Patient H is an American patient who was infected with hepatitis C virus (HCV) in 1977. The patient became chronically infected and has remained so for the past 13 years. In this study, we compared the nucleotide and predicted amino acid sequences of the HCV genome obtained from plasma collected in 1977 with that collected in 1990. We find that the two HCV isolates differ at 123 of the 4923 (2.50%) nucleotides sequenced. We estimate that the mutation rate of the H strain of HCV is -1.92 x 10-3 base substitutions per genome site per year. The nucleotide changes were exclusively base substitutions and were unevenly distributed throughout the genome. A relatively high rate of change was observed in the region of the HCV genome that corresponds to the nonstructural protein 1 gene region of flaviviruses, where 44 of 960 (4.6%) nucleotides were different. Within this region there was a 39-nucleotide domain in which 28.2% of the nucleotides differed between the two isolates. In contrast, relatively few nucleotide substitutions were observed in the 5' noncoding region, where only 2 of 276 (0.7%) nucleotides were different. Our results suggest that the mutation rate of the HCV genome is similar to that of other RNA viruses and that genes appear to be evolving at different rates within the virus genome.
Some individuals infected with hepatitis C virus (HCV) experience multiple episodes of acute hepatitis. It is unclear whether these episodes are due to reinfection with HCV or to reactivation of the original virus infection. Markers of viral replication and host immunity were studied in five chimpanzees sequentially inoculated over a period of 3 years with different HCV strains of proven infectivity. Each rechallenge of a convalescent chimpanzee with the same or a different HCV strain resulted in the reappearance of viremia, which was due to infection with the subsequent challenge virus. The evidence indicates that HCV infection does not elicit protective immunity against reinfection with homologous or heterologous strains, which raises concerns for the development of effective vaccines against HCV.
BACKGROUND Compared with other treatments, microwave coagulation is a relatively less invasive treatment for various kinds of solid tumors. Although its effectiveness in primary hepatocellular carcinoma has been shown, its effectiveness in the treatment of hepatic metastases from colorectal carcinoma has been unclear. The aim of this study was to evaluate its effectiveness in the treatment of multiple hepatic metastases from colorectal carcinoma by comparing this technique with that of hepatic resection. METHODS Thirty patients with multiple metastatic colorectal tumors in the liver who were potentially amenable to hepatic resection were randomly assigned to treatment with microwave coagulation (14 patients) or hepatectomy (16 patients). Tumors in the microwave group were coagulated after laparotomy at an output of 60–100 W for 2–20 minutes under the guide of ultrasonography, whereas tumors in the hepatectomy group were treated with lobectomy, segmentectomy, subsegmentectomy, and/or wedge resection. RESULTS One‐, 2‐, and 3‐year survival rates and mean survival times were 71%, 57%, 14%, and 27 months, respectively, in the microwave group, whereas they were 69%, 56%, 23%, and 25 months, respectively, in the hepatectomy group. The difference between these two groups was statistically not significant (P = 0.83). On the other hand, the amount of intraoperative blood loss in the microwave group (360 ± 230 mL) was smaller than that in the hepatectomy group (910 ± 490 mL, P < 0.05). Blood transfusion was necessary for 6 patients in the hepatectomy group, but it was not necessary in the microwave group. CONCLUSIONS Microwave coagulation therapy is suggested to be equally effective as hepatic resection in the treatment of multiple (two to nine) hepatic metastases from colorectal carcinoma, whereas its surgical invasiveness is less than that of hepatic resection. Cancer 2000;89:276–84. © 2000 American Cancer Society.
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