No abstract

We report a case of acute liver injury probably due to fenofibrate. A 50-year-old female without a history of liver disease developed cholestatic hepatitis during her second week of fenofibrate treatment. Laboratory tests on admission showed serum bilirubin 534.0 mcmol/L (conjugated 444.0), alkaline phosphatase (AP) 8.76, gamma-glutamyl traspeptidase (GGT) 20.92, alanine aminotransferase (ALT) 2.6, aspartate aminotransferase (AST) 3.64 mckat/L. Fenofibrate withdrawal and ursodeoxycholic acid (750 mg daily) administration was rapidly followed by a favourable outcome.

Background Sunitinib and pazopanib are both oral small molecule multityrosine kinase inhibitors (MTKI) used in the treatment of renal cell carcinoma (RCC). Hepatotoxicity or “liver injury” is the most important adverse effect of pazopanib administration, but little is known about the underlying mechanism. Liver injury may also occur in patients treated with sunitinib, but severe toxicity is extremely rare. Herein we report two new cases of severe liver injury induced by MTKI. Both cases are unique and exceptional. We assessed both cases for drug-induced liver injury (DILI) using the updated score Roussel Uclaf causality assessment method (RUCAM). The literature on potential pathogenic mechanisms and precautionary measures is reviewed. Case presentation A case of a metastatic RCC (mRCC) patient treated with pazopanib who had manifestation of severe liver injury is presented. These manifestations consisted of grade 4 alanine aminotransferase (ALT) increase and grade 4 hyperbilirubinemia. Alternate causes of acute or chronic liver disease were excluded. The patient gradually recovered from the liver injury and refused any further therapy for mRCC. The patient was diagnosed with acute myeloid leukemia (AML) two years later and eventually succumbed to the disease. The second case describes a mRCC patient treated with sunitinib for 3,5 years and fatal liver failure after 2 weeks of clarithromycin co-medication for acute bronchitis. Conclusions Liver injury has been commonly observed in TKI-treated patients with unpredictable course. Management requires regular routine liver enzyme-monitoring and the collaboration of medical oncologist and hepatologist. There is an unmet medical need for a risk stratification and definition of predictive biomarkers to identify potential genetic polymorphisms or other factors associated with TKI-induced liver injury. Any potential unrecommended concomitant therapy has to be avoided.

II. interní klinika -gastroenterologická a geriatrická LF UP a FN Olomouc Jde o článek charakteru narrative review o onemocněních jater spojených s alkoholem. Věcný obsah je opřen o doporučené postupy (guidelines), které vydala European Association for the Study of the Liver v červenci roku 2018. V uvedeném článku je navíc historie a metabolismus alkoholu. Od minulých doporučení se toto poslední liší zejména důrazem na prevenci a časnou diagnostiku abúzu alkoholu a alkoholismu. Nejedná se o doslovný překlad celých guidelines. Doslovně jsou v článku zmíněna závěrečná doporučení.