Liver involvement in inflammatory bowel disease: What should the clinician know?

Inflammatory bowel disease (IBD) may show a wide range of extraintestinal manifestations. In this context, liver involvement is a focal point for both an adequate management of the disease and its prognosis, due to possible serious comorbidity. The association between IBD and primary sclerosing cholangitis is the most known example. This association is relevant because it implies an increased risk of both colorectal cancer and cholangiocarcinoma. Additionally, drugs such as thiopurines or biologic agents can cause drug-induced liver damage; therefore, this event should be considered when planning IBD treatment. Additionally, particular consideration should be given to the evidence that IBD patients may have concomitant chronic viral hepatitis, such as hepatitis B and hepatitis C. Chronic immunosuppressive regimens may cause a hepatitis flare or reactivation of a healthy carrier state, therefore careful monitoring of these patients is necessary. Finally, the spread of obesity has involved even IBD patients, thus increasing the risk of non-alcoholic fatty liver disease, which has already proven to be more common in IBD patients than in the non-IBD population. This phenomenon is considered an emerging issue, as it will become the leading cause of liver cirrhosis.

Sex Differences on Mitotane Concentration and Treatment Outcome in Patients with Adrenocortical Carcinoma.

(1) Background: In clinical settings, data regarding sex are rarely investigated. In women, factors such as body size and composition, hormonal variations, metabolism, and access to care systems and therapy could strongly influence the pharmacological management and the outcome of the therapy. To underline this sex-related difference, we retrospectively collected data from adrenocortical carcinoma patients treated with mitotane, and then evaluated sex-related pharmacokinetics parameters. (2) Methods: A fully validated chromatographic method was used to quantify mitotane concentration in plasma collected from adult patients, also considering the active metabolite ortho,para,dichlorodiphenylethene (o,p'-DDE). Statistical analyses were used to evaluate the sex influence on drugs pharmacokinetics. (3) Results: We found that sex resulted as predictive factor of plasma mitotane and o,p'-DDE concentrations and significantly influenced the attainment of the therapeutic target of mitotane, implying that female sex could be a risk factor of treatment failure. (4) Conclusions: These results suggest that mitotane therapy should be modulated according to patient sex. Furthermore, the proposed approach could contribute to facilitating and disseminating sex-specific pharmacology.