Advances In Hepatic Encephalopathy Drug Treatment

Hepatic encephalopathy is a reversible metabolic disease caused by central nervous system dysfunction in patients with acute or chronic liver disease. It is mainly manifested as a series of neuropsychiatric syndromes ranging from subclinical changes to coma, including abnormal changes in cognitive function, mood, behavior and motor function. The current hepatic encephalopathy drug treatment mainly aim at the pathogenesis of hepatic encephalopathy to reduce ammonia levels, including inhibiting the production and absorption of ammonia, and increasing the metabolic clearance of ammonia. In addition, there are nervous system and regulate the intestinal flora for the hepatic encephalopathy drug treatment. This article analyzes and expounds the hepatic encephalopathy drug treatment, in order to provide reference for its clinical treatment.

Drugs that inhibit ammonia production

Nonabsorptive disaccharides mainly include lactulose and lacttol. Lactulose is a synthetic disaccharide that has been approved by the U.S. Food and Drug Administration for the treatment of hepatic encephalopathy since 1976. Lactulose is the drug of choice for acute exacerbation of OHE and its secondary prevention recommended by the American Academy of Liver Diseases and the European Society of Liver Diseases in 2014. Lactitol is a disaccharide derivative composed of sorbitol and galactose. Lactitol is not decomposed by gastrointestinal disaccharidase, and enters the colon in its original form, and is degraded into short-chain organic acids by intestinal flora in the colon to acidify the colonic environment, thereby reducing the production and absorption of ammonia. However, there are few commercial preparations of lactitol, so it is not as widely used as lactulose.

Enteric nonabsorbable antimicrobials

Neomycin, an aminoglycoside antibiotic, was approved by the US FDA for the treatment of OHE in 1970, but it is only recommended as an alternative drug for OHE by the American Society of Liver Diseases and the European Society of Liver Diseases. Neomycin exerts a bacteriostatic effect in the gut after oral administration, reducing the production of ammonia and other toxins by bacteria in the colon. At the same time, neomycin can reduce the activity of glutaminase and inhibit the conversion of glutamine to ammonia in the intestinal mucosa.

Rifaximin is an oral non-absorbable broad-spectrum antibiotic. It has high activity against gram-positive and gram-negative aerobic and anaerobic bacteria in the intestine. Rifaximin has rare adverse reactions and drug interactions. It has also not been reported, and the risk of inducing bacterial resistance is low, so it is safe in clinical application.

Drugs that increase the clearance of ammonia metabolism

Sodium benzoate is a preservative widely used in food and beverages. As a separate drug, it has not been approved by the US FDA, but has been used since 1979 as an off-label use for the treatment of hyperammonemia in patients with HE. Through the non-urea cycle pathway, sodium benzoate combines with glycine to promote nitrogen excretion and ammonia removal in the form of phenylacetyl-glutamine in urine. A combination of sodium benzoate and sodium phenylacetate is currently FDA-approved for the treatment of hyperammonemia.

Medications to improve the nervous system

Recent studies have found that some patients with hepatic encephalopathy and Parkinson's disease patients have similar clinical manifestations. For patients with Parkinson's disease, dopamine drugs can significantly improve the neurological symptoms of patients by simulating the effect of the neurotransmitter dopamine. Therefore, some clinical studies have also been carried out on the efficacy of dopamine drugs in patients with hepatic encephalopathy. A clinical study in HE patients who had failed standard conventional treatment found that dopamine drugs significantly improved their mental status and EEG performance. Although dopamine drugs are well tolerated and safe in patients, they can only be used for the treatment of refractory HE that has failed first-line therapy.

Microecological preparation

Changes in the gut microbiome play an important role in the progression of cirrhosis and its complications. The study found that the intestinal flora of patients with liver cirrhosis has undergone important changes. As the disease progresses, the number of bacteria inherent in the intestine decreases, while the proportion of bacteria such as Enterobacteriaceae and Streptococcus is significantly increased. At the same time, gut microbes can lead to the production of ammonia and endotoxins. At present, the treatment of HE is mainly "gut-centered" treatment, so microecological preparations may play an important role in the treatment of HE by changing the intestinal flora.

Conclusion

Hepatic encephalopathy is still a serious clinical problem, and the long-term survival rate of patients is low. It is urgent to conduct more in-depth exploration and research on the pathogenesis of hepatic encephalopathy, so as to provide new hepatic encephalopathy drug treatment ideas. At the same time, new therapeutic drugs are urgently needed to relieve the symptoms of hepatic encephalopathy as soon as possible. Although there are many kinds of hepatic encephalopathy drug treatment and their mechanism of action is complex, there are still some problems in their clinical application, especially in terms of efficacy and safety. The quality of evidence from previous clinical studies of these drugs is often low, and the findings are often significantly divergent, so there is a lack of robust clinical research validation, and guidelines for the treatment of hepatic encephalopathy lack further updates. At present, the best application scheme for the treatment of hepatic encephalopathy is still being explored, and the appropriate treatment drugs need to be selected according to the specific analysis of the patient's disease and tolerance. At the same time, in the process of treatment, it is necessary to strengthen pharmaceutical care, closely evaluate the patient's condition, and adjust the drugs in time.