NSAID-induced liver damage with cholestasis

2021 ◽  
pp. 37-48
Author(s):  
A. P. Pereverzev ◽  
O. D. Ostroumova ◽  
O. V. Golovina ◽  
A. V. Filippova ◽  
Е. Е. Pavleeva

he liver is one of the organs most often affected by medication (MP) intake. Drug-induced liver damage with cholestasis (LIPCH), on the one hand, rarely leads to death in comparison with the hepatocellular type, but, on the other hand, is more often characterized by a long, in some cases chronic course. This type of liver damage is characterized by an increase in the activity of alkaline phosphatase (ALP) > 2 upper limits of normal (ULN) or the ratio of alanine aminotransferase (ALT) / ALP < 2 in chronic course. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most readily available (including over-the-counter) and widely used drugs in clinical practice and are often the cause of LIPCH. This article summarizes the available data at the time of preparation of the article on the prevalence, mechanisms of development and features of LIPPH while taking NSAIDs. A separate section is highlighted on the features of the management of such patients. In particular, in accordance with both domestic and foreign clinical guidelines for the drug genesis of liver damage, it is recommended to stop taking the inducer drug and prescribe ursodeoxycholic acid (UDCA). The efficacy of UDCA in patients with LIPCH, including those associated with the use of NSAIDs, has been confirmed by the results of a large number of randomized placebo-controlled clinical trials. Among the UDCA preparations on the market of the Russian Federation, one cannot fail to pay attention to Exho® (CJSC «Canonpharma Production»), which is bioequivalent to the reference drug, is produced in compliance with GMP standards on a high-tech production base, which ensures its quality, and an affordable price and a large the choice of dosage forms makes it possible to successfully use this drug, including in special categories of patients, for example, elderly patients and/or those suffering from dysphagia.

2021 ◽  
pp. 31-43
Author(s):  
O. D. Ostroumova ◽  
A. P. Pereverzev ◽  
E. E. Pavleeva ◽  
R. R. Romanovsky

Drug-induced liver injury (DILI) is a fairly frequent adverse drug reaction, which accounts for about half (40–50 %) of cases of acute liver damage. The cholestatic variant of DILI is characterized by an increase in the activity of alkaline phosphatase (ALP) above the two upper limits of the norm (ULN) or the ratio of alanine aminotransferase (ALT) / ALP ≤ 2 in chronic course. A common cause of the cholestatic variant of DILI is a use of drugs for the treatment of infectious diseases, such as beta-lactam antibiotics, Aminoglycosides, Amphenicol, Lincosamides, macrolides, fluoroquinolones, antituberculosis drugs, etc. This problem has acquired particular urgency during the COVID-19 pandemic. The widespread use of azithromycin, hydroxychloroquine, interferons, lopinavir, and other drugs for the treatment of COVID-19 also contributed to an increase in the incidence of DILI. In accordance with clinical guidelines in case of suspicion of a drug-induced liver damage, one should stop use of suspected drug and, if necessary, prescribe hepatoprotectors, for example, ursodeoxycholic acid (UDCA). The effectiveness of the use of UDCA in patients with DILI, including those caused by the intake of antibacterial drugs, has been confirmed by randomized placebo-controlled clinical trials. The effectiveness of UDCA -drug Ursosan® has been confirmed in real life clinical practice. This drug can be used for long-term (up to several months), or lifelong treatment with hepatotoxic drugs like antituberculosis and antirheumatic drugs. The daily dose of Ursosan® is 12–15 mg/kg, if necessary – 20 mg / kg (with a weight of a patient about 75–100 kg, daily dose will be equal to two tablets of Ursosan Forte®, 500 mg).


2020 ◽  
Vol 10 (3) ◽  
pp. 244-248
Author(s):  
Mehr Fatima ◽  
Syed Zaidi

Drug induced liver injury is one of the main factor of liver failure and acute liver damage world wide with high incidence in western countries. Liver injury can be intrinsic (dose dependant) or idiosyncratic (dose independent). However idiosyncratic type is considered to be mainly responsible for drug induced liver damage. Binding of reactive metabolites of drugs to tissue proteins and oxidative stress is the possible cellular mechanism involved in this process. Moreover, some antibiotics, anti-epileptics, nonsteroidal anti-inflammatory drugs etc are more likely to induce liver damage in high risks groups that includes females, elderly and obese people. HLA halotype and variation in protein expression also plays an important role in this context. Various studies are available regarding clinical features, histopathological features, diagnosis and management related to antibiotics and acetaminophen induced liver damage. N acetylcysteine is commonly available antidote for drug induced hepatic damage. Role of other pharmacological agents as an antidote requires further studies. However, liver transplantation should be considered with drug induced lethal liver failure


2019 ◽  
pp. 84-88
Author(s):  
E. I. Sas ◽  
V. B. Grinevich

Drug-induced liver injuries (DILI) remain today one of the most pressing problems not only in gastroenterology, but also in all therapy. Up to 10% of the changes in laboratory parameters can be attributed to the use of drugs. The importance of DILI has increased significantly in recent years, due to the increase in the number of over-the-counter medicines on the pharmaceutical market, as well as non-compliance with the methods and modes of administration. There are common links in the pathogenesis of DILI, including hypoxia, de-energization (deficit of ATP production), damage to hepatocyte membranes and suppression of antioxidant protection. Therefore, pathogenetic pharmacotherapy and prevention of liver damage are based on drugs with an action mechanism aimed at eliminating one or more links in the pathogenesis. One of these drugs is Remaxol, which includes antihypoxantantioxidants of metabolic type: natural metabolites, substrates and cofactors involved in energy metabolism. Remaxol was administered to 30 patients with duodenal ulcer (DU) in the acute phase in addition to the main eradication therapy in the case of cytolytic syndrome by the end of the first week of therapy intravenously dripping at a rate of 40-60 drops/min in a daily dose of 400 ml for 10 days a day. Against the background of Remaxol application, the patients with DILI had stabilization of the main biochemical parameters: the level of AST, ALT, direct bilirubin, GGT and alkaline phosphatase. These changes were accompanied by a positive dynamics of the general state of health. The use of Remaxol in patients with DILI will allow to achieve clinical and biochemical remission, preventing the development of severe liver damage, and contributes to the preservation of the recommended duration of treatment of the underlying disease.


2021 ◽  
pp. 110-121
Author(s):  
D. I. Trukhan ◽  
E. L. Davydov

Medicinal liver damage is an important problem not only in the framework of hepatology and gastroenterology, but also for internal medicine in  general, which is due to the  difficulties of  correct and timely diagnosis of  this pathology. In  the  first part of the review, the main mechanisms of liver tissue damage and clinical and formological manifestations of drug-induced liver damage are considered.The pandemic of the new coronavirus infection (COVID-19), spread by the SARS-CoV-2 virus, has become a challenge to health systems around the world. The global clinical experience gained over the past year in the management of patients with a new coronavirus infection makes it possible to highlight a number of relevant clinical aspects, one of which is drug-induced liver damage associated with the treatment of COVID-19. In the second part of the review, the possible mechanisms of influence of COVID-19 on the hepatobiliary system are considered, which include viral cytotoxicity, a secondary effect of immune dysregulation; hypoxia as a result of respiratory failure and subsequent ischemic liver damage; reactivation of already existing liver pathology and drug damage to the liver. It has been established that a large number of drugs used to treat COVID-19 - antiviral agents, antibacterials, non-steroidal anti-inflammatory drugs, steroids and others - have hepatoxic effects and can cause liver damage. In the context of the COVID-19 pandemic, for patients with a new coronavirus infection and drug-induced liver damage, a rational, pathogenetically justified choice of a hepatoprotective drug is of particular importance. In the final part of the review, the possibilities of the polyionic succinate-methionine complex in the treatment of drug-induced liver damage are considered and a clinical example of the drug application in a patient with drug-induced liver damage during treatment with COVID-19 is given.


2021 ◽  
Vol 13 (1) ◽  
pp. 233-238
Author(s):  
Seyed Mohammad Mousavi Mirzaei ◽  
Zahra Ahmadi

Drug-induced aseptic meningitis (DIAM) is a rare complication of certain drugs, most commonly reported with ibuprofen use. The present study reports on a male adolescent with intracranial hypertension and visual impairment accompanied by DIAM. We present a 16-year-old male patient who after ibuprofen consumption displayed headache, fever, photophobia, and blurred vision following heavy exercises. Examination of cerebrospinal fluid showed a mononuclear pleocytosis and an increase in protein concentration. Other examinations had normal results. The development of common clinical signs following ibuprofen use reflected DIAM. The patient’s vision was found to improve with supportive care and stopping of the drug during follow-up. Given the widespread use of nonsteroidal anti-inflammatory drugs and the fact that these drugs are the most common cause of DIAM, the probability of occurrence of this event should be always kept in mind, and screening for autoimmune diseases in these patients is of great importance.


2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110066
Author(s):  
Qinghong Meng ◽  
Na Li ◽  
Lianmei Yuan ◽  
Xiaona Gao

Aims To explore the causes of liver damage among children 12 years and younger in Weifang and to provide a theoretical basis for early diagnosis of liver damage in children. Methods Retrospective study of clinical data from pediatric patients (age ≤12 years) with liver damage in diagnosed at Weifang People's Hospital from June 2010 to May 2020. Results A total of 2632 children (1572 boys, 1060 girls) aged ≤12 years were diagnosed with liver damage including infectious liver damage (2100 cases), non-infectious liver damage (446 cases) and liver damage of unknown etiology (86 cases). The most common causes of infectious liver damage were viral infection (1515 cases), Mycoplasma pneumoniae infection (343 cases), and bacterial infection (197 cases). The most common causes of viral liver damage were Epstein–Barr virus, cytomegalovirus, and enterovirus. The most common causes of non-infectious liver damage were drug-induced liver damage, Kawasaki disease, and genetic metabolic diseases. There were 31 cases of severe liver damage. Conclusion There were many causes of liver damage among children in Weifang. Infections, and especially viral infections such as Epstein–Barr virus, were the most common causes of liver damage. Severe liver damage was primarily caused by drugs or poisons.


2005 ◽  
Vol 47 (3) ◽  
pp. 171-176 ◽  
Author(s):  
Walter Belda Junior ◽  
Ana Carolina Junqueira Ferolla

Acute Generalized Exanthematous Pustulosis (AGEP) is a drug-induced dermatosis characterized by an acute episode of sterile pustules over erythematous-edematous skin. It is accompanied by an episode of fever, which regresses a few days after discontinuation of the drug that caused the condition or as a result of corticosteroid treatment. The main triggering drugs are antibiotics, mainly beta-lactam ones. Other medications, such as antifungal agents, non steroid anti-inflammatory drugs, analgesics, antiarrhythmic, anticonvulsant and antidepressant drugs, may also be responsible. Histologically, it is characterized by the existence of vasculitis, associated with non-follicular subcorneal pustules. A case of a Caucasian female outpatient unit of Dermatology with AGEP, who presented with generalized pustulosis lesions after the use of cephalosporin for urinary infection is related. The diagnosis was confirmed by the clinical and pathological correlations, the resolution of the dermatosis after discontinuation of the drug and use of systemic corticosteroid treatment, and the recurrence of the disorder after the introduction of a similar drug. The importance of the recognition of this drug-induced dermatosis is given by its main differential clinical and histological diagnoses: generalized pustular psoriasis and subcorneal pustulosis.


2007 ◽  
Vol 4 (7) ◽  
pp. 403-408 ◽  
Author(s):  
Igino Rigato ◽  
Monica Cravatari ◽  
Claudio Avellini ◽  
Euro Ponte ◽  
Saveria Lory Crocè ◽  
...  
Keyword(s):  

Author(s):  
R. Kokenov ◽  
◽  
◽  

Due to the fact that the modern world is in the context of globalization, the development of the countries of the world is accompanied by a qualitative increase in technology in the field of science and technology, in connection with which, there is an internationalization of scientific developments, high-tech production, as well as competition between countries over the distribution of resources is intensifying, in terms of new developments and development in general. Cooperation in itself bears the potential of mutual assistance, joint solution of a set of international, scientific problems by the participating countries. For this reason, modern scientific cooperation is a consequence of well-built scientific diplomacy. Scientific diplomacy is called upon to promote the development of scientific cooperation; it is aimed at maintaining partner diplomatic relations, which, on the one hand, can use science to bring together interstate priorities, and, on the other hand, contribute to the development of science itself. The latest diplomacy has adopted scientific approaches and is actively solving modern challenges facing governments and countries. The article discusses the work of international organizations in the designated area of research, provides Kazakhstani experience in resolving the issue


2022 ◽  
Author(s):  
Urmila Jagtap ◽  
Sandeep Basu ◽  
Lavanya Lokhande ◽  
Nikhil Bharti ◽  
Chetana Sachidanandan

The use of many essential drugs is restricted due to their deleterious effects on the liver. Molecules that can prevent or protect the liver from drug induced liver injury (DILI) would be valuable in such situations. We used hepatocyte-specific expression of bacterial nitroreductase in zebrafish to cause temporally controlled liver damage. This transgenic line was used to run a whole organism based chemical screen in zebrafish larvae. In this screen we identified BML-257, a potent small molecule AKT inhibitor, that protected the liver against metronidazole-induced liver injury. BML-257 also showed potent prophylactic and pro-regenerative activity in this liver damage model. BML-257 also showed remarkable protective action in two independent toxicological models of liver injury caused by acetaminophen and Isoniazid. This suggests that BML-257 may have the potential to protect against multiple kinds of drug induced liver injury.


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