Seoul St. Mary’s Hospital Professor Seong Pil-soo proves 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 of as alcoholic, caused by excessive drinking, but 80% of non-alcoholic fatty liver occurs without drinking alcohol. Diagnosis is made by ultrasound of the liver and abdomen and blood tests that measure the 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 examinations for other purposes. Non-alcoholic fatty liver 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 who visited the hospital for non-alcoholic fatty liver increased by more than 40% in the last 5 years from 283,038 in 2017 to 405,950 in 2021. If non-alcoholic fatty liver is left untreated, it can progress to non-alcoholic 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 chronic hepatitis B treatment is effective in improving non-alcoholic fatty liver.
The Catholic University of Korea Seoul St. Mary’s Hospital Department of Gastroenterology Professor Seong Pil-soo (corresponding author) and the Department of Biomedical Health Sciences master’s course Researcher Purun Noh (first author) research team used an animal model (rat) to determine whether tenofovir alafenamide (TAF) is non-alcoholic It was revealed on the 24th that it was the first to identify the improvement of 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 active ingredients to hepatocytes with improved plasma stability compared to existing chronic hepatitis B drugs. A prodrug is a drug that has a chemical structure or essential composition that is different from existing drugs, and that 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, this is to show 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 about 89% and kidney and bone safety were improved. The important thing is that tenofovir alafenamide has a strong antiviral effect like the existing drug, but additionally improves liver function (ALT normalization rate is further improved), but the mechanism has not been identified so far.
Professor Sung’s team used a non-alcoholic fatty liver animal model and confirmed that blood ALT (alanine aminotransferase) and AST (aspartate aminotransferase) levels were improved and liver cell damage was reduced when tenofovir alafenamide was administered. did. In addition, for the first time, it was identified that tenofovir alafenamide inhibits the activation of AKT protein in hepatocytes (mononuclear phagocytes in the liver) to obtain an anti-inflammatory effect and improve non-alcoholic fatty liver. ATK is an important protein that induces inflammation by activation.
Professor Pil-Soo Seong said, “This study is meaningful in providing a theoretical basis to explain that tenofovir alafenamide has a significantly higher liver function normalization rate than other antiviral drugs.” There is no drug approved for treatment, so patients are advised to actively lose weight, proper diet, and aerobic exercise. It can be prevented,” he said.
The results of this study were published on November 3rd in ‘Biomedicine & Pharmacotherapy’ (citation index 7.419), an international journal in the field of pharmacology. She received support from Seoul St. Mary’s Hospital leader researcher research fund and technology commercialization research fund, and individual basic research from the National Research Foundation. Byung-moon Lee Senior Medical Reporter