The decision over its surgical management is complicated, based on risk factors, clinical presentations, radiographic evidence, surgical risk assessment, and specific considerations tailored to individual case. Because of her stable clinical picture and low surgical risk, we proceeded with stone extractions, fistula take-down, and common bile duct exploration in a one-stage procedure. Her postoperative course was complicated by bile stained drainage through closed suction drain that resolved with conservative management.

The Creation of a Novel Low-Cost Bench-Top Kidney Transplant Surgery Simulator and a Survey on Its Fidelity and Educational Utility.

Introduction Resident inexperience during time-sensitive vascular anastomoses of a kidney transplant can negatively impact outcomes. In light of this, we created a low-cost bench-top kidney transplant surgery simulator to help residents practice vascular anastomoses. Methods We searched for inexpensive materials to design an iliac fossa and kidney allograft. Eighteen residents with real-life kidney transplant experience trialed the simulator and scored its fidelity and educational utility on a 0-100 visual analog scale (VAS) survey. Results A 35.9 x 19.4 x 12.4 cm plastic box mimicked the iliac fossa. Hooks attached to the box's sidewall held under tension 1.27 and 0.64 cm diameter Penrose drains to replicate the external iliac vein and artery. A modified kidney-shaped stress ball with 1.27 x 4, 0.64 x 4, and 0.64 x 15 cm Penrose drains replicated a kidney allograft with its vein, artery, and ureter, respectively. Residents performed and assisted in vascular anastomoses on the simulator. The iliac fossa and allograft cost $20.20 and each practice run cost $7.20. Residents thought that the simulator was less difficult than real-life procedure, had acceptable fidelity levels, and they highly rated its educational utility. Conclusion Our novel low-cost bench-top kidney transplant surgery simulator focusing on vascular anastomoses received positive educational feedback from residents.

Asymptomatic Intestinal Malrotation Progressing to Midgut Volvulus in a Decompensated Alcoholic Cirrhotic Adult: A Rare Scenario Requiring Special Considerations.

Intestinal malrotation usually presents in the pediatric population with midgut volvulus requiring emergency Ladd's procedure. Rarely, it remains asymptomatic and is discovered incidentally only during adulthood when it seldom causes intestinal complications. The scenario of a cirrhotic adult being diagnosed with asymptomatic intestinal malrotation with subsequent intestinal complications is thus extremely rare and to our knowledge has not been previously reported. We describe a 56-year-old man with decompensated alcoholic cirrhosis (Child-Pugh class C, MELD score 22) who was initially observed after an incidental diagnosis of intestinal malrotation on computed tomography. Observation continued as his liver disease improved with alcohol cessation (Child-Pugh class A, MELD score 8). He later presented with a closed loop bowel obstruction secondary to midgut volvulus at the time of alcohol relapse and liver redecompensation (Child-Pugh class C, MELD score 22-29). He underwent emergency Ladd's procedure during which his midjejunum was volvulized into an internal hernia space created by a thick Ladd's band containing large varices. The postoperative course was complicated by ileus and loculated bacterial peritonitis. Based on our experience, we discuss special considerations with regard to the surgical technique and timing of Ladd's procedure when encountering intestinal malrotation in a cirrhotic adult with portal hypertension.

Establishment of a Patient-Derived Xenograft Tumor From Hepatitis C-Associated Liver Cancer and Evaluation of Imatinib Treatment Efficacy.

BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) infection is one of the major causal factors for hepatocellular carcinoma (HCC). The treatment options for HCC are limited for lack of a convenient animal model for study in HCV infection and liver pathogenesis. This study aimed to develop a patient-derived xenograft (PDX) tumor in mice by using a tumor from a patient with HCV-associated HCC and evaluating this model's therapeutic potential. APPROACH AND RESULTS: After resection of the primary tumor from the patient liver, excess viable tumor was implanted into highly immunodeficient mice. A mouse xenograft tumor line was developed, and the tumor was successfully passaged for at least three rounds in immunodeficient mice. The patient's primary tumor and the mouse xenografts were histologically similar. Genetic profiling by short-tandem-repeat analysis verified that the HCC-PDX model was derived from the HCC clinical specimen. HCV RNA present in the patient liver specimen was undetectable after passage as xenograft tumors in mice. Human albumin, α1 -antitrypsin, glypican-3, α-smooth muscle actin, and collagen type 1A2 markers were detected in human original tumor tissues and xenograft tumors. Both the patient primary tumor and the xenograft tumors had a significantly higher level of receptor tyrosine kinase (c-Kit) mRNA. Treatment of HCC-PDX xenograft tumor-bearing mice with the c-Kit inhibitor imatinib significantly reduced tumor growth and phospho-Akt and cyclin D1 expression, as compared with untreated control tumors. CONCLUSIONS: Our results demonstrated establishment of an HCV-associated HCC-PDX model as a powerful tool for evaluating candidate drugs. Information on molecular changes in cancer-specific gene expression facilitates efficient targeted therapies and treatment strategies.

Utilization of Vicryl Bridging Mesh in Orthotopic Liver Transplantation to Achieve Tension-Free Abdominal Wall Closure: A Case Series.

Difficulty in primary fascial closure of the abdomen in transplant patients is a common challenge. Abdominal wall tension may have detrimental effects on the newly transplanted graft due to compression, and blood flow hindrance, potentially leading to ischemia or thrombosis and possibly graft failure. Furthermore, patients will be at risk of developing fascial ischemia and dehiscence. Myocutaneous flaps, temporary closure with silastic mesh, abdominal wall transplants, and even graft reduction, bowel resection, and splenectomies have been practiced with varying degrees of success. In this study, we present four cases of patients who underwent orthotopic liver transplantation (OLT) with bridging Vicryl knitted mesh (ETHICON VKML VICRYL-Polyglactin 910-30 × 30 cm) to relieve the tension during the closure. Our results show that these patients, despite having a high average Model End-Stage Liver Disease (MELD) score of 25, had a good liver function at the time of discharge and continue to upon follow-up. They had a relatively short length of stay (LOS) in both the intensive care unit (ICU) and in the hospital, an average of 3.5 days and 9 days, respectively. Our case series successfully show that utilizing a bridging Vicryl knitted mesh is a reasonable approach to attain tension-free abdominal closure in OLT with satisfying results.

Center-driven and Clinically Driven Variation in US Liver Transplant Maintenance Immunosuppression Therapy: A National Practice Patterns Analysis.

BACKGROUND: Variation in the use of immunosuppression regimens after liver transplant has not been well described. METHODS: Immunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice. RESULTS: In the first 6 months after transplant, triple immunosuppression (tacrolimus, antimetabolite, corticosteroids) was the most common regimen (42.9%). By months 7 to 12, immunosuppression regimens were more commonly antimetabolite sparing (33.7%) or steroid sparing (26.9%), followed by triple (14.4%), mammalian target of rapamycin inhibitor (mTORi)-based (12.1%), or cyclosporine-based (9.2%). Based on intraclass correlation analysis, clinical characteristics explained less than 10% of the variation in immunosuppression choice, whereas program preference/practice explained 23% of steroid sparing, 26% of antimetabolite sparing, 28% of mTORi, and 21% of cyclosporine-based regimen use. Although case factors were not dominant practice drivers, triple immunosuppression in months 7 to 12 was more common among retransplant recipients and those with prior acute rejection. Hepatocellular carcinoma as cause of liver failure (adjusted odds ratio [aOR], 2.15; P<0.001), cancer within 6 months (aOR, 6.07; P<0.001), and 6-month estimated glomerular filtration rate less than 30 mL/min per 1.3 m2 (aOR, 1.98; P<0.001) were associated with mTORi use compared with triple immunosuppression in months 7 to 12, whereas acute rejection predicted lower use (aOR, 0.72; P=0.003). CONCLUSIONS: Liver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.

Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies.

Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.