METHODS： Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled, Liver stiffness was obtained noninvasively by using Fibroscan （Echosen...METHODS： Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled, Liver stiffness was obtained noninvasively by using Fibroscan （Echosens, Paris, France）, The date of blood transfusion was obtained by interview, Duration of infection was derived from the interval between the date of bloodtransfusion and the date of liver stiffness measurement （LSM）. Patients were stratified into four groups based on the duration of infection （17-29 years; 30-39 years; 40-49 years; and 50-70 years）. The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness.RESULTS： A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis （225 with HCC and 291 without）. The patients were 244 men and 272 women, with a mean age of 67.8 ±9.5 years. The median liver stiffness was 14.3 kPa （25.8 in HCC group and 7.6 in non HCC group）. The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC （r = 0.132, P = 0.024） but not in patients with HCC （r = -0.103, P = 0.123）. Liver stiffness was significantly higher in patients with HCC than in those without in each duration group （P 〈 0.0001）. The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion （P 〈 0.0001）, duration of infection （P = 0.0015）, and heavy alcohol consumption （P = 0.043）CONCLUSION： Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.展开更多
AIM: To determine fibrosis progression and hepatocellular carcinoma (HCC), using simultaneous gene expression analysis. METHODS: Total RNA samples were extracted from liver biopsies from 19 patients with hepatitis C v...AIM: To determine fibrosis progression and hepatocellular carcinoma (HCC), using simultaneous gene expression analysis. METHODS: Total RNA samples were extracted from liver biopsies from 19 patients with hepatitis C virus (HCV) infection and 3 patients without HCV infection. Among the 19 HCV-infected patients, 7 and 12 patients had grade Fl-2 and F3-4 fibrosis, respectively. Of the 12 patients with F3-4 fibrosis, 8 had HCC. Gene expression in the liver samples was determined using an oligonucleotide microarray. The following comparisons were performed: normal livers vs HCV-infected livers; F1-2 vs F3-4; and F3-4 with HCC vs F3-4 without HCC. Genes that were differentially expressed between these groups were identified based on signal-to-noise ratios. RESULTS: In the HCV-infected livers, genes involved in immune responses were highly expressed. Expression levels of genes for plasma proteins and drug-metabolizing enzymes were decreased and those of genes involved in the cell cycle and oncogenesis were increased in the F3-4 cases as compared to the F1-2 cases. Among the F3-4 cases, genes involved in carbohydrate metabolism tended to be more highly expressed in patients with HCC than in patients without HCC. CONCLUSION: We identified genes that are associated with fibrosis progression and hepatocarcinogenesis. This information may be used to detect increased carcinogenic potential in the livers of patients with HCV infection.展开更多
A 42-year-old Japanese man with liver cirrhosis by hepatitis C virus (HCV) had successful interferon therapy in May 1991. Since then, serum HCV-RNA and liver function tests had been negative. He had continued to drink...A 42-year-old Japanese man with liver cirrhosis by hepatitis C virus (HCV) had successful interferon therapy in May 1991. Since then, serum HCV-RNA and liver function tests had been negative. He had continued to drink more than 100 g/d of alcohol as before. In June 2003, a 5-cm tumor was found in the posterior segment of the liver. The tumor was curatively resected and the surgical specimen showed a well-differentiated hepatocellular carcinoma (HCC). Non-cancerous lesions of the liver revealed fibrosis at stage F3 with minimal to mild inflammation of grade A1. Heavy drinking may retard the dissolution of fibrosis and accelerate HCC development in patients with sustained virological response.展开更多
文摘METHODS： Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled, Liver stiffness was obtained noninvasively by using Fibroscan （Echosens, Paris, France）, The date of blood transfusion was obtained by interview, Duration of infection was derived from the interval between the date of bloodtransfusion and the date of liver stiffness measurement （LSM）. Patients were stratified into four groups based on the duration of infection （17-29 years; 30-39 years; 40-49 years; and 50-70 years）. The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness.RESULTS： A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis （225 with HCC and 291 without）. The patients were 244 men and 272 women, with a mean age of 67.8 ±9.5 years. The median liver stiffness was 14.3 kPa （25.8 in HCC group and 7.6 in non HCC group）. The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC （r = 0.132, P = 0.024） but not in patients with HCC （r = -0.103, P = 0.123）. Liver stiffness was significantly higher in patients with HCC than in those without in each duration group （P 〈 0.0001）. The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion （P 〈 0.0001）, duration of infection （P = 0.0015）, and heavy alcohol consumption （P = 0.043）CONCLUSION： Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.
基金Supported by the Nishi Cancer Research Fund and by grants-inaid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of JapanResearch Grants for Research on Hepatitis from the Ministry of Health, Labour and Welfare, Japan
文摘AIM: To determine fibrosis progression and hepatocellular carcinoma (HCC), using simultaneous gene expression analysis. METHODS: Total RNA samples were extracted from liver biopsies from 19 patients with hepatitis C virus (HCV) infection and 3 patients without HCV infection. Among the 19 HCV-infected patients, 7 and 12 patients had grade Fl-2 and F3-4 fibrosis, respectively. Of the 12 patients with F3-4 fibrosis, 8 had HCC. Gene expression in the liver samples was determined using an oligonucleotide microarray. The following comparisons were performed: normal livers vs HCV-infected livers; F1-2 vs F3-4; and F3-4 with HCC vs F3-4 without HCC. Genes that were differentially expressed between these groups were identified based on signal-to-noise ratios. RESULTS: In the HCV-infected livers, genes involved in immune responses were highly expressed. Expression levels of genes for plasma proteins and drug-metabolizing enzymes were decreased and those of genes involved in the cell cycle and oncogenesis were increased in the F3-4 cases as compared to the F1-2 cases. Among the F3-4 cases, genes involved in carbohydrate metabolism tended to be more highly expressed in patients with HCC than in patients without HCC. CONCLUSION: We identified genes that are associated with fibrosis progression and hepatocarcinogenesis. This information may be used to detect increased carcinogenic potential in the livers of patients with HCV infection.
文摘A 42-year-old Japanese man with liver cirrhosis by hepatitis C virus (HCV) had successful interferon therapy in May 1991. Since then, serum HCV-RNA and liver function tests had been negative. He had continued to drink more than 100 g/d of alcohol as before. In June 2003, a 5-cm tumor was found in the posterior segment of the liver. The tumor was curatively resected and the surgical specimen showed a well-differentiated hepatocellular carcinoma (HCC). Non-cancerous lesions of the liver revealed fibrosis at stage F3 with minimal to mild inflammation of grade A1. Heavy drinking may retard the dissolution of fibrosis and accelerate HCC development in patients with sustained virological response.
