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.

Risk Perception About HIV Among University Students in One of the Last Hotspots for HIV Transmission in Europe.

BACKGROUND: HIV testing in the Northern Kosovo province is challenging, because the infrastructure is being rebuilt after the ethnic conflict. The purpose of this research was to examine self-perceived risk for acquiring HIV infection and factors associated with risk assessment among university students. METHODS: Students completed a questionnaire on socio-demographic data, knowledge about HIV prevention and transmission, attitudes toward people living with (PLHIV) and self-perceived risk for HIV infection. The self-perceived risk was categorized as low, unknown and high. RESULTS: The majority of students (72.5%) assessed their risk as low, 8.5% assessed their risk as high and 19.1% did not know their risk. Compared to low self-perceived risk, high self-perceived HIV risk was associated with being male, having lower knowledge about HIV prevention, less strong Segregation and protection attitude toward PLHIV, stronger Ignorance and indifference attitude toward PLHIV and positive opinion about gays/lesbians. Students who perceived own risk for acquiring HIV as high had lower knowledge about HIV transmission and prevention. However, those who were previously tested for HIV, despite their poorer knowledge about HIV prevention, assess their HIV-related risk as low. CONCLUSIONS: Students assessed their risk of HIV infection mostly as low. Still, lower knowledge of HIV prevention has been consistently associated with a high and unknown risk of HIV. Moreover, being ignorant and indifferent about PLHIV was associated with increased self-perceived HIV risk. These findings highlight the need for continuous specialized HIV-related education to reduce fear and stigma of PLHIV and HIV testing as well as risky behaviors.

Tularemia in Pregnant Woman, Serbia, 2018.

Tularemia was diagnosed for a 33-year-old pregnant woman in Serbia after a swollen neck lymph node was detected at gestation week 18. Gentamicin was administered parenterally (120 mg/d for 7 d); the pregnancy continued with no complications and a healthy newborn was delivered. Treatment of tularemia optimizes maternal and infant outcomes.

The measles epidemic in northern Kosovo and Metohija, Serbia, October 2017-August 2019.

INTRODUCTION: Measles is among the most contagious and vaccine-preventable respiratory diseases. The aim of this research was to describe the socio-demographic profile, clinical manifestations and laboratory parameters of measles patients hospitalized at Kosovska Mitrovica Clinical Centre during the 2017-2019 outbreak. METHODOLOGY: The prospective study included all patients that had contracted measles (107) who were hospitalized at Kosovska Mitrovica Clinical Centre during the outbreak. All complications that led to hospitalization were analyzed and the frequencies of complications with respect to patient age and vaccination status were recorded. RESULTS: More than half (51%) of the patients were unvaccinated. Patients' age varied statistically significantly with respect to vaccination status. Pneumonia was noted in 65% of the patients from the younger age group, compared to 32% of adults, and this difference was statistically significant. Hepatitis was a significantly more frequent complication in adults, affecting 36% of measles patients in this age group, compared to only 7% of those aged below 18 years. In the unvaccinated group, 71% pneumonia frequency was noted, compared to 11% and 35% in the vaccinated and unknown vaccination status groups, respectively. The differences in frequencies based on vaccination status were statistically significant. CONCLUSIONS: Most hospitalized patients were unvaccinated. Complications showed a significant difference with respect to the age and vaccination status of patients. Therefore, it is necessary to carry out continuous health promotion activities to raise awareness among the entire population of the importance and need for vaccination of children against measles, but also adults who have not been previously vaccinated.

Serological status of childbearing-aged women for Toxoplasma gondii and cytomegalovirus in northern Kosovo and Metohija.

INTRODUCTION: Toxoplasma gondii and cytomegalovirus (CMV) are pathogens associated with congenital anomalies. METHODS: Serum was collected from 79 reproductive-age women and tested for IgM and IgG antibodies to T. gondii and CMV. RESULTS: Seropositivity for T. gondii was detected in 24.1% of women and CMV in 96.2%. High seropositivity for CMV was found for all ages. The highest seropositivity for T. gondii was observed among older participants. CONCLUSIONS: T. gondii remains an important pathogen owing to low seropositivity.

Tick-borne encephalitis in Serbia: A case series.

INTRODUCTION: In the Europe, the number of tick-borne encephalitis (TBE) has been increased in the last decade, and the number of endemic areas has been also increased and is still growing. In the present case series, we present clinical and socio-epidemiological data of patients with TBE hospitalized in the period of TBE virus epidemic in Serbia. METHODOLOGY: A case series was conducted in Serbia in 2017. Patients with confirmed TBE were included in the study. Biochemical and serological analysis of blood and CSF, as well as radiological imaging (CT and MRI) were done. RESULTS: In total, 10 patients with TBE were included in the study. M:F ratio was 1.5:1, while average age was 45.1 years. Half of the patients had severe clinical picture. Endocranial CT scan and MRI did not reveal any abnormality, except in the patient with the most severe CNS infection (meningoencephalomyelitis). Mean value of sedimentation and CRP was slightly elevated (29.6 mm/1hours and 20.1 mg/L, respectively) in 80% of the patients, although elevation was almost negligible. The average number of leucocytes in the cerebrospinal fluid (CSF) was 171×106/L, the mean value of the CSF protein was 1.1g/L. There were no fatal outcomes. CONCLUSION: Since other CNS infections have similar clinical picture and CSF finding as TBE, serological analysis for TBE should be included in routine diagnostic practice.

IL-28B genotypes as predictors of long-term outcome in patients with hepatitis C-related severe liver injury.

INTRODUCTION: Patients with severe fibrosis or cirrhosis are at high risk for liver-related complications, even after successful antiviral treatment and/or regression of fibrosis. These are the first published results concerning the role of IL-28B genotypes as predictors of the durability of sustained virological response (SVR) and long-term outcome, in patients with baseline severe fibrosis and cirrhosis caused by hepatitis C (HCV) infection. METHODOLOGY: Genetic testing for three different single nucleotide polymorphisms (SNP) near the IL28B gene, rs12979860, rs12980275 and rs8099917, was performed in 42 patients with HCV-related advanced fibrosis and cirrhosis, who achieved SVR after successful interferon-based treatment. Baseline clinical and laboratory parameters were analysed, as well as IL28B genotype association with late virological relapse, fibrosis progression and clinical outcomes. RESULTS: The most prevalent genotypes in all three tested SNP positions were: CCrs12979860 genotype in 69% of patients, GTrs8099917 in 78.6% and GGrs12980275 in 47.6% of patients. The presence of IL28B CCrs12979860 genotype was identified as a negative predictor of late virological relapse. Further analysis did not confirm the association of other IL28B genotypes with the progression of fibrosis and clinical outcomes. CONCLUSIONS: Varying long-term prognosis in patients with HCV-related severe fibrosis and cirrhosis is due to multiple interactions between host genetic factors, virus and environment. These are first published results demonstrating the significance of IL28B CCrs12979860 genotype as a negative predictor of late virological relapse. A further investigation concerning genetic factors is necessary to identify patients under risk for late relapse, complications and unfavorable outcomes, so that they can be reevaluated and offered new treatment options.

Serological status of childbearing-aged women for Toxoplasma gondii and cytomegalovirus in northern Kosovo and Metohija

Abstract INTRODUCTION: Toxoplasma gondii and cytomegalovirus (CMV) are pathogens associated with congenital anomalies. METHODS: Serum was collected from 79 reproductive-age women and tested for IgM and IgG antibodies to T. gondii and CMV. RESULTS: Seropositivity for T. gondii was detected in 24.1% of women and CMV in 96.2%. High seropositivity for CMV was found for all ages. The highest seropositivity for T. gondii was observed among older participants. CONCLUSIONS: T. gondii remains an important pathogen owing to low seropositivity.

Oral teicoplanin versus oral vancomycin for the treatment of severe Clostridium difficile infection: a prospective observational study.

The aim of this study was to compare clinical cure rate, recurrence rate and time to resolution of diarrhea in patients with severe and severe-complicated Clostridium difficile infection (CDI) treated with teicoplanin or vancomycin. This two-year prospective observational study included patients with first episode or first recurrence of CDI who had severe or severe-complicated CDI and were treated with teicoplanin or vancomycin. Primary outcomes of interest were clinical cure rate at discharge and recurrence rate after eight weeks follow up, and secondary outcomes were all-cause mortality and time to resolution of diarrhea. Among 287 study patients, 107 were treated with teicoplanin and 180 with vancomycin. The mean age of patients was 73.5 ± 10.6 years. One hundred eighty six patients (64.8%) had prior CDI episode. Severe complicated disease was detected in 23/107 (21.5%) and 42/180 (23.3%) patients treated with teicoplanin and vancomycin, respectively. There was no statistically significant difference in time to resolution of diarrhea between two treatment arms (6.0 ± 3.4 vs 6.2 ± 3.1 days, p = 0.672). Treatment with teicoplanin resulted in significantly higher clinical cure rate compared to vancomycin [90.7% vs 79.4%, p = 0.013, odds ratio (OR) (95% confidence interval (CI)) 2.51 (1.19-5.28)]. Recurrence rates were significantly lower in patients treated with teicoplanin [9/97 (9.3%) vs 49/143 (34.3%), p < 0.001, OR (95%CI) 0.20 (0.09-0.42)]. There was no statistically significant difference in overall mortality rate. Teicoplanin might be a good treatment option for patients with severe CDI. Patients treated with teicoplanin experienced remarkably lower recurrence rates compared to vancomycin-treated patients.

The prevalence and the risk factors for hepatitis C virus infection in Serbia.

INTRODUCTION: The epidemiological characteristics of the hepatitis C virus (HCV) infection in Republic of Serbia have not been studied sufficiently so far. The aim of this study was to estimate the prevalence of anti-HCV positivity in the general population of Serbia and determine the risk factors for this infection. METHODOLOGY: Estimation of the prevalence was done using the median ratio method with data from several regional countries to a previously determined prevalence of anti-HCV positivity among volunteer blood donors of 0.19%. In order to determine the risk factors a matched case-control study was conducted of 106 subjects with confirmed HCV infection from the Clinic for Infectious and Tropical Diseases, Clinical Center of Serbia and the same number of hospital controls matched by sex and age. RESULTS: The estimated prevalence of anti-HCV positivity in the general population of Serbia was 1.13% (95% CI: 1.0-1.26%). The most important predictive risk factors of HCV infection were: intravenous drug use (OR = 31.0; 95% CI: 3.7-259.6), blood transfusions (OR = 3.7; 95% CI: 1.6-8.7), invasive dental treatment (OR = 3.1; 95% CI: 1.4-6.8), and low level of education (OR = 2.2; 95% CI:1.1-4.7). A total of 91.5% of the persons with hepatitis C had at least one of the significant risk factors. CONCLUSION: The prevalence of anti-HCV positivity ranks Serbia in the range of mid-endemic European countries. Preventive measures should be directed at preventing drug use, on education about getting the infection, creating safe conditions for blood transfusions, and strict adherence to adopted practices in dentistry.

[Therapeutic approach to actinomycosis--experience gained at the department of infectious and tropical diseases].

INTRODUCTION: Actinomycosis is a chronic infectious disease caused by anaerobic, gram-positive microorganisms from the order of Actinomyce or Propionobacterium. The disease manifests iself mostly in cervicofacial form and less frequently in thoracic and abdominal form. The study was aimed at reviewing clinical manifestations and therapeutic approaches in treatment of patients with Actinomycosis. MATERIAL AND METHODS: The study sample consisted of four patients with different clinical manifestations of Actinomycosis, who had been treated at the Institute for Infectious and Tropical Diseases in Belgrade in 2002, 2003, 2006 and 2008. RESULTS: Four patients with Actinomycosis were treated during the above mentioned periods of time. One patient had kidney Actinomycosis, which developed into generalized Actinomycosis. Two patients had the most common cervical form, while the forth one had abdominal form; all patients received Penicillin G followed by Ampicillin, during the period of four weeks to up to a year. CONCLUSION: Actinomycosis is a rare disease, which imposes great diagnostic dilemmas. The treatment of this disease requires long term use of antibiotics.

[Varicella complications: is it time to consider a routine varicella vaccination?].

BACKGROUND/AIM: Varicella is a common and benign disease of childhood. Complications are rare, but in some patients, even without risk factors, severe, life treathening complications could be seen. The aim of this study was to establish the type and frequency of varicella complications among hospitalised patients over an 8-year period. METHODS: This retrospective analysis included medical charts of the patients hospitalised in the Infectious Disease Clinic, Belgrade, Serbia, from 2001-2008 (4.85% of all registered patients with varicella in Belgrade, 2001-2008). Among hospitalised patients dermografic characteristics were analysed: hospitalisation lenght, presence and type of complications, presence of immunocompromising conditions and outcome of the disease. The diagnosis of varicella was made on clinical grounds, and in persons >40 years, with negative epidemiological data of contacts, serological confirmation (ELISA VZV IgM/IgG BioRad) and avidity of IgG antibodies were done to exclude the possibility of disseminated herpes zoster. RESULTS: A total of 474 patient were hospitalised over an 8-year period. The age of patients was from 5 months to 75 years (mean 22.4 +/- 16.1, median 23.5 years). The majority of patients were adults (n=279; 58.9%) and 195 (41.1%) patients were < or =15 years old. Complications were found in 321/474 (67.7%) patients. The registered complications were: varicella pneumonia (n=198; 41.38%), bacterial skin infections (n=40; 8.4%), cerebelitis (n=28; 5.9%), bacterial respiratory infection (n=21; 4.4%), viral meningitis (n=10; 2.31%), encephalitis (n=9; 1.9%), thrombocytopenia (n=2; 0.4%); 11 (2.3%) patients had more than one complication, among them were sepsis, myopericarditis and retinal hemorrhages. When complications were analysed according to the age, there were no statistical significance, but when type of complication was analysed statistical significance was found (p < 0.05). In adults, pneumonia was the most common complication: 173/279 (62%), followed by skin infections (2.9%), bacterial respiratory infections (2.2%), and more than one complication (2.3%). Pneumonia was more common in adults than in children (7:1). In children skin infections were the most common complications (16.4%), followed by cerebelitis (13.3%), viral pneumonia (12.8%), bacterial respiratory infections (7.7%), encephalitis (3.6%), and more than one complication (4.1%). Neuroinfections were more common in children than in adults (6:1), as well as bacterial skin infections (4:1). Two patients died (0.4%). CONCLUSION: There was no difference in the incidence of varicella complication in children and adults, but the type of complication differed. In children the most common complications were skin and neurological infections, while in adults it was varicella pneumonia. These data provide a baseline for estimating the burden of varicella in Belgrade and support the inclusion of varicella vaccine in childhood immunisation program in Serbia.