Survival rates of early-stage HCV-related liver cirrhosis patients without hepatocellular carcinoma are decreased by alcohol

Although alcohol abuse is the most common cause of liver cirrhosis in the United States, the enhancing effects of alcohol on the long-term prognosis of hepatitis C virus (HCV) related liver cirrhosis has not been clarified. To investigate how alcohol abuse influences the prognosis of hepatitis virus related liver cirrhosis, we studied 716 Japanese patients. Cumulative survival and hepatocellular carcinoma (HCC) development rates were analyzed in alcohol abusive, cirrhotic patients with or without hepatitis virus infection. Patients who abused alcohol were younger (p<0.0001) than HCV infected, non-abusive patients. The overall survival rate among patients with alcoholic cirrhosis (Al group), HCV related cirrhosis (HCV group), and HCV infected + alcoholic cirrhosis (HCV + Al group), showed no significant differences, although the 10-year cumulative survival rate of Al group was the highest of the three groups. The HCC development rate of Al group was the lowest. In addition, alcohol abuse decreased the survival rates of HCV group in the early stage with no HCC (p = 0.0028). In conclusion, alcohol abuse might affect the progression of liver damage in HCV infected patients with liver cirrhosis in the early stage, although the influence of alcohol abuse on the long term prognosis seems to be rather small.     

Transferrin and iron uptake by isolated rat liver mitochondria.

Isolated rat liver mitochondria accumulate iron from the suspending medium when [59Fe]transferrin is used as a model compound. The accumulation proceeds by two different mechanisms, i.e. by an energy-independent and an energy-dependent (uncoupler sensitive) mechanism, which have different time, pH, and temperature dependencies. The energy-dependent accumulation, which is inhibited by ruthenium red and sulphydryl reagents, reaches a saturation level of approx. 30 pmoles iron/mg protein during 30 min incubation. The energy-independent accumulation of iron-transferrin reveals no saturation kinetics, it is inhibited neither by ruthenium red nor by N-ethylmaleimide, and it proceeds linearly for at least 90 min. With [125I]transferrin as a model compound, quantitatively the energy-independent accumulation is as reported for [59Fe]transferrin. There is, however, no energy-dependent accumulation of [125I]transferrin. The results indicate that the energy-dependent accumulation of [59Fe]transferrin represents a process by which mitochondria accumulate iron from transferrin.     

Carotenoids and liposoluble vitamins in liver cirrhosis.

The role played by carotenoids, retinol and tocopherol in quencing oxidative cellular damage and combatting tumor growth is well documented, but little is known about their activity in human liver cirrhosis (LC), where oxidative damage and tumoral complications are common-place. We investigated 59 patients with LC of different etiology on admission to hospital and compared them with 32 healthy controls, matched for age and sex. Nutritional (cutaneous skinfolds, creatinine-height index) and serum parameters were determined; of these, alpha- and beta-carotene, cryptoxanthin, lycopene, retinol and alpha-tocopherol were detected by an high-performance liquid chromatographic (HPLC) technique, devised in our laboratory, which afforded an accurate and simultaneous resolution of all six compounds. The results point to a significant reduction in almost all the vitamin factors in LC, as well as in total serum lipids. In consequence, the ratio tocopherol/total serum lipids remains almost unchanged: 2.45 +/- 0.08 (m +/- se) in controls and 2.34 +/- 0.16 in patients. The effects of age, sex, nutritional habits, alcohol, malnutrition and the severity of the disease were also evaluated in relation to the vitamin-factor levels. It is suggested that the reduced levels observed in LC patients are due to a number of factors including portal hypertension and lymphatic circulation impairment, and it is concluded that thorough screening and improved diet are beneficial in the follow-up of LC.     

Efficient clearance of non-transferrin-bound iron by rat liver. Implications for hepatic iron loading in iron overload states.

In hemochromatosis and other disorders associated with iron overload, a significant fraction of the total iron in plasma circulates in the form of low molecular weight complexes not bound to transferrin. Efficient and unregulated clearance of this form of iron by the liver may account for the hepatic iron loading and toxicity that characterize these diseases. We tested this possibility by examining the hepatic removal process for representative iron complexes in the single-pass perfused rat liver. Hepatic uptake of both ferrous and ferric 55Fe from ultrafiltered human serum was found to be highly efficient and effectively irreversible (single-pass extraction of 1 microM iron, 58-75%). Similar high efficiencies were seen for iron complexed to specific physiologic and nonphysiologic coordinators, including histidine, citrate, fructose, oxalate and glutamate, and tricine. Because of lower plasma flow rates, single-pass extraction of these iron complexes in vivo should be even greater. Autoradiography confirmed that most iron had been removed by parenchymal cells. Hepatic removal from Krebs-tricine buffer was saturable with similar kinetic parameters for ferrous and ferric iron (apparent Km, 14-22 microM; V max, 24-38 nmol min-1 g liver-1). These findings suggest that high levels of non-transferrin-bound iron in plasma may be an important cause of hepatic iron loading in iron overload states.     

酒精性肝硬化患者外周血激活素结合蛋白水平变化

目的探讨酒精性肝硬化患者外周血激活素结合蛋白（FS）水平变化。方法采集临床诊断酒精性肝硬化患者40例及健康对照者40例,酶联免疫吸附试验检测外周血FS及激活素A（Activin A）水平。结果酒精性肝硬化患者外周血ALT、AST及GGT水平均高于健康对照组,统计学比较差异显著（P〈0.01）;同时可见酒精性肝硬化患者外周血Activin A水平明显升高,与对照组比较差异显著,P〈0.01;FS水平略升高,与对照组比较无明显差异,P〉0.05;酒精性肝硬化患者Activin A/FS比值升高,与对照组比较差异显著,P〈0.01。结论酒精性肝硬化患者Activin A/FS比值升高,提示Activin A-FS系统失衡可能与酒精性肝硬化形成有关,检测Activin A/FS比值有助于酒精性肝硬化辅助诊断。