Predictors of azathioprine toxicity in children with autoimmune hepatitis.

AIM OF THE STUDY: Azathioprine (AZA) is an important steroid-sparing drug in the management of autoimmune hepatitis (AIH). Avoidance of its adverse events that could be severe and carry a risk of mortality in a few cases is important, preferably with cheap and easy assessments that could be feasible in developing countries with the unavailability of molecular assays. Assessment of thiopurine methyltransferase (TPMT), the key enzyme for the inactivation of AZA, as a predictor of AZA toxicity had been a matter of conflict. This work aimed to study the role of TPMT serum level assessment and other host-, disease-, and treatment-related factors in predicting AZA toxicity. MATERIAL AND METHODS: Sixty-six children with AIH, divided into two groups, were recruited. Group 1 included twelve children with AZA toxicity and group 2 included fifty-four children without AZA toxicities. Both groups were compared for demographic, clinical, laboratory, histopathological, and treatment-related factors, and serum TPMT level, measured by ELISA. RESULTS: TPMT serum level was comparable in both groups (p = 0.363). Duration of treatment until enzyme normalization and duration of AZA therapy were significantly associated with AZA toxicity (p = 0.007 and p = 0.01, respectively). At the first follow-up treatment with AZA, total leucocyte count (TLC) and neutrophil counts were significantly lower in group 1 (p = 0.005 and p = 0.002, respectively). Moreover, the percentage reduction of TLC and neutrophil counts were significantly higher in group 1 (p < 0.001, for both). CONCLUSIONS: Monitoring for AZA adverse events in those with the defined predictors of AZA-related adverse events is more important than TPMT assessment.

Serum ferritin in neonatal cholestasis: A specific and active molecule or a non-specific bystander marker?

BACKGROUND: Serum ferritin (SF) and consequently hepatic iron have long been considered important in liver fibrosis progression. They have been studied in different liver diseases with no previous reports in neonatal cholestasis (NC). This study aimed to measure SF in different etiologies of NC and investigate its relation to hepatic iron and fibrosis. METHODS: SF was measured in 75 infants, including 50 with NC and 25 with sepsis. SF was compared between these two groups. Biochemical parameters, hepatic iron grades, and liver fibrosis and other histopathological characteristics and correlated with SF were assessed in NC group. Finally, a comparison between intrahepatic cholestasis and obstructive etiology was performed. RESULTS: SF was elevated in NC (1598 ± 2405 ng/mL) with no significant difference from those with sepsis (P = 0.445). NC and sepsis constituted augmenting factors leading to more elevation of SF (2589 ± 3511 ng/mL). SF was significantly correlated with hepatic iron grades (r = 0.536, P < 0.0001) and a cut-off value of 803.5 ng/mL can predict higher grades (≥ grade 3) of iron deposition with sensitivity of 100%, specificity of 70% and accuracy of 85%. Moreover, SF was significantly higher (P < 0.0001) in those with intrahepatic cholestasis (2602 ± 3154 ng/mL) and their prevalent pathological findings of giant cell transformation (P = 0.009) and hepatocyte swelling (P = 0.023) than those with obstructive etiology (672 ± 566 ng/mL) and their prevalent pathological findings of ductular proliferation (P = 0.003) and bile plugs (P = 0.002). SF was unrelated to the grade of liver fibrosis (P = 0.058). CONCLUSIONS: SF is non-specifically elevated in NC, with positive correlation to hepatic iron grades. SF ≥ 803.5 ng/mL can predict higher grades (≥ grade 3) of hepatic iron. However, an active role of increased SF and hepatic iron in disease progression remains questionable.