The usefulness of a newly developed full-core biopsy needle in liver biopsy.

AIM: To evaluate the usefulness and safety of a newly developed full-core biopsy needle. METHODS: We selected 149 patients who underwent percutaneous liver biopsy at our institution from February 2019 to April 2021. We excluded 35 patients with hepatic fibrosis stage F3 or higher, which made it histopathologically difficult to measure the number of complete portal triads. The patients were divided into two groups as follows: 62 cases with the 18-G conventional automated needle (TruCore needle: T needle), and 52 cases with the 18-G full-core needle (CorVocet needle: C needle). We measured the number of complete portal triads in the liver tissue specimens, and the sum of the length and width of the collected tissues. Moreover, we compared the number of session counts, fragmentations, and complications. RESULTS: The sum of the length and the width was 12.8 mm (11.2-14.3) and 15.9 mm (13.1-17.3; p < 0.001), and 0.68 mm (0.63-0.74) and 0.82 mm (0.78-0.90; p < 0.001) for the T needle and C needle, respectively. The number of complete portal triads and fragmentation was six (3-8) and 10 (6-13; p < 0.001), and one (1-10) and one (1-3; p < 0.001), for the T needle and C needle, respectively. There was one session count (1-2) in both groups; however, there were significantly higher cases of two sessions with the T needle than that with the C needle (p = 0.018). There were no serious adverse events. CONCLUSIONS: Compared with the conventional needles, the newly developed full-core needles enabled the acquisition of a larger amount of tissue sample in liver biopsy.

Alanine aminotransferase levels as therapeutic targets after nucleotide/nucleoside analog therapy in patient with chronic hepatitis B.

AIM: Alanine aminotransferase (ALT) is a criterion for the introduction of nucleotide/nucleoside analog (NA), and ALT levels are decreased by NA treatment. However, the association between post-treatment ALT levels and hepatocellular carcinoma (HCC) risk remains unclear. To fill this gap, we aimed to establish a target value of ALT level during NA treatment. METHODS: In total, 413 patients with chronic hepatitis B who received entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate were enrolled. The subsequent development of HCC was examined and a target value of ALT level during NA treatment as a risk marker for HCC was evaluated. RESULTS: The median follow-up duration was 5.1 years, during which time 27 patients (8.6%) developed HCC. ALT level at the start of treatment was not associated with HCC development (p = 0.08). When stratified by ALT at 1 year after NA initiation, the cumulative 3- and 5-year rates of HCC for patients with ALT ≥21 IU/L were 11.5% and 18.1%, and those with ALT <21 IU/L was 2.3% and 6.5%, respectively. Patients with ALT <21 IU/L had a significantly lower risk of HCC development compared with patients with ALT ≥21 IU/L (p = 0.002). In multivariable analysis adjusting age, sex, and platelet counts, ALT ≥21 IU/L was an independent risk factor of HCC development with hazard ratio of 4.5 (95% confidence interval: 1.01-20.4). CONCLUSIONS: ALT <21 IU/L at 1 year after NA initiation has a lower risk of HCC and could be used as a target value for NA treatment.

Tumor steatosis and glutamine synthetase expression in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab therapy.

AIM: The anti-programmed death-ligand 1 antibody atezolizumab and vascular endothelial growth factor-neutralizing antibody bevacizumab in combination (Atezo + Bev) have become the first-line therapy in advanced hepatocellular carcinoma (HCC). Distinct types of tumor immune microenvironment (TIME) and their associations with specific molecular subclasses and driver gene mutations have been identified in HCC; however, these insights are mainly based on surgically resected early-stage tumors. The current study aimed to reveal the biology and TIME of advanced HCC and their significance in predicting clinical outcomes of Atezo + Bev therapy. METHODS: Thirty-three patients with advanced HCC who were scheduled for treatment with Atezo + Bev therapy were included in this study. Pretreatment tumor biopsy, pre- and posttreatment diffusion-weighted magnetic resonance imaging (MRI) with nine b values (0-1500 s/mm2 ), and other clinicopathologic factors were analyzed. RESULTS: Compared with resectable HCC, advanced HCC was characterized by higher proliferative activity, a higher frequency of Wnt/ß-catenin-activated HCC, and lower lymphocytic infiltration. Prognostically, two metabolism-related factors, histopathologically determined tumor steatosis and/or glutamine synthetase (GS) expression, and MRI-determined tumor steatosis, were the most significant prognostic indicators for progression-free survival (PFS) and overall survival after Atezo + Bev therapy. Furthermore, changes in the pre- and posttreatment true diffusion coefficients on MRI, which might reflect changes in TIME after treatment, were significantly associated with better PFS. CONCLUSIONS: The biology and TIME of HCC were strikingly different in advanced HCC compared with those of surgically resected HCC. Two metabolism-related factors, pathologically determined tumor steatosis and/or GS expression, and MRI-determined tumor steatosis, were found to be the most significant prognostic indicators for Atezo + Bev therapy in advanced HCC.

Diagnostic Accuracy of Two-Dimensional Shear Wave Elastography for Liver Fibrosis: A Multicenter Prospective Study.

Chronic liver disease (CLD) leads to the development of hepatocellular carcinoma, which is one of the leading causes of cancer-related deaths globally.1 Liver fibrosis is the most important prognostic factor for hepatocellular carcinoma development and prognosis in CLD, and accurate staging of liver fibrosis is pivotal in clinical practice.2 Although liver biopsy is the gold standard for evaluating liver fibrosis, liver biopsy has several limitations including invasiveness, sampling error, and intraobserver and interobserver reproducibility.3 To resolve these problems, several noninvasive methods for evaluating liver fibrosis have been developed using serum fibrosis markers, ultrasound-based modalities, and magnetic resonance imaging-based modalities.4.

Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice.

BACKGROUND: We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alpha-fetoprotein (AFP) response in real-world practice. METHODS: A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to evaluate radiological responses. RESULTS: The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rd-line (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. According to RECIST, the objective response rate (ORR) and disease control rate (DCR) in all patients were 15.4% and 57.7%. In the 1st-line patients, ORR and DCR based on RECIST 1.1 were 27.3% and 81.8%. The median time to progression (TTP) assessed by RECIST was significantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P < 0.001). Patients with an AFP response (reduction ≥ 20% from baseline) at 6 weeks had a significantly longer TTP assessed by RECIST than those without an AFP response (P = 0.02). CONCLUSION: Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6 weeks could be a predictor of disease progression.

Comparison of modified CEUS LI-RADS with sonazoid and CT/MRI LI-RADS for diagnosis of hepatocellular carcinoma.

AIM: To compare the diagnostic performance based on the modified CEUS Liver Imaging Reporting and Data System (LI-RADS), which includes Kupffer-phase findings as a major imaging feature, with that of CT and MRI (CT/MRI) LI-RADS for liver nodules in patients at high risk of HCC. METHODS: A total of 120 patients with 120 nodules were included in this retrospective study. The median size of the lesions was 20.0 mm (interquartile range, 14.0-30.8 mm). Of these lesions, 90.0% (108 of 120) were confirmed as HCCs, 6.7% (8 of 120) were intrahepatic cholangiocarcinomas, 1.7% (2 of 120) were metastases, and 1.7% (2 of 120) were dysplastic nodules. All nodules were diagnosed histopathologically. Each nodule was categorized according to the modified CEUS LI-RADS and CT/MRI LI-RADS version 2018. The diagnostic performance and inter-modality agreement of each criterion was compared. RESULTS: The inter-modality agreement for the modified CEUS LI-RADS and CT/MRI LI-RADS was slight agreement (kappa = 0.139, p = 0.015). The diagnostic accuracies of HCCs for the modified CEUS LR-5 and CT/MRI LR-5 were 70.0% (95% confidence interval [CI]: 61.0%, 78.0%) versus 70.8% (95% CI: 61.8%, 78.8%) (p = 0.876), respectively. The diagnostic accuracies of non-HCC malignancies for the modified CEUS LR-M and CT/MRI LR-M were 84.2% (95% CI: 76.4%, 90.2%) versus 96.7% (95% CI: 91.7%, 99.1%) (p = 0.002), respectively. CONCLUSIONS: The diagnostic performance for HCCs on the modified CEUS LR-5 and CT/MRI LR-5 are comparable. In contrast, CT/MRI LR-M has better diagnostic performance for non-HCC malignancy than that of the modified CEUS LR-M.

Multiparametric US for Identifying Patients with High-Risk NASH: A Derivation and Validation Study.

Background Nonalcoholic fatty liver disease (NAFLD) is common in the general population but identifying patients with high-risk nonalcoholic steatohepatitis (NASH) who are candidates for pharmacologic therapy remains a challenge. Purpose To develop a score to identify patients with high-risk NASH, defined as NASH with an NAFLD activity score (NAS) of 4 or greater and clinically significant fibrosis (stage 2 [F2] or higher). Materials and Methods This was a cross-sectional secondary analysis of data prospectively collected between April 2017 and March 2019 for a group of patients with NAFLD in Japan (Japan NAFLD, the derivation data set) with contemporaneous two-dimensional shear-wave elastography and biopsy-proven NAFLD (age range, 20-89 years). Three US markers (liver stiffness [LS, measured in kilopascals], attenuation coefficient [AC, measured in decibels per centimeter per megahertz], and dispersion slope [DS, measured in meters per second per kilohertz]) were determined, together with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the AST-to-ALT ratio. The best-fit multivariate logistic regression model for identifying patients with high-risk NASH was determined. Diagnostic performance was assessed by using the area under the receiver operating characteristic curve (AUC). The findings were validated in an independent data set (Korea NAFLD; age range, 20-78 years). Results The Japan NAFLD data set included 111 patients (mean age, 53 years ± 18 [standard deviation]; 57 men), 84 (76%) with NASH. The Korea NAFLD data set included 102 patients (mean age, 48 years ± 18; 43 men), 55 (36%) with NASH. The most predictive model (LAD NASH score) combined LS, AC, and DS. Performance was satisfactory in both the derivation sample (AUC, 0.86; 95% CI: 0.79, 0.93) and the validation sample (AUC, 0.88; 95% CI: 0.80, 0.95). The LAD NASH score showed a positive predictive value of 86.5% and a negative predictive value of 87.5% for high-risk NASH in the derivation sample. Conclusion A score combining three US markers may be useful for noninvasive identification of patients with high-risk nonalcoholic steatohepatitis for inclusion in clinical trials and pharmacologic therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lockhart in this issue.

[A case of endoscopic injection sclerotherapy for duodenal varices].

A 67-year-old man with a history of esophageal and gastric varices that were treated endoscopically was treated for Budd-Chiari syndrome and immunoglobulin G4-related sclerosing cholangitis in our facility. Varices in the second portion of the duodenum were revealed in follow-up upper endoscopy. The draining vein formed a venous plexus that was detected on computed tomography. Treatment with interventional radiology was difficult;therefore, endoscopic injection sclerotherapy (EIS) was performed instead. No recurrence has been observed to date. Thus, in this case, EIS for duodenal varices was effective.

Deep learning approach for discrimination of liver lesions using nine time-phase images of contrast-enhanced ultrasound.

PURPOSE: Contrast-enhanced ultrasound (CEUS) shows different enhancement patterns depending on the time after administration of the contrast agent. The aim of this study was to evaluate the diagnostic performance of liver nodule characterization using our proposed deep learning model with input of nine CEUS images. METHODS: A total of 181 liver lesions (48 benign, 78 hepatocellular carcinoma (HCC), and 55 non-HCC malignant) were included in this prospective study. CEUS were performed using the contrast agent Sonazoid, and in addition to B-mode images before injection, image clips were stored every minute up to 10 min. A deep learning model was developed by arranging three ResNet50 transfer learning models in parallel. This proposed model allowed inputting up to nine datasets of different phases of CEUS and performing image augmentation of nine images synchronously. Using the results, the correct prediction rate, sensitivity, and specificity between "benign" and "malignant" cases were analyzed for each combination of the time phase. These accuracy values were also compared with the washout score judged by a human. RESULTS: The proposed model showed performance superior to the referential standard model when the dataset from B-mode to the 10-min images were used (sensitivity: 93.2%, specificity: 65.3%, average correct answer rate: 60.1%). It also maintained 90.2% sensitivity and 61.2% specificity even when the dataset was limited to 2 min after injection, and this accuracy was equivalent to or better than human scoring by experts. CONCLUSION: Our proposed model has the potential to identify tumor types earlier than the Kupffer phase, but at the same time, machine learning confirmed that Kupffer-phase Sonazoid images contain essential information for the classification of liver nodules.

Favorable liver and skeletal muscle changes in patients with MASLD and T2DM receiving glucagon-like peptide-1 receptor agonist: A prospective cohort study.

To investigate changes in skeletal muscle mass and fat fraction in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) undergoing treatment with Semaglutide for 6months. This single-arm pilot study included 21 patients with MASLD who received semaglutide for T2DM. Body weight, metabolic parameters, liver enzymes, fibrosis markers, skeletal muscle index (cm2/m2), and fat fraction (%) at the L3 level using the two-point Dixon method on magnetic resonance imaging (MRI), as well as liver steatosis and liver stiffness assessed using MRI-based proton density fat fraction (MRI-PDFF) and MR elastography, respectively, were prospectively examined before and 6 months after semaglutide administration. The mean age of the patients was 53 years and 47.6% were females. The median liver steatosis-fraction (%) and skeletal muscle steatosis-fraction values (%) significantly decreased (22.0 vs 12.0; P = .0014) and (12.8 vs 9.9; P = .0416) at baseline and 6 months, respectively, while maintaining muscle mass during treatment. Semaglutide also dramatically reduced hemoglobin A1c (%) (6.8 vs 5.8, P = .0003), AST (IU/L) (54 vs 26, P < .0001), ALT (IU/L) (80 vs 34, P = .0004), and γ-GTP (IU/L) levels (64 vs 34, P = .0007). Although not statistically significant, Body weight (kg) (79.9 vs 77.4), body mass index (BMI) (kg/m2) (28.9 vs 27.6), and liver stiffness (kPa) (28.9 vs 27.6) showed a decreasing trend. Fibrosis markers such as M2BPGi, type IV collagen, and skeletal muscle area did not differ. Semaglutide demonstrated favorable effects on liver and skeletal muscle steatosis, promoting improved liver function and diabetic status.

Advanced fibrosis leads to overestimation of steatosis with quantitative ultrasound in individuals without hepatic steatosis.

PURPOSE: The effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)-derived proton density fat fraction (MRIderived PDFF) as the reference standard. METHODS: Between February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness. RESULTS: AC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P<0.001), MR elastography value (P=0.037), and MRI-derived PDFF (P<0.001) in patients without hepatic steatosis. In 52 of 982 patients (5%), the correlation between AC and MRIderived PDFF fell outside the 95% confidence interval for the regression line slope. Patients with MRI-derived PDFF lower than their AC (n=36) had higher fibrosis-4 scores, albumin-bilirubin scores, and MR elastography values than patients with MRI-derived PDFF greater than their AC (n=16; P=0.018, P=0.001, and P=0.011, respectively). CONCLUSION: AC is affected by liver fibrosis (MR elastography value ≥6.7 kPa) only in patients without hepatic steatosis (MRI-derived PDFF <5.2%). These values should be interpreted with caution in patients with advanced liver fibrosis.

Comparisons of Radiofrequency Ablation, Microwave Ablation, and Irreversible Electroporation by Using Propensity Score Analysis for Early Stage Hepatocellular Carcinoma.

BACKGROUND: Despite the diversity of thermal ablations, such as radiofrequency ablation (RFA) and microwave ablation (MWA), and non-thermal ablation, such as irreversible electroporation (IRE) cross-comparisons of multiple ablative modalities for hepatocellular carcinoma (HCC) treatment remain scarce. Thus, we investigated the therapeutic outcomes of different three ablation modalities in the treatment of early stage HCC. METHODS: A total of 322 consecutive patients with 366 HCCs (mean tumor size ± standard deviation: 1.7 ± 0.9 cm) who underwent RFA (n = 216, 59.0%), MWA (n = 91, 28.3%), or IRE (n = 15, 4.7%) were included. Local tumor progression (LTP) rates for LTP were compared among the three modalities. Propensity score-matched analysis was used to reduce selection bias. RESULTS: A significant difference in 2-year LTP rates between the IRE and RFA groups (IRE, 0.0% vs. RFA, 45.0%; p = 0.005) was found. There was no significant difference in 2-year LTP rates between the IRE and MWA groups (IRE, 0.0% vs. MWA, 25.0%; p = 0.103) as well as between the RFA and MWA groups (RFA, 18.2% vs. MWA, 20.6%; p = 0.586). CONCLUSION: IRE provides better local tumor control than RFA as a first-line therapeutic option for small perivascular HCC.

Modified CEUS LI-RADS using Sonazoid for the diagnosis of hepatocellular carcinoma.

This review outlines several modified versions of the contrast-enhanced ultrasonography Liver Imaging Reporting and Data System (CEUS LI-RADS) that utilize Sonazoid. Furthermore, it discusses the advantages and challenges of diagnosing hepatocellular carcinoma using these guidelines, as well as the authors' expectations and opinions regarding the next CEUS LI-RADS version. It is possible that Sonazoid could be incorporated into the next version of CEUS LI-RADS.

Add-on Therapeutic Effects of Rifaximin on Treatment-resistant Hepatic Encephalopathy.

Objective Rifaximin is used to treat hepatic encephalopathy. However, whether or not rifaximin and lactulose combination therapy can enhance the treatment outcomes and reduce the hospitalization rate of patients with hepatic encephalopathy that are resistant to lactulose has yet to be determined. The present study investigated the hospitalization rate before and after rifaximin add-on therapy in patients resistant to lactulose. Methods A total of 36 patients who were resistant to lactulose with add-on rifaximin therapy were enrolled. Patients who were hospitalized and/or did not achieve normalization of ammonia levels under lactulose administration were defined as treatment-resistant. The primary outcome was the change in hospitalization rate due to hepatic encephalopathy at 24 weeks before and after rifaximin administration. Results Before rifaximin administration, 15 (41.6%) patients were hospitalized due to hepatic encephalopathy. After rifaximin administration, 8 (22.2%) patients were hospitalized due to hepatic encephalopathy. The hospitalization rates were significantly reduced after rifaximin administration (p=0.02). The median (interquartile range) ammonia levels upon rifaximin administration (baseline) and 8, 12, and 24 weeks after rifaximin administration were 124 (24-310) µg/dL, 78 (15-192) µg/dL, 67 (21-233) µg/dL, and 77 (28-200) µg/dL, respectively. Furthermore, the ammonia levels were significantly reduced by rifaximin add-on therapy (p=0.005, p=0.01, and p=0.01). Conclusion The addition of rifaximin to lactulose treatment in treatment-resistant patients decreases the hospitalization rate among patients with hepatic encephalopathy and may be used as an add-on treatment.

Detecting advanced liver fibrosis using ultrasound shear wave velocity measurement in the general population.

Background: Advanced fibrosis detection in the general population is an unmet need. Additionally, screening method for advanced fibrosis in the general population is not established. Thus, this study aimed to examine the use of shear wave measurement (SWM), which measures liver stiffness by ultrasound elastography as a screening tool for advanced fibrosis in health checkups that represents the general population. Methods: SWM was performed in all subjects. Magnetic resonance elastography (MRE) was performed in those with SWM shear wave velocity (Vs) ≥1.3 m/s to determinate advanced fibrosis. The diagnostic accuracy of SWM Vs for advanced fibrosis (determined by MRE of ≥3.62 kPa) was examined. This prospective study was registered with the University Hospital Medical Information Network clinical trial registry (UMIN000041609). Results: A total of 2,233 subjects were included. SWM Vs of 1.64 m/s was selected as the best threshold for advanced fibrosis. Using the threshold of SWM Vs at ≥1.64 m/s, subjects were narrowed down to 1.7%, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for advanced fibrosis were 53.3%, 92.4%, 47.1%, and 94.0%, respectively, among these subjects. The multivariable analysis, after adjusting the age, sex, body mass index (BMI), hypertension, diabetes mellitus (DM), dyslipidemia, and alcohol use, revealed an SWM Vs of ≥1.64 m/s as the significant factor for advanced fibrosis with an odds ratio (95% confidence interval) of 14.5 (3.4-62; P<0.001). Conclusions: SWM has high diagnostic accuracy for advanced fibrosis (PPV 47.1%) and may be used as a screening tool for liver fibrosis in the general population.

Noninvasive Diagnosis of Hepatocellular Carcinoma on Sonazoid-Enhanced US: Value of the Kupffer Phase.

The aim of this study was to compare the diagnostic performance of Contrast-Enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) version 2017, which includes portal- and late-phase washout as a major imaging feature, with that of modified CEUS LI-RADS, which includes Kupffer-phase findings as a major imaging feature. Participants at risk of hepatocellular carcinoma (HCC) with treatment-naïve hepatic lesions (≥1 cm) were recruited and underwent Sonazoid-enhanced US. Arterial phase hyperenhancement (APHE), washout time, and echogenicity in the Kupffer phase were evaluated using both criteria. The diagnostic performance of both criteria was analyzed using the McNemar test. The evaluation was performed on 102 participants with 102 lesions (HCCs (n = 52), non-HCC malignancies (n = 36), and benign (n = 14)). Among 52 HCCs, non-rim APHE was observed in 92.3% (48 of 52). By 5 min, 73.1% (38 of 52) of HCCs showed mild washout, while by 10 min or in the Kupffer phase, 90.4% (47 of 52) of HCCs showed hypoenhancement. The sensitivity (67.3%; 35 of 52; 95% CI: 52.9%, 79.7%) of modified CEUS LI-RADS criteria was higher than that of CEUS LI-RADS criteria (51.9%; 27 of 52; 95% CI: 37.6%, 66.0%) (p = 0.0047). In conclusion, non-rim APHE with hypoenhancement in the Kupffer phase on Sonazoid-enhanced US is a feasible criterion for diagnosing HCC.

Conversion surgery for hepatocellular carcinoma after tyrosine kinase inhibitor treatment.

Background and Aim: Conversion surgery (CS), which aims to cure after systematic therapy, is only scarcely reported in the field of hepatocellular carcinoma (HCC). However, advancements in systemic therapy for HCC are expected to increase the candidates eligible for CS because of the higher response rate. The aim of this study was to clarify the characteristics of patients who underwent CS after tyrosine kinase inhibitor (TKI) therapy. Methods: In all, 364 patients who were treated with first-line sorafenib (SOR; n = 292) and lenvatinib (LEN; n = 72) from July 2009 to October 2020 were retrospectively enrolled. The endpoint of this analysis was overall survival (OS), and factors associated with CS are revealed. Results: Six patients underwent CS after TKI therapy, and of these four (1.4%) and two (2.7%) patients received SOR and LEN, respectively. At baseline, patients who underwent CS were significantly younger (median 52 [range, 46-83] years of age, P = 0.019), and their etiology included viral hepatitis, especially hepatitis B virus (HBV) (P = 0.049). Improvements or maintenance of preoperative modified albumin-bilirubin grade from baseline were observed in five (83.3%) patients, and partial radiologic response was observed in four (66.7%) patients. The median OS and 3-year survival rate of patients treated with CS were "not reached" and 80.0%, respectively. Conclusion: The patients who underwent CS after TKI therapy for HCC experienced long survival, were relatively young, and exhibited radiologic response to TKIs, and their liver function was either maintained or improved. Therefore, CS may lead to a better prognosis in patients with advanced HCC.

Clinical evaluation of Elecsys PIVKA-II for patients with advanced hepatocellular carcinoma.

BACKGROUND: Prothrombin induced by vitamin K absence-II (PIVKA-II) was reported as a diagnosis and prognosis marker for hepatocellular carcinoma (HCC). Although the development of systemic therapies for advanced HCC has been remarkable, the role of PIVKA-II is unclear. This prospective study aimed to verify Elecsys PIVKA-II compared with Lumipulse PIVKA-II in a cohort with advanced HCC undergoing systemic therapy. METHODS: A total of 62 HCC patients who were treated with atezolizumab and bevacizumab (ATZ+BEV) and molecular targeted agents (MTAs) were prospectively enrolled at Musashino Red Cross Hospital from January 2020 to December 2020. A total of 208 serum samples from 52 patients were tested using Elecsys PIVKA-II and Lumipulse PIVKA-II assays. Furthermore, the relationship of Elecsys PIVKA-II and progression-free survival (PFS) was investigated with 48 patients (24 ATZ+BEV and 24 MTAs) whose Lumipulse PIVKA-II levels were >40 mAU/mL. RESULTS: In the test accuracy analysis, the Elecsys assay has a correlation coefficient (R) of 0.92 compared with that of the Lumipulse assay (ATZ+BEV, 0.95; MTAs, 0.91). In the PFS analysis, the number of patients who received ATZ+BEV and MTAs as first- and late-line therapy were 9 and 13, and 15 and 11, respectively. The PIVKA-II response was defined for patients who had a reduction in the Elecsys PIVKA-II level on the first month of treatment evaluation. The PFS of patients with Elecsys PIVKA-II response was significantly longer than that of nonresponse patients (5.8 months vs 3.8 months, p = 0.0205). CONCLUSION: The Elecsys PIVKA-II was not only as useful as the Lumipulse PIVKA-II but also for stratifying the PFS of patients with advanced HCC.

Simple algorithm to narrow down the candidates to receive echocardiography in patients with chronic liver disease for suspected pulmonary hypertension.

Aims: Portopulmonary hypertension (PoPH) is a subtype of pulmonary arterial hypertension related to portal hypertension. The definitive diagnosis of PoPH is made by invasive right heart catheterization. Alternatively, pulmonary arterial hypertension may be recognized noninvasively from the tricuspid regurgitant pressure gradient (TRPG), measured by echocardiography. In this study, we aimed to establish a simple algorithm to identify chronic liver disease patients with a high TRPG value in order to narrow down the candidates to receive echocardiography. Methods and Results: TRPG was measured by echocardiography in 152 patients with chronic liver disease. Factors predictive of TRPG >30 mmHg were investigated. There were 28 (18%) cases with TRPG >30 mmHg. Independent factors associated with a high TRPG were the presence of shortness of breath, high serum brain natriuretic peptide (BNP), and low serum albumin. Child-Pugh class or the presence of ascites, varices, or encephalopathy was not associated with TRPG. There was a correlation between the serum BNP and TRPG, and the optimal cutoff value of BNP by the Youden index was 122 pg/mL, and by 100% sensitivity was 50 pg/mL. A combination of these factors identified patients with a high probability of TRPG >30 mmHg (n = 12, positive predictive value [PPV] of 83%), no probability (n = 80, PPV 0%), and intermediate probability (n = 60, PPV 25-34%). This algorithm has reduced the number of patients needing echocardiography by 53%. Conclusions: A simple algorithm using the presence of shortness of breath, serum BNP, and albumin levels can narrow down the candidates to receive echocardiography.

The most appropriate region-of-interest position for attenuation coefficient measurement in the evaluation of liver steatosis.

PURPOSE: Attenuation imaging (ATI) is a new noninvasive ultrasound technique for assessing steatosis grade (S). However, validated region-of-interest (ROI) sampling strategies are not currently available. We investigated the diagnostic performance of various ATI-ROI positions for determining histopathologic S in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This retrospective study included 105 patients with biopsy-proven NAFLD. All attenuation coefficient (AC, dB/cm/MHz) measurements were obtained by the same hepatologist using a commercially available ultrasound system on the same day as liver biopsy. Mean (± standard deviation) age and body mass index of the patients were 53 (± 18) years and 27.1 (± 4.1) kg/m2, respectively. The numbers of patients with steatosis affecting < 5%, 5-33%, 33-66%, and > 66% of hepatocytes were 8, 50, 29, and 18, respectively. The ATI-ROI was placed at three different positions for AC measurement using a dedicated workstation: the upper edge of the area ROI, twice the depth of the liver capsule, and the lower edge of the area ROI. Diagnostic performance was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS: The AUCs of AC at the three ATI-ROI positions were 0.734 (95% confidence interval [CI]: 0.470-0.998), 0.750 (0.639-0.861), and 0.878 (0.788-0.968) for S ≥ 1; 0.503 (0.392-0.615), 0.824 (0.741-0.907), and 0.809 (0.724-0.895) for S ≥ 2; and 0.606 (0.486-0.726), 0.849 (0.767-0.932), and 0.737 (0.626-0.848) for S = 3, respectively. CONCLUSION: For accurate steatosis grade assessment, the ATI-ROI should not be placed at the upper edge of the area ROI.