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 Table of Contents  
MANAGING A SIDE EFFECT
Year : 2021  |  Volume : 7  |  Issue : 2  |  Page : 106-112

Drug-induced liver injury: What a dermatologist should know?


1 Department of Dermatology, MH Kirkee, Pune, Maharashtra, India
2 Department of Dermatology, AFMC, Pune, Maharashtra, India
3 Department of Gastroenterology, AFMC, Pune, Maharashtra, India

Date of Submission03-Aug-2020
Date of Decision15-Oct-2020
Date of Acceptance02-Jun-2021
Date of Web Publication14-Dec-2021

Correspondence Address:
Shekhar Neema
Department of Dermatology, AFMC, Pune - 411 040, Maharashtra.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_53_20

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  Abstract 

Dermatological practice involves the use of systemic drugs; some of them carrying boxed warnings of hepatotoxicity while others causing inadvertent or idiosyncratic liver damage. Drug-induced liver injury (DILI) is a common problem faced by dermatologists and refers to liver damage caused by medications, herbs, or other xenobiotics which can sometimes be fatal. Diagnosis of DILI remains challenging due to nonspecific clinical presentations compounded by a lack of knowledge in this area. With careful patient selection and systematic monitoring, liver injury should be rare in the dermatological setup. This review article is written with the aim of increasing awareness of DILI among dermatologists and thereby preventing liver injuries from common drugs.

Keywords: Drug induced liver injury, DILI, dermatology, liver function tests


How to cite this article:
Sinha A, Neema S, Manrai M, Vasudevan B, Radhakrishnan S. Drug-induced liver injury: What a dermatologist should know?. Indian J Drugs Dermatol 2021;7:106-12

How to cite this URL:
Sinha A, Neema S, Manrai M, Vasudevan B, Radhakrishnan S. Drug-induced liver injury: What a dermatologist should know?. Indian J Drugs Dermatol [serial online] 2021 [cited 2022 Jan 25];7:106-12. Available from: https://www.ijdd.in/text.asp?2021/7/2/106/332426




  Introduction Top


Drugs are estimated to be responsible for 10% of cases of hepatitis in adults and account for about 25% of cases of fulminant hepatitis.[1] Drug-induced liver injury (DILI) is a term used to describe the damage caused by drugs to liver cells with presentations ranging from asymptomatic liver enzyme elevations to acute liver failure (ALF). A plethora of common drugs used in dermatology such as methotrexate (MTX), dapsone, azathioprine, tumor necrosis factor alpha inhibitors, and oral antifungals are implicated in causing DILI, making it imperative for dermatologists to be aware of the intricacies of this condition. Diagnosis of DILI is challenging because of its relatively low incidence, variable clinical phenotype, and absence of specific biomarkers. Moreover, the unsupervised rampant use of herbal and dietary supplements (HDSs) for chronic dermatological disorders further adds to this conundrum. This review article focuses on the mechanisms, risk factors, diagnosis, prevention, and management of DILI with special interest to dermatological pharmacotherapy.


  Pathomechanisms of Drug-Induced Liver Injury: Top


The susceptibility of the liver to adverse drug reactions occurs because of its central role in drug metabolism.[2] The phases of drug metabolism include Phase I (oxidative reactions) mediated by cytochrome P-450 enzymes followed by Phase II (conjugation reactions) mediated by enzymes such as UDP glucuronyl transferase, N-acetyl transferases, and sulfotransferases. The overall goal of these reactions is detoxification, i.e., conversion of reactive metabolic intermediates to more stable compounds, and biotransformation, i.e. conversion of pharmacologically active, relatively lipophilic drugs, into inactive, relatively hydrophilic metabolites to facilitate renal or biliary excretion.[3]

DILI is classified into intrinsic and idiosyncratic type based on the mechanism of action of drug.[4] Intrinsic or direct DILI is a predictable event due to toxic drug dosages, while idiosyncratic DILI is an unpredictable event, determined by interaction of environment or host factors with the drug.[5] Idiosyncratic reactions can occur due to metabolic or immunologic idiosyncrasies. The common dermatological drugs causing direct DILI are cyclosporin A (CsA), MTX, highly active antiretroviral therapy, and anabolic steroids, while drugs causing idiosyncratic DILI include isoniazid, ketoconazole, amoxicillin-clavulanate, cephalosporins, minocycline, fluoroquinolones, and terbinafine.[6]

DILI is attributed to the presence of reactive metabolic intermediates and a defect in the cellular detoxification systems, leading to the persistence of these reactive intermediates.[7] Glutathione (GSH) is part of scavenging system which contributes to detoxification by binding to electrophilic compounds.[8] GSH can be depleted with heavy load of reactive intermediates as with drug overdosages and is further depleted by excessive alcohol consumption, HIV infection, and malnutrition, thus increasing a risk of DILI in these settings.[9] DILI can also result from inhibition of the bile salt export pump (BSEP), leading to increased intracellular concentrations of bile salts, which can damage mitochondria causing cytotoxicity and liver injury.[6] Potent BSEP inhibitors including CsA can lead to drug-induced cholestasis.[10] DILI can also be classified according to the pattern of liver injury based on abnormalities in liver function tests (LFTs), as hepatocellular, cholestatic, or mixed [Table 1]. Hepatocellular type of DILI is more likely to be associated with a poor outcome and a higher mortality compared to other variants.[4] Specific phenotypes of DILI seen with dermatological drugs are summarized in [Table 2].
Table 1: Patterns of drug-induced liver injury based on liver function tests abnormalities

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Table 2: Other specific phenotypes of drug induced liver injury

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  Risk Factors for Drug-Induced Liver Injury Top


In a susceptible patient, various patient- and drug-related factors work synchronously causing DILI as summarized in [Table 3]. Early phases of DILI are more drug-specific and are influenced by drug variables such as dosing and duration, whereas later phases are determined by the patient’s response to toxic stress.
Table 3: Risk factors for drug-induced liver injury

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  Clinical Features Top


The clinical manifestations of DILI are heterogeneous mimicking acute and chronic liver diseases of various etiologies, ranging from asymptomatic biochemical alterations to ALF and chronic liver damage. Serum enzyme elevations without clinical symptoms constitute the most common pattern of direct DILI.[4] Nonspecific symptoms such as fever, fatigue, nausea, vomiting, jaundice, dark urine, pruritus, and right upper quadrant pain may be present and have been associated with worse outcome. In severe cases, signs of hepatic failure such as ascites, coagulopathy, hyperammonemia, encephalopathy, or coma arise within days. Sinusoidal obstruction syndrome can present as hepatomegaly, abdominal pain, and weight gain, followed by jaundice, and may progress rapidly to hepatic failure.[6]


  Drug-Induced Liver Injury with Skin Reactions Top


Concomitant DILI and drug-induced skin injury have been reported in 10%–28% of patients in DILI registries.[30] Liver injury typically manifests concurrent or subsequent to skin injury and only rarely (<10%) does it precede skin manifestations.[31] Clinical features of hypersensitivity reactions drug rash with eosinophilia and systemic symptoms (DRESS) may include fever, nonspecific morbilliform rash or blisters, eosinophilia, lymphadenopathy, and mucositis. Antiepileptic drugs, sulfonamides, allopurinol, antibiotics, and nevirapine are the top five causes of concomitant liver and skin injury.[30] The type of liver injury depends on the implicated drug and timing of presentation; however, cholestatic or mixed hepatitis is more common than hepatocellular pattern in DRESS.[31] Atypical erythema multiforme-like eruption is associated with severe hepatic involvement and higher mortality.[32] More severe liver dysfunction has been found in association with DRESS compared to milder liver dysfunction with Steven Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN) and acute generalised exanthematous pustulosis.[33] Vanishing bile duct syndrome may rarely occur as a complication of liver injury in SJS/TEN.[34]


  Diagnosis Top


Diagnosis of DILI requires a detailed clinical history and cautious documentation of drugs including HDS, along with liver biochemistry, biomarkers, imaging, and in rare cases, liver biopsy. For a vast majority of dermatology drugs, serum aminotransferases alanine transaminase/aspartate transaminase (ALT/AST), alkaline phosphatase ALP, and total bilirubin levels remain mainstay for detecting and classifying liver damage. Serial testing of liver biochemistries should be done in patients with DILI until complete normalization. A steady decline of aminotransferases supports the diagnosis, whereas slow or incomplete resolution suggests other etiologies or chronic outcome.[35] Liver imaging is routinely used at baseline in all suspected DILI patients, with abdominal ultrasonography used to exclude biliary obstruction and focal lesions.[36] Since DILI is a diagnosis of exclusion, other causes of liver injury must be excluded. The panel of tests used in the evaluation of suspected DILI is summarized in [Table 4]. Common dermatological drugs implicated in liver injury along with hepatic monitoring guidelines are highlighted in [Table 5].
Table 4: Investigations for suspected drug induced liver injury

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Table 5: Dermatological drugs, liver injury, and hepatic monitoring guidelines

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  Management Top


The goal of management of DILI is similar to other adverse drug reactions where a balance has to be maintained between preventing target organ damage and continuing essential drugs. Minor increases in ALT or AST should be treated with reduction in the drug dose and careful follow-up of the transaminases, while increase more than threefold should prompt indefinite discontinuation of the likely culprit drug, unless an alternative etiology is detected.[64]

Nonspecific treatment

  1. Discontinue the implicated agent or all nonessential drugs if culprit drug is unclear. Causality assessment can be done using tools such as Roussel Uclaf Causality Assessment Method


  2. Monitor LFT closely


  3. Seek appropriate consultation with a hepatologist when the patient has persistent elevation of transaminases or signs of ALF


  4. Institute supportive care.[65]


In the large majority of DILI, spontaneous recovery occurs, without the need for any treatment or specific measure. In fact, spontaneous recovery after discontinuation of the offending drug is an important criterion in the causality assessment. Old age, dyslipidemia, and the severity of the acute episode are the risk factors for chronic DILI, which is defined as persistence of biochemical abnormality for more than 1 year.[6] Deliberate re-challenge with the causative drug is not advocated, as it can cause more severe hepatotoxicity with a higher risk of mortality. However, re-challenge with lower dosage can be done under close monitoring in lifesaving drugs such as antitubercular drugs.

Specific therapies

Pharmacotherapy has variable level of efficacy and should be used in specific circumstances with the hepatologist consultation.

  • i. Cholestyramine: Bile acid resin such as cholestyramine (4 g every 6 h for 2 weeks) has been recommended to speed up drug clearance. Cholestyramine in association with antihistamines has been reported to accelerate the improvement of chronic cholestasis induced by terbinafine and leflunomide[66]


  • ii. N-acetyl cysteine (NAC): Besides its use in paracetamol intoxication, NAC has been occasionally used as a treatment for other types of DILI[67]


  • iii. Steroids: Systemic corticosteroids are the first-line agents for severe cutaneous and hepatic toxicity features DRESS.[68] Corticosteroids are also used frequently in patients with ALF and autoimmune hepatitis or to treat hepatotoxicity due to immune-checkpoint inhibitors along with other immunosuppressants such as mycophenolate mofetil[69]


  • iv. Ursodeoxycholic acid (UDCA): Chronic cholestasis following DILI is often treated with UDCA[70]


  • v. Carnitine: L-carnitine with its antioxidant activity has been found to have a protective effect in antitubercular-induced liver injury and alcoholic liver disease.[71]



  Conclusion Top


Knowledge of DILI can help prevent unnecessary morbidity and rare deaths from systemic drugs, while maximizing the overall safety and efficacy of important systemic drugs used in dermatology. The awareness of hepatotoxic nature of commonly used drug in practice, protocol for baseline and follow-up liver biochemistry, advising patients against excessive alcohol intake, and use of HDS will go a long way in ensuring successful dermatologic pharmacotherapy with minimal risk of DILI.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lee WM. Drug-induced hepatotoxicity. N Engl J Med 2003;349:474-85.  Back to cited text no. 1
    
2.
Corsini A, Bortolini M. Drug-induced liver injury: The role of drug metabolism and transport. J Clin Pharmacol 2013;53:463-74.  Back to cited text no. 2
    
3.
Grant DM. Detoxification pathways in the liver. J Inherit Metab Dis 1991;14:421-30.  Back to cited text no. 3
    
4.
Andrade RJ, Aithal GP, Björnsson ES, Kaplowitz N, Kullak-Ublick GA, Larrey D, et al EASL clinical practice guidelines: Drug-induced liver injury. J Hepatol 2019;70:1222-61.  Back to cited text no. 4
    
5.
Bell LN, Chalasani N. Epidemiology of idiosyncratic drug-induced liver injury. Semin Liver Dis 2009;29:337-47.  Back to cited text no. 5
    
6.
Andrade RJ, Chalasani N, Björnsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, et al Drug-induced liver injury. Nat Rev Dis Primers 2019;5:58.  Back to cited text no. 6
    
7.
Gu X, Manautou JE. Molecular mechanisms underlying chemical liver injury. Expert Rev Mol Med 2012;14:e4.  Back to cited text no. 7
    
8.
Forman HJ, Zhang H, Rinna A. Glutathione: Overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 2009;30:1-12.  Back to cited text no. 8
    
9.
Lieber CS. Relationships between nutrition, alcohol use, and liver disease. Alcohol Res Health 2003;27:220-31.  Back to cited text no. 9
    
10.
Kolarić TO, Ninčević V, Smolić R, Smolić M, Wu GY. Mechanisms of hepatic cholestatic drug injury. J Clin Transl Hepatol 2019;7:86-92.  Back to cited text no. 10
    
11.
Hoofnagle JH, Björnsson ES. Drug-induced liver injury – types and phenotypes. N Engl J Med 2019;381:264-73.  Back to cited text no. 11
    
12.
Martinez-Cabriales SA, Shear NH, Gonzalez-Moreno EI. Liver involvement in the drug reaction, eosinophilia, and systemic symptoms syndrome. World J Clin Cases 2019;7:705-16.  Back to cited text no. 12
    
13.
Desmet VJ. Vanishing bile duct syndrome in drug-induced liver disease. J Hepatol 1997;26 Suppl 1:31-5.  Back to cited text no. 13
    
14.
Tomaszewski M, Dahiya M, Mohajerani A, Punja H, Ko H, Ramji A. A186 hepatic steatosis predicts fibrosis in long-term methotrexate use. J Can Assoc Gastroenterol 2020;3:57-8.  Back to cited text no. 14
    
15.
Kleiner DE. Drug-induced liver injury: The hepatic pathologist’s approach. Gastroenterol Clin North Am 2017;46:273-96.  Back to cited text no. 15
    
16.
Björnsson E, Talwalkar J, Treeprasertsuk S, Kamath PS, Takahashi N, Sanderson S, et al Drug-induced autoimmune hepatitis: Clinical characteristics and prognosis. Hepatology 2010;51:2040-8.  Back to cited text no. 16
    
17.
Clare KE, Miller MH, Dillon JF. Genetic factors influencing drug-induced liver injury: Do they have a role in prevention and diagnosis? Curr Hepatol Rep 2017;16:258-64.  Back to cited text no. 17
    
18.
Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: Basic principles and practical applications. Br J Clin Pharmacol 2004;57:6-14.  Back to cited text no. 18
    
19.
Castiella A, Zapata E, Lucena MI, Andrade RJ. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease. World J Hepatol 2014;6:160-8.  Back to cited text no. 19
    
20.
Horning K, Schmidt C. Azathioprine-induced rapid hepatotoxicity. J Pharm Technol 2014;30:18-20.  Back to cited text no. 20
    
21.
Teschke R, Danan G. Drug-induced liver injury: Is chronic liver disease a risk factor and a clinical issue? Expert Opin Drug Metab Toxicol 2017;13:425-38.  Back to cited text no. 21
    
22.
Wolverton SE. Major adverse effects from systemic drugs: Defining the risks. Curr Probl Dermatol 1995;7:6-38.  Back to cited text no. 22
    
23.
Kaplowitz N. Avoiding idiosyncratic DILI: Two is better than one. Hepatology 2013;58:15-7.  Back to cited text no. 23
    
24.
Vahlquist A. Long-term safety of retinoid therapy. J Am Acad Dermatol 1992;27:S29-33.  Back to cited text no. 24
    
25.
Roenigk HH Jr., Auerbach R, Maibach H, Weinstein G, Lebwohl M. Methotrexate in psoriasis: Consensus conference. J Am Acad Dermatol 1998;38:478-85.  Back to cited text no. 25
    
26.
Andrade RJ, Tulkens PM. Hepatic safety of antibiotics used in primary care. J Antimicrob Chemother 2011;66:1431-46.  Back to cited text no. 26
    
27.
Harmon EG, McConnie R, Kesavan A. Minocycline-induced autoimmune hepatitis: A rare but important cause of drug-induced autoimmune hepatitis. Pediatr Gastroenterol Hepatol Nutr 2018;21:347-50.  Back to cited text no. 27
    
28.
McEuen K, Borlak J, Tong W, Chen M. Associations of drug lipophilicity and extent of metabolism with drug-induced liver injury. Int J Mol Sci 2017;18:1335.  Back to cited text no. 28
    
29.
Ramappa V, Aithal GP. Hepatotoxicity related to anti-tuberculosis drugs: Mechanisms and management. J Clin Exp Hepatol 2013;3:37-49.  Back to cited text no. 29
    
30.
Devarbhavi H, Raj S. Drug-induced liver injury with skin reactions: Drugs and host risk factors, clinical phenotypes and prognosis. Liver Int 2019;39:802-11.  Back to cited text no. 30
    
31.
Lin IC, Yang HC, Strong C, Yang CW, Cho YT, Chen KL, et al Liver injury in patients with DRESS: A clinical study of 72 cases. J Am Acad Dermatol 2015;72:984-91.  Back to cited text no. 31
    
32.
Walsh S, Diaz-Cano S, Higgins E, Morris-Jones R, Bashir S, Bernal W, et al Drug reaction with eosinophilia and systemic symptoms: Is cutaneous phenotype a prognostic marker for outcome? A review of clinicopathological features of 27 cases. Br J Dermatol 2013;168:391-401.  Back to cited text no. 32
    
33.
Lin YF, Yang CH, Sindy H, Lin JY, Rosaline Hui CY, Tsai YC, et al Severe cutaneous adverse reactions related to systemic antibiotics. Clin Infect Dis 2014;58:1377-85.  Back to cited text no. 33
    
34.
Li L, Zheng S, Chen Y. Stevens-Johnson syndrome and acute vanishing bile duct syndrome after the use of amoxicillin and naproxen in a child. J Int Med Res 2019;47:4537-43.  Back to cited text no. 34
    
35.
Andrade RJ, Robles-Díaz M. Diagnostic and prognostic assessment of suspected drug-induced liver injury in clinical practice. Liver Int 2020;40:6-17.  Back to cited text no. 35
    
36.
Minissale MG, Soresi M, Galia M, Agnello F, Giannitrapani L, Midiri M, et al Optimizing diagnostic approach to drug-induced liver injury. Ital J Med 2018;12:180-9.  Back to cited text no. 36
    
37.
David S, Hamilton JP. Drug-induced liver injury. US Gastroenterol Hepatol Rev 2010;6:73-80.  Back to cited text no. 37
    
38.
Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011;89:806-15.  Back to cited text no. 38
    
39.
Labadie JG, Jain M. Noninvasive tests to monitor methotrexate-induced liver injury. Clin Liver Dis (Hoboken) 2019;13:67-71.  Back to cited text no. 39
    
40.
Ezhilarasan D. Dapsone-induced hepatic complications: It’s time to think beyond methemoglobinemia. Drug Chem Toxicol 2021;44:330-3.  Back to cited text no. 40
    
41.
Kurien G, Jamil RT, Preuss CV. Dapsone. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2020. Available from: http://www.ncbi.nlm.nih.gov/books/NBK470552/. [Last accessed on 2020 Jun 13; Last updated on 2020 Feb 22].  Back to cited text no. 41
    
42.
Lawrenson RA, Seaman HE, Sundström A, Williams TJ, Farmer RD. Liver damage associated with minocycline use in acne: A systematic review of the published literature and pharmacovigilance data. Drug Saf 2000;23:333-49.  Back to cited text no. 42
    
43.
Conway R, Carey JJ. Risk of liver disease in methotrexate treated patients. World J Hepatol 2017;9:1092-100.  Back to cited text no. 43
    
44.
Thomas JA, Aithal GP. Monitoring liver function during methotrexate therapy for psoriasis: Are routine biopsies really necessary? Am J Clin Dermatol 2005;6:357-63.  Back to cited text no. 44
    
45.
Lo Re V 3rd, Carbonari DM, Lewis JD, Forde KA, Goldberg DS, Reddy KR, et al Oral azole antifungal medications and risk of acute liver injury, overall and by chronic liver disease status. Am J Med 2016;129:283-91.e5.  Back to cited text no. 45
    
46.
Itraconazole. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548273/. [Last accessed on 2020 Jun 13; Last updated on 2017 May 17].  Back to cited text no. 46
    
47.
Lewis JH, Zimmerman HJ, Benson GD, Ishak KG. Hepatic injury associated with ketoconazole therapy. Analysis of 33 cases. Gastroenterology 1984;86:503-13.  Back to cited text no. 47
    
48.
Kaushal M, Tolani P, Kumar N, Sharma S. Terbinafine-induced liver injury. Natl Med J India 2017;30:321-3.  Back to cited text no. 48
[PUBMED]  [Full text]  
49.
Patton T, Ferris L. Systemic retinoids. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy. 3rd ed. Philadelphia, USA: Saunders Elsevier; 2013. p. 265.  Back to cited text no. 49
    
50.
Kızılyel O, Metin MS, Elmas ÖF, Çayır Y, Aktaş A. Effects of oral isotretinoin on lipids and liver enzymes in acne patients. Cutis 2014;94:234-8.  Back to cited text no. 50
    
51.
Roenigk HH Jr., Callen JP, Guzzo CA, Katz HI, Lowe N, Madison K, et al Effects of acitretin on the liver. J Am Acad Dermatol 1999;41:584-8.  Back to cited text no. 51
    
52.
Tumor Necrosis Factor Antagonists. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548852/. [Last accessed on 2020 Jun 13; Last updated on 2017 Feb 10].  Back to cited text no. 52
    
53.
Rossi RE, Parisi I, Despott EJ, Burroughs AK, O’Beirne J, Conte D, et al Anti-tumour necrosis factor agent and liver injury: Literature review, recommendations for management. World J Gastroenterol 2014;20:17352-9.  Back to cited text no. 53
    
54.
Cyclosporine. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548753/. [Last accessed on 2020 Jun 13; Last updated on 2020 Feb 17].  Back to cited text no. 54
    
55.
Bhutani T, Lee C. Cyclosporine. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy. 3rd ed. Philadelphia, USA: Saunders Elsevier; 2013. p. 209.  Back to cited text no. 55
    
56.
Siramolpiwat S, Sakonlaya D. Clinical and histologic features of azathioprine-induced hepatotoxicity. Scand J Gastroenterol 2017;52:876-80.  Back to cited text no. 56
    
57.
Anstey AV, Wakelin S, Reynolds NJ; British Association of Dermatologists Therapy, Guidelines and Audit Subcommittee. Guidelines for prescribing azathioprine in dermatology. Br J Dermatol 2004;151:1123-32.  Back to cited text no. 57
    
58.
Nguyen RH, Cruz PD Jr. Hepatitis due to mycophenolate mofetil used to treat atopic dermatitis and allergic contact dermatitis. Dermatitis 2014;25:284-5.  Back to cited text no. 58
    
59.
Schadt CR, Zwerner JP. Mycophenolate mofetil and mycophenolic acid. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy. 3rd ed. Philadelphia, USA: Saunders Elsevier; 2013. p. 197.  Back to cited text no. 59
    
60.
Subramaniam SR, Cader RA, Mohd R, Yen KW, Ghafor HA. Low-dose cyclophosphamide-induced acute hepatotoxicity. Am J Case Rep 2013;14:345-9.  Back to cited text no. 60
    
61.
High WA. Cytotoxic agents. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy. 3rd ed. Philadelphia, USA: Saunders Elsevier; 2013. p. 224.  Back to cited text no. 61
    
62.
Tofacitinib. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Available from: http://www.ncbi.nlm.nih.gov/books/NBK547848/. [Last accessed on 2020 Jun 13; Last updated on 2018 Jun 22].  Back to cited text no. 62
    
63.
Takyar V, Stolz A. Spectrum of drug induced liver injury caused by anabolic androgenic steroids abuse. Curr Hepatol Rep 2019;18:417-24.  Back to cited text no. 63
    
64.
Oh RC, Hustead TR, Ali SM, Pantsari MW. Mildly elevated liver transaminase levels: Causes and evaluation. Am Fam Physician 2017;96:709-15.  Back to cited text no. 64
    
65.
Giordano C, Rivas J, Zervos X. An update on treatment of drug-induced liver injury. J Clin Transl Hepatol 2014;2:74-9.  Back to cited text no. 65
    
66.
Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: Causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol 2010;105:2396-404.  Back to cited text no. 66
    
67.
Chughlay MF, Kramer N, Spearman CW, Werfalli M, Cohen K. N-acetylcysteine for non-paracetamol drug-induced liver injury: A systematic review. Br J Clin Pharmacol 2016;81:1021-9.  Back to cited text no. 67
    
68.
Cho YT, Yang CW, Chu CY. Drug reaction with eosinophilia and systemic symptoms (DRESS): An interplay among drugs, viruses, and immune system. Int J Mol Sci 2017;18:1243.  Back to cited text no. 68
    
69.
Imoto K, Kohjima M, Hioki T, Kurashige T, Kurokawa M, Tashiro S, et al Clinical features of liver injury induced by immune checkpoint inhibitors in Japanese patients. Can J Gastroenterol Hepatol 2019;2019:6391712.  Back to cited text no. 69
    
70.
Padda MS, Sanchez M, Akhtar AJ, Boyer JL. Drug-induced cholestasis. Hepatology 2011;53:1377-87.  Back to cited text no. 70
    
71.
Hatamkhani S, Khalili H, Karimzadeh I, Dashti-Khavidaki S, Abdollahi A, Jafari S. Carnitine for prevention of antituberculosis drug-induced hepatotoxicity: A randomized, clinical trial. J Gastroenterol Hepatol 2014;29:997-1004.  Back to cited text no. 71
    



 
 
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