Rifampin Hepatotoxicity Associated With Treatment of Latent Tuberculosis Infection

Fountain, Francis F.; Tolley, Elizabeth A.; Jacobs, Anna; Self, Timothy H.

doi:10.1097/maj.0b013e31818c0134

Cited by 33 publications

(17 citation statements)

References 19 publications

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“…The studies of adults have shown improved adherence with and better tolerance of RIF regimens compared with INH [61][62][63][64][65]. A large retrospective study involving over 2,000 adults showed that completion rates of RIF therapy given for 4-6 months were three times higher than for 9 months of INH and patients on RIF [65].…”

Section: Rif Adherence and Side Effectsmentioning

confidence: 99%

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Current Diagnosis and Treatment of Pediatric Latent Tuberculosis Infection

Hatzenbuehler

Starke

2014

Curr Pediatr Rep

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The goal of diagnosing and treating latent tuberculosis infection (LTBI) in children is to prevent future cases of tuberculosis (TB) disease. In low-prevalence countries, LTBI screening, testing, and treatment are risk based. Testing is limited by lack of a reference standard; both available methods-the tuberculin skin test (TST) and interferon gamma release assays (IGRAs)-have significant limitations. The antigens used in IGRAs are not found in BCG-Mycobacterium bovis or most nontuberculous mycobacteria, making these tests more specific for Mycobacterium tuberculosis infection than the TST. The two methods have similar sensitivity, and neither performs well in immunosuppressed children. Children with LTBI are given treatment because it decreases their risk of developing TB disease, and the rate of significant adverse events is low. The most commonly used treatment regimen of 6-9 months of isoniazid is limited in effectiveness by poor adherence. New treatment regimens, using 4 months of rifampin, 3 months of isoniazid and rifampin, or 12 weekly doses of isoniazid and rifapentine, are safe and have significantly higher completion rates.

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Section: Rif Adherence and Side Effectsmentioning

confidence: 99%

“…Children receiving 4 months of RIF were more likely (80.5 %) to complete treatment than those taking INH (53.1 %). This study did not evaluate the efficacy of 6 months versus 4 months of RIF; however, several observational studies in adults suggest a high efficacy associated with 4 months of RIF therapy [61][62][63][64][65].…”

Section: Rifampin (Rif)mentioning

confidence: 99%

Current Diagnosis and Treatment of Pediatric Latent Tuberculosis Infection

Hatzenbuehler

Starke

2014

Curr Pediatr Rep

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“…The hepatotoxicity induced by RMP was first reported in 1971, and it has an incidence rate of 5 to 12.5% (4,5). RMP-induced hepatotoxicity can be divided into three categories: hepatocellular, cholestatic or mixed-type injury (6). In spite of the well-accepted toxicity of RMP in vivo, its toxic mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

SLCO1B1 *15 haplotype is associated with rifampin-induced liver injury

Chen

Deng

et al. 2012

Mol Med Report

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Abstract. The organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1) plays an important role in the transport of endogenous and xenobiotic compounds, such as bile acids and rifampin. In this study, the association between OATP1B1 polymorphisms and rifampin hepatotoxicity was investigated using integrated population genetic analysis and functional studies. A total of 273 unrelated patients treated with rifampin were recruited. The allele frequencies were examined in patients with drug (rifampin)-induced liver injury (DILI) (n=118) and without (non-DILI) (n=155). Functional analyses were conducted to determine whether the inhibition of bile acids by rifampin was associated with OATP1B1 variants. In the present study, 24 single nucleotide polymorphisms (SNPs) in OATP1B1 were detected in a Chinese population, with two of them causing an amino acid change (rs2306283 and rs4149056). The haplotypes constructed by these two SNPs were OATP1B1 IntroductionRifampin (RMP) is one of the major antituberculosis drugs, a second-choice antistaphylococcal agent and an effective medicine in controlling pruritus in primary biliary cirrhosis (1-3). The common adverse reactions to RMP include fever, nausea, vomiting, diarrhea, abdominal pain, hemolytic anemia, thrombocytopenia, liver injury and tubular defects. The hepatotoxicity induced by RMP was first reported in 1971, and it has an incidence rate of 5 to 12.5% (4,5). RMP-induced hepatotoxicity can be divided into three categories: hepatocellular, cholestatic or mixed-type injury (6). In spite of the well-accepted toxicity of RMP in vivo, its toxic mechanism remains unclear. Recently, one important mechanism was determined to be a rise in serum bilirubin via competitive inhibition of hepatocyte bilirubin transport by RMP (7). The inhibition of the hepatic uptake of bile acid has been proposed as the mechanism responsible for RMP-induced cholestasis (8). Notably, the genetic polymorphisms of bile acid transporters have been reported to be closely related to the susceptibility to RMP hepatotoxicity (9).Organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1) is one of the most important bile acid transporters. It is mainly expressed on the basolateral membrane of human hepatocytes and is responsible for bilirubin uptake (10,11). Several studies have demonstrated that OATP1B1 plays an important role in the hepatic uptake of RMP (12). In particular, it has displayed a great capability for RMP transport in HeLa cells, with RMP uptake being markedly decreased by the OATP1B1 allelic variants (13). To date, however, many studies of RMP hepatotoxicity have concentrated on the transporters that export RMP, and few studies have been published concerning the importance of the transporters that uptake RMP. In fact, RMP inhibits the uptake of bile acids by OATP1B1 (14). For example, RMP inhibits OATP1B1-mediated substrate uptake into the liver in a Xenopus laevis oocyte expression system (13

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“…21,70,73 Rifampin alone seldom induces DILI (in up to 2.7% of patients); however, it may occur in patients with pre-existing liver disease. 72,[74][75][76] Mechanistically, rifampin competes with bilirubin for the bile salt export pump, and results in hyperbilirubinemia and cholestatic liver disease. 77 In addition, drug-induced hypersensitivity may also be responsible for a minority of cases.…”

Section: Antimicrobial Medicationsmentioning

confidence: 99%

Drug-Induced Liver Injury

Hamilton

Collins‐Yoder

Collins

2016

AACN Advanced Critical Care

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Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but preexisting liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. KeywordsDrug-induced liver injury (DILI); drug-induced hepatitis; drug-induced cholestasis; acetaminophen; vanishing bile duct syndrome; herbal toxicity Adverse drug reactions are an important cause of liver injury that may require discontinuation of the offending agent, hospitalization, or even liver transplantation. 1 Indeed, drug-induced hepatotoxicity is the most frequent cause of acute liver failure in US. 2 Because the liver is responsible for concentrating and metabolizing a majority of medications, it is a prime target for medication-induced damage. Among hepatotoxic drugs, acetaminophen (paracetamol) is the most often studied. However, a broad range of different pharmacological agents can induce liver damage, including anesthetics, anticancer drugs, antibiotics, antituberculosis agents, antiretrovirals, and cardiac medications. In addition, a plethora of traditional medical therapies and herbal remedies may also be hepatotoxic.Depending on the duration of injury and the histological location of damage, drug-induced liver injury (DILI) is categorized as acute or chronic, and either as hepatitis, cholestatic, or a mixed pattern of injury. The hepatitis pattern is characterized by hepatocyte necrosis and is associated with a poor prognosis. There are three types of acute cholestatic drug-induced injury: bland cholestasis is the result of abnormal biliary secretion, and is not accompanied by significant hepatocellular damage; cholestatic hepatitis (mixed type) refers to cholestasis with concomitant hepatic parenchymal damage; and the third form of acute cholestasis is

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Rifampin Hepatotoxicity Associated With Treatment of Latent Tuberculosis Infection

Cited by 33 publications

References 19 publications

Current Diagnosis and Treatment of Pediatric Latent Tuberculosis Infection

Current Diagnosis and Treatment of Pediatric Latent Tuberculosis Infection

SLCO1B1 *15 haplotype is associated with rifampin-induced liver injury

Drug-Induced Liver Injury

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