Yuji Kojima

Increased lipid peroxidation in patients with non-alcoholic fatty liver disease and chronic hepatitis C as measured by the plasma level of 8-isoprostane.

Background:  Oxidative stress plays an important role in the pathogenesis of chronic liver diseases. The plasma level of 8‐isoprostane, a product of lipid peroxidation, is a marker of oxidative stress in vivo. The aim of the present study was to clarify whether the degree of lipid peroxidation, as measured by the plasma level of 8‐isoprostane, influences the progression of chronic liver diseases and hepatocarcinogenesis.

Effect of lactoferrin in patients with chronic hepatitis C: Combination therapy with interferon and ribavirin

Objectives:  Lactoferrin has been reported to inhibit hepatitis C virus (HCV) infection in cultured human hepatocytes and HCV viremia in patients with chronic hepatitis C (CHC). The aim of this study was to evaluate the effect of combined triple therapy of lactoferrin, interferon and ribavirin in patients with CHC.

Decreased protein C activation in patients with fulminant hepatic failure

Objective. Abnormalities of the blood coagulation system have an influence on outcome in patients with fulminant hepatic failure (FHF). The protein C (PC) pathway is one of the main modulators of the blood coagulation system. The role of the PC pathway in FHF is not clear. In the present study, we evaluated endothelial cell injury and the grade of activated protein C (APC) generation in FHF patients. Material and methods. The effect of APC on the expression of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 from LI90 stellate cells was also evaluated. This study comprised 5 patients with FHF, 6 with acute hepatitis (AH), 12 with chronic hepatitis (CH) and 20 healthy subjects. Results. The plasma concentrations of thrombin-antithrombin complex and thrombomodulin were significantly increased in FHF patients compared with those in AH patients and healthy subjects. The circulating levels of activated protein C-protein C inhibitor (APC-PCI) complex and the APC-PCI/PC ratio were significantly decreased in patients with FHF compared to healthy controls. APC significantly inhibited in vitro the expression of TNFα and MCP-1 from LI90 stellate cells. Conclusions. This study demonstrated enhanced endothelial cell injury in association with decreased PC activation and hypercoagulability in FHF.

Iron reduction therapy by phlebotomy reduces lipid peroxidation and oxidative stress in patients with chronic hepatitis C

To the Editor: Lipid peroxidation and oxidative stress play important roles in the pathogenesis of chronic hepatitis C (CHC).1–3 Chronic infection with hepatitis C virus (HCV) is associated with excessive iron deposition in the liver.4 It is believed that that ironassociated free-radical production is involved in liver injury during CHC. Iron reduction therapy by phlebotomy has been reported to improve hepatic inflammation in patients with CHC.5–7 On the other hand, the plasma level of 8-isoprostane has been found to be the most reliable marker of lipid peroxidation and oxidative stress in vivo.3,8–10 Recently, we reported that the plasma level of 8-isoprostane is elevated in patients with CHC and nonalcoholic fatty liver disease.11 In the present study, we investigated whether iron reduction therapy by phlebotomy reduces the plasma level of 8-isoprostane in patients with CHC. This study comprised patients that consulted our clinic department from April 2004 through October 2005. Twenty-five patients with CHC [13 men, 12 women; 58.5 ± 2.17 (mean ± SE) years old], including five smokers and four patients with diabetes mellitus, and 25 matched control patients with CHC [13 men, 12 women; 58.3 ± 2.12 (mean ± SE) years old], including five smokers and four patients with diabetes mellitus were enrolled in the phlebotomy group and in the control group, respectively. The inclusion criteria were as follows: (1) elevation of alanine aminotransferase (ALT) levels above the upper normal limit for 3 months or more; (2) high viral load of more than 100 KIU/ml (Amplicor monitor; Roche Diagnostic Systems, Basel, Switzerland) and HCV genotype 1b; and (3) absence of other causes of chronic hepatitis. All patients had been treated with 600 mg of ursodeoxycholic acid for more than 3 months before entering the study and continued this treatment during the entire observation period. Phlebotomy of 240 ml was performed biweekly or monthly until the serum ferritin level reached the endpoint of 20 ng/ml. The median duration of the phlebotomy treatment was 3 months (range, 2–6 months). The patients of the control group were followed up for 3 months with blood tests. The blood levels of 8-isoprostane,11 aspartate aminotransferase (AST), ALT, albumin, total cholesterol (TCHO), triglycerides, plasma glucose (PG), HCV RNA, iron, ferritin, transferrin, and unsaturated iron binding (UIBC), and complete blood count and body mass index (BMI) were measured to assess liver function and nutrition status, and the data before and immediately and 3 months after phlebotomy were compared. This study was approved by the ethics committee of each institution, and written informed consent was obtained from each patient enrolled in the study. Data are expressed as means ± standard deviation (SD). Student’s t test was used to evaluate statistical differences. P < 0.05 was considered to be statistically significant. Twenty-four patients successfully completed the protocol therapy of phlebotomy. One patient stopped the therapy because of leg edema 6 weeks after entry. The plasma concentration of 8-isoprostane was significantly decreased from 14.2 ± 7.20 to 8.28 ± 3.46 pg/ml after phlebotomy (P < 0.001). In the phlebotomy group, the blood levels of ferritin, iron, transferrin saturation, AST, ALT, albumin, T-CHO, red blood cells, hemoglobin, and hematocrit were significantly decreased after phlebotomy compared with baseline values (Table 1). The blood levels of UIBC, transferrin, and platelets significantly increased after phlebotomy (Table 1). BMI and the blood levels of triglyceride, PG, HCV RNA, and white blood cells did not change after phlebotomy. In the control group, the plasma concentration of 8-isoprostane remained unchanged (12.6 ± 4.05 vs. 13.2 ± 4.80 pg/ml) after 3 months, and the other values did not change after 3 months compared with baseline values (Table 2). These findings suggest that iron reduction therapy by phlebotomy definitely reduces lipid peroxidation and oxidative stress in patients with CHC. Iron reduction therapy by phlebotomy may be useful in other diseases caused by lipid peroxidation and oxidative stress such as nonalcoholic fatty liver disease,11 diabetes mellitus,8 and obesity.10 Table 1. Changes in blood parameters in the phlebotomy group

Efficacy of daclatasvir plus asunaprevir in patients with hepatitis C virus infection undergoing and not undergoing hemodialysis: Daclatasvir plus asunaprevir in non-HD and HD patients

To evaluate the virologic responses and clinical course of daclatasvir plus asunaprevir treatment in non‐hemodialysis (non‐HD) and hemodialysis (HD) patients infected with genotype 1 hepatitis C virus (HCV).

Validity of Japanese version of SARC-F questionnaire in patients with chronic liver disease: Japanese version of SARC-F questionnaire

We aimed to examine the validity of the Japanese version of SARC‐F questionnaire (SARC‐F‐J) that employs the diagnostic criteria for sarcopenia established by the Japan Society of Hepatology in patients with chronic liver disease.

A 10-year Follow-up Study of a Japanese Family with Ferroportin Disease A: Mild Iron Overload with Mild Hyperferritinemia Co-occurring with Hyperhepcidinemia May Be Benign

This is a 10-year follow-up study of a family with ferroportin disease A. The proband, a 59-year-old man showed no noteworthy findings with the exception of an abnormal iron level. The probands 90-year-old father showed reduced abilities in gait and cognition; however, with the exception of his iron level, his biochemistry results were almost normal. Brain imaging showed age-matched atrophy and iron deposition. In both patients, the serum levels of ferritin and hepcidin25, and liver computed tomography scores declined over a 10-year period. These changes were mainly due to a habitual change to a low-iron diet. The iron disorder in this family was not associated with major organ damage.

Real-world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group: Sofosbuvir therapy for HCV GT2

This study aimed to describe the real‐world efficacy and safety of sofosbuvir (SOF) + ribavirin (RBV) for chronic hepatitis C, genotype 2.

Endoscopic Hemostasis in Patients with Dieulafoy Ulcer

Abstract: Dieulafoy ulcer was defined based on endoscopic findings as an ulcer (1) of 10 mm or less in diameter, (2) of grade Ul‐ll or less and (3) showing vascular protrusion in its floor. We evaluated the clinical background and endoscopic findings of Dieulafoy ulcer and studied the usefulness and problems of endoscopic hemostasis. Patients with Dieulafoy ulcer accounted for 8.7 % of 321 patients with diseases treated by endoscopic hemostasis excluding sclerotherapy. The patients were predominantly males, and their average age was 61 years. An association with other diseases was noted in 21 patients (75%). Therefore, more than 50 % of the patients were treated with NSAIDs such as aspirin. The most frequent site of this disease was the posterior wall of the upper gastric body. In particular, the ulcer was located in the superior duodenal angle. In six of the 28 patients, the ulcer and the exposed vessel were similar in size. Endoscopic hemostasis was successful in 25 patients (89%). Hemostasis was acheived by emergency surgery in two and by transcatheter arterial embolization (TAE) in one. No patient showed recurrence. Most Dieulafoy ulcers can be conservatively treated by endoscopic hemostasis. However, a few cases can not be managed conservatively and shock develops due to fatal massive bleeding. In such patients, the timing of TAE or surgery must be carefully considered.