Human Alveolar Echinococcosis, Croatia.

Alveolar echinococcosis is a parasitic disease caused by the tapeworm larval stage of Echinococcus multilocularis. This zoonotic disease has not been known to occur in Croatia. We report a confirmed case of human alveolar echinococcosis in a patient in Croatia who had never visited a known E. multilocularis-endemic area.

Treatment of chronic hepatitis C in Croatian war veterans: experiences from Croatian reference center for viral hepatitis.

AIM: To examine the risk factors, comorbidity, severity of liver disease, treatment course, and outcome in Croatian war veterans with chronic hepatitis C, especially those suffering from posttraumatic stress disorder (PTSD). METHODS: We collected medical records of 170 adult men diagnosed with chronic hepatitis C who started treatment with a combination of pegylated interferon-alpha and ribavirin between January 2003 and June 2009 at the Croatian Reference Centre for Viral Hepatitis. RESULTS: Participants' mean age was 43 ± 9 years. Among 170 participants, there were 37 war veterans (22%). The main risk factor in veteran patients were operative procedures with transfusions (46% vs 5% in non-veterans; P < 0.001) and in non-veteran patients intravenous drug use (42.1% vs 13%; P < 0.001). The average duration of infection was longer in war veterans (14.5 ± 3.4 vs 12.2 ± 7.2 years; P = 0.020). The percentage of PTSD comorbidity in the whole group was 11% (18/170) and in the war veterans group 49% (18/37). The prevalence of sustained virological response in patients with PTSD was 50% and in patients without PTSD 56%. Treatment reduction in patients with PTSD (33%) was higher than in patients without PTSD (12%; P = 0.030). CONCLUSION: Croatian war veterans are a group with high risk of chronic hepatitis C infection because many of them were wounded during the Croatian War 1991-1995. Considerations about PTSD as a contraindication for interferon treatment are unjustified. If treated, patients with PTSD have an equal chance of achieving sustained virological response as patients without PTSD.

Training in infectious diseases across Europe in 2021 - a survey on training delivery, content and assessment.

OBJECTIVES: To define the status of infectious diseases (ID) as an approved specialty in Europe; to enumerate the number of specialists (in general and in relation to the overall population) and specialist trainees and describe the content, delivery and evaluation of postgraduate training in ID in different countries. METHODS: Structured web-based questionnaire surveys in March 2021 of responsible national authorities, specialist societies and individual country representatives to the Section of Infectious Diseases of the European Union for Medical Specialties. Descriptive analysis of quantitative and qualitative responses. RESULTS: In responses received from 33/35 (94.3%) countries, ID is recognized as a specialty in 24 and as a subspecialty of general internal medicine (GIM) in eight, but it is not recognized in Spain. The number of ID specialists per country varies from <5 per million inhabitants to 78 per million inhabitants. Median length of training is 5 years (interquartile range 4.0-6.0 years) with variable amounts of preceding and/or concurrent GIM. Only 21.2% of countries (7/33) provide the minimum recommended training of 6 months in microbiology and 30% cover competencies such as palliative care, team working and leadership, audit, and quality control. Training is monitored by personal logbook or e-portfolio in 75.8% (25/33) and assessed by final examinations in 69.7% (23/33) of countries, but yearly reviews with trainees only occur in 54.5% (18/33) of countries. CONCLUSIONS: There are substantial gaps in modernization of ID training in many countries to match current European training requirements. Joint training with clinical microbiology (CM) and in multidisciplinary team working should be extended. Training/monitoring trainers should find greater focus, together with regular feedback to trainees within many national training programmes.

Trends of Late Presentation to Care in Patients with Chronic Hepatitis C during a 10-Year Period in Croatia.

Late presentation to care is the major obstacle to receiving treatment for chronic hepatitis C (CHC). Our aim was to analyze the prevalence and trends of late presenters (LP) at first consultations in Croatia during a 10-year period. This retrospective cross-sectional study included all adult CHC patients (n = 854) entering specialist medical care at the University Hospital for Infectious Diseases Zagreb between 2009 and 2018. LP was defined as liver stiffness measurement ≥ 9.5 kPa or biopsy METAVIR F ≥ 3. During the study period, mean patients' age increased from 37 to 52 years while HCV genotype distribution changed leading to the replacement of genotype 1b with 1a (g1b 32% to 21%; g1a 19% to 38%). A total of 320 (37.4%) were LP; they were older (47.5, IQR 40.5-57.6), and more commonly infected with g1b (34.1%) and g3 (42.5%). The prevalence of LP significantly increased from 31.9% in 2009 to 46.5% in 2018. Late presentation for care of CHC is increasing in Croatia suggesting a gap of diagnosing strategies in patients over 50 years.

[Molecular diagnosis of hepatitis C and hepatitis B infection]. / Molekularna dijagnostika infekcije virusom hepatitisa C i hepatitisa B.

Molecular methods are a well-established part of routine diagnostic work-up in patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). Confirmation of active viral replication in infected patients is based on detection and/or quantification of viral genome in serum by molecular assays. Diagnostic algorithm for hepatitis C includes detection and/or quantification of HCV RNA in serum of infected patients and HCV genotyping. Diagnostic work-up in patients with hepatitis B includes quantification of HBV DNA in serum, HBV genotyping, and determination of resistance to nucleoside and nucleotide analogues. Real-time polymerase chain reaction (PCR) is the standard recommended molecular method for quantification of HCV RNA and HBV DNA in clinical samples. Due to superior sensitivity, real-time PCR assays can provide both qualitative detection of viral genome and quantification. Molecular diagnosis of HCV and HBV infections in clinical laboratories should be limited to certified standardized assays.

Treatment of Elderly Patients with Chronic Hepatitis C: A Retrospective Cohort Study.

The prevalence of chronic hepatitis C increases in elderly patients. The aims of this study were to identify the factors associated with hepatocellular carcinoma (HCC) and end-stage liver disease development and to evaluate the efficacy and safety of pegylated interferon (PEG-IFNα) plus ribavirin (RBV) therapy in elderly patients. A retrospective cohort study included all consecutive pa-tients with hepatitis C virus (HCV) infection treated with PEG-IFNα+RBV between 2003 and 2013. Elderly patients had a higher frequency of poor prognostic factors including genotype 1 infec-tion, high fibrosis, and high fibrosis index based on four factors (FIB-4) score. The sustained virologic response (SVR) rate for genotype 1 was significantly lower (35.8% vs. 57.1%), while the frequency of PEG-IFNα (27.2% vs. 7.8%), RBV dose reduction (19.6% vs. 9.7%) and treatment discontinuation (13.0% vs. 4.1%) was significantly higher in elderly patients. However, age was not associated with SVR in multivariate analysis, and comparable SVR rates were achieved when adjusted for fibrosis score (Ishak ≤3: 66.7% vs. 69.8%). During the follow-up, HCC was diagnosed in 18 elderly patients (3 SVR+, 4 SVR- and 9 untreated patients). In conclusion, selected elderly patients can achieve comparable SVR rates as younger patients, but with a higher rate of side effects. Since complications of HCV infection occur more frequently in elderly patients, they should be given priority for antiviral therapy.

[Immunosupression and viral infections in rheumatic diseases]. / Imunosupresija i virusne infekcije u reumatskim bolestima.

Infections are one of the leading causes of morbidity and mortality in patients with rheumatic diseases. Although bacterial pathogens are the most common cause of infections, a wide variety of viral pathogens can also cause serious clinical manifestations mostly due to immunosupressive therapy primarily targeting cellular immunity (steroids, cyclosporins, cyclophosphamid, leflunomid, TNF-alfa antagonists etc.). Depleted cellular immunity can lead to reactivation of latent viruses such as members of Herpesvirus family, or hepatitis B and C viruses. Symptoms of viral infection may mimic exacerbation of rheumatic disease. In this paper authors present the main clinical characteristics, diagnostics and tretment possibilities for most common viral infections in immunosupressed host with a rheumatic disease.

Chemokine CXCL10 at week 4 of treatment predicts sustained virological response in patients with chronic hepatitis C.

The aim of this study was to analyze the predictive value of CXCL9, CXCL10, and CXCL11 concentrations before and after 4 and 12 weeks of treatment with pegylated interferon-α2b and ribavirin in patients with chronic hepatitis C infected with the hepatitis C virus genotype 1. The study included 46 adult patients (29 women and 17 men). Chemokine quantification in the serum was performed at baseline and after 1, 3, and 6 months of treatment by enzyme immunoassay. Chemokine responses were compared in patients achieving a sustained virological response to treatment (SVR, n=26) and the non-SVR group (n=20). The differences in the CXCL9 and CXCL10 concentrations between the SVR and non-SVR groups were statistically significant. A multivariant analysis showed a significant association between treatment failure and higher concentrations of CXCL10. A higher predictive value of CXCL10 concentrations after 4 weeks of treatment compared to pretreatment values has been found (area under the curve 0.9288 and 0.7942, respectively, P=0.016). CXCL10 concentrations above 250 pg/mL 4 weeks after the start of treatment were independently associated with non-SVR. In conclusion, the results of this study have shown that CXCL10 concentrations at the time of a rapid viral response (4 weeks) are better predictors of achieving SVR compared to baseline levels. Additionally, this study suggests an important role of CXCL9 as a biomarker of SVR in patients with chronic hepatitis C.

Intravenous Drug Users Can Achieve a High Sustained Virological Response Rate: experience From Croatian Reference Center for Viral Hepatitis.

BACKGROUND: Hepatitis C virus (HCV) is one of the major infectious disease agents among injecting drug users (IVDUs). However, most of the IVDUs are not still treated. OBJECTIVES: To examine the treatment course, adherence, tolerability and safety profiles and SVR rates in IVDUs compared to non-IVDUs. PATIENTS AND METHODS: Demographic and clinical data were collected from medical records of 345 adult patients diagnosed with chronic hepatitis C (CHC) who were treated with a PEG-IFN-α and ribavirin in Croatian Reference Center for Viral Hepatitis in Zagreb between January 2003 and January 2010. Efficacy, safety and tolerability treatment profiles were analyzed in IVDUs vs. non-IVDUs. Positive predictors for treatment outcome were evaluated by univariate and multivariate logistic regression. RESULTS: A total of 106 (30.46%) IVDUs were identified. The IVDUs were mainly male (81.13% vs. 52.30%, P = 0.0001), young (mean ± SD age: 32.46 ± 5.33 y vs. 46.12 ± 11.48 y, P = 0.0001), had lower fibrosis and HAI score (measured by ISHAK) and shorter duration of infection (mean ± SD: 8.98 ± 5.87 vs. 16.79 ± 8.99 y, P = 0.0001) compared to non-IVDU group. In IVDUs, genotype 1a (24.52%) and 3a (38.68%) were predominant. There were no differences in completion rate between the two studied groups. IVDUs achieved a significantly higher rate of overall SVR (70.75% vs. 51.04%, P < 0.0009) and in genotypes 1 and 4 (65.08% vs. 48.73%, P = 0.0294) vs. non-IVDUs. Treatment discontinuation rates due to side-effects were not significantly different in IVDUs and non-IVDUs (2.83% vs. 7.11%, P = 0.1390). IVDU group had a higher rate of lost to follow-up (13.21% vs. 4.60%, P = 0.0071). There were no statistically significant differences in SVR rate between IVDUs with, or without substitution therapy (55.55% vs. 74.62%, P = 0.0866). Independent predictors of SVR were age < 40 years and genotypes 2 and 3. Type of PEG-IFN-α used was not associated with SVR. CONCLUSIONS: Treatment of CHC in IVDUs should strongly be encouraged as they have positive predictors for achieving SVR such as younger age, shorter duration of infection, and consequently favorable histological stage of the disease, and good adherence to treatment. There is no difference in safety and tolerability profiles of treatment in IVDUs compared to patients with no history of drug abuse.

Academic profile of students who transferred to Zagreb School of Medicine from other medical schools in Croatia.

AIM: To assess the academic performance of students who transferred to the Zagreb School of Medicine from other three medical schools in Croatia. METHODS: Academic performance of medical students who moved from Rijeka, Osijek, or Split University Medical Schools to the Zagreb University School of Medicine at the second or third year was compared with academic performance of students enrolled at the Zagreb University School of Medicine. Using the Zagreb Medical School's registry, we made a list of 57 transfer students to Zagreb Medical School in the 1985-1994 period. Control group was formed of students enrolled at the Zagreb School of Medicine in the same period, whose names followed in alphabetical order after the names of transfer students. Students' performance was analyzed according to their grade average before transfer, grade average in the first year after transfer, total grade average after transfer, overall grade average, and duration of studies. We also analyzed the proportion of students in each group who did not pass the admission test at the Zagreb School of Medicine in the year before the enrollment in Zagreb, Osijek, Rijeka, and Split Medical Schools. Nineteen transfer students, transferred between 1985 and 1988, and their controls were excluded from the analysis because of incomplete data. RESULTS: Transfer students had significantly lower grade average before transfer (3.2-/+0.6 vs 3.5-/+0.7, p=0.03, Student t-test), lower grade average in the first year after transfer (3.2-/+0.6 vs 3.5-/+0.7, p=0.03), lower total grade average after transfer (3.6-/+0.5 vs 4.0-/+0.6, p<0.001), and lower overall grade average (3.5-/+0.5 vs 3.9-/+0.6, p<0.001) than control students. Median time to graduate for transfer students was 7 years (range, 5-9) and 6 years (range, 5-9) for control students (p=0.375, Mann-Whitney test). There were significantly more students among transfer students who did not pass the admission test at the Zagreb School of Medicine in the year before the final enrollment than their controls (15/38 vs 4/38, p=0.009, chi-square test). CONCLUSION: Transfer students had poorer academic performance than students who passed the admission test and were enrolled at the Zagreb School of Medicine from the first year of studies.