Key words : Adverse drug reaction, Fulminant hepatic failure, Helminth infection

Introduction
Drug-induced liver injuries (DILIs), depending of methods of analysis and diagnosis, have been reported to range from 1 of 600 to 3500 of all admitted patients, with 2% to 3% of patients admitted because of drug-induced toxicity. Some approved drugs can cause hepatitis, with frequency of 1 in 100 000.^1-3 So far, over 900 medical preparations (drugs, dietary supplements, and herbal medications) that can lead to liver damage have been described, and this list is expected to grow.^4-6 The proportion of patients hospitalized because of irrational drug use is 10% to 20%, and 5% of patients die from serious adverse drug reactions (ADRs).^7,8 Drug-induced liver injury accounts for numerous clinically significant events each year and can cause severe injury, which can result in need for liver transplant or fatality. Drug-induced liver injury can be idiosyncratic or dose dependent. Idiosyncratic DILI develops independently of drug dose or route or duration of administration.^9,10

The use of albendazole in the treatment of helminth infections in humans has been permitted since 1996.⁶ Liver injury triggered by albendazole is relatively common, resulting in mild to moderate changes in liver enzymes, and has been reported in approximately 16% of patients who use this medication. However, liver failure secondary to the use of albendazole is extremely rare, with few reported cases in the medical literature. Albendazole-induced liver injury and jaundice have been previously documented, but a case of fulminant hepatic failure requiring liver transplant has not yet been described. With regard to antiparasitic drugs, the general population frequently ingests them for prophylactic purposes. Drug-induced hepatitis is defined as hepatitis caused by a medication with or without prescription. Toxic hepatitits can also occur from use of traditional, alternative, or natural medications.² Albendazole is the medication of choice to treat multiple diseases caused by parasites from the nematode and cestode types, including alveolar echinococcosis and neurocysticercosis.^11-13 In addition, the drug has been successfully implemented as an alternative therapy in other parasitosis, without generating clinically relevant adverse effects.^13-15

Acute liver failure is a clinical syndrome, potentially reversible, characterized by the emergence of hepatic encephalopathy within 8 weeks after the onset of signs and symptoms of acute hepatitis, which occurs in patients without evidence of chronic hepatic disease.^16,17 Clinically, idiosyncratic DILI may take many forms, varying from asymptomatic, often self-limiting, and transient elevations in liver biochemical tests to jaundice and severe life-threatening acute liver failure, although rarely to chronic liver disease. It may cause transient liver enzyme abnormalities, especially after prolonged use, but significant hepatotoxicity is rare.^13,17-19

Hepatotoxicity can manifest itself in the entire spectrum, from asymptomatic transaminase elevations to fulminant hepatic failure requiring liver transplant, whereas chronic liver disease is extremely rare. Liver injury occurs as a result of dose-dependent reactions, dose-independent reactions (idiosyncratic hepatotoxicity), or unwanted reactivation of liver disease. Drug-induced liver injury can resemble liver damage from other causes and may occur while patients are on treatment; however, DILI can sometimes manifest even months after the discontinuation of medication. Hence, a well-taken medical history is vital to reach a diagnosis, as well as additional laboratory testing.^5,6,20 Liver injury induced by drugs is a well-documented condition in the scientific environment, and its annual incidence in patients with prescribed medication is around 1 in 10 000 to 100 000 exposed people. Drug-induced liver injury accounts for about 10% of ADRs.^17,21

With the use of idiosyncratic agents, liver injury usually cannot be predicted and presentation is not dose dependant. However, patients may present with extrahepatic hypersensitivity symptoms like skin eruptions, arthralgia, fever, leukocytosis, and eosinophilia. Morris and Smith previously reported abnormalities of liver function tests among 7 of 40 patients treated for Echinococcus granulosus with oral albendazole. Six of the patients had the hepatocellular type of abnormality, and 1 patient developed obstructive jaundice.²² Jagota also reported a case of jaundice as a result of albendazole use in a patient with hydatid disease of the liver, who was confirmed in a rechallenge with recurrence of hepatitis.^1,2,23

Albendazole binds to the β-tubulin of the parasitic cell and impedes microtubule polymerization, which interferes with mitototic spindle formation and glucose uptake; albendazole also inhibits mitochondrial fumarate reductase, which alters oxidative phosphorylation and the parasite’s energy metabolism; this produces the cell’s immobility, spastic paralysis, and finally death. The secondary effects of the medication are usually mild; reports have been made of constipation, abdominal pain, nausea, drowsiness, dizziness, pruritus, transient hair loss, anorexia, and mild aminotransferase increase. Significant adverse reactions compromising the liver and bile ducts are rare; in up to 15.6% of the cases, elevation of hepatic enzymes has been reported, which decreases with the temporary withdrawal of the medication without generating any comorbidity.^13,14,24-26

The diagnosis of DILI is based on clinical, epidemiological, and laboratory findings. The clinical picture is vast, characterized by prodromal symptoms, such as nausea, vomiting, low appetite, and abdominal discomfort; the clinical picture can even include the famous triad of jaundice, coagulopathy and encephalopathy. Patients usually have dramatic elevations of liver enzyme levels that often exceed 40 times the normality, besides changes to electrolytes and coagulation and hematologic tests.^17,27

Drug-induced liver injury is a disease of variable clinical presentation, with a spectrum that goes from the lack of symptoms to acute liver failure and even chronic liver disease. It is an underregistered condition, and the diagnosis is of exclusion; hence, it is based on the clinical history, antecedents of drug intake, evaluation of paraclinical examinations, and exclusion of other possible causes that mask the toxicity. Hydatidosis has been the indication for albendazole use, and albendazole has been effectively implemented without clinically significant adverse effects on the liver in similar cases, making it unlikely that inflammatory reactions caused by the parasite’s death are responsible for hepatocellular damage.^13,28-30

In Georgia, the use of antiparasitic agents is common, both as a treatment for intestinal parasites and also for prophylaxis, often without medical prescription because of ease of public access to the drug. Investigations of liver disease should include research of albendazole use and other imidazoles during anmnesis. This theme also deserves further study to better understand the pathophysiology related to the hepatotoxicity of this agent.

Materials and Methods
We aimed to describe drug-induced fulminant and subfulminant hepatic failures among pediatric patients. Our 6 cases were children aged 2 to 14 years who were seen between 2018 and 2023 in Georgia. Patients were transferred to Batumi Center for Liver Diseases and Transplantation.

Results
Among the 6 children included in our study, 2 died (patients N5 and N6), 2 were transplanted with good outcomes (patients N3 and N4), and 2 recovered from acute liver failure within 3 weeks (patients N1 and N2). Of note, although acute liver failure is potentially reversible, 2% of liver transplants are performed because of acute liver failure.

Patients had dramatic elevations of liver enzyme levels that often exceeded 40 times above normal, along with changes in electrolytes and coagulation and hematologic tests (Table 1). Levels did not seem to correlate with prognosis; however, a rapid decline of liver enzyme values, especially more than 60% of their values in 24 hours, is a signal of liver failure.

The 6 patients were hospitalized because of fever, chills, myalgia, nausea, vomiting, and skin rash on both forearms for 6 to 72 ± 3.5 hours after antiparasitic drug ingestion, which occurred 2 to 14 ± 4.5 days earlier. Four patients received medication for prophylactic use for 3 days, and 2 patients received medication for parasitic infection for 3 days. Patients had no history of specific medication. Before patients were admitted to our center, patients had been treated in different pediatric hospitals for 2 to 6 ± 1.5 days. Patients had ingested albendazole levels at maximal treatment dose according to the World Health Organization’s recommended doses for age and weight. According to the manufacturer (GlaxoSmithKline), the actual recommended dose of albendazole for patients with hydatid disease who weigh <60 kg is 15 mg/kg/day. Another recommendation was a dose of albendazole of 400 mg twice daily, taken with meals, for a total of 28 days; 3 such 28-day cycles may be given at 14-day intervals.²

At presentation, 1 patient had the following initial vital signs: blood pressure of 90 ± 17/55 ± 23 mm Hg, heart rate of 92 ± 28 beats/min, respiratory rate of 18 ± 7 breaths/min, and body temperature of 36.3 ± 2.6 °C. The patient had no recent history compatible with acute hypotension or underlying heart disease. Physical examination showed palpable liver, normal liver percussion span, and icteric sclerae. White blood cell count was 6790 ± 5324/μL (eosinophil 8.2 ± 1.75%), hemoglobin level was 12.7 ± 3.45 g/dL, and platelet count was 126 000 ± 10 343/μL, showing mild increase of eosinophil count. Prothrombin time was 25.4 ± 9.45 seconds (international normalized ratio of 2.34 ± 2.4), aspartate aminotransferase (AST) level was 1328 ± 2653 IU/L, alanine aminotransferase (ALT) level was 1245 ± 2548 IU/L, alkaline phosphatase was 40 ± 38 IU/L, total bilirubin was 20.03 ± 32.45 mg/dL, recipient gamma-glutamyl transferase was 201 ± 307 IU/L, lactate dehydrogenase was 8.799 ± 7.46 IU/L, total protein was 6.9 ± 1.35 g/dL, albumin was 1.9 ± 2.6 g/dL, serum glucose was 115 ± 24 mg/dL, and creatinine was 0.73 ± 1.2 mg/dL.

Immunoglobulin M (IgM) anti-hepatitis A virus, HBsAg, IgM anti-HBc, and anti-hepatitis C virus antibodies were negative. Anti-cytomegalovirus, anti-Epstein-Barr virus, and anti-herpes simplex virus were also negative. Antinuclear antibody was weakly positive with homogeneous pattern, and anti-mitochondrial antibody and anti-smooth muscle antibody were negative. Level of copper (urine) was 0.9 ± 1.73 mg/dL, ceruloplasmin was 26.1 ± 5.7 mg/dL, immunoglobulin G (IgG) was 1313.2 ± 0.56 mg/ dL, and IgM was 56.2 ± 13.24 mg/dL, showing normal values.

Sonography of the liver showed no significant abnormality except increased liver echogenicity. Sonography-guided liver biopsy showed periportal invasion of inflammatory cells, cytotoxic necrosis, and different sizes of steatosis. We suspected drug-induced hepatitis due to albendazole. We again reviewed the patient’s medical history, which showed previous history of albendazole ingestion before hospital admission. We diagnosed the patient as toxic acute hepatitis, according to the Council for International Organizations of Medical Sciences (CIOMS) score of “definite or highly probable” (score of 9) and performed conservative medical treatment.

Two patients (patients N1 and N2) showed rapid improvement of liver function test, with AST of 35 ± 23 IU/L, ALT of 101 ± 76 IU/L, alkaline phosphatase of 45 ± 13 IU/L, and total bilirubin of 1.8 ± 1.2 mg/dL on day 8 of admission. Patients were discharged and showed no significant symptoms on follow-up at the outpatient department.

Two patients (patients N5 and N6) were admitted to our hospital with hepatic encephalopathy and were on mechanical ventilation. With ongoing medical treatment, liver function tests did not improve, with AST of 3055 ± 1316 IU/L, ALT of 2101 ± 1676 IU/L, alkaline phosphatase of 145 ± 113 IU/L, and total bilirubin of 21.8 ± 11.2 mg/dL on day 4 of admission, Computed tomography angiography of brain showed brain damage. Electroencephalogram showed decrease of brain activity. Because of brain electrical inactivity and probable brain death, liver transplant was not performed.

Two patients (patients N3 and N4) were admitted to our hospital with hepatic encephalopathy. With ongoing medical treatment, liver function tests did not improve with AST of 1355 ± 1516 IU/L, ALT of 1191 ± 1376 IU/L, alkaline phosphatase of 145 ± 113 IU/L, and total bilirubin of 21.8 ± 11.2 mg/dL on day 4 of admission. Computed tomography-angiography of brain showed adequate brain perfusion. Electroencephalogram showed positive brain activity. Because of increase in liver function tests and ammonia, emergency liver transplant was performed. Patients were discharged after successful transplant and showed no significant symptoms on follow-up at the outpatient department.

Discussion
Liver injuries are classified as 3 types: hepatocellular, cholestatic, and combined.^2,31 As a broad-spectrum antiparasitic drug, albendazole can selectively and irreversibly inhibit the aggregation of intestinal parasites and intestinal parietal cell cytoplasmic microtubule system, thereby blocking the uptake of various nutrients and glucose and absorption. Albendazole has been included in the list of essential medicines by the World Health Organization. To date, a literature search reveals only 10 cases of albendazole-induced liver injury, one in which drug-induced liver failure required liver transplantation.^8,32

Cytotoxic lesions consist of direct hepatocellular damage by viruses (except C viruses), drugs, metabolites, or toxins; among the most commonly known associated medications are the analgesics, in particular acetaminophen, antiepileptic, antibiotics, antifungal agents, and antihypertensives. On the other hand, cytopathic injury is mediated by an immune response against hepatocytes.^17,33 In all of our cases where albendazole-induced hepatic damage was seen, we believe the lesions were both cytotoxic and cytopathic. Cytotoxic lesions were direct damage from albendazole toxicity, but cytopathic lesions were immune-mediated. In all 6 cases seen at our center, patient medical history included immune-mediated or allergic reactions.

Acute liver failure is acute and serious deterioration of hepatocellular function secondary to cytotoxicity, mainly caused by external factors, usually by drugs or even by cholestasis. The current incidence of acute fulminant hepatitis is unknown. There are no data about the incidence of liver failure in Georgia; however, it is known that 2% of worldwide liver transplants are performed because of acute liver failure.^17,33

Toxicity levels do not seem to correlate with prognosis, but a rapid decline of liver enzyme values, especially >60% of their values in 24 hours, is a signal of liver failure.^17,34 We found that prognosis of acute liver failure did not correlate with static value of liver transaminases. However, although acute liver failure was shown in patients, rapid decline of enzyme levels was not observed.

Liver injury is likely to be more severe in hepatocellular type than in cholestatic/mixed type, and elevated bilirubin levels in hepatocellular type can indicate serious liver injury.^10,35 For idiosyncratic reactions, hepatotoxicity is unpredictable, independent of dose and route of administration, and dependent on the patient’s individual characteristics.^6,20 We believe that this individual characteristic is actually an immune system predisposition.

The mechanism of idiosyncratic hepatotoxicity can be metabolic, due to the action of one of the compounds formed in the process of drug metabolism in the liver, or immune. Activation of the immune system in DILI is a complex, sometimes genetically determined process and often is difficult to distinguish between drug-induced autoimmune hepatitis and immune-mediated DILI. Independent of the mechanism, the drug or its metabolite can damage any cell in the liver (hepatocytes, cholangiocytes, stellate cells, or sinusoidal endothelial cells) and can cause acute, subacute, or chronic liver damage.^4-6,36,37 Acute DILI has 3 phenotypes: hepatocellular, cholestatic, and mixed.

During assessment of severity of DILI, in addition to determining levels of transaminases, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin, it is necessary to assess coagulation, encephalopathy, the involvement of other organ systems, the risk of a fatal outcome, and the need for emergency liver transplant.^5,6 In our patients, we found that 4 of 6 patients required transplant. However, 2 patients could not have liver transplant because of late evaluation with presence of brain death. Determining the HLA genotype can enhance both accuracy and confidence to distinguish DILI from autoimmune hepatitis.^5,6

In recent years, many studies have found that DILI shows strong HLA associations. HLA participates in the regulation of the immune system by presenting antigenic peptides to T lymphocytes. Adverse drug reactions are divided into predictable type A adverse reactions and unpredictable type B adverse reactions. Type B adverse reactions often have more severe consequences, since type B is an immune-mediated ADR (IM-ADR) independent of drug activity. According to the type of immune cells, IM-ADRs can be divided into B-cell-mediated IM-ADRs and T-cell-mediated IM-ADRs.^8,38-43

Depending on the CIOMS score, DILI is excluded (≤0), unlikely (1-2), possible (3-5), probable (6-8), or highly probable (≥8).6,44 In our study cases, CIOMS was >8, meaning that liver lesions were drug-induced (particularly from albendazole).

According to the literature, there is just one published article on albendazole-induced autoimmune hepatitis in a pediatric patient. The patient had albendazole-induced hepatotoxicity and elevation of IgG and antinuclear antibody levels. After the patient started corticosteroids and azathioprine, there was rapid normalization of transaminases, IgG, and antinuclear antibody.^6,45 Given the lack of long-term follow-up data, the question remains whether this patient had albendazole-induced liver injury or whether albendazole initiated autoimmune hepatitis. In all our cases, antinuclear antibody levels were normal; however, during medical treatment, corticosteroids were given. Unfortunately, enzyme levels did not decline; thus perhaps DILI rather than albendazole initiated autoimmune hepatitis.

Treatment of acute liver failure consists of specific measures of support, such as hospitalization in an intensive care unit and treatment of complications, like infections and bleeding. Importantly, liver transplant should be considered in patients who have poor prognostic factors, such as serum level of factor V, lactate level, and activated prothrombin time. The use of APACHE criteria is not specific for these patients, but it can be used for evaluation. The Model for End-Stage Liver Disease score, which is the model score for patients with end-stage liver disease, is useful for patients with chronic hepatocytic failure, but it does not apply for patients with acute liver failure.¹⁷ We found studies on a possible trial of steroids in drug-induced hepatitis patients with allergic symptoms; in cholestatic drug-induced hepatitis, ursodiol could be of use.^2,46,47

Conclusions
Although the Model for End-Stage Liver Disease score is useful for patients with chronic hepatocytic failure, it does not apply for patients with acute liver failure. When patients with DILI had transplant on time, the results were favorable. The key here was to keep the brain alive.

The use of these easily accessible antiparasitic drugs for prophylactic purposes must be contraindicated and must be consulted with a physician about its indication. That is, when albendazole is used in treatment of parasitic infections, clinicians should be aware of the potential for hepatic injury and routinely monitor liver function tests throughout the course of treatment. If the patient carries disease susceptibility-related HLA alleles, the risk of severe liver injury increases exponentially.

At the first signs of disease development, we suggest that patients should be referred to the transplant center and the preparation of a living donor should be started immediately, so that the organ transplant can be performed without any lapses in time.

References:

1. Kwak SJ, Oh HY, Yeo MA, et al. Fluoxetine-induced acute toxic hepatitis. Clin Mol Hepatol. 2000;6(2):236-240.
   CrossRef - PubMed
   
2. Choi GY, Yang HW, Cho SH, et al. Acute drug-induced hepatitis caused by albendazole. J Korean Med Sci. 2008;23(5):903-905. doi:10.3346/jkms.2008.23.5.903
   CrossRef - PubMed
   
3. Chae HB. Clinical features and diagnosis of drug-induced liver injury. Korean J Hepatol. 2004;10:7-18.
   CrossRef - PubMed
   
4. Sandhu N, Navarro V. Drug-induced liver injury in GI practice. Hepatol Commun. 2020;4(5):631-645. doi:10.1002/hep4.1503
   CrossRef - PubMed
   
5. CIOMS. Drug-induced liver injury (DILI): Current status and future directions for drug development and the postmarket setting. A consensus by a CIOMS Working Group 2020. Accessed March 10, 2022.
   CrossRef - PubMed
   
6. Dragutinovic N, Barac A, Stevanovic G, et al. Acute hepatitis in a paediatric patient: immune-mediated drug-induced liver injury or albendazole-induced autoimmune hepatitis? J Infect Dev Ctries. 2022;16(10):1660-1663. doi:10.3855/jidc.16594
   CrossRef - PubMed
   
7. Fossouo Tagne J, Yakob RA, Dang TH, McDonald R, Wickramasinghe N. Reporting, monitoring, and handling of adverse drug reactions in Australia: scoping review. JMIR Public Health Surveill. 2023;9:e40080. doi:10.2196/40080
   CrossRef - PubMed
   
8. Liao JM, Zhan Y, Zhang Z, Cui JJ, Yin JY. HLA-targeted sequencing reveals the pathogenic role of HLA-B*15:02/HLA-B*13:01 in albendazole-induced liver failure: a case report and a review of the literature. Front Pharmacol. 2023;14:1288068. doi:10.3389/fphar.2023.1288068
   CrossRef - PubMed
   
9. Fontana RJ. Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives. Gastroenterology. 2014;146(4):914-928. doi:10.1053/j.gastro.2013.12.032
   CrossRef - PubMed
   
10. Bilgic Y, Yilmaz C, Cagin YF, Atayan Y, Karadag N, Harputluoglu MM. Albendazole induced recurrent acute toxic hepatitis: a case report. Acta Gastroenterol Belg. 2017;80(2):309-311.
    CrossRef - PubMed
    
11. Vuitton DA. The WHO informal working group on echinococcosis. The Coordinating Board of the WHO-IWGE. Acta Trop. 1997;67(1-2):147-148. doi:10.1016/s0001-706x(97)00059-4
    CrossRef - PubMed
    
12. Garcia HH, Evans CA, Nash TE, et al. Current consensus guidelines for treatment of neurocysticercosis. Clin Microbiol Rev. 2002;15(4):747-756. doi:10.1128/CMR.15.4.747-756.2002
    CrossRef - PubMed
    
13. Rios D, Restrepo JC. Albendazole-induced liver injury: a case report. Colomb Med (Cali). 2013;44(2):118-120.
    CrossRef - PubMed
    
14. Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000;121 Suppl:S113-S132. doi:10.1017/s0031182000007290
    CrossRef - PubMed
    
15. Singthong S, Intapan PM, Wongsaroji T, Maleewong W. Randomized comparative trial of two high-dose albendazole regimens for uncomplicated human strongyloidiasis. Southeast Asian J Trop Med Public Health. 2006;37 Suppl 3:32-34.
    CrossRef - PubMed
    
16. Benichou C, Danan G, Flahault A. Causality assessment of adverse reactions to drugs--II. An original model for validation of drug causality assessment methods: case reports with positive rechallenge. J Clin Epidemiol. 1993;46(11):1331-1336. doi:10.1016/0895-4356(93)90102-7
    CrossRef - PubMed
    
17. Freire J, Carolina Rocha L, Lima L, Raposo P. Subfulminant acute liver failure by albendazole: case report. J Med Cases. 2015;6(8):342-345.
    CrossRef - PubMed
    
18. Devarbhavi H. An update on drug-induced liver injury. J Clin Exp Hepatol. 2012;2(3):247-259. doi:10.1016/j.jceh.2012.05.002
    CrossRef - PubMed
    
19. Ben Fredj N, Chaabane A, Chadly Z, Ben Fadhel N, Boughattas NA, Aouam K. Albendazole-induced associated acute hepatitis and bicytopenia. Scand J Infect Dis. 2014;46(2):149-151. doi:10.3109/00365548.2013.835068
    CrossRef - PubMed
    
20. European Association for the Study of the Liver. Clinical Practice Guideline Panel Chair, Panel Members, EASL Governing Board. EASL clinical practice guidelines: drug-induced liver injury. J Hepatol. 2019;70(6):1222-1261. doi:10.1016/j.jhep.2019.02.014
    CrossRef - PubMed
    
21. Shapiro MA, Lewis JH. Causality assessment of drug-induced hepatotoxicity: promises and pitfalls. Clin Liver Dis. 2007;11(3):477-505, v. doi:10.1016/j.cld.2007.06.003
    CrossRef - PubMed
    
22. Morris DL, Smith PG. Albendazole in hydatid disease--hepatocellular toxicity. Trans R Soc Trop Med Hyg. 1987;81(2):343-344. doi:10.1016/0035-9203(87)90259-8
    CrossRef - PubMed
    
23. Jagota SC. Jaundice due to albendazole. Indian J Gastroenterol. 1989;8(1):58.
    CrossRef - PubMed
    
24. Brunton L, Lazo JS, Parker KL. Goodman Gilman’s the Pharmacological Basis of Therapeutics. 11th ed. McGraw-Hill; 2006.
    CrossRef - PubMed
    
25. Sinxadi P, Maartens G. Pharmacology of anthelmintics : albendazole, mebendazole and praziquantel: clinical pharmacology. CME: Your SA J CPD. 2009;27:274-276.
    CrossRef - PubMed
    
26. Horton J. Albendazole: a broad spectrum anthelminthic for treatment of individuals and populations. Curr Opin Infect Dis. 2002;15(6):599-608. doi:10.1097/00001432-200212000-00008
    CrossRef - PubMed
    
27. Fontana RJ. Acute liver failure. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. Saunders; 2006.
    CrossRef - PubMed
    
28. Ghabril M, Chalasani N, Bjornsson E. Drug-induced liver injury: a clinical update. Curr Opin Gastroenterol. 2010;26(3):222-226. doi:10.1097/MOG.0b013e3283383c7c
    CrossRef - PubMed
    
29. Gil-Grande LA, Rodriguez-Caabeiro F, Prieto JG, et al. Randomised controlled trial of efficacy of albendazole in intra-abdominal hydatid disease. Lancet. 1993;342(8882):1269-1272. doi:10.1016/0140-6736(93)92361-v
    CrossRef - PubMed
    
30. Bildik N, Cevik A, Altintas M, Ekinci H, Canberk M, Gulmen M. Efficacy of preoperative albendazole use according to months in hydatid cyst of the liver. J Clin Gastroenterol. 2007;41(3):312-316. doi:10.1097/01.mcg.0000225572.50514.e6
    CrossRef - PubMed
    
31. Seo JC, Jeon WJ, Park SS, et al. Clinical experience of 48 acute toxic hepatitis patients. Korean J Hepatol. 2006;12(1):74-81.
    CrossRef - PubMed
    
32. Aasen TD, Nasrollah L, Seetharam A. Drug-induced liver failure requiring liver transplant: report and review of the role of albendazole in managing Echinococcal infection. Exp Clin Transplant. 2018;16(3):344-347. doi:10.6002/ect.2015.0313
    CrossRef - PubMed
    
33. Bucuvalas J, Yazigi N, Squires RH, Jr. Acute liver failure in children. Clin Liver Dis. 2006;10(1):149-168, vii. doi:10.1016/j.cld.2005.10.006
    CrossRef - PubMed
    
34. Polson J, Lee WM; American Association for the Study of Liver Diseases. AASLD position paper: the management of acute liver failure. Hepatology. 2005;41(5):1179-1197. doi:10.1002/hep.20703
    CrossRef - PubMed
    
35. Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol. 2008;14(44):6774-6785. doi:10.3748/wjg.14.6774
    CrossRef - PubMed
    
36. Nicoletti P, Aithal GP, Bjornsson ES, et al. Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in HLA and other genes in a genome-wide association study. Gastroenterology. 2017;152(5):1078-1089. doi:10.1053/j.gastro.2016.12.016
    CrossRef - PubMed
    
37. National Institute of Diabetes and Digestive and Kidney Diseases. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012.
    CrossRef - PubMed
    
38. Stephens C, Andrade RJ. Genetic predisposition to drug-induced liver injury. Clin Liver Dis. 2020;24(1):11-23. doi:10.1016/j.cld.2019.08.003
    CrossRef - PubMed
    
39. Spraggs CF, Budde LR, Briley LP, et al. HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer. J Clin Oncol. 2011;29(6):667-673. doi:10.1200/JCO.2010.31.3197
    CrossRef - PubMed
    
40. Redwood AJ, Pavlos RK, White KD, Phillips EJ. HLAs: Key regulators of T-cell-mediated drug hypersensitivity. HLA. 2018;91(1):3-16. doi:10.1111/tan.13183
    CrossRef - PubMed
    
41. Bohm R, Proksch E, Schwarz T, Cascorbi I. Drug hypersensitivity. Dtsch Arztebl Int. 2018;115(29-30):501-512. doi:10.3238/arztebl.2018.0501
    CrossRef - PubMed
    
42. Karnes JH, Miller MA, White KD, et al. Applications of immunopharmacogenomics: predicting, preventing, and understanding immune-mediated adverse drug reactions. Annu Rev Pharmacol Toxicol. 2019;59:463-486. doi:10.1146/annurev-pharmtox-010818-021818
    CrossRef - PubMed
    
43. Yip VL, Alfirevic A, Pirmohamed M. Genetics of immune-mediated adverse drug reactions: a comprehensive and clinical review. Clin Rev Allergy Immunol. 2015;48(2-3):165-175. doi:10.1007/s12016-014-8418-y
    CrossRef - PubMed
    
44. Danan G, Teschke R. RUCAM in drug and herb induced liver injury: the update. Int J Mol Sci. 2015;17(1):14. doi:10.3390/ijms17010014
    CrossRef - PubMed
    
45. Koca T, Akcam M. Albendazole-induced autoimmune hepatitis. Indian Pediatr. 2015;52(1):78-79.
    CrossRef - PubMed
    
46. Ahn BM. Acute toxic hepatitis: RUCAM application to drug-induced liver injury and its limitations. Korean J Hepatol. 2006;12(1):1-4.
    CrossRef - PubMed
    
47. Lee WM. Drug-induced hepatotoxicity. N Engl J Med. 1995;333(17):1118-1127. doi:10.1056/NEJM199510263331706
    CrossRef - PubMed