Effect of vitamin K2 on the development of hepatocellular carcinoma in type C cirrhosis.

BACKGROUND/AIMS: Hepatocellular carcinoma occurs frequently in cirrhosis related to hepatitis C virus (type C cirrhosis), and preventative treatment with interferon is costly and likely to cause adverse reactions. Menatetrenone, a vitamin K2 preparation, has recently been reported to inhibit the posttreatment relapse of hepatocellular carcinoma. We therefore examined whether menatetrenone could prevent the development of hepatocellular carcinoma in patients with type C cirrhosis. METHODOLOGY: This prospective, randomized trial recruited patients with type C cirrhosis, platelet count of 10 x 10(4) microl or less, and no history of hepatocellular carcinoma. Patients were assigned to a menatetrenone group (n = 22, 4 5mg of menatetrenone daily, orally) or a control group (n = 18). Follow-up with image diagnosis was performed every 3-6 months. RESULTS: No adverse events of menatetrenone treatment were observed. Hepatocellular carcinoma occurred in 2 of 22 patients in the menatetrenone group (9.1%) and 5 of 18 patients in the control group (27.8%); however, this difference did not reach statistical significance. CONCLUSIONS: The present findings suggest that menatetrenone has some inhibitory effect on development of hepatocellular carcinoma in patients with type C cirrhosis. Consequently, to further validate its benefits, we believe that menatetrenone should be actively administered to patients with intractable (interferon-resistant) cirrhosis.

Frequency of nonsteroidal anti-inflammatory drug-associated ulcers.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for treatment of orthopedic diseases, inflammatory diseases, etc., and low-dose aspirin is a common antiplatelet therapy given mainly for secondary prevention of atherothrombosis (e.g., myocardial infarction and cerebral infarction). As to the history of NSAID-induced gastric mucosal injury in Japan, the first case of an aspirin-induced gastric ulcer was reported as early as 1934. Based on a meta-analysis of risk factors for peptic ulcers, Helicobacter pylori infection and NSAIDs are the main etiologies of peptic ulcers. NSAIDs alone increase the odds ratio for ulcer development to 19.4 and that for ulcer bleeding to 4.85. In fact, the Japan Rheumatism Foundation reported in 1991 that active gastric ulcers and active duodenal ulcers were detected in 15.5 and 1.9 % of 1008 patients, respectively, taking oral NSAIDs for 3 months or longer. In Japan, which is becoming an increasingly aged society, the numbers of patients taking NSAIDs and low-dose aspirin are expected to increase dramatically in the future. It is hoped that accumulation of evidence on gastrointestinal risk will allow many patients to rationally avoid gastrointestinal complications while receiving the benefits of NSAIDs and low-dose aspirin.

Evaluation of esophageal varices using contrast-enhanced coded harmonic ultrasonography.

AIM: To investigate if esophageal varices can be evaluated using external contrast-enhanced ultrasonography with Levovist and coded harmonic angio (CHA). METHODS: Subjects were six healthy adult volunteers and 23 patients with liver cirrhosis. After identification of the lower esophagus under B-mode scanning, 300 mg/mL of Levovist was intravenously injected into the cubital vein at a rate of 1 mL/s under observation by CHA-mode scanning. Approximately 30 s after intravenous administration, interval-delay scanning was performed every second to visualize the area around the lower esophageal lumen. The degree of ultrasonographic enhancement was assessed as either no enhancement (negative); linear enhancement along the esophageal wall (weak) or full enhancement of the esophageal lumen (strong). Endoscopic evaluation of esophageal varices was also performed. RESULTS: The CHA enhancement around the lower esophageal lumen was identified in 21 of the 23 patients. Of these 21 patients, endoscopic assessments of varices were as follows: F0 in four patients, F1 in seven patients, F2 in three patients, and F3 in seven patients. Nine patients were red color sign (RCS)-positive. Regarding the relationship between ultrasonographic enhancement and endoscopic assessment, enhancement was identified as negative in all four F0 patients, negative in three and weak in three and strong in one of the seven F1 patients, weak in one and strong in two of the three F2 patients, and weak in two and strong in five of the seven F3 patients, respectively. Furthermore, of the nine RCS-positive patients, enhancement was recognized as strong in seven and weak in two patients. Ultrasonographic enhancement was identified as negative in all six healthy volunteers. CONCLUSIONS: By performing contrast-enhanced CHA ultrasonography using Levovist, ultrasonographic enhancement was detectable in all patients with varices categorized as F2 or above. Because the present method is easy to perform and causes less pain to patients compared to endoscopy, it is useful for following and assessing esophageal varices in patients with liver cirrhosis.