Antituberculosis Drug-Induced Hepatotoxicity in Children

Abstract

Recent increases in the dosages of the essential antituberculosis agents isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) for use in children recommended by World Health Organization have raised concerns regarding the risk of hepatotoxicity. Published data relating to the incidence and pathogenesis of antituberculosis drug-induced hepatotoxicity (ADIH), particularly in children, is reviewed. Amongst 12,708 children receiving chemoprophylaxis, mainly with INH, but also other combinations of INH, RMP and PZA only 1 case (0.06%) of jaundice was recorded and abnormal liver functions documented in 110 (8%) of the 1225 children studied. Excluding tuberculous meningitis (TBM) 8984 were children treated for tuberculosis disease and jaundice documented in 75 (0.83%) and abnormal liver function tests in 380 (9.9%) of the 3855 children evaluated. Amongst 717 children treated for TBM, however, jaundice occurred in 72 (10.8%) and abnormal LFT were recorded in 174 (52.9%) of those studied. Case reports document the occurrence of ADIH in at least 63 children. Signs and symptoms of ADIH were frequently ignored in the recorded cases. ADIH can occur in children at any age or at any dosage of INH, RMP or PZA, but the incidence of.ADIH is is considerably lower in children than in adults. Children with disseminated forms of disease are at greater risk of ADIH. The use of the higher dosages of INH, RMP and PZA recently recommended by WHO is unlikely to result in a greater risk of ADIH in children.

Hospitalized pediatric antituberculosis drug induced hepatotoxicity: Experience of an Indonesian referral hospital

“…Approximately one million children were diagnosed with TB worldwide in 2014, with Indonesia ranking second after India amongst countries with the highest burden of TB in the world [1]. Antituberculosis drugs are proved effective to eradicate TB, although they can cause some serious adverse events, namely, gastrointestinal disturbances, hepatotoxicity, rash, and fever [2,3]. Recently, the new increased dosage recommendations of the essential antituberculosis drugs (isoniazid, rifampicin and pyrazinamide) by the World Health Organization in 2010, although effective and well-tolerated by children, have also raised concerns regarding antituberculosis drug induced hepatotoxicity (ADIH) [4].…”

“…Isoniazid, rifampicin and pyrazinamide could all potentially cause varying severity of hepatotoxicity [1,3]. Hepatotoxicity, a serious and often fatal side effect of TB treatment, is otherwise known as ADIH/ ATDIH [2,6], drug-induced hepatic injury [7], antituberculosis drug induced liver injury (DILI) [8,9], and antituberculosis drug induced hepatitis [10]. Clinical manifestation of ADIH could range from asymptomatic increase of serum transaminases and bilirubin, to acute liver failure [2,8,9].…”

“…The diagnosis of ADIH was made by the presence of clinical jaundice and/or raised serum total bilirubin level (> 1.5 mg/dL) and/or 3-5 fold rise of serum alanine aminotransferase (ALT) above normal levels in patients receiving antituberculosis therapy, in exclusion of known viral hepatitis (HBV, HCV), chronic liver disease, and liver dysfunction due to any other hepatotoxic drug [2,9,11].…”

Pediatric tuberculosis: A 5-year experience from a Turkish tertiary pediatric hospital

“…Literatürde erişkin hastalarda STR kullanımı ile ilgili bir çalış-mada parastezi görülme sıklığı %4.5 saptanmış ve anafilaksi gelişimi belirtilmemiştir. Genel olarak STR erişkin hastalarda iyi tolere edildiği bildirilmiş-tir (38) . Çocuklarda ise STR ile anafilaksi gibi yaşamı tehdit eden yan etkiler görülebilmekte olup, çalışma-mızda 5 yılık sürede bir vakada anafilaksi ve bir vakada parestezi gelişmişti.…”

“…Donald ve ark. (38) çoklu anti-TB tedavisi alan çocuklarda %8-10 oranında karaciğer enzimlerinde geçici yükselme saptamışlardır. Aynı çalışmada, ciddi hepatotoksisite oranı %0.22-1.3 olarak bildirilmiştir.…”