HCV and HCC Tango-Deciphering the Intricate Dance of Disease: A Review Article.

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) accounting for around one-third of all HCC cases. Prolonged inflammation in chronic hepatitis C (CHC), maintained through a variety of pro- and anti-inflammatory mediators, is one of the aspects of carcinogenesis, followed by mitochondrial dysfunction and oxidative stress. Immune response dysfunction including the innate and adaptive immunity also plays a role in the development, as well as in the recurrence of HCC after treatment. Some of the tumor suppressor genes inhibited by the HCV proteins are p53, p73, and retinoblastoma 1. Mutations in the telomerase reverse transcriptase promoter and the oncogene catenin beta 1 are two more important carcinogenic signaling pathways in HCC associated with HCV. Furthermore, in HCV-related HCC, numerous tumor suppressor and seven oncogenic genes are dysregulated by epigenetic changes. Epigenetic regulation of gene expression is considered as a lasting "epigenetic memory", suggesting that HCV-induced changes persist and are associated with liver carcinogenesis even after cure. Epigenetic changes and immune response dysfunction are recognized targets for potential therapy of HCC.

Clostridioides difficile ribotype distribution in a large teaching hospital in Serbia.

BACKGROUND: The global epidemic of nosocomial diarrhea caused by Clostridioides (Clostridium) difficile started in 2000, with high mortality rates and emergence of a new hypervirulent strain NAP1/BI/027. The aim of this study was to assess the presence of ribotype 027 and other C. difficile ribotypes in a Serbian University Hospital, compare the temporal variability of ribotypes 3 years apart, as well as to compare clinical, demographic and laboratory characteristics and disease outcome among patients infected with 027 and non-027 ribotype. This was a prospective observational cohort study addressing 4-month intervals during 2014/2015 and 2017/2018. RESULTS: Ribotyping was performed in 64 non-duplicate C. difficile strains. Ribotype 027 was the most prevalent, and was detected in 53 (82.8%) patients (43/45 and 10/19 patients in 2014-2015 and 2017/2018, respectively). Other detected ribotypes were 001/072 in 4 (6.3%), 002 in 4 (6.3%), 014/020 in 2 (3.1%) and 176 in 1 (1.5%) patient. The percentage of the patients infected with ribotype 027 significantly decreased during the 3-year period, from 95.6 to 52.6% (p < 0.001). Ribotype 027 infection was associated with fluoroquinolone treatment more frequently than infection with other ribotypes [33 (62.3%) vs. 2 (18.2%), p = 0.010)]. A severe C. difficile infection was diagnosed more often in patients with the detected ribotype 027 compared to those infected with non-027 ribotypes (p = 0.006). No significant difference in the mortality and recurrence rates was found between the patients infected with ribotype 027 and those infected with other ribotypes [10/53 (18.8%) vs. 2/11 (18.2%), p = 0.708, and 10/35 (28.6%) vs. 0/2 (0%), p = 1.000, respectively]. CONCLUSION: Clostridium difficile ribotype 027 was the most prevalent ribotype among patients in a large Serbian hospital, but there is a clear decreasing trend.

ANTIVIRAL TREATMENT OF HEPATITIS C IN SERBIAN PRISON SETTING: MEDICAL TREATMENT OUTCOMES AND PATIENTS' ADHERENCE.

INTRODUCTION: Seroprevlence of chronic hepatitis C viral infection in correctional facilities ranges from 16% to 49%. However, there are only very limited data available on the course of hepatitis C viral infection and outcomes oftreatment with pegylated interferon plus ribavirin in correctional settings. The aim ofthis study was to assess the feasibility and effectiveness of use of pegylated interferon plus ribavirin treatment in the Serbian correctional setting. MATERIAL AND METHODS: The study sample consisted of the patients with hepatitis C hospitalized in the Special Hospital for Prisoners in Belgrade (Serbia) during 2007-2013. Health authorities approved treatment for 32 patients out of 76 treatment-naive patients referred to this institution. The patients (N=32) received 180 mcg pegylated interferon alfa-2a once a week plus oral ribavirin in dosage of 800 mg or 1000/1200 mg/day for 24 or 48-week treatment. All patients who completed therapy were assessed at the end of an additional 24-week treatment-free period for a sustained virological response. RESULTS: Sustained virological response was achieved in 53.8% of hepatitis C viral infection genotype I patients and in 73.3% and 66.6% of patients with hepatitis C viral infection genotype 3 and 4, respectively. One patient with mixed genotype (1, 2) did not achieve sustained virological response. The overall safety profile of the treatment regimen was very good. The incidence of influenza-like symptoms and depression were low A serious adverse event was recorded only in 6.4% of patients. CONCLUSION: The results showed that pegylated interferon alfa-2a plus ribavirin given once a week was well tolerated among prisoners and the regimen had the same adherence and effectiveness as in general population.