Nobuaki Azemoto

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.

Biochemical response to ursodeoxycholic acid predicts long-term outcome in Japanese patients with primary biliary cirrhosis.

Aim:  There is an ongoing need for predictors of long‐term outcomes for patients with primary biliary cirrhosis (PBC). Biochemical response to ursodeoxycholic acid (UDCA) has been introduced to predict development of symptoms by our group (Ehime criteria) and to predict long‐term outcomes in Western countries (Paris, Barcelona and Rotterdam criteria). The aim of this study was to evaluate whether these criteria are also useful to predict long‐term outcomes in Japanese patients with PBC.

Clinical significance of B cell-activating factor in autoimmune pancreatitis.

Objectives: Overexpression of B Cell-activating factor (BAFF) is involved in autoimmunity, but little is known about its role in autoimmune pancreatitis (AIP). The aim of this study was to investigate the role of BAFF in the diagnosis and pathogenesis of AIP. Methods: Patients with AIP (n = 19) were compared with 2 disease control groups (chronic pancreatitis [n = 17] and pancreatic cancer [n = 15]) and a healthy subject group (n = 19). Serum BAFF levels were assessed using an enzyme-linked immunosorbent assay. The expressions of BAFF and BAFF receptor in the pancreatic tissue of patients with AIP were estimated using immunohistochemistry. Results: Mean serum BAFF levels were higher in the patients with AIP than in the patients with chronic pancreatitis, the patients with pancreatic cancer, and the healthy subjects (P < 0.0001 for all groups). Using the cutoff value of 1389 pg/mL, the sensitivity and specificity to differentiate AIP from disease and healthy controls were 89.5% and 92.2%, respectively. Glucocorticoid therapy decreased serum BAFF levels below 1389 pg/mL in all patients with AIP (P < 0.0001). B Cell-activating factor and BAFF receptor were expressed on cells infiltrating the pancreas of patients with AIP. Conclusions: B Cell-activating factor could be a novel marker for diagnosis and treatment response in AIP and may contribute to its pathogenesis.

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.

Increased B Cell-Activating Factor Promotes Tumor Invasion and Metastasis in Human Pancreatic Cancer

B cell-activating factor (BAFF) is a cytokine belonging to the tumor necrosis factor (TNF) superfamily. It has been reported that BAFF is elevated in patients with autoimmune pancreatitis and contributes to the malignant potential of blood cancers and solid tumors. In this study, clinical evidence of increased BAFF levels in patients with pancreatic ductal adenocarcinoma (PDAC) was obtained, and the roles and mechanisms of BAFF in PDAC were clarified in human tissues of PDAC and from in vitro data of PDAC cell lines. Serum levels of BAFF in patients with PDAC were significantly higher than in healthy subjects (p = 0.0121). Patients with UICC stage IV PDAC (T1-4, N0-1, M1) had significantly higher levels of serum BAFF compared to patients with PDAC (p = 0.0182). BAFF was remarkably expressed in infiltrating B lymphocytes surrounding pancreatic cancer in human pancreatic tissues, suggesting that BAFF may play a role in progression of pancreatic cancer. PDAC cell lines were cultured with human recombinant BAFF, and morphology and gene expression were analyzed; pancreatic cancer cells changed to a fibroblast-like morphology, and showed altered gene expression of E-cadherin, vimentin and Snail. These BAFF-induced changes reflect enhanced cell motility and invasion. BAFF-R-overexpressing cell clones confirmed the association between these BAFF-induced changes and epithelial-mesenchymal transition (EMT)-related genes. BAFF was elevated in patients with metastatic advanced PDAC and induced alterations in PDAC cells via regulation of EMT-related genes. Elucidation of the precise role and mechanism of control of BAFF may lead to new therapeutic approaches with the aim of improving pancreatic cancer survival.

Liver/spleen volume ratio as a predictor of prognosis in primary biliary cirrhosis.

BackgroundThe course of primary biliary cirrhosis (PBC) is determined by clinical symptoms and histological findings. The present study examined the prognostic importance of imaging parameters in PBC.MethodsThe volumes of the liver and spleen of patients with PBC were assessed by computed tomography (CT). The volume ratio of liver to spleen (LV/SV ratio) was evaluated and used for further analyses.ResultsThe prognosis was significantly poorer in PBC patients with a low, rather than high, LV/SV ratio. The Cox proportional hazard regression model showed that the serum bilirubin level and the LV/SV ratio could predict the prognosis of PBC patients. In addition, the LV/SV ratio was significantly lower in patients who developed symptoms (s-PBC) than in those who remained asymptomatic (a-PBC) during the observation period.ConclusionsThe LV/SV ratio is of prognostic importance in patients with PBC.

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.

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.

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.

Utility of Contrast-Enhanced Transabdominal Ultrasonography to Diagnose Early Chronic Pancreatitis.

Purpose. The purpose of this study was to establish the relationship between the grade of chronic pancreatitis (CP) and pancreatic blood flow as measured by contrast-enhanced transabdominal ultrasonography (CEUS) and to diagnose early CP easily. Methods. This pilot study was conducted in 8 patients with CP, 7 patients with early CP, and 6 control participants. After injecting 0.015 mL/kg of perflubutane by manual bolus, values in one region of interest (ROI) in pancreatic parenchyma and one ROI including the superior mesenteric artery (SMA) were measured. Results. The ratio of blood flow in the SMA and pancreatic parenchyma increased with grade of CP and was significantly higher in patients with CP (5.41; 2.10–11.02) than in patients with early CP (2.46; 1.41–5.05) and control participants (2.32; 1.25–3.04) (P = 0.0279, P = 0.0142, resp.). The ratio of blood flow in the SMA and pancreatic parenchyma correlated with grade of CP (rs = 0.5904, P = 0.0048). Conclusion. The ratio of blood flow correlates with grade of CP on CEUS. This safe and convenient method may be useful to diagnose early CP.