RESULTS:

Background: Despite the high prevalence of viral hepatic cirrhosis all over the world the characteristic motor features of related Parkinsonism (extrapyramidal manifestations) are not well described. The current study aimed to characterize such disorder in a sample of Egyptian patients with chronic viral liver disease (CLD) and their clinical correlates. Methods: Ninety-six (96) patients with CLD were examined for the presence of extrapyramidal signs. Parkinsonism was assessed using the UPDRS-III scale and its sub scores. Ataxia and dystonia were also assessed by related scales. Patients with Parkinsonism were compared to other patients and correlations with clinical features of CLD were done. Results: The clinical diagnosis of extrapyramidal manifestations was justified in 57 patients (59.4%) with predominant akinetic rigid syndrome (ARS) (87.7%). Bradykinesia and axial features were the most frequent signs (89.5% and 70.2% respectively). 38.6% of patients had postural tremors whereas only 3.5% had rest tremors. Gait and postural abnormalities were detected in 38.6% and 36.8% respectively. Parkinsonism was associated with advanced hepatic cirrhosis (p=0.02) and increased episodes of hepatic encephalopathy (HE) (p=0.006). Severity of parkinsonian features was correlated to patients' age age of onset of CLD and rapid progression while impaired speech and gait were rather correlated to a number of episodes of HE. Conclusion: Advanced viral cirrhosis is associated with high prevalence of parkinsonism that is characterized by symmetrical ARS with frequent axial features postural tremor gait and postural impairment. Severity of these signs is correlated to age age of onset rapid progression and frequency of HE.

Rifaximin is a poorly absorbed rifamycin drug with unique pharmacokinetic properties: bile solubility making it highly active against pathogenic and non-pathogenic bacterial flora in the bile-rich small bowel and low water solubility making it active only against highly susceptible bacteria primarily anaerobes in the aqueous colon. The drug has anti-inflammatory gut mucosal stabilization properties that are important to its sustained effects in non-infectious diseases. Rifaximin is used chronically or recurrently for hepatic encephalopathy and diarrhea-predominant irritable bowel syndrome. Monitoring of long-term use of rifaximin for development of resistance and then determining whether developed resistance is associated with reduced efficacy are needed. Studies of changes of intestinal flora during therapy and the health implications of these changes are also needed.

Purpose: Intrahepatic Portosystemic Shunts (PSSs) draining to the Inferior Vena Cava (IVC) via the right adrenal vein has been reported as very rare and all the patients who have been recorded have had hepatic encephalopathy. Here we present a patient with intrahepatic PSS via the right adrenal vein diagnosed incidentally without encephalopathy. Case Presentation: A 51-year-old patient who was diagnosed with chronic liver parenchyma disease and a suspecting nodule on the ultrasound was examined by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). A 4 cm in diameter Hepatocellular Carcinoma (HCC) was detected. In addition to HCC an abnormal shunt between the right posterior portal vein and the IVC via the right adrenal vein was also detected. Results: To the best of our knowledge this is the first case with intrahepatic PSS via the right adrenal vein diagnosed incidentally in the absence of encephalopathy and the fourth case with this abnormal shunt in English literature. Conclusion: Intrahepatic PSS via the right adrenal vein is rare. It may be asymptomatic at the time of diagnosis but has the potential to cause various problems later on especially hepatic encephalopathy. The radiologist must be aware of this abnormal shunt.

Background: Fatty liver hepatitis cirrhosis and hepatic encephalopathy are clinically distinct progressively deteriorating conditions in alcoholic liver disease (ALD). Factors responsible for the progression of ALD are poorly understood. Therefore we compared various biochemical parameters in these conditions to correlate them with disease progression. Methods: Thirty patients of alcoholic liver disease reporting to our hospital were recruited in the study. Analysis included hematological parameters liver function tests ammonia amino acids and measurement of oxidative stress by measuring malanodialdehyde. Based on ultrasonography patients were classified as fatty liver alcoholic hepatitis and cirrhosis. Results: Hematological parameters showed significant change in the levels with the progression of the disease. Levels of aspartate transaminase alanine amino transferase alkaline phosphatase biluribin were elevated in all the ALD conditions but were more pronounced in hepatitis and cirrhosis than fatty liver. Oxidative stress was increased with progression of disease. Also significant differences in the levels of ammonia and amino acids were obtained. Conclusions: Alcohol induced oxidative stress is the primary cause of the liver injury. The progressive deterioration of various parameters indicates the extent of liver injury. Therefore antioxidant therapy may be best course that may halt or slow down the progression of ALD. These observations together provide a rationale for the possible clinical application of antioxidants in the therapy for ALD. Thus prevention and therapy opposing the development of steatosis and its progression to more severe injury can be attempted by a multifactorial approach.

Cerebral complications of liver failure either due to chronic or acute manifestations lead to a neurological disorder known as Hepatic encephalopathy (HE). Neurosteroids synthesized in the brain mainly by astrocytes but also in other brain cells independently from peripheral steroidal sources such as adrenal and gonads are suggested to play a role in the pathogenesis of HE. The mechanisms by which neurosteroids affect brain function are not totally elucidated but may involve both genomic and non genomic effects. On the one hand neurosteroids bind and modulate different types of neuronal memebrane receptors. While neurosteroids may affect directly postsynaptic receptors including GABAA 5-HT3 NMDA glycine and opioid receptors which have been involved in HE neurosteroids effects through GABAA receptors may also compromise indirectly the function of neurons networking with GABAergic interneurons. On the other hand some neurosteroids bind to intracellular receptors through which they also regulate gene expression and there is substantial evidence confirming that expression of genes coding for key astrocytic and neuronal proteins is altered in HE. The mechanisms that trigger brain neurosteroid changes in HE are not yet established but could involve (i) ammonia and manganese (in chronic HE)-induced translocator protein (TSPO) activation (ii) neuroinflammation or (iii) blood-brain transfer of lipophylic neuroactive steroids. The present review summarizes evidence for the involvement of neurosteroids in HE and possible mechanisms for their altered brain production and central effects in human and experimental HE.

Hepatic encephalopathy is a brain functional disorder characterized by neuropsychiatric abnormalities with liver failure. High blood ammonia causing glutamate neurotoxicity is the basic cause finally leading to low-grade cerebral edema. Its manifestation is more likely in patients of sepsis oxidative stress generalized inflammation gut mal-functioning amoebiaesis viral hepatitis nervous imbalance etc. Thus the therapeutic goals primarily include the maintenance of proper blood supply and prevention of hypoxic condition in liver along with management of factors responsible for high blood ammonia oxidative stress inflammation and high GI- serotonin. The drugs in clinical practice include lactulose sodium benzoate flumazenil and rifaximin supplementation of zinc branched chain amino acids (BCAA) l-ornithine-l aspartate antioxidants and iNOS inhibitors. However herbal formulations would be of great importance as it shows multi-targeted action because it possesses a natural cocktail of secondary metabolites. It can collectively act as an antioxidant anti-inflammatory prebiotic hepatoprotective and neuron-protective agents. We have briefly outlined some of these plants and also recent patents useful in the management of hepatic encephalopathy.

Liver failure can lead to generalized hyperammonemia which is thought to be the underlying cause of hepatic encephalopathy. This neuropsychiatric syndrome is accompanied by functional changes of astrocytes. These glial cells enter ammonia-induced self-amplifying cycle characterized by brain oedema oxidative and osmotic stress that causes modification of proteins and RNA. Consequently protein expression and function are affected including that of glutamine synthetase and plasmalemmal glutamate transporters leading to glutamate excitotoxicity; Ca2+-dependent exocytotic glutamate release from astrocytes contributes to this extracellular glutamate overload.

Hepatic encephalopathy is a neurological condition that affects people who have an insufficient liver function. However its pathophysiology is yet unclear. For hepatic encephalopathy pharmacotherapy is the primary treatment choice. Lowering ammonia levels enhancing neurotransmitter signal transduction and modifying gut microbiota tackles the pathophysiology of hepatic encephalopathy. The intestinal microbiota of liver disease patients differs greatly from that of healthy people and this difference is linked to the development of hepatic encephalopathy. Additionally gut microbiota is intimately linked to several theories in the pathophysiology of hepatic encephalopathy such as the GABA-ergic tone hypothesis bile acid circulation ammonia poisoning theory and neuroinflammation all of which exacerbate patients' cognitive and motor impairments. Providing some probiotics or reestablishing the intestinal bacteria's balance has a substantial impact on neurological illnesses in hepatic encephalopathy. The goal of this review is to determine the possible metabolic impacts and microbiological pathways in the gut-brain axis mediated progression of hepatic encephalopathy as well as its potential function as a therapeutic target.

>Introduction: Linezolid is increasingly utilized to treat gram-positive bacteria that are resistant to other antibiotics like vancomycin-resistant Staphylococcus aureus methicillinresistant Staphylococcus aureus as well as drug-resistant tuberculosis. It acts by inhibiting protein synthesis in bacteria. Although it is a relatively safe medicine many reports of hepatotoxicity and neurotoxicity linked to long-term usage have been received but patients with pre-existing risk factors such as diabetes and alcoholism may have toxicity even after short-term use of linezolid. Case Presentation: Here we are presenting a case of a 65-year-old female with diabetes who developed hepatic encephalopathy after one week of treatment with linezolid prescribed for nonhealing diabetic ulcer after a culture sensitivity test. After the use of linezolid 600 mg BD for 8 days patient developed altered sensorium and breathlessness and had high bilirubin SGOT and SGPT. She was diagnosed with hepatic encephalopathy. Linezolid was withdrawn and after 10 days all laboratory parameters for liver function test were improved. Conclusion: Care should be taken when prescribing linezolid in such patients with pre-existing risk factors as they are prone to develop hepatotoxic and neurotoxic adverse effects even after short-term use of linezolid.