A Guide to the Management of Tuberculosis in Patients with Chronic Liver Disease

Abstract

Tuberculosis remains one of the 'Captains of the Men of Death' even today, particularly in the developing world. Its frequency is increased 14-fold in patients with chronic liver diseases (CLD) and liver cirrhosis, more so in those with decompensated disease, probably due to the cirrhosis-associated immune dysfunction syndrome, and case-fatality rates are high. The diagnosis of tuberculosis, particularly the interpretation of the Mantoux test, is also fraught with difficulties in CLD, especially after previous BCG vaccination. However, the greatest challenge in the patient with CLD or liver cirrhosis and tuberculosis is managing their therapy since the best first-line anti-tuberculosis drugs are hepatotoxic and baseline liver function is often deranged. Frequency of hepatotoxicity is increased in those with liver cirrhosis, chronic hepatitis B and chronic hepatitis C, possibly related to increased viral loads and may be decreased following antiviral therapy. If hepatotoxicity develops in those with liver cirrhosis, particularly decompensated cirrhosis, the risk of severe liver failure is markedly increased. Currently, there are no established guidelines for anti-tuberculosis therapy (ATT) in CLD and liver cirrhosis although the need for such guidelines is self-evident. It is proposed that ATT should include no more than 2 hepatotoxic drugs (RIF and INH) in patients with CLD or liver cirrhosis and stable liver function [ChildTurcotte-Pugh (CTP) #7], only a single hepatotoxic drug (RIF or INH) in those with advanced liver dysfunction and no hepatotoxic drugs with very advanced liver dysfunction (CTP $11). A standard protocol should be followed for monitoring ATT-related hepatotoxicity and for stop rules and reintroduction rules in all these patients, on the lines proposed here. It is hoped that these proposals will introduce uniformity and result in streamlining the management of these difficult patients. ( J CLIN EXP HEPATOL 2012;2:260-270)

Good outcome of living donor liver transplantation in drug‐induced acute liver failure: A single‐center experience

“…Major cases of DLIL‐ALF are acetaminophen, antitubercular drugs, antiepileptics, and antibiotics . Out of first‐line antitubercular drugs, isoniazid, pyrazinamide, and rifampicin are hepatotoxic while aminoglycosides, fluoroquinolones, and ethambutol are relatively safe and can be given in cases of ATT hepatotoxicity as modified ATT . Hepatotoxic potential is most common with an isoniazid and rifampicin combination (2.7%) as compared to isoniazid (0.6%) and rifampicin (least among all) .…”

“…Out of first‐line antitubercular drugs, isoniazid, pyrazinamide, and rifampicin are hepatotoxic while aminoglycosides, fluoroquinolones, and ethambutol are relatively safe and can be given in cases of ATT hepatotoxicity as modified ATT . Hepatotoxic potential is most common with an isoniazid and rifampicin combination (2.7%) as compared to isoniazid (0.6%) and rifampicin (least among all) . While acetaminophen is the most common cause in the Western world, ATT is the leading cause of DILI‐ALF in India .…”

Answers to Multiple Choice Questions

“…Thirdly, monitoring of drug-induced hepatitis may be confounded in the presence of underlying liver disease due to fluctuating liver function tests related to the preexisting liver disease. 21 Isoniazid itself is not hepatotoxic; toxicity is mediated through its metabolite, hydrazine. Isoniazid is metabolized in the liver through two main pathways.…”

“…Hepatic damage is rare in patients less than 20 years old; it is observed in 0.3% of those in the 20-34 years age group, increasing to 1.2% in the 35-49 years age group and 2.3% in those older than 50 years of age. 21 Mechanism is idiosyncratic, and rechallenge with isoniazid can be tried once enzymes have returned to normal. 21 Conjugated hyperbilirubinemia is seen with rifampicin due to inhibition of the major bile salt exporter pump, impeding secretion of conjugated bilirubin at the canalicular level.…”

“…21 Mechanism is idiosyncratic, and rechallenge with isoniazid can be tried once enzymes have returned to normal. 21 Conjugated hyperbilirubinemia is seen with rifampicin due to inhibition of the major bile salt exporter pump, impeding secretion of conjugated bilirubin at the canalicular level. 25 Occasionally rifampicin can cause hepatocellular injury although less commonly than isoniazid or pyrazinamide but importantly it can potentiate hepatotoxicity of other antitubercular drugs when given in combination.…”