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Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma.

ABSTRACT: Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients), were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were observed to be lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p < 0.001). According to serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ? 70 µg/dL (p < 0.001). Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dL.

SUBMITTER: Hosui A

PROVIDER: S-EPMC6316561 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma.

Hosui Atsushi A Kimura Eiji E Abe Sumiko S Tanimoto Takashi T Onishi Kousaku K Kusumoto Yukihiro Y Sueyoshi Yuka Y Matsumoto Kengo K Hirao Motohiro M Yamada Takuya T Hiramatsu Naoki N

Nutrients 20181210 12

Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), o ...[more]

PMID: 30544767

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Project description:BACKGROUND/AIMS: Our policy for the surgical treatment of hepatocellular carcinoma (HCC) has been to minimize the extent of liver resection using a microwave tissue coagulator (MTC) and to not perform Pringle's maneuver for the prevention of ischemic injury to the liver routinely. We verify the safety of liver resection using MTC in HCC patients with poor liver functional reserve, and clarify the long-term outcome of HCC patients who underwent curative resection using MTC. METHODOLOGY: One hundred sixty-eight patients who underwent curative resection using MTC between 1992 and 2001 were divided into two groups according each patient's score in the Indocyanin Green Retension 15 Test (ICG-R15 test). The high (ICG-R15 values>20) and low ICG-R15 groups (ICG-R15 values<20) included 100 and 68 HCC patients, respectively. Clinical characteristics of each group were evaluated, and operative mortality and morbidity, as well as overall and disease-free survival rates, were compared between the two groups to determine risk factors for overall and disease-free survival. RESULTS: Although there were significant differences in liver function-related parameters between the low and high ICG-R15 groups, no differences in surgical or tumor factors were found. No patients in this study developed post-operative liver failure, and there was no significant difference in morbidity between the low and high ICG-R15 groups. The overall survival rate of the low ICG-R15 group was significantly longer than the high ICG-R15 group (p=0.0003). Cox's multivariate analysis showed that an ICG-R15 value less than 20 was the only significant independent factor for overall survival. Disease-free survival rates in the low ICG-R15 group were significantly longer than in the high ICG-R15 group (p=0.0007). Multivariate analysis showed that serum albumin level and number of tumors were significant independent factors for disease-free survival. CONCLUSION: The long-term outcome of HCC patients with low ICG-R15 following curative resection using MTC was acceptable. This procedure was safe even for patients with high ICG-R15.

Project description:There are conflicting reports on the link between the micronutrient selenium and the prevalence of diabetes. To investigate the possibility that selenium acts as a "double-edged sword" in diabetes, cDNA microarray profiling and two-dimensional differential gel electrophoresis coupled with mass spectrometry were used to determine changes in mRNA and protein expression in pancreatic and liver tissues of diabetic db/db mice in response to dietary selenate supplementation. Fasting blood glucose levels increased continuously in db/db mice administered placebo (DMCtrl), but decreased gradually in selenate-supplemented db/db mice (DMSe) and approached normal levels after termination of the experiment. Pancreatic islet size was increased in DMSe mice compared with DMCtrl mice, resulting in a clear increase in insulin production and a doubling of plasma insulin concentration. Genes that encode proteins involved in key pancreatic β-cell functions, including regulation of β-cell proliferation and differentiation and insulin synthesis, were found to be specifically upregulated in DMSe mice. In contrast, apoptosis-associated genes were downregulated, indicating that islet function was protected by selenate treatment. Conversely, liver fat accumulation increased in DMSe mice together with significant upregulation of lipogenic and inflammatory genes. Genes related to detoxification were downregulated and antioxidant enzymatic activity was reduced, indicating an unexpected reduction in antioxidant defense capacity and exacerbation of fatty liver degeneration. Moreover, proteomic analysis of the liver showed differential expression of proteins involved in glucolipid metabolism and the endoplasmic reticulum assembly pathway. Taken together, these results suggest that dietary selenate supplementation in db/db mice decreased hyperglycemia by increasing insulin production and secretion; however, long-term hyperinsulinemia eventually led to reduced antioxidant defense capacity, which exacerbated fatty liver degeneration.

Dataset Information

Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma.

Publications

Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma.

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