Tomomi Konishi

Serial assay of hepatitis C virus RNA in serum for predicting response to interferon-α therapy

To determine whether the loss of serum hepatitis C virus RNA (HCV-RNA) early in interferon therapy would indicate a sustained response to this agent, we detected serum HCV-RNA successively during and after therapy. Serum samples for detection of HCV-RNA were obtained serially from 36 patients with chronic hepatitis C treated with interferon-α. In 28 of these patients, results of the assay were compared with genotypes and quantitative levels of HCV-RNA in serum before therapy. HCV-RNA was detected by a reverse transcription polymerase chain reaction using the 5′-noncoding region as a primer. Genotypes were determined by using type-specific primers, and serum levels of HCV-RNA were determined by a competitive reverse transcription polymerase chain reaction (RT-PCR). HCV-RNA disappeared from serum in eight of 10 responders (80%), but in only one of the 26 nonresponders (3.8%) at the second week of therapy (P<0.0005). The time until the disappearance of HCV-RNA was correlated with the serum level of HCV-RNA present before therapy (P<0.05). The early disappearance of HCV-RNA from serum during interferon therapy was useful in predicting a sustained response in patients with chronic hepatitis C.

A new therapeutic trial of secretin in the treatment of intrahepatic cholestasis

SummaryMany animal experiments have been studied on the choleretic effects of secretin. We intended to estimate secretin choleresis in human (15 patients) who had received PTCD or T-tube insertion into the common bile duct. Based upon these data of secretin and choleresis, secretin was administered to 11 patients with prolonged jaundice due to intrahepatic cholestasis in order to evaluate this as a new therapy for intrahepatic jaundice. As controls, eleven patients with intrahepatic cholestasis treated with steroid hormones and/or phenobarbital were used. In all cases with biliary drainage, secretin produced a remarkable choleretic effect with a high concentration of bicarbonate. In 9 out of 11 patients with intrahepatic cholestasis who were treated with secretin, levels of serum bilirubin decreased linearly and other liver function tests returned to the normal range. The mean values of T1/2 (number of days required for reduction by half) of serum bilirubin in 9 effective cases to secretin was 10.8 days. On the other hand, that in 11 effective cases treated with steroid hormones and/or phenobarbital was 23.2 days. These results suggest that secretin therapy may be an effective treatment for intrahepatic cholestasis.

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.

THERAPEUTIC EFFECT OF SECRETIN IN PATIENTS WITH JAUNDICE ; DOUBLE-BLIND PLACEBO-CONTROLLED MULTICENTRIC TRIAL

Secretin, a gastrointestinal hormone, has been shown to have a potent choleretic effect. Having already obtained some beneficial effects with secretin in patients with intrahepatic cholestasis, we sought to confirm its effects in a double-blind placebo-controlled study in patients with mild jaundice after acute or during chronic hepatitis, where total bilirubin level was in excess of 4.0 mg/dl for 3 days or more. Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and familiar hyperbilirubinemia were excluded from the study. Ninety-three patients were included in this analysis, but the final evaluation covered 69 of them. No statisticaly significant differences were found in the reduction of serum bilirubin levels between secretin and placebo groups. As a number of patients with liver cirrhosis had been included, the subjects were subdivided into one group with cholestasis in hepatitis and one with liver cirrhosis. In the subgroup of cirrhotic patients who received secretin, serum levels of AST were significantly increased compared with the placebo group. However, since the choleretic effect of secretin is unique, further studies seem to be warranted.

Relationship of serum 2.5 oligoadenylate synthetase activity during interferon therapy to pretreatment levels or genotypes of serum HCV-RNA

Abstract 2.5 oligoadenylate synthetase (2.5AS) activity is induced during interferon (IFN) therapy of patients with chronic hepatitis C. It is assumed that the genotype and quantitative level of hepatitis C virus RNA (HCV-RNA) in serum preceding IFN therapy are closely associated with the response to IFN. However, it is not clear whether these viral factors may affect 2.5AS activity during IFN therapy. We analyzed 2.5AS activity during IFN therapy in patients with different genotypes or levels of serum HCV-RNA. However, there were no statistical differences es in 2.5AS activity among them. In the present study, those viral factors were not associated with the induction of 2.5AS activity during IFN therapy, and it is unlikely that differences in response to IFN among patients with different genotypes or quantitative levels of HCV-RNA depend on the 2.5AS pathway.