Haruyuki Hayashi

Mode of hepatitis C infection not associated with blood transfusion among chronic hemodialysis patients.

In a retrospective study carried out on about 730 patients with chronic renal failure who underwent ambulatory hemodialysis from January 1991 to June 1994, 49 patients were found to have developed acute hepatitis C, as confirmed by seroconversion for anti-HCV antibodies without blood transfusion in the preceding 6-month period. Epidemiological survey disclosed that two patients undergoing dialysis at consoles separated by one console developed acute hepatitis C in October 1992, and another three patients at adjacent consoles also developed acute hepatitis C within 2 weeks in April/May, 1993. It was found that some negligent nurses could have withdrawn needles from these patients one after another without changing gloves at the termination of the dialysis procedure. After reeducation of the staff members and introduction of a new type of adhesive pad to be placed on the needle wounds at the time of needle withdrawal, no new case of acute hepatitis C occurred for more than 1 year, suggesting nosocomial spread of HCV infection among hemodialysis patients in a mode that is preventable with very strict aseptic precautions.

EFFECTS OF COMBINATION TREATMENT WITH FK506 AND CYCLOSPORINE ON SURVIVAL TIME AND VASCULAR CHANGES IN RENAL-ALLOGRAFT-RECIPIENT DOGS

In our previous experiments studying the effects of FK506 on renal allografting in the dog, we encountered two major problems. One problem was anorexia and the other problem was vascular changes mainly in the recipient heart. Anorexia was generally dose dependent, but the vascular changes were seen to be more prominent at lower doses rather than at higher immunosuppressive doses. The present study was undertaken to study these two problems. A nonanorexic, vascular change-related, nonimmunosuppressive dose of FK506 was combined with a low dose of cyclosporine or prednisolone in beagle dogs after renal allografting. Treatment with either FK506 alone at a dose of 0.32 mg/kg or cyclosporine alone at 2.5 mg/kg was not effective in prolonging renal recipient survival. The recipient dogs died of rejection, and a variety of vascular changes were observed in the hearts of both groups. Combined treatment with FK506 and cyclosporine at these same doses resulted in statistically significant prolongation of the survival time of the renal recipient (P less than 0.01), and histologic studies showed that the frequency and severity of the vascular changes were suppressed in the recipient receiving the combined treatment. The combination of FK506 and prednisolone at 0.5 mg/kg was not effective in prolonging survival. Furthermore, the extent of vascular changes was similar to those found in recipients receiving FK506 alone. The data suggest that combined treatment with low doses of both FK506 and cyclosporine acted synergistically in prolonging canine renal allografts and that the vascular changes frequently seen at low doses of FK506 were reduced by additional immunosuppression with a low dose of cyclosporine.

Expression of c‐myc oncogene in colorectal polyps as a biological marker for monitoring malignant potential

The expression of oncogenes (c‐myc, c‐fos, c‐Ki‐ras, c‐Ha‐ras, and p53) was examined by Northern blot analysis using freshly isolated human colorectal and gastric cancers and noncancerous portions as the controls. Remarkably high levels of c‐myc expression were found in colorectal cancers (eight of 11), but not in gastric cancers. High levels of c‐myc expression were also detected in colorectal polyps and in metastatic liver tumors. In colorectal polyps, the transcript levels significantly correlated with the histologic malignancy and the size. In contrast, neither c‐fos nor c‐Ki‐ras was overexpressed in colorectal and gastric cancers, and transcripts of c‐Ha‐ras and p53 were not evident in any tissue examined. In light of these observations the c‐myc expression may be specifically associated with the evolution of colorectal cancer as well as progression and maintenance stages, hence may prove to be a useful marker to evaluate the malignant potential of colorectal polyps.

Hepatitis C infection unrelated to blood transfusion in hemodialysis patients

Hepatitis C virus antibodies were studied using both the 1st and 2nd generation tests in 485 patients who were on maintenance hemodialysis. One hundred and eighty-seven tested positive for antibodies (38.6%); 139 of them had a history of past blood transfusion. There was a crude correlation between the amount of blood given and the antibody positivity rate among those who had a history of blood transfusion. Of 152 patients who had no blood transfusion history, 48 or 31.2% were positive for the antibodies. The length of the period during which these patients had undergone dialysis was closely correlated with the positivity rate; 50% of those who had been on dialysis for more than 10 years were positive for anti-HCV. The positivity rate among the new dialysis patients with chronic renal failure as the control was 4.6%. The difference may be accounted for by nosocomial hepatitis C virus infection. It appears that with two new needle holes made along the anastomosed blood vessels two to three times a week, the chances of patient exposure to hepatitis C virus may increase with time.

Interferon treatment for chronic hepatitis C in haemodialysis patients: Suggestions based on a small series

Chronic hepatitis C is endemic among chronic haemodialysis patients. There have been a number of reports on hepatocellular carcinoma developing in such patients in Japan. The present study reports on the treatment of 15 patients who showed elevated ALT levels due to biopsy proven chronic hepatitis C with interferon α‐2a (IFN). The dose schedule was 6 mega units (MU) daily for the first two weeks followed by 3 doses per week for 5.5 months. Side effects were so severe that IFN treatment was discontinued early in one patient, the dosage reduced in 11 and only tolerated in the original schedule by three patients. Excluding one patient who only recently completed the therapy, 13 were able to be evaluated for therapy efficacy by assessment of serum ALT and viral RNA. The overall results showed that IFN was effective in eight of 13 patients, a rate somewhat higher than the reported figures in this country. It is concluded that IFN therapy is indicated in haemodialysis patients with progressive chronic hepatitis C, but the dose administered should be lower and the dose schedule more flexible, perhaps 3 MU three times a week, in order to minimize untoward side effects.

Acute hepatitis C among renal failure patients on chronic haemodialysis

Hepatitis C virus (HCV) infection is common in haemodialysis units, yet little information is available about the clinical feature of acute hepatitis C among renal failure patients. The present study is based on 49 cases of acute hepatitis C seen at a haemodialysis centre where sporadic nosocomial infection was occurring up to June 1993. Liver function tests were done at 4 weekly intervals on all dialysis patients, anti‐HCV antibodies were tested by the C‐100 and second generation tests and serum HCV‐RNA was determined by the branched DNA and Amplicore tests. Diagnosis of acute hepatitis C was made on the basis of an acute rise in alanine aminotransferase (ALT) and seroconversion to positive anti‐HCV antibodies. Clinical presentation of acute hepatitis was generally mild with rare overt jaundice and the diagnosis was possible only from increased ALT, which was generally low. Spontaneous resolution of acute hepatitis within 8 months with clearance of viral RNA occurred in only four cases, 91.8% of patients developing chronic hepatitis. Biopsy in 12 cases with high ALT levels showed mild to moderate inflammatory activities. In conclusion, the clinical presentation of acute hepatitis C is generally mild in chronic haemodialysis patients, but spontaneous resolution is infrequent. A longer follow‐up period is required for defining the long‐term prognosis.

Depression of liver-specific gene expression in regenerating rat liver: A putative cause for liver dysfunction after hepatectomy

We carried out studies on the expression of liver-specific genes during regeneration of the liver and searched for changes in the expression of oncogenes and housekeeping genes. Albumin and ornithine transcarbamylase genes were the liver-specific genes examined by Northern blot analysis, using total RNAs isolated from residual livers of Sprague-Dawley rats subjected to a 68% partial hepatectomy. The mRNA levels of both genes began to decrease 8 hr after hepatectomy, both reaching the lowest levels at 24 hr, and then recovered to some extent at 48 hr. In contrast, these levels in the housekeeping and growth-related genes were augmented during this period. This would suggest that there is a selective expression of growth-related and housekeeping genes, in preference to liver-specific genes during liver regeneration. The expression of these genes in the regenerating liver was simulated in primary cultured hepatocytes during the dedifferentiation processes. It would appear that the first step in regeneration of the residual liver is dedifferentiation, in which the depression of liver-specific genes may be linked to liver dysfunction following hepatectomy.

Detection of minus-strand hepatitis C virus RNA in tumor tissues of hepatocellular carcinoma.

Background. Recently, the detection of hepatitis C virus (HCV) antibody has been widely performed for clinical serum testing of HCV infection and can be identified in most hepatocellular carcinoma (HCC) cases in Japan. In the current study, the authors detected not only plus‐strand but also minus‐strand HCV RNA as a template for RNA replication in hepatocytes in the resected tumors of HCC, and they investigated those significant for HCC.

Case–control study of calcification of the hepatic artery in chronic hemodialysis patients: Comparison with the abdominal aorta and splenic artery

Background and Aims: Studies of the hepatic artery are scarce. We have observed that hepatic artery calcification is very uncommon in patients with hyperparathyroidism that expedites calcification.

P21WAF1/CIP1 messenger RNA expression in hepatitis B, C virus-infected human hepatocellular carcinoma tissues.

The primary objective of this study was to clarify the significance of p21WAF1/CIP1(p21) gene expression in the tumorgenicity of hepatitis B virus (HBV) and hepatitis C virus (HCV) infected human hepatocelluar carcinoma (HCC).