Rapidly progressing severe coagulopathy and thrombocytopenia in extreme anorexia nervosa patient with small bowel strangulation: A case report.

INTRODUCTION: Anorexia nervosa (AN) is characterized by severe dietary restriction or other weight loss behaviors motivated by a strong fear of body weight gain and a disturbed body image. In this paper, we report a case of an extreme AN patient, in whom severe coagulopathy and thrombocytopenia rapidly progressed with strangulation obstruction. PRESENTATION OF CASE: A female patient in her 20's with previous history of AN came to our hospital complaining acute onset abdominal pain. Her body mass index at presentation was 12.1 kg/m2; thus, she was classified as an "extreme" AN (BMI <15) according to DSM-5 classification. Abdominal CT scan showed small bowel obstruction without strangulation. Although severe leukopenia appeared soon after admission, platelet count and coagulation tests were maintained relatively well. Due to her severe malnutrition, we proposed nutritional therapy and subsequent surgical adhesiolysis; however, she refused any kind of nutritional therapy. On admission day 13, she suddenly developed a strangulation obstruction. At the same time, severe coagulopathy and thrombocytopenia rapidly progressed. Emergency laparotomy was performed using a massive blood transfusion. Bowel strangulation was successfully released; however, intraabdominal bleeding was repeated postoperatively and three more operations were required until complete hemostasis and abdominal closure. After long rehabilitation, she was discharged from our hospital on day 116. DISCUSSION: The medical comorbidities associated with AN extend various organ systems; among them, the hematologic complication can be a life-threatening problem during emergency surgery for a patient with AN. CONCLUSION: Knowledge about the pathophysiology of AN is quite essential for all surgeons.

Diagnosis and outcomes of cachexia in Asia: Working Consensus Report from the Asian Working Group for Cachexia.

Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three-round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3-6 month period and suggested a tentative cut-off value of 21 kg/m2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ-5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient-reported outcomes. The AWGC consensus offers a comprehensive definition and user-friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co-morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.

Pretransplant Renal Dysfunction Negatively Affects Prognosis After Living Donor Liver Transplantation: A Single-Center Retrospective Study.

BACKGROUND: To evaluate the influence of preoperative renal function on prognosis after living donor liver transplantation (LDLT). METHODS: Living donor liver transplantation cases were categorized into 3 groups as follows: renal failure with hemodialysis (HD; n = 42), renal dysfunction (RD; n = 94) (glomerular filtration rate <60 mL/min/1.73 m2), and normal renal function (NF; n = 421). The study used no prisoners, and participants were neither coerced nor paid. The manuscript complies with the Helsinki Congress and the Declaration of Istanbul. RESULTS: Five-year overall survival (OS) rates were 59.0%, 69.3%, and 80.0% in the HD, RD, and NF groups, respectively (P < .01). The frequency of bacteremia within 90 days after LDLT was 76.2%, 37.2%, and 34.7%, respectively (P < .01 in HD vs RD and HD vs NF). Patients with bacteremia showed a worse outcome than those without (1-year OS, 65.6% vs 93.3%), thus corroborating the poor prognosis in the HD group. The high frequency of bacteremia in the HD group was mainly attributable to health care-associated bacterium, such as coagulase-negative Staphylococci, Enterococcus spp., and Pseudomonas aeruginosa. In the HD group, HD was started within 50 days before LDLT for acute renal failure in 35 patients, of which 29 (82.9%) successfully withdrew from HD after LDLT and demonstrated better prognosis (1-year OS, 69.0% vs 16.7%) than those who continued HD. CONCLUSIONS: Preoperative renal dysfunction is associated with poor prognosis after LDLT, possibly due to a high incidence of health care-associated bacteremia.

The first case of robotic-assisted transabdominal retrorectus repair for incisional hernia in Japan.

Extraperitoneal mesh repair for ventral hernia has garnered attention and its rate has been increasing due to concerns for the potential complications of intraperitoneal mesh repair. Recently, robotic-assisted ventral hernia repair is highlighted as a solution to the technically demanding nature of laparoscopic transabdominal or enhanced-view totally extraperitoneal retrorectus ventral hernia repair. A 78-year-old man, who had undergone robot-assisted radical prostatectomy 10 months earlier, presented with an incisional hernia of European Hernia Society Classification M3W2, length 4 cm, width 5 cm with rectus diastasis. A right single-docking robotic-assisted transabdominal retrorectus repair was performed using a 21 by 14 cm self-gripping mesh and anterior wall reconstruction was done by 0 barbed nonabsorbable running suture. There were no complications and recurrence observed during a 7 months postoperative period. Single-docking robotic-assisted transabdominal retrorectus repair was considered a good option for midline moderate-size incisional hernias from the point of view of the ease of suturing, adequateness of dissection and prevention of bowel injury.

Implementation of advance care planning decision aids for patients undergoing high-risk surgery: a field-testing study.

BACKGROUND: Patients undergoing high-risk surgery are at a risk of sudden deterioration of their health. This study aimed to examine the feasibility of the development of two patient decision aids (PtDAs) to assist patients undergoing high-risk surgeries in informed decision-making about their medical care in a crisis. METHODS: This field testing implemented two PtDAs that met the international criteria developed by the researchers for patients before surgery. Study participants were patients scheduled to be admitted to the intensive care unit after surgery at one acute care hospital in Japan and their families. The study used a mixed-methods approach. The primary outcome was patients' decision satisfaction evaluated by the SURE test. Secondary outcomes were the perception of the need to discuss advance care planning (ACP) before surgery and mental health status. The families were also surveyed on their confidence in proxy decision-making (NRS: 0-10, quantitative data). In addition, interviews were conducted after discharge to assess the acceptability of PtDAs. Data were collected before (preoperative outpatients, baseline: T0) and after providing PtDAs (in the hospital: T1) and following discharge (T2, T3). RESULTS: Nine patients were enrolled, of whom seven agreed to participate (including their families). The SURE test scores (mean ± SD) were 2.1 ± 1.2 (T0), 3.4 ± 0.8 (T2), and 3.9 ± 0.4 (T3). The need to discuss ACP before surgery was 8.7 ± 1.3 (T1) and 9.1 ± 0.9 (T2). The degree of confidence in family surrogate decision-making was 6.1 ± 2.5 (T0), 7.7 ± 1.4 (T1), and 8.1 ± 1.5 (T2). The patients reported that using PtDAs provided an opportunity to share their thoughts with their families and inspired them to start mapping their life plans. Additionally, patients wanted to share and discuss their decision-making process with medical professionals after the surgery. CONCLUSIONS: PtDAs supporting ACP in patients undergoing high-risk surgery were developed, evaluated, and accepted. However, they did not involve any discussion of patients' ACP treatment wishes with their families. Medical providers should be coached to provide adequate support to patients. In the future, larger studies evaluating the effectiveness of PtDAs are necessary.

Perioperative Oral ß-Hydroxy-ß-Methylbutyrate Supplementation Ameliorates Sarcopenia in Rats Undergoing Major Hepatectomy.

ß-Hydroxy-ß-methylbutyrate (HMB), a metabolite of leucine, is known to increase muscle mass and strength. However, the effect of perioperative HMB supplementation in liver surgery is unclear. Moreover, the impact of HMB on the skeletal muscle fiber type also remains unclear. We investigated the impact of HMB on the body composition and skeletal muscle fiber type in sarcopenic rats undergoing major hepatectomy. Nine-week-old male F344/NSlc rats were maintained in hindlimb suspension (HLS) and were forcedly supplemented with HMB calcium salt (HMB-Ca, 0.58 g/kg×2 times) or distilled water in addition to free feeding. After 2 wk of HLS, the rats underwent 70% hepatectomy and were sacrificed 3 d after surgery. Body composition factors and the proportion of slow-twitch fibers in hindlimb muscles were evaluated. HMB maintained the body composition and hindlimb force and acted against their deterioration in sarcopenic rats, exerting a particular effect on lean mass weight, which was significant. In the histological study, HMB significantly increased the proportion of slow-twitch fibers in the soleus (p=0.044) and plantaris (p=0.001) of sarcopenic rats. HMB ameliorated deterioration of the body composition and increased the proportion of slow-twitch fibers in sarcopenic rats undergoing major hepatectomy.

Factors associated with early postoperative exercise tolerance after living-donor liver transplantation.

BACKGROUND: Physical dysfunction, including exercise intolerance, is a major factor for delayed societal reintegration for patients who underwent living-donor liver transplantation (LDLT). However, what may contribute to early postoperative physical function is not well known. The purpose of this study is to elucidate the perioperative factors affecting early posttransplant exercise intolerance. METHODS: 103 consecutive patients who underwent LDLT were enrolled, and 68 patients were retrospectively analyzed. We examined the relationship between postoperative exercise tolerance evaluated by a 6-minute walking distance (6MWD) at discharge after surgery and demographic data, surgical information, preoperative physical function, clinical course, and the postoperative decline in physical function with univariate and multivariate analyses. RESULTS: Almost all patients were discharged within 3 months after surgery. The postoperative 6MWD was 408 ± 94 m (68 [61-84]% of the predicted value), and patients who had a low %6MWD at discharge had significantly lower preoperative physical function than patients who had a high %6MWD at discharge (grip strength: 29.8 ± 8.9 kgf vs. 23.0 ± 8.8 kgf, P < .01, knee extensor strength: 138.9 ± 59.4 Nm vs. 95.2 ± 42.1 Nm, P < .01). Multivariate analysis revealed that preoperative knee extensor strength (standardized ß = 0.35, P < .01) and first postoperative walking day (standardized ß = -0.22, P = .04) were independently associated with the postoperative %6MWD. CONCLUSION: These results suggest that maintaining preoperative muscle strength and allowing for early postoperative mobilization might help to enhance the recovery of physical function and facilitate the patient's social reintegration after LDLT.

Intraoperative High Fraction of Inspiratory Oxygen is Independently Associated with Worse Outcome After Living-Donor Liver Transplantation: A Retrospective Study.

BACKGROUND: Ischemia and reperfusion injury is an important factor that determines graft function after liver transplantation, and oxygen plays a crucial role in this process. However, the relationship between the intraoperative high fraction of inspiratory oxygen (FiO2) and living-donor-liver-transplantation (LDLT) outcome remains unclear. PATIENTS AND METHODS: A total of 199 primary adult-to-adult LDLT cases in Kyoto University Hospital between January 2010 and December 2017 were enrolled in this study. The intraoperative FiO2 was averaged using the total amount of intraoperative oxygen and air and defined as the calculated FiO2 (cFiO2). The cutoff value of cFiO2 was set at 0.5. RESULTS: Between the cFiO2 <0.5 (n = 156) and ≥0.5 group (n = 43), preoperative recipients' background, donor factors, and intraoperative parameters were almost comparable. Postoperatively, the cFiO2 ≥0.5 group showed a higher early allograft dysfunction (EAD) rate (P = 0.049) and worse overall graft survival (P = 0.036) than the cFiO2 <0.5 group. Although the cFiO2 ≥0.5 was not an independent risk factor for EAD in multivariable analysis (OR 2.038, 95%CI 0.992-4.186, P = 0.053), it was an independent risk factor for overall graft survival after LDLT (HR 1.897, 95%CI 1.007-3.432, P = 0.048). CONCLUSION: The results of this study suggest that intraoperative high FiO2 may be associated with worse graft survival after LDLT. Avoiding higher intraoperative FiO2 may be beneficial for LDLT recipients.

Muscularity Defined by the Combination of Muscle Quantity and Quality is Closely Related to Both Liver Hypertrophy and Postoperative Outcomes Following Portal Vein Embolization in Cancer Patients.

BACKGROUND: Portal vein embolization (PVE) is a common procedure for preventing hepatic insufficiency after major hepatectomy. While evaluating the body composition of surgical patients is common, the impact of muscularity defined by both muscle quantity and quality on liver hypertrophy after PVE and associated outcomes after major hepatectomy in patients with hepatobiliary cancer remain unclear. METHODS: This retrospective review included 126 patients who had undergone hepatobiliary cancer resection after PVE. Muscularity was measured on preoperative computed tomography images by combining the skeletal mass index and intramuscular adipose content. Various factors including the degree of hypertrophy (DH) of the future liver remnant and post-hepatectomy outcomes were compared according to muscularity. RESULTS: DH did not differ by malignancy type. Patients with high muscularity had better DH after PVE (P = 0.028), and low muscularity was an independent predictor for poor liver hypertrophy after PVE [odds ratio (OR), 3.418; 95% confidence interval (CI), 1.129-10.352; P = 0.030]. In subgroup analyses in which patients were stratified into groups based on primary hepatobiliary tumors and metastases, low muscularity was associated with higher incidence of post-hepatectomy liver failure (PHLF) ≥ grade B (P = 0.018) and was identified as an independent predictor for high-grade PHLF (OR 3.931; 95% CI 1.113-13.885; P = 0.034) among the primary tumor group. In contrast, muscularity did not affect surgical outcomes in patients with metastases. CONCLUSIONS: Low muscularity leads to poor liver hypertrophy after PVE and is also a predictor of PHLF, particularly in primary hepatobiliary cancer.

Guidelines for Perioperative Care for Liver Transplantation: Enhanced Recovery After Surgery (ERAS) Recommendations.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a multimodal, evidence-based, program of care developed to minimize the response to surgical stress, associated with reduced perioperative morbidity and hospital stay. This study presents the specific ERAS Society recommendations for liver transplantation (LT) based on the best available evidence and on expert consensus. METHODS: PubMed and ClinicalTrials.gov were searched in April 2019 for published and ongoing randomized clinical trials on LT in the last 15 y. Studies were selected by 5 independent reviewers and were eligible if focusing on each validated ERAS item in the area of adult LT. An e-Delphi method was used with an extended interdisciplinary panel of experts to validate the final recommendations. RESULTS: Forty-three articles were included in the systematic review. A consensus was reached among experts after the second round. Patients should be screened for malnutrition and treated whenever possible. Prophylactic nasogastric intubation and prophylactic abdominal drainage may be omitted, and early extubation should be considered. Early oral intake, mobilization, and multimodal-balanced analgesia are recommended. CONCLUSIONS: The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the e-Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Corticosteroid-associated osteonecrosis of the femoral head after orthotopic liver transplantation and the outcomes of subsequent total hip arthroplasty.

BACKGROUND: Corticosteroids are essential for immunosuppression after orthotopic liver transplantation (OLT), but also have many side effects. Osteonecrosis of the femoral head (ONFH) is one of the most serious complications requiring prostheses. However, few studies have investigated ONFH after OLT. The purpose of this study is to survey the incidence of corticosteroid-induced ONFH after OLT and the outcomes of total hip arthroplasty (THA). METHODS: Between January 2001 and December 2010, a series of 926 patients underwent OLT at our Hospital. A retrospective analysis was performed on a total of 738 patients who survived at least 2 years after OLT. The incidence of symptomatic ONFH, the interval from OLT to the initial diagnosis of ONFH, and the cumulative dose of corticosteroids were analyzed. The side effects related to OLT, such as other osteonecrosis lesions, osteoporotic fractures, and infection, were monitored. For patients who underwent THA, radiological findings and Japanese Orthopaedic Association (JOA) scores were evaluated. RESULTS: ONFH occurred in 10 patients (13 hips) (6 men [7 hips], 4 women [6 hips]), with an incidence of 1.36%. The average age at OLT was 51.4 years (range, 31-61 years). The average interval from OLT to ONFH was 86.7 months (range, 22-155 months). The average cumulative dose of corticosteroids was 7274 mg (range, 1342-29,514 mg). Twenty patients suffered from side effects related to OLT. Seven patients (8 hips) underwent THA. No adverse events including infection arose during the perioperative process. One hip dislocated, and one femoral stem displayed a radiolucent line. The average JOA score improved from 45.4 (range, 25-76) preoperatively to 86.9 (range, 73-99) at final follow-up. No patients required revision surgery. CONCLUSIONS: The incidence of symptomatic ONFH after OLT was 1.36%. Once the graft function becomes stable, THA can be a safe and effective treatment option for patients with ONFH after OLT.

Identifying Patients Who May Benefit from Liver Resection Compared to Living Donor Liver Transplantation for Hepatocellular Carcinoma Using 18F-FDG PET.

BACKGROUND: This study aimed to assess an oncologic setting where patients with hepatocellular carcinoma (HCC) could benefit from liver resection (LR) compared to living donor liver transplantation (LDLT) using 18F-fluorodeoxyglucose (FDG) positron emission tomography. METHODS: The consecutive data of patients with HCC who underwent 18F-FDG PET before LR (LR group, n = 314) and LDLT (LDLT group, n = 65) between 2003 and 2015 were retrospectively analyzed. Tumor 18F-FDG avidity was quantified as the tumor to liver standardized uptake value ratio (TLR, cut-off value was defined at 2). Multivariate analysis was performed to assess significant preoperative tumor factors in the LR group. Survival outcomes between the two groups were stratified by these factors. RESULTS: The 5-year overall survival (OS: 56.9% vs. 73.8%, LR vs. LDLT, p < 0.001) and recurrence-free survival rate (RFS: 27.4% vs. 70.7%, p < 0.001) were significantly better in the LDLT group compared to the LR group. In the LR study, multivariate analysis identified TLR and tumor multiplicity as significant preoperative tumor factors for OS. In patients with solitary and TLR < 2 HCC, the 5-year OS rate was not significantly different between the LR and LDLT groups (70.3% vs. 71.8%, p = 0.352); meanwhile, RFS rate was better in the LDLT group (34.3% vs. 71.8%, p = 0.001). CONCLUSIONS: LDLT is associated with better long-term outcomes than LR in patients with HCC; however, selected patients with solitary and TLR < 2 HCC may benefit from LR.

Evaluation of the Intention-to-Treat Benefit of Living Donation in Patients With Hepatocellular Carcinoma Awaiting a Liver Transplant.

Importance: Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC). Objective: To investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription. Design, Setting, and Participants: This multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020. Main Outcomes and Measures: Intention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created. Results: A total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated. Conclusions and Relevance: This study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.

Efficacy and Safety of Everolimus With Reduced Tacrolimus in Liver Transplant Recipients: 24-month Results From the Pooled Analysis of 2 Randomized Controlled Trials.

BACKGROUND AND METHODS: Data from 2 randomized liver transplant trials (N = 772; H2304 [deceased donor, n = 488], H2307 [living donor, n = 284]) were pooled to further evaluate the efficacy and safety of everolimus with reduced tacrolimus (EVR + rTAC) versus standard tacrolimus (sTAC) regimen at month 24. RESULTS: EVR + rTAC was comparable to sTAC for composite efficacy failure of treated biopsy-proven acute rejection, graft loss, or death (9.8% versus 10.8%; difference, -1.0%; 95% confidence interval, -5.4 to 3.4; P = 0.641) at month 24. EVR + rTAC was superior to sTAC for the mean change in estimated glomerular filtration rate (eGFR) from randomization to month 24 (-8.37 versus -13.40 mL/min/1.73 m2; P = 0.001). A subanalysis of renal function by chronic kidney disease (CKD) stage at randomization showed significantly lower decline in eGFR from randomization to month 24 for patients with CKD stage 1/2 (eGFR ≥ 60 mL/min/1.73 m2) in EVR + rTAC group versus sTAC (-12.82 versus -17.67 mL/min/1.73 m2, P = 0.009). In patients transplanted for hepatocellular carcinoma (HCC) beyond Milan criteria, HCC recurrence was numerically lower although not statistically significant with EVR + rTAC versus sTAC group (5.9% [1 of 17] versus 23.1% [6 of 26], P = 0.215), while comparable in patients within Milan criteria (2.9% [3 of 102] versus 2.1% [2 of 96], P = 1.000), irrespective of pretransplant alpha-fetoprotein levels. CONCLUSIONS: EVR + rTAC versus sTAC showed comparable efficacy and safety with significantly better renal function, particularly in patients with normal/mildly decreased renal function (CKD stage 1/2) at randomization and a trend toward lower HCC recurrence in patients transplanted with HCC beyond Milan at month 24. Further long-term data would be required to confirm these results.