6.4 Liver disorder

Anti-TB drugs can cause liver damage. Pyrazinamide is the most hepatotoxic, followed by isoniazid and rifampicin . When a patient develops hepatitis during TB treatment, it may be due to the effect of anti-TB drugs but may also be due to other causes/s. It is important to rule out other possible causes before concluding that the hepatitis is drug-induced.

If the diagnosis of drug-induced hepatitis is made, the anti-TB drugs should be stopped and withheld until the jaundice or hepatic symptoms have resolved and liver function tests have returned to normal. In most cases, the patient can be restarted on the same anti-TB drugs without the recurrence of hepatitis. This can be done either gradually (drugs reintroduced one after the other; less hepatotoxic to more hepatotoxic) or all at once (if the hepatitis was mild). However, if the hepatitis produced severe jaundice, it is advisable to avoid rifampicin and pyrazinamide altogether.

The alternative regimen depends on the suspected drug causing the toxic hepatitis, suggested regimens in such patients are as follows, if
• Pyrazinamide is involved: 2 HRE 7 HR or 9HRE
• Isoniazid is involved: 9 RZE
• Rifampicin is involved: 9 Lfx-HZE
• Pyrazinamide and rifampicin are involved: 10 Lfx-HE

TB treatment should be deferred until the acute hepatitis has resolved. Once the hepatitis resolves, patients can receive the usual anti-TB regimens provided there is no clinical and bio-chemical evidence of liver function impairment. However, hepatotoxicity to anti-tuberculosis drugs may be more common among these patients and should therefore be closely monitored with routine LFTs. In patients with unstable and persistent hepatitis, treat with 8 months of isoniazid, rifampicin plus ethambutol and avoid pyrazinamide.

Patients with chronic liver disease should not receive pyrazinamide. Isoniazid plus rifampicin plus ethambutol can be used for a total treatment duration of 9 months (2HRE/7HR).