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DNC News
Vitamin K-2 prevents liver cancer in hepatitis C patients: abstracts
Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. Habu D, Shiomi S, Tamori A, Takeda T, Tanaka T, Kubo S, Nishiguchi S.
Department of Hepatology, Graduate School of Medicine, Osaka City University , Osaka , Japan .
CONTEXT: Previous findings indicate that vitamin K2 (menaquinone) may play a role in controlling cell growth. OBJECTIVE: To determine whether vitamin K2 has preventive effects on the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. DESIGN, SETTING, AND PARTICIPANTS: Forty women diagnosed as having viral liver cirrhosis were admitted to a university hospital between 1996 and 1998 and were randomly assigned to the treatment or control group. The original goal of the trial was to assess the long-term effects of vitamin K2 on bone loss in women with viral liver cirrhosis. However, study participants also satisfied criteria required for examination of the effects of such treatment on the development of hepatocellular carcinoma. INTERVENTIONS: The treatment group received 45 mg/d of vitamin K2 (n = 21). Participants in the treatment and control groups received symptomatic therapy to treat ascites, if necessary, and dietary advice. MAIN OUTCOME MEASURE: Cumulative proportion of patients with hepatocellular carcinoma. RESULTS: Hepatocellular carcinoma was detected in 2 of the 21 women given vitamin K2 and 9 of the 19 women in the control group. The cumulative proportion of patients with hepatocellular carcinoma was smaller in the treatment group (log-rank test, P =.02). On univariate analysis, the risk ratio for the development of hepatocellular carcinoma in the treatment group compared with the control group was 0.20 (95% confidence interval [CI], 0.04-0.91; P =.04). On multivariate analysis with adjustment for age, alanine aminotransferase activity, serum albumin, total bilirubin, platelet count, alpha-fetoprotein, and history of treatment with interferon alfa, the risk ratio for the development of hepatocellular carcinoma in patients given vitamin K2 was 0.13 (95% CI, 0.02-0.99; P =.05). CONCLUSION: There is a possible role for vitamin K2 in the prevention of hepatocellular carcinoma in women with viral cirrhosis.
PMID: 15265851 [PubMed - indexed for MEDLINE]
Hepatology. 2004 Jul;40(1):243-51 Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation. Otsuka M, Kato N, Shao RX, Hoshida Y, Ijichi H, Koike Y, Taniguchi H, Moriyama M, Shiratori Y, Kawabe T, Omata M.
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo , Tokyo , Japan .
Hepatocellular carcinoma (HCC) is a common human malignancy. Its high mortality rate is mainly a result of high intrahepatic recurrence and portal venous invasion (PVI). We previously reported that the development of PVI is related to levels of des-gamma-carboxy prothrombin (DCP), a serum protein that increases at a notably higher rate in patients with HCC. Because DCP is produced by a vitamin K shortage, we examined the biological effects of extrinsic supplementation of vitamin K(2) in HCC cells in vitro and in vivo. Consequently, vitamin K(2) inhibits the growth and invasion of HCC cells through the activation of protein kinase A, which modulates the activities of several transcriptional factors and inhibits the small GTPase Rho, independent of suppression of DCP. In addition, administration of vitamin K(2) to nude mice inoculated with liver tumor cells reduced both tumor growth and body weight loss. In conclusion, similar to an acyclic retinoid--which was previously reported to prevent the recurrence of HCC--vitamin K(2), another lipid-soluble vitamin, may be a promising therapeutic means for the management of HCC.
PMID: 15239108 [PubMed - indexed for MEDLINE]
-------------------------------------------------------------------------------- Am J Gastroenterol. 2002 Apr;97(4):978-81. Comment in: Am J Gastroenterol. 2002 Apr;97(4):786-8. Vitamin K2 (menatetrenone) for bone loss in patients with cirrhosis of the liver. Shiomi S, Nishiguchi S, Kubo S, Tamori A, Habu D, Takeda T, Ochi H.
Third Department of Internal Medicine, Osaka City University Medical School , Osaka , Japan .
OBJECTIVE: Bone loss frequently appears in the natural history of liver disease. The effects of therapy for osteoporosis associated with cirrhosis of the liver are still controversial. We evaluated the effects of vitamin K2 on osteopenia in women with cirrhosis. METHODS: The subjects were 50 women with cirrhosis who had underlying hepatitis viral infections. Half of the patients were randomly assigned to receive vitamin K2 (menatetrenone). The bone mineral density (BMD) of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry at entry and at 1-yr intervals for 2 yr. RESULTS: The percentages of change from the initial BMD at 1 and 2 yr after initiation of the study were, respectively, +0.1 +/- 2.6% and -0.5 +/- 3.5% for the vitamin K2-treated group and -2.2 +/- 2.4% and -4.6 +/- 3.9% for the control group. The changes in BMD at each timepoint differed significantly between the control and treated groups (p = 0.008 for 1 yr and p = 0.002 for 2 yr). In the vitamin K2-treated group, the ratio of osteocalcin to undercarboxylated osteocalcin in those patients with increases in BMD after 1 yr of treatment was significantly lower than that in patients showing decreases in BMD (p = 0.017). No adverse effects of vitamin K2 were noted. CONCLUSIONS: Vitamin K2 can prevent bone loss and may therefore be useful in the management of bone disease in women with cirrhosis of the liver.
Publication Types: Clinical Trial Randomized Controlled Trial
PMID: 12003435 [PubMed - indexed for MEDLINE]
-------------------------------------------------------------------------------- Int J Vitam Nutr Res. 2003 Nov;73(6):411-5 Pilot clinical trial of the use of alpha-tocopherol for the prevention of hepatocellular carcinoma in patients with liver cirrhosis. Takagi H, Kakizaki S, Sohara N, Sato K, Tsukioka G, Tago Y, Konaka K, Kabeya K, Kaneko M, Takayama H, Hashimoto Y, Yamada T, Takahashi H, Shimojo H, Nagamine T, Mori M.
First Department of Internal Medicine, Gunma University Faculty of Medicine, 3-39-15, Showa Machi Maebashi , 371-8511, Japan . htakagi@med.gunma-u.ac.jp
Patients with chronic hepatitis C virus (HCV) infection often develop liver cirrhosis and hepatocellular carcinoma (HCC). The purpose of this study was to test the chemopreventive effect of alpha-tocopherol on hepatocarcinogenesis in patients with liver cirrhosis and a history of HCV infection. Eighty-three patients with liver cirrhosis and with positive history of HCV infection were divided at random into two groups. Forty-four patients were treated with alpha-tocopherol (Vit E group) while the other 39 were followed as controls. The clinical background (gender, age, and laboratory data) was similar in the two groups. Serum levels of alpha-tocopherol, albumin, alanine aminotransferase (ALT), and total cholesterol and platelet count were measured serially over a period of five years. The mean serum concentration of alpha-tocopherol was low in both groups at entry and was significantly higher in the Vit E group than in the control group one month after treatment. Platelet count, serum albumin, ALT, and total cholesterol were not different between the two groups during the five-year period. Cumulative tumor-free survival and cumulative survival rate tended to be higher in the Vit E group than in controls, albeit statistically insignificant. The serum level of alpha-tocopherol was low in patients with liver cirrhosis and positive for HCV. Although the administration of alpha-tocopherol normalized the level one month later, it could neither improve liver function, suppress hepatocarcinogenesis, nor improve cumulative survival. Patients treated with alpha-tocopherol tended to live longer without development of HCC but the difference was not statistically significant.
Publication Types: Clinical Trial Randomized Controlled Trial
Hepatology. 2001 Oct;34(4 Pt 1):714-8. The risk of liver and bile duct cancer in patients with chronic viral hepatitis, alcoholism, or cirrhosis. Kuper H, Ye W, Broome U, Romelsjo A, Mucci LA, Ekbom A, Adami HO, Trichopoulos D, Nyren O.
Department of Epidemiology and Public Health, University College London , London , UK . hannahk@public-health.ucl.ac.uk
No prospective study has analyzed simultaneously chronic viral hepatitis and alcoholism as risk factors for liver carcinogenesis, while taking into consideration the role of cirrhosis. Nor has the risk for hepatocellular carcinoma among patients with chronic viral hepatitis been prospectively evaluated in a low-risk Western population. Last, the relationship between hepatocellular carcinoma risk factors and bile duct cancer remains to be clarified. We analyzed prospectively the risk for primary liver and extrahepatic biliary tract cancer among 186,395 patients hospitalized with either chronic viral hepatitis, alcoholism, cirrhosis, or any combination of these conditions through linkages between national Swedish registers. Compared with the general population, the relative risk of hepatocellular carcinoma was 34.4 for chronic viral hepatitis alone, 2.4 for alcoholism alone, and 40.7 for cirrhosis alone. Among patients with combinations of these risk conditions, the relative risk of hepatocellular carcinoma was 27.3 for chronic viral hepatitis and alcoholism, 118.5 for chronic viral hepatitis and cirrhosis, 22.4 for alcoholism and cirrhosis, and 171.4 for all 3 conditions. We found limited evidence for an excess risk of intrahepatic, but not for extrahepatic, biliary duct cancer. Cirrhosis amplifies the risk of hepatocellular carcinoma among patients with chronic viral hepatitis, but it is not a prerequisite for liver carcinogenesis. In contrast, cirrhosis may be a necessary intermediate for the development of hepatocellular carcinoma among alcoholics.
PMID: 11584367 [PubMed - indexed for MEDLINE]
Int J Vitam Nutr Res. 2003 Nov;73(6):411-5. Pilot clinical trial of the use of alpha-tocopherol for the prevention of hepatocellular carcinoma in patients with liver cirrhosis. Takagi H, Kakizaki S, Sohara N, Sato K, Tsukioka G, Tago Y, Konaka K, Kabeya K, Kaneko M, Takayama H, Hashimoto Y, Yamada T, Takahashi H, Shimojo H, Nagamine T, Mori M.
First Department of Internal Medicine, Gunma University Faculty of Medicine, 3-39-15, Showa Machi Maebashi , 371-8511, Japan . htakagi@med.gunma-u.ac.jp
Patients with chronic hepatitis C virus (HCV) infection often develop liver cirrhosis and hepatocellular carcinoma (HCC). The purpose of this study was to test the chemopreventive effect of alpha-tocopherol on hepatocarcinogenesis in patients with liver cirrhosis and a history of HCV infection. Eighty-three patients with liver cirrhosis and with positive history of HCV infection were divided at random into two groups. Forty-four patients were treated with alpha-tocopherol (Vit E group) while the other 39 were followed as controls. The clinical background (gender, age, and laboratory data) was similar in the two groups. Serum levels of alpha-tocopherol, albumin, alanine aminotransferase (ALT), and total cholesterol and platelet count were measured serially over a period of five years. The mean serum concentration of alpha-tocopherol was low in both groups at entry and was significantly higher in the Vit E group than in the control group one month after treatment. Platelet count, serum albumin, ALT, and total cholesterol were not different between the two groups during the five-year period. Cumulative tumor-free survival and cumulative survival rate tended to be higher in the Vit E group than in controls, albeit statistically insignificant. The serum level of alpha-tocopherol was low in patients with liver cirrhosis and positive for HCV. Although the administration of alpha-tocopherol normalized the level one month later, it could neither improve liver function, suppress hepatocarcinogenesis, nor improve cumulative survival. Patients treated with alpha-tocopherol tended to live longer without development of HCC but the difference was not statistically significant.
Publication Types: Clinical Trial Randomized Controlled Trial
PMID: 14743544 [PubMed - indexed for MEDLINE]
Am J Epidemiol. 1999 Aug 15;150(4):367-74. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. Yu MW, Horng IS, Hsu KH, Chiang YC, Liaw YF, Chen CJ.
School of Public Health , College of Public Health , National Taiwan University , Taipei .
Both experimental and epidemiologic studies have linked a low dietary intake of selenium with an increased risk of cancer. The authors examined the association between plasma selenium levels and risk of hepatocellular carcinoma (HCC) among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men in Taiwan who were recruited by personal interview and blood draw during 1988-1992. After these men were followed up for an average of 5.3 years, selenium levels in the stored plasma were measured by using hydride atomic absorption spectrometry for 69 incident HCC cases who were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against hepatitis C virus (mostly HBsAg positive) and 139 matched, healthy controls who were HBsAg positive. Mean selenium levels were significantly lower in the HCC cases than in the HBsAg-positive controls (p = 0.01). Adjusted odds ratios of HCC for subjects in increasing quintiles of plasma selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively. The inverse association between plasma selenium levels and HCC was most striking among cigarette smokers and among subjects with low plasma levels of retinol or various carotenoids. There was no clear evidence for an interaction between selenium and alpha-tocopherol in relation to HCC risk.
PMID: 10453813 [PubMed - indexed for MEDLINE]
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