Novel Drugs for the Management of Hepatic Encephalopathy: Still a Long Journey to Travel

Abstract

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Possible pathogenetic role of ammonia in liver cirrhosis without hyperammonemia of venous blood: The so‐called latency period of abnormal ammonia metabolism

“…Treatment strategies for abnormal ammonia metabolism in cirrhosis can be broadly divided into two categories: the inhibition of ammonia production and the promotion of ammonia metabolism (Table 3). [30][31][32] Treatment to inhibit ammonia production in the digestive tract Therapies using nonabsorbable disaccharides, such as lactulose and lactitol, along with the antibiotic, rifaximin, have high levels of supporting evidence for their beneficial effects and are widely used in clinical practice. [30][31][32] Recent systematic reviews reported that a combination of these two agents (nonabsorbable disaccharide and rifaximin) improved and prevented hepatic encephalopathy, as well as reduced the risk of mortality and severe adverse events.…”

“…[30][31][32] Treatment to inhibit ammonia production in the digestive tract Therapies using nonabsorbable disaccharides, such as lactulose and lactitol, along with the antibiotic, rifaximin, have high levels of supporting evidence for their beneficial effects and are widely used in clinical practice. [30][31][32] Recent systematic reviews reported that a combination of these two agents (nonabsorbable disaccharide and rifaximin) improved and prevented hepatic encephalopathy, as well as reduced the risk of mortality and severe adverse events. 33 Furthermore, phase II, placebo-controlled randomized trials reported that rifaximin was effective at inhibiting fibrosis progression in alcoholic liver disease.…”

“…36 BCAA supplements stimulate the glutamine synthesis pathway in skeletal muscle, reducing the influx of ammonia into the downstream veins. 32 However, their effectiveness at lowering arterial blood ammonia concentrations is weak, and because the glutamine produced is metabolized, resulting in ammonia production in the digestive tract, [6][7][8] the overall reduction in body ammonia is limited.…”

Role of granulocyte colony stimulating factor in the treatment of cirrhosis of liver: a systematic review

“…However, recent advances in the management of liver cirrhosis have improved treatment outcomes and healthrelated quality of life (HRQOL). 4 A few recent studies have shown that bone marrow-derived cells, including multipotent stem cells, are capable of self-renewal and differentiation into various adult cell types, including hepatocytes. [5][6][7] In addition, one study has demonstrated a positive effect of bone marrow cells in vitro in models of acute and chronic liver damage, and that they can populate the liver and contribute to hepatic regeneration.…”

Blood-brain barrier permeability and increased levels of amino acids in cerebrospinal fluid are associated with brain alterations in rats with acute liver failure

“…These tools assess clinical characteristics of the disease (e.g., patient's age, ALF etiology and onset of jaundice) as well as blood biomarkers (e.g., prothrombin time and serum creatinine, among others) to predict the severity of liver failure and the need for more aggressive treatment strategies. As intracranial hypertension is a central cause of coma and death in ALF, searching for biomarkers of brain impairment is relevant to assess the progression or severity of the disease [13][14][15].…”