Citation ABSTRACTDrug-induced liver injury (DILI) accounts for approximately 10 percent of all cases of acute hepatitis. The patterns of acute injury include any form of hepatic injury, but the most common problems are cholestasis, hepatocellular damage, or a mixed type. DILI is often reversible, and discontinuation of the offending agent usually results in a complete recovery; however, some cases may lead to chronic liver injury, cirrhosis, and even death. Temozolomide (TMZ) is an alkylating, anti-neoplastic agent used for the treatment of refractory anaplastic astrocytoma, newly-diagnosed Glioblastoma multiforme (GBM) and metastatic melanoma. Levetiracetam (LEV) is an established second-generation antiepileptic drug and is most commonly approved as adjunctive treatment of partial-onset seizures with or without secondary generalization. When administered separately each of these drugs is considered to be relatively safe and only few cases of severe liver injury can be found throughout the literature; however, LEV and TMZ are commonly used together in the treatment of brain malignancies. We report three patients who presented with jaundice during treatment with TMZ and LEV, and propose a mechanism for liver sensitization by LEV for TMZ-induced injury.
Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders worldwide. Acute cholangitis (AC) is a serious and life-threatening illness. We aimed to determine whether NAFLD is a risk factor for severity of AC.Methods: We retrospectively studied hospitalized patients with diagnosis of AC over the span of 5 years. Subjects were divided into a NAFLD group and Non NAFLD group. We compared between the two groups in terms of demographic characteristics, comorbidities, laboratory data, and severity of AC (including Charlson Comorbidity index and Tokyo Consensus meeting criteria). Results: 298 of 419 patients who had AC and were hospitalized met the inclusion criteria and were included in the study. Of them, 73/298 (24.5%) were included in NAFLD group. NAFLD group patients were younger, diabetic and more obese than non NAFLD group. Subjects in the NAFLD presented with higher serum C-reactive protein and higher liver enzymes (p<0.05, for each parameter) and suffered more events of organ dysfunction(p<0.001) and bacteremia (p<0.005). Regarding the severity of AC according to Tokyo classification, among the NAFLD group more subjects presented with Grade II (39.7 Vs 33.3%, p <0.001) and Grade III (23.3 vs 18.3, p<0.001) cholangitis, as opposed more Grade I cholangitis among the non-NAFLD group (48.4 vs 37%, p<0.001). Multivariate logistic regression analysis showed that NAFLD is independently associated with severe AC, grade III (OR 3.25, 95% CI 1.65-6.45, p=0.038). Conclusions: NAFLD is as an independent risk factor for severity of AC.
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