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    Home > Active Ingredient News > Digestive System Information > Clinical thoughts: nonviral liver disease – from discovery to treatment

    Clinical thoughts: nonviral liver disease – from discovery to treatment

    • Last Update: 2022-11-05
    • Source: Internet
    • Author: User
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    For medical professionals only With

    the successive advent of hepatitis B immunization and hepatitis C cure drugs, great achievements have been made in the prevention and control of hepatitis B/C in China, and the overall prevalence is declining
    .
    However, the prevalence of non-viral liver diseases, such as fatty liver and drug-induced liver injury, shows a relatively obvious high incidence trend, which needs attention and attention
    .
    Finding, treating, managing.
    .
    .
    are all difficult problems
    that need to be faced clinically.


    The platform specially invited Professor Lin Bingliang from the Third Affiliated Hospital of Sun Yat-sen University, Professor Mao Yimin from Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, and Professor Fan Jiangao from Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine to share clinical thoughts and help clinicians fully understand the detection and management of non-viral liver diseases, and accurately grasp the mechanism and treatment points of
    liver injury.

    Question 1: In clinical practice, how to effectively detect non-viral liver diseases such as fatty liver and drug-induced liver injury?
    Professor Lin Bingliang:
    Since drug-induced liver injury may occur in various departments, in addition to hepatology, gastroenterology and other departments related to liver disease, doctors in other departments also need to pay more attention
    。 If the patient has unexplained liver function abnormalities, it is necessary to strengthen the inquiry
    about whether the patient takes drugs, health products, medicinal diets, Chinese herbal medicines, etc.
    If the patient has a history of chronic liver disease (such as hepatitis B), doctors should pay more attention to avoiding the use of hepatotoxic drugs
    as much as possible when taking medications.
    Drug-induced liver injury is mostly an exclusive diagnosis, so clinicians need to keep their eyes open, be alert to abnormalities, strengthen the inquiry and case analysis of relevant medical history, and finally get a clear diagnosis
    .

    At present, non-alcoholic fatty liver ranks first in the list of liver diseases in China and needs clinical attention
    .
    Patients with fatty liver are often accompanied by metabolic syndrome, if a patient with abnormal liver function is found, and there are high-risk factors such as obesity, hypertension, hyperuric, hyperlipidemia, diabetes, etc.
    , doctors need to pay attention to whether the patient has the possibility
    of fatty liver.
    Clinically, blood test, liver histology biopsy, B-ultrasound, FibroScan/FibroTouch can be performed to evaluate the degree of liver fat in patients, which is helpful for clinical diagnosis and beneficial to the treatment or control
    of diseases in the future.

    In addition to the doctor's level, it is also necessary to increase the intensity of science popularization, increase the attention to the disease from the public level, and guide patients to go to the hospital for examination
    as soon as possible.

    Nonalcoholic fatty liver disease is the most common cause of chronic liver disease, affecting 25% of the world's population
    .
    Although the prevalence of steatohepatitis is increasing, public awareness of the disease is limited
    .
    Surveys show that only 5% of fatty liver patients know they have the disease
    .
    Drug-induced liver injury is also very common and has become an important cause of clinical acute liver injury, and some patients with acute drug-induced liver injury may also turn into chronic drug-induced liver injury
    .
    For example, many patients think that taking supplements will not affect their health, but drug-induced liver damage often occurs, so it is very important
    to educate the public.
    Therefore, doctors need to educate these patients with high-risk factors and remind patients to go to the hospital for examination as soon as possible when relevant conditions arise, in order to detect and treat
    them early.


    Question 2: The largest epidemiological study of drug-induced liver injury in China so far shows that most patients with drug-induced liver injury are hepatocellular injury, how should these patients be managed? Professor Mao Yimin:
    For the management of patients with drug-induced liver injury, the following measures can be taken:
    1) For people at high risk of drug-induced liver injury or patients who are taking drugs that can cause liver damage, regular monitoring is very important, and regular monitoring is helpful to detect patients with drug-induced liver injury
    in clinical early practice 。 For example, if the patient has normal transaminases and normal liver biochemical indexes before treatment, but significantly increased after treatment, clinicians need to consider whether the patient is a suspected drug-induced liver injury patient; Some patients with underlying liver disease, before drug treatment, the patient's transaminases are higher than normal, if the transaminases are significantly increased after medication, but can not be explained by the original liver disease, at this time, it is clinically suspected whether the patient is liver damage
    caused by drugs.
    Therefore, in the population of drug-induced liver injury, it is very important
    to consider the possibility of liver damage caused by drugs in time and identify such groups in time.

    2) After finding a patient with suspected drug-induced liver injury, clinicians need to adopt a standardized diagnosis and treatment process
    according to the diagnosis and treatment guidelines for drug-induced liver injury.
    The patient is examined accordingly to rule out other possibilities of liver injury, and ultimately relies on causality to assess whether the patient is a patient
    with drug-induced liver injury.

    3) Once the patient has a clear diagnosis, or a high suspicion of drug-induced liver injury, the suspected drug should be stopped in time, which is the most important treatment measure
    for drug-induced liver injury.
    Then, drugs supported by evidence-based medical evidence can be used to intervene, such as glycyrrhizic acid and silymarin
    .


    Question 3: There are currently no specific drugs for the treatment of nonalcoholic fatty liver disease, which progresses to nonalcoholic steatohepatitis
    .
    It is estimated that the number of patients suffering from non-alcoholic steatohepatitis in China will exceed 48 million in 2030, due to the large patient population, how should these patients be managed?
    Professor Fan Jiangao:
    Non-alcoholic fatty liver can develop into steatohepatitis and liver fibrosis, and is a high-risk group
    for liver cirrhosis, liver cancer and death.
    For such groups, corresponding intervention countermeasures need to be taken:

    1) Move the threshold forward, do not let patients with non-alcoholic fatty liver develop steatohepatitis and liver fibrosis, and effectively intervene in the majority of non-alcoholic fatty liver disease groups
    that are still in the stage of simple fatty liver disease.

    2) Obesity, insulin resistance, glucose and lipid metabolism disorders, coexisting sarcopenia syndrome and other conditions are important driving factors for steatohepatitis and liver fibrosis, so timely and effective intervention
    is required for these conditions.
    Effective weight management, reducing body fat content, increasing the content of skeletal muscle, improving insulin resistance, controlling blood lipids and blood sugar can alleviate steatohepatitis and delay and prevent the progression of liver disease, and also reduce the risk
    of cardiovascular disease and extrahepatic malignancy.
    The essence of non-alcoholic steatohepatitis is steatohepatitis associated with metabolic dysfunction, which has a cause to follow, and drugs for weight loss, hypoglycemia and fat regulation can be applied to the cause
    .

    3) For patients who have developed steatohepatitis, especially liver fibrosis, and cannot effectively change their lifestyle, while applying relevant drugs to control weight, blood lipids, blood sugar, and blood pressure, anti-inflammatory hepatoprotective drugs, such as silymarin, can be used
    for a long time.

    Question 4: The causes of liver disease in China are diverse, and the mechanism of liver injury is complex, including oxidative stress, mitochondrial damage, cell membrane damage, inflammation, etc
    .
    In your experience, what are the main upstream shared pathways for different causes of liver injury?
    Professor Lin Bingliang:
    There are many causes of liver damage, Such as infectious factors represented by viral hepatitis, as well as non-infectious factors
    such as drug-induced liver injury and non-alcoholic fatty liver disease.
    Among non-infectious factors, in addition to toxins of origin and their metabolites, fats, bile acids, cellsEndogenous substances such as factors, cytokines and their metabolites can also change the structure and function of hepatocytes, leading to liver damage
    .

    With the deepening of research, it has been found that whether exogenous or endogenous, the toxic effects of these substances have a common key mechanism, which can also be described as a key pathway, that is, oxidative stress (OS).

    Oxidative stress is one of the early key events of
    liver injury that drives disease progression.
    Regardless of which nociceptive stimulus causes liver damage, cell death
    occurs.
    While releasing the contents, damaged cells produce excess reactive oxygen species (ROS), which in turn cause lipid peroxidation and tissue damage, which can further activate Kupffer cells and stellate cells, release a variety of pro-inflammatory and pro-fibrotic mediators, and ultimately trigger liver inflammation and liver fibrosis, and lead to more immune cell infiltration, which can further increase tissue oxidative stress and subsequent fibrosis
    .
    Therefore, oxidative stress is a very important upstream common pathway
    in terms of overall liver damage.

    At present, drug-induced liver injury, non-alcoholic fatty liver disease and other diseases, in addition to removing the cause, there is still a lack of effective specific treatment methods
    .
    Oxidative stress is a common pathophysiological mechanism of many liver diseases, so in clinical practice, drugs with antioxidant effects can be used to target oxidative stress to protect the liver from oxidative stress, inflammation, and fibrosis
    .
    Especially in the early stage of the disease, it may have a good effect on
    reducing inflammation and liver fibrosis.

    Q5: Based on your clinical experience, what are your expectations/recommendations for silymarin tablets to directly target liver origin and fibrosis? Professor Lin Bingliang:
    As a hepatologist, I hope that all patients can receive effective treatment
    when dealing with liver diseases every day.
    It is hoped that through drug treatment, the disease can be blocked, inflammation can be controlled, patients can be prevented from progressing to liver fibrosis, cirrhosis, and even the disease
    can be safely and effectively reversed.

    A common pathway for all types of liver disease to occur is oxidative stress
    .
    For oxidative stress, drugs such as silymarin tablets
    are widely used in clinical practice.
    From the perspective of pharmacological mechanism, it can scavenge free radicals and reduce liver cell damage and liver tissue inflammation
    caused by oxidative stress.
    The main component of silymarin tablets is silymarin, and studies have found that silymarin can directly downregulate type I collagen mRNA and inhibit metalloproteinase inhibitor-1 mRNA, which can indirectly or directly inhibit liver fibrosis by downregulating these two factors that are very important for liver fibrosis
    .

    Silymarin tablets have been on the market for a long time, and have accumulated more clinical data, and its efficacy and safety have also been recognized by everyone, widely used at home and abroad, and have gained a good reputation
    .
    In the future, we also need to accumulate more evidence-based medical evidence and translate experience into research results
    .

    At present, silymarin tablets have also accumulated a lot of clinical application data in patients with drug-induced liver injury and non-alcoholic fatty liver disease, and the data results are
    very gratifying.
    Although silymarin tablets are an old drug, I hope that under the condition that the disease spectrum changes, through clinical application, more patients can benefit
    .

    Professor Mao Yimin:
    Silymarin tablets are an old drug, which has been on the market in China for more than 20 years.
    The safety of its clinical application has been confirmed
    in a large number of long-term clinical practices.
    Studies have suggested that whether in the field of non-alcoholic fatty liver, in terms of evidence of reversing liver fibrosis, or in the application of drug-induced liver injury, there is relevant evidence that silymarin tablets have certain value
    in the treatment of non-alcoholic fatty liver and drug-induced liver injury.

    It is hoped that there will be more evidence-based medical evidence in the future to support and explore the applicable population of drugs to help clinicians make corresponding medical decisions
    .

    Professor Fan Jiangao:
    Silymarin tablets The main ingredient is silymarin, a chemical extracted from milk thistle, which can effectively protect liver cells (especially mitochondria), so as to better play many functions such as liver metabolism, detoxification, antioxidant and so on; In turn, it helps hepatocytes with steatosis to reduce lipotoxicity to prevent and treat liver damage caused by lipid peroxidation; This reduces or even delays the progression
    of liver fibrosis in individuals whose causative or primary driver status cannot be removed.

    Therefore, silymarin hepatoprotective drugs such as silymarin tablets are an important recommended hepatoprotective drug for individuals with nonalcoholic steatohepatitis with or without liver fibrosis, and it is one of
    the components of comprehensive therapy.
    In the state of effectively blocking the patient's weight/waist circumference growth, preventing the patient's excessive drinking, mobilizing the patient to diet and increase exercise, the application of silymarin tablets can make silymarin tablets play a better effect
    .

    In recent years, more and more evidence-based evidence has been confirmed from the inside out from a molecular perspective: the production of large amounts of reactive oxygen species (ROS) is an upstream and key mechanism
    of liver injury.
    Therefore, we need to grasp the source, intervene in time, and continue to protect the liver and prevent liver damage
    .

    ROS is not only an important upstream mechanism for the formation of drug-induced liver injury, but also can mediate oxidative stress and participate in the entire disease process of nonalcoholic steatohepatitis and play a central role
    .
    Therefore, in the treatment of drug-induced liver injury and non-alcoholic steatohepatitis, we continue to explore the clinical benefits
    that can be brought by the "clean source".

    Silymarin tablets can reduce upstream oxidative damage through antioxidant in various liver diseases, and play a therapeutic role through double protection (protecting cell membranes and mitochondria), directly hitting the origin of the liver; Through double anti-fiber, liver fibrosis is delayed or even reversed, thereby facilitating fibrosis
    .

    It is hoped that silymarin tablets can bring vitality to more Chinese patients with liver disease in the future and become a strong choice
    for more clinical medical workers in clinical drug selection.

    Where to see more clinical knowledge of digestive liver disease? Come to the "doctor station" to take a look 👇
    at the source of this article: hepatobiliary photography platform

    Disclaimer: This content is intended only for healthcare professionals in China and is intended to provide scientific information to healthcare professionals for personal learning and reference
    .
    If you are not a healthcare professional, do not participate or spread
    .

    - End -

    This article is for the sole purpose of providing scientific information to medical professionals and does not represent the position of
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