Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update.

Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients. However, with the introduction and validation of noninvasive tests (NITs) to evaluate advanced fibrosis, and the direct-acting antiviral agents for treatment of chronic hepatitis C virus (HCV), the role of NITs have become even more complex. There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response. The aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.

Glycosylation Alterations in Cancer Cells, Prognostic Value of Glycan Biomarkers and Their Potential as Novel Therapeutic Targets in Breast Cancer.

Although we are lately witnessing major improvements in breast cancer treatment and patient outcomes, there is still a significant proportion of patients not receiving efficient therapy. More precisely, patients with triple-negative breast cancer or any type of metastatic disease. Currently available prognostic and therapeutic biomarkers are not always applicable and oftentimes lack precision. The science of glycans is a relatively new scientific approach to better characterize malignant transformation and tumor progression. In this review, we summarize the most important information about glycosylation characteristics in breast cancer cells and how different glycoproteins and enzymes involved in glycosylation could serve as more precise biomarkers, as well as new therapeutic targets.

Anabolic androgenic steroid-induced liver injury: An update.

Anabolic androgenic steroids (AASs) are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic effects. These properties make them therapeutically beneficial in medical conditions such as hypogonadism. However, they are commonly bought illegally and misused for their anabolic, skeletal muscle building, and performance-enhancing effects. Supraphysiologic and long-term use of AASs affects all organs, leading to cardiovascular, neurological, endocrine, gastrointestinal, renal, and hematologic disorders. Hepatotoxicity is one of the major concerns regarding AASs treatment and abuse. Testosterone and its derivatives have been most often shown to induce a specific form of cholestasis, peliosis hepatis, and hepatic benign and malignant tumors. It is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors, upregulation of bile acid synthesis, and induction of hepatocyte hyperplasia. Most toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of AAS. However, some long-term consequences are irreversible. AAS-induced liver injury should be taken in consideration in patients with liver disorders, especially with the increasing unintentional ingestion of supplements containing AAS. In this paper, we review the most current knowledge about AAS-associated adverse effects on the liver, and their clinical presentations, prevalence, and pathophysiological mechanisms.

Drug-induced Fatty Liver Disease: Pathogenesis and Treatment.

Metabolic dysfunction-associated fatty liver disease (commonly known as MAFLD) impacts global health in epidemic proportions, and the resulting morbidity, mortality and economic burden is enormous. While much attention has been given to metabolic syndrome and obesity as offending factors, a growing incidence of polypharmacy, especially in the elderly, has greatly increased the risk of drug-induced liver injury (DILI) in general, and drug-induced fatty liver disease (DIFLD) in particular. This review focuses on the contribution of DIFLD to DILI in terms of epidemiology, pathophysiology, the most common drugs associated with DIFLD, and treatment strategies.

Molecular Mechanisms of Resistance to Immune Checkpoint Inhibitors in Melanoma Treatment: An Update.

Over the past decade, immune checkpoint inhibitors (ICI) have revolutionized the treatment of advanced melanoma and ensured significant improvement in overall survival versus chemotherapy. ICI or targeted therapy are now the first line treatment in advanced melanoma, depending on the tumor v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational status. While these new approaches have changed the outcomes for many patients, a significant proportion of them still experience lack of response, known as primary resistance. Mechanisms of primary drug resistance are not fully elucidated. However, many alterations have been found in ICI-resistant melanomas and possibly contribute to that outcome. Furthermore, some tumors which initially responded to ICI treatment ultimately developed mechanisms of acquired resistance and subsequent tumor progression. In this review, we give an overview of tumor primary and acquired resistance mechanisms to ICI and discuss future perspectives with regards to new molecular targets and combinatorial therapies.

The accuracy of breast cancer risk self-assessment does not correlate with knowledge about breast cancer and knowledge and attitudes towards primary chemoprevention.

The increase of breast cancer (BC) incidence has drawn attention to BC risk as means of reducing mortality and morbidity of the disease. The aim of this study was to determine the accuracy of BC risk perception, evaluate factors that affect risk perception and assess the correlation between BC risk perception and attitudes towards BC chemoprevention. A cross-sectional study included total of 258 women with average and high-risk for BC according to the Breast Cancer Risk Assessment Tool (BCRAT). All data were collected by face-to-face interview by three trained 6th year medical school students using a 54-item questionnaire. Each participant's actual BC risk was compared to a perceived risk and the accuracy of the BC risk self-assessment was determined. 72% of high-risk women underestimated their BC risk (p < 0.001). One third of subjects with a family history of BC have also underestimated their own risk (p = 0.002). Women who responded to screening mammography were more informed about BC risk factors (p = 0.001). General knowledge about BC chemoprevention was surprisingly low, regardless of the accuracy of BC risk self-assessment. High-risk women appear to be unrealistically optimistic, since there was a significant difference between the accuracy of self-perceived risk and the objective BC risk.

Impact of Breast Density Awareness on Knowledge about Breast Cancer Risk Factors and the Self-Perceived Risk of Breast Cancer.

Breast density (BD) reduces sensitivity of mammography, and is a strong risk factor for breast cancer (BC). Data about women's awareness and knowledge of BD are limited. Our aim is to examine whether the BD information disclosure and BD awareness among women without BC are related to their knowledge about BC risk factors. We examined self-reported BC risk perception and its association to BD awareness and level of health literacy. A cross-sectional, single site study included 263 Croatian women without BC who had mammographic examination. Data were collected by interviews using questionnaires and a validated survey. Of the total, 77.1% had never heard of BD, and 22.9% were aware of their BD. Most participants who knew their BD (88.2%, p < 0.001) had higher levels of education. Majority of subjects (66.8%) had non-dense breasts and 33.2% had dense breasts. Subjects aware of their BD knew that post-menopausal hormone replacement therapy (p = 0.04) and higher BD (p = 0.03) are BC risk factors. They could more easily access information about health promotion (p = 0.03). High-BD informed women assessed their lifetime BC risk as significantly higher than all others (p = 0.03). Comprehension of BD awareness and knowledge is crucial for reinforcement of educational strategies and development of amendatory BC screening decisions.