A Real-World Study to Compare the Safety and Efficacy of Paritaprevir/Ombitasvir/Ritonavir and Dasabuvir, with or without Ribavirin, in 587 Patients with Chronic Hepatitis C at the Fundeni Clinical Institute, Bucharest, Romania.

BACKGROUND In the European Union, a tablet with fixed doses of ombitasvir, paritaprevir, and ritonavir combined with dasabuvir is an authorized treatment for patients with chronic hepatitis C virus (HCV) infection. Ribavirin is a broad-spectrum antiviral used in several treatment regimens for patients with HCV infection. This real-world study aimed to compare the safety and efficacy of ombitasvir, paritaprevir, and ritonavir combined with dasabuvir, with or without ribavirin, in 587 patients with chronic hepatitis C attending the Fundeni Clinical Institute, Bucharest, Romania. MATERIAL AND METHODS This is an observational prospective study including 315 patients with F4 degree of fibrosis and compensated cirrhosis, 185 patients with F3 fibrosis, and 83 patients with F2 fibrosis. Liver fibrosis was evaluated by liver biopsy or Fibromax. Efficacy was defined as undetectable HCV-RNA at 12 weeks after the end of treatment. In terms of safety, we monitored the development of adverse reactions, liver cytolysis, cholestasis, and hematologic disorders. RESULTS Of the 587 patients, 2 patients with B-cell lymphoma died during therapy. In total, 3/585 patients (0.51%) did not achieve sustained virologic response. Common adverse effects were nausea and asthenia (especially in patients with other medical treatments; P=0.03 and P=0.04, respectively) and anemia in patients who received ribavirin (P<0.01). None of the patients discontinued antiviral treatment. Patients with kidney transplant or end-stage kidney disease did not receive or discontinued ribavirin. CONCLUSIONS Ombitasvir, paritaprevir, and ritonavir combined with dasabuvir, with or without ribavirin had an efficacy rate of over 99% in HCV genotype 1b infection. We report no serious adverse reactions.

The Role of Programmed Cell Death Receptor 1 in Lung Cancer.

BACKGROUND/AIM: Lung cancer is the most common cancer worldwide. Cancer immunotherapy is the activation of the immune system against cancer. The latest method of immunotherapy involves immune checkpoint inhibitors. Increased levels of programmed death ligand 1 (PD-L1) expression were observed on non-small-cell lung cancer. The association between PD-L1 expression and clinicopathological characteristics in lung cancer is still unclear. PATIENTS AND METHODS: This is a cross-sectional, observational study that evaluated a sample of 41 lung cancer patients diagnosed between March 2019 and December 2020. PD-L1 tumor expression is described as a percentage. RESULTS: Patients were diagnosed with non-microcellular lung cancer and aged 37 to 87 years. Most patients were diagnosed with adenocarcinoma. According to the analysis, the average age of patients with negative PD-L1 tumors was 65.6 years, and of those with positive PD-L1 tumors was 63.6 years. The average value of the tumor proportion score for males was 26.97%, and for females 25.55%. CONCLUSION: No correlation was found between PD-L1 tumor expression and the age and sex of patients.

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus Infection and Thyroid Disease with Follow-Up Thyroid Function and Autoantibody Testing.

BACKGROUND Thyroiditis is an important extrahepatic association in chronic hepatitis C virus (HCV) infection. There have been reports of an association between SARS-CoV-2 infection and the onset or re-activation of autoimmune hypothyroidism. Therefore, we performed this prospective observational study of 42 patients with COVID-19 infection and a history of hepatitis C virus infection and thyroid disease with follow-up thyroid function and autoantibody testing. MATERIAL AND METHODS From April 2020 to October 2020, we performed a prospective observational study of patients with cured hepatitis C virus (HCV) infection and documented thyroid disease who became infected with SARS-CoV-2 (confirmed by SARS-CoV-2 RNA detection via reverse-transcription polymerase chain reaction [RT-PCT] from the upper respiratory tract, both nasal and pharyngeal swabs). Evaluation at 1 and 3 months after SARS-CoV-2 infection included serum determination of antithyroid antibodies (anti-thyroglobulin [anti-Tg] and antithyroid peroxidase [ATPO]), thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and evaluation of thyroid medication, with dose adjustment if required. RESULTS One-month follow-up showed that both patients with autoimmune thyroiditis as well as patients without antibodies had increased ATPO levels. Also, levels of TSH, fT3, and fT4 were significantly decreased. At 3-month follow-up, levels of ATPO were decreased in all patient groups and the levels of thyroid hormones increased to normal values. CONCLUSIONS This study supports previous reports of an association between SARS-CoV-2 infection and thyroid dysfunction associated with thyroid autoantibodies. Thyroid function tests may be considered as part of the laboratory work-up in patients with COVID-19.

COVID-19 Mid-term Impact on Hepatocellular Carcinoma in Patients With Hepatitis C Chronic Infection.

BACKGROUND/AIM: Liver injury has been frequently reported in association with SARS-CoV-2 infection, but data are still lacking regarding the impact of pre-existing liver damage and neoplasia on SARS-CoV-2 infection outcome and vice-versa. This study aimed to assess the effects of SARS-CoV-2 infection on hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infected patients, both in therapeutic-naïve and patients treated with direct acting antivirals. PATIENTS AND METHODS: We conducted a retrospective cohort study on 21 patients with a personal history of HCV infection, that have been diagnosed with different forms of HCC and who were subsequently infected with SARS-CoV-2. Patients were monitored by liver function tests, tumoral markers, blood cell count, and coagulation profile periodically. RESULTS: Solitary HCC nodules were predominant among the subjects who achieved sustained virologic response, while multinodular and infiltrative patterns were mostly prevalent among the treatment-naïve group. Most patients had mild and moderate COVID-19 infections. CONCLUSION: Within the current global pandemic crisis, cancer patients are highly vulnerable and in need of constant monitoring. Among patients with HCC, the ones with cured HCV infection may be at a lower risk of fatality than those with active HCV infection, when diagnosed with SARS-CoV-2 infection.

Modulation of Immune System - Strategy in the Treatment of Breast Cancer.

BACKGROUND/AIM: In women, breast cancer is the most commonly diagnosed cancer type and at the same time the main cause of cancer-related death. Many mechanisms are involved in the tumor microenvironment to restrict the anti-tumor activity by the immune system. Identification of novel prognostic tools based on immunological data could make significant impact in developing innovative immunotherapy strategies that will restore the anti-tumor immune system efficacy. PATIENTS AND METHODS: The study was performed on patients diagnosed with breast cancer, who were divided into two groups depending on the expression of HER2. For the studied group, first we described the infiltrate inflammatory on slides stained with haematoxylin eosin (HE) and in the second part we used flow cytometry in order to measure the percentage of T lymphocytes from the peripheral blood before and after breast cancer treatment. RESULTS: High presence of tumor-infiltrating lymphocytes (TILs) was associated with prognostic improvement, better disease-free survival, distant disease-free survival and overall survival. In breast cancer, the presence of TILs predicts the full pathological response rate (pCR) after neoadjuvant chemotherapy. TILs are one of the best examples of the strict relationship existing between natural defence and carcinogenesis. CONCLUSION: Modulation of the immune system is a promising strategy in the treatment of breast cancer, especially in triple-negative and HER2-positive molecular subtypes, the most immunogenic subtypes with a poor prognosis.

Assessment of Immune Status in Dynamics for Patients with Cancer Undergoing Immunotherapy.

Immunotherapy using immune checkpoint inhibitors has revolutionized the treatment, and many types of cancer show a response rate of 20-40% and a significant increase in five-year survival. However, immunotherapy is expensive and may cause serious adverse events. Therefore, a predictive method allowing identification of responding patients before starting the treatment would be very useful. In this study, we aimed to identify and implement other individual prognosis factors, factors that could lead to an improved clinical decision made in regard to the patient to establish an individualized treatment. Materials and Methods. All patients recruited from October 2018 to July 2019 were treated in OncoFort Hospital, Bucharest, with nivolumab or pembrolizumab. We investigated T lymphocyte CD3+, CD4+, CD8+, and CD4/CD8 cells by flow cytometry in patients before and after receiving treatment with anti-PD-1 agents. Results. We found that the responder group showed higher expression on CD4+ cells than the nonresponder group after the first cycle of immunotherapy. The prediction of the immunotherapeutic effect revealed that the elevation of T lymphocytes CD8+ and CD4+ after the first cycle of immunotherapy was followed by a decrease in their expression after the second cycle and was followed by a return almost to that one after the first administration. Conclusion. Our work indicates that the evaluation of the cells of the immune system in relation to the tumor and immunotherapy may lead to a better understanding of the pathogenic mechanisms and the identification of prognostic and predictive factors that will more effectively model the therapeutic approach.

Long-term Response After Stopping Immunotherapy in a Patient With Metastatic Renal Cancer.

BACKGROUND/AIM: Kidney cancers account for about 2% of human malignancies. In recent decades, the incidence of this cancer type has gradually increased, mainly due to advances in imaging. The metastatic potential of these cancers is significant: a quarter of patients will immediately present with metastases and more than one third of patients treated with nephrectomy for a localized disease will develop metastases during their course. In total, more than half of patients will suffer from the consequences of metastasis. The median survival at this stage is only thirteen months, so the therapeutic challenge is immense. CASE REPORT: The present case report describes a case of left renal clear cell carcinoma with brain, lung, right adrenal, bone and lymph node metastases in a 55-year-old male. The patient received only one line of anticancer treatment with sunitinib, which could not be continued due to haemorrhagic manifestations in brain metastases. The treatment was changed with immunotherapy which showed its effect even if it was stopped due to the patient wishes in the context of the COVID-19 epidemic. CONCLUSION: Immunotherapy opens the doors to a new era in treatment of metastatic renal cancer and shows efficiency even after it has been stopped.

Lung Cancer, Covid-19 Infections and Chemotherapy.

BACKGROUND/AIM: The Covid-19 epidemic has severely strained health care systems across the globe. The impacts are multiple especially for patients cared for cancer. The Covid-19 epidemic has several impacts on the management of lung cancer patients. The aim of this work was to summarize the available epidemiological data on patients diagnosed with lung cancer infected with Covid-19 and describe the different strategies to improve the management of these patients by summarizing the recommendations in this area. PATIENTS AND METHODS: The Teravolt cohort is an observational multicenter registry, including patients with non-small cell cancer, small cell cancer or mesothelioma but also epithelial tumors and a diagnosis of Covid-19. The Theravolt registry indicates an unexpectedly high mortality rate in patients with thoracic malignancies with COVID-19. RESULTS: Between March 26 and April 12, 2020, 200 patients treated in 8 countries were included. They had a performance status (PS) of 0-1 in 72% of cases, were smokers or ex-smokers in 81% of cases, had non-small cell cancer (76% of cases), were under treatment in 74% of cases, and the majority were first-line cases (57%). The hospitalization rate was 76% and the mortality rate 33%; only 10% of patients with criteria for intensive care hospitalization were admitted to the intensive care. CONCLUSION: Data presented in this registry suggest a high mortality in patients with thoracic cancer and Covid-19. Therofere, the importance to create a safe healthcare system during Covid-19 pandemic is underlined along with the need for essential effective clinical service delivery to patients with lung cancer.

Management of Diagnosis and Treatment in a Case of Fibrolamellar Carcinoma.

Background/Aim: Fibrolamellar carcinoma is a rare primary hepatic malignancy that has recently been recognized as a distinct clinical entity, highly different from the well-known hepatocellular carcinoma. This report describes the clinical and paraclinical aspects of the fibrolamellar carcinoma, emphasizing its particularities. Case Report: A 30-year-old patient presented to the hospital with nonspecific symptoms and weight loss, with imaging findings showing abdominal and mediastinal masses. Multiple biopsies were performed, leading to a diagnosis of metastatic fibrolamellar carcinoma. Given the extent of the disease, systemic drug treatment was administered, although prognosis was poor with tumor growth, resulting in biliary duct invasion. Conclusion: Fibrolamellar carcinoma is a rare type of malignancy, with a difficult differential diagnosis in which imaging techniques are important but for which biopsy remains the gold standard. The prognosis depends on tumor extent and may include surgical methods or chemotherapy.