Tomoyuki Ninomiya

Usefulness of albumin-bilirubin grade for evaluation of prognosis of 2584 Japanese patients with hepatocellular carcinoma.

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.

Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients

Background and Aim:  With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (≥ 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively.

Amino acid imbalance in patients with chronic liver diseases.

Aim:  The aim of this study is to clarify the amino acid imbalance in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC).

Sarcopenia and two types of presarcopenia in Japanese patients with chronic liver disease.

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.

Muscle volume loss as a prognostic marker in hepatocellular carcinoma patients treated with sorafenib

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.

Tumor Markers AFP, AFP-L3, and DCP in Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization.

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.

Efficacy of branched-chain amino acid supplementation and walking exercise for preventing sarcopenia in patients with liver cirrhosis

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.

Prognosis and therapy for ruptured hepatocellular carcinoma: Problems with staging and treatment strategy

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.

Recent trends of Japanese hepatocellular carcinoma due to HCV in aging society.

BACKGROUND/AIMS The mean age of hepatocellular carcinoma (HCC) patients has increased (=65 years old). We want to identify the recent trend of the clinical features of HCC patients due to hepatitis C virus (HCV) (HCV-HCC). METHODOLOGY From 2000 to 2009, 855 naive HCC patients were admitted. HCV-HCC patients were divided into two groups, first period group (2000-04, n=270) and second period group (2005-09, n=343) and the clinical features of HCV-HCC were investigated. RESULTS There was no difference in gender, TNM stage and percentages of HCV-HCC between the periods. On the other hand, the ratio of HCV-HCC patients with worse liver function (Child-Pugh B or C), elderly (=75 years old) and the population of patients treated with low invasive radiofrequency ablation were increased (30.0% to 42.0%, 17.2% to 35.8% and 25.1% to 36.2%, respectively; p<0.01). The 1y-, 3y- and 5y-survival rate of HCV-HCC did not show differences (82.1%, 60.5% and 44.7% vs. 81.8%, 56.9% and 37.7%, respectively; p=0.219). CONCLUSIONS The ratio of aged HCV-HCC as well as HCV-HCC patients with worse liver function was increased. The less invasive treatment for HCC in these patients and the quick anti-viral treatment for HCV patients should be considered to avoid occurrence of HCC in Japan.

Ultrasonography screening for hepatocellular carcinoma in Japanese patients with diabetes mellitus

Effective surveillance for hepatocellular carcinoma (HCC) in diabetes mellitus (DM) has not been established. We elucidated the risk factors for HCC in DM patients.