Drug Induced Liver Disease (Hepatotoxicity)-Chapter 13-IMPORTANT EXAMPLES OF DRUG-INDUCED LIVER DISEASES DRUGS Part-4

Vitamins and Herbs

                 Excess intake of vitamin A, taken for years, can damage the liver. It is estimated that more than 30% of the U. S. population takes supplements of vitamin A, and some individuals are taking vitamin A at high doses that may be toxic to the liver (greater than 10,000 units/ day). Vitamin A-induced liver disease includes mild and reversible elevation in blood liver enzymes, hepatitis, chronic hepatitis with cirrhosis, and liver failure.

                The symptoms of vitamin A toxicity may include bone and muscle aches, orange discoloration of skin, fatigue, and headache. In advanced cases, patients will develop enlarged livers and spleens, jaundice, and ascites (abnormal buildup of fluid in the abdomen). Patients who drink alcohol heavily and have other preexisting liver disease are at increased risk of liver damage from vitamin A. Gradual improvement in the liver disease usually occurs after stopping vitamin A, but progressive liver damage and failure may occur in severe vitamin A toxicity with cirrhosis.

              Liver toxicity also has been reported with herbal teas. Examples include Ma Huang, Kava Kava , pyrrolizidine alkaloids in Comfrey, germander, and chaparral leaf. Amanita phylloides is a liver-toxic chemical found in poisonous mushrooms. Consumption of a single poisonous mushroom can lead to acute liver failure and death.

          The increasing use of alternative medicines has led to many reports of toxicity. The spectrum of liver disease is wide with these medicines.

• Senecio/crotalaria (Bush teas) can cause venoocclusive disease.

• Germander in teas is used for its anticholinergic and antiseptic properties. Jaundice with high transaminase levels may occur after 2 months of use, but it disappears after stopping the drug.

• Chaparral is used for a variety of conditions, including weight loss, cancer, and skin conditions. It may cause jaundice and fulminant hepatic failure.²

• Chinese herbs (Jin bu huan [Lycopodium serratum], Inchin-ko-to, Ma-huang [Ephedra equisetina]) have been associated with hepatotoxicity.

Recreational drugs

• Ecstasy is an amphetamine used as a stimulant and may cause hepatitis and cirrhosis.

• Cocaine abuse has been associated with acute elevation of hepatic enzymes. Liver histology shows necrosis and microvascular changes.

Table.13.1:- Characteristics of Antibiotic-Induced Hepatotoxicity

   

Table.13.2:-

 

S.No.	Spectrum of Hepatic Manifestations of Drug-Induced Liver Disease
1.	Acute hepatitis	Acetaminophen, isoniazid, troglitazone, bromfenac
2.	Chronic hepatitisaa	Nitrofurantoin, methyldopa, diclofenac, minocycline, dantrolene
3.	Acute cholestasis	Amoxicillin, clavulanic acid, erythromycins, sulindac, chlorpromazine, angiotensin-converting enzyme inhibitors
4.	Mixed hepatitis/cholestasis or atypical hepatitis	Phenytoin, sulfonamides
5.	Chronic cholestasisaa	Chlorpromazine, numerous others on rare occasion
6.	Non-alcoholic steatohepatitis	Amiodarone, tamoxifen
7.	Fibrosis/cirrhosis	Methotrexate
8.	Microvesicular fatty liver	Valproic acid, nucleoside reverse transcriptase inhibitors
9.	Veno-occlusive disease	Busulfan, cyclophosphamide
10.	Peliosis hepatitis	Azathioprine, hormones
11.	Adenoma and hepatocellular carcinoma	Hormones