Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
Print this page Email this page Users Online: 79

  Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 11  |  Issue : 6  |  Page : 542-544  

Drug-induced liver injury in children – Case series from Mumbai


Department of Pediatrics, Pediatric Liver Clinic, B J Wadia Hospital for Children, Mumbai, Maharashtra, India

Date of Submission31-Jan-2018
Date of Acceptance24-Jul-2018
Date of Web Publication15-Nov-2018

Correspondence Address:
Ira Shah
Pediatric Liver Clinic, B J Wadia Hospital for Children, Mumbai, Maharashtra - 400 012
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_24_18

Rights and Permissions
  Abstract 


Drug-induced liver injury is one of the most common and most important forms of injury to the liver, accounting for over 20%–40% of all instances of fulminant hepatic failure. We present five cases, of which four were started on antituberculosis therapy and one was started on a therapy for seizures with carbamazepine. All of them showed adverse reactions on the liver and its functioning as was evident by the raised liver enzymes or jaundice.

Keywords: Anti-tuberculosis treatment, drug-induced liver injury, fulminant hepatic failure, jaundice, raised liver enzymes


How to cite this article:
Deogaonkar VN, Shah I. Drug-induced liver injury in children – Case series from Mumbai. Med J DY Patil Vidyapeeth 2018;11:542-4

How to cite this URL:
Deogaonkar VN, Shah I. Drug-induced liver injury in children – Case series from Mumbai. Med J DY Patil Vidyapeeth [serial online] 2018 [cited 2018 Dec 19];11:542-4. Available from: http://www.mjdrdypv.org/text.asp?2018/11/6/542/245421




  Introduction Top


Drug-induced liver injury (DILI) is one of the most important reasons for discontinuation of drugs and failure of treatment. In a developing country like India, where the incidence of tuberculosis (TB) is as high as 171/1000,[1],[2] the toxicity of antituberculous therapy (ATT) toward the liver is one of the most important causes for first-line drugs in ATT, such as isoniazid (H), rifampicin (R), and pyrazinamide (Z), to be stopped. Not all patients develop DILI, but certain risk factors may play a prominent role in developing the liver injuries, such as silent chronic liver disease or an underlying hepatitis B virus infection.[3] If the responsible drugs are stopped in the early course of DILI, it is possible to reintroduce them after the features of DILI have resolved.


  Case Reports Top


Case 1

A 1½-year-old boy on ATT from 8 months of age was detected to have elevated liver enzymes on screening. There was no jaundice or vomiting. At 8 months of age, he was diagnosed to have pulmonary TB for which he received 2 months of H (10 mg/kg/day), R (10 mg/kg/day), Z (30 mg/kg/day), and ethambutol (E) (20 mg/kg/day) and he was continued on HR. However, at 1 year of age, he developed tuberculous meningitis (TBM) for which a ventriculoperitoneal shunt was inserted. He was restarted on HRZE, and ofloxacin (O) and kanamycin (Km) were added. However, within 1 month of starting above treatment, he developed elevated liver enzymes and HRZ were withheld. On examination, he had mild hepatomegaly. His parents subsequently took discharge against medical advice.

Case 2

A 4-year-old girl presented with jaundice and fever for 2 months along with rash and black discoloration of skin for 15 days. She had received carbamazepine 2 months ago for a suspected seizure. On examination, she was pale, had jaundice, and hepatosplenomegaly. Other general and systemic examination findings were normal. Investigations showed severe anemia (hemoglobin n = 3.9 g/dl), white blood cell count of 8400/cumm, platelet count of 1,79,000/cumm, bilirubin of 44.6 mg/dl (direct = 28.1 mg/dl), serum glutamic oxaloacetic transaminase (SGOT) of 419 IU/L, serum glutamic pyruvic transaminase (SGPT) of 323 IU/L, total proteins of 4.2 g/dl, and albumin of 2.2 g/dl. Her urine for heavy metal screening was negative, and hepatitis B surface antigen, human immunodeficiency virus, and hepatitis C antibody by enzyme-linked immunosorbent assay were negative. Autoimmune markers were also negative. Twenty-four hours urine copper was normal and there was no Kayser–Fleischer ring. Liver biopsy showed focal spotty parenchymal necrosis with a paucity of bile ducts and cholestasis. The child took discharge against medical advice.

Case 3

A 10-year-old visually impaired girl was on treatment for TBM with pulmonary TB. Within 15 days of starting ATT, she developed melena and vomiting with a severe headache. She was detected to have bilirubin of 2.3 mg/dl, SGOT of 2025 IU/L, SGPT of 695 IU/L, total proteins of 7.5 g/dl, and albumin of 3.2 g/dl. She had received 1st course of ATT 1½ years ago for 6 months and 2nd course of ATT 9 months ago for 3 months in view of sputum positive for acid-fast bacillus. On examination, she was blind and had tender hepatomegaly. Other systems were normal. She was treated with fresh frozen plasma for melena and HRZ were stopped and the patient was shifted to streptomycin (S), O and E was continued. Once liver enzymes (alanine transaminase and aspartate transaminase) normalized in 15 days, the child was reintroduced on HR and SOE were gradually omitted.

Case 4

A 12-year-old girl was on ATT for the past 60 days in view of a focal seizure which on computed tomography brain was due to a calcified granuloma. Her Mantoux test was positive. She again had a seizure after 1½ months of ATT for which phenytoin was added. After addition of phenytoin, she developed a maculopapular rash all over the body and right-sided abdominal pain. On examination, she had scaly hyperpigmented lesions over the body and tender hepatomegaly. Other systems were normal. She was found to have elevated liver enzymes. Thus, phenytoin was omitted and HRZ were stopped and the patient was shifted to ofloxacin and ethambutol. The patient gradually improved and ATT was reintroduced. Electroencephalogram was normal and thus no anticonvulsants were subsequently added.

Case 5

A 4½-year-old girl was detected to have TBM with psoas abscess and was started on ATT consisting of HRZE. After 23 days of treatment, she had fever and elevated liver enzymes along with maculopapular rash. Her HRZ were stopped and ES and ofloxacin were added. She was gradually restarted on HRZ monitoring liver enzymes and is currently asymptomatic.


  Discussion Top


DILI may be acute or chronic, with the acute cases being attributed to the formation of reactive metabolites in the liver. The chronic variety typically occurs in cases where the symptoms are not detected or when a drug-induced etiology is not considered. This was most likely in case 1; however, due to the patient taking discharge against medical advice, it could not be confirmed.

DILI may present with a variety of presentations ranging from asymptomatic elevation of liver enzymes to hepatic failure in extreme cases. Elevation of aminotransferases points to hepatocellular injury while cholestatic injury is seen with alkaline phosphatase elevation.[1] In a few cases, a hypersensitivity reaction may be seen, as evident in the 4th and the 5th patient by the presence of maculopapular rash. Jaundice, right-sided abdominal pain, mild hepatomegaly, and melena are seen in these patients because of inadequate functioning of the liver secondary to hepatocellular damage by the drugs.[4]

DILI may be due to drugs which are intrinsically hepatotoxins, such as paracetamol, which if given in high doses are bound to cause hepatotoxicity. Other drugs such as HRZ and carbamazepine do not depend on the doses, and so their toxicity cannot be predicted.[4] However, certain risk factors are known to increase the chances of causing hepatitis with these drugs. The case 4 shows this, as the patient developed the adverse effects after the addition of phenytoin, which in itself is a known hepatotoxin. However, as is evident from the cases that we are studying, the hepatitis is difficult to predict and so can rarely be prevented.

Adequate monitoring of liver function is necessary for early detection of DILI in asymptomatic cases and is also necessary for charting the prognosis in symptomatic patients and should be done in all patients who are started on known hepatotoxins.[5]

In patients who do not show any clinical signs, discontinuation of the hepatotoxic drugs is required if liver transaminases are found to be >3 times the upper limit of normal (ULN) with bilirubin >2 times the ULN, alkaline phosphatase >1.5 times the ULN in combination with bilirubin 3 times the ULN, SGPT >5 times ULN for 2 weeks, SGPT >8 times ULN, or international normalized ratio >1.5.[6]

If DILI is strongly suspected, it is also important to rule out other more common causes of hepatitis such as viral, autoimmune, nonalcoholic steatohepatitis, and Budd–Chiari syndrome. Transaminase and alkaline phosphatase level monitoring form an important part of the diagnosis. Transaminase levels normalizing in response to drug discontinuation, if present, can be considered an important indicator of DILI. In all our patients, the SGOT and SGPT levels were significantly raised, and cases 3, 4, and 5 also showed improvement in response to drug discontinuation. However, this was not found to be true in cases 1 and 2, which can be attributed to their loss to follow-up.

For all DILI patients, discontinuation of the suspected drugs is necessary. However, it has been found, as seen in cases 3, 4, and 5, that reintroduction of these drugs is possible in most of the patients after the resolution of the DILI.[5]

In cases where resolution of DILI does not occur after drug discontinuation, liver transplantation is another treatment modality which is available for DILI and needs to be seriously considered in such nonresponsive patients.[6]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Mehta N, Ozick LA, Gbadehan E. Drug-Induced Hepatotoxicity. Available from: http://www.emedicine.medscape.com/article/169814-overview. [Last accessed on 2018 Mar 15].  Back to cited text no. 1
    
2.
The World Bank Database. Incidence of Tuberculosis (per 1000 people). Available from: http://www.data.worldbank.org/indicator/SH.TBS.INCD. [Last accessed on 2018 Mar 15].  Back to cited text no. 2
    
3.
Anand AC, Seth AK, Paul M, Puri P. Risk factors of hepatotoxicity during anti-tuberculosis treatment. Med J Armed Forces India 2006;62:45-9.  Back to cited text no. 3
    
4.
Zimmerman HJ. Drug-induced liver disease. Drugs 1978;16:25-45.  Back to cited text no. 4
    
5.
Singh J, Garg PK, Tandon RK. Hepatotoxicity due to antituberculosis therapy. Clinical profile and reintroduction of therapy. J Clin Gastroenterol 1996;22:211-4.  Back to cited text no. 5
    
6.
Ong E, Conradie F, Berhanu R, Black A, John MA, Meintjes J, et al. Consensus statement: Management of drug-induced liver injury in HIV-positive patients treated for TB. South Afr J HIV Med 2013;14:113-9. [Last accessed on 2018 Mar 15].  Back to cited text no. 6
    




 

Top
   
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
   Abstract
  Introduction
  Case Reports
  Discussion
   References

 Article Access Statistics
    Viewed58    
    Printed3    
    Emailed0    
    PDF Downloaded10    
    Comments [Add]    

Recommend this journal