QuantiFERON-TB Gold Plus (QFT-Plus) is a new-generation QuantiFERON-TB Gold In-Tube (QFT-GIT) assay which has two antigen-coated tubes called TB1, which contains long peptides derived from ESAT-6 and ...CFP-10, and TB2, which contains the same components as TB1 and additional short peptides which potentially stimulate CD8
T cells through the presentation of major histocompatibility complex class I. This is the first study to compare QFT-Plus and QFT-GIT for use in the diagnosis of latent tuberculosis infection (LTBI) among immunocompromised patients in the Republic of Korea. Among 317 consecutive patients who underwent screening for LTBI before solid organ or hematopoietic stem cell transplantation and tumor necrosis factor alpha inhibitor treatment, LTBI was identified in 92 (29.0%) and 88 (27.8%) patients by QFT-GIT and QFT-Plus, respectively. The rate of concordance between QFT-GIT and QFT-Plus was 93.7% (κ value, 0.860), and the indeterminate rate (3.2%) was similar between QFT-GIT and QFT-Plus. Of 20 (6.3%) samples with discordant results, 11 (55.0%) and 7 (35.0%) were positive by QFT-GIT alone and QFT-Plus alone, respectively, and 2 (15.0%) were indeterminate by each assay. The interferon gamma level in samples with discordant results ranged from 0.39 to 1.10 IU/ml, except for one sample, in which the gamma interferon level was 2.97 IU/ml only in TB2. Conclusively, there was a high degree of agreement between the results of QFT-GIT and QFT-Plus for the screening of immunocompromised patients for LTBI. The reactivity in TB2 contributed substantially to the difference between QFT-GIT and QFT-Plus, particularly in solid organ transplant candidates. The significance of the discrete responses in TB1 and TB2 of QFT-Plus needs to be explored further by means of an immunological and clinical approach in different patient groups and clinical settings.
Graft versus host disease (GVHD) after liver transplantation (LT) is a rare, fatal disease. This study aimed to evaluate the risk factors of GVHD after LT including the human leukocyte antigen (HLA) ...donor-recipient relationship after LT. LT recipients, who underwent HLA typing together with donors, were included in the study. The donor against recipient (D → R) one-way mismatch of HLA loci was evaluated. HLA relationships, along with basic characteristics, were analyzed as variable factors of GVHD, graft survival, and patient survival. A total of 994 living donor LT (LDLT) and 393 deceased donor LT (DDLT) patients were included. Nine patients had suffered GVHD, four LDLT with D → R one-way at three loci, one LDLT without D → R one-way at three loci, and four DDLT without D → R one-way at three loci. Four (57.1%) of seven LDLT patients, with D → R one-way mismatch at three loci, developed GVHD. D → R one-way mismatch at three loci was related to high GVHD incidence (HR 787, p < 0.001, multivariate). D → R one-way mismatch at three loci was related to graft failure and patient death (HR 9.90, p = 0.020 and HR 12.8, p < 0.001, respectively, multivariate). Only one GVHD without D → R one-way mismatch at three loci, survived despite receiving multiple modalities including tumor necrosis factor-alpha inhibitors. D → R one-way mismatch at three loci was significantly related to GVHD incidence after LT.
Muscle depletion in patients undergoing liver transplantation affects the recipients' prognosis and therefore cannot be overlooked. We aimed to evaluate whether changes in muscle and fat mass during ...the preoperative period are associated with prognosis after deceased donor liver transplantation (DDLT).
This study included 72 patients who underwent DDLT and serial computed tomography (CT) scans. Skeletal muscle index (SMI) and fat mass index (FMI) were calculated using the muscle and fat area in CT performed 1 year prior to surgery (1 yr Pre-LT), just before surgery (Pre-LT), and after transplantation (Post-LT). Simple aspects of serial changes in muscle and fat mass were analyzed during three measurement time points. The rate of preoperative changes in body composition parameters were calculated (preoperative ΔSMI % = SMI at Pre-LT - SMI at 1 yr Pre-LT / SMI at Pre-LT × 100; preoperative ΔFMI % = FMI at Pre-LT - FMI at 1 yr Pre-LT / FMI at Pre-LT × 100) and assessed for correlation with patient survival.
SMI significantly decreased during the preoperative period (mean preoperative ΔSMI, -13.04%,
< 0.001). In the multivariable analysis, preoperative ΔSMI (
= 0.016) and model for end-stage liver disease score (
= 0.011) were independent prognostic factors for overall survival. The mean survival time for patients with a threshold decrease in the preoperative ΔSMI (≤ -30%) was significantly shorter than for other patients (
= 0.007). Preoperative ΔFMI was not a prognostic factor but FMI increased during the postoperative period (
= 0.009) in all patients.
A large reduction in preoperative SMI was significantly associated with reduced survival after DDLT. Therefore, changes in muscle mass during the preoperative period can be considered as a prognostic factor for survival after DDLT.
Background
Early recurrence after liver resection of hepatocellular carcinoma (HCC) has a great effect on the survival of patients. The aims of this study were to identify risk factors for early ...recurrence and to clarify whether early recurrence is related to patient survival rate.
Methods
We identified a total of 1010 patients with HCC recurrence after hepatic resection between 2009 and 2014 in Samsung Medical Center and Seoul National University Hospital. Inclusion criteria were preoperative solitary tumor Child-Pugh class A and curative hepatectomy. Early recurrence was defined as HCC recurrence < 1 year after surgery.
Results
A total of 628 patients were included in this study: 302 with early recurrence and 326 with late recurrence. Multivariate analysis showed that HCC grade 3 or 4, tumor size > 3 cm, and microvascular invasion were closely associated with early recurrence after liver resection for solitary HCC. When HCC recurred, the early recurrence group had large tumor size, increased tumor numbers and AFP levels, and high incidence of diffuse intrahepatic recurrence compared with the late recurrence group. The overall survival curve for the early recurrence group was lower than that for the late recurrence group (
P
< 0.001). Multivariate analysis demonstrated early recurrence was closely associated with patient survival.
Conclusions
Patients with early recurrence had different characteristics compared to patients with late recurrence after hepatic resection in solitary HCC. Early detection of recurrence is necessary through active postoperative surveillance in hepatectomy patients with poor prognostic factors.
Blood neutrophil-to-lymphocyte ratio (NLR) is one index representing systemic inflammation, and high preoperative NLR has been suggested as an independent prognostic factor in HCC. However, the NLR ...cutoff value with the highest prognostic significance is not consistent, and the mechanism of this phenomenon remains unclear. Preoperative NLR was calculated from complete blood counts obtained before 14 days from operation day in 234 patients who underwent curative resection for primary HCC. The presence of tumor necrosis and degree of tumor-infiltrating lymphocytes (TILs) was determined histologically. High preoperative NLR (≥ 2.5) was observed in 28 (12.0%) of 234 HCCs and was significantly associated with younger age, larger tumor size, high Edmonson grade, microvascular invasion, major portal invasion, advanced AJCC T or BCLC stage, and low albumin level. Patients with high preoperative NLR showed shorter disease-specific survival (DSS) (
p
= 0.002) and a tendency for shorter recurrence-free survival (RFS) (
p
= 0.096). High preoperative NLR was associated with presence of tumor necrosis and low TIL. On multivariable analysis, preoperative NLR was an independent prognostic factor for DSS (hazard ratio: 2.050 (95% confidence interval 1.139–3.691),
p
= 0.017). However, the independent prognostic effect of NLR for DSS disappeared when tumor necrosis and TILs were added as co-variables. High NLR is an independent prognostic factor in patients with HCC who undergo curative resection. The prognostic effect of high NLR might originate from the prognostic effect of tumor necrosis or TILs.
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•Satellite nodules and peritumoral hypointensity can be seen by hepatobiliary MRI.•These features were associated with tumor recurrence after liver transplantation.•This association ...has been applied to all patients within and out of Milan criteria.•Hepatobiliary MRI can be a useful tool to select candidates for transplantation.
Hepatobiliary magnetic resonance imaging (MRI) provides additional information beyond the size and number of tumours, and may have prognostic implications. We examined whether pretransplant radiological features on MRI could be used to stratify the risk of tumour recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC).
A total of 100 patients who had received a liver transplant and who had undergone preoperative gadoxetic acid-enhanced MRI, including the hepatobiliary phase (HBP), were reviewed for tumour size, number, and morphological type (e.g. nodular, nodular with perinodular extension, or confluent multinodular), satellite nodules, non-smooth tumour margins, peritumoural enhancement in arterial phase, peritumoural hypointensity on HBP, and apparent diffusion coefficients. The primary endpoint was time to recurrence.
In a multivariable adjusted model, the presence of satellite nodules hazard ratio (HR) 3.07; 95% confidence interval (CI) 1.14–8.24 and peritumoural hypointensity on HBP (HR 4.53; 95% CI 1.52–13.4) were identified as independent factors associated with tumour recurrence. Having either of these radiological findings was associated with a higher tumour recurrence rate (72.5% vs. 15.4% at three years, p <0.001). When patients were stratified according to the Milan criteria, the presence of these two high-risk radiological findings was associated with a higher tumour recurrence rate in both patients transplanted within the Milan criteria (66.7% vs. 11.6% at three years, p <0.001, n = 68) and those who were transplanted outside the Milan criteria (75.5% vs. 28.6% at three years, p <0.001, n = 32).
Radiological features on preoperative hepatobiliary MRI can stratify the risk of tumour recurrence in patients who were transplanted either within or outside the Milan criteria. Therefore, hepatobiliary MRI can be a useful way to select potential candidates for LT.
High-risk radiological findings on preoperative hepatobiliary magnetic resonance imaging (either one of the following features: satellite nodule and peritumoural hypointensity on hepatobiliary phase) were associated with a higher tumour recurrence rate in patients transplanted either within or outside the Milan criteria.
Intrahepatic cholangiopathy is a life-threatening sequela of ABO-incompatible liver transplantation. We analyzed the clinical impact of pretransplant administration of mycophenolate mofetil in ...reducing intrahepatic cholangiopathy in ABO-incompatible liver transplantation. Patients who underwent living donor liver transplantation between 2010 and April 2022 were included. Pretransplant mycophenolate mofetil was started in November 2020. A comparison between patients who experienced intrahepatic cholangiopathy and who did not among ABO-incompatible transplantation was performed. Recipients of ABO-incompatible transplantations were categorized based on donor surgery into open, laparoscopy without pretransplant mycophenolate mofetil, and laparoscopy with pretransplant mycophenolate mofetil groups. Cox analysis of intrahepatic cholangiopathy was performed. A total of 234 ABO-incompatible transplantations were included. Intrahepatic cholangiopathy occurred in 1.1% (n=1/94), 13.3% (n=12/90), and 2.0% (n=1/50) of patients who received an ABO-incompatible liver with open surgery, laparoscopic donor surgery without pretransplant mycophenolate mofetil and laparoscopic donor surgery with pretransplant mycophenolate mofetil. ( p = 0.001) Multivariable analysis showed that transplantations involving a donor who underwent a laparoscopic hepatectomy and a recipient who did not receive pretransplant mycophenolate mofetil were associated with a higher risk of intrahepatic cholangiopathy (HR=13.449, CI=1.710-105.800, p = 0.02) compared with transplantations from donors who underwent open surgery. Transplantations involving a donor who underwent laparoscopic donor surgery and a recipient who received pretransplant mycophenolate mofetil resulted in no increased risk compared with transplantations from donors who underwent open surgery. (HR=5.307, CI=0.315-89.366, p = 0.25) Laparoscopic donor hepatectomy was a risk factor for intrahepatic cholangiopathy in ABO-incompatible liver transplantation, while pretransplant mycophenolate mofetil was related to risk reduction of intrahepatic cholangiopathy.
Background
Despite widespread adoption and technological advances in laparoscopic liver resection (LLR), conversion to laparotomy can still occur unexpectedly. Several studies have explored risk ...factors of open conversion (OC). However, most of these studies were conducted before 2018 and included all patients who underwent surgery at an early stage after starting LLR. The purpose of this study was to analyze the incidence and risk factors of OC in patients within the past 5 years (2017–2021).
Methods
Patients who underwent LLR at Samsung Medical Center from January 2017 to December 2021 were investigated. The incidence and causes of OC were investigated and risk factors associated with OC were also analyzed.
Results
A total of, 1951 patients were investigated. OC was observed in 34 patients (1.74%). The percentage of previous surgeries (50% vs. 25.5%,
P
< 0.001), history of hepatectomy (23.5% vs. 5.4%,
P
= 0.002), multi-focal disease (29.4% vs. 13.9%,
P
= 0.037), and posterosuperior (PS) location (64.7% vs. 39%,
P
= 0.004) were higher in the OC group. The most common cause of OC was adhesion (44.1%). In the analysis of risk factors associated with OC, PS location (OR 2.79,
P
= 0.007) and maximum tumor size (OR 0.92,
P
= 0.037) were statistically significant factors in multivariate analysis.
Conclusion
The updated incidence of OC was 1.74%. The main cause of OC was adhesion. In addition, PS location and smaller tumor size were risk factors associated with OC.
Background and Purpose
Several hepatectomy patients with HCC who are initially transplantable (within MC) developed untransplantable HCC recurrence (beyond MC) after primary curative liver resection. ...The purpose of our study is to identify the risk factors of untransplantable hepatocellular carcinoma (HCC) recurrence after primary curative resection of solitary HCC and solitary HCC within Milan criteria (MC).
Methods
We retrospectively reviewed 592 patients with recurrent HCC who underwent liver resection due to solitary HCC between 2005 and 2011.
Results
All patients were Child-Pugh class A. At primary curative hepatectomy, 411 patients (69.4%) were diagnosed with HCC within MC and 181 patients (30.6%) had HCC beyond MC. The mean time from primary hepatectomy to recurrence was 14 months (range, 1–116 months). At HCC recurrence, 93 patients (15.7%) were diagnosed beyond MC. Multivariate analysis showed that microvascular invasion and a tumor grade of 3 or 4 were closely associated with a high risk of HCC recurrence beyond MC in patients who had hepatectomy for solitary HCC. Of the 411 patients within MC at primary curative hepatectomy, 54 patients (13.9%) developed HCC recurrence beyond MC. Multivariate analysis also showed that microvascular invasion and a tumor grade of 3 or 4 were closely associated with HCC recurrence beyond MC in these patients.
Conclusions
The present study suggests that the presence of certain unfavorable histological factors in patients who underwent initial liver resection of transplantable HCC within MC with good liver function predicted the development of recurrent HCC beyond MC.
Greater graft-failure-risk of female-to-male liver transplantation (LT) is thought to be due to acute decrease in hepatic-estrogen-signaling. Our previous research found evidence that female ...hepatic-estrogen-signaling decreases after 40 years or with macrosteatosis. Thus, we hypothesized that inferiority of female-to-male LT changes according to donor-age and macrosteatosis. We stratified 780 recipients of grafts from living-donors into four subgroups by donor-age and macrosteatosis and compared graft-failure-risk between female-to-male LT and other LTs within each subgroup using Cox model. In recipients with ≤ 40 years non-macrosteatotic donors, graft-failure-risk was significantly greater in female-to-male LT than others (HR 2.03 1.18-3.49, P = 0.011). Within the subgroup of recipients without hepatocellular carcinoma, the inferiority of female-to-male LT became greater (HR 4.75 2.02-11.21, P < 0.001). Despite good graft quality, 1y-graft-failure-probability was 37.9% (23.1%-57.9%) in female-to-male LT within this subgroup while such exceptionally high probability was not shown in any other subgroups even with worse graft quality. When donor was > 40 years or macrosteatotic, graft-failure-risk was not significantly different between female-to-male LT and others (P > 0.60). These results were in agreement with the estrogen receptor immunohistochemistry evaluation of donor liver. In conclusion, we found that the inferiority of female-to-male LT was only found when donor was ≤ 40 years and non-macrosteatotic. Abrogation of the inferiority when donor was > 40 years or macrosteatotic suggests the presence of dominant contributors for post-transplant graft-failure other than graft quality/quantity and supports the role of hepatic-estrogen-signaling mismatch on graft-failure after female-to-male LT.
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