- Received November 30, -0001
- Accepted November 30, -0001
- Publication January 13, 2021
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- DOI 10.18231/j.ijcaap.2020.033
-
CrossMark
- Citation
Hepatotoxicity: A comprehensive review
Introduction
The liver assumes a significant part in the digestion and expulsion of medications. Detoxification of medications and xenobiotic in the liver by drug utilizing chemicals (DMEs) is a significant wonder in the securing of homeostasis.[1] The liver is an imperative organ and its key area and multidimensional capacities uphold pretty much every other organ in the body. Liver is likewise the primary organ for digestion and disposal of medications.[2] Poisonous hepatitis is the most extreme antagonistic response to antituberculosis drugs, it as a rule starts in the initial not many long stretches of treatment alongside liver rot, which may advance to encephalopathy and demise. Alcoholic liver illnesses with cirrhosis (development of stringy tissue in liver) brought about by unreasonable liquor utilization is a typical event. Liver can once in a while be harmed by certain synthetic substances called hepatotoxins. [3] Drug-induced liver injury (DILI) is the most continuous sign for drug withdrawal from the drug market because of its relationship with noteworthy antagonistic impacts, dismalness, and mortality. [4] DILI is liable for most of intense liver disappointment cases and is currently the main source for liver transplantation among patients. [5] It is critical to perceive that DILI is generally named characteristic (or direct) versus particular. Natural DILI is regularly portion related and happens in a huge extent of people presented to the medication (unsurprising) and beginning is inside a brief timeframe length (hours to days). [6]
|
Types |
Prognosis |
Enzymatic Profile |
|
Hepatocellular |
More Severe prognosis |
Alanine transaminase >2ULN, Serum ALT/Serum Alk. |
|
Cholestatic |
More prone to chronic disease |
Alk phos> 2 Upper limit of normal, Serum Alanine transaminase, serum Alk. |
|
Mixed |
More prone to chronic disease |
Alanine transaminase > 2 Upper limit of normal, Phos between 2 & 5 |
Types of liver diseases and its symptom
There are various types of liver disease mentioned bellow in the table.[8], [9], [10]
|
Liver Disease |
Characterization |
Causes/Conditions of Disease |
|
Acute liver failure |
Reduction in liver function |
Drugs, toxic chemicals, various liver diseases |
|
Autoimmune related |
Development of antibodies against self- liver cells, Inappropriate immune response against hepatic cells |
Primary biliary cirrhosis, Primary sclerosing cholangitis, Autoimmune hepatitis |
|
Genetic disease |
Gene mutations that causes liver injury |
Hemochromatosis, Wilson's disease, deficiency of α-1 antitrypsin |
|
Liver infections |
Infections that leads to several type of liver damage and blockage of bile ducts |
Viral hepatitis (Hepatitis A, B, C, D and E), Parasitic infections (yellow fever virus, herpes viruses) |
|
Hepatitis (A,B,C,D and E) |
Acute or chronic liver damage |
Hepatotropic viruses, alcohol assumption, drugs, xenobiotics, autoimmune disease, non-alcoholic fatty liver disease (NAFLD) |
|
Liver cancer |
Cancerous tumour in the liver |
Increased risk of chronic Hepatitis ; hepatocellular carcinoma (HCC) |
|
Hepatic vein obstruction |
Blood clots obstruct , blood flow from the liver; development of symptoms such like jaundice enlarged liver, ascites, and abdominal pain |
Hypercoagulable disorders, thrombosis of the hepatic vein, hepatic cancer, parasitic infection |
|
Bile ducts obstruction |
Blockage of bile ducts |
Tumours, Gallbladder stones, inflammation, sudden physical injury |
|
Liver diseases |
Drugs |
Mechanism |
|
Zonal necrosis |
Paracetamol, carbon tetrachloride, Amatoxins |
Cessation of protein synthesis due to the inhibition of RNA synthesis, largely confined to a particular zone of the liver lobule [1] |
|
Cholestasis |
Chlorpromazine, estrogen, erythromycin and its derivatives [11] |
Impairment of bile flow, itching and jaundice. Injury to canalicular membrane and transporters (Kaplowitz; 2004). |
|
Steatosis |
Carbamazepine [12] |
Triglyceride accumulation which leads to either small droplet [micro vesicular] or large droplet [macro vesicular] fatty liver |
|
Micro vesicular fats Non-alcoholic steatohepatitis Lactic acidosis |
Didanosine, tetracycline, acetylsalicylic acid, valproic acid Amiodarone, tamoxifen Zidovudine, riboflavin, metformin |
Altered mitochondrial respiration, β- oxidation leads to lactic acidosis and triglyceride accumulation[12] |
|
Granuloma |
Diltiazem, sulfa drugs, quinidine |
Granulomas located in periportal or portal areas and show features of systemic vasculitis and hypersensitivity, Macrophages, lymphocytes infiltrate hepatic lobule. |
|
Vascular lesions/collapse [13] |
Nicotinic acid, cocaine, methylenedioxymeth amphetamine |
Injury to the vascular endothelium/ Causes ischemic or hypoxic injury. |
|
Oncogenesis |
Oral contraceptives, androgens |
Encourages tumor formation [13] |
|
Veno- occlusive [14] |
Busulfan, cyclophosphamide |
Injury to the hepatic venous endothelium. |
|
Antimicrobial |
Anti- epileptics |
Analgesics and Anti- Tuberculosis drug |
Immunomodulator |
Others |
|
Amoxicillin |
Phenytoin |
NSAIDs |
Interferon- β |
Methotrexate |
|
Isoniazid |
Lamotrigine |
Rifampicin, Rifabutin |
Interferon-α |
Androgen- containing steroids |
|
Sulfamethoxazole |
Valproic Acid |
Pyrazinamide |
Anti-TNF agents Azathioprine |
Amiodarone |
|
Trimethoprim |
Carbamazepine |
Prothionamide |
Cyclophosphamide |
Inhaled anaesthetics |
Conclusion
Drug induced Liver Injury harm goes from the unusual and non-portion identified with that happening typically after overdoses. It may include digestion to harmful, receptive intermediates, obstruction, with film transport or with cell natural chemistry, for example, protein amalgamation, or immunological instruments and contrasts in resistant responsiveness, hereditary, dietary and different variables. The liver is dependent upon expected harm from a gigantic exhibit of drug operators, Natural poisons, metals and metalloids, mycotoxins, endotoxins.
Acknowledgment
The authors acknowledge the chairman of Mr. Anil Chopra, Vice Chairperson Ms.Sangeeta Chopra & Pro-Chairman Mr. Prince Chopra, St. Soldier Group of Educational Society, Jalandhar for providing the necessary facilities to complete this review work.
Conflicts of Interest
All contributing authors declare no conflicts of interest.
Source of Funding
None.
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