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Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Background. The purpose of this study was to clarify the relationships between patients who had fatal liver failure during the course of chronic hepatitis B and those who were also superinfected with hepatitis A, C, D, or E virus, as well as their hepatitis B virus e system status, so that suitable measures could be adopted to decrease the mortality of patients with chronic hepatitis B. Methods. This study detected superinfections of hepatitis A, C, D, or E virus and the hepatitis B virus e system status in cases of fatal liver failure during the course of chronic hepatitis B by enzyme-lined immunosorbent assay. Results. The frequency of superinfections of hepatitis A, C, D, and E virus was 1.4% (4/282), 6.4% (18/282), 1.8% (5/282), and 28.4% (80/282), respectively, overall, 37.9% (107/282). Hepatitis E was prominent and steady in superinfection rates during the past 12 years. In 62.1% (175/282) of patients, the causes of fatal liver failure were not clear. The serological status frequency of HBeAg(+) and anti-HBe(-), HBeAg (-) and anti-HBe(-), and HBeAg(-) and anti-HBe(+) was 20.6% (22/107), 23.4% (25/107), and 56.1% (60/107), respectively, in the group with superinfections of hepatitis A, C, D, or E virus and 31.4% (55/175), 21.1% (37/175), and 47.4% (83/175), respectively, in the group in which causes were not clear. The serological status HBeAg(+) and anti-HBe(-) was more frequent in the group in which causes were not clear than in the group with superinfections of hepatitis A, C, D, or E virus (P < 0.05). Statistically, there were no differences (P > 0.05) between the serological status HBeAg(-), anti-HBe(-) and HBeAg(-), anti-HBe(+) between the two groups. Conclusions. These results suggest that superinfection (107/282) is an important factor in fatal liver failure. The mortality of chronic hepatitis B can be decreased by strict food sanitation and the use of safe blood products. There were no significant relationships between hepatitis B e antigen seroconversion and fatal liver failure during the course of chronic hepatitis B. [ABSTRACT FROM AUTHOR]