Hepatitis: Tateishi R

Anonymous00371, McCaughan GW, Omata M, Amarapurkar D, Bowden S, Chow WC, Chutaputti A, Dore G, Gane E, Guan R, Hamid SS, Hardikar W, Hui CK, Jafri W, Jia JD, Lai MY, Wei L, Leung N, Piratvisuth T, Sarin S, Sollano J, Tateishi R. · Centenary Research Institute, AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, NSW 2006, Australia. · J Gastroenterol Hepatol. · Pubmed #17444847 No free full text.

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Masuzaki R, Yoshida H, Tateishi R, Shiina S, Omata M. · Department of Gastroenterology, University of Tokyo, Bunkyo-ku, Tokyo, Japan. · Best Pract Res Clin Gastroenterol. · Pubmed #19187872 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is a common malignancy worldwide, and its incidence is increasing in the United States and elsewhere. The prognosis of HCC patients depends not only on tumour stage but also on the background liver function reservoir. Current options for the treatment of HCC are surgical resection, liver transplantation, transcatheter arterial embolization, chemotherapy, and percutaneous ablation therapy. The choice of optimal treatment for individual patients, especially those at an earlier cancer stage, is sometimes controversial. Short-term prognosis of HCC patients has been much improved recently due to advances in early diagnosis and treatment, although long-term prognosis is as yet far from satisfactory as indicated by the overall survival at 10 years after apparently curative treatment of only 22-35%. Prevention of HCC recurrence, or tertiary prevention, is one of the most challenging tasks in current hepatology.

Tateishi R, Yoshida H, Omata M. · Department of Gastroenterology, University of Tokyo. · Nippon Rinsho. · Pubmed #15359865 No free full text.

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Kondo Y, Tateishi R, Yoshida H, Omata M. · Department of Gastroenterology, University of Tokyo. · Nippon Rinsho. · Pubmed #15359853 No free full text.

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Tanaka Y, Takayanagi M, Shiratori Y, Imai Y, Obi S, Tateishi R, Kanda M, Fujishima T, Akamatsu M, Koike Y, Hamamura K, Teratani T, Ishikawa T, Shiina S, Kojiro M, Omata M. · Department of Gastroenterology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. · J Gastroenterol. · Pubmed #12673454 No free full text.

Abstract: Congenital absence of the portal vein is an extremely rare anomaly, in which enteric blood bypasses the liver and drains into the inferior vena cava. A 16-year-old girl was referred to our hospital presenting with liver tumor. Although she had suffered from galactosemia soon after birth, the galactosemia had improved spontaneously 1 year later. Between the ages of 8 and 12 years, chronic hepatitis with a mild elevation of aspartate transaminase (AST) and alanine transaminase (ALT) was observed, but liver tumor had not been detected on computed tomography (CT) in regular medical examinations. However, at age 16, liver tumors, 10 cm in diameter, were found. Abdominal angiography indicated complete absence of the portal vein, suggesting that enteric blood was bypassing the liver and draining into the inferior vena cava. In biopsy specimens obtained under ultrasonographic guidance, liver tumors were confirmed histologically as hyperplastic nodules. In addition to this case report, the clinical features of 25 reported cases of congenital absence of the portal vein are reviewed.

Masuzaki R, Tateishi R, Yoshida H, Goto E, Sato T, Ohki T, Imamura J, Goto T, Kanai F, Kato N, Ikeda H, Shiina S, Kawabe T, Omata M. · Department of Gastroenterology, University of Tokyo, Tokyo, Japan. · Hepatology. · Pubmed #19434742 No free full text.

Abstract: Liver stiffness, noninvasively measured by transient elastography, correlates well with liver fibrosis stage. The aim of this prospective study was to evaluate the liver stiffness measurement (LSM) as a predictor of hepatocellular carcinoma (HCC) development among patients with chronic hepatitis C. Between December 2004 and June 2005, a total of 984 HCV-RNA positive patients, without HCC or a past history of it, visited the University of Tokyo Hospital. LSM was performed successfully in 866 patients, who gave informed consent. During the follow-up period (mean, 3.0 years), HCC developed in 77 patients (2.9% per 1 person-year). The cumulative incidence rates of HCC at 1, 2, and 3 years were 2.4%, 6.0%, and 8.9%, respectively. Adjusting for other significant factors for HCC development, patients with higher LSM were revealed to be at a significantly higher risk, with a hazard ratio, as compared to LSM < or =10 kPa, of 16.7 (95% confidence interval [CI], 3.71-75.2; P < 0.001) when LSM 10.1-15 kPa, 20.9 (95% CI, 4.43-98.8; P < 0.001) when LSM 15.1-20 kPa, 25.6 (95%CI, 5.21-126.1; P < 0.001) when LSM 20.1-25 kPa, and 45.5 (95% CI, 9.75-212.3; P < 0.001) when LSM >25 kPa. CONCLUSIONS: This prospective study has shown the association between LSM and the risk of HCC development in patients with hepatitis C. The utility of LSM is not limited to a surrogate for liver biopsy but can be applied as an indicator of the wide range of the risk of HCC development.

Ohki T, Tateishi R, Shiina S, Goto E, Sato T, Nakagawa H, Masuzaki R, Goto T, Hamamura K, Kanai F, Yoshida H, Kawabe T, Omata M. · Department of Gastroenterology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. · Gut. · Pubmed #19174415 No free full text.

Abstract: BACKGROUND AND AIMS: Visceral fat accumulation reportedly increases the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. However, it has not been fully elucidated whether visceral fat accumulation increases the risk of HCC recurrence after curative treatment in patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was investigated in the current study. METHODS: 62 patients with naive HCC with suspected NASH were enrolled. All were curatively treated with percutaneous radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was determined in each patient from CT images, taken at the time of HCC diagnosis. Patients were divided into two groups based on VFA: the high VFA group (>130 cm(2) in males, >90 cm(2) in females, n = 27) and the others (n = 35). The effects of VFA on HCC recurrence were analysed together with other factors including patients' background, tumour-related factors and liver function-related factors. RESULTS: The cumulative recurrence rates differed significantly between the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p = 0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio 1.08, per 10 cm(2), p = 0.046) and older age (risk ratio 1.06 per 1 year, p = 0.04) as independent risk factors of HCC recurrence. CONCLUSIONS: Visceral fat accumulation is an independent risk factor of HCC recurrence after curative treatment in patients with suspected NASH.

Masuzaki R, Tateishi R, Yoshida H, Goto E, Sato T, Ohki T, Goto T, Yoshida H, Kanai F, Sugioka Y, Ikeda H, Shiina S, Kawabe T, Omata M. · Department of Gastroenterology, University of Tokyo, Bunkyo-ku, Tokyo, Japan. · Can J Gastroenterol. · Pubmed #18818788 No free full text.

Abstract: BACKGROUND: Liver stiffness measurement (LSM) by transient elastography has recently been validated for the evaluation of liver fibrosis in chronic liver diseases. The present study focused on cases in which liver biopsy and LSM were discordant. METHODS: Three hundred eighty-six patients with chronic hepatitis C who underwent a liver biopsy between December 2004 and April 2007 were studied. First, the optimal cut-off value of LSM was selected for the determination of cirrhosis based on the receiver operating characteristic curve. Then, the cases in which liver histology and evaluation by LSM were discordant were selected. Laboratory test results such as serum total bilirubin concentration, prothrombin activity, albumin concentration, platelet count and the aspartate aminotransferase to platelet ratio index, together with the presence of esophageal varices, were analyzed. RESULTS: The optimal cut-off value was chosen to be 15.9 kPa for cirrhosis (fibrosis stage [F] 4) determination to maximize the sum of sensitivity (78.9%) and specificity (81.0%). There were 78 discordant cases: 51 patients showed an LSM of 15.9 kPa or higher and a fibrosis stage of F1 to F3 (high LSM group), and 27 patients had an LSM lower than 15.9 kPa and a fibrosis stage of F4 (low LSM group). Esophageal varices were seen in 11 patients in the high LSM group (n=51) and in no patients in the low LSM group (n=27) (P=0.0012). The aspartate aminotransferase to platelet ratio index was significantly higher in the high LSM group (1.49 versus 0.89, P=0.019). Other parameters did not differ significantly. However, platelet count, prothrombin activity and albumin concentration tended to be lower in the high LSM group. CONCLUSIONS: Patients with a high LSM need proper attention for cirrhosis, even if liver biopsy does not reveal cirrhosis.

Kanda M, Tateishi R, Yoshida H, Sato T, Masuzaki R, Ohki T, Imamura J, Goto T, Yoshida H, Hamamura K, Obi S, Kanai F, Shiina S, Omata M. · Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan. · Liver Int. · Pubmed #18710423 No free full text.

Abstract: BACKGROUND: Extrahepatic metastasis of hepatocellular carcinoma (HCC) is of growing importance as the survival of patients has been improved owing to advances in treatments to intrahepatic lesions. METHODS: To elucidate the incidence and risk factors of extrahepatic metastasis of HCC, we enrolled 1573 (1131 treatment-naïve and 442 previously treated on referral) patients with HCC without extrahepatic tumour spread treated at the authors' department between 1990 and 2003. Patients received medical treatment including percutaneous ablation and transcatheter arterial chemoembolization, and followed by dynamic computed tomography (CT) or magnetic resonance imaging (MRI) and tumour markers every 3-4 months. Extrahepatic metastasis was diagnosed by plain X-ray, CT, MRI and scintigraphy. Clinical parameters at the time of treatment to intrahepatic lesions were evaluated as a predictor of subsequent extrahepatic metastasis among the 1131 treatment-naïve patients by Cox's proportional hazard model. RESULTS: During the average observation period of 3.9 years, extrahepatic metastasis was diagnosed in 123 in the treatment-naïve and 53 in the patients treated previously. The incidence rate of extrahepatic metastasis, as detected during the lifetime after medical treatment of HCC, was approximately 13% at 5 years. Multivariate analysis with Cox proportional hazard model revealed that positivity for viral markers, lager tumour diameter, multiple tumour nodules, presence of vascular tumour invasion and elevated tumour markers were associated with the development of extrahepatic metastasis. CONCLUSION: The incidence of extrahepatic metastasis of HCC diagnosed during clinical course was not frequent. Advanced intrahepatic lesions, presence of vascular tumour invasion, elevated tumour markers and presence of viral hepatitis were risk factors for extrahepatic metastasis.

Masuzaki R, Tateishi R, Yoshida H, Yoshida H, Sato S, Kato N, Kanai F, Sugioka Y, Ikeda H, Shiina S, Kawabe T, Omata M. · Department of Gastroenterology, The University of Tokyo Hospital, Tokyo, Japan. · J Clin Gastroenterol. · Pubmed #18668703 No free full text.

Abstract: OBJECTIVE: The degree of liver fibrosis is the strongest indicator of risk for hepatocellular carcinoma (HCC) development. Recently developed transient elastography (Fibroscan, Echosens, France) noninvasively measures liver stiffness, and the correlation between the stiffness and liver fibrosis stage has been validated. In this cross-sectional study, we investigated the relationship between liver stiffness and HCC presence. METHODS: Liver stiffness was measured in chronic hepatitis C patients (85 with HCC and 180 without) by transient elastography. Multivariate logistic regression was applied to assess the association with HCC presence. We computed the receiver operating characteristics (ROC) curves concerning the prediction of HCC presence and compared the areas under ROC curve (AUROC). We also calculated stratum-specific likelihood ratios (SSLR). RESULTS: Multivariate analysis showed that HCC presence was significantly associated with liver stiffness (P<0.0001) along with age, male, and alpha-fetoprotein concentration. AUROC was 0.805, 0.741, 0.714, 0.673, 0.670, and 0.654 for liver stiffness, alpha-fetoprotein, albumin, prothrombin activity, AST-platelet ratio index, and platelet count, respectively. Other parameters showed smaller AUROC. SSLR for HCC presence by liver stiffness was 0.22 (95% confidence interval: 0.11-0.42) in <10 kPa, 0.73 (0.39 to 1.39) in 10.1 to 15 kPa, 1.30 (0.80 to 2.12) in 15.1 to 25 kPa, and 5.0 (2.96 to 8.47) in >25 kPa. CONCLUSIONS: Liver stiffness measured by transient elastography is useful in demarcating chronic hepatitis C patients at a high risk for HCC, who require frequent check-up by imaging examinations.

Ohki T, Tateishi R, Sato T, Masuzaki R, Imamura J, Goto T, Yamashiki N, Yoshida H, Kanai F, Kato N, Shiina S, Yoshida H, Kawabe T, Omata M. · Department of Gastroenterology, University of Tokyo, Hongo, Tokyo, Japan. · Clin Gastroenterol Hepatol. · Pubmed #18387499 No free full text.

Abstract: BACKGROUND & AIMS: It is not fully elucidated whether obesity enhances hepatocarcinogenesis in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between body weight and risk of hepatocarcinogenesis in chronic hepatitis C patients. METHODS: We enrolled 1431 patients with chronic hepatitis C who visited our liver clinic between 1994 and 2004, excluding those with hepatocellular carcinoma (HCC) at their visit or with a previous history of HCC. They were divided into 4 groups according to body mass index (BMI): underweight (< or =18.5 kg/m(2), N = 112); normal (18.5 to less than 25 kg/m(2), N = 1023); overweight (25 to less than 30 kg/m(2), N = 265); and obese (>30 kg/m(2), N = 31). We assessed the impact of obesity on the hepatocarcinogenesis adjusted by multivariate Cox proportional hazard regression with other risk factors found significant in univariate analysis. RESULTS: During the follow-up period (mean, 6.1 y), HCC developed in 340 patients, showing cumulative incidence rates of 10.5%, 19.7%, and 36.8% at 3, 5, and 10 years, respectively. The incidence differed significantly among the BMI groups (P = .007). Adjusting for other significant factors, overweight and obesity were shown to be an independent risk factor of HCC, with a hazard ratio of 1.86 (95% confidence interval, 1.09-3.16; P = .022) and 3.10 (95% confidence interval, 1.41-6.81; P = .005) as compared with the underweight patients. CONCLUSIONS: The risk of HCC in patients with chronic hepatitis C increases in proportion to BMI in a wide range of its values, from underweight to obese.

Ibukuro K, Sugihara T, Tanaka R, Fukuda H, Abe S, Tobe K, Tateishi R, Tagawa K. · Department of Radiology, Mitsui Memorial Hospital, Tokyo, Japan. · J Vasc Interv Radiol. · Pubmed #17296712 No free full text.

Abstract: A direct shunt between the inferior mesenteric vein and the inferior vena cava was detected in a patient with hepatic encephalopathy. The authors performed balloon-occluded retrograde transvenous obliteration (BRTO) for this shunt. Before the obliteration, the shunt was occluded by using a balloon catheter and it was confirmed that the portal venous flow was redirected to the liver. The encephalopathy disappeared immediately after BRTO. The improvement of the liver function, the disappearance of the shunt, and the increase in the size of the portal vein and liver volume were confirmed at computed tomography performed 5 months after treatment.

Kondo Y, Yoshida H, Tateishi R, Shiina S, Mine N, Yamashiki N, Sato S, Kato N, Kanai F, Yanase M, Yoshida H, Akamatsu M, Teratani T, Kawabe T, Omata M. · Department of Gastroenterology, University of Tokyo, Tokyo, Japan. · J Gastroenterol Hepatol. · Pubmed #17295871 No free full text.

Abstract: BACKGROUND AND AIM: Impaired health-related quality of life has been reported in patients with cirrhosis and chronic hepatitis. However, only limited data are available concerning the influence of hepatocellular carcinoma. METHODS: Health-related quality of life was assessed in 97 patients with hepatocellular carcinoma who had been treated successfully with percutaneous ablation therapy, and 97 patients with chronic liver disease without hepatocellular carcinoma matched for age and sex, using the Japanese version of Short-Form 36. Raw scores were transformed using norm-based scoring. The relations with objective variables including status of hepatocellular carcinoma and laboratory data were analyzed. RESULTS: Health-related quality of life was lower in both groups than in the general population. Patients with hepatocellular carcinoma and patients in the control group showed similar scores. By multivariate analysis, liver function, especially serum albumin, strongly predicted health-related quality of life, but status of hepatocellular carcinoma did not. CONCLUSIONS: Impaired health-related quality of life was not associated with the presence of hepatocellular carcinoma but dependent on the level of liver function, indicating the importance of preserving liver function in following up patients. Serum albumin level was a useful objective variable to assess health-related quality of life of patients with chronic liver disease.

Fujishima T, Ishikawa T, Shiratori Y, Kanda M, Tateishi R, Akamatsu M, Koike Y, Sato S, Obi S, Hamamura K, Teratani T, Shiina S, Yoshida H, Kawabe T, Omata M. · Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Japan. · Hepatogastroenterology. · Pubmed #17153452 No free full text.

Abstract: BACKGROUND/AIMS: It is not known whether the putative etiologic factors and clinical and pathological features of hepatocellular carcinoma differ between young adults and older patients. Therefore this study aims to evaluate whether the clinicopathological features in young patients with HCC significantly differ from those of elderly patients. METHODOLOGY: A total of 1014 consecutive patients with HCC were divided into two groups based on age. Among them, 73 patients younger than 50 years of age comprised the first group and 941 patients 50 years and older made up the second. Clinical, laboratory, and pathological characteristics were compared between the two age groups. RESULTS: The male: female ratio and the incidence of positive hepatitis B surface antigen were significantly higher in young patients than in elderly patients. Tumor size, pathological grading of the tumor, and the severity of liver disease did not differ between the two groups. Especially in those patients demonstrating positive antibody to hepatitis C virus, alanine aminotransferase was higher in the younger, and platelet count was lower. Younger patients also had a higher ratio of alcohol consumption compared to elderly patients. CONCLUSIONS: There were age-related differences in the clinicopathological characteristics of HCC patients. Concerning hepatocarcinogenesis, male and HBsAg positive patients were at high risk in young. Of the HCV-related HCC patients, heavy drinking may accelerate the progression from chronic hepatitis to cirrhosis and HCC.

Muroyama R, Kato N, Yoshida H, Otsuka M, Moriyama M, Wang Y, Shao RX, Dharel N, Tanaka Y, Ohta M, Tateishi R, Shiina S, Tatsukawa M, Fukai K, Imazeki F, Yokosuka O, Shiratori Y, Omata M. · Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. · J Hepatol. · Pubmed #17050029 No free full text.

Abstract: BACKGROUND/AIMS: The hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC). In addition, the HBV X gene, which encodes the pleiotropic transactivator HBx, has also been associated with the development of HCC. In this study, we investigated whether nucleotide changes in the X gene of genotype C are associated with the development of HCC. METHODS/RESULTS: We sequenced the X gene in age- and sex-matched 39 HBV-infected patients with HCC and 36 HBV-infected patients without HCC. A novel nucleotide change that resulted in a proline to serine substitution at codon 38 in HBx (codon-38 change) was preferentially found in patients with HCC. Then, sera were collected from a new group of age- and sex-matched 52 patients with HCC and 51 patients without HCC. In this cohort also, the codon-38 change was associated with HCC. Multiple logistic regression analysis showed the prevalence of the codon-38 change was significantly associated with HCC in all patients (P=0.001, odds ratio: 4.89). CONCLUSION: The codon-38 change in genotype C is an independent risk factor for the development of HCC and may serve as a useful molecular marker for predicting the clinical outcomes in patients infected with HBV.

Akamatsu M, Yoshida H, Shiina S, Teratani T, Obi S, Tateishi R, Mine N, Kondo Y, Kawabe T, Omata M. · Department of Gastroenterology, The University of Tokyo Hospital, Tokyo, Japan. · Liver Int. · Pubmed #16761997 No free full text.

Abstract: BACKGROUND: We conducted this retrospective study to evaluate the position of interferon therapy in the curative treatment of hepatitis C virus-associated hepatocellular carcinoma (HCC). METHODS: We compared overall and recurrence-free survival rates between 191 patients who received interferon therapy before HCC development (15 with sustained virologic response (SVR)), 53 who received interferon therapy after HCC ablation (17 with SVR), and 399 HCC patients with Child-Pugh class A liver function who did not receive interferon (controls). RESULTS: The overall survival rate in the controls was 82.4%, 53.2%, and 28.3% at 3, 6, and 9 years, respectively, whereas that in patients who developed HCC after achieving SVR was 93.3%, 93.3%, and 93.3%; those with HCC after non-SVR, 87.8%, 56.5%, and 35.8%; SVR after HCC, 100%, 87.5%, and 59.7%; and non-SVR after HCC, 94.3%, 70.9%, and 53.2%. Cox proportional hazard regression analysis revealed that the risk of death was significantly reduced in patients with HCC after SVR and those with SVR after HCC, with a risk ratio of 0.124 (95% confidence interval (95% CI): 0.017-0.890, P = 0.0378) and 0.388 (95% CI: 0.169-0.887, P = 0.0250), respectively, compared with the controls. Improved survival was attributable mainly to sustained liver function among patients with SVR, and recurrence-free survival did not differ significantly. CONCLUSION: Interferon therapies before and after HCC development were both significantly associated with prolonged survival when SVR was achieved.

Ito Y, Yamamoto N, Nakata R, Kato Y, Iori M, Sakai K, Takemura T, Tateishi R, Yoshida H, Kawabe T, Omata M. · Department of Endoscopy, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. · World J Gastroenterol. · Pubmed #16437676 links to  free full text

Abstract: 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.

Fujishima T, Yoshida H, Obi S, Shiina S, Kanda M, Tateishi R, Akamatsu M, Koike Y, Sato S, Teratani T, Kawabe T, Shiratori Y, Omata M. · Department of Gastroenterology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. · J Gastroenterol. · Pubmed #15830286 No free full text.

Abstract: BACKGROUND: This study was performed to investigate the situations in which computed tomography (CT) combined with arterial portography and hepatic arteriography surpassed dynamic CT in the detection of hepatocellular carcinoma. METHODS: Computed tomography combined with arterial portography and hepatic arteriography was performed on 137 patients with chronic hepatitis (92 men and 45 women; mean age, 66.5 years) with hepatocellular carcinoma (HCC) as revealed or suspected by dynamic CT. We analyzed the clinical factors leading to the discovery of additional HCC lesions on CT combined with arterial portography and hepatic arteriography that were undetected by dynamic CT. RESULTS: Computed tomography combined with arterial portography and hepatic arteriography detected additional HCC lesions that had not been revealed by dynamic CT in 33 of 137 patients. Univariate analysis revealed that in the event of HCC recurrence (vs. primary), multiple HCC lesions detected by dynamic CT (vs. single) and decreased liver function (Child's classification B/C vs. A) significantly favored the additional detection of HCC lesions. Multivariate logistic regression indicated that recurrence was the strongest predicting factor for finding additional lesions on computed tomography combined with arterial portography and hepatic arteriography. CONCLUSIONS: Computed tomography combined with arterial portography and hepatic arteriography is capable of finding additional HCC lesions undetectable by dynamic CT, especially in advanced cases such as HCC recurrence, which may affect the choice of treatment.

Shao RX, Hoshida Y, Otsuka M, Kato N, Tateishi R, Teratani T, Shiina S, Taniguchi H, Moriyama M, Kawabe T, Omata M. · Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Tokyo 113-8655, Japan. · World J Gastroenterol. · Pubmed #15800993 links to  free full text

Abstract: 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 F1-2 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.

Omata M, Tateishi R, Yoshida H, Shiina S. · Department of Gastroenterology, University of Tokyo, Tokyo, Japan. · Gastroenterology. · Pubmed #15508080 No free full text.

Abstract: In Japan, approximately 30,000 patients died of hepatocellular carcinoma (HCC) in 2003. Ten percent had hepatitis B virus infection and 80% had hepatitis C virus (HCV) infection, indicating that viral hepatitis accounted for >90% of cases of HCC. In comparison, only 3% (1.5%, hepatitis B virus; 1.5%, HCV) of the general population is infected with these viruses. We treated 1238 patients between 1992 and the end of 2003 by means of percutaneous tumor ablation (PTA): 524 patients, by percutaneous ethanol injection therapy (PEIT); 85 patients, by percutaneous microwave coagulation therapy; and 629 patients, by radiofrequency ablation (RFA). Three-, 5-, 7-, and 10-year survival rates of the 1238 patients were 69%, 50%, 34%, and 19%, respectively. When limited to tumors </=3 cm in diameter and </=3 in number of cancer nodules (3-3 rule), 5-year survival rates reached 64.7% for PEIT. However, to achieve a 40% survival rate in year 5 after PEIT, the indication for treatment can be expanded to a 4 (size)-3 (number) rule or 5 (size)-1 (number) rule. The recent introduction of RFA may further change the rules. HCV-related HCC generally develops on the background of advanced fibrosis/cirrhosis. An issue of much concern is that it may subsequently recur in a location other than that of the primary lesion. We initiated a prospective controlled study to evaluate treatment with PTA and interferon. Results suggest that if the virus is eradicated, a 5-year survival rate as high as 80% can be expected.

Yoshida H, Tateishi R, Omata M. · Department of Gastroenterology, University of Tokyo Graduate School of Medicine. · Nippon Rinsho. · Pubmed #15359852 No free full text.

This publication has no abstract.

Akamatsu M, Yoshida H, Shiina S, Teratani T, Tateishi R, Obi S, Sato S, Koike Y, Fujishima T, Ishikawa T, Shiratori Y, Omata M. · Department of Gastroenterology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. · Eur J Gastroenterol Hepatol. · Pubmed #15097037 No free full text.

Abstract: OBJECTIVE: Hepatitis C virus (HCV) genotype and virus load, the strongest determinants of the efficacy of interferon therapy, have been presumed to be associated with risk for hepatocellular carcinoma (HCC). This study was conducted to elucidate whether these two factors are capable of predicting the prognosis of patients with HCC. METHODS: A total of 371 patients with HCV infection (258 men and 113 women; median age, 66 years; range, 37-88 years) who developed HCC between January 1993 and December 1999 were enrolled. Overall survival and recurrence-free survival were analysed with the Cox proportional hazard regression according to HCV genotype (type 1 versus type 2) and virus load (above versus below 100 kIU/ml). RESULTS: Of the 371 patients, 346 received locoregional treatments (ethanol injection, microwave, radiofrequency, or surgery), and 307 achieved complete response as determined by subsequent imaging studies. The remaining 25 patients underwent arterial embolization or chemotherapy. Cox proportional hazard regression showed that neither genotype (P = 0.814) nor virus load (P = 0.958) were significant predictors for survival (P = 0.814 and 0.958, respectively) and recurrence (P = 0.505 and 0.736, respectively). CONCLUSIONS: Neither genotype nor virus load of HCV affected prognosis of HCC patients.

Yoshida H, Tateishi R, Arakawa Y, Sata M, Fujiyama S, Nishiguchi S, Ishibashi H, Yamada G, Yokosuka O, Shiratori Y, Omata M. · Department of Gastroenterology, University of Tokyo, Tokyo, Japan. · Gut. · Pubmed #14960528 links to  free full text

Abstract: BACKGROUND: An increase in the incidence of hepatocellular carcinoma (HCC) in Japan since the 1980s suggests an imminent outbreak in other countries where viral spread occurred more recently. Interferon therapy for chronic hepatitis C, in general, has been shown to prevent HCC. AIMS: To determine the scale of benefit in individual patients. SUBJECTS: Histologically proven chronic hepatitis C patients in the Inhibition of Hepatocarcinogenesis by Interferon Therapy (IHIT) cohort (Ann Intern Med 1999;131:174), as updated in March 2003. METHODS: The lifetime risk for HCC was calculated based on HCC incidence rates, stratified by sex, age, fibrosis stage, and outcome of interferon therapy. The gain in HCC free survival was defined as the difference between expected HCC free survival with sustained virological response and that without. RESULTS: The gain in HCC free survival was greater when a patient was younger and fibrosis was more advanced. For example, a 30 year old male with F3 fibrosis gained 12.4 years by attaining sustained response while a patient with F1 fibrosis older than 60 years gained less than one year. For a treatment protocol with a given sustained response rate, prior estimation of the gain can be obtained by multiplying the calculated HCC free survival for responders by the response rate. CONCLUSIONS: The gain in HCC free survival may serve as an indicator of the benefit of interferon therapy in terms of HCC prevention and be useful in the consideration of indication and selection of treatment protocol for individual patients.

Watabe H, Shiratori Y, Tateishi R, Fujishima T, Akamatsu M, Koike Y, Obi S, Hamamura K, Sato S, Teratani T, Shiina S, Omata M. · Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. · Hepatogastroenterology. · Pubmed #14696486 No free full text.

Abstract: BACKGROUND/AIMS: The aim of this study is to clarify the clinical features of hepatocellular carcinoma that are negative for both hepatitis B surface antigen and anti-hepatitis C antibody. METHODOLOGY: Patients were classified according to viral markers: 45 patients (82%) had hepatitis B (B-HCC), 467 patients (82%) had hepatitis C (C-HCC), and 53 patients (9%) had neither hepatitis B nor hepatitis C (NBNC-HCC). Differences in clinical parameters among these three groups were analyzed. RESULTS: Patients with NBNC-HCC were older than B-HCC and C-HCC patients. The incidence of alcoholism in NBNC-HCC patients was higher than in C-HCC patients. Patients with NBNC-HCC had similar rates of positive antibody to hepatitis B core antigen as did patients with C-HCC. NBNC-HCC patients were further classified according to median age. The younger group showed a greater tendency towards alcoholism than did the aged group. Liver functioning in the younger group was worse than in the older group. The older group had larger tumors than the younger group. CONCLUSIONS: The livers of younger NBNC-HCC patients were more cirrhotic, possibly because of alcoholism. Older NBNC-HCC patients presented with larger tumors, possibly because they did not receive regular medical check-ups due to their relatively preserved liver function.