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We have shown, using the proline:ornithine dual label method, that in normal rats, hepatocytes contribute in vivo about 80 to 90% of the newly synthesized hepatic collagen. In order to quantify the contribution of hepatocytes and nonparenchymal cells to collagen synthesis in vivo in hepatic fibrogenesis, rats with CCl4-induced liver fibrosis were given [5(3H)]proline and [14C]ornithine intraperitoneally. About 80% of the 14C in albumin and transferrin was present as arginine, following conversion of [14C]ornithine via the urea cycle. In contrast to hepatocyte proteins, in nonparenchymal cells and serum a negligible percentage of the radioactivity was present as [14C]arginine. These combined findings indicate that, in spite of the hepatocellular damage, the labeling of hepatocyte proteins was efficient and specific, validating the use of the proline:ornithine method in this experimental model of hepatic fibrosis. We calculated the [3H]proline/[14C]arginine ratio in hepatic collagen (after correcting for the relative frequencies of amino acids) as a percentage of the same ratio in either albumin or transferrin, the index hepatocyte proteins. In this experimental model, during active fibrogenesis, both hepatocytes and nonparenchymal cells increase their production of collagen 2-fold when compared to normal animals, and hepatocytes produce the majority of the newly synthesized hepatic collagen.

The treatment of chronic hepatitis C has been a challenge to most hepatologists and gastroenterologists. Approximately half of the patients demonstrate a response at the end of treatment with standard interferon (IFN) therapy. Of these responders, only half will eventually have sustained responses 6 months after the end of treatment. 1-3 There appear to be 2 challenges to achieving responses to IFN therapy in hepatitis C virus (HCV). The first is to initiate an antiviral response, and the second is to maintain the response after therapy and prevent a relapse. Longer IFN treatment durations, i.e., 12 to 18 months rather than 6 months, increases the chance of a sustained response. 4 However, the former issue of how to increase the initial response rate has not been resolved, although ''induction'' therapy may enhance initial IFN responsiveness. The issue of initial response rate is further complicated by the phenomenon of breakthroughs. A breakthrough occurs when a patient achieves a response while on IFN therapy and then loses the response despite continued IFN therapy. Breakthroughs have largely been defined by a transient normalization of alanine transaminase (ALT) values, because ALT has been the primary measure of efficacy in most HCV clinical trials. However, sensitive assays to measure HCV RNA have now become the standard in assessment of efficacy. Thus, patients could have either an ALT breakthrough or an HCV-RNA breakthrough. The latter would be a transient undetectable serum HCV-RNA value that returns to detectable levels during continued IFN Abbreviations: IFN, interferon; HCV, hepatitis C virus; ALT, alanine transaminase; CIFN, consensus interferon.From the

Endoscopic resection of gastrointestinal tumors is being performed with increased frequency. Submucosal mass lesions pose a particular problem, because of the risk of malignancy and the risk of complications associated with endoscopic removal. Increased incidences of both perforation and bleeding have been reported. We report here on a case in which we used a combined approach that included gastrointestinal endoscopy, laparoscopy, and laparoscopic ultrasound to resect a gastric leiomyoma. We consider that this approach enhanced our diagnostic capabilities, provided intraoperative options for resection, and enhanced the safety of the procedure.