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Aim: This study aimed to establish the shear wave measurement (SWM) cut-off value for each fibrosis stage using magnetic resonance (MR) elastography values as a reference standard., Methods: We prospectively analyzed 594 patients with chronic liver disease who underwent SWM and MR elastography. Correlation coefficients (were analyzed, and the diagnostic value was evaluated by the area under the receiver operating characteristic curve. Liver stiffness was categorized by MR elastography as F0 (<2.61 kPa), F1 (≥2.61 kPa, <2.97 kPa, any fibrosis), F2 (≥2.97 kPa, <3.62 kPa, significant fibrosis), F3 (≥3.62 kPa, <4.62 kPa, advanced fibrosis), or F4 (≥4.62 kPa, cirrhosis)., Results: The median SWM values increased significantly with increasing fibrosis stage (p < 0.001). The correlation coefficient between SWM and MR elastography values was 0.793 (95% confidence interval 0.761-0.821). The correlation coefficients between SWM and MR elastography values significantly decreased with increasing body mass index and skin-capsular distance; skin-capsular distance values were associated with significant differences in sensitivity, specificity, accuracy, or positive predictive value, whereas body mass index values were not. The best cut-off values for any fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis were 6.18, 7.09, 8.05, and 10.89 kPa, respectively., Conclusions: This multicenter study in a large number of patients established SWM cut-off values for different degrees of fibrosis in chronic liver diseases using MR elastography as a reference standard. It is expected that these cut-off values will be applied to liver diseases in the future., (© 2024 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Aim: Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events., Methods: A total of 282 patients with liver biopsy-proven MASLD were included. Liver-related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child-Pugh class B and C, as well as treatment-eligible esophageal and gastric varices., Results: Multivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver-related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver-related events, including the occurrence of HCC and complications of liver cirrhosis., Conclusions: While the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver-related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC., (© 2024 Japan Society of Hepatology.)

Aim: Elderly patients are believed to have a reduced immune capacity, which may make immunotherapy less effective. The aim of this study was to compare the therapeutic outcome of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) for advanced hepatocellular carcinoma (HCC) in patients aged 80 years and older., Methods: From March 2018 to July 2022, 170 and 92 elderly patients who received LEN and Atez/Bev as first-line treatment, respectively, were retrospectively analyzed., Results: The median ages of the Atez/Bev and LEN groups were 83.0 (8.01-86.0) and 83.0 (82.0-86.0) years (p = 0.3), respectively. Men accounted for approximately 70% of the patients in both groups. The objective response rate was 35.9% in the LEN group and 33.7% in the Atez/Bev group (p = 0.8), whereas the disease control rates in the LEN and Atez/Bev groups were 62.9% and 63.0%, respectively (p = 1.0). The median progression-free survival (PFS) in the LEN and Atez/Bev groups was 6.3 and 7.2 months, respectively, which were not significantly different (p = 0.2). The median overall survival (OS) was 17.9 months in the LEN group and 14.0 months in the Atez/Bev group. This difference was not statistically significant (p = 0.7). In multivariate analyses, the choice of treatment (LEN vs. Atez/Bev) showed no association with PFS or OS. The Atez/Bev group had a significantly higher rate of postprogression treatment (59.0% vs. 35.7%, p = 0.01) and a lower rate of discontinuation due to adverse events (69 [40.6%] vs. 19 [20.7%], p < 0.001) compared to the LEN group., Conclusions: Atezolizumab plus bevacizumab showed comparable effectiveness to LEN in HCC patients aged 80 years and older. Given the results of postprogression treatment and discontinuation due to adverse events, Atez/Bev could serve as a first-line treatment even for elderly HCC patients., (© 2023 Japan Society of Hepatology.)

Aim: The present study focused on Geriatric Nutritional Risk Index (GNRI), which is based on bodyweight and serum albumin, and known as an easy-to-use nutritional assessment tool in clinical settings, to elucidate the prognostic predictive ability of GNRI in patients treated with atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC)., Methods: A total of 525 HCC patients treated with Atez/Bev, based on their classification of unsuitable status for curative treatments and/or transarterial catheter chemoembolization, were enrolled (Child-Pugh A:B:C = 484:40:1, Barcelona Clinic Liver Cancer stage 0:A:B:C:D = 7:25:192:283:18). Prognosis was evaluated retrospectively using GNRI., Results: Atez/Bev was used in 338 of the present cohort as first-line systemic chemotherapy (64.4%). Median progression-free survival based on GNRI indicating normal, mild decline, moderate decline, and severe decline was 8.3, 6.7, 5.3, and 2.4 months, respectively, whereas median overall survival was 21.4, 17.0, 11.5. and 7.3 months, respectively (both p < 0.001). The concordance index (c-index) values of GNRI for predicting prognosis (progression-free survival/overall survival) were superior to those of Child-Pugh class and albumin-bilirubin grade (0.574/0.632 vs. 0.527/0.570 vs. 0.565/0.629). As a subanalysis, muscle volume loss was observed in 37.5% of 256 patients with computed tomography data available. Along with GNRI decline, frequency of muscle volume loss became progressively larger (normal vs. mild vs. moderate vs. severe = 17.6% vs. 29.2% vs. 41.2% vs. 57.9%, p < 0.001), and a GNRI value of 97.8 was predictive of its occurrence (AUC 0.715, 95% CI 0.649-0.781; specificity/sensitivity = 0.644/0.688)., Conclusion: These findings indicate that GNRI is an effective nutritional prognostic tool for predicting prognosis and muscle volume loss complication in HCC patients treated with Atez/Bev., (© 2023 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Aim: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance., Methods: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results., Results: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome., Conclusions: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status., (© 2023 Japan Society of Hepatology.)

Aim: This retrospective study aimed to investigate the impact of proton pump inhibitor treatment (PPI) and antibiotic treatment on the therapeutic outcomes of hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab (Atez/Bev)., Methods: The present study included a total of 441 HCC patients who were treated with Atez/Bev in 20 Japanese institutions from September 2020 to April 2022. We adopted the inverse probability of treatment weight to adjust for imbalance in the baseline characteristics of patients with and without PPI treatment as well as patients with and without antibiotic treatment., Results: The progression-free survival (PFS) and overall survival (OS) of patients with and without PPI treatment did not differ to a statistically significant extent. In the weighted cohort, the difference in PFS and OS between the patients with and without PPI did not reach statistical significance (median PFS, 7.0 vs. 6.5 months, p = 0.07; 1-year survival rate 66.3% and 73.8%, p = 0.9). The PFS and OS in patients with antibiotic treatment were worse in comparison to patients without antibiotic treatment (median PFS, 3.8 vs. 7.0 months, p = 0.007; 1-year survival rate 58.8% and 70.3%, p = 0.01). In the weighted cohort, the PFS and OS of the two groups did not differ to a statistically significant extent (median PFS, 3.8 vs. 6.7 months, p = 0.2; 1-year survival rate, 61.8% and 71.0%, p = 0.6)., Conclusions: The therapeutic outcomes of Atez/Bev in HCC patients did not differ between patients with and without PPI treatment or between patients with and without antibiotic treatment., (© 2023 Japan Society of Hepatology.)

Aim: It is unclear whether prognosis differs by age for early-stage hepatocellular carcinoma (HCC). We aimed to examine prognosis and recurrence after radiofrequency ablation (RFA) for early-stage HCC and to determine its prognostic factors for different age groups., Methods: This retrospective study enrolled 1079 patients with initial early-stage HCC treated with RFA at two institutions. All patients in this study were divided into four groups: <70 years old (group1, n = 483), 70-74 years old (group2, n = 198), 75-79 years old (group3, n = 201), and ≥80 years old (group4, n = 197). Prognostic factors were evaluated by comparing survival and recurrence rates between each group., Results: The median survival time and 5-year survival rates for each group were 113 months and 70.8% in group1, 99.2 months and 71.5% in group2, 91.3 months and 66.5% in group3, and 71 months and 52.6% in group 4, respectively. Group4 had a significantly shorter survival than the other groups (p < 0.05). There were no significant differences in recurrence-free survival among the groups. In group4, the most common cause of death was nonliver-related disease (69.4%). In all groups, modified albumin-bilirubin index grade was a factor contributing to prolonged prognosis, but only in group4 performance status (PS) was a significant factor (hazard ratio, 2.46; 95% confidence interval, 1.16-3.00; p = 0.009)., Conclusion: For early-stage HCC in the elderly, preoperative evaluation of PS and management of other diseases could contribute to a prolonged prognosis., (© 2023 Japan Society of Hepatology.)

Background: The novel 2-D shear wave elastography (2D-SWE) can measure two ultrasound parameters: shear wave dispersion (SWD) and shear wave speed (SWS). We investigated the ability of 2D-SWE in measuring spleen stiffness using ultrasound multiparametric imaging., Methods: This cross-sectional study included patients with chronic liver disease who underwent esophagogastroduodenoscopy and ultrasonographic examinations of the spleen between September 2018 and December 2021. In total, 157 patients were enrolled in this study: 81 and 67 patients were included in the pilot set for hepatic venous pressure gradient (HVPG) measurements and validation cohort without HVPG measurements, respectively. To confirm reproducibility between the two examiners, an additional 30 patients were enrolled., Results: The Bland-Altman plots revealed no significant bias in the SWD as measured by two examiners. The splenic SWS (r = 0.752) and SWD (r = 0.444) were correlated with the HVPG. Regarding high-risk varices, as per the Youden index, the cut-off value for splenic SWS was 3.30 m/s, with a sensitivity of 85.7%, specificity of 92.5%, positive predictive value of 85.7%, and negative predictive value of 92.4% in the pilot set. In the validation set, good diagnostic performance by the splenic SWS was observed. However, SWD did not perform as well as SWS., Conclusions: The splenic SWS, measured using ultrasound multiparametric imaging, was closely correlated with the HVPG. Thus, SWS is a useful predictive marker for high-risk varices., (© 2022 Japan Society of Hepatology.)

Background/aim: Atezolizumab plus bevacizumab (Atez/Bev) treatment is recommended for unresechepatocellular carcinoma (u-HCC) patients classified as Child-Pugh A (CP-A). This study aimed to elucidate the prognosis of patients treated with Atez/Bev, especially CP-A and -B cases., Materials/methods: From September 2020 to March 2022, 457 u-HCC patients treated with Atez/Bev were enrolled (median age 74 years, male:female = 368:89, CP-A:CP-B = 427:30, Child-Pugh score [CPS] 5:6:7:8:9 = 271:156:21:8:1). Therapeutic response was evaluated using RECIST ver.1.1. Clinical features and prognosis were retrospectively evaluated., Results: There were no significant differences between CP-A and -B patients in regard to best response (CR:PR:SD:PD = 16:91:194:81 vs. 0:7:13:8, p = 0.739; objective response rate/disease control rate = 28.0%/78.8% vs. 25.0%/71.4%). Analysis performed using inverse probability weighting adjustments of clinical factors other than those related to hepatic reserve function with a p value < 0.10 for comparisons between patients with CP-A and -B showed that the progression-free survival (PFS) rate for CP-A cases was better (6-/12-/18-month: 58.2%/36.1%/27.8% vs. 49.6%/8.7%/non-estimable [NE], p < 0.001), as was overall survival (OS) rate (6-/12-/18-month: 89.9%/71.7%/51.4% versus 63.6%/18.4%/NE; p < 0.001). Median PFS (mPFS) and median OS (mOS) for the CPS-5 were 9.5 months/NE, and 5.1/14.0 months for the CPS-6 (both p < 0.001). Furthermore, for modified albumin-bilirubin grade (mALBI)-1/2a/2b, mPFS was 9.4/8.5/5.3 months (p < 0.001) and mOS was NE/17.8/13.4 months (p < 0.001)., Conclusion: Better hepatic function, such as mALBI grade 1 or 2a are thought to indicate a better condition for obtaining sufficient prognosis with Atez/Bev treatment for u-HCC patients, whereas for CP-B patients, who mainly shown an mALBI grade of 2b or 3, Atez/Bev might have less therapeutic efficacy., (© 2022 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Aim: The present study focused on the association of early bevacizumab (Bev) interruption with the clinical outcome of atezolizumab plus bevacizumab., Methods: This retrospective study included 239 patients with advanced hepatocellular carcinoma receiving atezolizumab/Bev from September 2020 to June 2021 at 16 different institutions in Japan. We conducted a 9-week landmark analysis to investigate the association of Bev interruption due to adverse events with the therapeutic efficacy., Results: The median age was 73.0 (68.0-80.0) years old, with 195 (81.6%) men. The objective response rate was significantly higher in patients without Bev interruption than in those with it (34.5% vs. 17.3%, p = 0.038). The median progression-free survival (PFS) was 6.5 months (95% confidence interval [CI] 4.5-9.7) and 9.0 months (95% CI 7.1-not applicable) in patients with and without Bev interruption, respectively, with statistical significance (p = 0.021). The 12-month overall survival (OS) rates in patients with and without Bev interruption were 49.4% (CI 27.7%-67.9%) and 82.2% (95% CI 70.3%-89.6%), respectively, showing a significant difference (p = 0.004). The presence of Bev interruption was a significant factor associated with the PFS (p = 0.021) and OS (p = 0.008). A multivariate analysis showed that modified albumin-bilirubin 2b (p < 0.001) and later-line treatment (p = 0.018) were unfavorable factors associated with Bev interruption. Liver injury, appetite loss, protein urea, and ascites or hepatic edema were more frequently found in patients with Bev interruption than in those without it., Conclusions: Early Bev interruption was an unfavorable factor associated with the PFS and OS. Good liver function and treatment settings may be associated with maintaining Bev treatment., (© 2022 Japan Society of Hepatology.)

Background/aim: Although systemic therapy is recommended for patients with multiple intermediate stage unresectable hepatocellular carcinoma (u-HCC) classified as beyond the up-to-7 criteria (UT-7 out/multiple) as a transcatheter arterial chemoembolization (TACE) unsuitable condition, few reports have examined the therapeutic efficacy of atezolizumab plus bevacizumab combination therapy (Atez/Bev) in such cases. This study aimed to elucidate the therapeutic response of Atez/Bev in u-HCC patients classified as UT-7 out/multiple., Material/methods: From September 2020 to September 2021, 95 u-HCC Japanese patients classified as UT-7 out/multiple/Child-Pugh A were enrolled from 21 institutions (median age 76 years, males 73, Child-Pugh 5:6 = 68:27, TNM stage II:III = 17:78). Therapeutic response was retrospectively evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1 and modified RECIST (mRECIST)., Results: Atez/Bev was given as first-line treatment to 52 (54.7%). Objective response rate (ORR)/disease control rate (DCR) at six weeks of RECIST and mRECIST were 17.7%/84.7% and 42.5%/86.2%, respectively. Median PFS was 8.0 months (median observation period: 6.0 months). Child-Pugh A/modified Albumin-bilirubin grade (mALBI) 1 and 2a at baseline, 3, 6, and 9 weeks, were 100%/69.4%, 89.8%/57.3%, 94.8%/65.3%, and 91.4%/60.0%, respectively. Among adverse events (any-grade, >10%) during the present observation period, general fatigue was most frequent (23.2%), followed by urine protein (21.1%), appetite loss (20.0%), and hypertension (13.7%)., Conclusion: Atez/Bev treatment showed favorable therapeutic response with less influence on hepatic function, suggesting it as a useful therapeutic option for patients with such condition., (© 2021 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Aim: To validate an appropriate spleen size measurement technique for the prediction of high-risk esophagogastric varices., Methods: This retrospective cross-sectional study included 369 patients who underwent ultrasonography and computed tomography (CT) of the spleen and esophagogastroduodenoscopy between January 2018 and December 2020. Maximum spleen length, width, and craniocaudal length were measured in a longitudinal view. The two-dimensional (2D) spleen index (maximum length × maximum width in the longitudinal view) was calculated. A three-dimensional (3D) spleen index was then defined as follows: 2D spleen index × maximum length in the transverse view. The similarity in spleen volume measured by CT and ultrasonography (spleen index) was assessed by the correlation coefficient. The diagnostic accuracies of the spleen index, platelet/spleen length, and platelet/spleen index were calculated to determine the overall diagnostic accuracy., Results: Compared to the other spleen indices, our 3D spleen index was significantly better correlated with spleen volume on CT (r = 0.91, 95% confidence interval 0.89-0.92, p < 0.001). Receiver-operating characteristic curve analyses revealed no significant difference between the 3D and 2D indices (p = 0.228) but did show a significant difference between the 3D and one-dimensional indices (p = 0.020). Although the area under the curve for the platelet count combined with the spleen index or length was higher than that for our 3D index, there was no significant difference between platelet count and spleen index or length (p = 0.078)., Conclusions: Platelet/spleen length has a reasonable ability to predict high-risk esophagogastric varices, even though measurement of two or three factors can be correlated with spleen volume., (© 2021 Japan Society of Hepatology.)

Aim: Regorafenib is a second-line treatment for unresectable hepatocellular carcinoma after sorafenib-refractory treatment. This study examined the effects of regorafenib administration on hepatic functional reserve and the treatment course after regorafenib discontinuation., Methods: This retrospective, multicenter study involved 51 patients treated with regorafenib after sorafenib-refractory treatment for u-HCC at seven institutions before March 2021., Results: Fourteen, 13, and 24 patients were classified based on modified albumin-bilirubin (mALBI) grade 1, 2a, and 2b, respectively. The median survival time and progression-free survival were 16.7 and 3.3 months, respectively. Only mALBI grade 2b or 3 was significantly associated with survival rate (hazard ratio, 2.13; 95% confidence interval, 1.01-4.49; p = 0.047). A comparison of median ALBI scores at the initiation of regorafenib (-2.35) with those at 4 weeks (-1.93) revealed a significant relative change (p = 0.0001). After 4 weeks, grade 1 or 2a persisted in 15 patients (Group 1); grade 1 or 2a deteriorated to 2b in 12 patients (Group 2); grade 2b or 3 before regorafenib administration was present in 22 patients (Group 3); and MST was 33.3, 12.8, and 11.3 months in the three groups, respectively (p = 0.05). Patients treated with lenvatinib (LEN) (n = 27, MST = 23.4 months) after regorafenib had a significantly longer survival time from regorafenib initiation than those not treated with LEN (n = 24, 11.8 months; p = 0.043)., Conclusions: Hepatic functional reserve significantly declined after regorafenib administration. During regorafenib treatment, favorable hepatic functional reserve before administration and maintenance of favorable hepatic reserve after administration lead to prolonged prognosis., (© 2021 Japan Society of Hepatology.)

Aim: Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma. This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after regorafenib failure., Methods: From June 2017 to October 2020, 63 patients with Child-Pugh A and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, Barcelona Clinic Liver Cancer B:C = 23:40). They were divided into two groups, those treated with lenvatinib after regorafenib treatment (R-L group, n = 47) and those who did not receive lenvatinib after regorafenib (non-R-L group, n = 16). Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting., Results: Serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the R-L and non-R-L groups, whereas the albumin-bilirubin score, Child-Pugh class, and tumor burden were not. Progression-free survival was also not significantly different (median 4.1 vs. 3.8 months, p = 0.586). As for overall survival, the R-L group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (MST 19.7 vs. 10.3 months, 33.8 vs. 15.3 months, p < 0.001 and p = 0.022, respectively). Modified albumin-bilirubin grade 2b (score >-2.27) at the start of regorafenib (HR 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (HR 0.355, p = 0.004) were found to be significant prognostic factors in Cox proportional hazards multivariate analysis, after inverse probability weighting adjustment., Conclusion: These results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinoma patients with better hepatic reserve function., (© 2021 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Aim: Portal hypertension induces pancreatic congestion and impaired insulin secretion in patients with liver cirrhosis (LC). However, its mechanism is unclear, with no established noninvasive imaging method for the evaluation of its pathogeneses. The present study focused on pancreas stiffness, as assessed by shear wave elastography (SWE), and examined its association with portal hypertension and insulin secretion., Methods: Shear wave elastography and contrast-enhanced ultrasonography were utilized to evaluate pancreas stiffness and congestion, respectively. A glucagon challenge test was used for insulin secretion assessment. Furthermore, rat models of carbon tetrachloride (CCl 4 )-induced LC and portal hypertension were used to identify the direct effects of pancreatic congestion. Immunohistochemistry staining of the pancreas was carried out on human autopsy samples., Results: Pancreas stiffness measured by SWE was higher in patients with LC than in controls and showed significant correlation with pancreatic congestion. The glucagon challenge test indicated a lower value for the change in C-peptide immunoreactivity in the LC group, which was inversely correlated with pancreas stiffness and congestion. Additionally, portal hypertension and insulin secretion dysfunction were confirmed in CCl 4 rat models. Autopsy of human samples revealed congestive and fibrotic changes in the pancreas and the relationship between insulin secretion and their factors in patients with LC., Conclusions: In patients with LC, pancreas stiffness measured by SWE could be a potential noninvasive test for evaluating pancreatic congestion and fibrosis due to portal hypertension. Moreover, it was associated with impaired insulin secretion, and could aid in guiding the treatment for hepatogenous diabetes., (© 2021 The Japan Society of Hepatology.)

Aim: The FibroScan-aspartate aminotransferase (FAST) score comprises an easy and feasible method for identifying advanced non-alcoholic steatohepatitis. Recently, shear-wave elastography and attenuation coefficient measurement on B-mode ultrasound (US) have become widely utilized. We investigated the diagnostic accuracy of the FAST score as calculated using US-elastography compared with that using vibration-controlled transient elastography (VCTE)., Methods: Patients with chronic liver disease who underwent VCTE, point-shear-wave elastography with attenuation coefficient measurement, and liver biopsy on the same day between January 2015 and September 2020 were retrospectively reviewed., Results: Of 189 patients, 94 underwent VCTE using both M and XL probes. The C-statistics were similar for VCTE (0.846) and US-elastography (0.814; p = 0.251), and for M (0.857) and XL probes (0.833; p = 0.412). Scatter and Bland-Altman plots showed good reproducibility for the FAST score. For VCTE, a cut-off of ≤0.35 had a sensitivity of 92.3%, negative predictive value of 85.5%, and negative likelihood ratio of 0.14, and a cut-off of ≥0.67 had a specificity of 90.6%, positive predictive value of 88.1%, and positive likelihood ratio of 6.03, for ruling out and in advanced non-alcoholic steatohepatitis, respectively. For US-elastography, a cut-off of ≤0.35 had a sensitivity of 90.4%, negative predictive value of 83.3%, and negative likelihood ratio of 0.16, and a cutoff of ≥0.67 had a specificity of 91.8%, positive predictive value of 85.1%, and positive likelihood ratio of 4.67, for ruling out and in advanced non-alcoholic steatohepatitis, respectively., Conclusions: The FAST score is highly reproducible, even when different echo equipment or probes are used., (© 2021 The Japan Society of Hepatology.)

Aim: Liver stiffness measured using transient elastography (TE) is affected by tissue viscosity. The role of intrahepatic lymphatic fluid in liver stiffness is unclear. The present study aimed to investigate the effects of lymphatic vessel dilatation on liver stiffness., Methods: Patients with chronic liver disease (n = 116) were enrolled from June 2018 to March 2020. All specimens were acquired by laparoscopic liver biopsy. Biopsy samples were stained with D2-40 for lymphatic vessel quantification based on a five-point scale for each specimen. Independent associations of liver stiffness measured by TE, strain elasticity (liver fibrosis index), and controlled attenuation parameter with fibrosis, lymphatic vessels, alanine aminotransferase, bilirubin, and steatosis were evaluated., Results: Fibrosis, splenic stiffness measurement, and splenic volume were significantly correlated with the area of lymphatic vessels. Fibrosis, lymphatic vessels, and alanine aminotransferase were independent factors significantly associated with liver stiffness measurement (LSM; standardized coefficient [β] = 0.375, P < 0.001; β = 0.342, P < 0.001; and β = 0.359, P < 0.001, respectively). Fibrosis was the only independent factor significantly associated with liver fibrosis index (β = 0.360, P < 0.001), whereas the fat deposit area was the only independent factor significantly associated with controlled attenuation parameter (β = 0.455, P < 0.001). The areas under the receiver operating characteristic curves for diagnosing controlled ascites based on LSM, liver fibrosis index, splenic stiffness measurement, collagen proportionate area, and area of lymphatic vessels were 0.94, 0.66, 0.76, 0.64, and 0.79, respectively., Conclusions: Lymphatic vessel dilatation can affect liver stiffness measured using TE. Liver stiffness measurement is a predictive factor for ascites., (© 2021 The Japan Society of Hepatology.)

Aim: For radiofrequency ablation to treat patients diagnosed with liver cancer, the ablation area cannot be envisaged beforehand, even by experts. This study aimed to assess the clinical feasibility of applying a combination of electric (E)-field and coronal (C)-plane simulations to ultrasound-ultrasound (US-US) fusion images., Methods: The study protocols were approved by the institutional ethics committee. Between October 2017 and July 2019, 151 patients with 151 hepatocellular carcinoma nodules (80 treated with navigation images and 71 without navigation images) were retrospectively compared in this cross-sectional study. The E-field, which is a simulated image that predicts the ablation area, was applied to the US-US fusion images. The C-plane is defined as a sagittal plane in relation to the original 2-D US images. The positions of each E-field area in the maximum cross-sectional area of the tumor were easily identified from C-plane results. The primary end-point of this study was achievement of an adequate safety margin (greater than 5 mm). The sphericity of the ablation volume was used as a secondary end-point., Results: The rate of achieving a sufficient safety margin was significantly higher in the group treated with navigation images (71/80) than in the group treated without navigation images (31/71, P < 0.001). The median sphericity was 0.55 with navigation images and 0.42 without navigation images (P < 0.001)., Conclusion: Using the combination of an E-field and a C-plane on US-US fusion images can be a feasible method for acquiring a sufficient safety margin., (© 2020 The Japan Society of Hepatology.)

Aim: An easily performed method for examination of muscle abnormalities is anticipated. We aimed to elucidate the clinical usefulness of simple assessments for muscle abnormality including a simple five-item questionnaire (SARC-F) in chronic liver disease patients., Methods: From February to July 2019, 383 outpatients (median age 71 years, 259 men; chronic hepatitis (CH) : liver cirrhosis Child-Pugh A : liver cirrhosis Child-Pugh B : liver cirrhosis Child-Pugh C = 157:176:39:11) who underwent a computed tomography examination were enrolled. SARC-F, previously reported cut-off values for muscle strength decline (MSD; handgrip), pre-muscle volume loss (pre-MVL), calf circumference and finger-circle test results were used, and these results were analyzed retrospectively., Results: A high SARC-F score (≥4) was observed in 25 patients, and a low score (<4) in 358 patients. The frequency of high SARC-F increased significantly with progression of chronic liver disease (chronic hepatitis : liver cirrhosis Child-Pugh A : liver cirrhosis Child-Pugh B/C = 2.5%:8.0%:14.0%, P=0.010). MSD frequency was 22.4% in men and 41.1% in women. Muscle volume loss and pre-MVL were noted in 22% and 30.5%, respectively, of the male patients, and 9.7% and 32.3%, respectively, of the female patients. In cases with high SARC-F and MSD, calf circumference and finger-circle abnormalities were found in 56% and 40.0% of patients, respectively, whereas those values for patients with low SARC-F and MSD were 14.5% and 10.6%, respectively (P < 0.001, for each; positive/negative predictive values: 0.560/0.855 and 0.400/0.894, respectively). Each SARC-F item showed a good area under the curve for MSD, but not pre-MVL., Conclusion: SARC-F score in combination with MSD and calf circumference or finger-circle test results may be an easy and simple method for surveillance of chronic liver disease patients with a high risk of sarcopenia and decline of quality of life., (© 2019 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Aim: Although a reduced serum zinc level is often observed in patients with chronic liver disease due to hepatitis virus, its prognostic importance has not been adequately investigated. This study aimed to elucidate the association of zinc deficiency with prognosis, especially in early hepatocellular carcinoma (HCC) patients., Methods: From 2005 to 2018, 466 patients with naïve HCC due to hepatitis virus were enrolled (327 men, 139 women; median age 70 years; hepatitis C virus [HCV] n = 389, hepatitis B virus [HBV] n = 69, hepatitis C virus and hepatitis B virus n = 8; Child-Pugh A n = 367, Child-Pugh B n = 82; Child-Pugh C n = 17; TNM-LCSGJ stage I n = 150, stage II n = 181, stage III n = 91, stage IVa n = 26, state IVb n = 18). Of the 466 patients, 287 were within the Milan criteria (early HCC) and treated curatively. Zinc deficiency was defined as <60 μg/dL. Clinical records and prognostic factors were retrospectively evaluated., Results: The levels of serum zinc became lower with chronic liver disease progression (Child-Pugh A, B, C: 64.3 ± 14.3, 52.3 ± 15.7, 48.4 ± 13.5 μg/dL, respectively; P < 0.001). In early HCC patients treated curatively, overall survival and recurrence rates were better in patients treated curatively and without zinc deficiency as compared with patients with zinc deficiency (3-year overall survival 86.5% vs. 77.2%, 5-year overall survival 73.5% vs. 43.8%, P < 0.001; 3-year recurrence 44.8% vs. 58.3%, 5-year recurrence 56.8% vs. 77.5%, P = 0.002). Not only infection control of hepatitis virus (sustained virological response in HCV or nucleos(t)ide analogs in HBV; HR 0.078, P < 0.001), but also zinc deficiency (HR 1.773, P = 0.041) were significant prognostic factors for death., Conclusion: Serum levels of zinc were reduced in association with chronic liver disease grade progression. In addition to infection control of hepatitis virus, zinc deficiency might be a significant prognostic factor for survival in patients with early HCC due to viral hepatitis treated curatively., (© 2019 The Japan Society of Hepatology.)

Aim: Lenvatinib has become available as first-line therapy for patients with unresectable hepatocellular carcinoma (HCC). However, the safety and efficacy of lenvatinib in elderly patients with HCC has not been sufficiently investigated. We compared the frequency of adverse events and prognosis between elderly and non-elderly patients with HCC who received lenvatinib., Methods: A total of 100 patients with HCC who received lenvatinib were selected using propensity score matching: 50 patients were elderly (age ≥75 years) and 50 patients were non-elderly., Results: In the elderly group, >20% of patients experienced fatigue (36.0%), decreased appetite (26.0%), hypothyroidism (24.0%), proteinuria (22.0%), palmar-plantar erythrodysesthesia (22.0%), and hypertension (20.0%) of any grade as treatment-related adverse events. In addition, >10% of patients experienced grade ≥3 treatment-related fatigue (12.0%). In the non-elderly group, >20% of patients experienced palmar-plantar erythrodysesthesia (42.0%), fatigue (28.0%), decreased appetite (22.0%), and diarrhea (20.0%) of any grade as treatment-related adverse events. In addition, >10% of patients experienced grade ≥3 treatment-related proteinuria (10.0%). There were no significant differences between the elderly and non-elderly groups in the frequency of adverse events. Regarding overall and progression-free survival, there were no significant differences between the elderly and non-elderly groups (hazard ratio 0.972, 95% confidence interval 0.374-2.529; and hazard ratio 1.362, 95% confidence interval 0.687-2.700, respectively). Palmar-plantar erythrodysesthesia (hazard ratio 0.117, 95% confidence interval 0.015-0.916) was independently associated with overall survival in a multivariate analysis., Conclusions: Lenvatinib can be used safely and efficaciously regardless of age in patients with HCC., (© 2019 The Japan Society of Hepatology.)

Aim: Falling is known to be associated with cognitive function. We evaluated the relationship between muscle function and falls in patients with chronic liver disease (CLD)., Methods: We enrolled 100 sequential CLD patients without dementia who were admitted to our institution for scheduled treatment from July 2017 to May 2018 (age 71.0 ± 10.2 years; 76 men). All subjects were self-reliant in regard to activities of daily living. On admission, handgrip strength was determined and falls within 1 month of admission were noted. For determining handgrip strength decline (HSD), previously reported values were used (men, <26 kg; women, <18 kg). The relationship between HSD and falls in CLD patients was evaluated in a retrospective manner., Results: Thirty-two patients had chronic hepatitis and 49 had liver cirrhosis (LC) Child-Pugh A, 17 had LC Child-Pugh B, and 2 had LC Child-Pugh C. Twelve (12.0%) had a history of falling, including 8 (26.7%) of 30 with and 4 (5.7%) of 70 without HSD (P = 0.006). The cut-off value for age in relationship to falling was 69.0 years old (area under the receiver operating characteristic curve, 0.668; 95% confidence interval, 0.514-0.821). A fall during hospitalization was noted more often in patients with a history of falling than in those without (16.7% [2/12] vs. 2.3% [2/88], P = 0.018)., Conclusion: In CLD patients, the presence of HSD and older age might be independent risk factors for predicting a fall. Assessment of handgrip strength could be an effective clinical tool for easily assessing the risk of falling, especially in elderly CLD patients., (© 2019 The Japan Society of Hepatology.)

Aim: The predictors for the development of hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment were investigated., Methods: A total of 1174 patients with chronic hepatitis C virus infection were treated with DAA therapy (sofosbuvir and ledipasvir [n = 615], sofosbuvir and ribavirin [n = 380], and daclatasvir and asunaprevir [n = 179]) and achieved sustained virologic response (SVR). The HCC development rate and the factors that might contribute to the development of HCC after the end of DAA treatment were analyzed., Results: During the median observation period of 537 days, HCC developed in 33 cases. The incidence of HCC was 1.9%, 3.2%, and 4.1% at 1, 1.5, and 2 years after the end of DAA therapy, respectively. Multivariate analysis with pre- and post-treatment factors identified the Fibrosis-4 (FIB-4) index (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.021-1.178; P = 0.011) and post-treatment α-fetoprotein (AFP) (HR = 1.11; 95% CI, 1.054-1.172; P < 0.001) as independent factors that contributed to the development of HCC after DAA therapy. Using these identified parameters, a new scoring system (0 to 2 points) was established. Patients in the high-score group (2 points) could be identified as having a significantly higher risk of HCC development, and the respective 1- and 2-year cumulative incidence rates of HCC were 6.1% and 14.4%., Conclusions: A high FIB-4 index and a high post-treatment AFP at the end of DAA treatment were the independent predictors for developing HCC after DAA treatment. For patients with these risk factors, extra attention to the possibility of HCC development is needed., (© 2018 The Japan Society of Hepatology.)

Aim: Lenvatinib (LEN) has recently become available as a first-line tyrosine-kinase inhibitor (TKI) for unresectable hepatocellular carcinoma (u-HCC). In patients who showed intolerability or failure in other TKI treatments, alternative treatment options are needed. This retrospective study evaluated the therapeutic potential of LEN in clinical practice., Methods: We enrolled 57 u-HCC patients treated with LEN from March to June 2018. Lenvatinib was given orally to patients weighing <60 kg at 8 mg/day and at 12 mg/day to those ≥60 kg. Following the exclusion of patients whose initial LEN dose was reduced, 49 patients were evaluated in regard to their characteristics and early therapeutic response using modified Response Evaluation Criteria in Solid Tumors for findings of follow-up computed tomography (CT)/magnetic resonance imaging (MRI) examinations at 4 weeks after introducing LEN., Results: The average patient age was 72.4 ± 9.3 years and 38 (77.6%) were men. The LEN dose was 8 and 12 mg in 32 and 17 patients, respectively. Twenty-nine (59.2%) had history of treatment with sorafenib and six of them (20.7%) with regorafenib. Of the 49 patients, 27 were evaluated using findings obtained by enhanced CT/MRI at 4 weeks after introducing LEN. Partial response was shown in 11, stable disease in 12, and progressive disease in four (overall response rate [ORR], 40.7%; disease control rate [DCR], 85.2%). The ORR and DCR of TKI-naïve patients (n = 8) were 50.0% and 87.5%, respectively, whereas those of TKI-experienced patients (n = 19) were 36.8% and 84.2%, respectively (P = 0.675 and P = 1.00, respectively)., Conclusion: Early therapeutic response to LEN was favorable. This new TKI could have therapeutic potential both in patients with and without past TKI treatments., (© 2018 The Japan Society of Hepatology.)

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., (© 2018 The Japan Society of Hepatology.)

Aim: There are few reports regarding relative changes in muscle function of patients with chronic liver disease (CLD). We examined CLD patients to evaluate relative changes in handgrip strength and muscle volume., Methods: We enrolled 413 CLD outpatients who underwent handgrip strength measurements in both 2015 and 2017 (age 67.9 ± 10.0 years; male / female = 242/171; hepatitis C virus [HCV] / hepatitis B virus [HBV] / HBV and HCV / alcohol / others = 239/92/4/22/56; Child-Pugh score [CPS] in 2015 [5/6/7/8/9/≥10 = 335/51/12/11/3/1]). Relative change in muscle volume (ΔPI) from 2015 to 2017 was evaluated using computed tomography findings in 230 of the patients, using a previously reported method. Clinical characteristics, as well as relative changes of handgrip strength (ΔHGS) and ΔPI were analyzed., Results: For the patient cohort as a whole, CPS became significantly worse in 2017 (5/6/7/8/9/≥10 = 319/56/13/11/5/9; P = 0.002). In individual patients with CPS decline, serum albumin level was significantly decreased (3.78 ± 0.50 to 3.33 ± 0.61 g/dL; P < 0.001), whereas no decrease was seen in those without such a decline (4.16 ± 0.48 to 4.20 ± 0.44 g/dL; P = 0.028). Furthermore, ΔHGS (-1.4 ± 4.8 [n = 59] vs. 0.7 ± 4.8 kg [n = 354]; P = 0.002) and ΔPI (-0.44 ± 0.88 [n = 38] vs. 0.03 ± 0.64 cm 2 /m 2 [n = 192]; P = 0.003) were worse in patients with, compared to those without, a decline in CPS. Age was not significantly different between patients with and without handgrip strength decline (66.5 ± 10.3 vs. 65.3 ± 9.9 years; P = 0.256). There was a significant relationship between ΔHGS, ΔPI and relative change in serum albumin (r = 0.161, P = 0.001 and r = 0.225, P < 0.001, respectively)., Conclusion: Decline in CPS, especially decreasing serum albumin level, showed a significant relationship with muscle function reduction and muscle volume loss., (© 2018 The Japan Society of Hepatology.)

Aim: To evaluate the efficacy of the newly proposed albumin-bilirubin (ALBI) grade for therapy selection, clinical features of patients treated with radiofrequency ablation (RFA) were elucidated., Methods: From 2000 to 2015, 1101 patients with HCC (<3 cm, ≤3 tumors) treated with RFA were enrolled, with the following clinical features: 734 men and 367 women; 779 with hepatitis C virus, 153 with hepatitis B virus, 5 with hepatitis C and B, and 164 others; and Child-Pugh classification (CP) A : B ratio of 842:259. Liver damage classification (LD) using the indocyanine green retention rate at 15 min and ALBI-grade were compared in regard to the prognoses of those patients., Results: Median tumor size was 1.7 cm (interquartile range, 1.4-2.2 cm) and single tumors were found in 802 cases (72.8%) (tumor-node-metastasis stage of the Liver Cancer Study Group of Japan I : II : III = 536:454:111). In the LD-A group, the number of cases with ALBI-grade 1, 2, and 3 were 294, 224, and 1, respectively, while those in the LD-B group were 47, 490, and 12, respectively. In the LD-C group, 19 and 14 patients were ALBI-2 and -3, respectively. Akaike Information Criterion values for CP, LD-grade, and ALBI-grade were 6015.4, 5988.8, and 5990.7, respectively. However, there was no significant difference regarding prognosis between LD-A/B (n = 228) and C (n = 31) (median survival time, 4.8 vs. 3.9 years, P = 0.0818) in CP-B, whereas a significant difference was observed regarding prognosis for ALBI-1/2 (n = 232) and ALBI-3 (n = 27) (median survival time, 4.8 vs. 2.7 years, P = 0.0168)., Conclusion: Albumin-bilirubin grade showed an assessment ability similar to that of LD-grade. Furthermore, there was a small improvement in prognosis following RFA in patients with an ALBI-grade of 3. Although only two serological parameters, albumin and total bilirubin, are used, assessment with ALBI-grade may be more useful than with LD-grade for avoiding a non-beneficial RFA procedure., (© 2017 The Japan Society of Hepatology.)

Aim: We examined the prognosis of liver cirrhosis (LC) patients with and without portal hypertension (PHT) and muscle volume loss (MVL)., Methods: From 2006 to 2016, 346 LC outpatients (PHT/non-PHT = 173/173) were enrolled (median age, 69 years; men / women, 204/142; Child-Pugh A / B, 230/116; and presence of MVL 15.6% in each group) after propensity matching, following exclusion of those with hepatocellular carcinoma (HCC) beyond the Milan criteria and Child-Pugh C. Portal hypertension was defined as positive for significant esophagogastric varices; MVL was diagnosed based on a previously reported index using CT imaging. Overall survival rate (OSR) was evaluated from the viewpoints of PHT and MVL., Results: There were no significant differences in clinical background (age, gender, etiology, presence of HCC [within Milan criteria], or Child-Pugh class) between the groups. Although there was no significant difference regarding OSR between patients with and without MVL in the non-PHT group (P = 0.076, Holm's method), the OSR of patients with MVL in the PHT group was lower compared to those without MVL in both groups (P = 0.017 and P = 0.012, respectively, Holm's method). As a result, the OSR of patients with MVL (n = 54) was lower than the other patients (n = 292) (3- and 5-year OSR, 69.0% vs. 86.4% and 35.8% vs. 74.1%, respectively; P < 0.001). Multivariate Cox hazard analysis showed that positive for HCC (hazard ratio [HR], 2.028; 95% confidence interval [CI], 1.189-3.460; P = 0.009) and positive for MVL (HR, 2.768; 95% CI, 1.575-4.863; P < 0.001) were significant independent prognostic factors for death., Conclusion: Muscle volume loss and HCC, but not PHT, were found to be independent prognostic factors for death in LC patients., (© 2017 The Japan Society of Hepatology.)

Aim: Assessing disease progression in patients with primary biliary cholangitis (PBC) is necessary in order to evaluate therapeutic effectiveness. Therefore, the aims of this study were to evaluate both the diagnostic accuracy of both real-time tissue elastography (RTE) and vibration-controlled transient elastography (VCTE), and the usefulness of hepatic and splenic elasticity as predictive markers for the progression of symptomatic PBC., Methods: The study participants were 44 patients with PBC. We assessed hepatic and splenic elasticity using RTE and VCTE and measured serum markers related to fibrosis and hepatic and splenic blood flow using Doppler ultrasonography. We then compared RTE and VCTE for diagnostic accuracy. Patients with asymptomatic PBC were followed every 1-3 months., Results: Both RTE and VCTE performed well and had superior diagnostic accuracy compared with biochemical markers. The areas under the receiver operating characteristic curve for RTE and VCTE were 0.92 and 0.92, 0.95 and 0.91, and 0.97 and 0.91 for F ≥ 2, F ≥ 3, and F = 4, respectively. During follow-up, nine patients (25.0%) developed liver-related symptoms. Multivariate analysis revealed that splenic elasticity assessed using RTE was a significant independent factor for the development of liver-related symptoms (odds ratio, 2.19; P = 0.024)., Conclusions: Real-time tissue elastography offered better diagnostic accuracy for severe fibrosis and cholangitis than VCTE. Splenic elasticity determined using RTE is a useful parameter for evaluating liver-related symptoms and an effective predictive marker of disease progression in patients with asymptomatic PBC., (© 2017 The Japan Society of Hepatology.)

Aim: This study aimed to compare multipolar radiofrequency ablation (RFA) with monopolar RFA as the major treatment for nodules of hepatocellular carcinoma in the caudate lobe., Methods: This retrospective study was approved by the institutional review board. Data were reviewed from 101 patients who met the Milan criteria and were treated by multipolar RFA (n = 22) or monopolar RFA (n = 79). After propensity score matching, complications and local tumor progression were compared between the two groups., Results: Before propensity score matching (n = 101), the 2-year relapse-free survival rates for multipolar and monopolar RFA (65.1% vs. 38.8%, respectively; P = 0.064) and the local tumor progression rate (12.5% vs. 14.9%, respectively; P = 0.313) were not significantly different. There were no significant differences between the two RFA techniques by treatment efficacy of transcatheter hepatic arterial embolization, location of tumor, and puncture route. After matching (n = 44), the 2-year relapse-free survival rate for the multipolar and monopolar groups (65.1% vs. 22.7%, respectively; P = 0.004) was significantly different, and the local tumor progression rate (12.5% vs. 22.9%, respectively; P = 0.004) was significantly different. No severe complications occurred in the patients treated by multipolar RFA., Conclusion: Multipolar RFA appears to be a safe and effective method for hepatocellular carcinoma nodules in the caudate lobe., (© 2016 The Japan Society of Hepatology.)

Aim: To elucidate the clinical significance of muscle wasting in regard to survival of hepatocellular carcinoma (HCC) patients undergoing sorafenib treatment, we evaluated prognostic factors including muscle wasting at the start of sorafenib treatment., Methods: We enrolled 93 patients with unresectable HCC (68.3 ± 9.4 years old, 81 men, 12 women, Child-Pugh score 5:6:7 = 69:22:2) who were treated with sorafenib. Muscle wasting was evaluated based on psoas muscle area index (psoas muscle area at level of middle of third lumbar vertebra [cm 2 ] / height [m] 2 ) calculated from computed tomography findings. Previously reported cut-off values for muscle wasting in men and women (4.24 and 2.50 cm 2 /m 2 , respectively) were used. Patients were divided into those with (muscle-atrophy group, n = 20) and without (non-atrophy group, n = 73) muscle wasting., Results: There were no significant differences in regard to etiology, Child-Pugh classification, and tumor-node-metastasis stage between the groups. In contrast, body mass index in the muscle-atrophy group was lower (20.9 ± 2.4 vs. 23.5 ± 3.4, P = 0.003). Although time to progression was not different (median 2.1 vs. 2.8 months, P = 0.242), the 6-, 12-, and 18-month survival rates were worse in the muscle-atrophy group (62.7%, 32.3%, and 32.3% vs. 78.3%, 64.7% and 48.1%, respectively, P = 0.042). In multivariate Cox hazard analysis, des-γ-carboxy prothrombin level (≥100 mAU/mL) (hazard ratio, 2.540; P = 0.018) and positive for muscle wasting (hazard ratio, 2.158; P = 0.032) were significant prognostic factors at the start of sorafenib treatment., Conclusion: Muscle wasting is an important prognostic factor in patients treated with sorafenib., (© 2016 The Japan Society of Hepatology.)

Aim: During radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), a hyperechoic rim develops around the HCC nodules. The usefulness of the hyperechoic rim to guide treatment was assessed., Methods: RFA was first performed in pig livers to determine the significance of the hyperechoic rim. Fifty-five patients with 75 HCC nodules had received RFA for the treatment of HCC. For those patients, we evaluated whether conventional ultrasonography (US) could be used instead of contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasonography (CEUS) using virtual imaging. Finally, 31 patients with 45 HCC nodules received RFA, and the degree of ablation was assessed based on the hyperechoic rim. Repeated RFA was done when ablation appeared incomplete., Results: In the pig livers, the hyperechoic rim was found to be related to the presence of dead cells. The preliminary study showed that US could be used instead of CECT and CEUS to evaluate the degree of ablation caused by RFA. Because hepatic vessels in the back side of the hyperechoic rim were not clear by the artifact, we used the distance from the surface of the liver to the hyperechoic rim for evaluation. By analyzing the extent of the hyperechoic rim, it was noted that incomplete ablation was achieved in 17 of 31 patients (21 of 45 HCC nodules). These patients were re-treated with RFA within 5-15 min of the first RFA., Conclusion: This study shows that the hyperechoic rim is related to the presence of dead and necrotic tissues. Thus, assessment of the hyperechoic rim's characteristics allows one to evaluate the efficacy of RFA.

Aim: Chemotherapy for advanced hepatocellular carcinoma (HCC) patients with hypersplenism is generally unsatisfactory, as a lower-dose therapy is usually administered. Splenectomy may represent a better approach to overcoming the complication due to hypersplenism in patients with advanced HCC. This retrospective study was conducted to evaluate whether HCC patients who undergo splenectomy show improved prognosis., Methods: We examined 34 HCC patients. Twenty-two had thrombocytopenia and/or leucopenia and underwent laparoscopic splenectomy. The completion rate of full-dose drug regimens, the response rate, the toxicity of chemotherapy and the cumulative survival rate were compared between the splenectomy and non-splenectomy groups., Results: The response rate and the cumulative survival rate in the splenectomy group were significantly better than that in the non-splenectomy group., Conclusions: Splenectomy is an efficient method for advanced HCC patients with hypersplenism treated by chemotherapy.

Aim: The aim of this study is to clarify the cerebral functions in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC)., Methods: We studied 58 patients with CH (20 in fibrosis stage F1, 20 in F2, 18 in F3), 77 with LC (46 rated as Child-Pugh class A, 24 as B, 7 as C), and 20 healthy volunteers (HV). Computer-aided quantitative neuropsychiatric function test systems, including eight neuropsychiatric tests were performed., Results: Subjects with results over the cut-off value for healthy subjects ranged from 11.1-28.6% in CH and 19.5-36.4% in LC. The percentages with abnormality in at least one test in CH and LC were 72.4% and 80.6%, respectively, which were significantly higher than that in the HV group (35.0%) (P = 0.003, P = 0.0003, respectively). Among CH subjects, those with three or more abnormal results in the F1, F2 and F3 subgroups were 15.0%, 20.0% and 38.9%, respectively. Among LC subjects, those with three or more abnormal results in the Child-Pugh class A, B and C subgroups comprised 30.4%, 50.0% and 57.1%, respectively. The rate in the CH F3 subgroup (P = 0.011) and in all three LC subgroups (P = 0.023, P = 0.001, P = 0.002, respectively) were significantly higher than that in the HV group., Conclusion: The percentage of patients with neuropsychiatric function impairment was high in both LC and CH, especially in stage F3. Neuropsychiatric dysfunction may initiate in CH in a considerable number of patients.