Value of Doppler ultrasonography in predicting clinical outcomes for patients with acute cellular rejection after liver transplantation.

PURPOSE: This study investigated the value of Doppler ultrasonography in predicting clinical outcomes after antirejection treatment for patients with acute cellular rejection (ACR) following liver transplantation (LT). METHODS: This retrospective study included 84 patients who were pathologically diagnosed with ACR and received antirejection treatment within 90 days following LT. Two radiologists searched for abnormal Doppler parameters at ACR diagnosis and within 7 days after antirejection treatment initiation, including portal blood velocity (PBV) <20 cm/s, hepatic artery resistive index <0.5, and a monophasic hepatic vein flow pattern. Interval PBV changes were also evaluated. The frequencies of abnormal Doppler parameters and PBV changes were compared by treatment outcome. RESULTS: The frequency of abnormal PBV in the early post-treatment phase (PBVearly post-treatment) was significantly higher among poor responders (50.0% [10/20]) than among good responders (7.8% [5/64]) (P<0.001). The sensitivity, specificity, and accuracy of abnormal PBVearly post-treatment as a predictor of poor response to antirejection treatment were 50.0% (10/20), 92.2% (59/64), and 82.1% (69/84), respectively. A decrease (>10%) from the PBV at event (PBVevent) to PBVearly post-treatment was significantly more common among poor responders (50.0% [10/20]) than among good responders (20.3% [13/64]) (P=0.019). The sensitivity, specificity, and accuracy of this PBV decrease in predicting poor treatment response were 50.0% (10/20), 79.7% (51/64), and 72.6% (61/84), respectively. CONCLUSION: Abnormal PBVearly post-treatment and a decrease between PBVevent and PBVearly post-treatment were significantly associated with poor treatment response in patients with ACR after LT. Consequently, Doppler ultrasonography may be useful for predicting clinical outcomes in these patients.

Cutoff Values for Diagnosing Hepatic Steatosis Using Contemporary MRI-Proton Density Fat Fraction Measuring Methods.

OBJECTIVE: To propose standardized MRI-proton density fat fraction (PDFF) cutoff values for diagnosing hepatic steatosis, evaluated using contemporary PDFF measuring methods in a large population of healthy adults, using histologic fat fraction (HFF) as the reference standard. MATERIALS AND METHODS: A retrospective search of electronic medical records between 2015 and 2018 identified 1063 adult donor candidates for liver transplantation who had undergone liver MRI and liver biopsy within a 7-day interval. Patients with a history of liver disease or significant alcohol consumption were excluded. Chemical shift imaging-based MRI (CS-MRI) PDFF and high-speed T2-corrected multi-echo MR spectroscopy (HISTO-MRS) PDFF data were obtained. By temporal splitting, the total population was divided into development and validation sets. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the MRI-PDFF method. Two cutoff values with sensitivity > 90% and specificity > 90% were selected to rule-out and rule-in, respectively, hepatic steatosis with reference to HFF ≥ 5% in the development set. The diagnostic performance was assessed using the validation set. RESULTS: Of 921 final participants (624 male; mean age ± standard deviation, 31.5 ± 9.0 years), the development and validation sets comprised 497 and 424 patients, respectively. In the development set, the areas under the ROC curve for diagnosing hepatic steatosis were 0.920 for CS-MRI-PDFF and 0.915 for HISTO-MRS-PDFF. For ruling-out hepatic steatosis, the CS-MRI-PDFF cutoff was 2.3% (sensitivity, 92.4%; specificity, 63.0%) and the HISTO-MRI-PDFF cutoff was 2.6% (sensitivity, 88.8%; specificity, 70.1%). For ruling-in hepatic steatosis, the CS-MRI-PDFF cutoff was 3.5% (sensitivity, 73.5%; specificity, 88.6%) and the HISTO-MRI-PDFF cutoff was 4.0% (sensitivity, 74.7%; specificity, 90.6%). CONCLUSION: In a large population of healthy adults, our study suggests diagnostic thresholds for ruling-out and ruling-in hepatic steatosis defined as HFF ≥ 5% by contemporary PDFF measurement methods.

Sex-specific Cutoff Values of Visceral Fat Area for Lean vs. Overweight/Obese Nonalcoholic Fatty Liver Disease in Asians.

Background and Aims: Visceral obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD). We investigated sex-specific optimal cutoff values for visceral fat area (VFA) associated with lean and overweight/obese NAFLD in an Asian population. Methods: This retrospective study included 678 potential living liver donors (mean age, 30.8±9.4 years; 434 men and 244 women) who had undergone abdominal computed tomography (CT) imaging and liver biopsy between November 2016 and October 2017. VFA was measured using single-slice abdominal CT. NAFLD was evaluated by liver biopsy (≥5% hepatic steatosis). Receiver operating characteristic curve analysis was used to determine cutoff values for VFA associated with lean (body mass index [BMI] <23 kg/m2) and overweight/obese (BMI ≥23 kg/m2) NAFLD. Results: Area under the curve (AUC) values with 95% confidence intervals (CI) for VFA were 0.82 (95% CI, 0.75-0.88) for lean and 0.74 (95% CI, 0.69-0.79) for overweight/obese men with NAFLD. The AUC values were 0.67 (95% CI, 0.58-0.75) for lean and 0.71 (95% CI, 0.62-0.80) for overweight/obese women with NAFLD. The cutoff values for VFA associated with lean NAFLD were 50.2 cm2 in men and 40.5 cm2 in women. The optimal cutoff values for VFA associated with overweight/obese NAFLD were 100.6 cm2 in men and 68.0 cm2 in women. Conclusions: Sex-specific cutoff values for VFA may be useful for identifying subjects at risk of lean and overweight/obese NAFLD.

Oral effervescent agent improving magnetic resonance cholangiopancreatography.

Background: The purpose of our study was to validate the oral effervescent agent improving magnetic resonance cholangiopancreatography (MRCP) in patients with suspicious pancreatobiliary disease. Methods: One hundred and eleven consecutive patients with alleged or suspected pancreatobiliary tree problems who had undergone two-dimensional (2D) MRCP imaging both before and after oral effervescent enhancement (conventional-MRCP and enhanced-MRCP) were included. Two radiologists independently scored overall image quality, visualization of ten ductal segments, and gastroduodenal fluid signal intensity score. In consensus, they assessed the presence of gastroduodenal fluids and pancreatobiliary tree overlapping. The data were analyzed using Wilcoxon's signed-rank test, McNemar test, and paired t-test. Results: The grades of overall image quality and individual biliary duct visualization for ten targeted ductal segments, and gastroduodenal fluid signal intensity scores increased significantly on enhanced-MRCP by both readers (P≤0.02), but there was no significant increase for pancreatic duct (PD) at head and tail. On enhanced-MRCP, gastroduodenal fluids except for gastric fundus were less detected rather than those on conventional-MRCP. Anatomic structures of gastroduodenal fluids overlapping extrahepatic bile duct were mainly gastric antrum, duodenal bulb, and 2nd portion on conventional-MRCP. However, these fluids were less overlapped on enhanced-MRCP (P<0.001). Gastric body and antrum were main anatomic structures of gastroduodenal fluids overlapping PD on conventional-MRCP, and fluid in these locations significantly less overlapped PD on enhanced-MRCP (P≤0.02). Conclusions: Oral administration of effervescent agent provided effective elimination of gastroduodenal fluid overlapping pancreatobiliary ductal system at MRCP and can improve the quality of the examination in the patients with known or suspected pancreatobiliary disease.

CT-based visual grading system for assessment of hepatic steatosis: diagnostic performance and interobserver agreement.

BACKGROUND: Hepatic steatosis (HS) can be comprehensively assessed by visually comparing the hepatic and vessel attenuation on unenhanced computed tomography (CT). We aimed to evaluate the reliability and reproducibility of a CT-based visual grading system (VGS) for comprehensive assessment of HS. METHODS: In this retrospective study, a four-point VGS based on the visual comparison of liver and hepatic vessels was validated by six reviewers with diverse clinical experience using the unenhanced CT images of 717 potential liver donors. The diagnostic performance of VGS and quantitative indices (difference and ratio of the hepatic and splenic attenuation) to diagnose HS were evaluated using multi-reader multi-case receiver operating characteristics (ROC) analysis (reference: pathology). The interobserver agreement was assessed using Fleiss κ statistics. RESULTS: Using the VGS, all six reviewers showed areas under the ROC curves (AUROCs) higher than 0.9 for diagnosing total steatosis (TS) ≥ 30%, macrovesicular steatosis (MaS) ≥ 30%, and MaS ≥ 10%. No difference was noted between the AUROCs of the VGS and quantitative indices (p ≥ 0.1). The reviewers showed substantial agreement (Fleiss κ, 0.61). Most discrepancies occurred between the two lowest grades of VGS (81.5%; 233/283), in which most subjects (97.0%; 226/233) had a MaS < 10%. The average-reader sensitivity and specificity of the VGS were 0.80 and 0.94 to detect TS ≥ 30% and 0.93 and 0.81 to detect MaS ≥ 10%. CONCLUSION: VGS was reliable and reproducible in assessing HS. It may be useful as a non-invasive and simple tool for comprehensive HS assessment.

Progression of Portal Hypertension in Acute Cellular Rejection After Liver Transplantation.

OBJECTIVES: This study was designed to investigate the frequency of computed tomography features indicating progression of portal hypertension and their clinical relevance in patients who experienced acute cellular rejection after liver transplantation. MATERIALS AND METHODS: This retrospective study included 141 patients with pathologically diagnosed acute cellular rejection following liver transplant. Patients were divided into early and late rejection groups according to the time of diagnosis. Two radiologists analyzed the interval changes in spleen size and variceal engorgement on computed tomography images obtained at the times of surgery and biopsy. Aggravation of splenomegaly and variceal engorgement were considered computed tomography features associated with the progression of portal hypertension. Clinical outcomes, including responses to treatment and graft survival, were compared between patients with and without these features. RESULTS: The frequency of progression of portal hypertension was 31.9% and did not differ significantly in patients who experienced early (30.8% [28/91]) and late (34.0% [17/50]) rejection (P = .694). In the late rejection group, computed tomography features indicating progression of portal hypertension were significantly associated with poor response to treatment (P = .033). Graft survival in both the early and late rejection groups did not differ significantly in patients with and without progression of portal hypertension. CONCLUSIONS: Computed tomography features suggesting the progression of portal hypertension were encountered in about one-third of patients who experienced acute cellular rejection after liver transplant. Progression of portal hypertension was significantly related to poor response to treatment in the late rejection group.

Relationship of body mass index and abdominal fat with radiation dose received during preoperative liver CT in potential living liver donors: a cross-sectional study.

Background: Although contrast-enhanced computed tomography (CT) is currently the most widely-used imaging modality for the preoperative evaluation of potential living liver donors, radiation exposure remains a major concern. The present study aimed to determine the relationship of body mass index (BMI) and abdominal fat with the effective radiation dose received during liver CT scans as part of a pre-donation work-up in potential living donors. Methods: This retrospective cross-sectional study included 695 potential living donors (mean age, 30.5±9.7 years; 445 men and 250 women) who had undergone preoperative liver CT scans between 2017 and 2018. The following measures were evaluated: BMI, abdominal fat as measured at the level of the third lumbar vertebra, and effective dose based on the dose length product (DLP). Correlations between the effective dose and other variables were evaluated using Pearson's correlation coefficient. Results: The mean BMI, total fat area (TFA), and effective dose were 23.6±3.3 kg/m2, 218.7±110.0 cm2, and 9.4±3.3 mSv, respectively. The effective dose during liver CT scans had a strong positive correlation with both BMI (r=0.715; P<0.001) and TFA (r=0.792; P<0.001). As BMI and TFA increased, so did the effective dose. Conclusions: Higher BMI and TFA significantly increased the radiation dose received during liver CT scans in potential living donors.

Visceral Fat Area Is an Independent Risk Factor for Overweight or Obese Nonalcoholic Fatty Liver Disease in Potential Living Liver Donors.

BACKGROUND: The present study aimed to evaluate the correlation between hepatic steatosis (HS), determined by biopsy, and visceral adiposity, measured by computed tomography (CT), in overweight or obese potential living liver donors, and to investigate the risk factors for overweight or obese nonalcoholic fatty liver disease (NAFLD). METHODS: This retrospective study included 375 overweight or obese (body mass index ≥23 kg/m2) potential living liver donors (mean age, 30.4 ± 9.5 years; 273 men) who underwent liver biopsies and abdominal CT examinations in 2017 and 2018. Anthropometry, laboratory parameters, body composition, and HS were assessed. Correlations were analyzed using Pearson's correlation coefficient, and logistic regression was used to identify independent predictors of overweight or obese NAFLD. RESULTS: Visceral fat area (VFA) was positively correlated with the degree of HS in men (r = 0.307; P < .001) and women (r = 0.387; P < .001). Multivariable logistic regression analysis showed that alanine aminotransferase (odds ratio [OR], 1.017; 95% confidence interval [CI], 1.001-1.033; P = .033) and VFA (OR, 1.015; 95% CI, 1.008-1.022; P < .001) were independent risk factors for overweight or obese NAFLD in men, and VFA (OR, 1.029; 95% CI, 1.011-1.047; P = .002) was an independent risk factor for overweight or obese NAFLD in women. CONCLUSION: Visceral adiposity was positively correlated with the degree of HS in overweight or obese potential living liver donors. Additionally, visceral adiposity may be an independent risk factor for overweight or obese NAFLD in potential living liver donors.

Comparison of gadoxetate disodium-enhanced MRI sequences for measuring hepatic observation size and its implication of LI-RADS classification.

PURPOSE: We aimed to determine the optimal image sequence for measurement of hepatic observations on gadoxetate disodium-enhanced MRI in comparison with pathologic measurement, and to evaluate its clinical impact on the Liver Imaging Reporting and Data System (LI-RADS) v2018 classification. METHODS: Two hundred and fifty-three patients (279 hepatic observations) who underwent gadoxetate disodium-enhanced MRI and subsequent hepatectomy were retrospectively included. Two radiologists independently evaluated the visualization score (five-point scale) and size of each observation on six MRI sequences (T1-weighted, T2-weighted, arterial-phase, portal venous-phase, transitional-phase [TP], and hepatobiliary-phase [HBP] images) and assigned a LI-RADS category. Correlations between MRI and pathologic measurements were evaluated using Pearson correlation coefficients. A repeated measures analysis of variance with Bonferroni post hoc comparison tests was used to compare the visualization scores and absolute differences between MRI sequences and pathologic measurements. The LI-RADS classification according the size measurement of each MRI sequence was compared using Cochran's Q test with a post hoc McNemar's test. RESULTS: Of the MRI sequences, HBP had the highest visualization score (4.1 ± 0.6) and correlation coefficient (r = 0.965). The absolute difference between MRI and pathologic measurement was lowest on TP (2.3 mm ± 2.2), followed by HBP (2.4 mm ± 2.1). In the LI-RADS classifications, HBP did not have any non-visible observations. Regarding LR-3, LR-4, and LR-5, there was no significantly different LI-RADS classification among the six MRI sequences (p ≥ 0.122). CONCLUSION: Hepatobiliary-phase images are clinically useful for measuring hepatic observations on gadoxetate disodium-enhanced MRI, especially regarding visibility and correlation with pathologic findings.

Improving the Specificity of CT Angiography for the Diagnosis of Hepatic Artery Occlusion after Liver Transplantation in Suspected Patients with Doppler Ultrasound Abnormalities.

OBJECTIVE: To investigate whether the diagnostic performance of CT angiography (CTA) could be improved by modifying the conventional criterion (anastomosis site abnormality) to diagnose hepatic artery occlusion (HAO) after liver transplantation (LT) in suspected patients with Doppler ultrasound (US) abnormalities. MATERIALS AND METHODS: One hundred thirty-four adult LT recipients (88 males and 46 females; mean age, 52.7 years) with suspected HAO on Doppler US (40 HAO and 94 non-HAO according to the reference standards) were included. We evaluated 1) abnormalities in the HA anastomosis, categorized as a cutoff, ≥ 50% stenosis at the anastomotic site, or diffuse stenosis at both graft and recipient sides around the anastomosis, and 2) abnormalities in the distal run-off, including invisibility or irregular, faint, and discontinuous enhancement. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the conventional (considering anastomosis site abnormalities alone) and modified CTA criteria (abnormalities in both the anastomosis site and distal run-off) for the diagnosis of HAO were calculated and compared using the McNemar test. RESULTS: By using the conventional criterion to diagnose HAO, the sensitivity, specificity, PPV, NPV, and accuracy were 100% (40/40), 74.5% (70/94), 62.5% (40/64), 100% (70/70), and 82.1% (110/134), respectively. The modified criterion for diagnosing HAO showed significantly increased specificity (93.6%, 88/94) and accuracy (93.3%, 125/134) compared to that with the conventional criterion (p = 0.001 and 0.002, respectively), although the sensitivity (92.5%, 37/40) decreased slightly without statistical significance (p = 0.250). CONCLUSION: The modified criterion considering abnormalities in both the anastomosis site and distal run-off improved the diagnostic performance of CTA for HAO in suspected patients with Doppler US abnormalities, particularly by increasing the specificity.

Controlled attenuation parameter measured using transient elastography for the noninvasive assessment of macrovesicular steatosis in potential living liver donors.

PURPOSE: This study aimed to determine the diagnostic performance of the controlled attenuation parameter (CAP) measured using transient elastography (TE) for assessing macrovesicular steatosis (MaS) in potential living liver donors using same-day biopsy as a reference standard. METHODS: This retrospective study included 204 living liver donor candidates who underwent TE and liver biopsy on the same day between July 2013 and June 2014. The histologic degree of MaS was determined. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of CAP for diagnosing MaS of >10%, and the optimal cutoff value was identified using the maximal Youden index. RESULTS: Based on liver biopsy, 185 subjects had MaS of ≤10% and 19 had MaS of >10%. The CAP value was significantly correlated with the percentage of MaS on liver biopsy (r=0.635, P<0.001), and the median CAP value was significantly higher in subjects with MaS of >10% than in those with MaS of ≤10% (300 dB/m vs. 209 dB/m, P<0.001). The AUROC for diagnosing MaS of >10% by CAP was 0.938 (95% confidence interval, 0.896 to 0.967), and a CAP of >259 dB/m yielded a sensitivity of 84.2% and a specificity of 92.4%. CONCLUSION: The CAP measured using TE was significantly correlated with MaS and accurately detected substantial MaS in potential living liver donors. The CAP is a promising tool for the noninvasive diagnosis of MaS and may be used to screen unsuitable living liver donor candidates.

Nanoparticle delivery of recombinant IL-2 (BALLkine-2) achieves durable tumor control with less systemic adverse effects in cancer immunotherapy.

Recent strategies in cancer immunotherapy based on interleukin-2 (IL-2) are generally focused on reducing regulatory T cell (Treg) development by modifying IL-2 receptor alpha (IL-2Rα) domain. However, the clinical utility of high-dose IL-2 treatment is mainly limited by severe systemic toxicity. We find that peritumorally injectable 'BALLkine-2', recombinant human IL-2 (rIL-2) loaded porous nanoparticle, dramatically reduces systemic side effects of rIL-2 by minimizing systemic IL-2 exposure. Notably, in cynomolgus monkeys, subcutaneous (SC)-injection of BALLkine-2 not only dramatically reduces systemic circulation of rIL-2 in the blood, but also increases half-life of IL-2 compared to IV- or SC-injection of free rIL-2. Peritumorally-injected BALLkine-2 enhances intratumoral lymphocyte infiltration without inducing Treg development and more effectively synergizes with PD-1 blockade than high-dose rIL-2 administration in B16F10 melanoma model. BALLkine-2 could be a highly potent therapeutic option due to higher anti-tumor efficacy with lower and fewer doses and reduced systemic toxicity compared to systemic rIL-2.

Impact of the preoperative skeletal muscle index on early remnant liver regeneration in living donors after liver transplantation.

Background: We investigated the correlation between the preoperative skeletal muscle index (SMI) and remnant liver regeneration after right hemihepatectomy for living-donor liver transplantation and aimed to identify preoperative predictors of greater early remnant liver regeneration in living donors. Methods: This retrospective study included 525 right hemiliver donors (mean age, 28.9±8.3 years; 345 male patients) between 2017 and 2018, who underwent computed tomography before surgery and on postoperative day (POD) 7. Preoperative anthropometry, laboratory parameters, skeletal muscle area at the third lumbar vertebral level, and liver volume before and after surgery were evaluated. Correlations were analyzed using Pearson correlation coefficients, and stepwise multiple regression analysis was performed to identify independent predictors of greater remnant liver regeneration. Results: Remnant liver regeneration volume on POD 7 was positively correlated with body mass index (BMI; r=0.280, P<0.001) and SMI (r=0.322, P<0.001), and negatively correlated with age (r=-0.154, P<0.001) and the ratio of future remnant liver volume (FRLV) to total liver volume (TLV; r=-0.261, P<0.001). Stepwise multiple regression analysis showed that high BMI (ß=0.146; P=0.001) and SMI (ß=0.228, P<0.001), young age (ß=-0.091, P=0.025), and a low FRLV/TLV ratio (ß=-0.225, P<0.001) were predictors of greater remnant liver regeneration. Conclusions: High SMI and BMI, young age, and a low FRLV/TLV ratio may predict greater early remnant liver regeneration in living donors after LDLT.

Visceral adiposity as a risk factor for lean non-alcoholic fatty liver disease in potential living liver donors.

BACKGROUND AND AIM: This study aimed to investigate the relationship between hepatic steatosis (HS) evaluated by biopsy and visceral adiposity assessed by computed tomography in lean living liver donor candidates and to determine the risk factors for lean non-alcoholic fatty liver disease (NAFLD). METHODS: This retrospective study included 250 lean (body mass index, < 23 kg/m2 ) potential living liver donors (mean age, 31.1 ± 8.6 years; 141 men) who had undergone liver biopsy and abdominal computed tomography between 2017 and 2018. Anthropometry, laboratory parameters, body composition, and the degree of HS were evaluated. Logistic regression was used to identify independent predictors of lean NAFLD. RESULTS: The visceral fat area (VFA) was significantly correlated with the degree of HS in men (r = 0.408; P < 0.001) and women (r = 0.360; P < 0.001). The subcutaneous fat area was significantly correlated with the degree of HS in men (r = 0.398; P < 0.001), but not in women. The skeletal muscle area did not correlate with the degree of HS in either men or women. In the multivariable logistic regression analysis, the VFA (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.013-1.044; P < 0.001) and subcutaneous fat area (OR, 1.016; 95% CI, 1.004-1.028; P = 0.009) were independent risk factors for lean NAFLD in men, and the VFA (OR, 1.036; 95% CI, 1.013-1.059; P = 0.002) was an independent risk factor for lean NAFLD in women. CONCLUSIONS: The severity of non-alcoholic fatty liver was positively correlated with visceral fat accumulation in a lean Asian population. Visceral adiposity may be a risk factor for lean NAFLD in potential living liver donors.

Reference Values for Skeletal Muscle Mass at the Third Lumbar Vertebral Level Measured by Computed Tomography in a Healthy Korean Population.

BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and is associated with negative clinical outcomes. This study aimed to establish sex-specific cutoff values for the skeletal muscle area (SMA) and skeletal muscle index (SMI) at the third lumbar vertebral (L3) level using computed tomography (CT) imaging to identify sarcopenia in healthy Korean liver donors. METHODS: This retrospective study included 659 healthy liver donors (408 men and 251 women) aged 20 to 60 years who had undergone abdominal CT examinations between January 2017 and December 2018. Assessment of body composition was performed with an automated segmentation technique using a deep-learning system. Sex-specific SMA and SMI distributions were assessed, and cutoff values for determining sarcopenia were defined as values at either two standard deviations (SDs) below the mean reference value or below the fifth percentile. RESULTS: Using the SD definition, cutoff values for SMA and SMI were 117.04 cm2 and 39.33 cm2/m2, respectively, in men and 71.39 cm2 and 27.77 cm2/m2, respectively, in women. Using the fifth percentile definition, cutoff values for SMA and SMI were 126.88 cm2 and 40.96 cm2/m2, respectively, in men and 78.85 cm2 and 30.60 cm2/m2, respectively, in women. CONCLUSION: Our data provide sex-specific cutoff values for the SMA and SMI at the L3 level measured by CT imaging in a healthy Korean population, which may be applicable for identifying sarcopenia in this population.

Reduction of Visceral Adiposity as a Predictor for Resolution of Nonalcoholic Fatty Liver in Potential Living Liver Donors.

This study aimed to determine the factors associated with resolution of nonalcoholic fatty liver (NAFL) after lifestyle intervention in potential living liver donors as assessed by the gold standards in a longitudinal setting. This retrospective study included 115 potential living liver donors (mean age, 30.5 ± 7.5 years; 101 men) with NAFL who underwent paired liver biopsies and abdominal computed tomography (CT) examinations before and after lifestyle intervention between January 2011 and December 2018. Anthropometry, laboratory parameters, body composition, and hepatic steatosis (HS) were evaluated before and after lifestyle intervention. Anthropometry, laboratory parameters, body composition, and HS were significantly decreased after lifestyle intervention (all, P < 0.001). Relative changes in HS were weakly correlated with relative changes in the visceral fat area (VFA; r = 0.278; P = 0.003) and subcutaneous fat area (r = 0.382; P < 0.001), but not with body weight, body mass index, or skeletal muscle area. Patients with resolved NAFL after lifestyle intervention had significantly lower VFA at follow-up than those with persistent NAFL (mean ± standard deviation, 69.8 ± 39.1 versus 91.5 ± 41.4 cm2 ; P = 0.01). Multivariable logistic regression analysis demonstrated that the relative reduction of VFA (odds ratio per percent, 1.031; 95% confidence interval, 1.010-1.053; P = 0.004) was a significant independent factor associated with resolved NAFL after lifestyle intervention. In potential living liver donors with NAFL, the reduction of VFA is a significant factor associated with the resolution of NAFL after lifestyle intervention.

Liver Imaging Reporting and Data System Category on Magnetic Resonance Imaging Predicts Recurrence of Hepatocellular Carcinoma After Liver Transplantation Within the Milan Criteria: A Multicenter Study.

BACKGROUND: This study was designed to investigate the association between Liver Imaging Reporting and Data System (LI-RADS) category and recurrence of hepatocellular carcinoma (HCC) after primary liver transplantation (LT) within the Milan criteria. METHODS: This multicenter, retrospective study included 140 recipients who underwent living donor LT (LDLT) for treatment-naïve HCC and pretransplant contrast-enhanced magnetic resonance imaging (MRI) between 2009 and 2013. LI-RADS categories were assigned using LI-RADS version 2018. Recurrence-free survival (RFS) and associated factors were evaluated using Cox proportional hazards regression analysis, Kaplan-Meier analysis, and log-rank test. Histological grading and microvascular invasion (MVI) were analyzed on the pathologic examinations of explanted livers. RESULTS: The overall 1-, 3-, 5-, and 7-year RFS rates were 95.6%, 92.6%, 90.2%, and 89.3%, respectively. In the multivariable analysis, independent predictors of recurrence included HCCs categorized as LR-M (hazard ratio [HR], 18.68; 95% confidence interval [CI], 5.79-60.23; P < 0.001) and the largest tumor size of ≥ 3 cm on MRI (HR, 4.18; 95% CI, 1.42-12.37; P = 0.010). The 5-year RFS rate was significantly lower in patients with HCCs categorized as LR-M than in those with HCCs categorized as LR-5 or 4 (LR-5/4) (36.9% vs. 95.8%, respectively; P < 0.001). HCCs categorized as LR-M exhibited significantly more MVI than HCCs categorized as LR-5/4 (57.1% vs. 17.5%, respectively; P = 0.002). CONCLUSIONS: Patients with HCCs categorized as LR-M using LI-RADS version 2018 may have a worse prognosis after primary LT within the Milan criteria than those with HCCs categorized as LR-5/4.

Change in hepatic volume profile in potential live liver donors after lifestyle modification for reduction of hepatic steatosis.

PURPOSE: We aimed to evaluate changes in hepatic volume and hemiliver volume percentage in potential liver donors after hepatic steatosis (HS) reduction through lifestyle modification. METHODS: Fifty liver donor candidates with HS (macrovesicular fat [MaF] ≥ 20%) underwent abdominal computed tomography (CT) and liver biopsy before (baseline) and after (follow-up) lifestyle modification. According to the change in MaF, subjects were classified as group A (MaF reduction ≥ 20%, n = 25), and group B (MaF reduction < 20%, n = 25). The hepatic volume and hemiliver volume percentage were measured using CT volumetric analysis. RESULTS: Volume percentage of the left hemiliver + S1 (over the whole liver) significantly increased at follow-up in group A (P < 0.001) but not in group B (P = 0.598). The absolute volume change of the right hemiliver and its percentage change from the baseline were significantly greater than those of the left hemiliver + S1 in group A (P < 0.007). There were no significant differences in these values in group B (P = 0.064 and 0.507, respectively). The percentage of subjects that earned the benefit of becoming suitable donors from the change in hepatic volume distribution caused by HS improvement was 52.0% (13/25) and 40.0% (10/25) in group A and group B, respectively. Regarding posthepatectomy liver failure, none was identified in group A after donation, whereas 12% (3/25) was identified in group B. CONCLUSION: Hepatic volume profile may change considerably in potential liver donors with HS (MaF ≥ 20%) after HS reduction through lifestyle modification. Reevaluation of the hepatic volume is required before liver procurement after lifestyle modification in these subjects.

Reappraisal of the prognostic value of Epstein-Barr virus status in monomorphic post-transplantation lymphoproliferative disorders-diffuse large B-cell lymphoma.

The role of the Epstein-Barr virus (EBV) status in the blood for predicting survival in post-transplantation lymphoproliferative disorders-diffuse large B-cell lymphoma (PTLD-DLBCL) is unknown. We evaluated the prognostic values of pre-treatment EBV-encoded small RNA (EBER) detected with in situ hybridization in tissues and EBV DNA in the whole blood (WB) and plasma in 58 patients with monomorphic PTLD-DLBCL after solid organ transplantation. There were no significant differences in the rates of overall response, complete response, and survival according to EBER EBV and WB EBV status. In contrast, patients with positive plasma EBV DNA had significantly lower rates of overall response (60.0% vs. 94.4%, P = 0.043) and complete response (40.0% vs. 88.9%, P = 0.019) as well as worse progression-free survival (PFS) (P = 0.035) and overall survival (OS) (P = 0.039) compared with patients with negative plasma EBV DNA. In multivariate analysis, plasma EBV DNA positivity was a significantly unfavorable prognostic factor for PFS [hazard ratio (HR) 4.92, 95% confidence interval (CI) 1.22-19.86, P = 0.025] and OS (HR 4.48, 95% CI 1.14-17.63, P = 0.032). Despite small number of 6 patients with plasma EBV positivity, plasma EBV DNA positivity might be more prognostic for survival than EBER or WB EBV DNA positivity in patients with monomorphic PTLD-DLBCL.