Magnetic resonance imaging-based risk factors of hepatocellular carcinoma after direct-acting antiviral therapy: A multicenter observational study.

AIM: To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct-acting antiviral (DAA) therapy. METHODS: We enrolled patients with chronic hepatitis C who underwent direct-acting antiviral therapy and achieved sustained virologic response at 12 weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow up when the absence of HCC was confirmed. Uni- and multivariate Cox proportional hazards models were used to identify factors contributing to HCC development, including gadoxetic acid-enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. RESULTS: The final study cohort comprised 482 patients (median age 70.5 years; 242 men). The median follow-up period was 36.8 months. Among 482 patients, 96 developed HCC (19.9%). The 1-, 3-, and 5-year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were independent risk factors significantly associated with HCC development (p < 0.001-0.04). The highest risk group included patients with both a history of HCC and the presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement (the 1- and 3-year cumulative HCC development rates were 14.2% and 62.2%, respectively). CONCLUSION: History of HCC and presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were strong risk factors for HCC development following direct-acting antiviral therapy.

Effect of a combination of pemafibrate and a mild low-carbohydrate diet on obese and non-obese patients with metabolic-associated fatty liver disease.

BACKGROUND AND AIM: Recently, pemafibrate and a low-carbohydrate diet (LCD) have each been reported to improve fatty liver disease. However, it is unclear whether their combination improves fatty liver disease and is equally effective in obese and non-obese patients. METHODS: In 38 metabolic-associated fatty liver disease (MAFLD) patients, classified by baseline body mass index (BMI), changes in laboratory values, magnetic resonance elastography (MRE), and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) were studied after 1 year of combined pemafibrate plus mild LCD. RESULTS: The combination treatment resulted in weight loss (P = 0.002), improvement in hepatobiliary enzymes (γ-glutamyl transferase, P = 0.027; aspartate aminotransferase, P < 0.001; alanine transaminase [ALT], P < 0.001), and improvement in liver fibrosis markers (FIB-4 index, P = 0.032; 7 s domain of type IV collagen, P = 0.002; M2BPGi, P < 0.001). Vibration-controlled transient elastography improved from 8.8 to 6.9 kPa (P < 0.001) and MRE improved from 3.1 to 2.8 kPa (P = 0.017) in the liver stiffness. MRI-PDFF improved from 16.6% to 12.3% in liver steatosis (P = 0.007). In patients with a BMI of 25 or higher, improvements of ALT (r = 0.659, P < 0.001) and MRI-PDFF (r = 0.784, P < 0.001) were significantly correlated with weight loss. However, in patients with a BMI below 25, the improvements of ALT or PDFF were not accompanied by weight loss. CONCLUSIONS: Combined treatment with pemafibrate and a low-carbohydrate diet resulted in weight loss and improvements in ALT, MRE, and MRI-PDFF in MAFLD patients. Although such improvements were associated with weight loss in obese patients, the improvements were observed irrespective of weight loss in non-obese patients, indicating this combination can be effective both in obese and non-obese MAFLD patients.

Effect of decreased contrast injection flow rate on aortic enhancement in 80-KV peak CT with contrast dose reduction.

BACKGROUND: Effect of decreased injection flow rate of contrast agent at the same iodine dose and delivery rate on aortic enhancement has not been clearly elucidated. PURPOSE: To evaluate the effect of decreased injection flow rate of contrast agent on aortic peak enhancement in a dynamic flow phantom and on aortic enhancement in clinical dynamic 80-kVp computed tomography (CT) with contrast dose reduction. MATERIAL AND METHODS: In the dynamic flow phantom experiment, the effect of a decreased injection flow rate at the same total iodine dose and delivery rate on simulated aortic peak enhancement was evaluated. In the clinical retrospective study, we searched 312 patients with renal dysfunction who underwent an 80-kVp abdominal dynamic CT with 40% reduction of contrast agent from a standard 120-kVp protocol and measured the aortic enhancement at the level of the hepatic hilum. Independent predictors for aortic enhancement were determined by multiple linear regression analysis, and after adjustment of significant predictors, independent variables for acquiring optimal aortic enhancement, ≥300 HU, were determined by multiple logistic regression analysis. RESULTS: In the phantom experiment, decreased flow rate showed a significant but small descent effect (6%-9%) on simulated aortic peak enhancement. In the multiple linear regression analysis, only age was an independent predictor of aortic enhancement; there was no independent predictor for optimal age-adjusted aortic enhancement of ≥300 HU. CONCLUSIONS: Decreased injection flow rate had a small influence on aortic enhancement in vitro but had no significant effect on the aortic enhancement in clinical dynamic 80-kVp CT.

Four-dimensional flow magnetic resonance imaging for assessment of hemodynamic changes in the portal venous system before and after balloon-occluded retrograde transvenous obliteration: a pilot feasibility study.

BACKGROUND: The effectiveness of four-dimensional (4D) flow magnetic resonance imaging (MRI) for assessing hemodynamic changes before and after balloon-occluded retrograde transvenous obliteration (BRTO) remains unclear. PURPOSE: To evaluate the feasibility of 4D flow MRI for assessing hemodynamic changes in the portal venous system before and after BRTO. MATERIAL AND METHODS: We included 10 patients (7 men, 3 women; mean age = 67 years) with liver cirrhosis who had a high risk of gastric variceal bleeding or hepatic encephalopathy. Non-contrast 4D flow MRI of the upper abdomen was performed before and after BRTO. In addition, we compared the blood flow rates in the portal vein (PV), superior mesenteric vein (SMV), splenic vein (SV), left renal vein, and inferior vena cava before and after BRTO. Moreover, the flow directions of the SMV and SV before and after BRTO were assessed using both portography and 4D flow MRI. RESULTS: There was a significant post-BRTO increase in the blood flow rate in the PV and SV (P < 0.05). There was no significant post-BRTO change in the blood flow rates in the SMV, inferior vena cava, and left renal vein. In four patients, portography confirmed that hepatofugal flow in the SV and SMV changed to hepatopetal flow after BRTO. Moreover, 4D flow MRI correctly assessed the flow directions in the SMV and SV in 70%-100% of the patients. CONCLUSION: 4D flow MRI can be used to detect hemodynamic changes in the portal venous system before and after BRTO.

Distinction Between Hepatocellular Carcinoma and Hypervascular Liver Metastases in Non-cirrhotic Patients Using Gadoxetate Disodium-Enhanced Magnetic Resonance Imaging.

Purpose: This study aims to identify the hallmarks of gadoxetate disodium-enhanced magnetic resonance imaging distinguishing hepatocellular carcinoma (HCC) from hypervascular liver metastases (HLMs). Methods: Between January 2008 and October 2020, among patients who underwent gadoxetate disodium-enhanced MRI, those who met the following criteria were retrospectively included: without chronic hepatitis or liver stiffness ≤ 2.5 kPa on magnetic resonance elastography or F0/F1 on pathological assessment. Two blinded radiologists reviewed the imaging findings to judge the presence or absence of the enhancing capsule, nonperipheral washout, corona enhancement, hypointensity in the transitional/hepatobiliary phase (HBP), hyperintensity on T2-weighted/diffusion-weighted imaging (DWI), mosaic architecture, and blood products/fat in mass. The lesion-to-liver signal intensity ratios in HBP and DWI were also calculated. Univariate and multivariate analyses were performed to identify the imaging hallmarks distinguishing HCC from HLM. Interobserver agreement was calculated using kappa values and intraclass correlation coefficients (ICCs). Results: The final study cohort comprised 72 lesions in 44 patients (mean age, 65.0±11.9 years). Univariate analysis revealed higher frequencies of the following features in HCC than in HLM (P < .10): nonperipheral washout, corona enhancement, transitional phase hypointensity, mosaic architecture, and fat in mass (P = .002-.073). Multivariate analysis revealed that nonperipheral washout and mosaic architecture favored the diagnosis of HCC over that of HLM with odds ratios of 7.66 and 14.6, respectively (P = .038 and .029, respectively). The interobserver agreement for each item was moderate or substantial (kappa or ICC = .447-.792). Conclusion: Peripheral washout and mosaic architecture may be reliable imaging hallmarks for distinguishing HCC from HLM.

Effect of Ultra High-Resolution Computed Tomography and Model-Based Iterative Reconstruction on Detectability of Simulated Submillimeter Artery.

OBJECTIVE: To evaluate the effect of ultra high-resolution computed tomography (UHRCT) and model-based iterative reconstruction (MBIR) on the detectability of simulated submillimeter artery. METHODS: A small vessel phantom ranging from 0.4 to 2.0 mm in diameter and edge phantoms of low to high attenuation values were scanned by UHRCT (super-high-resolution mode and normal-resolution-mode) and conventional CT, and data were reconstructed by MBIR and filtered back projection (FBP). Vessel detectability was assessed subjectively and the effective size at which 50% of response was achieved (ES50 [mm]) was calculated. Modulation transfer function (MTF) was calculated by an edge spread function method. RESULTS: ES50 of super high-resolution mode (0.36 mm for MBIR and 0.50 mm for FBP) was significantly smaller than those of normal-resolution mode (P < 0.01). In the MTF analysis, the MTF of MBIR improved as the edge phantom attenuation increased, whereas that of FBP was stable. CONCLUSIONS: Both UHRCT and MBIR are effective for the detectability of simulated submillimeter artery.

Dose-dependence of transient respiratory motion artifacts on gadoxetic acid-enhanced arterial phase MR images.

PURPOSE: To compare the occurrence of transient respiratory motion (TM) artifacts between 0.05 mmol/kg and 0.025 mmol/kg gadoxetic-acid on arterial phase MRI intra-individually for evaluating dose-dependence of gadoxetic acid. MATERIALS AND METHODS: This retrospective study involved 91 patients who underwent dynamic MRI at 1.5T at different times, one time with 0.05 mmol/kg and the other 0.025 mmol/kg gadoxetic-acid. Examinations with 0.05 mmol/kg totaled 91 scans, and examinations with 0.025 mmol/kg totaled 375 scans (due to multiple exams for several patients). The scan with 0.025 mmol/kg closest in time to the 0.05 mmol/kg scan was selected to minimize temporal effects. Two radiologists graded TM artifacts in the arterial phase images using a four-point scale: no, mild, moderate, and severe artifacts. Results were compared between the two protocols (0.05 mmol/kg versus all 0.025 mmol/kg and 0.05 mmol/kg versus selected 0.025 mmol/kg), and the odds ratio for moderate-to-severe artifacts was calculated. RESULTS: Significantly more TM artifacts were observed in the double dose (16/91 [17%]) scans compared with either all (17/375 [4%]; P < 0.01) or selected (3/91 [3%]; P = 0.01) standard dose scans. The odds ratio of the moderate-to-severe artifacts with the higher dose was 4.99-5.33. CONCLUSION: There appears to be dose-dependence of gadoxetic-acid and the occurrence of TM artifacts. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:433-438.

Magnetic resonance elastography is as accurate as liver biopsy for liver fibrosis staging.

BACKGROUND: Liver MR elastography (MRE) is available for the noninvasive assessment of liver fibrosis; however, no previous studies have compared the diagnostic ability of MRE with that of liver biopsy. PURPOSE: To compare the diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver biopsy using the resected liver specimens as the reference standard. STUDY TYPE: A retrospective study at a single institution. POPULATION: In all, 200 patients who underwent preoperative MRE and subsequent surgical liver resection were included in this study. Data from 80 patients were used to estimate cutoff and distributions of liver stiffness values measured by MRE for each liver fibrosis stage (F0-F4, METAVIR system). In the remaining 120 patients, liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle. FIELD STRENGTH/SEQUENCE: 2D liver MRE with gradient-echo based sequence on a 1.5 or 3T scanner was used. ASSESSMENT: Two radiologists independently measured the liver stiffness value on MRE and two types of MRE-based methods (threshold and Bayesian prediction method) were applied. Two pathologists evaluated all biopsy samples independently to stage liver fibrosis. Surgically resected whole tissue specimens were used as the reference standard. STATISTICAL TESTS: The accuracy for liver fibrosis staging was compared between liver biopsy and MRE-based methods with a modified McNemar's test. RESULTS: Accurate fibrosis staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with liver biopsy. Accuracies of MRE-based methods for diagnoses of ≥F2 (90-91% [108-9/120]), ≥F3 (79-81% [95-97/120]), and F4 (82-85% [98-102/120]) were statistically equivalent to those of liver biopsy (≥F2, 79% [95/120], P ≤ 0.01; ≥F3, 88% [105/120], P ≤ 0.006; and F4, 82% [99/120], P ≤ 0.017). DATA CONCLUSION: MRE can be an alternative to liver biopsy for fibrosis staging. LEVEL OF EVIDENCE: 3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1268-1275.

Comparison of diagnostic accuracies of two- and three-dimensional MR elastography of the liver.

PURPOSE: To evaluate the effect of imaging sequence (spin-echo echo-planar imaging [EPI] and gradient-echo [GRE]) and postprocessing method (two-dimensional [2D] and 3D inversion algorithms) on liver MR elastography (MRE) and to validate the diagnostic performance of EPI-MRE3D versus conventional GRE-MRE2D for liver fibrosis staging. MATERIALS AND METHODS: Three MRE methods (EPI-MRE3D , EPI-MRE2D , and GRE-MRE2D ) were performed on soft and mildly stiff phantoms and 58 patients with chronic liver disease using a 3 Tesla clinical MRI scanner, and stiffness values were compared among the three methods. A validation study comprised 73 patients with histological liver fibrosis (F0-4, METAVIR system). Areas under the receiver operating characteristic curves (AUCs) and accuracies for diagnosing significant fibrosis (F3-4) and cirrhosis (F4) were compared between EPI-MRE3D and GRE-MRE2D . RESULTS: Stiffness values of the soft and mildly stiff phantoms were 2.4 kPa and 4.0 kPa by EPI-MRE3D ; 2.6 kPa and 4.2 kPa by EPI-MRE2D ; and 2.7 kPa and 4.2 kPa by GRE-MRE2D . In patients, EPI-MRE3D provided significantly lower stiffness values than other methods (P < 0.001). However, there was no significant difference between GRE-MRE2D and EPI-MRE2D (P = 0.12). The AUCs and accuracies of EPI-MRE3D and GRE-MRE2D were statistically equivalent in the diagnoses of significant fibrosis (F3-4) and cirrhosis (F4) (all P < 0.005). CONCLUSION: EPI-MRE3D showed modestly lower liver stiffness values than conventional GRE-MRE2D . The diagnostic performances of EPI-MRE3D and GRE-MRE2D were equivalent for liver fibrosis staging. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:1163-1170.

Outcome of hypovascular hepatic nodules with positive uptake of gadoxetic acid in patients with cirrhosis.

OBJECTIVES: To evaluate the longitudinal risk to patients with cirrhosis of hypervascular hepatocellular carcinoma (HCC) developing from hypovascular hepatic nodules that show positive uptake of gadoxetic acid (hyperintensity) on hepatocyte phase images. METHODS: In 69 patients, we evaluated findings from serial follow-up examinations of 633 hepatic nodules that appeared hypovascular and hyperintense on initial gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) until the nodules demonstrated hypervascularity and were diagnosed as hypervascular HCC. Cox analyses were performed to identify risk factors for the development of hypervascular HCCs from the nodules. RESULTS: The median follow-up was 663 days (range, 110 to 1215 days). Hypervascular HCCs developed in six of the 633 nodules (0.9 %) in five of the 69 patients. The only independent risk factor, the nodule's initial maximum diameter of 10 mm or larger, demonstrated a hazard ratio of 1.25. The one-year risk of hypervascular HCC developing from a nodule was 0.44 %. The risk was significantly higher for nodules of larger diameter (1.31 %) than those smaller than 10 mm (0.10 %, p < 0.01). CONCLUSIONS: Hypervascular HCC rarely develops from hypovascular, hyperintense hepatic nodules. We observed low risk even for nodules of 10 mm and larger diameter at initial examination. KEY POINTS: • Hypervascularization was rare on follow-up examination of hypovascular, hyperintense nodules • The risk of hypervascularization in a nodule increased with large size • Hypovascular, hyperintense nodules require neither treatment nor more intense follow-up.

Gadoxetic acid disodium-enhanced MR imaging of cholangiolocellular carcinoma of the liver: imaging characteristics and histopathological correlations.

OBJECTIVES: To review the gadoxetic acid disodium (EOB)-enhanced magnetic resonance (MR) imaging features of cholangiolocellular carcinoma (CoCC) of the liver and compare them with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: EOB-enhanced MR images of 19 patients with CoCC, 23 with ICC, and 51 with HCC were retrospectively evaluated qualitatively and quantitatively. Univariate and multivariate analyses were performed to determine the characteristic MR features of CoCC with histopathological-imaging correlation. RESULTS: Multivariate logistic regression analysis showed that dot-/band-shaped internal enhancement during the arterial and portal phases (P < 0.001), and larger arterial ring enhancement ratio (CoCC, 0.13 ± 0.04; ICC, 0.074 ± 0.04; P = 0.013) were significantly independently associated with CoCC in contrast to ICC, whereas several MR features including progressive enhancement during the portal and late phases (P < 0.001), target appearance in the hepatocyte phase (P = 0.004), and vessel penetration (P = 0.013) were significantly more frequently associated with CoCC than HCC. The dot-/band-like internal enhancement (78.9% of CoCCs) histopathologically corresponded to the tumour cell nest with vascular proliferations and retained Glisson's sheath structure. CONCLUSIONS: EOB-enhanced MR features of CoCC largely differ from those of HCC but are similar to those of ICC. However, the finding of thicker arterial ring enhancement with dot-/band-like internal enhancement could help differentiate CoCC from ICC. KEY POINTS: • Gadoxetic acid-enhanced MR features of cholangiolocellular carcinoma (CoCC) resembled those of intrahepatic cholangiocarcinoma (ICC). • Gadoxetic acid-enhanced MR features of CoCC largely differed from those of hepatocellular carcinoma. • Dot-/band-like internal enhancement of CoCC may be helpful for differentiating from ICC. • Arterial ring enhancement of CoCC was larger than that of ICC.

Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications.

BACKGROUND & AIMS: Human hepatocarcinogenesis in cirrhosis is thought to be multistep and characterized by a spectrum of nodular lesions, ranging from low to high grade dysplastic nodules (LGDN and HGDN) to early and progressed hepatocellular carcinoma (eHCC and pHCC). The aim of this study was to investigate the morphophenotypical changes of this sequence and their potential translational significance. METHODS: We scored the vascular profile, ductular reaction/stromal invasion and overexpression of five biomarkers (GPC3, HSP70, GS, CHC, and EZH2), in a series of 100 resected nodules (13 LGDN, 16 HGDN, 42 eHCC and 29 small pHCC). RESULTS: The score separated the four groups of nodules as individual entities (p<0.01). In the sequence, biomarker's overexpression progressively increased with parallel decrease of ductular reaction; the vascular remodeling started very early (LGDN) but did not further develop in a proportion of HCC. eHCC was the most heterogeneous entity, with marginal overlap with HGDN and pHCC. Liver environment (fibrosis, etiology) did not impact on the phenotype of the different nodules. A subclass of eHCC (16/42) without evidence of stromal invasion was identified, suggesting a "preinvasive stage" (p<0.05). For diagnosis, the application of four and five biomarkers (rather than the usual three) improved the sensitivity of the assay for the detection of eHCC (76% and 93% vs. 52%); biomarkers in alternative combinations, and also increased the sensitivity of the assay (GS+CHC+EZH2: 76%; GS+CHC+EZH2+HSP70: 90%). CONCLUSIONS: This study supports the multistep nature of human hepatocarcinogenesis, and suggests that eHCC is more heterogeneous than previously thought. This provides further information of the potential translational significance into clinical practice.

Usefulness of MR elastography for detecting clinical progression of cirrhosis from child-pugh class A to B in patients with type C viral hepatitis.

PURPOSE: To evaluate the usefulness of magnetic resonance elastography (MRE) in detecting the clinical progression of cirrhosis from Child-Pugh class A to B in patients with hepatitis C. MATERIALS AND METHODS: We reviewed the data of 101 consecutive patients with type C viral hepatitis and clinically suspected cirrhosis who fulfilled the all following criteria: available MRE at 1.5 Tesla (T) or 3.0T and laboratory tests within a month, Child-Pugh class A, platelet count less than 155 × 10(3) /µL, no clinical history of hepatocellular carcinoma, and ≥6 months of follow-up after MRE. We longitudinally analyzed the incidence of cirrhosis progression as defined by the clinical progression from Child-Pugh class A to B at two subsequent follow-up points. Risk of cirrhosis progression was assessed by Cox analyses and Kaplan-Meyer methods. RESULTS: Cirrhosis progression was noted in 25 patients during the follow-up period. Liver stiffness (hazard ratio [HR] by 1 kPa increase = 1.397; P = 0.0074), Child-Pugh score of 6 versus score 5 (HR of 3.085; P = 0.0276), and treatment responses to anti-viral therapy versus nonresponse (HR of <0.001, P = 0.0006) were independent risk factors of cirrhosis progression. The 1-year risk (0.7%; 95% confidence interval, 0.1-4.2%) of cirrhosis progression was negligible in patients with liver stiffness of <3.3 kPa or response to anti-viral treatment. CONCLUSION: MRE is useful to stratify the risk of cirrhosis progression in patients with hepatitis C. J. Magn. Reson. Imaging 2016;44:715-722.

Association of splenic MR elastographic findings with gastroesophageal varices in patients with chronic liver disease.

PURPOSE: To identify magnetic resonance imaging (MRI)-based parameters associated with gastroesophageal varices (GEVs) in patients with chronic liver disease. MATERIALS AND METHODS: Ninety-three patients were divided into three groups based on endoscopic findings: group 1 with no GEVs (n = 49), group 2 with mild GEVs (n = 30), and group 3 with severe GEVs (n = 14). We used a multivariate logistic regression analysis to assess liver stiffness, aspartate aminotransferase-to-platelet ratio index, spleen stiffness and volume, portal vein velocity, cross-sectional area, and flow volumes potential independent associators of any (mild and severe) GEVs or severe GEVs. RESULTS: The analysis showed that spleen and liver stiffness and spleen volume were independently associated with any GEVs (spleen stiffness, odds ratio [95% confidence interval], 1.25 [1.04-1.68], P = 0.018; liver stiffness, 1.52 [1.13-2.17], P = 0.006; spleen volume, 1.01 [1.00-1.01], P = 0.016), whereas spleen stiffness was associated with severe GEVs (1.82 [1.25-2.95]; P = 0.005). CONCLUSION: Liver and spleen stiffness and spleen volume are associated with GEVs in patients with chronic liver disease. Compared with liver stiffness and spleen volume, spleen stiffness is more strongly associated with severe GEVs.

MRI-based staging of hepatic fibrosis: Comparison of intravoxel incoherent motion diffusion-weighted imaging with magnetic resonance elastography.

PURPOSE: To evaluate the use of intravoxel incoherent motion (IVIM) imaging for staging hepatic fibrosis, and compare its staging ability with that of magnetic resonance elastography (MRE). MATERIALS AND METHODS: This study included 129 patients with pathologically staged liver fibrosis, and 53 patients with healthy livers. All patients underwent both MRE and IVIM imaging. Four diffusivity indices were calculated with 11 b-values; slow diffusion coefficient related to molecular diffusion (D), fast diffusion coefficient related to perfusion in micro-vessels (D*), perfusion-related diffusion fraction (f), and apparent diffusion coefficient (ADC). Receiver operating characteristic curve analysis was performed to determine the accuracy of IVIM imaging and MRE for staging hepatic fibrosis. RESULTS: D*, f, and ADC values decreased significantly with fibrosis stage (P < 0.0124), and liver stiffness increased (P < 0.0001). The Az value of MRE was significantly higher than that of D* for all fibrosis stages (D* vs. MRE for ≥ F1, 0.851 vs. 0.992 [P < 0.0001]; ≥ F2, 0.898 vs. 0.998 [P = 0.0003]; ≥ F3, 0.904 vs. 0.995 [P = 0.0004]; F4, 0.885 vs. 0.996 [P < 0.0001]). CONCLUSION: IVIM imaging is a useful technique for evaluating hepatic fibrosis, but MRE is better able to discriminate fibrosis stages than IVIM imaging.

Hepatitis activity should be considered a confounder of liver stiffness measured with MR elastography.

PURPOSE: To evaluate the effect of hepatitis activity on liver stiffness measurements and the role of serum alanine aminotransferase (ALT) in liver fibrosis staging by MR elastography (MRE). MATERIALS AND METHODS: We measured liver stiffness (kPa) in 135 patients by MRE and histologically assessed fibrosis and hepatitis activity within 2 months. Stepwise multiple linear regression was performed to determine the maximum adjusted R(2) against liver stiffness, after adjusting for nothing (model 1), ALT/upper limit of normal categories (model 2), and hepatitis activity (A grade) by METAVIR (model 3). Logistic regression was used to identify independent factors associated with pathologically proven cirrhosis. RESULTS: Platelet count and METAVIR F score were strongly associated with liver stiffness. The adjusted R(2) value of model 3 (0.7026) was higher than those of models 1 (0.6472) and 2 (0.6564), showing that hepatitis activity affected liver stiffness measurement. High ALT levels (odds ratio, 0.0066; P = 0.0003) as well as MRE (odds ratio, 9.91; P < 0.0001) were independently associated with cirrhosis. CONCLUSION: Hepatitis activity may be a confounder of liver stiffness measurement during liver fibrosis staging using MRE. MRE can potentially make an overdiagnosis of liver cirrhosis if the patient has high ALT levels.