Liver Dysfunction Associated with Intravenous Methylprednisolone Pulse Therapy in Patients with Graves’ Orbitopathy

Intravenous methylprednisolone (IVMP) pulse therapy is the first-line treatment for the active phase of moderate to severe Graves’ orbitopathy (GO). However, acute and severe liver damage has been reported during and after IVMP therapy. In this retrospective study, we investigated risk factors for liver dysfunction during and after IVMP therapy based on 175 Japanese patients with moderate to severe GO and treated at our center between 2003 and 2011. The results showed that seven patients developed severe liver dysfunction with elevated serum alanine aminotransferase (ALT > 300 U/L). Mild (40–100 U/L) and moderate (100–300 U/L) increases of ALT occurred in 62 patients (35%) and 10 patients (6%), respectively. Liver dysfunction was more frequently observed in males, in patients receiving high-dose methylprednisolone, and patients aged over 50 years. Preexistent viral hepatitis was significantly associated with liver dysfunction (65% in patients positive for hepatitis B core antibody and patients positive for hepatitis C virus antibodies). Our study confirmed the association of liver dysfunction with IVMP during and after treatment. It suggests that, in patients with GO, evaluation of preexisting risk factors—including viral hepatitis—and careful weekly monitoring of liver function during IVMP therapy and monthly thereafter for 12 months are warranted

Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats - Fig 6

<p><b>The protein expressions of pAMPK and pACC in the liver of SD rats at 15 weeks old.inhibo</b> A; Western blot analysis, B; Densitometric quantification. Open bars denote control group and black bars denote metformin-treated group. Data are presented as mean ± S.E. (n = 3 in each group). *P<0.05 vs. control groups.</p

Pyruvate tolerance test in SD rats at 15 weeks old.

<p>Data are presented as mean ± S.E. (n = 6 in each group). Paired t-test was used for the comparison between groups. Open circle and dotted line; control group, closed circle and solid line; metformin-treated group. *P<0.05 vs. the value of control group at each time point.</p

Fat oxidation-related gene expressions in the liver of SD rats at 15 weeks old.

<p>A; <i>Cpt1</i>, B; <i>Acs</i>, C; <i>Acad</i>, D; <i>Pdk</i> expression corrected by <i>Gapdh</i> expression. Open bars denote control group and black bars denote metformin-treated group. Data are presented as mean ± S.E. (n = 6 in each group). *P<0.05, **P<0.01 vs. control groups.</p

Anthropometric factors, food intake and water consumption in control and metformin-treated rats.

<p>Anthropometric factors, food intake and water consumption in control and metformin-treated rats.</p