Isoniazid-Associated Hepatitis

Garibaldi, Richard A.; Drusin, Ronald E.; Ferebee, Shirley H.; Gregg, Michael B.

doi:10.1164/arrd.1972.106.3.357

Cited by 204 publications

(53 citation statements)

References 10 publications

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“…In the early 1970s it became apparent that severe hepatic injury leading to death may occur in some individuals receiving INH. 26 Additional studies in adults and children have confirmed this, the characteristic pathological process being bridging and multilobular necrosis. INHinduced hepatotoxicity is seen mainly as hepatocellular steatosis and necrosis, and it has been suggested that toxic INH metabolites may bind covalently to cell macromolecules.…”

Section: First-line Drugs Isoniazidmentioning

confidence: 78%

“…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. 26,27,[32][33][34] Up to 12% of patients receiving INH may have elevated plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. 32,33 Recent treatment studies have reported significant transaminase elevation in 1-4% of those treated with INH for latent tuberculosis infection.…”

Section: First-line Drugs Isoniazidmentioning

confidence: 99%

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

Dhiman

Saraswat

Rajekar

et al. 2012

Journal of Clinical and Experimental Hepatology

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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)

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Section: First-line Drugs Isoniazidmentioning

confidence: 78%

Section: First-line Drugs Isoniazidmentioning

confidence: 99%

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

Dhiman

Saraswat

Rajekar

et al. 2012

Journal of Clinical and Experimental Hepatology

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“…There are various metabolic products of isoniazid, including monoacetyl hydrazine, hydrazine and isonicotinic acid, which have been suggested as being hepatotoxic. The onset of injury is usually after 6 weeks, and maybe up to 1 year after beginning [2, 6,7]. Concomitant use of rifampicin leads to earlier and more frequent injury, some in less than 10 days [8].…”

Section: Isoniazid (Inh)mentioning

confidence: 99%

“…Symptomatic liver disease occurs less commonly, being reported in 0.5-3% [6,[13][14][15]. A recent meta-analysis revealed a clinical hepatitis rate of 0.6% when isoniazid was used alone, and 1.6% when used in multidrug regimens not including rifampicin [16].…”

Section: Isoniazid (Inh)mentioning

confidence: 99%

Anti-tuberculosis medication and the liver: dangers and recommendations in management

Thompson

Caplin²,

Hamilton³

et al. 1995

Eur Respir J

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“…Hepatotoxicity, mainly related to INH and PZA, has been widely reported. [2][3][4] This hepatotoxicity ranges from liver function test abnormalities to acute liver failure (ALF). In most cases, ALF associated with INH and RIF occurs within 10 days of the initiation of the anti-TB regimen, whereas liver failure due to PZA develops Abbreviations: ADP, adenopathy; AFB, acid-fast bacillus; ALF, acute liver failure; ALS, anti-lymphocyte serum; ALT, alanine aminotransferase; AMK, amikacin; AMOX, amoxicillin; ARDS, acute respiratory distress syndrome; ATT, antitubercular treatment; AZA, azathioprine; BAS, basiliximab; BTC, belatacept; CFX, ciprofloxacin; CSA, cyclosporine A; CTM, clarithromycin; DDLT, deceased donor liver transplantation; DRESS, drug rash with eosinophilia and systemic symptoms; ETH, ethambutol; F, female; FQ, fluoroquinolone; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HE, hepatic encephalopathy; HIV, human immunodeficiency virus; IMS, immunosuppressive treatment; INH, isoniazid; INR, international normalized ratio; LDLT, living donor liver transplantation; LFX, levofloxacin; LT, liver transplantation; M, male; MMF, mycophenolate mofetil; MOF, multiorgan failure; MOX, moxifloxacin; NA, not applicable; ND, not done; OFX, ofloxacin; P, prednisolone; PT, prothrombin; PZA, pyrazinamide; RFB, rifabutin; RFP, rifapentine; RIF, rifampicin; SMC, streptomycin; TB, tuberculosis; TCR, tacrolimus.…”

mentioning

confidence: 99%

Acute liver failure due to antitubercular therapy: Strategy for antitubercular treatment before and after liver transplantation

et al. 2010

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The standard antitubercular treatment (ATT), which consists of isoniazid (INH), rifampicin (RIF), ethambutol, and pyrazinamide (PZA), is the best available treatment for tuberculosis (TB). However, the hepatotoxicity of INH and PZA can be severe, and even after drug withdrawal, patients may require liver transplantation (LT). In these cases, the strategy for the treatment of TB is poorly defined. Between 1986 and 2008, 14 patients presented at our department with severe hepatitis secondary to INH and PZA treatment. Four of these patients were immunosuppressed: 2 after renal transplantation and 2 because of human immunodeficiency virus infection. In seven of the 14 patients an alternative ATT was begun on admission, which was well tolerated. Hepatitis improved spontaneously in 5 patients, and alternative ATT was continued for 9.3 6 4.2 months; 1 patient deteriorated and underwent LT, and 1 patient died. ATT was stopped definitively in 2 patients. Six patients required urgent LT, and alternative ATT was started after transplantation and was successful. Five patients receiving RIF had an episode of acute rejection. In conclusion, hepatitis secondary to ATT can be successfully treated with alternative anti-TB regimens. The use of RIF in LT patients may lead to acute rejection. RIF should therefore be avoided in these patients.

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Isoniazid-Associated Hepatitis

Cited by 204 publications

References 10 publications

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

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

Anti-tuberculosis medication and the liver: dangers and recommendations in management

Acute liver failure due to antitubercular therapy: Strategy for antitubercular treatment before and after liver transplantation

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