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Background/aim: Low branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is known as an indicator of amino acid imbalance. We elucidated usefulness of newly developed albumin-bilirubin (ALBI) score as alternative methods of BTR in patients with naïve hepatocellular carcinoma (HCC) retrospectively., Materials/methods: In 842 patients with HCC and without BCAA supplementation (71 years, male 614, Child-Pugh A:B:C = 689:116:37), relationships among BTR and clinical features were evaluated. Of those, 438 patients, with Milan criteria HCC, treated curatively were divided into the high-BTR (>4.4) (n = 293) and low-BTR (≤4.4) (n = 145) groups. The prognostic value of BTR was evaluated using inverse probability weighting (IPW) with propensity score., Results: The low-BTR group showed worse prognosis than the other (3-, 5-, 10-year overall survival rates: 88.9% vs. 86.3%/70.5% vs. 78.1%/38.1% vs. 52.3%, respectively; p < 0.001). Multivariate Cox-hazard analysis adjusted for IPW showed elderly (≥65 years) HR 2.314, p = 0.001), female gender (HR 0.422, p < 0.001), ECOG PS ≥2 (HR 3.032, p = 0.002), low platelet count (HR 1.757, p = 0.010), and low BTR (≤4.4) (HR 1.852, p = 0.005) to be significant prognostic factors. Both serum albumin level (r = 0.370, p < 0.001) and ALBI score (r = -0.389, p < 0.001) showed a significant relationship with BTR. Child-Pugh class B, modified ALBI grade (mALBI) 2a, and mALBI 2b predictive values for BTR were 3.589, 4.509, and 4.155 (AUC range: 0.735-0.770), respectively, while the predictive value of ALBI score for low-BTR (≤4.4) was -2.588 (AUC 0.790)., Conclusion: ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective This study evaluated cases of pruritus, which is known to be associated with sleep disorder, in chronic liver disease (CLD) patients. Methods Questionnaires were given to 339 enrolled CLD outpatients in winter (November 2019 to March 2020) and again in summer (April to October 2020) (median interval: 104 days). Relative changes in symptoms shown by a visual analogue scale (VAS) and Kawashima's pruritus score between winter and summer were evaluated in Study 1 (n=199), while Study 2 examined the clinical features of patients with sleep disorder based on the results of the second questionnaire (n=235, median age 70 years old; 141 men, liver cirrhosis 37%). Results Study 1. There was a significant relationship in VAS between daytime and nighttime for each season, as well as between winter and summer for each time period (p<0.001). A comparison of Kawashima's pruritus scores for the daytime and nighttime showed no significant seasonal differences (p=0.436 and 0.828, respectively). When Kawashima's score increased, so did the average VAS for both daytime (0:1:2:3:4=0.4±0.2:1.4±0.9:3.0±1.8:5.9±2.1:6.2±2.3) and nighttime (0:1:2:3:4=0.3±0.1:1.4±1.5:3.5±2.3:6.7±2.6:6.9±1.8) (p<0.001 for both). Study 2. Twenty subjects (8.5%) complained of sleep disorder. An elevated FIB-4 index (≥3.07) showed a good predictive value for sleep disorder (p<0.01). The cut-off for the daytime and nighttime VAS values for existing sleep disorder were 1.6 [area under the curve (AUC) 0.901] and 3.4 (AUC 0.931). The respective sensitivity, specificity, and positive and negative predictive values for sleep disorder based on Kawashima's score (≥2) were 0.85, 0.28, 0.10, and 0.95 for the daytime and 1.00, 0.29, 0.12, and 1.00 for the nighttime. Conclusion Intervention against pruritus is recommended in CLD patients with a high Kawashima's score (≥2) in any season, especially with an elevated FIB-4 index.

We treated a 66-year-old Japanese male with unresectable hepatocellular carcinoma (u-HCC) for multiple (>5) liver tumors (maximum 2.6 cm in size, Child-Pugh B score 7) in September 2018. The patient had a history of psoriasis vulgaris and sorafenib (SOR) was introduced (800 mg/day) because of transcatheter arterial chemoembolization (TACE) refractoriness. However, psoriasis vulgaris exacerbation and a high fever were observed 2 weeks later, and the patient was admitted, after which improvement of psoriasis vulgaris was obtained with external medicine administration and SOR intake discontinuation. Few reports have noted exacerbation of psoriasis vulgaris caused by SOR treatment.

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.)

A man in his 40s visited a facility with the chief complaint of abdominal pain;liver dysfunction was detected, and consequently, he was referred to our hospital for further examinations. His medical history was unremarkable. He used to drink alcohol (beer, 1500mL) every day. Magnetic resonance imaging and computed tomography showed stenosis of the distal bile duct and slight dilation of the upstream bile duct. Common bile duct stones and gallbladder stones were not detected. Malignant tumors in the bile duct biopsy were not discovered. The patient underwent subtotal stomach preserving pancreatoduodenectomy. The pathological diagnosis was chronic pancreatitis with amputation neuroma-like neurogenesis of the bile duct.

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.)

To examine the effectiveness of ultrasonography (US) for hepatocellular carcinoma (HCC) surveillance, the prognosis of HCC patients who underwent such screening at an expert medical institution or at general clinics were analyzed, as well as those without US surveillance. From October 2006 to December 2014, 872 patients with naïve HCC were enrolled and divided into the surveillance (S)-group (n=398), who underwent follow-up examinations with US, and the non-S group (n=474). The S-group was further subdivided into patients who underwent follow-up surveillance at Ehime Prefectural Central Hospital, an expert medical institution (SE-group, n=189), and those who received surveillance at general clinics (SG-group, n=209). Prognosis and clinical characteristics were analyzed. In the non-S group, the frequency of patients without viral hepatitis (NBNC-HCC) and Tumor, Node, Metastasis stage was greater. As a result, the median survival time (MST) of the non-S group was reduced, compared with the S group (non-S group, 34.1 vs. S group, 68.2 months; P<0.001). Tumor size was significantly different between the SE- and SG-groups (SE-group, 2.0±1.0 vs. SG-group, 2.5±1.3 cm; P<0.001), whereas tumor number (SE-group: 1.5±1.1 vs. SG-group, 1.7±1.2; P=0.164) and MST (SE-group, 72.1 vs. SG-group, 67.1 months; P=0.931) were not significantly different. Surveillance performed at either an expert medical institution or general clinic improved the prognosis of HCC patients. Dissemination of findings demonstrating the importance of surveillance for HCC to all clinicians as well as patients with chronic liver disease is important, and establishment of an effective surveillance strategy for NBNC-HCC is required.

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.)

Background: Muscle atrophy (MA) and muscle strength decline are important clinical features in chronic liver disease (CLD) patients. An easy to perform MA screening method without need for special equipment would be helpful. We evaluated the usefulness of the previously reported finger-circle test as screening for MA in CLD patients., Methods: We retrospectively enrolled 358 Japanese CLD outpatients (70.8 ± 10.2 years, male/female = 234/124) who had undergone a computed tomography examination from December 2017 to March 2018, of whom 137 had chronic hepatitis, 169 had liver cirrhosis Child-Pugh A, and 52 had liver cirrhosis Child-Pugh B/C. Bilateral psoas muscle area at the middle of the third lumber vertebra (L3) was evaluated with computed tomography findings, which was performed as a screening of hepatocellular carcinoma, using a previously reported parameter for MA [psoas index (PI): total psoas muscle area (cm 2 )/height (m) 2 ] [mean PI ± standard deviation (SD) of male patients: 6.50 ± 1.13 cm 2 /m 2 and those of female patients: 4.30 ± 0.90 cm 2 /m 2 ]. We then evaluated the correlation between MA and finger-circle test results in these patients., Results: The mean PI values for finger-circle test results Bigger, Just-fits, and Smaller were 5.64 ± 1.34, 5.00 ± 1.25, and 4.83 ± 1.46 cm 2 /m 2 , respectively, in male patients (P < 0.001) and 4.31 ± 1.06, 3.93 ± 0.97, and 3.42 ± 0.94 cm 2 /m 2 , respectively, in female patients (P = 0.001). We found that a finger-circle test result in male patients other than Bigger (Just-fits and Smaller) predicted a decline in psoas muscle area of L3 to PI 5.25 cm 2 /m 2 (sensitivity/specificity 0.619/0.667, area under the curve 0.654, 95% confidence interval 0.583-0.724), which was approximately mean minus 1 SD (5.37 cm 2 /m 2 ). On the other hand, a Smaller test result in female patients predicted a decline in psoas muscle area of L3 to PI 3.33 cm 2 /m 2 (sensitivity/specificity 0.740/0.583, area under the curve 0.698, 95% confidence interval 0.583-0.813), approximately mean minus 1 SD (3.40 cm 2 /m 2 )., Conclusions: The finger-circle test is an easy to perform and effective screening method for predicting earlier stage of MA in CLD patients without the need for special equipment., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background and Aim: To develop a scoring method using with common clinical data for predicting hepatocellular carcinoma (HCC) development after sustained virological response at 24 weeks (SVR24) after treatment with direct acting antivirals (DAAs), we retrospectively evaluated clinical features of patients who obtained SVR24., Methods: From October 2014 to December 2017, 1069 hepatitis C virus patients without a past history of HCC, who obtained SVR24 by DAAs at two different areas, were enrolled (the training [n = 484, ChuShikoku-group] and validation [n = 585, Chubu-group] sets). All were examined by ultrasonography as surveillance for HCC at the time of starting DAAs and twice a year after SVR24. We identified three parameters at SVR24, male gender, FIB-4 index > 3.25, and α-fetoprotein level > 5.0 ng/mL, as risk factors for HCC development and gave them point values, with the sum used as After DAAs Recommendation for Surveillance (ADRES) score., Results: In the ChuShikoku-group, the respective 1-/2-year rates for HCC incidence rates ADRES score 0 were 0.0%/0.0%, for a score 1 were 1.1%/2.1%, score 2 were 8.8%/15.9%, and score 3 were 17.1%/28.1%. On the other hand, those respective scores for the Chubu-group were 0.0%/0.0%, 0.0%/0.7%, 7.9%/10.6%, and 19.5%/not available. The c-index of the predictive value for HCC development in the training set after SVR24 was 0.835 while 0.899 in the validation set. Finally, those of the entire cohort were 0.0%/0.0%, 0.5%/1.6%, 8.4%/13.4%, and 18.0%/32.8%., Conclusion: The present ADRES score was simple and easy to use and may be useful for predicting risk of HCC development in short term after reaching SVR24 by DAAs., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aim/background: In HCC patients with multiple tumors in separate segments, monotherapy with surgical resection is often difficult when the estimated residual liver volume after surgery is thought to be inadequate. We evaluated the usefulness of resection combined with low invasive radiofrequency ablation (RFA) for treatment of such cases., Materials/methods: We analyzed 115 HCC patients with countable multiple tumors (≤5) without vascular invasion and/or extrahepatic metastasis, and treated solely with resection (SR group: n = 82), or with both resection and RFA (Comb group: n = 33) from January 2000 to December 2017. Clinical characteristics, overall survival rate (OSR), and disease-free survival rate (DFSR) were analyzed in a retrospective manner., Results: There were 88 males (76.5%) and the average age of all patients was 67.8 ± 8.9 years. The average number of tumors and average maximum tumor size were 2.4 ± 0.7 and 4.1 ± 2.1 cm, respectively. Forty-two (36.5%) patients were classified as beyond up-to-7 criteria. The 3- and 5-year OSRs in the SR group were 82.0 and 67.0%, respectively, and in the Comb group were 75.2 and 65.6%, respectively (p = 0.244), while the 3- and 5-year DFSRs in the SR group were 45.2 and 28.0%, respectively, and those in the Comb group were 37.3 and 23.3%, respectively (p = 0.257)., Conclusion: The combination of surgical resection and complementary RFA may be an effective strategy for treating HCC patients with countable multiple tumors, who are otherwise difficult to treat with surgical resection or RFA alone., (© 2019 S. Karger AG, Basel.)

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.)

Background and Aim: This study investigated the prognostic impact of muscle volume loss (MVL) and muscle function decline in patients undergoing resection for hepatocellular carcinoma (HCC)., Methods: This study enrolled 171 naïve HCC patients treated with resection from 2007 to 2015, after excluding those lacking spirometry or computed tomography findings, who had received non-curative treatments, or with restrictive or obstructive lung disorders. The median peak expiratory flow rate (%PEF) was set as the cut-off value for muscle function decline, and MVL was diagnosed using a previously reported value. Clinical backgrounds and prognosis were retrospectively evaluated., Results: Overall survival rate was lower in the MVL (n = 35) as compared with the non-MVL (n = 136) group (1/3/5-year overall survival rate = 88.2%/81.6%/55.6% vs 91.0%/81.5%/74.8%, respectively; P = 0.0083), while there were no differences regarding hepatic function or tumor burden between the groups. Child-Pugh class B (hazard ratio [HR] 3.510, 95% confidence interval [CI]: 1.558-7.926, P = 0.0025), beyond Milan criteria (HR 1.866, 95%CI: 1.024-3.403, P = 0.042), and presence of MVL (HR 1.896, 95%CI: 1.052-3.416, P = 0.033) were significant prognostic factors. The decreased %PEF group (n = 84) showed a higher rate of postoperative delirium than the others (n = 87) (27.4% vs 11.5%, P = 0.0088). The cut-off values for %PEF and age for postoperative delirium were 63.3% (area under receiver operating characteristic [AUROC] 0.697) and 73 years old (AUROC 0.734), respectively. Delirium was observed in 50.0% (14/28) of patients with both factors, 23.8% (15/63) of those with 1 factor, and 5.0% (4/80) of those without either factor., Conclusion: Muscle volume loss is an independent prognostic factor in HCC patients treated with surgical resection, while advanced age and decreased muscle function might indicate high risk for postoperative delirium., (© 2017 The Authors Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

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.)

Background/aim: Sarcopenia is recognized as a condition related to quality of life and prognosis in patients with chronic liver disease, although no useful strategy for improving muscle volume and strength has been established. Here, we evaluated the efficacy of supplementation with branched-chain amino acid (BCAA) administration and walking exercise., Patients and Methods: From December 2015 to July 2016, 33 Japanese outpatients with liver cirrhosis were enrolled (median: 67 years, HCV : HBV : alcohol : others=26 : 2 : 2 : 3, male : female=13 : 20, Child-Pugh A : B=30 : 3). None had a history of BCAA supplementation. After calculating the average number of daily steps using a pedometer for a 2-3-week period, BCAA supplementation (protein 13.5 g, 210 kcal/day) as a late evening snack and walking exercise (additional 2000 steps/day prescribed) were started. Body composition including muscle volume was analyzed using a bioelectrical impedance analysis method, and serological data and muscle strength (leg, handgrip) were evaluated at enrollment, and then 1, 2, and 3 months after starting the protocol., Results: The median average number of daily steps was 3791 (interquartile range: 2238-5484). The average period of BCAA supplementation was 2.7±0.7 months. During the period from enrollment to 3 months after starting the protocol, HbA1c and NH3 were not significantly changed, whereas the BCAA/tyrosine ratio improved (4.3±1.35 to 5.24±2.04, P=0.001). In addition, the ratios for average daily steps (1.595, P=0.02) as well as muscle volume, leg strength, and handgrip strength (1.013, 1.110, and 1.056, respectively; all P<0.01) were increased at 3 months., Conclusion: BCAA supplementation and walking exercise were found to be effective and easily implemented for improving muscle volume and strength in liver cirrhosis patients.

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.)

Background/aim: Determination of failure of transarterial chemoembolization (TACE) for treatment of Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) has become important because of the development of tyrosine kinase inhibitor (TKI) treatment. We evaluated the usefulness and efficacy of the newly proposed time to TACE progression (TTTP)., Patients and Methods: From 2006 to 2016, 192 BCLC-B HCC patients [median age 72 years, male/female ratio = 149/43, Child-Pugh score 5/6/7 = 106/56/30, albumin-bilirubin (ALBI) grade 1/2 = 64/128, Kinki criteria B1/B2 = 64/128] were enrolled. TTTP was defined based on a previous report and first imaging performed 3 months after initial TACE had been used to obtain baseline images. The patients were divided into three groups according to TTTP (<5, 5-10, and ≥10 months; group I, II, and III, respectively). We evaluated the relationship between TTTP and overall survival (OS) as well as the prognostic factors for death., Results: The median number of TACE procedures was 4 (interquartile range 3-7). There was a moderate correlation between TTTP and OS (r = 0.527, 95% CI 0.416-0.622, p < 0.001). The median survival for group I (n = 78), II (n = 49), and III (n = 65) was 24.6, 34.7, and 49.5 months, respectively (group I vs. group II, p = 0.023; group I vs. group III, p < 0.001; group II vs. group III, p = 0.037; Holm's method). ALBI grade 2 (HR 1.548, 95% CI 1.004-2.388, p = 0.048), alpha-fetoprotein (>100 ng/mL) (HR 1.540, 95% CI 1.035-2.291, p = 0.033), and TTTP (<5 months) (HR 2.157, 95% CI 1.447-3.215, p < 0.001) were significant prognostic factors for death in multivariate Cox hazard analysis., Conclusion: In patients with reduced TTTP, especially <5 months, it might be difficult to improve prognosis with a repeated TACE procedures. In such cases, reconsideration of the therapeutic strategy might be needed when possible., (© 2017 S. Karger AG, Basel.)

Aim/background: Evaluations of abdominal ultrasonography (US) findings of primary and secondary tumor-forming hepatic malignant lymphoma (HML) have not been adequately reported. In this study, we elucidated US and contrast-enhanced US (CEUS) findings in patients with HML., Materials/methods: From January 2006 to March 2017, 25 patients with HML were enrolled (primary 7, secondary 18), each of whom was diagnosed pathologically. They were divided into 2 groups based on tumor diameter (cutoff, 30 mm). US imaging findings were retrospectively analyzed., Results: All tumors in patients with a small HML (<30 mm in diameter, small group, n = 14) were revealed as homogeneous hypo-echoic type (100%), with penetrating sign observed in only 1 patient. Tumors in 11 patients in the small group, examined with CEUS, showed homogeneous enhancement in the early vascular phase (91%) and a washout pattern in the portal phase (100%), and they were revealed as defective in the post-vascular phase (100%). In the large group (≥30 mm; n = 11), tumors were revealed as a heterogeneous hypo-echoic lesion in 10 (91%) and penetrating sign was observed in 8 (73%). Dilatation of the distal intrahepatic bile duct by the tumor was observed in 4 patients in the large group. In 7 large group patients examined with CEUS, imaging findings in the early vascular phase varied, with 5 (71%) showing a washout pattern in the portal phase and 5 (71%) revealed as defective in the post-vascular phase., Conclusion: We found that US imaging features of HML differ depending on the tumor diameter., (© 2017 S. Karger AG, Basel.)

Background: Effective surveillance for hepatocellular carcinoma (HCC) in diabetes mellitus (DM) has not been established. We elucidated the risk factors for HCC in DM patients., Methods: From 2000 to 2014, 80 patients diagnosed with HCC for the first time who had concomittant DM but no other etiology of liver disease were enrolled as the DM-HCC group. From 2005 October to 2014, after introduction of the abdominal ultrasonography (US) report database, 2083 DM patients with no viral hepatitis, no known autoimmune hepatic diseases, and/or no evidence of alcohol abuse (>60 g/day) were enrolled as the DM-US group. Findings from the first US screening were evaluated. "Elderly" patients were defined as those aged >65 years. Clinical features of DM-HCC patients were evaluated and compared with those of DM-US patients., Results: In the DM-HCC group (54 men, 26 women), the mean (± SD age was 74.1 ± 8.5 years, and mean HbA1c and fibrosis-4 (FIB-4) index were 7.3 ± 1.3% and 4.50 ± 3.42, respectively. Mean tumor diameter was 5.7 ± 3.5 cm, there were 63/13/2/2 patients classified as Child-Pugh A/B/C/unknown, and 56/24 were single/multiple lesions. In the DM-US group, HCC was detected in three patients (0.14%; 0.3% of those classified as elderly). The mean age and FIB-4 index of these three patients (one man, two women) were 75.6 years (range 67-92 years) and 4.84 (range 2.87-6.98), respectively. Mean tumor diamter was 7.6 cm and there were one and two single and multiple lesions, respectively. In elderly DM-US patients with a high FIB-4 index (≥4), the rate of HCC detection was 5.0%., Conclusions: Being elderly and having a high FIB-4 index are characteristic features of DM-HCC. Similar characteristics were noted for patients with HCC in the DM-US group. HCC surveillance with US is recommended for DM patients, especially those who are elderly (≥65 years) and have a high FIB-4 index., (© 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background/aim: The frequency of sarcopenia, defined as loss of both muscle volume and strength, was analyzed in chronic liver disease (CLD)., Methods and Materials: From April to September 2015, 807 Japanese CLD patients treated as outpatients were enrolled (67.1±10.0 years, men : women=466 : 341, hepatitis C virus : hepatitis B virus : hepatitis B and C virus : alcohol : other=511 : 134 : 3 : 45 : 114). Sarcopenia was diagnosed when the patient showed muscle volume loss and reduced handgrip strength, whereas those with only muscle volume loss were classified as 'v-presarcopenia' and those with only reduced handgrip strength were classified as 's-presarcopenia'. Muscle volume loss was determined using computed tomography findings and a previously reported index (psoas index), and cut-off values for reduced handgrip strength presented by the Asia Working Group for Sarcopenia (AWGS) (AWGS/grip criteria) and European Working Group on Sarcopenia in Older People (EWGSOP) (EWGSOP/grip criteria) (men; 26 and 30 kg, women; 18 and 20 kg, respectively) were used. Clinical features were analyzed for diagnoses of chronic hepatitis (CH, n=381), liver cirrhosis Child-Pugh A (n=330), and liver cirrhosis Child-Pugh B/C (n=96)., Results: When the AWGS/grip criteria were used, the frequencies of sarcopenia, v-presarcopenia, and s-presarcopenia in CH were 3.9, 7.9, and 19.4%, whereas those in Child-Pugh A were 4.8, 17.6, and 21.8% and those in Child-Pugh B/C were 16.7, 11.5, and 39.6%, respectively. When the EWGSOP/grip criteria were used, these frequencies were 7.1, 4.7, and 33.1%, in CH, 11.8, 10.6, and 32.7%, in Child-Pugh A, and 21.9, 6.3, and 49.0%, in Child-Pugh B/C, respectively. The incidence rates of sarcopenia and both types of presarcopenia increased with progression of CLD., Conclusion: Evaluation of handgrip strength and psoas index is an easy and effective method for the detection of sarcopenia and presarcopenia.

Background and Aim: The Child-Pugh classification has some non-objective factors, with chronic hepatitis indistinguishable from early liver cirrhosis in Child-Pugh A. We retrospectively evaluated the efficacy of albumin-bilirubin (ALBI) grade, which has been proposed as a new classification for hepatic function, for grading hepatocellular carcinoma (HCC) patients based on hepatic function and predicting their prognosis., Method: From 2000 to 2014, 2584 naïve HCC [69.0 ± 9.8 years old, 1850 men, 734 female, Child-Pugh class A:B:C = 1871:558:155] were enrolled. TNM staging was determined using the classification of the Liver Cancer Study Group of Japan and ALBI grade, instead of Child-Pugh classification (ALBI with TNM score: ALBI-T score) (Table 1), and is similar to the Japan Integrated Staging (JIS) score. We retrospectively compared ALBI-T and JIS scores in these patients., Results: Of patients classified as Child-Pugh A (n = 1871), 1285 with 5 points were divided into 858 with ALBI grade 1 and 427 with grade 2, while 586 with 6 points were divided into 53 with grade 1 and 533 with grade 2. The ratio of ALBI grade 2 patients with a Child-Pugh score of 6 points (91.0%) was similar to that of those with 7 points (91.8%). Patients with a lower ALBI-T score (0-5 points) showed a better median survival time than those with a corresponding lower JIS score [137.7:83.2:53.4:27.4:5.0:1.4 vs 97.6:74.9:39.7:15.0:4.0:1.0 months]., Conclusion: Albumin-bilirubin grade was found to be superior for distinguishing patients with better hepatic function. ALBI-T scoring may be a better total prognostic scoring system for predicting survival of Japanese patients with HCC., (© 2015 The Authors Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

A 63-year-old Japanese man whose white blood cell count and total-bilirubin and aminotransferase levels were elevated was referred to our hospital. Computed tomography did not reveal any abnormalities, and there was no evidence of gastritis or colitis on esophagogastroduodenoscopy. Although the patient had no history of drug use or allergies, a high concentration of eosinophils (80%) was noted. A liver biopsy revealed hepatitis with eosinophilic infiltration. The patient's alanine aminotransferase and eosinophil levels improved with the administration of steroids. A second biopsy, performed 6 months later, showed the improvement of the eosinophilic infiltration. The patient was diagnosed with eosinophilic hepatitis due to the presence of hypereosinophilic syndrome without the dysfunction of other organs.

Background/aim: The definition of muscle atrophy (pre-sarcopenia) and its diagnostic criteria have not been well reported. To elucidate the frequency of pre-sarcopenia in chronic liver disease (CLD), we examined clinical features of Japanese CLD patients using abdominal computed tomography (CT) findings., Methods: We enrolled 988 CLD (736 with naïve hepatocellular carcinoma) and 372 normal control subjects (NCs). The psoas muscle area index [PI, psoas muscle area at the mid-L3 level in CT (cm(2))/height (m)(2)] was calculated using personal computer software. The cut-off level for pre-sarcopenia was defined as less than two standard deviations (SDs) below the mean PI value in the NCs under 55 years old [males, 45.6 ± 5.7 years (n = 61), 4.24 cm(2)/m(2); females, 47.0 ± 6.1 years (n = 49), 2.50 cm(2)/m(2)]. Elderly was defined as 65 years or older. Clinical features were retrospectively evaluated., Results: In the CLD group (HCV:HBV:HBV and HCV:alcohol:non-HBV and HCV = 652:88:7:82:159), pre-sarcopenia was observed in 15.3% of patients with chronic hepatitis (CH), 24.4% of those with liver cirrhosis (LC) Child-Pugh A, 37.7% of those with LC Child-Pugh B, and 37.1% of those with LC Child-Pugh C. A comparison between NC and CH by age (<55, 55-64, 65-74, ≥75 years) showed that the frequency of pre-sarcopenia was higher in CH regardless of age (1.8 vs. 3.6%, 3.2 vs. 15.9%, 4.9 vs. 13.4%, 14.3 vs. 20.2%, respectively). PI values showed correlations with BMI (r = 0.361), age (r = -0.167), albumin (r = 0.115), and branched-chain amino acids (r = 0.199) (P < 0.01)., Conclusion: Retrospective evaluate for pre-sarcopenia was easy to perform with CT findings. Nutrition and exercise instruction should be considered for early stage and even non-elderly CLD as well as LC.

Background: There are no clear criteria established for treating a ruptured hepatocellular carcinoma (HCC). To elucidate the clinical features of affected patients, we examined prognosis and therapy choices., Materials/methods: We enrolled 67 patients treated for a ruptured HCC (HCV 44, HBV 5, HBV+HCV 1, alcohol 2, others 15; naïve HCC 34, recurrent 33) from 2000 to 2013, and investigated their clinical background and prognosis., Results: Median survival time (MST) for all cases was 4 months. For patients who survived for more than 1 year after rupture, the percentages of Child-Pugh C and positive for portal vein tumor thrombosis (PVTT)/extrahepatic metastasis were less than for those who died within 1 year. Child-Pugh classification (A:B:C=14:15:5 vs. 4:9:20, P<0.001) was better, while the percentage of patients with multiple tumors was lower [19/34 (55.9%) vs. 29/33 (87.9%), respectively; P<0.001] in the naïve group. The 1- and 3-year survival rates were better in the naïve as compared to the recurrent group (60.6% and 33.3% vs. 12.6% and 0%, respectively; P<0.01). MST according to modified TNM stage (UICC 7th) calculated after exclusion of T4 factor of rupture, stage I was better than others (22.7 vs. (II) 2.2, (III) 1.2, and (IV) 0.7 months) (P=0.010)., Conclusion: In patients with a ruptured HCC, especially those with a single tumor, and without decompensated liver cirrhosis and PVTT/extrahepatic metastasis, better prognosis can be expected with curative treatment. The present naïve group included more of such cases than the recurrent group, indicating the effectiveness of curative therapy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background/aim: We examined tumor marker levels to assess in more detail transcatheter arterial chemoembolization (TACE)-refractory hepatocellular carcinoma (HCC)., Materials and Methods: We enrolled patients treated from 2000 to 2011 for HCC beyond the Milan criteria who had good hepatic reserve function (Child-Pugh A) and no portal vein thrombosis or metastases (n = 154). The modified criteria for being TACE-refractory according to the Liver Cancer Study Group of Japan (m-LCSGJ), from which the tumor marker item was excluded, and the Assessment for Retreatment with TACE (ART) score were used for determining whether the HCC was TACE refractory. α-Fetoprotein ≥ 100 ng/ml, fucosylated α-fetoprotein ≥ 10%, and des-gamma-carboxy prothrombin ≥ 100 mAU/ml were used to define whether tumor markers were positive. We added up the number of positive tumor markers as a prognostic score to assess in more detail the evaluation of TACE-refractory HCC., Results: In order to divide the patients into a refractory and nonrefractory group, the m-LCSGJ criteria [mean survival time (MST) 27.1 vs. 49.9 months; p < 0.001] were superior to the ART score (MST 22.0 vs. 35.1 months; p = 0.051). In the refractory group according to the m-LCSGJ criteria, the patients with a low score of positive tumor markers (<2) after 2 sessions of TACE (n = 36) showed a better prognosis than the others (n = 72) (MST 37.7 vs. 23.2 months; p = 0.014)., Conclusion: Patients being nonrefractory according to the m-LCSGJ criteria had a better response, and using the number of tumor markers (≥ 2) is an easy method for predicting the response to TACE and for a more detailed evaluation of TACE-refractory HCC., (© 2015 S. Karger AG, Basel.)

Background/aims: We evaluated the diagnostic efficacy for advanced fibrosis of real-time tissue elastography (RTE), is a newly introduced non-invasive method, in hepatitis C virus (HCV) patients., Methodology: Sixty-six chronic liver diseases with HCV (CLD-HCV) were evaluated by RTE, FIB-4, and APRI, as well as biopsy or hepatectomy findings. Seventeen healthy volunteers, and 1 with elevation of transaminase and 5 with liver tumors within their normal liver were enrolled for normal controls. Severe fibrosis was defined as METAVIR score 3 or 4. The tissue elasticity value was expressed by LF-index created by the program incorporated in the ultrasound device. The percentage of fibrosis area in each specimen (%FA) was determined with a personal computer. A receiver operating characteristic curve (ROC) was calculated for each non-invasive method of estimation of fibrosis., Results: The values for the area under the ROC for LF-index, APRI, and FIB-4 were 0.88, 0.81, and 0.84, respectively. Accuracy, sensitivity, and specificity for prediction of LF-index (>2.8) for severe fibrosis were 86.5%, 78.6%, and 93.6%, respectively, which were better than those of FIB-4 and APRI. LF-index showed a good relationship to %FA (r=0.276, P=0.020)., Conclusion: RTE is an effective method for predicting severe fibrosis in CLD-HCV.

Actin is a major antigen involved in the reaction of smooth muscle antibody positive sera from patients with chronic active hepatitis. In the present study, actin extracted from rabbit skeletal muscle was denatured by sodium dodecyl sulfate and was immunized into the rabbit, a homologous animal for actin. The rabbits, thus immunized, produced antibodies reactive with actins of homologous and heterologous animals. In addition, the antibodies showed reactivity with autologous actin. It indicates that the denatured homologous actin is capable of terminating immunological tolerance to actin and induces formation of autoantibody to rabbit actin. This phenomenon may be implicated in the occurrence of anti-actin antibody in sera from patients with chronic liver disease and several other diseases.