Evaluation of terlipressin-related patient outcomes in hepatorenal syndrome-acute kidney injury using point-of-care echocardiography.

BACKGROUND AND AIMS: Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary complications. We analyzed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo) and cardiac and renal biomarkers. APPROACH: Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6 hours of admission, at the time of starting terlipressin (48 h), and at 72 hours. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic cardiomyopathy (CCM) was defined per 2020 criteria. RESULTS: One hundred and forty patients were enrolled (84% men, 59% alcohol-associated disease, mean MELD-Na 25±SD 5.6). A median daily dose of infused terlipressin was 4.3 (interquartile range: 3.9-4.6) mg/day; mean duration 6.4 ± SD 1.9 days; the complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cutoffs for prediction of terlipressin nonresponse were cardiac variables [ratio of early mitral inflow velocity and mitral annular early diastolic tissue doppler velocity > 12.5 (indicating increased left filling pressures, C-statistic: 0.774), tissue doppler mitral velocity < 7 cm/s (indicating impaired relaxation; C-statistic: 0.791), > 20.5% reduction in cardiac index at 72 hours (C-statistic: 0.885); p < 0.001] and pretreatment biomarkers (CysC > 2.2 mg/l, C-statistic: 0.640 and N-terminal proBNP > 350 pg/mL, C-statistic: 0.655; p <0.050). About 6% of all patients with HRS-AKI and 26% of patients with CCM had pulmonary edema. The presence of CCM (adjusted HR 1.9; CI: 1.8-4.5, p = 0.009) and terlipressin nonresponse (adjusted HR 5.2; CI: 2.2-12.2, p <0.001) were predictors of mortality independent of age, sex, obesity, DM-2, etiology, and baseline creatinine. CONCLUSIONS: CCM and reduction in cardiac index, reliably predict terlipressin nonresponse. CCM is independently associated with poor survival in HRS-AKI.

Predictors of renal recovery in recipients of liver transplant alone who met 2017 simultaneous liver-kidney transplant criteria.

BACKGROUND: Severe renal dysfunction is common among liver transplant (LT) candidates and often prompts simultaneous liver-kidney transplantation (SLKT) consideration. In view of 2017 United Network of Organ Sharing (UNOS) criteria for SLKT, we investigated the likelihood and predictors of renal recovery among patients who met the aforementioned criteria yet received liver transplant alone (LTA). METHODS: We retrospectively analyzed relative renal recovery (RRR; increase in eGFR to >30 ml/min) in adult LTA recipients between 1/2009 and 1/2019. RESULTS: Of 1165 LT recipients, 54 met 2017 UNOS criteria, with 37 receiving LTA. RRR occurred in 84% of LTA recipients, none of whom had pre-LT eGFR <20 ml/min. Sustained RRR (>180 days) occurred in 43% of patients. While prolonged pre-LT severe renal impairment (eGFR <30 ml/min) predicted failure to have sustained RRR (HR .19 per 90-day, CI .04-.87, p < .005), having an eGFR measurement of >30 ml/min within 90 days pre-LT (HR 5.52, CI 1.23-24.79, p .01) associated with achieving sustained RRR. Sustained RRR was protective against the composite outcome of renal replacement therapy, kidney transplant, and death (HR .21, p .01). CONCLUSION: LT candidates who meet 2017 UNOS criteria for SLKT yet undergo LTA can still have relative renal recovery post-LT, exceeding 80% on short-term follow-up and 40% on long-term follow-up. eGFR trends within 90 days pre-LT can predict sustained renal recovery, which appears protective of adverse outcomes. These recovery rates advocate for applying the more restrictive criteria for SLKT outlined in this article and increasing utilization of the safety net (SN) policy for those who do not meet the proposed criteria.

Waitlist mortality and post-liver transplant outcomes of pediatric patients with hepatocellular carcinoma and hepatoblastoma in the United States.

BACKGROUND: Liver transplantation (LT) is offered in cases of advanced disease for both pediatric patients with hepatoblastoma (HBL) and those with hepatocellular carcinoma (HCC). Current United States organ allocation priorities differ between the two groups. METHODS: We retrospectively examined the waitlist and posttransplant outcomes of pediatric LT candidates with HBL and HCC using the United Network for Organ Sharing registry (February 2002 to September 2020). RESULTS: Six hundred sixty-eight children with HBL and 95 children with HCC listed for first LT were identified. Patients with HBL were younger (p < .001), had lower laboratory Model for End-stage Liver Disease (MELD)/Pediatric End-stage Liver Disease (PELD) scores (p < .001), and had lesser proportion with encephalopathy (p = .01). Patients with HCC had an increased risk of waitlist mortality in univariable (unadjusted subdistribution hazard ratio [sHR] = 4.37, 95% confidence interval [CI], 2.01-9.51, p < .001) and multivariable competing risk regression (adjusted sHR = 3.08, 95% CI 1.13-8.37, p = .03) accounting for age and laboratory MELD/PELD score. Five hundred ninety-five children underwent LT for HBL and 76 for HCC. Patients transplanted for HBL had a significantly higher proportion with status 1B exception (71.3% vs. 7.9%, p < .001). No difference was observed in patient (unadjusted log-rank test, p = .52; adjusted hazard ratio [HR] = 0.77, 95% CI, 0.40-1.48, p = .43) or graft survival (unadjusted log-rank test, p = .93; adjusted HR = 0.74, 95% CI 0.42-1.33, p = .32) between HCC and HBL recipients. CONCLUSION: Waitlist mortality for pediatric LT candidates with HCC is significantly higher than for HBL, while posttransplant patient and graft survival are similar. This highlights an opportunity to improve equitable prioritization for children with HCC who may have reduced access to size-appropriate deceased donor organs and less effective bridge-to-transplant therapies.

North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

Personalizing Diabetes Management in Liver Transplant Recipients: The New Era for Optimizing Risk Management.

Post-transplant diabetes mellitus (PTDM) is a significant contributor to morbidity and mortality in liver transplant recipients (LTRs). With concurrent comorbidities and use of various immunosuppression medications, identifying a safe and personalized regimen for management of PTDM is needed. There are many comorbidities associated with the post-transplant course including chronic kidney disease, cardiovascular disease, allograft steatosis, obesity, and de novo malignancy. Emerging data suggest that available diabetes medications may carry beneficial or, in some cases, harmful effects in the setting of these co-existing conditions. Sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists have shown the most promising beneficial results. Although there is a deficiency of LTR-specific data, they appear to be generally safe. Effects of other medications are varied. Metformin may reduce the risk of malignancy. Pioglitazone may be harmful in patients combatting obesity or heart failure. Insulin may exacerbate obesity and increase the risk of developing malignancy. This review thoroughly discusses the roles of these extra-glycemic effects and safety considerations in LTRs. Through weighing the risks and benefits, we conclude that alternatives to insulin should be strongly considered, when feasible, for personalized long-term management based on risk factors and co-morbidities.

Pancreatic adenocarcinoma in liver transplant recipients: a case series.

BACKGROUND: Malignancy is one of the known leading causes of death among long-term liver transplantation (LT) survivors. Pancreatic cancer has an incidence of 7.6/100,000 in North America and constitutes a diagnostic challenge post-LT. METHODS: This is a single-center, retrospective review of the electronic health records (EHRs) of LT recipients with pancreatic adenocarcinoma (1990-2019). The prevalence of pancreatic adenocarcinoma in our institutional non-LT population was assessed using an institutional de-identified database (Synthetic Derivative). RESULTS: Six out of 2,232 (0.27%) LT recipients were diagnosed with pancreatic adenocarcinoma. Median age at diagnosis was 66.0 years (IQR, 57.8-71.8 years). Median time from LT to pancreatic adenocarcinoma diagnosis was 8.9 years (IQR, 4.7-16.2 years), the median size on imaging was 3.2 cm (IQR, 3.1-4.7 cm), and all tumors were located on the head of the pancreas. Three patients underwent surgical resection (one with adjuvant chemotherapy), two underwent palliative care, and one palliative chemotherapy with gemcitabine and abraxane. Over a median follow-up of 220.5 days (IQR, 144.8-399.5 days), all six patients died due to disease progression (100%). Pancreatic adenocarcinoma was diagnosed in 5,033 out of 2,484,772 (0.20%) individuals in the Synthetic Derivative. CONCLUSIONS: Our findings identified an increased incidence of pancreatic adenocarcinoma following LT compared to the general population.

Liver Transplantation for Cholangiocarcinoma: Charting a Path With Lessons Learned From Center Experience.

BACKGROUND: While liver transplantation (LT) with neoadjuvant chemoradiation is increasingly utilized for the management of unresectable cholangiocarcinoma (CCA), data on post-LT survival are limited. METHODS: We identified 844 patients who underwent LT (2002-2019) for nonincidental (CCA listing) or incidental (CCA on explant, not at listing) CCA in the Scientific Registry of Transplant Recipients. Kaplan-Meier and multivariable proportional hazards regression methods evaluated the effects of patient characteristics, donor type, transplant era (before/after 2010), and center volume (center-level CCALTs/active year) on the risk of graft failure and patient mortality. RESULTS: One center performed >12 CCALTs/y, and the rest performed ≤4. Five-year graft survival was 50.6%. Multivariable models demonstrated laboratory model of end-stage liver disease ≥40 versus <15 and center volumes of 1, >1 to ≤2, and >2 to ≤4 CCALTs/y compared to >12 were associated with increased risk of graft failure and mortality (all P ≤ 0.002). Extra vessel use was associated with center volume. Among all recipients, extra vessel use occurred in 55.4% of CCALTs performed at the highest volume center and in 14.0% of cases at centers having ≤4 CCAs/y (P < 0.05). CONCLUSIONS: Center volume-related differences in outcomes and extra vessel use highlight the importance of establishing a unified, effective treatment protocol and the potential utility of regionalization of LT for CCA.

Comparison of Survival Outcomes After Deceased Donor Split Versus Whole Liver Transplant for Hepatocellular Carcinoma.

OBJECTIVES: To mitigate waiting time forlivertransplant for hepatocellular carcinoma, partial or split liver transplant has been utilized. There was concern that regeneration of these grafts would negatively affect oncologic outcomes. MATERIALS AND METHODS: We compared posttransplant graft survival between hepatocellular carcinoma whole livertransplant and partial/splitlivertransplant using Scientific Registry of Transplant Recipients data (2002-2017). The 330 partial/split liver transplant recipients were compared with a logistic regressionbased propensity score 1:1 matched whole liver transplant cohort (n = 330) and a random unmatched whole livertransplant cohort(n = 4143). Kaplan-Meier and multivariable Cox regression models evaluated the effects of partial/split and whole liver transplant on survival. RESULTS: Unadjusted analysis demonstrated no difference in graft survivalbetween thepartial/split and whole liver transplant cohorts (overall log-rank P = .78). After adjustments for recipient age, last laboratory Modelfor End-stage LiverDisease score, hepatitisBviral infection co-diagnosis, liver donor risk index, donor historyofdiabetes, anddonorbodymass index category were made (all P ⟨ .05), multivariable analysis demonstrated no statistically significant difference in the risk of graftfailure in thepartial/splitlivertransplant cohort compared with either the matched or random whole livertransplant cohort (both P ≥ .23). CONCLUSIONS: Partial/split liver transplant was not an independent risk factor for graft failure. Additional studies are needed to further elucidate differences in these populations to determine the "right" candidate for partial/split liver transplant.

Bariatric surgery proves long-term benefit in patients with cirrhosis.

BACKGROUND: Obesity is commonly observed in patients with cirrhosis, especially with the increasing prevalence of non-alcoholic steatohepatitis (NASH). Bariatric surgery has been avoided in these patients given concerns about increased perioperative risk; therefore, data are lacking regarding long-term outcomes. In this study, we aimed to evaluate the long-term outcomes of patients with cirrhosis who underwent bariatric surgery. METHODS: We reviewed the charts of adult patients with compensated cirrhosis who underwent bariatric surgery after they were prospectively enrolled between February 23, 2009 and November 9, 2011, and followed in a pilot study for evaluation of bariatric surgery outcomes. Only patients with more than 4 years of follow-up were included in the analysis. Data regarding their liver disease, metabolic status, and survival were collected. A descriptive analysis was performed. RESULTS: The cohort consisted of 10 patients, of whom 7 were females. The median post-surgical follow-up was 8.7 years (± 1.4 years). All patients had biopsy-proven NASH; two patients had concurrent, untreated hepatitis C infection. During the observation period, there was a mean weight loss of 24 kg (19.2% of total body weight pre surgery, P < 0.001) and only one patient regained weight to the baseline pre-surgical measurement. One patient who was not eligible for transplant developed hepatic encephalopathy 3 years after surgery and later died. The remainder of the patients did not have any hepatic decompensation, cardiovascular event, or mortality. Except for one patient with Gilbert syndrome, bilirubin was normal in all patients at last follow-up. CONCLUSIONS: Bariatric surgery in patients with compensated cirrhosis can lead to sustained weight loss and stable hepatic function on long-term follow-up.

Liver chemistries in glycogenic hepatopathy associated with type 1 diabetes mellitus: A systematic review and pooled analysis.

BACKGROUND & AIMS: Glycogenic hepatopathy (GH) in type 1 diabetes-mellitus (T1DM) is characterized by hepatomegaly and perturbations of liver chemistries (LC) that have not been well studied. Furthermore, misdiagnosis with other hepatic complications of T1DM, such as nonalcoholic fatty liver disease, has been described. We perform a systematic review of biopsy-proven GH reports in T1DM patients to identify LC patterns. METHODS: A systematic review identified reports of biopsy-proven GH in patients with T1DM. We excluded GH with other liver diseases, Mauriac syndrome, or GH without T1DM. Two reviewers screened and extracted studies and assessed their methodological quality. LC elevation magnitude, AST-to-ALT ratio, R-ratio to designate hepatocellular, cholestatic or mixed pattern of hepatic injury, and evolution of transaminases after glycemic control were analyzed. RESULTS: A total of 192 patients were included, with median age of 20 years, 73% adults, 66% females, median duration of T1DM before diagnosis 10 years, median adult body mass index 21 kg/m2 , median HbA1c 12%, at least one episode of diabetic ketoacidosis 70%, and hepatomegaly 92%. ALT and AST showed moderate-to-severe elevation in 78% and 76%, respectively, AST/ALT >1 in 71% and hepatocellular to mixed pattern of hepatic injury in 81%. Transaminase improvement with glycemic control was the rule, regardless of other factors in multilinear regression analysis. CONCLUSION: GH tends to have AST-predominant elevation with a median of 13 times the upper normal limit and R-ratio >2, which may distinguish it from other etiologies of AST-predominant LC elevation, and in the appropriate clinical context, may obviate invasive tests.

Management of hepatoblastoma in the United States: Can we do better?

BACKGROUND: Hepatoblastoma is the most common type of liver cancer in children. Refined therapeutic approaches combining risk-adapted chemotherapy along with complete tumor resection has led to improved survival. We aimed to evaluate the current state of management and outcomes for hepatoblastoma in the United States. METHODS: We retrospectively reviewed 794 children (<18 years) with hepatoblastoma from the National Cancer Database (2004-2015). We assessed overall survival by means of Kaplan-Meier method, log-rank tests, and multivariable Cox regression. RESULTS: Median age was 1 year (interquartile range: 0-2) and 170 (21.4%) presented with metastatic disease. Surgical resection was included in the treatment of 614 (77.3%) children (resection in 66.8% and liver transplantation in 10.6%). In the entire cohort, 95.1% of children received chemotherapy. In the surgical cohort, 575 (93.6%) received chemotherapy (34.5% neoadjuvant, 28.7% adjuvant, 30.5% both neoadjuvant and adjuvant). The 5-year overall survival was 76.6% for the entire cohort (no-surgery group: 55.3% vs surgery group: 82.8%). In multivariable analysis for all children, age ≥8 years (P = .009), metastasis (P < .001), surgery only (P = .009), and chemotherapy only (P < .001) were risk factors for mortality. In multivariable analysis for the surgical cohort, metastasis (P = .001), multifocality (P = .02), no chemotherapy (P = .03), and margin-positive resection (P = .02) were risk factors for mortality. CONCLUSION: Excellent long-term overall survival is achievable with a combination of chemotherapy and surgical resection when a negative resection margin is achieved. However, nearly a quarter of children never received surgical treatment, representing a potential opportunity for improvement in care.

Pharmacotherapy for Weight Loss in Cirrhosis and Liver Transplantation: Translating the Data and Underused Potential.

BACKGROUND AND AIMS: Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs). APPROACH AND RESULTS: While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed. CONCLUSIONS: The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications.

Surgical management of pediatric hepatocellular carcinoma: An analysis of the National Cancer Database.

PURPOSE: This study evaluates overall survival (OS) between liver transplantation (LT) and liver resection (LR), while assessing the effect of margin status, in children with hepatocellular carcinoma (HCC). METHODS: The National Cancer Database was queried (2004-2015) for children (<18 years) with non-metastatic HCC undergoing surgery. RESULTS: One hundred six children with HCC treated surgically (LT 34, LR 72) were identified. For T1 stage, no difference in OS was observed for LT vs. margin-negative liver resection [LR(-)] (log-rank, p = 0.47). For T2/T3/T4 stage, no difference in OS was observed for LT vs. LR(-) (log-rank, p = 0.08); both subgroups exhibited superior OS vs. margin-positive liver resection [LR(+)] (log-rank, LT vs. LR(+): p = 0.001 and LR(-) vs. LR(+): p = 0.04). On multivariable Cox regression: (i) histology (fibrolamellar vs. not) and T stage (T1 vs. T2/T3/T4) were not associated with OS (both p = 0.06), (ii) chemotherapy and size >5 cm were not associated with OS (both p ≥ 0.42), (iii) when compared to LT, both LR(-) (p = 0.03) and LR(+) (p = 0.001) were associated with increased likelihood of mortality. CONCLUSION: Although margin-negative resection may be obtained with LT or LR, early LT consultation is warranted for children at high risk of LR(+) regardless of Milan criteria due to the negative impact of LR(+) on OS. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: III.

Neurologic Toxicities Associated with Tumor Necrosis Factor Inhibitors and Calcineurin Inhibitors.

The calcineurin inhibitors cyclosporine and tacrolimus are used for their immunosuppressive effects. Neurotoxic side effects include tremor, paresthesia, and headache. Rarer neurotoxicities include seizure, posterior reversible encephalopathy syndrome, and encephalopathy. Tacrolimus tends to be more neurotoxic than cyclosporine. Management of toxicities associated with calcineurin inhibitors includes dose reduction, switching between calcineurin inhibitors, or switching to a calcineurin-free regimen. Tumor necrosis factor (TNF) inhibitors are used in autoimmune diseases. Management of demyelinating conditions among patients treated with anti-TNF should follow standard of care and withdrawal of the anti-TNF. This drug class should be avoided in patients with a history of demyelinating conditions.

Comparison of Wait-List Mortality Between Cholangiocarcinoma and Hepatocellular Carcinoma Liver Transplant Candidates.

Despite the divergent disease biology of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC), wait-list prioritization is identical for both diagnoses. We compared wait-list and posttransplant outcomes between CCA and HCC liver transplantation patients with Model for End-Stage Liver Disease exceptions using Scientific Registry of Transplant Recipients data. The 408 CCA candidates listed between 2003 and mid-2017 were matched to 2 HCC cohorts by listing date (±2 months, n = 816) and by Organ Procurement and Transplantation Network (OPTN) region and date (±6 months, n = 408). Cumulative incidence competing risk regression examined the effects of diagnosis, OPTN region, and center-level CCA listing volume on wait-list removal due to death/being too ill (dropout). Cox models evaluated the effects of diagnosis, OPTN region, center-level CCA volume, and waiting time on graft failure among deceased donor liver transplantation (DDLT) recipients. After adjusting for OPTN region and CCA listing volume (all P ≥ 0.07), both HCC cohorts had a reduced likelihood of wait-list dropout compared with CCA candidates (HCC with period matching only: subdistribution hazard ratio [SHR] = 0.63; 95% CI, 0.43-0.93; P = 0.02 and HCC with OPTN region and period matching: SHR = 0.60; 95% CI, 0.41-0.87; P = 0.007). The cumulative incidence rates of wait-list dropout at 6 and 12 months were 13.2% (95% CI, 10.0%-17.0%) and 23.9% (95% CI, 20.0%-29.0%) for CCA candidates, 7.3% (95% CI, 5.0%-10.0%) and 12.7% (95% CI, 10.0%-17.0%) for HCC candidates with region and listing date matching, and 7.1% (95% CI, 5.0%-9.0%) and 12.6% (95% CI, 10.0%-15.0%) for HCC candidates with listing date matching only. Additionally, HCC DDLT recipients had a 57% reduced risk of graft failure compared with CCA recipients (P < 0.001). Waiting time was unrelated to graft failure (P = 0.57), and there was no waiting time by diagnosis cohort interaction effect (P = 0.47). When identically prioritized, LT candidates with CCA have increased wait-list dropout compared with those with HCC. More granular data are necessary to discern ways to mitigate this wait-list disadvantage and improve survival for patients with CCA.

Population-Based Analysis of Hepatocellular Carcinoma in Children: Identifying Optimal Surgical Treatment.

BACKGROUND: Hepatocellular carcinoma (HCC) constitutes 0.5% of childhood malignancies and exhibits poor prognosis. Complete tumor extirpation either by partial liver resection (LR) or liver transplantation (LT) is the only curative treatment. Due to the poor initial outcomes of LT, LR has remained the mainstay of treatment for all but select children fulfilling the Milan criteria (originally designed for adults). METHODS: We conducted a retrospective cohort study of pediatric HCC patients (younger than 18 years of age) registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Survival analysis was performed by means of Kaplan-Meier methods, 2-sided stratified log-rank tests, and Cox regression models. RESULTS: Of 127 children with HCC, 46 did not undergo operation (36.2%), 32 underwent LT (25.2%), and 49 underwent LR (38.6%). Using the Kaplan-Meier method, the 5-year cancer-specific survival (CSS) rates for LT and LR were 87% and 63%, respectively. LT exhibited superior CSS vs LR (log-rank, p = 0.007). For T1 stage, LT showed equivalent CSS compared with LR (log-rank, p = 0.23), and for T2 and T3 stage, LT exhibited superior CSS (log-rank, p = 0.047 and p = 0.01, respectively). On multivariable Cox regression analysis, T3/T4 stage (adjusted hazard ratio 13.63; 95% CI, 2.9 to 64.07; p = 0.001), and LR (adjusted hazard ratio 7.51; 95% CI, 2.07 to 27.29; p = 0.002) were found to be independently associated with cancer-specific mortality. Fibrolamellar histology and lymph node status were not found to be associated with mortality. CONCLUSIONS: Our findings suggest that children diagnosed with nonmetastatic advanced-stage HCC have a favorable prognosis after LT compared with LR. Early inclusion of an LT consultation after the initial diagnosis is warranted, especially in children with unresectable HCC or when complete tumor extirpation with LR is not feasible.

Understanding and managing cardiovascular outcomes in liver transplant recipients.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is a common cause of mortality after liver transplantation. The transplant community is focused on improving long-term survival. Understanding the prevalence of CVD in liver transplant recipients, precipitating factors as well as prevention and management strategies is essential to achieving this goal. RECENT FINDINGS: CVD is the leading cause of death within the first year after transplant. Arrhythmia and heart failure are the most often cardiovascular morbidities in the first year after transplant which could be related to pretransplant diastolic dysfunction. Pretransplant diastolic dysfunction is reflective of presence of cirrhotic cardiomyopathy which is not as harmless as it was thought. Multiple cardiovascular risk prediction models have become available to aid management in liver transplant recipients. SUMMARY: A comprehensive prevention and treatment strategy is critical to minimize cardiovascular morbidity and mortality after liver transplant. Weight management and metabolic syndrome control are cornerstones to any prevention and management strategy. Bariatric surgery is an underutilized tool in liver transplant recipients. Awareness of 'metabolic-friendly' immunosuppressive regimens should be sought. Strict adherence to the cardiology and endocrine society guidelines with regard to managing metabolic derangements post liver transplantation is instrumental for CVD prevention until transplant specific recommendations can be made.

Recurrent or De Novo Allograft Steatosis and Long-term Outcomes After Liver Transplantation.

BACKGROUND: Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft, but the impact on survival and long-term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long-term posttransplant outcomes. METHODS: A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time-dependent) was used to evaluate differences in time to steatosis post-LT, patient survival, and cardiovascular outcomes. RESULTS: Mean age 51.9 ± 10.6 years, 64.6% males, underlying nonalcoholic steatohepatitis (NASH) (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.09-2.00; P = 0.014), hepatitis C virus diagnosis (HR, 2.49; 95% CI, 1.77-3.94; P < 0.001), and time-dependent BMI (per unit: HR, 1.08; 95% CI, 1.05-1.10; P < 0.001). Allograft steatosis was not associated with post-LT survival (P = 0.25) nor cardiovascular events (HR, 1.08; 95% CI, 0.73-1.59; P = 0.70). Underlying NASH associated with cardiovascular events (HR, 2.04; 95% CI, 1.37-3.04; P < 0.001). CONCLUSIONS: Allograft steatosis is common but not associated with survival or cardiovascular events in this study. Larger prospective studies are needed to better define the natural history of allograft steatosis.