Professor Seong Pil-soo of St. Mary’s Hospital in Seoul demonstrates antiviral drug “tenofovir alafenamide (TAF)” in animal tests
A healthy liver has about 5% of its weight in fat, and if more fat is deposited, it is called fatty liver. Fatty liver is often thought to be alcoholic, caused by excessive drinking, but 80% of nonalcoholic fatty liver disease occurs without drinking alcohol. Diagnosis is made by ultrasound of the liver and abdomen and blood tests that measure levels of liver enzymes such as ALT and AST, which are released into the blood when the liver is damaged. Most are asymptomatic and are often found incidentally during tests for other purposes. Nonalcoholic fatty liver disease occurs in association with metabolic diseases such as diabetes and hyperlipidemia. The main causes are a westernized diet, lack of exercise and individual genetic defects. According to the Health Insurance Review and Assessment Service, patients visiting hospital for nonalcoholic fatty liver disease have increased more than 40% in the past 5 years, from 283,038 in 2017 to 405,950 in 2021. If fatty liver is not alcohol is not treated, it can progress to nonalcoholic steatohepatitis, which can develop into cirrhosis and liver cancer.
In the midst of this, a research result was published in an international journal that oral treatment of chronic hepatitis B is effective in improving nonalcoholic fatty liver disease.
Professor Seong Pil-soo (corresponding author) from the Department of Gastroenterology of Seoul Catholic University St. Mary’s Hospital and research team Purun Noh (first author) from the Department of Biomedical Health Sciences used an animal model (rat) to determine if tenofovir alafenamide (TAF) is non-alcoholic It was revealed on the 24th that it was the first to identify improvement in fatty liver.
Tenofovir alafenamide, a novel targeted prodrug of tenofovir, was first approved in the United States in 2016 as an oral treatment for adults with chronic hepatitis B. Tenofovir alafenamide has a differentiated mechanism of action that more efficiently delivers the active ingredients to hepatocytes with better plasma stability than existing drugs for chronic hepatitis B. A prodrug is a drug that has a different chemical structure or essential composition from existing drugs and which has an effect through a metabolic process in the body. A prodrug is a drug that has no medicinal effect outside the body, but when it enters the body and is metabolized by metabolic enzymes, it shows a medicinal effect. In other words, it is about showing the effect of a substance on a desired target through a change in the chemical structure of the drug.
As a result of the study, systemic drug exposure in plasma was reduced by approximately 89%, and renal and bone safety improved. The important thing is that tenofovir alafenamide has a strong antiviral effect like the existing drug, but it further improves liver function (ALT normalization rate is further improved), but the mechanism has not yet been identified.
Professor Sung’s team used an animal model of non-alcoholic fatty liver disease and confirmed that ALT (alanine aminotransferase) and AST (aspartate aminotransferase) blood levels were improved and liver cell damage was reduced when tenofovir alafenamide was administered. Also, for the first time, tenofovir alafenamide was identified to inhibit the activation of AKT protein in hepatocytes (mononuclear phagocytes in the liver) to achieve anti-inflammatory effect and improve non-alcoholic fatty liver disease. ATK is an important protein that induces inflammation by activation.
Professor Pil-Soo Seong said: ‘This study is significant in providing a theoretical basis for explaining that tenofovir alafenamide has a significantly higher rate of normalization of liver function than other antiviral drugs.’ lose weight, proper diet and aerobic exercise. It can be prevented, ”he said.
The results of this study were published November 3 in ‘Biomedicine & Pharmacotherapy’ (citation index 7.419), an international journal in the field of pharmacology. It received support from Seoul St. Mary’s Hospital’s Leading Investigator Research Fund and Technology Commercialization Research Fund, and individual basic research from the National Research Foundation. Byung-moon Lee Senior Medical Reporter
