Successful treatment ofl-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors

<smlcap>L</smlcap>-Carnitine for Treatment of Pegasparaginase-Induced Hepatotoxicity

“…In a rat model of asparaginase-induced injury to an already steatotic liver, treatment with L -carnitine was effective in reducing the elevation of liver enzymes to levels comparable to those of normal baseline livers [9]. Recently, a case series by Al-Nawakil et al [1] described 3 patients with ALL who developed asparaginase-induced severe hepatotoxicity with major liver steatosis and cytolytic and cholestatic features who dramatically recovered after treatment with B-complex vitamins and L -carnitine (50 mg/kg/day), although there was no clear demonstration of which compound represented the active component [10]. Our case supports these results and suggests that L -carnitine, rather than B vitamins, is what drove the laboratory improvement.…”

“…However, its use, especially in adults, has been limited by a unique profile of side effects, with high-grade hepatotoxicity being the most common. L -Carnitine is a naturally produced amino acid derivative that has been proposed as hepatoprotective against a variety of liver-insulting agents such as valproic acid, acetaminophen, and others [1,2]. …”

Hepatology Clinical

“…Most episodes are self‐resolving; however, fulminant hepatic failure has been reported . Relatively few reports include histological examination, which typically shows moderate to severe diffuse micro‐ or macro‐steatosis with minimal inflammatory changes . We present a case of severe hepatic steatosis secondary to L‐asparaginase and a review of cases seen at our institution.…”

Is N-acetylcysteine infusion an effective treatment option in L-asparaginase associated hepatotoxicity?

“…However, the mechanism of L-asparaginase-associated hepatotoxicity is not clear. There are few reports on the treatment of L-asparaginase-associated hepatotoxicity [234]. An experimental study conducted by Roesmann et al [2] reported that when L-carnitine is administered in combination with L-asparaginase for steatosis, carnitine reduces the toxicity associated with L-asparaginase.…”

“…Alshiekh-Nasany and Douer [3] reported that polyethylene glycol (PEG)-asparaginase related high-grade liver toxicity in adult patients could be rapidly and permanently reversed using the amino acid derivate L-carnitine. Al-Nawalki et al [4] reported that histopathological macrovesicular steatosis was detected in 3 adult patients who developed L-asparaginase toxicity, and that the hepatotoxicity resolved after administration of carnitine and a vitamin B complex.…”