Prognostic Evaluation and Survival Prediction for Combined Hepatocellular-Cholangiocarcinoma Following Hepatectomy.

Purpose: This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors. Materials and Methods: Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA. Results: A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival (PFS) was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival (HPFS), and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion and histologic compact type. Postoperative CA19-9, tumor necrosis, LVI, and close/positive margin were associated with poor overall survival. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively). Conclusion: The prognosis of cHCC-CCA is notably poor when combined with lymphovascular invasion. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.

Small graft size and hepatocellular carcinoma outcomes in living donor liver transplantation: a retrospective multicentric cohort study.

INTRODUCTION: This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and HCC outcomes. MATERIALS AND METHODS: Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014-2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR<0.7% vs. GRWR≥0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. RESULTS: The eligible cohort consisted of 2005 LDLT recipients (GRWR<0.7 [n=59] vs. GRWR≥0.7 [n=1946]). In the entire cohort, 5-year RFS was significantly lower in the GRWR<0.7 than in the GRWR≥0.7 group (66.7% vs. 76.7%, P =0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P =0.234). This trend was similar in the matched cohort ( P =0.014 for RFS and P =0.096 for HCC recurrence). In multivariable analyses, GRWR<0.7 was an independent risk factor for RFS (adjusted HR [aHR] 1.89, P =0.012), but the result was marginal for HCC recurrence (aHR 1.61, P =0.066). In the pretransplant tumor burden subgroup analysis, GRWR<0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P <0.001 for RFS; aHR 2.92, P =0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P <0.001 for RFS; aHR 2.61, P =0.019 for HCC recurrence). CONCLUSIONS: A GRWR<0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high.

TEMPORARY REMOVAL: A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure.

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Insights from Seoul National University Hospital's experience: a systematic review of pure laparoscopic donor hepatectomy progression.

Following its initial execution in November 2015, pure laparoscopic donor hepatectomy (PLDH) has gained acceptance as a conventional practice at Seoul National University Hospital (SNUH). It is noteworthy that a significant proportion of cases entail full right hepatectomies, which are acknowledged to be technically demanding. As expertise and knowledge have been accrued, the pure laparoscopic technique has been extended to encompass liver recipients as a viable option in SNUH. The aim of this review is to present the developmental progression of PLDH, with a focus on pure laparoscopic donor right hepatectomy (PLDRH), at SNUH. This includes the standardization process, which can be achieved by sharing the hospital's accumulated experience and previous reports. Various types of graft, including full right, left, left lateral section, and monosegment, were procured by pure laparoscopic technique. The criteria for selection were expanded to include donors with variations in the anatomy of the portal vein and bile duct. Additionally, the procedure of PLDRH was determined to be safe and viable for donors with high body mass index and larger graft weight. In conclusion, this review demonstrates the alterations implemented throughout our evolution from restricted to inclusive criteria for donor selection, leading to a complete shift from open surgery to pure laparoscopic procedures in donor hepatectomy and eventually pure laparoscopic living donor liver transplantation (LDLT) in recipient.

Donor body mass index over 30 is no barrier for pure laparoscopic donor right hepatectomy.

Backgrounds/Aims: Challenges arise when translating pure laparoscopic donor right hepatectomy (PLDRH) results from Asian to Western donors, due to differences in body mass index (BMI). This study compares the outcomes of PLDRH and conventional open donor right hepatectomy (CDRH) in donors with BMI over 30. Methods: Medical records of live liver donors (BMI > 30) undergoing right hepatectomy (2010-2021) were compared: 25 PLDRH cases vs. 19 CDRH cases. Donor and recipient demographics, operative details, and outcomes were analyzed. Results: PLDRH and CDRH had similar donor and recipient characteristics. PLDRH had longer liver removal and warm ischemic times, but a shorter post-liver removal duration than CDRH. Donor complication rates were comparable, with the highest complication being grade IIIa in PLDRH, necessitating needle aspiration for biloma on postoperative day 11. Fortunately, this donor fully recovered without additional treatment. No complications exceeding Clavien-Dindo grade IIIa occurred in either group. Recipient outcomes between the groups were similar. Conclusions: This study supports PLDRH as a viable option for donors with BMI over 30, challenging the notion that high BMI should deter considering PLDRH. The findings provide valuable insights into the safety and feasibility of PLDRH, encouraging further exploration of this technique in diverse donor populations.

Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection.

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex-mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

Criteria for selecting living liver donors to optimize recipient outcomes in pure laparoscopic donor right hepatectomy: a cohort study.

BACKGROUND: Although the adoption of pure laparoscopic donor hepatectomy has expanded driven by considerations of donor cosmesis and function, the criteria for selecting candidates for pure laparoscopic donor right hepatectomy (PLDRH) continue to be debated. This study aimed to delineate the distinctive characteristics of donors and recipients who underwent conventional open-donor right hepatectomy (CDRH) during the era of PLDRH. MATERIALS AND METHODS: The authors conducted a retrospective review of a prospectively collected single-centre database encompassing all right hepatectomies at Seoul National University Hospital from April 2016 to December 2021, a period during which there were no absolute contraindications for PLDRH. RESULTS: During the exclusive PLDRH period, there were still 63 cases of CDRH alongside 362 cases of PLDRH. The CDRH donors were older, had a lower estimated remnant liver volume, and a higher incidence of expected multiple openings in the portal vein and bile duct based on preoperative imaging compared with PLDRH donors. In the subgroup analysis, including only donors meeting two or more criteria (age ≥40 years, estimated remnant liver volume ≥35%, or multiple anticipated vessel openings), recipients in the PLDRH group exhibited significantly more early major complications ( P =0.029) compared with those in the CDRH group. CONCLUSION: As PLDRH gains traction in practice, it is essential to acknowledge that specific donor conditions, such as advanced age, limited remnant liver volume, and anticipation of multiple portal or bile duct openings, may merit contemplating CDRH as a means of optimizing recipient outcomes.

Impact of Preformed Donor-specific Antibodies in Comparison to ABO Incompatibility in Living Donor Liver Transplantation: A Propensity Score-Matched Analysis.

BACKGROUND: Immunological factors play a pivotal role in the outcomes of solid organ transplantation. We aimed to elucidate the effects of donor-specific antibodies (DSAs) and ABO compatibility on living donor liver transplantation (LDLT) outcomes. METHODS: A retrospective analysis was conducted on 584 LDLT recipients from 2015 to 2020. The recipients were stratified into 3 groups: ABO-compatible recipients without DSAs (group 1), ABO-compatible recipients with DSAs (group 2), and ABO-incompatible recipients without DSAs (group 3). Propensity score matching was used for balanced comparisons. RESULTS: In the matched comparisons, group 2 exhibited a higher incidence of T cell-mediated rejection compared with group 1 (22.7% versus 4.5%, P = 0.030). Despite this, the 5-y survival rates were similar between groups 1 and 2 (81.6% versus 95.5%, P = 0.085). Group 3, in comparison with group 1, showed elevated rates of cytomegalovirus infection (23.2% versus 7.3%, P = 0.008), T cell-mediated rejection (28.0% versus 7.3%, P = 0.001), and antibody-mediated rejection (13.4% versus 0%, P = 0.001). However, the survival rates were comparable between group 3 and group 1 (82.0% versus 86.5%, P = 0.220, respectively). Comparisons between group 2 and group 3 did not reveal significant differences in postoperative outcomes or survival rates (P > 0.05). CONCLUSIONS: DSA positivity and ABO incompatibility contribute to distinct posttransplant complications in LDLT. The integrated consideration of both factors in pretransplant assessment may enhance risk stratification and inform tailored interventions. Further research is required to corroborate these findings and provide mechanistic insights.

Safety and efficacy of early corticosteroid withdrawal in liver transplant recipients: A randomized controlled trial.

Backgrounds/Aims: Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. Methods: This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Results: Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. Conclusions: The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.

Risk factors for incisional hernia after liver transplantation in the era of mammalian target of rapamycin inhibitors use: a retrospective study of living donor liver transplantation dominant center in Korea.

Purpose: Incisional hernia (IH) is a common complication after liver transplantation (LT) with an incidence rate of 5% to 46%. This retrospective study aimed to evaluate the risk factors for IH development after LT in the era of mammalian target of rapamycin (mTOR) inhibitors use. Methods: Data on patients who underwent LT between 2015 and 2021 were retrospectively reviewed. The patients were divided into 2 groups (IH group and non-IH group) according to the postoperative occurrence of IH. Results: We analyzed data from 878 patients during the study period, with 28 patients (3.2%) developing IH. According to multivariate analysis, body mass index exceeding 25 kg/m2 and the use of mTOR inhibitors within the first month after LT were the sole significant factors for both IH occurrence and the subsequent need for repair operations. Notably, a history of wound complications, a Model for End-stage Liver Disease score, and the timing of LT-whether conducted during regular hours or at night-did not emerge as significant risk factors for IH after LT. Conclusion: Our study reveals a higher incidence of IH among obese patients following LT, often requiring surgical repair, particularly in cases involving mTOR inhibitor usage within the initial month after LT. Consequently, it is crucial to exercise increased vigilance, especially in obese patients, and exercise caution when considering early mTOR inhibitor administration after LT.

Comparison of postoperative ascites replacement strategies on time to first flatus after living donor liver transplantation: Albumin vs. lactated Ringer's solution.

INTRODUCTION: There is insufficient evidence regarding the optimal regimen for ascites replacement after living donor liver transplantation (LT) and its effectiveness. The aim of this study is to evaluate the impact of replacing postoperative ascites after LT with albumin on time to first flatus during recovery with early ambulation and incidence of acute kidney injury (AKI). METHODS: Adult patients who underwent elective living donor LT at Seoul National University Hospital from 2019 to 2021 were randomly assigned to either the albumin group or lactated Ringer's group, based on the ascites replacement regimen. Replacement of postoperative ascites was performed for all patients every 4 h after LT until the patient was transferred to the general ward. Seventy percent of ascites drained during the previous 4 h was replaced over the next 4 h with continuous infusion of fluids with a prescribed regimen according to the assigned group. In the albumin group, 30% of a total of 70% of drained ascites was replaced with 5% albumin solution, and remnant 40% was replaced with lactated Ringer's solution. In the lactated Ringer's group, 70% of drained ascites was replaced with only lactated Ringer's solution. The primary outcome was the time to first flatus from the end of the LT and the secondary outcome was the incidence of AKI for up to postoperative day 7. RESULTS: Among the 157 patients who were screened for eligibility, 72 patients were enrolled. The mean age was 63 ± 8.2 years, and 73.0 % (46/63) were male. Time to first flatus was similar between the two groups (66.7 ± 24.1 h vs. 68.5 ± 25.6 h, p = .778). The albumin group showed a higher glomerular filtration rate and lower incidence of AKI until postoperative day 7, compared to the lactated Ringer's group. CONCLUSIONS: Using lactated Ringer's solution alone for replacement of ascites after living donor LT did not reduce the time to first flatus and was associated with an increased risk of AKI. Further research on the optimal ascites replacement regimen and the target serum albumin level which should be corrected after LT is required.

Urinary microbiome-based metagenomic signature for the noninvasive diagnosis of hepatocellular carcinoma.

BACKGROUND: Gut microbial dysbiosis is implicated in chronic liver disease and hepatocellular carcinoma (HCC), but the role of microbiomes from various body sites remains unexplored. We assessed disease-specific alterations in the urinary microbiome in HCC patients, investigating their potential as diagnostic biomarkers. METHODS: We performed cross-sectional analyses of urine samples from 471 HCC patients and 397 healthy controls and validated the results in an independent cohort of 164 HCC patients and 164 healthy controls. Urinary microbiomes were analyzed by 16S rRNA gene sequencing. A microbial marker-based model distinguishing HCC from controls was built based on logistic regression, and its performance was tested. RESULTS: Microbial diversity was significantly reduced in the HCC patients compared with the controls. There were significant differences in the abundances of various bacteria correlated with HCC, thus defining a urinary microbiome-derived signature of HCC. We developed nine HCC-associated genera-based models with robust diagnostic accuracy (area under the curve [AUC], 0.89; balanced accuracy, 81.2%). In the validation, this model detected HCC with an AUC of 0.94 and an accuracy of 88.4%. CONCLUSIONS: The urinary microbiome might be a potential biomarker for the detection of HCC. Further clinical testing and validation of these results are needed in prospective studies.

Aborted living-donor liver transplantation in the real-world setting, lessons from 13 937 cases of Vanguard Multi-center Study of International Living Donor Liver Transplantation Group.

There are exceedingly uncommon but clearly defined situations where intraoperative abortions are inevitable in living-donor liver transplantation (LDLT). This study aimed to summarize the cases of aborted LDLT and propose a strategy to prevent abortion or minimize donor damage from both recipient and donor sides. We collected data from a total of 43 cases of aborted LDLT out of 13 937 cases from 7 high-volume hospitals in the Vanguard Multi-center Study of the International Living Donor Liver Transplantation Group and reviewed it retrospectively. Of the 43 cases, there were 24 recipient-related abortion cases and 19 donor-related cases. Recipient-related abortions included pulmonary hypertension (n = 8), hemodynamic instability (n = 6), advanced hepatocellular carcinoma (n = 5), bowel necrosis (n = 4), and severe adhesion (n = 1). Donor-related abortions included graft steatosis (n = 7), graft fibrosis (n = 5), primary biliary cholangitis (n = 3), anaphylactic shock (n = 2), and hemodynamic instability (n = 2). Total incidence of aborted LDLT was 0.31%, and there was no remarkable difference between the centers. A strategy to minimize additional donor damage by delaying the donor's laparotomy or trying to open the recipient's abdomen with a small incision should be effective in preventing some causes of aborted LDLT, such as pulmonary hypertension, advanced cancer, and severe adhesions.

Recurrence-free Survival After Liver Transplantation Versus Surgical Resection for Hepatocellular Carcinoma: Role of High-risk MRI Features.

BACKGROUND: This study aimed to evaluate recurrence-free survival (RFS) and overall survival (OS) after liver transplantation (LT) or liver resection (LR) for hepatocellular carcinoma (HCC) and perform subgroup analysis for HCC with high-risk imaging findings for recurrence on preoperative liver magnetic resonance imaging (MRI; high-risk MRI features). METHODS: We included patients with HCC eligible for both LT and LR and received either of the treatments between June 2008 and February 2021 from 2 tertiary referral medical centers after propensity score-matching. RFS and OS were compared between LT and LR using Kaplan-Meier curves with the log-rank test. RESULTS: Propensity score-matching yielded 79 patients in the LT group and 142 patients in the LR group. High-risk MRI features were noted in 39 patients (49.4%) in the LT group and 98 (69.0%) in the LR group. The Kaplan-Meier curves for RFS and OS were not significantly different between the 2 treatments among the high-risk group (RFS, P = 0.079; OS, P = 0.755). Multivariable analysis showed that treatment type was not a prognostic factor for RFS and OS ( P = 0.074 and 0.937, respectively). CONCLUSIONS: The advantage of LT over LR for RFS may be less evident among patients with high-risk MRI features.

Pure laparoscopic donor hepatectomy: Experience of 556 cases at Seoul National University Hospital.

Pure laparoscopic donor hepatectomy (PLDH) has become a routine procedure at Seoul National University Hospital, and the pure laparoscopic method is now being applied to liver recipients as well. This study aimed to review the procedure and outcomes of PLDH to identify any areas that required improvement. Data from 556 donors who underwent PLDH between November 2015 and December 2021 and their recipients were retrospectively reviewed. Among these, 541 patients underwent pure laparoscopic donor right hepatectomy (PLDRH). The mean hospital stay of the donor was 7.2 days, and the rate of grade I, II, IIIa, and IIIb complications was 2.2%, 2.7%, 1.3%, and 0.9%, respectively, without any irreversible disabilities or mortalities. The most common early and late major complications in the recipient were intraabdominal bleeding (n = 47, 8.5%) and biliary problems (n = 198, 35.6%), respectively. Analysis of the PLDRH procedure showed that operative time, liver removal time, warm ischemic time, Δhemoglobin%, Δtotal bilirubin%, and postoperative hospital stay decreased significantly as the number of cases accumulated. In conclusion, the operative outcomes of PLDRH improved as the number of cases increased. However, continuous caution is needed because major complications still occur in donors and recipients even after hundreds of cases.

Feasible living donor liver transplantation for patients on chronic hemodialysis: a multicenter study in East Asian countries.

PURPOSES: End-stage liver and kidney disease is an indication for simultaneous liver and kidney transplantation. However, in countries where deceased donor transplantation is not well established, living donor liver transplantation (LDLT) is a realistic option for patients on hemodialysis (HD). We investigated the outcomes of LDLT for patients on HD. METHODS: We conducted a retrospective multicenter survey of patients on chronic HD who underwent LDLT in East Asian countries. The characteristics of donors and recipients and the short and long-term outcomes were analyzed. RESULTS: Between 2001 and 2021, 45 patients on HD underwent LDLT and 11 of these patients also underwent kidney transplantation (KT). The overall survival rate at 5 years of the 34 patients who underwent only LDLT was 44.5%. Multivariate analysis identified a low graft recipient weight ratio (< 1%) (p = 0.048) and long HD duration (≥ 10 years) (p = 0.046) as independent predictors of poor overall survival. The major complication was posttransplant bleeding, which occurred in12 patients (35%). CONCLUSION: It is important to establish the indications for LDLT, taking into consideration graft size and HD duration in candidate patients on HD.

An international survey of venous thromboembolic events and current practices of peri-operative VTE prophylaxis after living donor hepatectomy.

BACKGROUND: Venous thromboembolic complications are an uncommon but significant cause of morbidity & mortality after live donor hepatectomy . The precise incidence of these events and the current practices of centers performing living donor liver transplantation worldwide are unknown. METHODS: An online survey was shared amongst living donor liver transplantation centers containing questions regarding center activity, center protocols for donor screening, peri-operative thromboembolic prophylaxis and an audit of -perioperative venous thromboembolic events after live donor hepatectomy in the previous five years (2016-2020). RESULTS: Fifty-one centers from twenty countries completed the survey. These centers had cumulatively performed 11500 living donor liver transplants between 2016-2020. All centers included pre-operative l assessment for thromboembolic risk amongst potential liver donors in their protocols. Testing for inherited prothrombotic conditions was performed by 58% of centers. Dual-mode prophylaxis was the most common practice (65%), while eight and four centers used single mode or no routine prophylaxis respectively. Twenty (39%) and 15 (29%) centers reported atleast one perioperative deep venous thrmobosis or pulmonary embolism event respectively. There was one donor mortality directly related to post-operative pulmonary embolism. Overall incidence of deep venous thrombosis and pulmonary embolism events was 3.65 and 1.74 per 1000 live donor hepatectomies respectively. Significant variations in center practices and incidence of thromboembolic events was identified in the survey primarily divided along world regions. 75% of participating centers agreed on the need for clear international guidelines. CONCLUSION: Venous thromboembolic events after live donor hepatectomy are an uncommon but important cause of donor morbidity. There is significant variation in practice among centers. Evidence-based guidelines regarding risk assessment, and peri-operative prophylaxis are needed.

Evaluation of the efficacy and safety of conversion from the tacrolimus capsule to tablet in stable liver transplant recipients with maintenance therapy: a 24-week, open-label, single-center, phase IV exploratory clinical study.

Purpose: The tablet form of tacrolimus is more convenient for drug ingestion than the capsule form. We examined the efficacy and safety of tacrolimus tablets and a satisfaction survey after formula conversion in liver transplant (LT) recipients. Methods: This study was an open-label, prospective clinical trial for tacrolimus formula 1:1 conversion from capsule to tablet in 41 adult LT recipients with tacrolimus maintenance therapy of more than 1 month. The primary endpoint was incidence of biopsy-proven acute rejection (BPAR) within 24 weeks. Surveys 1 week before and 4 weeks after formula conversion were conducted for total daily dose of medication, number, scale of discomfort and satisfaction. Results: The overall incidence of BPAR was 0% and there was no graft loss or patient death. The incidence of adverse effects was 34.1% (n = 14) after formula conversion. The most common severe adverse effect was abnormal liver function test (n = 5): biliary complications (n = 4) and alcoholic recidivism (n = 1). Total daily dose and number of tacrolimus doses were significantly lower after formula conversion (P < 0.05) without changes in trough level. According to survey analysis, there was no significant difference in discomfort and satisfaction scales from capsule to tablet conversion (P < 0.05). Conclusion: The present study suggests that the new tablet formula can be a useful treatment option to maintain a consistent level of tacrolimus with a lower total daily dose and number in adult LT recipients.

Soluble suppression of tumorigenicity 2 is a potential predictor of post-liver transplant renal outcomes.

Acute kidney injury is considered an independent prognostic factor for mortality in patients with liver cirrhosis. Non-treated acute kidney injury can progress to hepatorenal syndrome with a poor prognosis. As suppression of tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor family that aggravates inflammation and fibrotic changes in multiple organs, we measured soluble ST2 (sST2) level in the serum and urine of liver-transplant recipients at the time of transplantation. The serum sST2 level significantly increased in liver-transplant recipients with suppressed kidney function compared with that in recipients with normal function. In recipients with severely decreased liver function (model for end-stage liver disease score ≥ 30), the serum sST2 level was higher than that in recipients with preserved liver function (model for end-stage liver disease score ≤ 20, P = 0.028). The serum sST2 level in recipients with hepatorenal syndrome was higher than that in liver-transplant recipients without hepatorenal syndrome (P = 0.003). The serum sST2 level in patients with hepatorenal syndrome was higher than that in recipients without a history of acute kidney injury (P = 0.004). Recipients with hepatorenal syndrome and recovered kidney function showed higher sST2 levels than those who did not recover (P = 0.034). Collectively, an increase in the serum sST2 level reflects a decrease in both kidney and liver functions. Thus, measuring sST2 level at the time of liver transplantation can help predict renal outcomes.

Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma.

Palmitic acid (PA) is the most common fatty acid in humans and mediates palmitoylation through its conversion into palmitoyl coenzyme A. Although palmitoylation affects many proteins, its pathophysiological functions are only partially understood. Here we demonstrate that PA acts as a molecular checkpoint of lipid reprogramming in HepG2 and Hep3B cells. The zinc finger DHHC-type palmitoyltransferase 23 (ZDHHC23) mediates the palmitoylation of plant homeodomain finger protein 2 (PHF2), subsequently enhancing ubiquitin-dependent degradation of PHF2. This study also reveals that PHF2 functions as a tumor suppressor by acting as an E3 ubiquitin ligase of sterol regulatory element-binding protein 1c (SREBP1c), a master transcription factor of lipogenesis. PHF2 directly destabilizes SREBP1c and reduces SREBP1c-dependent lipogenesis. Notably, SREBP1c increases free fatty acids in hepatocellular carcinoma (HCC) cells, and the consequent PA induction triggers the PHF2/SREBP1c axis. Since PA seems central to activating this axis, we suggest that levels of dietary PA should be carefully monitored in patients with HCC.