Tokiko Nakamura

Long-term phlebotomy with low-iron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C.

BackgroundWe have previously demonstrated that in patients with chronic hepatitis C (CHC), iron depletion improves serum alanine aminotransferase (ALT) levels as well as hepatic oxidative DNA damage. However, it has not been determined whether continuation of iron depletion therapy for CHC favorably influences its progression to hepatocellular carcinoma (HCC).MethodsWe conducted a cohort study on biopsy-proven CHC patients with moderate or severe liver fibrosis who failed to respond to previous interferon (IFN) therapy or had conditions for which IFN is contradicted. Patients were divided into two groups: subjects in group A (n = 35) underwent weekly phlebotomy (200 g) until they reached a state of mild iron deficiency, followed by monthly maintenance phlebotomy for 44–144 months (median, 107 months), and they were advised to consume a low-iron diet (5–7 mg iron/day); group B (n = 40) comprised CHC patients who declined to receive iron depletion therapy.ResultsIn group A, during the maintenance phase, serum ALT levels decreased to less than 60 IU/l in all patients and normalized (<40 IU/l) in 24 patients (69%), whereas in group B no spontaneous decrease in serum ALT occurred. Hepatocarcinogenesis rates in groups A and B were 5.7% and 17.5% at the end of the fifth year, and 8.6% and 39% in the tenth year, respectively. Multivariate analysis revealed that iron depletion therapy significantly lowered the risk of HCC (odds ratio, 0.57) compared with that of untreated patients (P = 0.0337).ConclusionsLong-term iron depletion for CHC patients is a promising modality for lowering the risk of progression to HCC.

Suppressive effect of ethanol on the expression of hepatic asialoglycoprotein receptors augmented by interleukin-1β,interleukin-6, and tumor necrosis factor-α

Abstract: Blood levels of inflammatory-related cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, are elevated in patients with alcoholic liver diseases. We investigated the effects of these cytokines and ethanol on the expression of hepatic asialoglycoprotein receptors (AGPRs) in a human hepatoblastoma cell line, HepG2. An [125I]-asialo-orosomucoid binding assay showed significant increases in surface AGPR numbers in HepG2 cells by treatment with IL-1β, IL-6, and TNF-α, to levels which were approximately 130% of the values in untreated control cells. However, the enhanced AGPR numbers induced by treatment with these cytokines were markedly suppressed, to 70%–80% of the number in the untreated cells, by treatment with ethanol. Immunological detection of AGPR with a specific antibody demonstrated that the modulation of surface AGPR numbers was correlated with the cellular expression levels of AGPR. These results suggest that, although IL-1β, IL-6, and TNF-α stimulate the synthesis of hepatic AGPR, ethanol suppresses the expression of AGPR augmented by these cytokines. This leads to an increase in serum asialo-orosomucoid levels caused by the disordered catabolism mediated by AGPR in patients with alcoholic liver disease.

A novel treatment for early gastrointestinal carcinoma by ultrasonic endoscopic mucosal stripping.

PurposeThe aim of this study was to clarify the indications for a new endoscopic mucosal resection (EMR) technique that employs a cavitational ultrasonic surgical aspirator (CUSA). Endoscopic mucosal resection has proved an effective technique for treating early mucosal gastrointestinal cancer. However, resecting a lesion larger than 2 cm en bloc requires special devices and a long processing time; and it engenders the risk of bleeding, perforation, and other complications.MethodsWe investigated application of the CUSA for detaching the mucosa from the muscularis propria of extracted porcine stomachs and then clarified the specification of an endoscopic ultrasonic scalpel for endoscopic mucosal resection by investigating characteristics of two original, handmade prototype cavitational ultrasonic surgical aspirators.ResultsUse of a cavitational ultrasonic surgical aspirator should improve the ease and safety of detaching the mucosa. A small, high-power ultrasonic cylindrical vibrator should be developed to make possible a probe-type scalpel with a piezoelectric vibrator mounted in the tip of a catheter. An ultrasonic transmission-type scalpel could lead to the development of a new endoscopic mucosal resection device for clinical use.ConclusionsThe CUSA should enable us to develop a safer, simpler, time-saving scalpel for endoscopic mucosal resection, although some resolvable technical problems remain. The CUSA might enable us to diagnose carcinoma invasion into the submucosa in aspirated specimens and then aspirate out the entire invading submucosal carcinoma.