CT of acute rejection after liver transplantation: a matched case-control study.

PURPOSE: This study was conducted in order to investigate computed tomography (CT) findings associated with acute cellular rejection (ACR) following liver transplantation (LT) and their relevance to clinical outcomes. MATERIALS AND METHODS: We analyzed 120 patients with newly diagnosed ACR following LT for various liver diseases and 119 controls matched for age, sex, type of liver graft, and date of CT exam following LT. Two radiologists analyzed the images for morphological characteristics of the graft, morphological change in the major draining vein, graft enhancement in the portal venous phase, graft attenuation on noncontrast CT, and periportal halo. Univariate analysis was used to determine the association between radiological findings and ACR. Clinical outcomes, including treatment response and graft survival, were compared between patients with and without associated radiological findings. RESULTS: Morphological characteristics of the graft (i.e., globular swelling), morphological change in the major draining vein (i.e., nonanastomotic luminal narrowing), and heterogeneous enhancement were significantly associated with ACR (all p < 0.001). On univariate analysis, the severity of morphological characteristics of the grafts (mild/severe: odds ratio [OR], 19.98/32.24) and morphological change in the major draining vein (without/with prestenotic dilatation: OR, 4.17/22.5) were significantly associated with the increased possibility of an ACR diagnosis. Clinical outcomes for treatment response and graft survival were not significantly different between patients with and without associated radiological findings. CONCLUSIONS: Globular swelling, nonanastomotic stenosis with or without prestenotic dilatation of the major draining vein, and heterogeneous enhancement of the graft on portal venous-phase CT were significantly associated with ACR. KEY POINTS: • Globular swelling of the graft, nonanastomotic narrowing in the major vein, and heterogeneous graft enhancement on CT were significantly associated with acute cellular rejection (ACR). • Associated CT findings were highly specific but not sensitive for differentiating ACRs from matched controls.

CT indices for the diagnosis of hepatic steatosis using non-enhanced CT images: development and validation of diagnostic cut-off values in a large cohort with pathological reference standard.

OBJECTIVES: To compare the performances of CT indices for diagnosing hepatic steatosis (HS) and to determine and validate the CT index cut-off values. METHODS: Three indices were measured on non-enhanced CT images of 4413 living liver donor candidates (2939 men, 1474 women; mean age, 31.4 years): hepatic attenuation (CTL), hepatic attenuation minus splenic attenuation (CTL-S), and hepatic attenuation divided by splenic attenuation (CTL/S). The performances of these CT indices in diagnosing HS, relative to pathologic diagnosis, were compared in the development cohort of 3312 subjects by receiver operating characteristic (ROC) analysis. The cut-off values for diagnosing HS > 33% in the development cohort were determined at 95% specificity and 95% sensitivity using bootstrap ROC analysis, and the diagnostic performance of these cut-off values was validated in the test cohort of 1101 subjects. RESULTS: CTL-S showed the highest performance for diagnosing HS ≥ 5% and HS > 33% (areas under the curve (AUCs) = 0.737 and 0.926, respectively), followed by CTL/S (AUCs = 0.732 and 0.925, respectively) and CTL (AUCs = 0.707 and 0.880, respectively). For CT scans using 120 kVp, the CTL-S cut-off values for highly specific (i.e., - 2.1) and highly sensitive (i.e., 7.6) diagnosis of HS > 33% resulted in a specificity of 96.4% with a sensitivity of 64.0% and a sensitivity of 97.3% with a specificity of 54.9%, respectively, in the test cohort. CONCLUSION: CT indices using liver and spleen attenuations have higher performance for diagnosing HS than indices using liver attenuation alone. The CTL-S cut-off values in this study may have utility for diagnosing HS in clinical practice and research. KEY POINTS: • CT indices based on both liver attenuation and spleen attenuation (CTL-Sand CTL/S) have higher diagnostic performance than CTLbased on liver attenuation alone in diagnosing HS using various CT techniques. • The CT index cut-off values determined in this study can be utilized for reliable diagnosis or to rule out subjects with moderate to severe HS in clinical practice and research, including the selection of living liver donors and the development of cohorts with HS or healthy controls.

Development and Validation of a Deep Learning System for Staging Liver Fibrosis by Using Contrast Agent-enhanced CT Images in the Liver.

Purpose To develop and validate a deep learning system (DLS) for staging liver fibrosis by using CT images in the liver. Materials and Methods DLS for CT-based staging of liver fibrosis was created by using a development data set that included portal venous phase CT images in 7461 patients with pathologically confirmed liver fibrosis. The diagnostic performance of the DLS was evaluated in separate test data sets for 891 patients. The influence of patient characteristics and CT techniques on the staging accuracy of the DLS was evaluated by logistic regression analysis. In a subset of 421 patients, the diagnostic performance of the DLS was compared with that of the radiologist's assessment, aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 index by using the area under the receiver operating characteristic curve (AUROC) and Obuchowski index. Results In the test data sets, the DLS had a staging accuracy of 79.4% (707 of 891) and an AUROC of 0.96, 0.97, and 0.95 for diagnosing significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), respectively. At multivariable analysis, only pathologic fibrosis stage significantly affected the staging accuracy of the DLS (P = .016 and .013 for F1 and F2, respectively, compared with F4), whereas etiology of liver disease and CT technique did not. The DLS (Obuchowski index, 0.94) outperformed the radiologist's interpretation, APRI, and fibrosis-4 index (Obuchowski index range, 0.71-0.81; P ˂ .001) for staging liver fibrosis. Conclusion The deep learning system allows for accurate staging of liver fibrosis by using CT images. © RSNA, 2018 Online supplemental material is available for this article.

Longterm prognosis of combined hepatocellular carcinoma-cholangiocarcinoma following liver transplantation and resection.

Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is a rare disease. We investigated the clinicopathological features of cHCC-CC and compared the longterm outcomes following liver transplantation (LT) and hepatic resection (HR). We identified 32 LT patients with cHCC-CC through an institutional database search. The HR control group (n = 100) was selected through propensity score-matching. The incidence of cHCC-CC among all adult LT patients was 1.0%. Mean patient age was 53.4 ± 6.7 years, and 26 patients were male. Thirty patients had hepatitis B virus infection. All patients of cHCC-CC were diagnosed incidentally in the explanted livers. Mean tumor diameter was 2.5 ± 1.3 cm, and 28 patients had single tumors. Tumor stage was stage I in 23 and II in 9. Concurrent hepatocellular carcinoma (HCC) was detected in 12 patients with stage I in 5 and II in 7. Mean tumor diameter was 1.9 ± 1.2 cm, and 5 had single tumors. Tumor recurrence and survival rates were 15.6% and 84.4% at 1 year and 32.2% and 65.8% at 5 years, respectively. Patients with very early stage cHCC-CC (1 or 2 tumors ≤ 2.0 cm) showed 13.3% tumor recurrence and 93.3% patient survival rates at 5 years, which were significantly improved than those with advanced tumors (P = 0.002). Tumor recurrence and survival rates did not differ significantly between the LT and HR control groups (P = 0.22 and P = 0.91, respectively); however, postrecurrence patient survival did (P = 0.016). In conclusion, cHCC-CC is rarely diagnosed following LT, and one-third of such patients have concurrent HCC. The longterm posttransplant prognosis was similar following LT and HR. Very early cHCC-CC resulted in favorable posttransplant prognosis, thus this selection condition can be prudently considered for LT indication. Liver Transplantation 23 330-341 2017 AASLD.

Post-resection Prognosis of Combined Hepatocellular Carcinoma-Cholangiocarcinoma According to the 2010 WHO Classification.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHC) has wide histological diversity. We intended to investigate the prognostic influence of tumor types of cHC. METHODS: We analyzed the clinical and pathological features of cHC along 2010 WHO classification. Study group was 100 cHC patients who underwent primary resection. Control group comprised 200 propensity score-matched patients with intrahepatic cholangiocarcinoma (ICC). RESULTS: In cHC group, tumor diameter was 4.4 ± 2.8 cm and 95 patients had single tumor. They were classified as classical type in 46 and subtypes with stem cell (SC) features in 54. Subtypes with SC features included typical in 16, intermediate cell in 22, and cholangiolocellular in 16. Their 1- and 3-year tumor recurrence rates were 31.7 and 59.8%; and 1- and 3-year patient survival rates were 92.5 and 77.3%, respectively. Tumor recurrence (p = 0.008) and patient survival (p = 0.005) rates were different according to tumor types. Further stratification by subtypes with SC features resulted in prognostic stratification in tumor recurrence (p = 0.045) and patient survival (p = 0.042). However, tumor stage was the only independent risk factor for tumor recurrence and patient survival. Comparing with ICC control group, cHC group showed no significant difference in rates of tumor recurrence (p = 0.523), but better survival outcomes (p = 0.008). Median post-recurrence patient survival period was 20 months in cHC patients and 6 months in ICC patients (p = 0.001). CONCLUSIONS: Our results indicated that there would be close relationship between the post-resection prognosis and histological types according to the 2010 WHO classification, but these histological types did not become an independent prognostic factor.

Clinicopathological Features and Post-resection Prognosis of Double Primary Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

BACKGROUND: Simultaneous double primary hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) (dpHCC-ICC) is very rare. This study investigated the clinicopathological features and post-resection prognosis of dpHCC-ICC. METHODS: We identified 10 patients with dpHCC-ICC through an institutional database search. Three control groups with HCC, ICC and combined HCC-cholangiocarcinoma (cHCC-CC) were selected (each n = 120) using propensity score matching. RESULTS: The incidence of dpHCC-ICC was 0.23%. The mean age was 57.4 ± 11.7 years, and 8 were male. Hepatitis B virus infection was associated with 8 patients. All dpHCC-ICC were diagnosed incidentally from surgical specimens. Only two patients demonstrated simultaneous elevation of alpha-fetoprotein/des-γ-carboxy prothrombin and carbohydrate antigen 19-9. All patients underwent macroscopic curative resection. The HCC component was classified as stage I in 7 and stage II in 3, and ICC component was classified as stage I in 5, stage II in 2 and stage IV in 3. Tumor recurrence and patient survival rates were 30.0 and 90.0% at 1 year and 52.0 and 77.1% at 3 years, respectively. Tumor recurrence rates were not different between the dpHCC-ICC and the three control groups (p = 0.505). The overall and post-recurrence patient survival rates were similar between the dpHCC-ICC and cHCC-CC groups (p > 0.2); however, these were inferior to those in the HCC group but comparable with those in the ICC group. CONCLUSIONS: The post-resection prognosis of dpHCC-ICC was more dependent on the tumor stage of the ICC component than that of the HCC component. Therefore, they can be clinically regarded as ICC with concurrent HCC.

Hepatic Angiomyolipoma Versus Hepatocellular Carcinoma in the Noncirrhotic Liver on Gadoxetic Acid-Enhanced MRI: A Diagnostic Challenge.

OBJECTIVE: The purpose of this study is to describe the imaging characteristics of hepatic angiomyolipoma (AML) on gadoxetic acid-enhanced MRI and to identify imaging features that are helpful for differentiating it from hepatocellular carcinoma (HCC) in a noncirrhotic liver. MATERIALS AND METHODS: We retrospectively identified 18 patients with pathologically proven hepatic AMLs who had undergone gadoxetic acid-enhanced MRI between 2008 and 2012. We randomly chose 36 patients with noncirrhotic liver who had a single HCC diagnosed radiologically during the same period. None of the HCCs was of the fibrolamellar variant. Two readers reviewed images in consensus to assess the lesion size, the presence of fat, signal intensity characteristics, enhancement profile, early draining veins, intratumoral vessels, and tumor capsules. The tumor-to-liver contrast ratios were measured. These features and the measurements were compared between the two groups. RESULTS: AMLs are more commonly found in women (83.3%), whereas HCCs are more common in men (75%) (p < 0.01). The size of AMLs (3.4 cm) and HCCs (4.3 cm) did not differ significantly. Intratumoral fat was identified in both AMLs (50.0%) and HCCs (30.6%). The dynamic enhancement profile (arterial hypervascularity and hypointensity during the delayed phase) was similar qualitatively and quantitatively except for the portal phase. AMLs and HCCs differed significantly with regard to isointensity on DWI (16.7% vs 0.0%; p = 0.03), washout in the portal phase (61.1% vs 88.9%; p = 0.03), early draining veins (27.8% vs 2.8%; p = 0.01), intratumoral vessels (55.6% vs 22.2%; p = 0.03), and presence of capsule (11.1% vs 50.0%; p = 0.01). CONCLUSION: On gadoxetic acid-enhanced MRI of noncirrhotic liver, AML is often indistinguishable from HCC on the basis of the enhancement profiles. Female sex and some imaging features including DWI could facilitate the differentiation.

Intravoxel incoherent motion MRI for liver fibrosis assessment: a pilot study.

BACKGROUND: There has been a growing need for an imaging method for the accurate diagnosis and staging of liver fibrosis as a non-invasive alternative to liver biopsy. PURPOSE: To evaluate the feasibility of intra-voxel incoherent motion (IVIM) imaging for classifying the severity of liver fibrosis. MATERIAL AND METHODS: Fifty-seven patients who underwent navigator-triggered, diffusion-weighted imaging (DWI) of the liver on a 1.5-T system using nine b-values and had a reliable reference standard for the diagnosis of liver fibrosis (histopathologic findings [n = 27] or clinical findings for normal [n = 18] or cirrhotic liver [n = 12]), were included in our study. Liver apparent diffusion coefficient (ADC), pure diffusion (Dslow), perfusion fraction (f), and perfusion-related diffusion (Dfast), and the product f · Dfast were compared with the liver fibrosis stages (F). The accuracies of these parameters in diagnosing severe liver fibrosis (F ≥3) were evaluated using the receiver-operating characteristic (ROC) curve analysis. RESULTS: The liver fibrosis stages had the strongest negative correlation with f · Dfast (ρ = -0.52). All of the parameters, except for Dslow, were significantly lower in patients with F ≥3 than in those with F ≤2 (P ≤ 0.001). The area under the ROC curve for diagnosing severe fibrosis was the largest for f · Dfast (0.844) with an overall accuracy of 79.0% (45/57) at the optimal cutoff value and followed by f (0.834), Dfast (0.773), ADC (0.762), and Dslow (0.656). CONCLUSION: IVIM imaging is a promising method for classifying the severity of liver fibrosis, with the product f · Dfast being the most accurate parameter.

CT differentiation of mucin-producing cystic neoplasms of the liver from solitary bile duct cysts.

OBJECTIVE: The purpose of this study was to identify the CT features required for differentiating mucin-producing cystic neoplasms of the liver (mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct) from solitary bile duct cysts. MATERIALS AND METHODS: CT images of pathologically confirmed mucinous cystic neoplasms (n = 15), cyst-forming intraductal papillary neoplasms of the bile duct (n = 16), and solitary bile duct cysts (n = 31) were reviewed. Analysis of the CT findings included shape, presence of septa, location of septa (peripheral vs central), thickness of septa (thin vs thick), mosaic pattern, mural nodules, intracystic debris, calcification, upstream bile duct dilatation, downstream bile duct dilatation, and communication between a cystic lesion and the bile duct. The maximum size of a cystic lesion and the maximum size of the largest mural nodule were measured. RESULTS: The presence of septa, central septa, mural nodules, upstream bile duct dilatation, and downstream bile duct dilatation were found to be significant CT findings for differentiating mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct from solitary bile duct cysts (p < 0.05 for each finding). When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucin-producing cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively. When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively [corrected]. CONCLUSION: With the use of specific CT criteria, mucin-producing cystic neoplasms of the liver can be differentiated from solitary bile duct cysts with a high degree of accuracy.

Clinical outcomes of rectal neuroendocrine tumors ≤ 10 mm following endoscopic resection.

BACKGROUND AND STUDY AIMS: This study was conducted to determine the clinical outcome of rectal neuroendocrine tumors (NETs)≤ 10 mm following conventional endoscopic resection. PATIENTS AND METHODS: A total of 107 patients who underwent conventional endoscopic treatment for rectal NETs (median size 5.0 mm [range 1.0-10.0]) were followed up for a median of 31 months (range 13-121). The following data were analyzed: lesion characteristics, clinical outcomes, and histological features determined using tissue microarray analysis (TMA), including the mitotic count and the Ki-67 index. RESULTS: En bloc removal was achieved for all tumors, and the complete resection rate was 49.5% (53/107). Resection margin status was indeterminate in 37 patients (34.6%) and positive in 17 (15.9%). Rectal NETs in 71 patients demonstrated a score of ≤2 % on the Ki-67 index and<2 for mitotic count on TMA. In another 28 tumors that did not undergo TMA, the mitotic count was 0-1 per 10 high-power fields. Neither recurrence nor metastasis was noted during the follow-up period following resection. CONCLUSIONS: Rectal NETs (≤10 mm in size) appear to demonstrate benign behavior based on the mitotic count and the Ki-67 index. These results suggest that the outcome of rectal NETs (≤10 mm in size) following conventional endoscopic resection might be comparatively excellent, regardless of the resection margin status. However, long term follow-up data are required to confirm this.

Value of the ultrasound attenuation index for noninvasive quantitative estimation of hepatic steatosis.

OBJECTIVES: To assess the value of the ultrasound (US) attenuation index for noninvasive estimation of hepatic steatosis and determine its optimal cutoff value for severe steatosis in potential living liver donors. METHODS: Two hundred forty potential donors underwent US-guided biopsy. The target site was scanned at 4 and 8 MHz. On the sonogram, the observer drew 3 × 3-mm square regions of interest in superficial (3-cm) and deep (5-cm) areas. The attenuation index was defined as the difference between superficial and deep echogenicity/superficial echogenicity × 100. On biopsy specimens, replacement of hepatic parenchyma was evaluated on a percentage scale. Severe steatosis was defined as macrovesicular fatty change of 30% or greater. Spearman rank correlation (ρ) was used to determine correlation coefficients between the attenuation index and steatosis degree; receiver operating characteristic analysis was performed to determine the optimal attenuation index cutoff value for severe steatosis. RESULTS: The median steatosis degree was 3% (interquartile range [IQR], 0%-10%). Severe steatosis was found in 10 donors. The attenuation index ranged from -27.4 to 36.6 (median, 4.0; IQR, -1.6-10.4) at 4 MHz and -18.0 to 78.1 (median, 14.5; IQR, 7.2-21.9) at 8 MHz. There was a minimal positive correlation between steatosis and the attenuation index at 4 MHz (total steatosis: ρ = 0.339; P < .001; macrovesicular steatosis: ρ = 0.360; P < .001). However, there was a significant moderate correlation between steatosis and the attenuation index at 8 MHz (total steatosis: ρ = 0.669; P < .001; macrovesicular steatosis: ρ = 0.645; P < .001). The optimal attenuation index cutoff value for severe steatosis at 8 MHz was 31.0. CONCLUSIONS: The US attenuation index at 8 MHz is a useful indicator for noninvasive quantitative estimation of hepatic steatosis and diagnosis of severe steatosis in potential living liver donors.

Single-shot multi-channel plasmonic real-time polymerase chain reaction for multi-target point-of-care testing.

Plasmonic nucleic acid amplification tests demand high-throughput and multi-target detection of infectious diseases as well as short turnaround time and small size for point-of-care molecular diagnostics. Here, we report a multi-channel plasmonic real-time reverse-transcription polymerase chain reaction (mpRT-qPCR) assay for ultrafast and on-chip multi-target detection. The mpRT-qPCR system features two pairs of plasmonic thermocyclers for rapid nanostructure-driven amplification and microlens array fluorescence microscopes for in situ multi-color fluorescence quantification. Each channel shows a physical dimension of 32 mm, 75 mm, and 25 mm in width, length, and thickness. The ultrathin microscopes simultaneously capture four different fluorescence images from two PCR chambers of a single cartridge at a single shot exposure per PCR cycle of four different excitation light sources. The experimental results demonstrate a single assay result of high-throughput amplification and multi-target quantification for RNA-dependent RNA polymerase, nucleocapsid, and human ribonuclease P genes in SARS-CoV-2 RNA detection. The mpRT-PCR increases the number of tests four times over the single RT-PCR and exhibits a short detection time of 15 min for the four RT-PCR reactions. This point-of-care molecular diagnostic platform can reduce false negative results in clinical applications of virus detection and decentralize healthcare facilities with limited infrastructure.

Highly Efficient On-Chip Photothermal Cell Lysis for Nucleic Acid Extraction Using Localized Plasmonic Heating of Strongly Absorbing Au Nanoislands.

Cell lysis serves as an essential role in the sample preparation for intracellular material extraction in lab-on-a-chip applications. However, recent microfluidic-based cell lysis chips still face several technical challenges such as reagent removal, complex design, and high fabrication cost. Here, we report highly efficient on-chip photothermal cell lysis for nucleic acid extraction using strongly absorbed plasmonic Au nanoislands (SAP-AuNIs). The highly efficient photothermal cell lysis chip (HEPCL chip) consists of a PDMS microfluidic chamber and densely distributed SAP-AuNIs with large diameters and small nanogaps, allowing for broad-spectrum light absorption. The SAP-AuNIs induce photothermal heat, resulting in a uniform temperature distribution within the chamber and rapidly reaching the target temperature for cell lysis within 30 s. Furthermore, the localized plasmonic heating of SAP-AuNIs expeditiously triggers phase transition and photoporation in the directly contacted lipid bilayer of the cell membrane, resulting in rapid and highly efficient cell lysis. The HEPCL chip successfully lysed 93% of PC9 cells at 90 °C for 90 s without nucleic acid degradation. This on-chip cell lysis offers a new sample preparation platform for integrated point-of-care molecular diagnostics.

Ultrafast Plasmonic Nucleic Acid Amplification and Real-Time Quantification for Decentralized Molecular Diagnostics.

Point-of-care real-time reverse-transcription polymerase chain reaction (RT-PCR) facilitates the widespread use of rapid, accurate, and cost-effective near-patient testing that is available to the public. Here, we report ultrafast plasmonic nucleic acid amplification and real-time quantification for decentralized molecular diagnostics. The plasmonic real-time RT-PCR system features an ultrafast plasmonic thermocycler (PTC), a disposable plastic-on-metal (PoM) cartridge, and an ultrathin microlens array fluorescence (MAF) microscope. The PTC provides ultrafast photothermal cycling under white-light-emitting diode illumination and precise temperature monitoring with an integrated resistance temperature detector. The PoM thin film cartridge allows rapid heat transfer as well as complete light blocking from the photothermal excitation source, resulting in real-time and highly efficient PCR quantification. Besides, the MAF microscope exhibits close-up and high-contrast fluorescence microscopic imaging. All of the systems were fully packaged in a palm size for point-of-care testing. The real-time RT-PCR system demonstrates the rapid diagnosis of coronavirus disease-19 RNA virus within 10 min and yields 95.6% of amplification efficiency, 96.6% of classification accuracy for preoperational test, and 91% of total percent agreement for clinical diagnostic test. The ultrafast and compact PCR system can decentralize point-of-care molecular diagnostic testing in primary care and developing countries.

Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: implications for the investigation of the natural history of incidental steatosis.

OBJECTIVES: To determine a highly specific liver attenuation threshold at unenhanced CT for biopsy-proven moderate to severe hepatic steatosis (≥30% at histology). METHODS: 315 asymptomatic adults (mean age ± SD, 31.5 ± 10.1 years; 207 men, 108 women) underwent same-day unenhanced liver CT and ultrasound-guided liver biopsy. Blinded to biopsy results, CT liver attenuation was measured using standard region-of-interest methodology. Multiple linear regression analysis was used to assess the relationship of CT liver attenuation with patient age, gender, BMI, CT system, and hepatic fat and iron content. RESULTS: Thirty-nine subjects had moderate to severe steatosis and 276 had mild or no steatosis. A liver attenuation threshold of 48 HU was 100% specific (276/276) for moderate to severe steatosis, with no false-positives. Sensitivity, PPV and NPV at this HU threshold was 53.8%, 100% and 93.9%. Hepatic fat content was the overwhelming determinant of liver attenuation values, but CT system (P < 0.001), and hepatic iron (P = 0.035) also had a statistically significant independent association. CONCLUSIONS: Unenhanced CT liver attenuation alone is highly specific for moderate to severe hepatic steatosis, allowing for confident non-invasive identification of large retrospective/prospective cohorts for natural history evaluation of incidental non-alcoholic fatty liver disease. Low sensitivity, however, precludes effective population screening at this threshold. KEY POINTS: • Unenhanced CT liver attenuation is highly specific for diagnosing moderate/severe hepatic steatosis. • Unenhanced CT can identify large cohorts for epidemiological studies of incidental steatosis. • Unenhanced CT is not, however, effective for population screening for hepatic steatosis.

Sclerosing angiomatoid nodular transformation of the spleen: clinical and radiologic characteristics.

BACKGROUND: Sclerosing angiomatoid nodular transformation (SANT) is a rare benign primary vascular lesion of the spleen. Although there have been many reports about the pathology of SANTs of the spleen, there have been no comprehensive descriptions of the imaging findings of SANTs of the spleen. PURPOSE: To determine the clinical characteristics and imaging findings of SANTs of the spleen. MATERIAL AND METHODS: We retrospectively evaluated seven patients with pathologically confirmed SANT, who underwent CT (n = 7), MRI (n = 4), ultrasonography (n = 4), and PET/CT (n = 3). Follow-up CT examinations were obtained in five patients. Clinical characteristics such as symptoms and concurrent disease were assessed. CT and MRI findings were evaluated by two radiologists, including the number, border, signal intensity, enhancement pattern, hemorrhage, and cystic change or necrosis. The longest diameter of each tumor was measured on CT. Echogenicity on ultrasonography and standardized uptake value on PET/CT were also evaluated. RESULTS: No specific symptom was associated with SANT. Two patients had a history of malignancy, one with cervical cancer and the other with early gastric cancer. Tumor growth was observed in four of five patients. On CT, all seven SANTs appeared as single, well-demarcated masses. CT showed a heterogeneous enhancement in seven patients. MRI showed centripetal progressive enhancement and absence of cystic change or necrosis in four patients, with three of these patients showing evidence of old hemorrhage. Ultrasonography showed heterogeneous hypoechoic mass in four patients. PET/CT showed increased standardized uptake value, ranging from 2.0 to 2.8, in three patients. CONCLUSION: SANT of the spleen is a single, well-demarcated solid mass without cystic change or necrosis. Increased FDG activity and tumor growth on follow-up imaging are common.

Doppler sonography of patients with and without acute cellular rejection after right-lobe living donor liver transplantation.

OBJECTIVES: To compare percent interval changes in the portal blood flow velocity (%PBV) and venous pulsatility index (%VPI), as determined by Doppler sonography, in patients with and without acute cellular rejection after right-lobe living donor liver transplantation. METHODS: Forty-seven patients with biopsy-proven acute cellular rejection underwent Doppler sonography. The control group consisted of 47 age- and sex-matched patients without acute cellular rejection. Doppler spectrograms of the portal vein and right hepatic vein were used to calculate mean peak PBVs and VPIs for the first 3 days after right-lobe living donor liver transplantation, defined as PBV(Baseline) and VPI(Baseline). The PBV and VPI closest in time to biopsy in the patient group or at a matched time in the control group were determined as PBV(Event) and VPI(Event), and %PBV and %VPI values were calculated. RESULTS: The mean PBV(Baseline) values ± SD in the rejection and control groups were 46.0 ± 21.8 and 44.4 ± 20.5 cm/s, respectively; the PBV(Event) values were 32.2 ± 14.5 and 34.4 ± 17.1 cm/s; and the %PBV values were 19.4% ± 39.9% and 2.2% ± 75.4% (P = .73; P = .38; P = .17, respectively). The VPI(Baseline) values were 0.92 ± 0.34 and 0.93 P = .94; P < .001); and the ± 0.38; the VPI(Event) values were 0.46 ± 0.33 and 0.84 ± 0.44 (%VPI values were 45.5% ± 40.1% and 5.6% ± 47.3%, with a greater than 50% VPI observed more frequently in the rejection than in the control group (61.7% versus 12.8%; P < .001). CONCLUSIONS: The VPI(Event) was significantly lower and a greater than 50% VPI was significantly more frequent in patients with than without acute cellular rejection after right-lobe living donor liver transplantation.

Biopsy-proven nonsteatotic liver in adults: estimation of reference range for difference in attenuation between the liver and the spleen at nonenhanced CT.

PURPOSE: To establish the reference range for hepatic attenuation minus splenic attenuation difference (CT(L-S)) values on nonenhanced computed tomographic (CT) images obtained in adults with a biopsy-proved nonsteatotic liver and determine the CT(L-S) criterion for diagnosing hepatic steatosis. MATERIALS AND METHODS: This retrospective study was institutional review board approved, and all subjects had provided written informed consent. The CT(L-S) was measured in 315 liver donor candidates (207 men, 108 women; mean age, 31.5 years ± 10.1 [standard deviation]) who underwent nonenhanced CT of the liver and subsequent ultrasonographically guided liver biopsy on the same day. Nonenhanced liver CT was performed with a 16-section multidetector scanner in 154 individuals and with a 64-section multidetector scanner in 161 individuals. Biopsy specimens were analyzed for degree of hepatic steatosis and iron deposition. The CT(L-S) reference range was determined according to Clinical and Laboratory Standards Institute guideline C28-A3 in individuals with a histologically proved nonsteatotic liver. The sensitivity of nonenhanced CT for the diagnosis of 5% or greater and 30% or greater hepatic steatosis with use of the lower limit of the reference range as the diagnostic cutoff was determined. The effects of subject age and sex, CT scanner type, and hepatic iron on the CT(L-S) were evaluated by using multiple linear regression analysis. RESULTS: Ninety-six subjects (48 men, 48 women) were found to have a histologically proved nonsteatotic liver, with an estimated reference range for CT(L-S) values of 1-18 HU. With a CT(L-S) of less than 1 HU as the criterion for hepatic steatosis, the sensitivities of nonenhanced CT for 5% or greater and 30% or greater hepatic steatosis were 18.6% (29 of 156 subjects) and 67% (26 of 39 subjects), respectively. Subject age had a significant but negligible effect on CT(L-S) (0.076-HU increase per year of age, P = .009), subject sex and scanner type had no effects on CT(L-S), and hepatic iron deposition significantly increased the CT(L-S) (1.434-HU increase per increase in iron deposition grade, P = .011). CONCLUSION: The histologically proved reference range of CT(L-S) values for nonsteatotic livers was 1-18 HU. A CT(L-S) of less than 1 HU could be used as a conservative criterion for diagnosing hepatic steatosis with nonenhanced CT more consistently.

Noninvasive diagnostic criteria for hepatocellular carcinoma in hepatic masses >2 cm in a hepatitis B virus-endemic area.

BACKGROUND: Noninvasive criteria for diagnosing hepatocellular carcinoma (HCC) suggested by the American Association for the Study of Liver Diseases (AASLD) in 2005 consisted of serum α-fetoprotein (AFP) level >200 ng/ml or a typical enhancement pattern (arterial enhancement and portal/delayed washed out) on dynamic imaging of hepatic mass(es) >2 cm in a cirrhotic liver. AIMS: To validate these criteria in a Korean population and to evaluate whether these criteria are applicable to patients without cirrhosis at a high risk of developing HCC. METHODS: We prospectively investigated 206 consecutive patients with hepatic mass(es) >2 cm who underwent biopsy or surgical resection. Patients were evaluated by four-phase dynamic computed tomography (CT) and by assays of serum AFP concentrations at baseline. Patients were classified according to the presence of risk factors or cirrhosis, and the diagnostic accuracy of each test was determined. RESULTS: The positive predictive values (PPV) of typical CT findings or serum AFP >200 ng/ml were 97.8% in cirrhotic patients, 89.6% in high-risk patients without cirrhosis and 82.4% in low-risk patients. The PPVs of typical CT findings alone in these groups were 98.8, 97.6 and 87.5% respectively. In high-risk patients without cirrhosis, the addition of serum AFP levels to typical CT findings minimally increased the diagnostic sensitivity from 81.6 to 87.8% but reduced the PPV from 97.6 to 89.6%. CONCLUSIONS: Serum AFP concentration is not a suitable diagnostic criterion for HCC. Typical CT findings can be used to diagnose HCC >2 cm both in cirrhotic patients and in high-risk patients without cirrhosis.

Focal nodular hyperplasia or focal nodular hyperplasia-like lesions of the liver: a special emphasis on diagnosis.

BACKGROUND AND AIM: Focal nodular hyperplasia (FNH) and FNH-like lesions are hypervascular masses that can mimic hepatocellular carcinoma (HCC). We have investigated the clinical, radiological and pathological features of FNH and FNH-like lesions of the liver, with particular focus on the aspect of diagnosis. METHODS: A total of 84 patients, 77 with pathologically-proven FNH and seven with FNH-like lesions of the liver, were analyzed retrospectively. RESULTS: Of the 84 patients, seven had underlying liver cirrhosis, including two with Budd-Chiari syndrome and one with cardiac cirrhosis. These cases were therefore classified as having FNH-like lesions. Two of the remaining 77 patients without underlying liver cirrhosis were positive for hepatitis B surface antigen. Seven of 50 (14.0%) patients evaluated by four-phase computed tomography (CT) showed portal or delayed washout, and three of 28 (10.7%) patients analyzed by three-phase CT showed washout on the portal phase. Collectively, three of nine (33.3%) patients with risk factors for HCC could have been wrongly diagnosed with HCC based on the non-invasive diagnostic criteria for HCC. A central scar was observed in 30 patients (35.7%) radiologically. Among 62 patients who underwent percutaneous needle biopsy, four patients (6.5%) were misdiagnosed as having HCC and two patients (3.2%) had inconclusive results by a first needle biopsy. CONCLUSIONS: The presence of a hepatic lesion with arterial hypervascularity and/or portal/delayed washout is not necessarily diagnostic of HCC, particularly in patients without risk factors for HCC. These radiological findings can also occur in cirrhotic patients with FNH-like lesions, including those with hepatic outflow obstruction.