Drugs-induced liver injury associated with non-steroidal anti-inflammatory drugs: a case report and clinical insights

Aim: To raise the awareness of general practitioners with special characteristics of the clinical manifestations of the drug-induced liver injury (DILI), which can manifest with various signs, symptoms and types of morphological injury, from asymptomatic increase in transaminases and liver steatosis to chronic hepatitis with advanced fibrosis. Key points: NSAID is one of the most commonly prescribed groups of agents worldwide. Most of them have low risk of liver toxicity. However, prolonged uncontrolled intake of NSAID by patients without proper medical follow-up and monitoring may lead to serious liver injury, illustrated by the clinical case presented. The case manifested as an extremely rare liver injury in the form of chronic hepatitis with advanced fibrosis that developed after prolonged NSAID use. Conclusion: DILI usually occur as idiosyncratic (non-predictable) reactions. This is an exclusion diagnosis requiring comprehensive medical knowledge and awareness on potential drug-induced liver toxicity, including that associated with drug interactions. To minimize potential risk of liver toxicity induced by NSAID, it is recommended to take them in the lowest effective dose and for a minimally required period. A thorough assessment of a patient's past history, monitoring of clinical chemistry parameters, and clinical judgment of the physician remain to be decisive for prevention, timely diagnosis, and treatment of DILI

Cholestasis syndrome in a comorbid patient: diagnostic difficulties

The purpose of the review article is to demonstrate generalized ideas on the classification and diagnosis of cholestasis syndrome of various etiologies, to consider the possibility of using laboratory and instrumental research methods in real clinical practice in a comorbid patient. The main provisions. According to the mechanism of development, cholestasis is conditionally divided into intrahepatic and extrahepatic, as well as a mixed type. Extrahepatic cholestasis develops with mechanical obstruction of the main extrahepatic or main intrahepatic ducts. Intrahepatic cholestasis as a result of a number of diseases, such as acute viral hepatitis, primary biliary cholangitis, drug damage to the liver, amyloidosis of the liver. In real clinical practice, a combination of several etiological factors leading to the development of cholestasis is possible in a comorbid patient. A clinical observation is given when, in a patient with gallstone disease, melanoma and ulcerative colitis, after excluding a number of possible causes of cholestasis, autoimmune cross syndrome, autoimmune hepatitis and primary sclerosing cholangitis (PSC), was diagnosed, which allowed the initiation of immunosuppressive therapy with 48 mg corticosteroid (per day) and the preparation of ursodeoxycholic acid (UDCA) exhol at a dose of 1500 mg per day. Regardless of the cause of intrahepatic cholestasis, UDCA remains the drug for the treatment of first-line cholestatic lesions. Conclusion. Only a consistent methodological approach, taking into account all the possible causes of cholestasis, can lead to a correct diagnosis and timely adequate treatment in each case

Biomarkers and signaling pathways of colorectal cancer stem cells

The progression of colorectal cancer is commonly characterized by accumulation of genetic or epigenetic abnormalities, altering regulation of gene expression as well as normal protein structures and functions. Nonetheless, there are some questions that remain to be elucidated, such as the origin of cancer cells and populations of cells initiating and propagating tumor development. Currently, there are two rival theories describing the process of carcinogenesis. One is the stochastic model, arguing that any cell is capable of initiating and triggering the development of cancer. Meanwhile, the cancer stem cell model hypothesizes that only a small fraction of stem cells possesses cancer-promoting properties. Typically, colorectal cancer stem cells (CSCs) share the same molecular signaling profiles with normal stem cells or embryonic stem cells, such as Wnt, Notch, TGF-β, and Hedgehog. Nevertheless, CSCs differ from normal stem cells and the bulk of tumor cells in their tumorigenic potential and susceptibility to chemotherapeutic drugs. This may be a possible explanation of the high percentage of cancer recurrence in patients who underwent chemotherapeutic treatment and surgery. This review article focuses on the colorectal cancer stem cell biomarkers and the role of upregulated signaling pathways implicated in the initiation and progression of colorectal cancer