Anti tubercular drug induced hepatitis/liver injury

1. ATT INDUCED HEPATITIS

2. HEPATOTOXIC DRUGS HEPATIC SAFE DRUGS
 Isonaizid
 Rifampicin
 Pyrazinamide(most
hepatotoxic)
 Rifabutin
 Streptomycin
 Ethambutol
 Flouroquinolones :
levofloxacin ,
moxifloxacin

3. ATT INDUCED HEPATITIS
 Derangement in liver function while the patient is on
ATT,provided other causes of deranged LFTs are
ruled out.
Diagnosisof exclusion
 Must rule out :
1. Excessive alcohol consumption
2. Hepatitis A or E (esp. in India )
3. Hepatitis B or C if not done at baseline
4. Other hepatotoxic drugs

4. Clinical Symptoms
 Abdominal pain
 Vomiting
 Unexplained fatigue
 Yellowing of sclera
 Altered sensorium
 Anorexia
 Coagulopathy, hypoglycaemia ,mental status changes
signify life-threatening hepatic dysfunction

5. MECHANISM OF HEPATOTOXICITY
 Idiosyncratic damage : Most Common
 Dose-dependent toxicity
 Induction of hepatic enzymes
 Drug-induced acute hepatitis
 Allergic reactions

6. WHEN TO STOP ATT
 AST/ALT >= 5 x ULN , in the absence of symptoms
or hyperbilirubinemia ( ATS )
OR
 AST /ALT >= 3 x ULN , in the presence of symptoms
or hyperbilirubinemia ( ATS )

7. Patients requiring urgent ATT
 Sputum + Pulmonary TB
 TB meningitis or CNS TB
 Pericardial TB
 Any form that is life
 threatening, eg.,
 Intestinal TB with
 intestinal obstruction
 Ocular TB
 Joint or Spinal TB

8. Alternate drugs in Patients requiring
urgent ATT
Change to non-hepatotoxic drugs
Fluroquinolones Ethambutol
Aaminoglycosides

9. SYMPTOMATIC MANAGEMENT OF ATT
INDUCED HEPATITIS
 Rest according to patient’s level of fatigue.
 IV Fluids and electrolyte replacement.
 Anti-emetic agents
(ondansetron,metoclopramide,etc)
 Small frequent feedings of high calorie low fat
diet,proteins are restricted.

10. REINTRODUCTION OF ATT HEPATOXIC
DRUGS
 Reintroduce only if ALT and AST < 2 ULN & normal
bilirubin
 Start one drug at time: helps identify the culprit
 If ATT hepatitis severe (liver failure, coagulopathy
or altered sensorium): Pyrazinamide reintroduction
may be avoided
 Another approach could be low dose of one drug
followed by full dose after three days
 Duration of ATT: count only when full ATT is
started

11. REINTRODUCTION OF ATT

13. ATT Selection for underlying Liver disease
 Based on CHILD PUGH SCORE

15. TAKE HOME MESSAGE
Patients with risk factors of DILI or those with
abnormal LFTs should be monitored timely
throughout ATT DILI is a diagnoses of exclusion ,
before diagnosing a patient with DILI other common
causes of deranged LFTs must be ruled out (esp.
hepatitis)
Patient and the family members must be EDUCATED
about the potential side effects and symptoms of ATT
induced hepatotoxicity . Patients should be told
to consult their doctor immediately if they
develop any such symptoms.

16. THANK YOU