Managing Hepatotoxicity and Drug-Induced Liver Injury During TB Treatment

Dr. Mohammad Zannatul Rayhan
MD Resident (Phase B , pulmonology )
On behalf of MU-XI , NIDCH
8/27/2019zannatulrayhan@gmail.com

Heliotherapy Treatment

 Liver disease
 Chronic kidney disease
 Diabetes mellitus
 Pregnancy
 Lactation
 Oral contraceptive
 Drug induced skin rash
TB Treatment

 It may occur in 3 clinical settings-
1. Drug induced hepatitis
2. Acute viral hepatitis
3. With pre-existing liver disease(CLD)

* Anti-TB drugs can damage the liver
* Among them –
Most common- Pyrazinamide, Rifampicin, Isoniazid
Less common - Ethambutol
*Hepatotoxicity sequence : PZA > R> INH
*It is important to rule out other possible causes of
hepatitis before deciding DIH
*DIH : ALT/AST˃ 3 times with S/S or ˃ 5times without
S/S

*Anti TB drugs must withheld until jaundice or
hepatic symptoms resolve & LFT return to normal
* In most cases, patient can restart same Anti TB
drugs either gradually (one by one ) or all at once
(if mild hepatitis)
* If hepatitis produce severe jaundice, advisable to
avoid Rifampicin & Pyrazinamide
- suggested regimen 2SHE/10HE

* A severely ill TB patient with drug induced
hepatitis may die without Anti-TB drugs
- treat with Streptomycin & Ethambutol
- after resolve of hepatitis , usual anti-TB
drugs should be re-started
* In extensive TB, Ofloxacin can consider in
conjunction with S & E as an interim non-
hepatotoxic regimen

* TB treatment should be deferred until acute
hepatitis has resolved
* If necessary to treat during AVH,
- Combination of S & E for 3 months is safest option
* If hepatitis has resolved, patient can receive a
continuation phase of 6 months with H & R
* If hepatitis not fully resolve, S & E continue for total
12 months

o Among patients with unstable or advanced
liver disease, liver function test should be
done at the start of treatment
o Hepatotoxic anti-TB drug should be withheld
and alternate regimen should be if -
 ALT ˃3 times
 S.bl˃2 times
o Treatment regimen depend upon Child-Pugh
score of the patient

 H,R,Z are either eliminated almost entirely by
biliary excretion or metabolized into non- toxic
compounds
 H,R can be given in normal doses to patient
with renal failure
 Renal failure patient should receive Pyridoxine
with INH to prevent peripheral neuropathy

 S & E can be given in reduced dose or
intermittently where close monitoring of renal
function are available
 Safest regimen for patient with chronic kidney
disease is depending upon the stage

 Both H and R in normal daily doses
 Both Z (25-30 mg/kg) and E (15-25 mg/kg) three
times weekly immediately after hemodialysis to
avoid premature removal from body

 If a DM patient on insulin develops TB ,then
adjust the dose of insulin
 If DM patient on OAD develops TB, then the
patient should be switched to insulin
 If DM is newly detected in a TB patient ,the
patient should be started on insulin for control
of DM
 Insulin dose decrease in CKD
 OAD – No: metformin and sulphonylurea
Yes: GLP1 agonist and DPP4 inhibitor

 Safety of 1st line ATT has been established except
Streptomycin( Ototoxic to fetus)
 Experience with 2nd line drugs is limited
 Regimen for New cases -> 2HRZE / 4HR
 Regimen for Re-treatment -> 3HRZE/5HRE
 Periodic evaluation of LFT is recommended (INH)
 Pyridoxine is recommended for all pregnant
women taking INH

 Rifampicin - risk of hypo-prothrombinaemia,
Vit- K should be given to both mother &
infant postpartum
 WHO recommends the use of PZA in
pregnancy
 Ainoglycosides – ototoxicity
 Ethionamide – CNS defect
 Fluoroquinolones – cartilage defects

 Breast feeding woman receive a full course
anti-TB drugs
 Breast feeding should continue
 Mother should use face mask
 Prophylactic Isoniazid should be given to baby
for 6 months or at least 3 months
ahead(which one is longer) of the time the
mother is considered non-infectious
 BCG vaccination of newborn postponed until
end of Isoniazid prophylaxis

 Rifampicin reduces the efficacy of estrogen
 OCP with higher dose of estrogen (50 micro) can
be used with rifampicin
 Or another form of non –hormonal
contraception may be used

* If itching with minor skin rash
- Anti-TB drugs may be continued
- exclude skin disease
- give antihistamine
- short course of steroids may be given
* If itching with moderate to severe skin rash
- Stop anti-TB drugs until reaction subsides
- Identify the offending drug/drugs by
challenging dose

 Challenging dose :
- when reaction subsides, start one drug &
see any skin rash
- If no skin rash occurs , start another drug
one after another
- start with low dose & full dose may be
given on 3rd day
- after challenging dose , offending drugs
should be stopped & a new drugs should be
added

Managing Hepatotoxicity and Drug-Induced Liver Injury During TB Treatment

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