Randomised trial of effects of interferon-α on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis

Nishiguchi, Shuhei; Kuroki, Tetsuo; Nakatani, Shinji; Morimoto, Hideki; Takeda, Tadashi; Nakajima, Shinya; Shiomi, Susumu; Seki, Shuichi; Kobayashi, Kenzo; Otani, Shuzo

doi:10.1016/s0140-6736(95)91739-x

Cited by 820 publications

(157 citation statements)

References 34 publications

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“…HCV seems to be a stronger risk factor than HBV in multicentric HCCs. The difference may be related to the higher incidence of HCC development in patients with HCV (about 7% per year in Japan 10,16) ) than in patients with HBV. 10,11) The high odds ratio for having HBcAb with or without HCV suggests that HBV infection in the past or present may be important for HCC development, especially in the presence of HCV.…”

Section: Discussionmentioning

confidence: 98%

“…Whether tumors in a particular patient are multicentric in origin can be found by examination of integrated HBV DNAs [1][2][3] in HBV-related HCC, the pattern of loss of heterozygosity on chromosome 16,4) and the mutation pattern of the p53 gene. 31) HCV is unlikely to be integrated into the genome, 9) and clonal analysis cannot be used to investigate the multicentricity of tumors in patients infected with HCV.…”

Section: Discussionmentioning

confidence: 99%

“…Serum was examined for HCV RNA by means of the polymerase chain reaction with reverse transcription (RT-PCR) and with primers derived from a conserved 5′-untranslated region of the viral genome. 16) Serum HBV DNA was assayed by nested PCR as reported previously.…”

Section: Patientsmentioning

confidence: 99%

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Clinicopathological Criteria for Multicentricity of Hepatocellular Carcinoma and Risk Factors for Such Carcinogenesis

Kubo

Nishiguchi

Hirohashi

et al. 1998

Japanese Journal of Cancer Research

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Multicentric occurrence is an important characteristic of hepatocellular carcinoma. We evaluated clinicopathological criteria for multicentric hepatocellular carcinoma and identified risk factors for such carcinogenesis. Subjects were 251 consecutive patients undergoing liver resection for hepatocellular carcinoma. One kind of multicentric hepatocellular carcinoma had at least one tumor consisting of well-differentiated hepatocellular carcinoma, together with moderately or poorly differentiated hepatocellular carcinoma located in a separate region. The other kind had an area of well-differentiated component around hepatocellular carcinoma with less differentiation in all occurrences. The outcome of patients with tumors classified in this way was studied. Univariate and multivariate analyses were done to identify risk factors for multicentric hepatocellular carcinoma. The cumulative survival rate was significantly higher in patients with multicentric hepatocellular carcinoma than in patients with hepatocellular carcinoma associated with intrahepatic metastasis. Analysis by Cox's proportional hazard model showed that multicentricity was not a factor in the outcome. The risk of multicentric occurrence increases with progression of chronic liver disease. Univariate analysis showed hepatitis C virus marker and hepatitis B core antibody to be risk factors. By multivariate analysis, the odds ratio for multicentric occurrence in patients infected with hepatitis C virus and with serum hepatitis B virus core antibody compared with patients without either hepatitis C virus or hepatitis B virus was 10.86. This ratio in patients with hepatitis C virus alone was 4.30. These criteria for multicentric hepatocellular carcinoma seem to be clinically useful. Hepatitis C virus infection with or without former infection by hepatitis B virus is a strong risk factor for multicentric hepatocarcinogenesis. Key words: Hepatocellular carcinoma -Hepatitis B virus -Hepatitis C virus -MulticentricityLiver cirrhosisRecent studies in molecular biology have shown that some hepatocellular carcinomas (HCCs) are multicentric in origin. [1][2][3][4][5] It is important to know for individual patients whether multiple tumors in the liver are multicentric or metastases originated from a main tumor to decide the most appropriate treatment, because the results of treatment for single (unicentric) HCCs, multicentric HCCs, and HCCs with intrahepatic metastasis differ.6-8) Hepatitis C virus (HCV) and hepatitis B virus (HBV) are risk factors for HCC. 9) In Japan 10-12) and Europe, 13) the incidence of HCC is higher in patients with HCV than in those with HBV. The difference in the incidence of HCC in patients with HCV or HBV affects decisions about treatment, because these viruses are factors in the outcome after surgery.14, 15) HCV-related HCCs tend to be multifocal, 7,9) but no large-scale studies on the incidence of and risk factors for multicentric occurrence of HCC have been reported. We retrospectively evaluated criteria for identification of multicen...

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Clinicopathological Criteria for Multicentricity of Hepatocellular Carcinoma and Risk Factors for Such Carcinogenesis

Kubo

Nishiguchi

Hirohashi

et al. 1998

Japanese Journal of Cancer Research

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“…Recent randomized controlled trials have shown that interferon therapy leads to a rapid decrease in ALT activity and to a disappearance of serum HCV RNA in about one-third of patients with chronic hepatitis C. 28,45,46) Patients who respond to interferon therapy with long-term remission of disease and sustained loss of HCV RNA generally are regarded as being unlikely to develop cirrhosis of the liver or HCC. Thus, interferon therapy may suppress postoperative carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Samples were examined for anti-HCV by second-or third-generation ELISA (Ortho Diagnostic Systems, Tokyo). Serum HCV RNA was detected using a polymerase chain reaction with reverse transcription and primers derived from a conserved 5′-untranslated region of the viral genome 28) as well as a branched DNA probe method (Quantiplex HCV-RNA, Chiron Corp., Emeryville, CA). When HCV RNA was not detected in the sera by these two methods, the results were further confirmed by a single-tube assay kit (Amplicor HCV test, Roche Diagnostic Systems/Nippon Roche Co., Branchburg, NJ).…”

Section: Methodsmentioning

confidence: 99%

Effects of Continuous Hepatitis with Persistent Hepatitis C Viremia on Outcome after Resection of Hepatocellular Carcinoma

Kubo¹,

Nishiguchi

Shuto³

et al. 1999

Japanese Journal of Cancer Research

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The effect of persistent hepatitis C viremia on the outcome after resection of hepatocellular carcinoma (HCC) was investigated in 59 consecutive patients with a single small HCC (≤ ≤ ≤ ≤3.0 cm in diameter). The presence of serum hepatitis C virus (HCV) RNA was evaluated using a reverse transcription polymerase chain reaction method as well as a branched DNA probe method. Clinicopathologic findings were compared between patients with and without viremia and the risk factors for poor outcome were evaluated. Hepatitis C virus (HCV) RNA was not detected in the sera from 7 patients (group 1), but was detected in the sera from the other 52 patients (group 2). Alanine aminotransferase (ALT) activity was significantly higher in group 2 than in group 1. The proportion of patients with active hepatitis was significantly higher in group 2. In group 2, new HCC often developed after the operation and four patients died of liver dysfunction. HCV viremia, high ALT activity, high concentration of total bilirubin, and liver cirrhosis were related to recurrence after the operation. Multivariate analysis indicated that HCV viremia and high ALT activity were independent risk factors for recurrence of HCC. Continuous hepatitis with persistent HCV viremia worsened the outcome after the resection of HCC by causing new development of HCC and deterioration of liver function. In patients with HCV-related HCC, but without HCV viremia, satisfactory results can be expected after liver resection.Key words: Hepatocellular carcinoma -Hepatitis C virus -Chronic hepatitis C -Liver resection -Histologic activity indexDespite improvements in medical imaging, surgical techniques, and perioperative management, outcomes after liver resection for hepatocellular carcinoma (HCC) still are unsatisfactory because of a high recurrence rate. 1)There have been many studies concerning factors related to recurrence and outcome after resection of HCC. [2][3][4][5][6][7][8][9][10][11][12][13] In some of these reports, hepatitis viral status was not evaluated. In others, hepatitis C virus (HCV) infection was determined by whether the patients had anti-HCV antibodies in their sera before the operation. The subjects in these studies thus might have included patients without HCV viremia at the time of or after the operation.In patients infected with HCV, cirrhosis with chronic inflammation, liver cell necrosis and regeneration, and extensive fibrosis are important in the development of HCC.14-18) HCC tends to develop or to become detectable when DNA synthesis increases in patients with HCVassociated cirrhosis. Increased DNA synthesis in hepatocytes also appears to accelerate recurrence after resection for HCC in patients with HCV-associated cirrhosis. 19) We have found that a high spermidine/spermine ratio, which is closely related to cell proliferation, in the noncancerous hepatic tissue is a risk factor for recurrence after liver resection for HCC.20) It has also been reported that the sustained elevation of the serum alanine aminotransferase (ALT) activity in HCV...

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Age-Related Response to Interferon Alfa Treatment in Women vs Men With Chronic Hepatitis C Virus Infection

Hayashi¹,

Kishihara²,

Ueno³

et al. 1998

Arch Intern Med

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Randomised trial of effects of interferon-α on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis

Cited by 820 publications

References 34 publications

Clinicopathological Criteria for Multicentricity of Hepatocellular Carcinoma and Risk Factors for Such Carcinogenesis

Clinicopathological Criteria for Multicentricity of Hepatocellular Carcinoma and Risk Factors for Such Carcinogenesis

Effects of Continuous Hepatitis with Persistent Hepatitis C Viremia on Outcome after Resection of Hepatocellular Carcinoma

Age-Related Response to Interferon Alfa Treatment in Women vs Men With Chronic Hepatitis C Virus Infection

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