Geriatric Hepatology: The Hepatic Diseases of the Elderly and Liver Transplant

Introduction: With the aging US population, chronic liver diseases are becoming more commonly diagnosed in the geriatric population. Advanced age leads to changes in liver blood flow, volume, morphology and normal physiology. This predisposes elderly patients to develop certain chronic liver diseases. Also, the clinical course and management differ in an older patient when compared to a younger patient. Some causes of chronic liver disease in the geriatric population include Hepatitis A, B, C, Non-Alcoholic Fatty liver disease, prolonged alcohol use and inflammation. Many chronic liver diseases are characterized by a slow, indolent course of progression with non-specific symptoms and thus may lead to diagnosis at a later age. The presence of an advanced liver disease, cirrhosis, and hepatocellular carcinoma are becoming more frequent in older patients and often the first clinical presentation. Aim: The aim of this study is to highlight hepatic diseases in the geriatric population to better understand the scope of the clinical management including liver transplantation. Method: PubMed, MEDLINE, EMBASE, and EMBASE classic were searched to research published articles, case reports, cross-sectional and case-control studies reporting regarding aging and the liver diseases. Result: Decreases in the functioning of the liver and other organs, as well as, alterations in immune functions should be taken into consideration in the management of the liver diseases. Aging has been shown to not only enhance vulnerability to acute liver injury but also increase the susceptibility of the fibrotic response. Aging has a significant impact on the risk and poor prognosis of various liver diseases including NAFLD, ALD, HCV, and liver transplantation. The diagnosis of advanced liver disease is important to make in the elderly population since many of the condition’s features are treatable and can lead to improved quality of life and, most importantly, decrease the likelihood of acute care hospitalization, which carries a high risk of nosocomial infections and therapeutic mishaps in the aged population. Conclusion: Geriatric patients show various changes in the liver, which play a role in the clinical characteristics of liver diseases in these patients. Geriatric patients with risk factors for hepatitis should be screened for liver disease, along with those that have a family history of liver diseases, or a history of long-term or heavy alcohol consumption. Age cannot be a single exclusion criterion from the liver transplantation, and an individualization strategy, which takes into consideration all risk factors of a recipient, needs to be considered. We suggest geriatric patients should be a candidate for liver transplant, and the healthcare team treating our elderly generation to collaborate for these patients for them to have a smoother transition both in pre-transplant phase and post-transplant phase

Management and treatment of hepatocellular carcinoma with immunotherapy: A review of current and future options

With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to be eligible for curative treatment. Several different treatment modalities are available, including locoregional therapy radiofrequency ablation, microwave ablation, percutaneous ethanol injection, trans-arterial chemoembolization, transarterial radio-embolization, cryoablation, radiation therapy, stereotactic radiotherapy, systemic chemotherapy, molecularly targeted therapies, and immunotherapy. Immunotherapy has recently become a promising method for inhibiting HCC tumor progression, recurrence, and metastasis. The term “Immunotherapy” is a catch-all, encompassing a wide range of applications and targets, including HCC vaccines, adoptive cell therapy, immune checkpoint inhibitors, and use of oncolytic viruses to treat HCC. Immunotherapy in HCC is a relatively safe option for treating patients with advanced disease in the USA who are either unable to receive or failed sorafenib/lenvatinib therapy and thus may offer an additional survival benefit for these patients. The purpose of this review is to elaborate on some of the most recent advancements in immunotherapy

Chamomile: An ancient pain remedy and a modern gout relief -A hypothesis

Matricaria chamomilla (MC) i

THE EFFECT OF QUINCE LEAF (CYDONIA OBLONGA MILLER) DECOCTION ON TESTES IN HYPERCHOLESTEROLEMIC RABBITS: A PILOT STUDY

Current medical literature lacks any evidence of the protective effects of quince leaf on testes. Therefore, the aim of the present study was to assess the effect of quince (Cydonia oblonga Miller) leaf decoction on testicular injury and impaired spermatogenesis induced by hypercholesterolemia in rabbits. Eleven mature New Zealand white male rabbits were randomly divided into three groups: group 1 (hypercholesterolemia, n=3), group 2 (hypercholesterolemia plus quince treatment, n=6), and group 3 (control, n=2). Groups 1 and 2 received a cholesterol-enriched diet for six weeks. Group 2 received C. oblonga leaf decoction as drinking supplement as well. After six weeks, a normal diet was substituted in groups 1 and 2 for another six weeks. Group 3 (control group) was maintained throughout the study on a regular diet. At the end of the 12th week, the left testes of the animals were resected for light microscopic study with particular attention to the maturity of germ cells in seminiferous tubules using Johnsen’s score. Increase in intertubular connective tissue and diameter of vessels, abundant spermatogonia and primary spermatocytes along the reduced germinal epithelium were noted in all rabbits of the group 1. The remaining animals in groups 2 and 3 had no significant changes in their testicular sections. The mean Johnsen’s score of group 1 (4.20±1.92) was significantly lower than that of group 2 (7.33±0.52) and group 3 (7.05±0.07). (P=0.01). In conclusion, quince leaf decoction (C. oblonga Miller) protected rabbit testes and spermatogenesis from damage induced by hypercholesterolemia

Effect of Pioglitazone on Plasma Levels of Phenytoin in Rats

Introduction: Interaction between drugs represents a major clinical concern for health care professionals and their patients. Patients affected by both type 2 diabetes and epilepsy may be prescribed pioglitazone and an anti-epileptic drug such as phenytoin  concurrently. The aim of this study was to consider the interaction of pioglitazone with phenytoin in an experimental model. According to the result of this study, concurrent use of phenytoin and pioglitazone in clinic may cause therapeutic failure of phenytoin which may cause seizures and during seizures the cardiac function may be affected. Material and Methods: Two groups of rats were treated for 30 days. In group 1 (control group) saline (10 ml/kg) and phenytoin   (30 mg/kg) were administered daily by intragastric gavage. In group 2 (test group) , pioglitazone (10 mg/kg) was administered daily 60 minutes before phenytoin  (30 mg/kg). Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 ml of blood was drawn from the heart into a syringe containing Ethylenediaminetetraacetic (EDTA), and phenytoin  concentration in rat plasma was determined by High performance liquid chromatography (HPLC).The study consisted of 2 groups of 10 male adult Wistar rats. Results: Compared with control group, concurrent use of pioglitazone and phenytoin   was associated with significantly lower mean plasma concentrations of phenytoin : 2.08 ± 0.03  µg/ml VS 1.2 ± 0.02  µg/ml. Conclusion: Concurrent use of pioglitazone and phenytoin was associated with a significant decrease in plasma concentration of phenytoin in this experimental model. In clinic, this interaction may cause seizures and it has been shown that both cardiac and respiratory functions may affected by seizures

Selenium Effect on Oxidative Stress Factors in Septic Rats

Purpose: Severe oxidative stress is an important event that occurs in patients with sepsis. The body has extensive and multiple defense mechanisms against the reactive oxygen species (ROS) produced during inflammation and sepsis. One of these mechanisms includes a group of enzymes that utilize selenium as their cofactor. The purpose of this study is investigating of Selenium effect on oxidative stress factors in animal model of sepsis. Methods: Sepsis was induced by caecal ligation and puncture (CLP) method. 30 Male Wistar rats were divided into following groups: sham group; CLP group; 100 μg/kg Selenium- treated CLP group. 12 hours after inducing sepsis animals were killed and lungs were removed. One of the lungs was frozen in liquid nitrogen and kept at -70°C for enzymatic activity analysis and the other was kept in formalin 10% until tissue section preparation performed for histopathological studies. Results: The Myeloperoxidase (MPO) activity was decreased in Selenium- treated CLP group. Inflammation score of lung tissue was lowered in Selenium- treated CLP group, but it wasn’t statically significant. Level of glutathione peroxidase (GPx) was higher in CLP and Selenium- treated CLP groups. Conclusion: It seems that Selenium has protective effect on lung inflammation during acute lung injury. Also it may improve some stress oxidative profile during CLP model of sepsis

Fast Dissolving Sublingual Films Containing Sumatriptan Alone and Combined with Methoclopramide: Evaluation in Vitro Drug Release and Mucosal Permeation

ackground: Sumatriptan succinate is a 5-HT1 receptor agonist which is used in the treatment of migraine. It shows low bioavailability (15%) due to high hepatic first pass metabolism. The present work intended to formulate mucoadhesive sublingual films of sumatriptan combined with metoclopramide and sumatriptan alone with the objective of improving the therapeutic efficacy, patient compliance, and bioavailability. Methods: The sublingual films were formulated by solvent casting technique using mucoadhesive polymer of hydroxypropyl methylcellulose and propylene glycol as plasticizers. This study was also designed to evaluate the physicochemical and mucoadhesive characteristics of the films. The films were evaluated for their mechanical strength, folding endurance, drug content uniformity, swelling, in vitro residence time, in vitro release, in vitro bioadhesion, and in vivo mucoadhesion. Results: They showed good appearance and elasticity. The best drugs of polymer ratio were S3 (1:2) and SM2 (2.7:1:8). The film of S3 and SM2 showed 10.6 and 11.01 mg weight, 2.2 and 22.5 µm thickness, 300 folding endurance, 55.9 and 100% content uniformity, respectively. The Differential Scanning Calorimetry (DSC) showed no stable sample of sumatriptan and metoclopramide in the drug loaded films and revealed amorphous form and transition of hydrate to anhydrous form for metoclopramide. The results showed that the films prepared were fast dissolving. The films (sumatriptan combined with metoclopramide and sumatriptan alone) exhibited very good mucoadhesive properties and shorter retention time (15-30 s). Conclusion: The formulations were found to be suitable candidates for the development of sublingual films for therapeutic uses