Impact of concurrent MASLD on early-stage HCC following curative resection in chronic hepatitis B.

In 2023, a new nomenclature, metabolic dysfunction-associated steatotic liver disease (MASLD), replaced the term non-alcoholic fatty liver disease (NAFLD). With the global rise in MASLD prevalence, concurrent MASLD and chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) are becoming increasingly common. This study aimed to evaluate the clinical impact of concurrent MASLD on long-term survival outcomes in patients with CHB-related early-stage HCC following curative resection. This retrospective study included patients diagnosed with CHB-related early-stage HCC who underwent curative hepatectomy between January 2010 and December 2019. We examined the association between histologically confirmed MASLD and clinical outcomes, with overall survival (OS) and recurrence-free survival (RFS) calculated using the Kaplan-Meier method and compared using the log-rank test. Of 587 eligible patients, 275 (46.8%) were diagnosed with concurrent MASLD. Patients with concurrent MASLD had a higher prevalence of diabetes, hypertension, body mass index (BMI) > 23 kg/m2, a lower proportion of AFP > 200 ng/ml, and microvascular invasion compared to those without MASLD. After a median follow-up of 66 months, patients with concurrent MASLD exhibited a lower risk of death (HR: 0.57, 95% CI: 0.34-0.95, P = 0.030) but no significant difference in HCC recurrence rates. Subgroup analysis revealed significantly higher OS in females, individuals with BMI ≥ 23 kg/m2, and non-cirrhotic patients (all P < 0.05). In conclusion, concurrent MASLD is associated with improved survival in patients with CHB-related HCC following curative resection, particularly in females, those with BMI ≥ 23 kg/m2, and non-cirrhotic patients.

Risk factors and crucial prognostic indicators of mortality in liver transplant recipients with bloodstream infections: A comprehensives study of 1049 consecutive liver transplants over an 11-year period.

BACKGROUND: Liver transplantation (LT) is a pivotal treatment for end-stage liver disease. However, bloodstream infections (BSI) in the post-operative period present a significant threat to patient survival. This study aims to identify risk factors for post-LT BSI and crucial prognostic indicators for mortality among affected patients. METHODS: We conducted a retrospective study of adults diagnosed with end-stage liver disease who underwent their initial LT between 2010 and 2021. Those who developed BSI post-LT during the same hospital admission were classified into the BSI group. RESULTS: In this cohort of 1049 patients, 89 (8.4%) developed BSI post-LT, while 960 (91.5%) did not contract any infection. Among the BSI cases, 17 (19.1%) patients died. The average time to BSI onset was 48 days, with 46% occurring within the first month post-LT. Of the 123 isolated microorganisms, 97 (78.8%) were gram-negative bacteria. BSI patients had significantly longer stays in the intensive care unit and hospital compared to non-infected patients. The 90-day and in-hospital mortality rates for recipients with BSI were significantly higher than those without infections. Multivariate analysis indicated heightened BSI risk in patients with blood loss >3000 mL during LT (odds ratio [OR] 2.128), re-operation within 30 days (OR 2.341), post-LT bile leakage (OR 3.536), and graft rejection (OR 2.194). Additionally, chronic kidney disease (OR 6.288), each 1000 mL increase in intraoperative blood loss (OR 1.147) significantly raised mortality risk in BSI patients, whereas each 0.1 mg/dL increase in albumin levels correlated with a lower risk of death from BSI (OR 0.810). CONCLUSIONS: This study underscores the need for careful monitoring and management in the post-LT period, especially for patients at higher risk of BSI. It also suggests that serum albumin levels could serve as a valuable prognostic indicator for outcomes in LT recipients experiencing BSI.

A single center analysis of long-term outcomes and survival related risk factors in liver retransplantation.

Background: Liver retransplant is the only option to save a patient with liver graft failure. However, it is controversial due to its poor survival outcome compared to primary transplantation. Insufficient deceased organ donation in Taiwan leads to high waitlist mortality. Hence, living-donor grafts offer a valuable alternative for retransplantation. This study aims to analyze the single center's outcome in living donor liver retransplantation (re-LDLT) and deceased donor liver retransplantation (re-DDLT) as well as the survival related confounding risk factors. Methods: This is a single center retrospective study including 32 adults who underwent liver retransplantation (re-LT) from June 2002 to April 2020. The cohort was divided into a re-LDLT and a re-DDLT group and survival outcomes were analyzed. Patient outcomes over different periods, the effect of timing on survival, and multivariate analysis for risk factors were also demonstrated. Results: Of the 32 retransplantations, the re-LDLT group (n=11) received grafts from younger donors (31.3 vs. 43.75 years, P=0.016), with lower graft weights (688 vs. 1,457.2 g, P<0.001) and shorter cold ischemia time (CIT) (45 vs. 313 min, P<0.001). The 5-year survival was significantly better in the re-LDLT group than in the re-DDLT group (100% vs. 70.8%, P=0.02). This difference was adjusted when only retransplantation after 2010 was analyzed. Further analysis showed that the timing of retransplantation (early vs. late) did not affect patient survival. Multivariate analysis revealed that prolonged warm ischemia time (WIT) and intraoperative blood transfusion were related to poor long-term survival. Conclusions: Retransplantation with living donor graft demonstrated good long-term outcomes with acceptable complications to both recipient and donor. It may serve as a choice in areas lacking deceased donors. The timing of retransplantation did not affect the long-term survival. Further effort should be made to reduce WIT and massive blood transfusion as they contributed to poor survival after retransplantation.

Long-term outcomes of active vaccination against de novo hepatitis B among pediatric recipients of living donor liver transplantations with anti-HBc (+) grafts: a retrospective case-control study.

BACKGROUND: Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation (LT). However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated. MATERIALS AND METHODS: Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Anti-viral therapy was given to patients with pre-transplant anti-HBs<1000 IU/ ml (non-robust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs>1000 IU/mL, while anti-viral therapy was not given in patients with an anti-HBs titer over 1000 IU/mL. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates. RESULTS: Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2% vs 93.4%, P=0.026; 85.1% vs 93.4%, P=0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and non-graft mortality values (90.8% vs 96.6%, P=0.036; 93.0% vs 98.3%, P=0.011, respectively). CONCLUSION: Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.

A preoperative model to predict overall survival in patients with hepatoma undergoing resection.

BACKGROUND: We aimed to develop a preoperative model to predict overall survival (OS) in patients with hepatoma undergoing liver resection (LR). METHODS: Patients who underwent LR for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or B hepatoma were enrolled. Tumor burden score (TBS) scores were determined using the following equation: TBS (Pinna et al., 2018) 2 = (largest tumor size [in cm])(Pinna et al., 2018) 2 â€‹+ â€‹(tumor number) (Pinna et al., 2018) 22. The cutoff values for radiographic TBS were based on our recently published paper: low, <2.6; medium, 2.6-7.9; high, >7.9. RESULTS: Multivariate analysis showed that radiographic TBS (low: referent; medium: HR â€‹= â€‹2.89; 95 â€‹% CI: 1.60-5.21; p â€‹< â€‹0.001; high, HR â€‹= â€‹7.60; 95 â€‹% CI: 3.80-15.2; p â€‹< â€‹0.001), AFP (<400 â€‹ng/mL: referent; ≧400 â€‹ng/mL: HR â€‹= â€‹1.67, 95 â€‹% CI: 1.11-2.52, p â€‹= â€‹0.014), and cirrhosis (absence: referent; presence: HR â€‹= â€‹1.88, 95 â€‹% CI: 1.30-2.72, p â€‹< â€‹0.001) were associated with OS. A simplified risk score was superior to BCLC system in concordance index (0.688 vs. 0.623). CONCLUSIONS: We have developed a preoperative model that performs better in predicting OS than the BCLC system.

Usefulness of Diffusion-Weighted Imaging in Evaluating Acute Cellular Rejection and Monitoring Treatment Response in Liver Transplant Recipients.

Acute cellular rejection (ACR) is a significant immune issue among recipients following liver transplantation. Although diffusion-weighted magnetic resonance imaging (DWI) is widely used for diagnosing liver disease, it has not yet been utilized for monitoring ACR in patients after liver transplantation. Therefore, the aim of this study was to evaluate the efficacy of DWI in monitoring treatment response among recipients with ACR. This study enrolled 25 recipients with highly suspected ACR rejection, and all subjects underwent both biochemistry and DWI scans before and after treatment. A pathological biopsy was performed 4 to 24 h after the first MRI examination to confirm ACR and degree of rejection. All patients were followed up and underwent a repeated MRI scan when their liver function returned to the normal range. After data acquisition, the DWI data were post-processed to obtain the apparent diffusion coefficient (ADC) map on a voxel-by-voxel basis. Five regions of interest were identified on the liver parenchyma to measure the mean ADC values from each patient. Finally, the mean ADC values and biochemical markers were statistically compared between ACR and non-ACR groups. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the ADC and biochemical data in detecting ACR, and correlation analysis was used to understand the relationship between the ADC values, biochemical markers, and the degree of rejection. The histopathologic results revealed that 20 recipients had ACR, including 10 mild, 9 moderate, and 1 severe rejection. The results demonstrated that the ACR patients had significantly lower hepatic ADC values than those in patients without ACR. After treatment, the hepatic ADC values in ACR patients significantly increased to levels similar to those in non-ACR patients with treatment. The ROC analysis showed that the sensitivity and specificity for detecting ACR were 80% and 95%, respectively. Furthermore, the correlation analysis revealed that the mean ADC value and alanine aminotransferase level had strong and moderate negative correlation with the degree of rejection, respectively (r = -0.72 and -0.47). The ADC values were useful for detecting hepatic ACR and monitoring treatment response after immunosuppressive therapy.

The outcomes and biliary complications of a staged biliary reconstruction in living donor liver transplantation: a propensity score matched analysis.

BACKGROUND: Uncontrolled massive bleeding and bowel edema are critical issues during liver transplantation. Temporal intra-abdominal packing with staged biliary reconstruction (SBR) yields acceptable outcomes in deceased donor liver transplantation; however, data on living donor liver transplantation (LDLT) are scarce. METHODS: A retrospective analysis of 1269 patients who underwent LDLT was performed. After one-to-two propensity score matching, patients who underwent LDLT with SBR were compared with those who underwent LDLT with one-stage biliary reconstruction (OSBR). The primary outcomes were graft survival (GS) and overall survival (OS), and the secondary outcomes were postoperative biliary complications. RESULTS: There were 55 and 110 patients in the SBR and OSBR groups, respectively. The median blood loss was 6500 mL in the SBR and 4875 mL in the OSBR group. Patients receiving SBR-LDLT had higher incidence of sepsis (69.0% vs. 43.6%; P < 0.01) and intra-abdominal infections (60.0% vs. 30.9%; P < 0.01). Biliary complication rates (14.5% vs. 19.1%; P = 0.47) and 1-and 5-year GS (87.27%, 74.60% vs. 83.64%, 72.71%; P = 0.98) and OS (89.09%, 78.44% vs. 84.55%, 73.70%; P = 0.752) rates were comparable between the two groups. CONCLUSIONS: SBR could serve as a life-saving procedure for patients undergoing complex critical LDLT, with GS, OS, and biliary outcomes comparable to those of OSBR.

Epidemiology and Risk Factors of Early Bacterial Infections After Pediatric Living Donor Liver Transplantation.

BACKGROUND: Advancements in surgical techniques, immunosuppression regimens, and peri-operative and postoperative care have resulted in marked improvement in outcomes after pediatric living donor liver transplantation (PLDLT). Despite these developments, infectious complications remain a major cause of morbidity and mortality. METHODS: This is a retrospective cohort analysis of pediatric recipients from January 2004 to December 2018. Patients were classified into infected and non-infected groups based on the occurrence of bacterial infection during the first 3 months after transplant. Perioperative risk factors for early post-transplant bacterial infections and postoperative outcomes were investigated. RESULTS: Seventy-two out of 221 children developed early bacterial infection (32.6%). The first episodes of bacterial infection most frequently occurred in the second week after LDLT (37.5%). In multivariate analysis, active infection before transplant and complications with Clavien-Dindo grading >3 were the only independent risk factors. Early bacterial infections were independently associated with longer intensive care unit stays, longer hospital stays, and a higher incidence of readmission for bacterial infection during the first year after transplant. Additionally, the overall patient survival rate was significantly higher in the non-infected group (P = .001). Risk factors for infection, such as age, weight, disease severity, ABO-incompatible, and other operative factors, were not identified as independent risk factors. CONCLUSION: We have demonstrated that there are similarities and disparities in the epidemiology and risk factors for early bacterial infection after transplant between centers. Identification and better characterization of these predisposing factors are essential in the modification of current preventive strategies and treatment protocols to improve outcomes for this highly vulnerable group.

Smoking as a Risk Factor for Very Late Recurrence in Surgically Resected Early-Stage Primary Hepatocellular Carcinoma.

Background: The risk of first recurrence of hepatocellular carcinoma (HCC) within years 5 to 10 after curative hepatectomy remains unknown. We aimed to assess the incidence and prognostic factors for very late recurrence among patients who achieved 5 years' recurrence-free survival (RFS) after primary resection. Methods: We retrospectively analyzed 337 patients with early-stage HCC underwent primary tumor resection and achieved more than 5 years' RFS. Results: A total of 77 patients (22.8%) developed very late recurrence. The cumulative very late recurrence rate increased from 6.9% and 11.7% to 16.6% at 6, 7, and 8 years, respectively. Patients stopped smoking had a higher rate of very late RFS. Conclusions: The high rates of very late recurrence in HCC indicate that patients warrant continued surveillance, even after 5 recurrence-free years. Moreover, smoking is a risk factor for very late HCC recurrence, and quitting smoking may reduce the risk of very late recurrence.

Sarcopenia Affects Liver Regeneration and Long-Term Survival Rate After Living-Donor Liver Transplantation in Patients With Hepatocellular Carcinoma.

PURPOSE: Despite technological and immunologic innovations, some living-donor liver transplant (LDLT) recipients still face poor liver regeneration. Sarcopenia is often recognized as a biomarker for poor outcomes in surgical patients. This study aimed to evaluate associations between sarcopenia and liver regeneration in LDLT recipients. MATERIALS AND METHODS: This retrospective review included consecutive patients who had received LDLT at Chang Gung Memorial Hospital between 2005 and 2017. Sarcopenia was assessed using the psoas muscle index (PMI) in cross-sectional images. Receiver operating characteristic curve analysis was used to determine the ability of PMI to predict relatively poor survival rates. Correlations between liver regeneration and sarcopenia were evaluated using regression analysis. RESULTS: A total of 109 LDLT recipients were included. The 1-, 3-, 5, 10-, and 15-year survival rates were 93.7%, 84.8%, 79.7%, 74.7%, and 73.3% in males and 93.3%, 83.3%, 83.3%, 71.4%, and 71.4% in females. PMIs were significantly different based on 10- and 15-year overall survival rates (P = .001 and P = .000) in male patients. Receiver operating characteristic curve analysis revealed the PMI cutoff point at 6.7 cm2/m2 (sensitivity = 48.3%, specificity = 81%, AUC (area under the ROC curve) = 0.685) based on 10-year survival. Linear regression analysis revealed that PMI was significantly associated with liver regeneration in males (P = .013). CONCLUSIONS: Sarcopenia and low PMI are associated with poor liver regeneration and long-term survival after LDLT in male patients. Further studies, including sarcopenia with conventional scores, may help to more reliably predict liver regeneration and mortality among LDLT patients with hepatocellular carcinoma.

Risk factors for pre-transplantation bacteremia in adults with end-stage liver disease: Effects on outcomes of liver transplantation.

BACKGROUND AND AIM: Limited data are available regarding pre-liver transplantation (LT) bacteremia in adults with end-stage liver disease. In this study, we investigated the risk factors independently associated with pre-LT bacteremia and their effects on clinical outcomes of LT. METHODS: This retrospective study performed between 2010 and 2021 included 1287 LT recipients. The study population was categorized into patients with pre-LT bacteremia and those without pre-LT infection. Pre-LT bacteremia was defined as bacteremia detected within 90 days before LT. RESULTS: Among 1287 LT recipients, 92 (7.1%) developed pre-LT bacteremia. The mean interval between bacteremia and LT was 28.3 ± 19.5 days. Of these 92 patients, seven (7.6%) patients died after LT. Of the 99 microorganisms isolated in this study, gram-negative bacteria were the most common microbes (72.7%). Bacteremia was mainly attributed to spontaneous bacterial peritonitis. The most common pathogen isolated was Escherichia coli (25.2%), followed by Klebsiella pneumoniae (18.2%), and Staphylococcus aureus (15.1%). Multivariate analysis showed that massive ascites (adjusted odds ratio [OR] 1.67, 95% confidence Interval [CI] 1.048-2.687) and a prolonged international normalized ratio for prothrombin time (adjusted OR 1.13, 95% CI 1.074-1.257) were independent risk factors for pre-LT bacteremia in patients with end-stage liver disease. Intensive care unit and in-hospital stay were significantly longer, and in-hospital mortality was significantly higher among LT recipients with pre-LT bacteremia than among those without pre-LT infection. CONCLUSIONS: This study highlights predictors of pre-LT bacteremia in patients with end-stage liver disease. Pre-LT bacteremia increases the post-transplantation mortality risk.

Impact of Sirolimus versus Mycophenolate Mofetil on Kidney Function after Calcineurin Inhibitor Dose Reduction in Liver Transplant Recipients.

Impaired kidney function is associated with increased morbidity and mortality in patients undergoing liver transplantation. Although immunosuppressants are essential in these patients, they impair kidney function. This study aimed to compare adverse kidney outcomes between patients treated with a reduced dose of tacrolimus (calcineurin inhibitor) plus sirolimus or mycophenolate mofetil (MMF) in the liver transplant center at Kaohsiung Chang Gung Memorial Hospital between April 2011 and December 2017. Propensity score matching was used to identify 232 patients. The risk of adverse kidney outcomes was estimated using Cox proportional hazards regression, and changes in kidney function over time were analyzed using linear mixed modeling. Acute kidney disease risks in this study cohort were not significantly different for the two immunosuppressants (aHR 1.04; 95% CI: 0.70-1.55, p = 0.8328). However, sirolimus use was significantly associated with a higher risk of estimated glomerular filtration rate decline > 30% than MMF (aHR, 2.09; 95% CI: 1.33-3.28; p = 0.0014). Our results demonstrate that sirolimus use may have worsened long-term kidney outcomes compared to MMF. Close monitoring of kidney function, dose adjustment, and timely transition to MMF is necessary for LT patients receiving sirolimus.

Living donor liver transplantation for Barcelona clinic liver cancer (BCLC) intermediate-stage hepatocellular carcinoma.

Background: Barcelona clinic liver cancer (BCLC) stage B (intermediate stage) hepatocellular carcinoma (HCC) is highly heterogeneous; thus, identifying the most effective treatment for individual patients represents a significant clinical challenge. However, transarterial chemoembolization (TACE) is the only recommended treatment option. Therefore, we aimed to investigate the patient characteristics and outcomes of living donor liver transplantation (LDLT) for BCLC stage B HCC. Methods: A total of 516 patients with BCLC stage B HCC who underwent LDLT (n=104) or did not undergo LDLT (non-LDLT; n=412) between 2004 to 2018 were analyzed by propensity score matching (PSM; 1:4) analysis. Factors influencing overall survival (OS) and recurrence were analyzed using Cox's proportional hazards models. Results: Patients treated with LDLT achieved better OS than the non-LDLT group, including liver- and non-liver related survival (all P<0.001). Multivariate Cox regression analysis showed age >60 years (P=0.006), a neutrophil-lymphocyte ratio (NLR) >4 (P=0.016) and >3 locoregional therapies (LRT) before LDLT (P<0.001) were independent risk factors for HCC recurrence. In addition, age >60 years (P<0.001) and >3 LRT before LDLT (P=0.001) were independent risk factors for OS. Using a combination of age, NLR, and LRT before liver transplantation (LT), the patients can be divided into low-risk (none of risk), intermediate-risk (one of risk), and high risk (more than two of risk) groups. There were significant differences in the cumulative HCC recurrence (P<0.001) and mortality (P<0.001) rates among the three groups. Conclusions: LDLT may represent a valuable therapeutic option for selected patients with BCLC stage B HCC.

Overexpression of miR-4669 Enhances Tumor Aggressiveness and Generates an Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma: Its Clinical Value as a Predictive Biomarker.

Accumulating evidence suggests the involvement of tumor-derived exosomes in the development and recurrence of hepatocellular carcinoma (HCC). We previously identified miR-4669 as a highly expressed microRNA in circulating exosomes obtained from patients with post-transplant HCC recurrence. This study aimed to explore how overexpression of miR-4669 affects HCC development and recurrence. The impact of miR-4669 overexpression in Hep3B cells on tumor cell behavior and the tumor microenvironment was evaluated in vitro. In addition, the clinical value of exosomal miR-4669 for the prediction of treatment response to HCC downstaging therapies and following post-transplant HCC recurrence was explored. Overexpression of miR-4669 enhanced migration ability and led to acquired sorafenib resistance with an elevation of sirtuin 1 and long noncoding RNA associated with microvascular invasion. Active release of tumor-derived exosomes and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) contributed to generating an immunosuppressive tumor microenvironment through the induction of M2 macrophage polarization. The retrospective analysis demonstrated the clinical value of exosomal miR-4669 for predicting treatment response to HCC downstaging therapies and for risk assessment of post-transplant HCC recurrence. In summary, the present data demonstrate the impact of exosomal miR-4669 on HCC recurrence through the enhancement of tumor aggressiveness and generation of an immunosuppressive tumor microenvironment.

Overall survival among patients who undergo resection does not differ significantly between T1a and T1b hepatocellular carcinoma based on the 8th American Joint Commission on Cancer.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been used since 2018. However, whether any significant difference in overall survival (OS) exists between patients with T1a and T1b HCC who undergo resection has been controversial. We aim to clarify this issue. METHODS: We consecutively enrolled newly diagnosed HCC patients who underwent liver resection (LR) from 2010 to 2020 at our institution. OS was estimated using the Kaplan-Meier method and compared using log-rank tests. Prognostic factors for OS were identified by multivariate analysis. RESULTS: This study enrolled 1250 newly diagnosed HCC patients who underwent LR. No significant differences in OS were identified between patients with T1a and T1b tumors among all patients (p = 0.694), cirrhotic patients (p = 0.753), non-cirrhotic patients (p = 0.146), patients with alpha-fetoprotein (AFP) > 20 ng/ml (p = 0.562), patients with AFP ≤ 20 ng/ml (p = 0.967), patients with Edmondson grade 1 or 2 (p = 0.615), patients with Edmondson grade 3 or 4 (p = 0.825), patients positive for hepatitis B surface antigen (HBsAg; p = 0.308), in patients positive for anti-hepatitis C virus (HCV) antibody (p = 0.781), or patients negative for both HBsAg and anti-HCV antibody (p = 0.125). Using T1a as the reference, multivariate analysis showed that T1b is not a significant predictive factor for OS (hazard ratio (HR): 1.338; 95% confidence interval (CI):0.737-2.431; p = 0.339). CONCLUSION: No significant difference in OS was observed between patients who underwent LR to treat T1a and T1b HCC tumors.

Long-term renal outcomes comparison between patients with chronic kidney disease and hepatorenal syndrome after living donor liver transplantation.

Background and aims: Hepatorenal syndrome (HRS) is a disastrous renal complication of advanced liver disease with a poor prognosis. Restoring normal liver function through liver transplantation (LT) is a standardized treatment with favorable short-term survival. However, the long-term renal outcomes in patients with HRS receiving living donor LT (LDLT) are controversial. This study aimed to investigate the prognostic impact of LDLT in patients with HRS. Methods: We reviewed adult patients who underwent LDLT between July 2008 and September 2017. Recipients were classified into 1) HRS type 1 (HRS1, N = 11), 2) HRS type 2 (HRS2, N = 19), 3) non-HRS recipients with pre-existing chronic kidney disease (CKD, N = 43), and 4) matched normal renal function (N = 67). Results: Postoperative complications and 30-day surgical mortality were comparable among the HRS1, HRS2, CKD, and normal renal function groups. The 5-year survival rate was >90% and estimated glomerular filtration rate (eGFR) transiently improved and peaked at 4 weeks post-transplantation in patients with HRS. However, renal function deteriorated and resulted in CKD stage ≥ III in 72.7% of HRS1 and 78.9% of HRS2 patients (eGFR <60 ml/min/1.73 m2). The incidence of developing CKD and end-stage renal disease (ESRD) was similar between the HRS1, HRS2, and CKD groups, but significantly higher than that in the normal renal function group (both P < 0.001). In multivariate logistic regression, pre-LDLT eGFR <46.4 ml/min/1.73 m2 predicted the development of post-LDLT CKD stage ≥ III in patients with HRS (AUC = 0.807, 95% CI = 0.617-0.997, P = 0.011). Conclusions: LDLT provides a significant survival benefit for patients with HRS. However, the risk of CKD stage ≥ III and ESRD among patients with HRS was similar to that in pre-transplant CKD recipients. An early preventative renal-sparing strategy in patients with HRS is recommended.

Radiographic tumor burden score is useful for stratifying the overall survival of hepatocellular carcinoma patients undergoing resection at different Barcelona Clinic Liver Cancer stages.

PURPOSE: The Barcelona Clinic Liver Cancer (BCLC) staging system has been recommended for prognostic prediction. However, prognosis is variable at different BCLC stages. We aimed to evaluate whether the radiographic tumor burden score (TBS) could be used to stratify prognosis in different BCLC stages. METHODS: Hepatocellular carcinoma (HCC) patients undergoing liver resection (LR) at BCLC-0, -A, or -B stage in our institution in 2007-2018 were divided into derivation and validation cohorts. Overall survival (OS) was analyzed according to the TBS and BCLC stage. TBS cutoff values for OS were determined with X-tile. RESULTS: Of the 749 patients in the derivation cohort, 138 (18.4%) had BCLC-0, 542 (72.3%) BCLC-A, and 69 (9.2%) BCLC-B HCC; 76 (10.1%) had a high TBS (> 7.9), 477 (63.7%) a medium TBS (2.6-7.9), and 196 (26.2%) a low TBS (< 2.6). OS worsened progressively with increasing TBS in the cohort (p < 0.001) and in BCLC-A (p = 0.04) and BCLC-B (p = 0.002) stages. Multivariate analysis showed that the TBS was associated with OS of patients with BCLC-A (medium vs. low TBS: hazard ratio [HR] = 2.390, 95% CI = 1.024-5.581, p = 0.04; high vs. low TBS: HR = 3.885, 95% CI = 1.443-10.456, p = 0.007) and BCLC-B (high vs. medium TBS: HR = 2.542, 95% CI = 1.077-6.002, p = 0.033) HCC. The TBS could also be used to stratify the OS of patients in the validation cohort (p < 0.001). CONCLUSION: The TBS could be used to stratify the OS of the entire cohort and BCLC stages A and B of HCC patients undergoing LR.

AFP Response to Locoregional Therapy Can Stratify the Risk of Tumor Recurrence in HCC Patients after Living Donor Liver Transplantation.

(1) Background: Alpha-fetoprotein (AFP) has been incorporated into the selection criteria of liver transplantation and been used to predict the outcome of hepatocellular carcinoma (HCC) recurrence. Locoregional therapy (LRT) is recommended for bridging or downstaging in HCC patients listed for liver transplantation. The aim of this study was to evaluate the effect of the AFP response to LRT on the outcomes of hepatocellular carcinoma patients after living donor liver transplantation (LDLT). (2) Methods: This retrospective study included 370 HCC LDLT recipients with pretransplant LRT from 2000 to 2016. The patients were divided into four groups according to AFP response to LRT. (3) Results: The nonresponse group had the worst 5-year cumulative recurrence rates whereas the complete-response group (patients with abnormal AFP before LRT and with normal AFP after LRT) had the best 5-year cumulative recurrence rate among the four groups. The 5-year cumulative recurrence rate of the partial-response group (AFP response was over 15% lower) was comparable to the control group. (4) Conclusions: AFP response to LRT can be used to stratify the risk of HCC recurrence after LDLT. If a partial AFP response of over 15% declineis achieved, a comparable result to the control can be expected.

A preoperative model for predicting early recurrence in patients undergoing resection for single hepatocellular carcinoma.

BACKGROUND AND AIM: The updated Barcelona Clinic Liver Cancer guidelines recommend liver resection (LR) for patients with single hepatocellular carcinoma (HCC) of any size. This study developed a preoperative model for predicting early recurrence in patients undergoing LR for single HCC. MATERIALS AND METHODS: We identified 773 patients undergoing LR for single HCC between 2011 and 2017 from the cancer registry database of our institution. Multivariate Cox regression analyses were performed to construct a preoperative model for predicting early recurrence, i.e., recurrence within 2 years of LR. RESULTS: Early recurrence was identified in 219 patients (28.3%). The final model of early recurrence included four predictive factors-alpha-fetoprotein level of ≥20 ng/mL, tumor size of >30 mm, Model for End-Stage Liver Disease score of >8, and cirrhosis. Preoperative application of this model provided three risk strata for recurrence-free survival (RFS): low risk, with 2-year RFS of 79.8% (95% confidence interval [CI]: 75.7-84.2%); intermediate risk, with 2-year RFS of 66.6% (95% CI: 61.1-72.6%); and high risk, with 2-year RFS of 51.1% (95% CI: 43.0-60.8%). CONCLUSION: We developed a preoperative model for predicting early recurrence after LR for single HCC. This model provides useful information for clinical decision-making.