Drugs & Liver - Panel Discussion

 

     Chairman: Dr. Philip Augustine MD, DM.; Moderator: Dr. Sunil K Mathai MD, DM
Panelists:  Dr. Benoy Sebastian, MD, DM; Dr. Jose Francis MD, DM; Dr. V V Raj MD, DM; Dr. Vinodan MD

 

     Hepatotoxic drugs

The commonly used hepatotoxic drugs are antibiotics like erythromycin, amoxycillin-clavulinic acid, antituberculous agents, statins, NSAIDs like nimesulide, diclofenac, anticonvulsants, oral contraceptive pills, anticancer drugs and herbal medicines. Nimesulide is being withdrawn from markets because of reports of hepatotoxicity. Statins also can produce dose dependent hepatotoxicity.

Mechanism of Liver Injury

Liver injury may be due to direct hepatotoxic effect of drugs or their reactive metabolites or due to idiosyncratic mechanism, which may be either immunoallergic or metabolic

Predisposing Factors for Liver Injury

Includes extremes of age, malnutrition, high dosages, longer duration of exposure, alcoholism, pre existing liver disease and  coadministration of enzyme inducing drugs

Approach to ATT Induced Jaundice

When a patient, which on ATT develops jaundice, the first step, is to exclude other causes of hepatitis by appropriate investigation. As per WHO guidelines, if the patient does not have severe TB, reintroduce the drugs once hepatitis resolves. When the drugs are reintroduced, avoid rifampicin and pyrazinamide if the patient has severe hepatitis. Substitute with 2SHE/10 HE regime.

On the other hand, if the patient has severe TB use streptomycin and ethambutol and restart the usual regime once hepatitis has resolved.

Reintroduction of Drugs
(British Thoracic Society Guidelines)

Restart drugs as soon as the LFT becomes normal. Introduce drugs sequentially in the order INH, Rifampicin, and PZA. Start with 50 mg INH /Day and increase by 50 mg once every 2 3 days, closely monitoring the liver enzymes. Once the Patient tolerates full doses of INH, introduce rifampicin at a starting dose of 75 mg/kg. Later add PZA at 75 mg/kg/day.

Viral Hepatitis and ATT

When a patient on ATT develops acute viral hepatitis, Stop the ATT. Patient may be started on non-hepatotoxic regimen (Streptomycin + Ethambutol +/- Ofloxacin). Standard treatment should be reintroduced once LFT becomes normal.

 

Chronic Liver Disease and ATT

Higher incidence of hepatotoxicity in chronic hepatitis B virus and HCV infection. Modified regimens may be advocated in cirrhosis. 8HRS+/-E or 2HRS +10HE. Avoid PZA. LFT should be monitored closely.

Anaesthesia and Chronic Liver Disease

Look for evidence of ascites, hypoxia, and CVS instability, renal failure, hyponatraemia and hypokalaemia. Optimize the treatable variables before surgery like correction of hypoalbuminaemia, coagulopathy, ascites, anaemia, electrolyte imbalance, and renal or cardiac dysfunction. Maintenance of fluid balance is very important. Selection of type of anesthesia and anesthetic agents may be done judiciously. Desflurane and Isoflurane are less hepatotoxic agents.  Propofol, Fentanyl and Isofluorane may be used for short procedures.

Post Operative Jaundice

The important causes are decompensation of preexisting liver disease, ischaemic hepatitis, drug hepatitis or benign post operative cholestasis.