OPTN/SRTR 2022 Annual Data Report: Liver.

In 2022, liver transplant activity continued to increase in the United States, with an all-time high of 9,527 transplants performed, representing a 52% increase over the past decade (2012-2022). Of these transplants, 8,924 (93.7%) were from deceased donors and 603 (6.3%) were from living donors. Liver transplant recipients were 94.5% adult and 5.5% pediatric. The overall size of the liver transplant waiting list contracted, with more patients being removed than added, although 10,548 adult patients still remained on the waiting list at the end of 2022. Alcohol-associated liver disease continued to be the leading diagnosis among both candidates and recipients, followed by metabolic dysfunction-associated steatohepatitis. Simultaneous liver-kidney transplant was the most common multiorgan combination, with 800 liver-kidney transplants performed in 2022; in addition, there were 303 new listings for kidney transplant via the safety net mechanism. Among adults added to the liver waiting list in 2021, 39.9% received a deceased donor liver transplant within 3 months; 45.7%, within 6 months; and 54.5%, within 1 year. Pretransplant mortality decreased to 12.3 deaths per 100 patient-years in 2022, although still 15.6% of removals from the waiting list were for death or being too sick for transplant. Graft and patient survival outcomes after deceased donor liver transplant improved, approximating pre-COVID-19 pandemic levels, with 5.1% mortality observed at 6 months; 6.8%, at 1 year; 12.7%, at 3 years; 19.8%, at 5 years; and 35.7%, at 10 years. Five-year graft and patient survival rates after living donor liver transplant exceeded those of deceased donor liver transplant. Candidates receiving model for end-stage liver disease exception points for hepatocellular carcinoma constituted 15.5% of transplants performed in 2022, with similar transplant rates and posttransplant outcomes compared to cases without hepatocellular carcinoma exception. In 2022, more pediatric liver transplant candidates were added to the waiting list and underwent transplant compared with either of the preceding 2 years, with an uptick in living donor liver transplant volume. Although pretransplant mortality has improved after the recent policy change prioritizing pediatric donors for pediatric recipients, still, in 2022, 50 children died or were removed from the waiting list for being too sick to undergo transplant. Posttransplant mortality among pediatric liver transplant recipients remained notable, with death occurring in 4.0% at 6 months, 6.0% at 1 year, 8.2% at 3 years, 9.8% at 5 years, and 13.9% at 10 years. Similar to adult living donor recipients, pediatric living donor recipients had better 5-year patient survival compared with deceased donor recipients.

Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.

OPTN/SRTR 2021 Annual Data Report: Liver.

In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle-based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle-based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points.

Outcomes of patients with acute liver failure listed for liver transplantation: A multicenter prospective cohort analysis.

Liver transplantation (LT) is a life-saving treatment for patients with acute liver failure (ALF). Currently, there are few detailed data regarding long-term outcomes after LT for ALF. We combined prospective data from the Acute Liver Failure Study Group (ALFSG) Registry with those of the Scientific Registry of Transplant Recipients (SRTR) to assess outcomes among consecutive patients with ALF listed for LT. Cohort analysis of detailed pretransplantation data for patients listed for LT for ALF in the ALFSG Registry between January 1998 and October 2018 matched with transplantation-related data from the SRTR. Primary outcomes were 1- and 3-year post-LT patient survival. Secondary outcome was receipt of LT; independent associations with successful receipt of LT were determined using multivariable logistic regression. Of 624 patients with ALF listed for LT, 398 (64%) underwent LT, 100 (16%) died without LT, and 126 (20%) recovered spontaneously. Among LT recipients, etiologies included seronegative/indeterminate (22%), drug-induced liver injury (18%), acetaminophen overdose (APAP; 16%), and viral hepatitis (15%). The 1- and 3-year post-LT patient survival rates were 91% and 90%, respectively. Comparing those dying on the waiting list versus with those who received LT, the former had more severe multiorgan failure, reflected by increased vasopressor use (65% vs. 22%), mechanical ventilation (84% vs. 57%), and renal replacement therapy (57% vs. 30%; p < 0.0001 for all). After adjusting for relevant covariates, age (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00-1.04), APAP etiology (aOR 2.72, 95% CI 1.42-5.23), requirement for vasopressors (aOR 4.19, 95% CI 2.44-7.20), Grade III/IV hepatic encephalopathy (aOR 2.47, 95% CI 1.29-4.72), and Model for End-Stage Liver Disease (MELD) scores (aOR 1.05, 95% CI 1.02-1.09; p < 0.05 for all) were independently associated with death without receipt of LT. Post-LT outcomes for ALF are excellent in this cohort of very ill patients. The development of multiorgan failure while on the transplantation list and APAP ALF etiology were associated with a lower likelihood of successful receipt of LT.

Patient-reported outcomes in HCC: A scoping review by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

BACKGROUND AND AIMS: HCC is a leading cause of mortality in patients with advanced liver disease and is associated with significant morbidity. Despite multiple available curative and palliative treatments, there is a lack of systematic evaluation of patient-reported outcomes (PROs) in HCC. APPROACH AND RESULTS: The American Association for the Study of Liver Diseases Practice Metrics Committee conducted a scoping review of PROs in HCC from 1990 to 2021 to (1) synthesize the evidence on PROs in HCC and (2) provide recommendations on incorporating PROs into clinical practice and quality improvement efforts. A total of 63 studies met inclusion criteria investigating factors associated with PROs, the relationship between PROs and survival, and associations between HCC therapy and PROs. Studies recruited heterogeneous populations, and most were cross-sectional. Poor PROs were associated with worse prognosis after adjusting for clinical factors and with more advanced disease stage, although some studies showed better PROs in patients with HCC compared to those with cirrhosis. Locoregional and systemic therapies were generally associated with a high symptom burden; however, some studies showed lower symptom burden for transarterial radiotherapy and radiation therapy. Qualitative studies identified additional symptoms not routinely assessed with structured questionnaires. Gaps in the literature include lack of integration of PROs into clinical care to guide HCC treatment decisions, unknown impact of HCC on caregivers, and the effect of palliative or supportive care quality of life and health outcomes. CONCLUSION: Evidence supports assessment of PROs in HCC; however, clinical implementation and the impact of PRO measurement on quality of care and longitudinal outcomes need future investigation.

Self-ejection of salts and other foulants from superhydrophobic surfaces to enable sustainable anti-fouling.

A recently discovered phenomenon in which crystalline structures grown from evaporating drops of saline water self-eject from superhydrophobic materials has introduced new possibilities for the design of anti-fouling materials and sustainable processes. Some of these possibilities include evaporative heat exchange systems using drops of saline water and new strategies for handling/processing waste brines. However, the practical limits of this effect using realistic, non-ideal source waters have yet to be explored. Here, we explore how the presence of various model aquatic contaminants (colloids, surfactants, and calcium salt) influences the self-ejection phenomena. Counterintuitively, we find that the addition of "contaminant" chemistries can enable ejection under conditions where ejection was not observed for waters containing only sodium chloride salt (e.g., from smooth hydrophobic surfaces), and that increased concentrations of both surfactants and colloids lead to longer ejection lengths. This result can be attributed to decreased crystallization nucleation time caused by the presence of other species in water.

Basic principles of liver allocation and development over the years.

PURPOSE OF REVIEW: Prior to the enactment of the National Organ Transplant Act in 1984, there was no organized system to allocate donor organs in the United States. The process of liver allocation has come a long way since then, including the development and implementation of the Model for End-stage Liver Disease, which is an objective estimate of risk of mortality among candidates awaiting liver transplantation. RECENT FINDINGS: The Liver Transplant Community is constantly working to optimize the distribution and allocation of scare organs, which is essential to promote equitable access to a life-saving procedure in the setting of clinical advances in the treatment of liver disease. Over the past 17 years, many changes have been made. Most recently, liver distribution changed such that deceased donor livers will be distributed based on units established by geographic circles around a donor hospital rather than the current policy, which uses donor service areas as the unit of distribution. In addition, a National Liver Review Board was created to standardize the process of determining liver transplant priority for candidates with exceptional medical conditions. The aim of these changes is to allocate and distribute organs in an efficient and equitable fashion. SUMMARY: The current review provides a historical perspective of liver allocation and the changing landscape in the United States.

Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1.

BACKGROUND & AIMS: Hepatorenal syndrome type 1 (HRS-1) in patients with cirrhosis and ascites is a functional, potentially reversible, form of acute kidney injury characterized by rapid (<2 wk) and progressive deterioration of renal function. Terlipressin is a synthetic vasopressin analogue that acts, via vascular vasopressin V1 receptors, as a systemic vasoconstrictor. We performed a phase 3 study to evaluate the efficacy and safety of intravenous terlipressin plus albumin vs placebo plus albumin in patients with HRS-1. METHODS: Adult patients with cirrhosis, ascites, and HRS-1 (based on the 2007 International Club of Ascites criteria of rapidly deteriorating renal function) were assigned randomly to groups given intravenous terlipressin (1 mg, n = 97) or placebo (n = 99) every 6 hours with concomitant albumin. Treatment continued through day 14 unless the following occurred: confirmed HRS reversal (CHRSR, defined as 2 serum creatinine [SCr] values ≤1.5 mg/dL, at least 40 hours apart, on treatment without renal replacement therapy or liver transplantation) or SCr at or above baseline on day 4. The primary end point was the percentage of patients with confirmed CHRSR. Secondary end points included the incidence of HRS reversal (defined as at least 1 SCr value ≤1.5 mg/dL while on treatment), transplant-free survival, and overall survival. The study was performed at 50 investigational sites in the United States and 2 in Canada, from October 2010 through February 2013. RESULTS: Baseline demographic/clinical characteristics were similar between groups. CHRSR was observed in 19 of 97 patients (19.6%) receiving terlipressin vs 13 of 99 patients (13.1%) receiving placebo (P = .22). HRS reversal was achieved in 23 of 97 (23.7%) patients receiving terlipressin vs 15 of 99 (15.2%) receiving placebo (P = .13). SCr decreased by 1.1 mg/dL in patients receiving terlipressin and by only 0.6 mg/dL in patients receiving placebo (P < .001). Decreases in SCr and survival were correlated (r(2) = .882; P < .001). Transplant-free and overall survival were similar between groups. A significantly greater proportion of patients with CHRSR who received terlipressin survived until day 90 than patients who did not have CHRSR after receiving terlipressin (P < .001); this difference was not observed in patients who did vs did not have CHRSR after receiving placebo (P = .28). There were similar numbers of adverse events in each group, but patients in the terlipressin group had more ischemic events. CONCLUSIONS: Terlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246.

Longterm health-related quality of life after living liver donation.

There are little data on longterm outcomes, health-related quality of life (HRQoL), and issues related to living donor right hepatectomy specifically. We studied longterm HRQoL in 127 living liver donors. A donor-specific survey (DSS) was used to evaluate the living liver donor morbidity, and the 36-item short-form health survey (short-form 36 health survey, version 1 [SF-36]) was used to assess generic outcomes. The DSS was completed by 107 (84.3%) donors and the SF-36 by 62 (49%) donors. Median follow-up was 6.9 years. Of the 107 donors, 12 (11.2%) donors reported their health as better, whereas 84 (78.5%) reported their health the same as before donation. Ninety-seven (90.7%) are currently employed. The most common postdonation symptom was incisional discomfort (34%). Twenty-four donors (22.4%) self-reported depression symptoms after donation. Ninety-eight (91.6%) rated their satisfaction with the donation process ≥ 8 (scale of 1-10). Three factors-increased vitality (correlation, 0.44), decreased pain (correlation, 0.34), and a recipient who was living (correlation, 0.44)-were independently related to satisfaction with the donor experience. Vitality showed the strongest association with satisfaction with the donor experience. Mental and physical component summary scale scores for donors were statistically higher compared to the US population norm (P < 0.001). Donors reported a high satisfaction rate with the donation process, and almost all donors (n = 104, 97.2%) would donate again independent of experiencing complications. Our study suggests that over a longterm period, liver donors continue to have above average HRQoL compared to the general population.

Frequency and prognosis of acute pancreatitis associated with acute hepatitis E: A systematic review.

BACKGROUND: The association of acute pancreatitis (AP) with viral hepatitis is well known, and is usually attributed to HAV, HBV, or HCV. AP related to acute hepatitis E (AHE) has been rarely described, and the typical profile is that of a young male, residing in an endemic area, presenting with mild to moderate pancreatitis, and improving with conservative management. RATIONALE: An increasing number of reports describe AP associated with AHE. Some life-threatening complications related to AP may occur, and death has been reported. In addition, it is possible that early diagnosis of these cases may help in reducing the morbidity and mortality. OBJECTIVE: Perform a systematic review to study cases of AP associated with AHE and to assess their prognosis. DATA SOURCES: PubMed, EMBASE, Scopus, and the Cochrane library. STUDY SELECTION: All available studies discussing AP associated with AHE. DATA EXTRACTION AND ASSESSMENT: Two blinded independent observers extracted and assessed the studies for diagnosis of AHE based on serological and/or molecular techniques, diagnosis of fulminant hepatitis based on the American Association for the study of Liver Diseases (AASLD) position paper, diagnosis of AP based on the American College of Gastroenterology (ACG) guidelines, diagnosis of AP associated with AHE based on Makharia's association, and diagnosis of AP severity based on the Revision of the Atlanta Classification (RAC). RESULTS: Thirteen case reports and 4 case series were found with 55 patients meeting the inclusion criteria. All patients originated from Southern Asia or had a recent travel to that area. The mean age at diagnosis was 28 years with a male to female ratio of 18:1. The mean interval between the onset of jaundice and the onset of AP pain was 10 days. AP was mild or moderately severe in 45 patients (82%), and severe in 10 patients (18%). Mortality was reported in 2 patients (3.6%). CONCLUSION: Fifty-five cases of acute pancreatitis associated with AHE are reported in the literature. Acute pancreatitis in this setting is severe in approximately one fifth of patients with an overall mortality rate similar to all other causes of AP.

Making the case for the development of a vaccination against hepatitis E virus.

Hepatitis E virus (HEV) infection is a global problem that affects 20 million individuals, and cause acute hepatitis in 3.5 million, with approximately 70,000 deaths worldwide per year. While the acute disease is generally self-limited, however, it may progress to fatal fulminant liver failure in certain individuals. Contaminated water supplies disseminate this virus through the faecal-oral route, and swine is thought to be its zoonotic reservoir. Attempts have been made to develop effective HEV vaccines, and two candidates have undergone successful clinical trials. In this review, we discuss HEV epidemiology, genotypes, microbiological structure, as well as the most recent advances in vaccination developments.

Health-related quality of life: two decades after liver transplantation.

In this study, we describe a cohort of patients who received liver transplants before January 1, 1989 at the University of Minnesota Medical Center (UMMC), and we evaluate the health-related quality of life (HRQOL) of the survivors of this group. One hundred sixty-one patients--66 adults and 95 children--received whole deceased donor liver transplants. Thirteen transplants occurred before 1980, and all these patients died within 6 months; they were excluded from the survival analysis because they came from the pre-cyclosporine era. The survival rates at 1, 5, 10, and 20 years were 72%, 57%, 49%, and 37%, respectively (34% when pre-1980 patients were included). The median survival time was approximately 10 years for adult and pediatric recipients. The causes of death were ascertained by chart reviews. Technical failures were common between the years 1980 and 1984, and they decreased to 0% by 1988. As for HRQOL, 53 patients (36%) survived and were contacted to complete a 12-item health survey [Short Form 12 (SF-12)]. Retransplants were excluded. Sixty-eight percent returned the SF-12 survey. The median age for all respondents was 31.4 years: the median was 67.4 years for adult survivors and 28.8 years for pediatric survivors. The Mental Component Summary (MCS) score was 54.6 for adult survivors and 48.6 for pediatric survivors. The Physical Component Summary (PCS) score was 39.3 for adult survivors and 49.2 for pediatric survivors. Both the MCS and the PCS were norm-based to the US population with a mean of 50 and a standard deviation of 10. In conclusion, 35.8% of liver transplant recipients from UMMC were alive 20 years after liver transplantation. Technical failure-related deaths decreased dramatically from 1980 to 1988. The mental health of pediatric and adult survivors was similar to that of the general population. The physical health of the pediatric survivors was equivalent to that of the general population, but it was slightly less than what was expected with adjustments for age. The physical health of the adult survivors was approximately 1 standard deviation below that of the general population.

Gastric bypass after liver transplantation.

Few data are available for assessing the outcomes of bariatric surgery for patients who have undergone orthotopic liver transplantation (OLT). The University of Minnesota bariatric surgery database and transplant registry were retrospectively reviewed to identify patients who had undergone OLT and then open Roux-en-Y gastric bypass (RYGB) surgery between 2001 and 2009. Comorbidity-appropriate laboratory values, body mass indices (BMIs), histopathology reports, and immunosuppressive regimens were collected. Seven patients were identified with a mean age of 55.4 ± 8.64 years and a mean follow-up of 59.14 ± 41.49 months from the time of RYGB. The mean time between OLT and RYGB was 26.57 ± 8.12 months. The liver disease etiologies were hepatitis C (n = 4), jejunoileal bypass surgery (n = 1), hemangioendothelioma (n = 1), and alcoholic cirrhosis (n = 1). There were 2 deaths for patients with hepatitis C 6 and 9 months after bariatric surgery due to multiple-organ dysfunction syndrome and metastatic esophageal squamous carcinoma, respectively. One patient with hepatitis C required a reversal of the RYGB because of malnutrition and an inability to tolerate oral intake. Four of the 7 patients had type 2 diabetes mellitus (T2DM), 4 had hypertension, and 6 patients had dyslipidemia. All patients were on immunosuppressive medications, but only 4 were on corticosteroids. Glycemic control was improved in all surviving patients with T2DM. The mean BMI was 34.27 ± 5.51 kg/m(2) before OLT and 44.34 ± 6.08 kg/m(2) before RYGB; it declined to 26.47 ± 5.53 kg/m(2) after RYGB. In conclusion, in this case series of patients undergoing RYGB after OLT, we observed therapeutic weight loss, improved glycemic control, and improved high-density lipoprotein levels in the presence of continued dyslipidemia. RYGB may have contributed to the death of 1 patient due to multiple-organ dysfunction syndrome.

Lower survival and higher rates of cirrhosis in patients with ROUX-EN-Y gastric bypass hospitalised with alcohol-associated hepatitis.

OBJECTIVE: The incidence of alcohol-associated liver disease (ALD) is increasing, and weight loss surgery is more common due to the obesity epidemic. Roux-en-Y gastric bypass (RYGB) is associated with alcohol use disorder and ALD; however, its impact on outcomes in patients hospitalised for alcohol-associated hepatitis (AH) is unclear. DESIGN: We performed a single-centre, retrospective study of patients with AH from June 2011 to December 2019. Primary exposure was the presence of RYGB. The primary outcome was inpatient mortality. Secondary outcomes included overall mortality, readmissions and cirrhosis progression. RESULTS: 2634 patients with AH met the inclusion criteria; 153 patients had RYGB. Median age of the entire cohort was 47.3 years; median Model for End Stage Liver Disease - Sodium (MELD-Na) was 15.1 in the study group versus 10.9 in the control group. There was no difference in inpatient mortality between the two groups. On logistic regression, increased age, elevated body mass index, MELD-Na >20 and haemodialysis were all associated with higher inpatient mortality. RYGB status was associated with increased 30-day readmission (20.3% vs 11.7%, p<0.01), development of cirrhosis (37.5% vs 20.9%, p<0.01) and overall mortality (31.4% vs 24%, p=0.03). CONCLUSIONS: Patients with RYGB have higher rates of readmissions, cirrhosis and overall mortality after discharge from hospital for AH. Allocation of additional resources on discharge may improve clinical outcomes and reduce healthcare expenditure in this unique patient population.

Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure.

Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF.

Renal dysfunction in liver transplant recipients: evaluation of the critical issues.

Major progress has been made in the field of liver transplantation since the first procedure was performed nearly 50 years ago. Despite these improvements, renal dysfunction before and after liver transplantation remains a major complicating factor associated with increased health care costs, morbidity, and mortality. Creatinine-based estimates of renal function are inaccurate in the setting of end-stage liver disease and often lead to underdiagnosis and late intervention. This issue is critical in that it is important to understand both the etiology and chronicity of renal dysfunction before liver transplantation because the treatment clearly varies, especially with respect to simultaneous liver-kidney (SLK) transplantation. Because of the scarcity of available grafts, identifying appropriate candidates for SLK transplantation is crucial. Hepatorenal syndrome is common in liver transplant candidates; however, other etiologies of renal dysfunction need to be considered. Renal dysfunction after liver transplantation is common and may have an acute or chronic presentation. Although calcineurin inhibitors (CNIs) have been associated with post-liver transplant nephrotoxicity, their role may be overestimated, and other contributing etiologies should remain in a clinician's differential diagnosis. Alternatives to CNIs have been evaluated; however, a safe immunosuppressive regimen that achieves the preservation of renal function in liver transplant recipients remains to be established. In this review of the literature, renal dysfunction in the setting of liver transplantation is evaluated, and the critical issues that are barriers to improved outcomes are highlighted.

Immunosuppression in HCV-positive liver-transplant recipients.

PURPOSE OF REVIEW: The purpose of this review is to evaluate the historical and recent literature as it pertains to current immunosuppression regimens in hepatitis C virus (HCV)-positive (+) liver-transplant recipients. RECENT FINDINGS: Recent findings suggest that there are unique differences between HCV transplant recipients and non-HCV transplant recipients, not only in the graft's inflammatory response, but also to the treatments used to prevent and combat rejection. SUMMARY: HCV (+) transplant recipients present unique challenges. Over the years, there has been progress but there is clearly no consensus regarding the optimal immunosuppressive medications or drug regimens; however, there continues to be advancements in the management of patients with HCV. Though current studies do not provide clear evidence as to optimal immunosuppression, they do identify questions ideally addressed by large, randomized controlled trials.