Hepatic Insufficiency: Prevention

To prevent liver failure, attention must be paid to reducing individual risk factors. Behavioral risk factors

• Consumption of stimulants
  • Alcohol
• Drug use
  • Ecstasy (also XTC and others) – collective name for a variety of phenylethylamines.
  • Cocaine

Drugs (hepatotoxic)

• Allopurinol
• Analgesics (incl. NSAIDs)
  • Acetylsalicylic acid (ASA), diclofenac, ibuprofen, indometacin, metamizole, acetaminophen* (paracetamol), sulindac* Non-alcoholic fatty liver (NAFLD)/non-alcoholic steatohepatitis (NASH) may potentiate the hepatotoxic effects of certain drugs, e.g., acetaminophen. However, for many potentially hepatotoxic drugs, no robust data currently exist on the impact on NAFL/NASH that would limit their use. (strong consensus)
  • Flupirtine (nonopioid analgesic) [Pharmacovigilance Risk Assessment Committee (PRAC) recommends withdrawal of marketing authorization, 2018]
• Antiarrhythmic drugs – amiodarone
• Antibiotics
  • Aminoglycoside antibiotics (gentamycin).
  • Aminopenicillins (amoxicillin) – especially common combination: amoxicillin and clavulanic acid.
  • Clavulanic acid
  • Gyrase inhibitors – quinolones: ciprofloxacin, levofloxacin, moxifloxacin.
  • Isoxazolylpenicillins (so-called staphylococcal penicillins) – oxacillin.
  • Ketolides
  • Lincosamide antibiotics (lincosamides) – clindamycin
  • Macrolide antibiotics (macrolides) – azithromycin, clarithromycin, erythromycin.
  • Nitroimidazoles (metronidazole).
  • Nitrofurantoin
  • Penicillins (flucloxacillin)
  • Sulfonamides (sulfasalazine, synonym: salazosulfapyridine).
  • Tetracyclines (doxycycline, minocycline).
  • Trimethoprim / sulfamethoxazole)
• Antidepressants
  • Dual-serotonergic antidepressants (DSAs) – nefazodone
  • Melatonin receptor agonists (MT1/MT) and serotonin 5-HT2C receptor antagonists – agomelatine; contraindicated in patients 75 years of age and older.
  • Noradrenergic and specific serotonergic antidepressants (NaSSA) – mirtazapine.
  • Selective serotonin reuptake inhibitors (SSRIs) – fluoxetine, paroxetine, sertraline, trazodone.
  • Selective dopamine and norepinephrine (slightly also serotonin) reuptake inhibitors (NDRI) – bupropion.
  • Tricyclic antidepressants (TCAs) – amitriptyline
• Antiepileptic drugs – carbamazepine, valproate.
• Antihistamines – cyproheptadine
• Antihypertensives – alphamethyldopa, nifedipine, diltiazem, lisinopril, fosinopril, captopril, enalapril,verapamil, losartan, irbesartan.
• Anticoagulants
  • Phenprocoumon (product names: Marcumar, Falithrom), Clopidogrel.
  • New oral anticoagulants (NOAK, NOAC; direct oral anticoagulants, DOAK).
    • Direct factor Xa inhibitor (apixaban, edoxaban, rivaroxaban).
    • Direct and selective factor Xa inhibitor (apixaban).
    • Selective thrombin inhibitor (dabigatran).
• Anticonvulsants – valproic acid/valproate, carbamazepine, gabapentin, phenopbarbital, phenytoin.
• Antifungals
  • Allylamines (terbinafine)
  • Ketoconazole (Ketoconazole)
  • Polyene macrolactone (amphotericin, liposomal amphotericin B).
• Antipsychotics (neuroleptics) – carbamazepine, chlorpromazine, phenobarbital, phenothiazines, phenytoin, risperidone, valproic acid.
• Antituberculostatics – isoniazid, pyrazinamide, rifampicin, rifabutin.
• Α-Methyldopa
• Chloral hydrate
• Disulfiram (INN), also tetraethylthiuram disulfide (TETD).
• Drugs
  • Ecstasy (collective name for a variety of phenylethylamines).
  • Cocaine
• EGFR tyrosine kinase inhibitor – lapatinib
• Endothelin receptor antagonists (endothelin receptor antagonists) – ambrisentan, bosentan.
• HMG-CoA reductase inhibitors (statins), unspecified.
• Hormones
  • Anabolic steroids (anabolic steroids)
  • Antiestrogens (tamoxifen)
  • Estrogens (ethinyl estradiol, estradiol)
  • Oral anticonceptives, unspecified.
  • Progesterone modulator ulipristal (ulipristal acetate).
  • Testosterone
• Immunosuppressants
  • Azathioprine, ciclosporin (cyclosporin A), daclizumab, fingolimod, mercaptopurine, natalizumab, teriflunomide.
  • Immune checkpoint inhibitors against PD-1, PD-L1, and CTLA-4.
  • Pirfenidone drug-induced liver injury (DILI) including cases with fatal outcomes.
• Intestinal anti-inflammatory drug (sulfasalcin).
• Motilin agonist
• Anesthetic (halothane)
• Norepinephrine reuptake inhibitor (atomoxetine).
• Oral antidiabetic agents – acarbose
• Orlistat
• Petadolex (butterbur) [rare].
• Phytopharmaceuticals – e.g., kava kava, Usnea barbata, celandine.
• Psychotropic substances such as modafinil [alkaline phosphatase ↑, gamma-GT ↑).
• Pyrrolizidine alkaloids (phytochemical).
• Thyrostatic drugs (thiamazole, carbimazole).
• Tyrosine kinase inhibitors (TKi) – bosutinib, nintedanib.
• Uricostats (febuxostat)
• Vitamins
  • Vitamin B3 (niacin) > 500 mg/d (NRV: 16 mg; safe daily maximum for nicotinic acid is 10 mg).
• Antivirals
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) – nevirapine
  • Nucleoside analogues (abacavir, fialuridine).
  • Protease inhibitors (PI; protease inhibitors) – amprenavir, ritonavir.
• Cytostatic drugs – anthracyclines, cytarabine, dacarbazine, flutamine, isoniazid, methotrexate (MTX), temozolomide (up to organ failure).
• Other – hypertonic saline, vitamin A intoxication, Thorotrast.

Researchers at the University of Iceland in Reykjavik had analyzed all cases of drug-induced liver injury over two years in their study. They found that, on average, 19 out of every 100,000 residents suffered liver damage from medications each year. The drugs that frequently affected the liver included paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as antibiotics. For example, the combination of amoxicillin and clavulanic acid was responsible for 22% of damage

Environmental exposures – intoxications

• Tuber leaf fungus intoxication (amanitins).
• Carbon tetrachloride