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    Home > Active Ingredient News > Digestive System Information > Summary: Classification, diagnosis, and treatment of drug-induced liver disease

    Summary: Classification, diagnosis, and treatment of drug-induced liver disease

    • Last Update: 2022-04-27
    • Source: Internet
    • Author: User
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    Introduction Drug-induced liver disease, also known as drug-induced liver injury (DILI), refers to all kinds of prescription or non-prescription chemical drugs, biological preparations, traditional Chinese medicines, natural medicines, health products, dietary supplements and their metabolites and even excipients.
    induced liver damage
    .

    Common drugs that cause DILI include: non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs (including anti-tuberculosis drugs), anti-tumor drugs, central nervous system drugs, cardiovascular system drugs, metabolic disease drugs, hormone drugs, Certain biologics and dietary supplements,
    etc.

    This article summarizes the classification, diagnosis and treatment of DILI in order to provide reference for clinicians
    .

    Classification 1.
    Based on the course of disease DILI can be divided into acute and chronic based on the course of disease
    .

    Acute DILI: The disease duration is less than 6 months
    .

    Within 6 months of DILI, the liver function returned to normal, and there was no obvious imaging and histological evidence of liver function damage
    .

    Chronic DILI: 6 months after DILI, serum liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil)] remain abnormal , or the presence of imaging and histological evidence of portal hypertension or chronic liver injury
    .

    2.
    Based on damaged target cell types DILI can be divided into four types based on damaged target cell types: hepatocyte damage type, cholestasis type, mixed type and hepatic vascular damage type
    .

    Hepatocyte damage type: The clinical manifestations are similar to viral hepatitis, and the diagnostic criteria are ALT ≥ 3 times the upper limit of normal (ULN), and R value ≥ 5
    .

    R value=serum (measured ALT/ALT ULN)/(measured ALP/ALP ULN)
    .

    Histologically characterized by hepatocyte necrosis with infiltration of eosinophils and lymphocytes in the portal area
    .

    Cholestatic type: Mainly manifested as jaundice and pruritus, ALP ≥ 2 times ULN and R value ≤ 2
    .

    Histologically, it is characterized by capillary bile duct-type cholestasis
    .

    Mixed type: both clinical and pathological manifestations of hepatocyte injury and cholestasis, ALT≥3 times ULN, ALP≥2 times ULN and 2<R value<5
    .

    Hepatic vascular injury type: This type is relatively rare, and the pathogenesis is still unclear
    .

    Clinical types include hepatic sinusoidal obstruction syndrome/hepatic veno-occlusive disease, purpuric liver disease, Budd-Chiari syndrome, portal cirrhosis, and portal vein thrombosis
    .

    Diagnosis of DILI is a diagnosis of exclusion, mainly based on the history of medication, recovery after drug discontinuation, response to re-medication, laboratory evidence of hepatocellular injury and cholestasis, and exclusion of other causes of liver injury
    .

    The RUCAM scale can be used to assess the causality of drug-induced liver injury, guiding the systematic and objective evaluation of patients with suspected DILI
    .

    The scale comprehensively evaluates the cause and effect of drugs and DILI, including 7 major elements, namely onset time, characteristics of biochemical changes, risk factors (drinking, pregnancy and age), combined drug use, exclusion of other liver damage, and previous liver injury.
    History of toxicity and re-dose reactions
    .

    The score of RUCAM scale ranges from -9 to +14 points.
    According to the comprehensive score of the above 7 elements, the possibility of DILI is judged and divided into 5 grades: ① very likely, score > 8; ② very likely, score 6 ~8 points; ③ Possible, score 3-5; ④ Unlikely, score 1-2; ⑤ Excluded, score ≤ 0
    .

    The principle of treatment for DILI is to stop and prevent the re-use of related drugs that cause liver damage, clear and excrete drugs from the body at an early stage, and try to avoid the use of drugs with the same and similar pharmacological effects or chemical structures.
    Symptomatic and supportive care for patients with liver failure
    .

    1.
    Discontinuation of drugs is the most important measure for the treatment of drug-induced liver damage
    .

    If the drug is clinically suspected to cause liver damage, the drug should be discontinued in time.
    Most patients can relieve themselves after the drug is discontinued
    .

    When a drug causes liver damage, the risk of progression of the primary disease caused by discontinuation of the drug should be fully weighed against the risk of aggravated liver damage caused by continued use of the drug, and other types of drugs can be used to treat the primary disease
    .

    2.
    Removal of drugs If a large number of liver-damaging drugs are taken by mistake, the residual drugs in the gastrointestinal tract can be removed by methods such as emesis, gastric lavage, catharsis, and enema
    .

    For drugs that have entered the blood, the excretion of drugs in the body can be accelerated by methods such as diuresis, hemodialysis, and blood perfusion
    .

    3.
    Drug therapy should choose appropriate drug therapy according to the clinical type of DILI
    .

    Mild to moderate hepatocellular injury type and mixed DILI, silymarin can be tried for mild inflammation, glycyrrhizic acid preparations (such as diammonium glycyrrhizinate or monoammonium glycyrrhizinate cysteine ​​compound preparation), other commonly used drugs Including arginine glutamate injection and bicyclol; ursodeoxycholic acid can be used for cholestatic DILI, but its effectiveness in reducing the severity of liver injury has not been proven, and adenosylmethionine (SAMe) has been reported in the treatment of cholestasis Type DILI is valid
    .

    At present, it is recommended to add N-acetylcysteine ​​(NAC) on the basis of comprehensive treatment in the treatment of early acute liver failure (ALF), but the efficacy of NAC on moderate to severe DILI needs further study
    .

    NAC is not recommended for the treatment of non-acetaminophen (APAP) drug-induced ALF in children, especially in children 0-2 years of age
    .

    The rate of administration should be strictly controlled during treatment to prevent adverse reactions
    .

    The China Food and Drug Administration (CFDA) approved the addition of acute DILI as the treatment indication of magnesium isoglycyrrhizinate, which can be used to treat acute hepatocellular injury or mixed DILI with significantly elevated ALT
    .

    4.
    Liver transplantation For patients with hepatic encephalopathy, severe coagulopathy with ALF/subacute liver failure (SALF) and decompensated cirrhosis, liver transplantation can be considered
    .

    References: [1] Yu Wenhao, Liu Wen.
    Research progress of drug-induced liver disease [J].
    China Journal of Integrative Medicine and Digestion, 2020,28(05):398-402.
    [2] Chinese Medical Association, Chinese Medical Association Journal She, Gastroenterology Branch of Chinese Medical Association, et al.
    Guidelines for primary diagnosis and treatment of drug-induced liver injury (2019)[J].
    Chinese Journal of General Practitioners, 2020,19(10):868-875.
    [3] Ge Junbo, Xu Yongjian , Wang Chen, et al.
    Internal Medicine (Ninth Edition)[M].
    People's Health Publishing House, 2018:401-404.
    [4] Xie Xinhe, Zhao Ruiling.
    Research progress in clinical diagnosis of drug-induced liver injury[J].
    Medical Review, 2019, 25(20): 4044-4048+4054.

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