Modulation of Autophagy: A Novel “Rejuvenation” Strategy for the Aging Liver

Aging is a natural life process which leads to a gradual decline of essential physiological processes. For the liver, it leads to alterations in histomorphology (steatosis and fibrosis) and function (protein synthesis and energy generation) and affects central hepatocellular processes (autophagy, mitochondrial respiration, and hepatocyte proliferation). These alterations do not only impair the metabolic capacity of the liver but also represent important factors in the pathogenesis of malignant liver disease. Autophagy is a recycling process for eukaryotic cells to degrade dysfunctional intracellular components and to reuse the basic substances. It plays a crucial role in maintaining cell homeostasis and in resisting environmental stress. Emerging evidence shows that modulating autophagy seems to be effective in improving the age-related alterations of the liver. However, autophagy is a double-edged sword for the aged liver. Upregulating autophagy alleviates hepatic steatosis and ROS-induced cellular stress and promotes hepatocyte proliferation but may aggravate hepatic fibrosis. Therefore, a well-balanced autophagy modulation strategy might be suitable to alleviate age-related liver dysfunction. Conclusion. Modulation of autophagy is a promising strategy for “rejuvenation” of the aged liver. Detailed knowledge regarding the most devastating processes in the individual patient is needed to effectively counteract aging of the liver without causing obvious harm.

A Study to Access the Correlation between Serum Alpha Fetoprotein and Radiological Image Finding in Patients with Malignant Liver Mass

Malignant liver mass remains a major health problem worldwide. Patients with chronic liver disease, the accuracy of ultrasound scan (US), spiral computed tomography (CT), magnetic resonance imaging (MRI), and alpha-fetoprotein (AFP) in diagnosing hepatocellular carcinoma (HCC) and malignant liver disease is assessed in this study. This study helps to find out the significance of serum alpha protein in patients with malignant liver mass. Retrospective cross-sectional study was done on patients with malignant liver mass. A total of 62 patients were diagnosed with malignant liver mass, out of which 44 are male, and 18 were female. They were grouped into three age groups 30-50 years, 51-70 years and above 70 years. In this study, out of the radiologically diagnosed malignant liver mass, HPE has proven hepatocellular carcinoma where 67.7% and liver secondaries where 29.03%. 55% of malignant liver mass has raised alpha feto proteins. 74% of HCC diagnosed and confirmed on biopsy have elevated alpha feto proteins. Only 11% of multiple malignant liver lesions have elevated alpha feto proteins.AFP receptors are expressed only in the AFP-positive HCC tissues. In the AFP-negative HCC, the rate of tumour growth would probably be expected to be relatively slow, and tumour staging might be lower than in AFP-positive. Based on this study, radiological imaging has been very useful in the diagnosis of various malignant liver masses in both elevated and normal AFP.

The Role of Nutritional Support in the Treatment of Liver Malignancies.

In order to describe the necessity and safety of nutritional support in liver malignancies, we performed a search and analysis of publications on the topic published in the medical databases eLibrary, PubMed, Medline. Based on the data obtained, it was shown that patients with malignant liver disease have anorexia-cachexia syndrome. Nutritional support for perioperative hepatic malignancies improves immediate surgical outcomes. Isocaloric enteral nutrition with a high protein content is considered the drug of choice. The additional use of branched chain amino acids (BCAA) is not unambiguously interpreted. When conducting modern anticancer treatment, nutritional support is considered as an integral component of complex therapy, contributing to the achievement of the best results at all stages of the treatment process.

Comparison of two techniques using EUS guided liver biopsies via 19g core biopsy needle to obtain optimal core specimen in benign disease

Background and Hypothesis: Endoscopic ultrasound (EUS) guided fine-needle biopsy (FNB) to obtain core liver specimen is shown to be effective and safe. However, prospective data is limited regarding EUS-FNB in non-malignant liver disease. This study evaluates two EUS-FNB techniques with the hypothesis that the modified wet suction (MWS) technique will produce greater pathological yield than the slow pull (SP) technique in patients with non-malignant liver disease. Experimental Design or Project Methods: In this prospective, randomized controlled trial we are evaluating efficacy and safety of EUS-FNB techniques (MWS versus SP) in patients with initial indication for an upper endoscopy plus need for a liver biopsy to assess non-malignant disease. The primary outcome is pathological yield defined as number of complete portal tracts (CPTs), specimen length, and fragmentation. Secondary outcomes include pathological yield between two specimen processing techniques, pathological yield between left versus right liver lobe biopsy, time for biopsy technique, and complications. Results: For this interim analysis, 8 patients (5 received MWS and 3 received SP) out of a projected total of 360 patients are enrolled. Independent t-test analysis reveals no statistical difference between CPTs (P=0.56), specimen length (P=0.12), and fragmentation (P=0.16). No differences are found between any secondary outcomes, and there have been no biopsy-related complications. Conclusion and Potential Impact: This underpowered interim analysis reveals no statistical difference in primary or secondary outcomes between MWS versus SP technique. The current results for both groups are consistent with specimen adequacy criteria determined by American Association for the Study of Liver Disease.

Selenium and oxidative stress in cancer patients

In order to identify the features of violations of free-radical processes in blood serum of 94 untreated cancer patients with different localization of the tumor (cancer of the stomach, colon, breast, ovarian, hemoblastoses) were determined selenium levels and indicators of oxidative stress (sum of metabolites of nitrogen - NOx, the level of superoxide dismutase - Cu/ZnSOD and malondiialdehyde-MDA, and the activity of catalase). In addition, 40 patients with malignant liver disease and clinical signs of liver failure in the early postoperative period was carried out a comparative evaluation of the efficacy of selenium-containing drug 'Selenaze' (sodium selenite pentahydrate). It was found that selenium levels in cancer patients by 25-30% below the norm of 110-120 mg/l at a rate of 73.0±2.6 mg/l. Low levels of NOx was detected in patients with all tumor localizations (22.1±1.1 mM, with normal range 28.4±0.9 mM). The exceptions were patients with extensive malignant process in the liver, in which the NOx levels were significantly higher than normal (p<0.001). The high level of NOx has a toxic effect on the hepatocyte, causing metabolic disorders and inflammatory-necrotic changes in the liver. Elevated levels of SOD and MDA in normal values of catalase activity was detected in all patients. The use of 'Selenaze' in postoperative patients with tumors of the liver increased selenium levels by 10-12%, which was accompanied by a decrease in the content of SOD and NOx, and contributed to earlier recovery of detoxic and synthetic liver function. These findings point to an intensification of oxidative stress and metabolic disorders in the malignant process, which is the basis for metabolic correction.