Satoyoshi Yamashita

Efficacy and safety of a 14-day administration of tolvaptan in the treatment of patients with ascites in hepatic oedema:

Objective To investigate the efficacy and safety of 14 days’ orally administered tolvaptan as adjunctive treatment for hepatic oedema in Japanese liver cirrhosis patients with insufficient response to conventional diuretics, with the option to increase dose in those who did not respond initially. Methods This multicentre, single-arm, phase 3 study allocated patients with liver cirrhosis and persistent ascites to 7-day treatment with 7.5 mg/day tolvaptan followed by an additional 7 days’ treatment. Responders at day 7 (achieving ≥1 kg body-weight reduction) continued on 7.5 mg/day tolvaptan; nonresponders (<1 kg body-weight reduction) received 15 mg/day tolvaptan. Conventional diuretic treatment continued throughout. The primary endpoint was change in body weight from baseline, as a marker of ascites volume. Results A total of 51 patients received 7.5 mg/day tolvaptan for 7 days, which caused a significant reduction in mean body weight (55% response rate). During the second 7-day treatment period, 30 patients received 7.5 mg/day tolvaptan and 13 patients received tolvaptan 15 mg/day: response rates were 43% and 23%, respectively. Two serious adverse events were observed. Serum sodium was within normal range. Conclusions Tolvaptan therapy for 14 days (with possible dose increase as necessary), in combination with conventional diuretics, effectively reduced body weight in patients with hepatic oedema.

Dose-finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A randomized, double-blind, placebo-controlled trial

Liver cirrhosis represents the end stage of any chronic liver disease, and it is associated with hepatic edema such as ascites. Many patients with ascites do not respond to diuretic therapy or require administration of diuretics at high doses that can cause adverse events. This 7‐day, multicenter, double‐blind trial of tolvaptan was designed to determine the optimal dose of tolvaptan for producing the intended pharmacological effect in hepatic edema.

Effect of a late evening snack on outpatients with liver cirrhosis.

Aims:  We have reported that one‐week administration of a late evening snack (LES) improved not only malnutrition but also glucose intolerance in hospitalized patients with liver cirrhosis. Thus, we investigated whether long‐term LES administration to outpatients for 3 months could reproduce the results obtained from hospitalized patients, especially improved glucose intolerance. If this treatment aggravated glucose intolerance, we tried to find any marker predicting this aggravation before the treatment.

417–2α-Tocopherol and ascorbic acid attenuates the ribavirin-induced decrease of eicosapentaenoic acid in erythrocyte membrane in chronic hepatitis C patients

Background:  Oxidative damage of the erythrocyte membrane plays an important role in ribavirin‐induced anemia. The purpose of the present paper was to assess whether supplementation of α‐tocopherol and ascorbic acid (vitamins) causes changes in the erythrocyte membrane fatty acid composition during interferon and ribavirin combination therapy for chronic hepatitis C patients.

Molecular epidemiologic analysis of hepatitis C virus infection in injecting drug users with acute hepatitis C in Japan

Background and Aim:  The aim of this study was to examine whether particular hepatitis C virus (HCV) subtypes are spreading among injecting drug users (IDUs) in Yamaguchi prefecture, on the south‐western tip of the island of Honshu in Japan, as found in European countries.

Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers

BACKGROUND There are few blood tests for an efficient detection of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection. METHODS The abilities of quantitative analyses of 7 genes hypermethylation in serum DNA, α-fetoprotein (AFP) and prothrombin-induced vitamin K absence II (PIVKA-II), and various combinations to detect HCC were evaluated in a training cohort of 164 HCV-infected patients (108 HCCs; 56 non-HCCs). An optimal hybrid detector, built using data for 2 methylated genes (SPINT2 and SRD5A2), AFP, and PIVKA-II, achieved the most satisfactory ability to detect HCC in the training cohort. We evaluated the ability of the optimal hybrid detector to detect HCC in an independent validation cohort of 258 consecutive HCV-infected patients (112 HCCs; 146 non-HCCs) who were newly enrolled in 4 distinct institutes. RESULTS In the validation cohort of 258 patients, accuracy, sensitivity, and specificity of the hybrid detector for detection of HCC were 81.4%, 73.2%, and 87.7%, respectively. Notably, even when detecting HCC ≤ 2 cm in diameter, the hybrid detector maintained markedly high abilities (84.6% accuracy, 72.2% sensitivity, 87.7% specificity). Youdens index (sensitivity+specificity - 1) for HCC ≤ 2cm was 0.60, vastly much superior to the 0.39 for AFP at a cut-off value of 20 ng/ml and the 0.28 for PIVKA-II at a cut-off value of 40 mAU/ml. CONCLUSIONS These results show that the optimal hybrid blood detector can detect HCV-related HCC more accurately.

Fulminant hepatitis complicated by small intestine infection and massive hemorrhage

Abstract: A 34-year-old man diagnosed with fulminant hepatitis, caused by hepatitis B virus, and acute renal failure was referred to our hospital. After admission to the intensive care unit, the liver and renal failure were ameliorated. Melena requiring transfusion occurred during the course of his illness. Endoscopic examination demonstrated pseudomembranes, erosions, ulcers, and hemorrhage in the duodenum, the upper jejunum, and the terminal ileum, suggesting widespread lesions throughout the small intestine. Pseudomonas putida, Xanthomonas maltophilia, and Candida glabrata were cultured from ileal fluid. Candida glabrata was also detected in sputum, feces, and on an intravenous catheter tip. The patient was treated with amphotericin B and miconazole. The melena was ameliorated, but inflammation of the small intestine persisted. Although we had difficulty in treating the enteritis, the patient survived, and 1 year later colonoscopic examination demonstrated no abnormalities. The small intestine is a difficult site to examine, but endoscopic examination of this site is important when massive hemorrhage develops.

Detection of hepatitis B virus DNA in liver by polymerase chain reaction for the diagnosis of fulminant hepatitis B

Abstract To assess the involvement of GB virus C (GBV-C) or hepatitis B virus (HBV) infection in fulminant hepatitis of unknown etiology, GBV-C RNA and HBV DNA in serum were retrospectively assayed by polymerase chain reaction (PCR) in six patients with fulminant hepatitis of unknown etiology (group A) and in three patients with fulminant hepatitis B (group B). Additionally, liver specimens were tested for both GBV-C RNA and HBV DNA in two patients and for only HBV DNA in another patient in group A. GBV-C RNA in serum and liver was not detected in any patient. HBV DNA in serum was detected only in patients in group B, while in liver it was detectable in three patients in group A. These results suggest that GBV-C infection is unlikely to be involved in fulminant hepatitis of unknown etiology and that the detection of HBV DNA in liver by PCR is useful for diagnosis of fulminant hepatitis B that shows no serologic evidence of the current infection.

Evaluation of Laparoscopic Findings in Chronic Hepatitis C

Abstract: To elucidate the differences in the progression of liver cirrhosis of chronic hepatitis B and C, the laparoscopic appearance of the liver surface and the histological findings were carefully assessed in 65 patients with chronic hepatitis B and 58 patients with chronic hepatitis C.

Erratum to: Clinical effectiveness of bipolar radiofrequency ablation for small liver cancers

The first sentence in the legend for Fig. 2 appeared incorrectly. The sentence should read as follows: Fig. 2 Differences in the electrical flow routes of a the bipolar (CelonPOWER System) and b the monopolar radiofrequency ablation (RFA) systems. In Fig. 4, in the next-to-last step on the right side of the flowchart, the correct number of weeks in the follow-up period should be 24, not 20. The correct figure should be shown as follows: