Predictive and Prognostic Potential of Liver Function Assessment in Patients with Advanced Hepatocellular Carcinoma: A Systematic Literature Review.

Introduction: We conducted a systematic literature review to assess the utility of liver function assessments for predicting disease prognosis and response to systemic anticancer therapy in patients with advanced hepatocellular carcinoma (aHCC). Methods: This was a PRISMA-standard review and was registered with PROSPERO (CRD42021244588). MEDLINE and Embase were systematically searched (March 24, 2021) to identify publications reporting the efficacy and/or safety of systemic anticancer therapy (vs. any/no comparator) in liver-function-defined subgroups in phase 2 or 3 aHCC trials. Screening was completed by a single reviewer, with uncertainties resolved by a second reviewer and/or the authors. English-language full-text articles and congress abstracts were eligible for inclusion. Included publications were described and assessed for risk of bias using the GRADE methodology. Results: Twenty (of 2,579) screened publications were eligible; seven categorized liver function using the albumin-bilirubin system, nine using the Child-Pugh system, four using both. GRADE assessment classified ten, nine, and one publication(s) as reporting moderate-quality, low-quality, and very-low-quality evidence, respectively. Analyses of cross-trial trends of within-exposure arm analyses (active and control) reported a positive relationship between baseline liver function and overall survival and progression-free survival, supporting liver function as a prognostic marker in aHCC. There were also signals for a modest relationship between more preserved baseline liver function and extent of systemic treatment benefit, and with more preserved liver function and lower incidence of safety events. Conclusion: This review supports liver function as a prognostic variable in aHCC and highlights the value of a priori stratification of patients by baseline liver function in aHCC trials. The predictive value of liver function warrants further study. Findings were limited by the quality of available data.

Consensus report from the 10th Global Forum for Liver Magnetic Resonance Imaging: developments in HCC management.

The 10th Global Forum for Liver Magnetic Resonance Imaging (MRI) was held as a virtual 2-day meeting in October 2021, attended by delegates from North and South America, Asia, Australia, and Europe. Most delegates were radiologists with experience in liver MRI, with representation also from specialists in liver surgery, oncology, and hepatology. Presentations, discussions, and working groups at the Forum focused on the following themes: • Gadoxetic acid in clinical practice: Eastern and Western perspectives on current uses and challenges in hepatocellular carcinoma (HCC) screening/surveillance, diagnosis, and management • Economics and outcomes of HCC imaging • Radiomics, artificial intelligence (AI) and deep learning (DL) applications of MRI in HCC. These themes are the subject of the current manuscript. A second manuscript discusses multidisciplinary tumor board perspectives: how to approach early-, mid-, and late-stage HCC management from the perspectives of a liver surgeon, interventional radiologist, and oncologist (Taouli et al, 2023). Delegates voted on consensus statements that were developed by working groups on these meeting themes. A consensus was considered to be reached if at least 80% of the voting delegates agreed on the statements. CLINICAL RELEVANCE STATEMENT: This review highlights the clinical applications of gadoxetic acid-enhanced MRI for liver cancer screening and diagnosis, as well as its cost-effectiveness and the applications of radiomics and AI in patients with liver cancer. KEY POINTS: • Interpretation of gadoxetic acid-enhanced MRI differs slightly between Eastern and Western guidelines, reflecting different regional requirements for sensitivity vs specificity. • Emerging data are encouraging for the cost-effectiveness of gadoxetic acid-enhanced MRI in HCC screening and diagnosis, but more studies are required. • Radiomics and artificial intelligence are likely, in the future, to contribute to the detection, staging, assessment of treatment response and prediction of prognosis of HCC-reducing the burden on radiologists and other specialists and supporting timely and targeted treatment for patients.

Three-Dimensional Radiological Assessment of Ablative Margins in Hepatocellular Carcinoma: Pilot Study of Overlay Fused CT/MRI Imaging with Automatic Registration.

BACKGROUND: We investigate the feasibility of image fusion application for ablative margin assessment in radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) and possible causes for a wrong initial evaluation of technical success through a side-by-side comparison. METHODS: A total of 467 patients with 1100 HCCs who underwent RFA were reviewed retrospectively. Seventeen patients developed local tumor progressions (LTPs) (median size, 1.0 cm) despite initial judgments of successful ablation referring to contrast-enhanced images obtained in the 24 h after ablation. The ablative margins were reevaluated radiologically by overlaying fused images pre- and post-ablation. RESULTS: The initial categorizations of the 17 LTPs had been grade A (absolutely curative) (n = 5) and grade B (relatively curative) (n = 12); however, the reevaluation altered the response categories to eight grade C (margin-zero ablation) and nine grade D (existence of residual HCC). LTP occurred in eight patients re-graded as C within 4 to 30.3 months (median, 14.3) and in nine patients re-graded as D within 2.4 to 6.7 months (median, 4.2) (p = 0.006). Periablational hyperemia enhancements concealed all nine HCCs reevaluated as grade D. CONCLUSION: Side-by-side comparisons carry a risk of misleading diagnoses for LTP of HCC. Overlay fused imaging technology can be used to evaluate HCC ablative margin with high accuracy.

Cost-Effectiveness of Lenvatinib in the Treatment of Patients With Unresectable Hepatocellular Carcinomas in Japan: An Analysis Using Data From Japanese Patients in the REFLECT Trial.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Japan. Prognosis is poor, and until recently sorafenib was the only treatment option available for patients with unresectable disease. Lenvatinib is the first therapy to demonstrate noninferiority to sorafenib. An analysis was conducted using clinical data from Japanese patients in the phase III REFLECT trial to assess the cost-effectiveness of lenvatinib versus sorafenib for first-line treatment of unresectable HCC in Japan. METHODS: A partitioned survival model was implemented adopting the perspective of the Japanese healthcare system, with costs and outcomes modeled over a lifetime horizon and using a discount rate of 2%, as per Japanese guidelines. Population data from the Japanese subpopulation of REFLECT were used to extrapolate outcomes, and costs and resource use were based on Japanese sources. The Japanese tariff was applied to EQ-5D data collected during the REFLECT clinical trial to obtain utility values reflecting the preferences of the Japanese population. RESULTS: Compared with sorafenib, lenvatinib is dominant because it is associated with a reduction in incremental costs of ¥156 799 and incremental quality-adjusted life-years of 0.31. These results were robust to changes in key assumptions, and probabilistic outcomes aligned with deterministic outcomes. CONCLUSION: Given the use of Japan-specific data in the cost-effectiveness model, it is expected that the use of lenvatinib as a first-line treatment in Japan will be associated with cost savings and improved clinical outcomes versus sorafenib for patients with unresectable HCC.

Phase I Study of the Bifunctional Fusion Protein Bintrafusp Alfa in Asian Patients with Advanced Solid Tumors, Including a Hepatocellular Carcinoma Safety-Assessment Cohort.

LESSONS LEARNED: Bintrafusp alfa had a manageable safety profile and demonstrated preliminary clinical activity in heavily pretreated patients with solid tumors (including hepatocellular carcinoma) with no or limited treatment options. Findings from this study suggest bintrafusp alfa may be a novel therapeutic approach for patients with advanced solid tumors. Additional trials are needed to further explore safety and efficacy of bintrafusp alfa in specific tumor types. BACKGROUND: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor-ß (TGF-ß) RII receptor (a TGF-ß "trap") fused to a human immunoglobulin (Ig) G1 antibody blocking programmed death-ligand 1 (PD-L1). Bintrafusp alfa is designed to neutralize TGF-ß signaling by "trapping" and sequestering all TGF-ß isoforms, and this trap function is physically linked to PD-L1 blockade in the tumor microenvironment. METHODS: NCT02699515 was a phase I, open-label, dose-escalation study of bintrafusp alfa (3, 10, and 20 mg/kg every 2 weeks) in Asian patients with advanced solid tumors, including a hepatocellular carcinoma (HCC) safety-assessment cohort. The primary objective was safety and tolerability; the secondary objective is best overall response. RESULTS: As of August 24, 2018, 23 patients (including 9 in the HCC cohort) received bintrafusp alfa. Eight patients experienced treatment-related adverse events (TRAEs). Three patients had grade 3 TRAEs (13.0%; hypoacusis, hyponatremia, hypopituitarism, increased blood creatine phosphokinase, and intracranial tumor hemorrhage); one had grade 4 hyponatremia (4.3%). No treatment-related deaths occurred. In the dose-escalation cohort, two patients had a confirmed partial response, and 3 had stable disease (SD), for an overall response rate of 14.3% and a disease control rate (DCR) of 35.7%. In the HCC cohort, one patient had SD (DCR, 11.1%). A dose-proportional pharmacokinetics profile was observed at doses of >3 mg/kg. CONCLUSION: Bintrafusp alfa had a manageable safety profile and preliminary efficacy in heavily pretreated patients with advanced solid tumors, including HCC.

Navigator-triggered and breath-hold 3D MRCP using compressed sensing: image quality and method selection factor assessment.

PURPOSE: To examine whether MRCP using a combination of compressed sensing and sensitivity encoding with navigator-triggered and breath-hold techniques (NT C-SENSE and BH C-SENSE, respectively) have comparable image quality to that of navigator-triggered MRCP using only sensitivity encoding (NT SENSE) at 1.5-T. METHODS: Fifty-one participants were enrolled in this prospective study between July and October 2018 and underwent the three 3D MRCP sequences each. The acquisition time and relative duct-to-periductal contrast ratios (RC values) of each bile duct segment were obtained. Visualization of the bile and main pancreatic ducts, background suppression, artifacts, and overall image quality were scored on 5-point scales. Mean and median differences in RC values and qualitative scores of NT C-SENSE and BH C-SENSE relative to NT SENSE were calculated with 95% confidence intervals (CIs). RESULTS: Acquisition time of NT SENSE, NT C-SENSE, and BH C-SENSE were 348, 143 (mean for both), and 18 s (for all participants), respectively. The RC value of each bile duct segment was inferior, but the lower limits of the 95% CIs of the mean differences were ≥ - 0.10, for both NT C-SENSE and BH C-SENSE. The visualization score of the intrahepatic duct in BH C-SENSE was inferior to that in NT SENSE (lower 95% CI limit, - 1.5). In both NT C-SENSE and BH C-SENSE, the 95% CIs of the median differences in the other qualitative scores were from - 1.0 to 0.0. CONCLUSION: NT C-SENSE and BH C-SENSE have comparable image quality to NT SENSE at 1.5-T.

Newly Proposed ALBI Grade and ALBI-T Score as Tools for Assessment of Hepatic Function and Prognosis in Hepatocellular Carcinoma Patients.

BACKGROUND: Because of the rapid progression of antiviral treatment options and the increasing frequency of nonviral-related hepatocellular carcinoma (HCC) due to the aging of society, the number of HCC patients with good hepatic function has been increasing and a more detailed method of assessment of hepatic function is needed. The Child-Pugh classification (CP) is used worldwide as an assessment tool for hepatic reserve function, even though it has some weaknesses. Recently, the albumin-bilirubin (ALBI) grade, calculated based on only albumin and total bilirubin, was proposed, and recent investigations have suggested that ALBI grade instead of CP can be used as an assessment tool for hepatic function as part of therapeutic strategies such as Barcelona Clinic Liver Cancer staging and a practical guideline presented by the Japan Society of Hepatology as well for total staging scoring systems. There has been an increasing number of reports showing that it has better capability than CP for HCC patients who undergo not only curative but also palliative treatments. Transcatheter arterial chemoembolization (TACE) is a major palliative treatment used for unresectable HCC, and the idea of TACE-refractory status has been proposed to indicate the possibility of switching to a tyrosine kinase inhibitor (TKI). However, TKI administration requires a maintained hepatic reserve function, thus the importance of assessment of hepatic function in patients undergoing TACE treatments has increased. We consider that ALBI grade might also play a significant role as part of a detailed assessment of relative changes in hepatic function during treatment. In this review, we evaluate the practical usefulness of ALBI grade for assessing hepatic function and HCC prognosis. KEY MESSAGE: A detailed assessment of hepatic function is required for recent HCC therapeutic strategies. ALBI grade may be a powerful tool to improve treatment options for affected patients.

Validation of Modified ALBI Grade for More Detailed Assessment of Hepatic Function in Hepatocellular Carcinoma Patients: A Multicenter Analysis.

BACKGROUND/AIM: The frequency of hepatocellular carcinoma (HCC) in patients with good hepatic reserve function has been increasing in Japan along with the progression of antiviral therapies and aging of the society. We evaluated the usefulness of modified albumin-bilirubin (ALBI) grade as a tool for assessment of hepatic reserve function. MATERIALS/METHODS: We enrolled 6,649 naïve HCC patients treated from 2000 to 2017 and divided them into training (Ehime Prefecture group: E group, n = 2,357) and validation (validation group: V group, n = 4,292) cohorts. Child-Pugh classification and ALBI and modified ALBI (mALBI) grading were compared using with Japan Integrated Staging (JIS), ALBI-TNM (ALBI-T), and mALBI-T scores, which were calculated based on TNM stage and each assessment tool, retrospectively. RESULTS: In the E group, Akaike's Information Criterion (AIC) and c-index values for mALBI-T (13,725.2/0.744) were better as compared to those of ALBI-T (13,772.6/0.733) and JIS score (13,874.7/0.720), with similar results observed in the V group (mALBI-T: 27,727.4/0.760; ALBI-T: 27,817.8/0.750; JIS: 27,807.5/0.748). Although there were some significant differences between the groups with regard to clinical background factors (age, etiology, tumor size, tumor number, treatment modalities), for all patients the AIC and c-index values of mALBI-T (45,327.1/0.755) were also better than those of ALBI-T (45,467.7/0.744) and JIS scores (45,555.8/0.739), indicating its superior stratification ability and prognostic predictive value in patients with HCC. CONCLUSION: The detailed stratification ability of mALBI grade for hepatic reserve function is suitable for the recent trend of HCC patients, while mALBI-T may provide a more accurate predictive value than existing total staging scoring systems.

Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan.

BACKGROUND: Lenvatinib demonstrated a treatment effect on overall survival by the statistical confirmation of non-inferiority to sorafenib for the first-line treatment of uHCC. The objective of this study was to evaluate the cost-effectiveness of lenvatinib compared with sorafenib for patients with uHCC in Japan. METHODS: A partitioned-survival model was developed to estimate the cost-effectiveness of lenvatinib versus sorafenib when treating uHCC patients over a lifetime horizon and considering total public healthcare expenditure. Efficacy and safety data were extracted from the REFLECT trial. Utility values were derived from the European Quality-of-Life 5-Dimension Questionnaire, conducted with patients enrolled in the REFLECT trial. Direct medical costs, such as primary drug therapy, outpatient visits, diagnostic tests, hospitalization, post-progression therapy, and adverse-event treatments, were included. Cost parameters unavailable in the clinical trial or publications were obtained based on the consolidated clinical standards from a Delphi panel of four Japanese medical experts. RESULTS: For lenvatinib versus sorafenib, the incremental cost was - 406,307 Japanese Yen (JPY), and the incremental life years and quality-adjusted life years (QALYs) were 0.27 and 0.23, respectively. Thus, lenvatinib dominated sorafenib, due to the mean incremental cost-effectiveness ratio falling in the fourth quadrant, conferring more benefit at lower costs compared with sorafenib. The probabilistic sensitivity analysis showed that 81.3% of the simulations were favorable to lenvatinib compared with sorafenib, with a payer's willingness-to-pay-per-QALY of 5 million JPY. CONCLUSIONS: Lenvatinib was cost-effective compared with sorafenib for the first-line treatment of uHCC in Japan.

Novel quantitative assessment system of liver steatosis using a newly developed attenuation measurement method.

AIM: The present study has developed and evaluated the effectiveness of a new echo attenuation measurement function combined with an ultrasonic diagnostic system for the accurate diagnosis of liver steatosis. METHODS: A multicenter prospective study involving patients with chronic hepatitis was carried out. All patients underwent liver biopsy, and attenuation coefficient (ATT) was measured on the same day. The fat area (%) of biopsy specimens was quantitatively evaluated. Correlations between ATT, steatosis grade, and fat area were evaluated. RESULTS: A total of 351 patients were enrolled in this study. The median values of fat area for steatosis grades S0, S1, S2, and S3 were 0.6%, 3.2%, 6.4%, and 15.5%, respectively. A significant correlation was found between fat area and steatosis grade (P < 0.001). Similarly, the median values of ATT for steatosis grades S0, S1, S2, and S3 were 0.55, 0.63, 0.69, and 0.85 dB/cm/MHz, respectively, and ATT increased with an increase in the steatosis grade (P < 0.001). Attenuation coefficient was significantly correlated with fat area (r = 0.50, P < 0.001). The area under the receiver operating characteristic curve corresponding to S ≥ 1, S ≥ 2, and S ≥ 3 were 0.79, 0.87, and 0.96, respectively. Similarly, the sensitivity and specificity of S ≥ 1, S ≥ 2, and S ≥ 3 were 72%, 82%, and 87% and 72%, 82%, and 89%, respectively. CONCLUSIONS: The newly developed ATT measurement for evaluation of liver steatosis was closely correlated with steatosis grade and automated quantification of fat area, and it provides clinically relevant information.

Cost-effectiveness of EOB-MRI for Hepatocellular Carcinoma in Japan.

PURPOSE: The objective of the study was to evaluate the cost-effectiveness of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in the diagnosis and treatment of hepatocellular carcinoma (HCC) in Japan compared with extracellular contrast media-enhanced MRI (ECCM-MRI) and contrast media-enhanced computed tomography (CE-CT) scanning. METHODS: A 6-stage Markov model was developed to estimate lifetime direct costs and clinical outcomes associated with EOB-MRI. Diagnostic sensitivity and specificity, along with clinical data on HCC survival, recurrence, treatment patterns, costs, and health state utility values, were derived from predominantly Japanese publications. Parameters unavailable from publications were estimated in a Delphi panel of Japanese clinical experts who also confirmed the structure and overall approach of the model. Sensitivity analyses, including one-way, probabilistic, and scenario analyses, were conducted to account for uncertainty in the results. FINDINGS: Over a lifetime horizon, EOB-MRI was associated with lower direct costs (¥2,174,869) and generated a greater number of quality-adjusted life years (QALYs) (9.502) than either ECCM-MRI (¥2,365,421, 9.303 QALYs) or CE-CT (¥2,482,608, 9.215 QALYs). EOB-MRI was superior to the other diagnostic strategies considered, and this finding was robust over sensitivity and scenario analyses. A majority of the direct costs associated with HCC in Japan were found to be costs of treatment. The model results revealed the superior cost-effectiveness of the EOB-MRI diagnostic strategy compared with ECCM-MRI and CE-CT. IMPLICATIONS: EOB-MRI could be the first-choice imaging modality for medical care of HCC among patients with hepatitis or liver cirrhosis in Japan. Widespread implementation of EOB-MRI could reduce health care expenditures, particularly downstream treatment costs, associated with HCC.

Magnetic resonance elastography in the assessment of hepatic fibrosis: a study comparing transient elastography and histological data in the same patients.

PURPOSE: To evaluate the quantitative measurement of liver stiffness (LS), compare the diagnostic performance of magnetic resonance elastography (MRE) and ultrasound-based transient elastography (TE), and evaluate two different MRE-based LS measurement methods. METHODS: Between October 2013 and January 2015, 116 consecutive patients with chronic liver disease underwent MRE to measure LS (kilopascals; kPa). Of the 116 patients, 51 patients underwent both TE and liver biopsy, and the interval between the liver biopsy and both the MRE and TE was less than 90 days. MRE-derived LS values were measured on the anterior segment of the right lobe (single small round regions of interest per slice; srROIs) and whole right lobe of the liver (free hand region of interest; fhROI), and these values were correlated with pathological fibrosis grades and diagnostic performance. RESULTS: Pathological fibrosis stage was significantly correlated with srROIs (r = 0.87, p < 0.001), fhROI (r = 0.80, p < 0.001), and TE (r = 0.73, p < 0.001). For detection of significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis, the area under the curve (AUC) associated with the srROIs was largest, and there was a significant difference between srROIs and TE (0.93 vs. 0.82, p = 0.006), srROIs and fhROI (0.93 vs. 0.89, p = 0.04) for detection of ≥F2. For advanced fibrosis and cirrhosis detection, AUCs were not significant (0.92-0.96). CONCLUSIONS: MRE and TE detected liver fibrosis with comparable accuracy. In particular, the srROIs method was effective for detecting of significant fibrosis.

Contrast-enhanced harmonic endoscopic ultrasonography for assessment of lymph node metastases in pancreatobiliary carcinoma.

AIM: To assess the usefulness of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for lymph node metastasis in pancreatobiliary carcinoma. METHODS: All patients suspected of pancreatobiliary carcinoma with visible lymph nodes after standard EUS between June, 2009 and January, 2012 were enrolled. In the primary analysis, patients with successful EUS-fine needle aspiration (FNA) were included. The lymph nodes were assessed by several standard EUS variables (short and long axis lengths, shape, edge characteristic and echogenicity), color Doppler EUS variable [central intranodal blood vessel (CIV) presence] and CH-EUS variable (heterogeneous/homogeneous enhancement patterns). The diagnostic accuracy relative to EUS-FNA was calculated. In the second analysis, N-stage diagnostic accuracy of CH-EUS was compared with EUS-FNA in patients who underwent surgical resection. RESULTS: One hundred and nine patients (143 lymph nodes) fulfilled the criteria. The short axis cut-off ≥ 13 mm predicted malignancy with a sensitivity and specificity of 72% and 85%, respectively. These values were 72% and 63% for the long axis cut-off ≥ 20 mm, 62% and 75% for the round shape variable, 81% and 30% for the sharp edge variable, 66% and 61% for the hypoechogenicity variable, 70% and 72% for the CIV-absent variable, and 83% and 91% for the heterogeneous CH-EUS-enhancement variable, respectively. CH-EUS was more accurate than standard and color Doppler EUS, except the short axis cut-off. Notably, three patients excluded because of EUS-FNA failure were correctly N-staged by CH-EUS. CONCLUSION: CH-EUS complements standard and color Doppler EUS and EUS-FNA for assessment of lymph node metastases.

Imaging Modalities for Assessment of Treatment Response to Nonsurgical Hepatocellular Carcinoma Therapy: Contrast-Enhanced US, CT, and MRI.

Tumor response and time to progression have been considered pivotal for surrogate assessment of treatment efficacy for patients with hepatocellular carcinoma (HCC). Recent advancements in imaging modalities such as contrast-enhanced ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are playing an important role in assessing the therapeutic effects of HCC treatments. According to some HCC clinical guidelines, post-therapeutic evaluation of HCC patients is based exclusively on contrast-enhanced dynamic imaging criteria. The recommended techniques are contrast-enhanced CT or contrast-enhanced MRI. Contrast-enhanced US is employed more in the positive diagnosis of HCC than in post-therapeutic monitoring. Although contrast enhancement is an important finding on imaging, enhancement does not necessarily depict the same phenomenon across modalities. We need to become well acquainted with the characteristics of each modality, including not only contrast-enhanced CT and MRI but also contrast-enhanced US. Many nonsurgical treatment options are now available for unresectable HCC, and accurate assessment of tumor response is essential to achieve favorable outcomes. For the assessment of successful radiofrequency ablation (RFA), the achievement of a sufficient ablation margin as well the absence of tumor vascular enhancement is essential. To evaluate the response to transcatheter arterial chemoembolization (TACE), enhanced tumor shrinkage is relied on as a measure of antitumor activity. Here, we give an overview of the current status of imaging assessment of HCC response to nonsurgical treatments including RFA and TACE.

Noninvasive diagnosis of liver fibrosis: utility of data mining of both ultrasound elastography and serological findings to construct a decision tree.

OBJECTIVE: Although liver biopsy is the gold standard for viral liver disease management, it is invasive and the sampling error rate is problematic. Real-time tissue elastography (RTE), a recently developed method of ultrasound elastography, can be used to assess liver fibrosis noninvasively but the overlap between fibrosis stages limits its ability to assess liver fibrosis adequately when used alone. METHODS: A multicenter collaborative study involving 542 patients with chronic viral hepatitis and cirrhosis who were scheduled to undergo liver biopsy compared the image features obtained from RTE image analysis, the liver fibrosis index (LFI), and pathological diagnosis. RTE and a blood test were performed on the same day as the liver biopsy. Data mining was also performed to construct a decision tree, and its diagnostic performance for assessing liver fibrosis was evaluated. RESULTS: The LFI was higher in patients with chronic hepatitis C (CHC) than in those with chronic hepatitis B (CHB). When a decision tree was constructed by data mining of RTE and serological findings, the diagnostic accuracy was very high for all fibrosis stages, with respective rates at F1, F2, F3, and F4 of 94.4, 54.1, 38.7, and 81.3% for patients with CHC and of 97.1, 50.0, 43.8, and 80.6% for patients with CHB. CONCLUSIONS: The variation in LFI values between the different etiologies appears to reflect the difference in the development style of liver fibrosis. The decision tree for assessing liver fibrosis constructed by data mining of both RTE and serological findings had a high diagnostic performance in assessing liver fibrosis and shows promising clinical utility.

Therapeutic response assessment of RFA for HCC: contrast-enhanced US, CT and MRI.

Radiofrequency ablation (RFA) is commonly applied for the treatment of hepatocellular carcinoma (HCC) because of the facile procedure, and the safety and effectiveness for the treatment of this type of tumor. On the other hand, it is believed that HCC cells should spread predominantly through the blood flow of the portal vein, which could lead to the formation of intrahepatic micrometastases. Therefore, monitoring tumor response after the treatment is quite important and accurate assessment of treatment response is critical to obtain the most favorable outcome after the RFA. Indeed, several reports suggested that even small HCCs of ≤ 3 cm in diameter might carry intrahepatic micrometastases and/or microvascular invasion. From this point of view, for preventing local recurrences, RFA should be performed ablating a main tumor as well as its surrounding non-tumorous liver tissue where micrometastases and microvascular invasion might exist. Recent advancement of imaging modalities such as contrast-enhanced ultrasonic, computed tomography, and magnetic resonance imaging are playing an important role on assessing the therapeutic effects of RFA. The local recurrence rate tends to be low in HCC patients who were proven to have adequate ablation margin after RFA; namely, not only disappearance of vascular enhancement of main tumor, but also an adequate ablation margin. Therefore, contrast enhancement gives important findings for the diagnosis of recurrent HCCs on each imaging. However, hyperemia of non-tumorous liver surrounding the ablated lesion, which could be attributed to an inflammation after RFA, may well obscure the findings of local recurrence of HCCs after RFA. Therefore, we need to carefully address to these imaging findings given the fact that diagnostic difficulties of local recurrence of HCC. Here, we give an overview of the current status of the imaging assessment of HCC response to RFA.

Comparison of systems for assessment of post-therapeutic response to sorafenib for hepatocellular carcinoma.

BACKGROUND: To test the hypothesis that use of the response evaluation criteria in cancer of the liver (RECICL), an improved evaluation system designed to address the limitations of the response evaluation criteria in solid tumors 1.1 (RECIST1.1) and modified RECIST (mRECIST), provides for more accurate evaluation of response of patients with hepatocellular carcinoma (HCC) to treatment with sorafenib, a molecularly targeted agent, as assessed by overall survival (OS). METHODS: The therapeutic response of 156 patients with advanced HCC who had been treated with sorafenib therapy for more than 1 month was evaluated using the RECIST1.1, mRECIST, and RECICL. After categorization as showing progressive disease (PD), stable disease (SD), or objective response, the association between OS and categorization was examined using the Kaplan-Meier method to develop survival curves. The 141 cases categorized as PD or SD by the RECIST1.1, but objective response by the mRECIST and RECICL, were further analyzed for determination of the association between OS and categorization. RESULTS: Only categorization using the RECICL was found to be significantly correlated with OS (p = 0.0033). Among the patients categorized as SD or PD by the RECIST1.1, reclassification by the RECICL but not the mRECIST was found to be significantly associated with OS and allowed for precise prediction of prognosis (p = 0.0066). CONCLUSIONS: Only the use of the RECICL allowed for identification of a subgroup of HCC patients treated with sorafenib with improved prognosis. The RECICL should, therefore, be considered a superior system for assessment of therapeutic response.

Assessment of liver fibrosis with real-time tissue elastography in chronic viral hepatitis.

OBJECTIVE: The aim of this study was to assess prospectively the accuracy of measurement of liver fibrosis with real-time tissue elastography (RTE) in patients with chronic viral hepatitis. METHODS: Two hundred and forty-five patients were prospectively enrolled. Nine image features were measured from strain images, and Liver Fibrosis Index (LFI) was calculated from these features. Fibrosis stage was diagnosed from pathological specimens obtained by ultrasound-guided biopsy. LFI and serological markers were compared with pathological diagnosis, and the diagnostic performance of RTE was compared. RESULTS: LFI in stages F0-F1, F2, F3 and F4 was 1.58, 2.03, 2.40 and 2.86, respectively, demonstrating a stepwise increase with increasing severity of liver fibrosis (p < 0.001). LFI in F2 did not significantly differ from that in F3, whereas for all other combinations of stages, there were significant differences. The area under the receiver operating characteristic curve of the LFI, platelet count, aspartate/alanine aminotransferase ratio, aspartate aminotransferase-to-platelet ratio, and FibroIndex for predicting F3 stage or higher (F0-F2 vs. F3-F4) was 0.865, 0.824, 0.708, 0.789 and 0.828, respectively. CONCLUSIONS: RTE is useful for diagnosis of liver fibrosis, regardless of stage, in patients with chronic viral hepatitis.

Therapeutic response assessment of transcatheter arterial chemoembolization for hepatocellular carcinoma: ultrasonography, CT and MR imaging.

Two randomized controlled trials identified that transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) shows a significant survival benefit compared with controls, after a long-term controversy. Thus, TACE is the current standard of care for patients presenting with multinodular HCC. Monitoring tumor response to TACE is part of the clinical management of HCC patients. Imaging, including ultrasonography, computed tomography and magnetic resonance imaging, has an important role in assessing therapeutic effects earlier and more objectively. Imaging assessment needs to detect not only a reduction in overall tumor load but also a reduction in viable tumor. Here, we give an overview of the current status of the imaging assessment of HCC response to TACE.