Implementation of Microelimination Strategy in Eradication of Chronic Hepatitis C Infection in Patients with Hemophilia in the Northern region of Serbia: Is Eradication Possible?

BACKGROUND: Treating HCV in people with hemophilia prevents the development of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) and greatly increases the quality of life for people living with hemophilia. There are many obstacles in reaching the WHO goal of globally eradicating HCV by 2030, mainly its scale, complexity, and implementation. That is why many countries have implemented a micro-elimination strategy: a pragmatic elimination approach in populations with the most efficacy. The aim of this publication is to present the morbidity and mortality rates, the clinical course and treatment outcomes of chronic HCV infection in people with hemophilia (PwH), as well as to show an example of a successfully conducted HCV micro-elimination strategy among people with hemophilia in the Province of Vojvodina. METHODS: A retrospective, single-center study, performed using medical documentation of all registered PwH in the Clinical Center of Vojvodina from 1994. until 2020. It included 74 hemophilia patients, out of which 32 were patients with hemophilia and chronic HCV infection. RESULTS: The mean age of HCV-positive positive people with hemophilia (PwH) was 42.3 years, with the duration of infection of 30-35 years. Co-infection with HIV was observed in 6.25% of cases. Furthermore, 18.75% of patients had spontaneous HCV elimination, and 75% were treated with antiviral protocols. Cirrhosis developed in 21.87% with an incidence rate of 0.6 per 100 patient-years. After treatment with Pegylated IFN and ribavirin (RBV), 58.3% achieved SVR. Side effects of IFN-based therapy regimens were recorded in 20.8% of treated (PwH). In 37.5% PWH, DAA protocols were administered, and these patients achieved SVR. HCV- PwH have a statistically higher mortality rate than non-infected people with hemophilia. Among the HCV-positive PwH, hemophilia-related deaths were 6.25%, and HCV-related deaths were 9.37%. Currently, in the Registry of PwH in Vojvodina, there are no patients with active HCV infection. CONCLUSION: The micro-elimination strategy in the subpopulation of PwH was successfully implemented in Vojvodina by hematologists and infectious diseases specialists in close collaboration.

DEPRESSION, ANXIETY AND QUALITY OF LIFE IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION IN VOJVODINA.

The objective of this study was to investigate the prevalence of depression and anxiety among patients with chronic hepatitis C and how depression and anxiety correlate with respective health-related quality of life (HRQoL) domains, sociodemographic factors, and clinico-epidemiological characteristics. This prospective study involved 150 patients with chronic hepatitis C awaiting interferon treatment for hepatitis C and 150 healthy subjects. All individuals enrolled in the study completed the Short Form 36 (SF-36) questionnaire and Hospital Anxiety Depression Scale. The symptoms showed greater severity/score among patients with chronic hepatitis C for both depression (t=3.37; p<0.01) and anxiety (t=2.35; p<0.05). Regression analysis was used for estimating the relationship between depression and the set of predictors (domains of the SF-36 questionnaire). Three HRQoL domains (Physical Functioning, Vitality, and Mental Health) were found to have the strongest predictive contribution to the occurrence of depression. A series of Kruskal-Wallis and Mann-Whitney tests showed a significant difference in depression level between marital status categories (χ2(2)=7.86, p<0.05). Divorced participants had significantly higher scores compared to married participants (Z=-2.40, p<0.05) and single participants (Z=-2.75, p<0.01). Unemployment was associated with a higher degree of depression and anxiety. There was no association identified between duration of the disease, route of hepatitis C virus transmission, existence of cirrhosis, and depression or anxiety. The findings of this study can assist in developing a standard protocol for the management of chronic hepatitis C that will include psychological assessment and support.

Validity of hepatitis B and hepatitis C case definitions.

BACKGROUND: Globally, an estimated 257 million people are living with chronic hepatitis B (HBV) infection and an estimated 71 million people with the chronic hepatitis C virus (HCV). The true public health dimensions and impact of hepatitis epidemics are poorly understood. Case definitions are fundamental parts of disease surveillance, representing sets of standardised criteria used to assess whether or not a person has a certain disease. The study evaluated the sensitivity and specificity of hepatitis B and hepatitis C case definitions, current at the time of data collection, recommended by the European Commission (EC) and the Centers for Disease Prevention and Control (CDC). METHODS: The study involved 150 hospital referrals with suspected cases of hepatitis from a Serbian clinic during 2014/2015. Case definitions of hepatitis B and C were tested for their sensitivity, specificity, positive and negative predictive values. RESULTS: EC 2008 and the CDC 2012 case definitions for acute hepatitis B, and the CDC 2012 case definition for probable case of chronic hepatitis B have low sensitivity. Case definitions which rely on laboratory confirmation only have maximal sensitivity. EC case definitions showed maximal sensitivity and specificity for hepatitis C confirmed cases. The CDC case definition for chronic hepatitis C showed low sensitivity (36.8%) and low negative predictive value (65.6%) for probable cases and maximal sensitivity and specificity for confirmed cases. Hepatitis C case definitions requiring presence of clinical criteria have low sensitivity and high specificity, resulting from presence of infection and absence of any clinical manifestation, but have high positive and negative predictive values. CONCLUSION: Syndromic case definitions show low sensitivity and are of limited use. They highlight the importance of laboratory diagnostics (offering maximal sensitivity and specificity, and high positive and negative predictive values), as well as the need for universal case definitions, for confirmed cases only.

Hepatitis C virus-induced hepatocellular carcinoma: a narrative review.

Hepatocellular carcinoma (HCC) is the most frequent primary liver carcinoma, accounting for about 80% of cases. In spite of advances in modern oncology, this neoplasia still holds the second place in overall cancer mortality. HCC is a multifactor disease: it results from accumulated oncogenic potentials made up of several groups of risk factors, the most significant of which is an infection with hepatotropic viruses. The hepatitis C virus (HCV) is one of the primary causes of morbidity and mortality across the world and affects 1.1% of worldwide population. It has been calculated that on average 2.5% of patients affected by chronic HCV infection develops HCC. Hepatocarcinogenesis is the result of the combination of superposing virus specific factors, immunological mechanisms, environmental factors and factors related to the individuals genetic background. Host-related factors include male gender, age of at least 50 years, family predisposition, obesity, advanced liver fibrosis or cirrhosis and coinfection with other hepatotropic viruses and human immunodeficiency virus. Environmental factors include heavy alcohol abuse, cigarette smoking, and exposure to aflatoxin. In the era of interferon (IFN)-based therapy, the risk of HCC development after established sustained virological response (SVR) was 1% yearly. Data reported in patients with SVR about the increase of HCC prevalence have appeared, after the initial enthusiasm on the efficacy of HCV direct acting antiviral drugs (DAA) protocols. Actually, these data are controversial, but they certainly suggest the need to undertake large, multicenter studies and caution in everyday clinical practice.

Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study.

BACKGROUND & AIMS: Long-term treatment with tenofovir disoproxil fumarate (TDF) alone, or in combination with emtricitabine (FTC) is associated with sustained viral suppression in patients with lamivudine resistant (LAM-R) chronic hepatitis B (CHB). METHODS: LAM-R CHB patients were randomised 1:1 to receive TDF 300mg or FTC 200mg and TDF 300mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA<69IU/ml (<400copies/ml) at week 96 (primary efficacy endpoint) was reported previously. Here we present week 240 follow-up data. RESULTS: Overall, 280 patients were randomised to receive TDF (n=141) or FTC/TDF (n=139), and 85.4% completed 240weeks of treatment. At week 240, 83.0% of patients in the TDF arm, and 82.7% of patients in the FTC/TDF treatment arm had HBV DNA<69IU/ml (p=0.96). Rates of normal alanine aminotransferase (ALT) and normalised ALT were similar between groups (p=0.41 and p=0.97 respectively). Hepatitis B e antigen loss and seroconversion at week 240 were similar between groups, (p=0.41 and p=0.67 respectively). Overall, six patients achieved hepatitis B surface antigen (HBsAg) loss and one patient (FTC/TDF arm) had HBsAg seroconversion by week 240. No TDF resistance was observed up to week 240. Treatment was generally well tolerated, and renal events were mild and infrequent (∼8.6%). The mean change in bone mineral density at week 240 was -0.98% and -2.54% at the spine and hip, respectively. CONCLUSIONS: TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240weeks. LAY SUMMARY: The goal of oral antiviral treatment for chronic hepatitis B (CHB) is to achieve and maintain undetectable HBV DNA levels. Treatment options with enhanced potency, and low risk of resistance development for patients infected with lamivudine resistant (LAM-R) HBV are required. Tenofovir disoproxil fumarate (TDF) monotherapy was effective and well tolerated without TDF resistance development in CHB patients with LAM-R, for up to 240weeks. Clinical trial number: NCT00737568.

Boceprevir in genotype 1 chronic hepatitis C: first experiences in Serbia.

INTRODUCTION: The triple therapy which consists of one of the protease inhibitor plus pegylated interferon and ribavirin (P/R) is the standard of care for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection both in treatment-naïve and experienced patients. OBJECTIVE: The aim of this study was to analyze the efficacy and tolerability of this regime in hospital practice in Serbia. METHODS: From July 2012 to October 2012, 20 previously treated patients with advanced fibrosis and HCV G1 infection were included in the triple antiviral regimen in six referral centers in Serbia. All patients were treated with response guide therapy (RGT) regime according to the boceprevir treatment protocol. During the 4-week lead-in period all patients received peginterferon plus ribavirin. After the lead-in pe- riod boceprevir was added in the dosage of 800 mg three times a day orally.The subsequent treatment varied according to virologic response and fibrosis. During the therapy HCV RNA level was measured at week 4, 8, 12, 24 of the treatment for the assessment of virologic response profile. All patients who completed therapy were assessed at the end of the treatment and at the end of an additional 24-week treatment-free period for a sustained virologic response (SVR). RESULTS: The total of 20 patients with advanced fibrosis was treated. Among patients with an undetectable HCV RNA level at week 8 the rate of SVR was 100%. No patient with decrease in the HCV RNA level < 1 log 10 IU/ml at treatment week 4 achieved SVR. The overall rate of SVR was 55%. The safety profile of the treatment regimen was good. Anemia was reported in 25% of patients. There was no life-threatening treatment adverse event. CONCLUSION: Boceprevir in combination with P/R achieved fairly good SVR rates in patients that were"most difficult to treat"who failed on dual therapy and was effective among patients with cirrhosis.

Treatment of acute hepatitis C in breast cancer patient: a case report.

Oncologists worldwide are often dealing with hepatitis C virus positive breast cancer patients, questioning adequate chemotherapy protocol, reduction of doses, delays, or even interruptions of treatment. We present a case of a woman in stage IIIB breast cancer, who after the completion of neoadjuvant treatment developed significant increase in liver enzymes and was diagnosed positive for HCV. She was treated with interferon and after the resolving of acute liver disease continued concomitant treatment with interferon, ribavirin, docetaxel, and trastuzumab. Grade 4 neutropenia and grade 3 hepatotoxicity occurred after the third cycle of chemo and 5 months of antiviral therapy. Interferon and chemotherapy were postponed for 1 week. There are no sufficient data in order to recommend the concomitant antiviral and antineoplastic therapy. Hepatitis C virus and antiviral therapy may increase the toxicities of antineoplastic treatment. However, when lifesaving oncologic treatment is necessary, concomitant antiviral therapy can be administered with more intensive follow up.

Randomized comparison of tenofovir disoproxil fumarate vs emtricitabine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis B.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is active against lamivudine-resistant hepatitis B virus (HBV) infection, but data to support its clinical efficacy in this setting are limited. METHODS: In a prospective, double-blind, 96-week trial, patients were randomly assigned (1:1) to groups given TDF (300 mg, n = 141) or a combination of emtricitabine (FTC, 200 mg; n = 139) and TDF (300 mg, FTC/TDF). Patients were hepatitis B e antigen (HBeAg)-positive or HBeAg-negative, with levels of HBV DNA ≥3 log10 IU/mL and lamivudine resistance mutations (HBV polymerase or reverse transcriptase amino acid substitutions rtM204I/V ± rtL180M by INNO-LiPA Multi-DR v3; Innogenetics, Inc, Alpharetta, GA). The primary end point was proportion with HBV DNA <69 IU/mL (Roche COBAS Taqman assay; Roche Molecular Systems, Inc, Pleasanton, CA). RESULTS: Patient groups were well matched for demographic and disease characteristics, including region (60% from Europe), HBV genotype (45% genotype D), HBeAg status (47% HBeAg-positive), and duration of lamivudine treatment (mean, 3.8 years). At week 96 of treatment, 89.4% of patients in the TDF group and 86.3% in the FTC/TDF group had levels of HBV DNA <69 IU/mL (P = .43). HBeAg loss and seroconversion did not differ between groups; only 1 patient (0.7%) in the FTC/TDF group lost hepatitis B surface antigen. Treatment was well tolerated; confirmed renal events (creatinine increase of ≥0.5 mg/dL [>44 umol/L], creatinine clearance <50 mL/min, or level of PO4 <2 mg/dL [<0.65 mmol/L]) were generally mild and infrequent (<1%). Small reductions (<2%) in mean bone mineral density of hip and spine were detected by dual-energy x-ray absorptiometry in both groups. No TDF resistance developed through 96 weeks of treatment. CONCLUSIONS: TDF alone is safe and effective for treatment of patients with lamivudine-resistant, chronic HBV infection. Clinical Trials.gov No, NCT00737568.

[Importance of adherence for efficacy of hepatitis C combined therapy].

INTRODUCTION: Dual antiviral therapy with pegylated interferon alfa-2a and ribavirin leads do sustained elimination of hepatitis C virus infection in over 50% patients with genotypes 1 and 4 and in over 80% with genotypes 2 and 3. In addition to genotype, for predicting success of therapy, important factors are baseline HCV RNA level, age, sex, stage of fibrosis, insulin resistance, degree of fat in liver, and patient's weight and genetics. Also, adherence to therapy could be a very important factor associated with success of therapy. OBJECTIVE: The aim of this study was to assess importance of therapy adherence and reduced doses of pegylated interferon alfa-2a and ribavirin on sustained virological response. METHODS: One hundred and sixteen patients with chronic hepatitis C were analyzed. Sustained virological response was analyzed in relation to whether the patients received a full cumulative dose of pegylated interferon alfa-2a, a full cumulative dose of pegylated interferon alfa-2a and ribavirin, and a full cumulative dose of pegylated interferon alfa-2a and at least 60% the expected cumulative dose of ribavirin. RESULTS: At the end of the follow-up period, sustained virological response was achieved in 26 (96.3%) patients who received full cumulative dose of pegylated interferon alfa-2a and in 66 (74.2%) who did not (p < 0.05). Sustained virological response was achieved in 18 (94.7%) patients who received full cumulative dose of pegylated inteferon alfa-2a and ribavirin, and in 73 (76%) who did not (p < 0.05). Sustained virological response was achieved in 25 (96.2%) patients who received full cumulative dose of pegylated inteferon alfa-2a and at least 60% of cumulative dose of ribavirin and in 66 (74.2%) who did not (p < 0.05). CONCLUSION: These findings indicate that adherence to therapy for chronic hepatitis C is a very important factor for achieving sustained virological response.

Treatment of chronic hepatitis C in injecting drug users--a 5-year follow-up.

BACKGROUND/AIM: Hepatitic C infection (HCV) is a systemic, generalised disease with the prevalence of inflammation in the liver. The aim of this study was to determine the success of treatment for chronic hepatitis C with pegilated interferon alfa 2a and ribavirin in injecting drug users. METHODS: This a 5-year follow-up study included 30 patients [63.3% men and 36.7% women, average age 30.2 years (SD 7.1 years)] injecting drug users in one-year abstinence, with chronic hepatitis C, treated with the pegilated interferon alpha 2a and ribavirin. Complete history with possible route of infection, the standard biochemical tests, liver biopsy, quantification of the viral genome in sera and HCV genotyping and subtyping were done prior to the therapy initiation. Depending on the HCV genotype, the therapy was conducted over a period of 48 weeks for genotype 1 and 24 weeks for genotype non 1. Five years later all 30 patients were invited on control examination; 22 of them appeared at the check-up and quantification of the viral genome in their sera were analized. RESULTS: The established degree of liver fibrosis was: F0 in 40%, F1 in 23.33%, F2 in 26.67%, F3 in 3.33% and F4 in 6.67% of the patients. Genotype 3a was dominant (50.0%), 1b was registered in 40.0%, 1a in 6.66% and 2b in 3.33% of the patients. Sustained virologic response (SVR) was achieved in 86.7% of the patients, 10.0% of the patients were non-responders, while 3.33% of them revealed recurrence of HCV. Opiate abuse recurrence during antiviral therapy happened in 6.7% of the patients. Five years after the antiviral therapy 73.3% of the patients appeared at the check-up and all of them were in stable abstinence from opiate abuse. All of those, with a sustained viral response of five-year duration, had the negative PCR HCV RNA test (< 50 IU ml(-1)). In the patients showing unsatisfactory therapy response 5 years before, antiviral therapy was repeated by the same therapeutic regimen, but without adequate therapeutic response. A total of 26.7% of the patients were lost from the records. CONCLUSION: In a 5-year follow-up period 73.3% of the patients used to come regularly to check-ups and among them neither the opiate abuse recurrence nor HCV infection recurrence were registered.

[Extrahepatic manifestations of chronic hepatitis C and their influence on response to treatment with pegylated interferon alfa-2a and ribavirin].

INTRODUCTION: Thirty to 50% of patients with chronic hepatitis C (CHC) have one or more extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection. OBJECTIVE: The aim of this study was to evaluate the frequency of EHMs and to investigate the efficacy of pegylated interferon (Peg-IFN)-alpha-2a plus ribavirin therapy in patients with HCV-related EHMs. METHODS: The study included 280 patients suffering from CHC and treated with Peg-IFN-alpha-2a and ribavirin.The patients were divided in two groups according to presence or absence of EHMs. We evaluated virological response to antiviral therapy. RESULTS: One or more EHMs were found among 27.9% of patients. Most frequently they had rheumatoid factor in serum (12.5%), organ-nonspecific antibodies ANA and AGMA (12.4%), thyroid hormone disorders (9.3%), vasculitis (5.7%), diabetes mellitus (4.65%), glomerulonephritis (0.71%), and porphyria cutanea tarda (0.36%). Among the patients with EHMs there was 52.6% of females vs. 30.2% of females in the group of patients without EHMs (p=0.001). HCV genotypes 1 and 4 had 85.9% patients with EHMs vs. 58.4% of patients without EHMs (p=0.000). Progressive fibrosis and cirrhosis were more frequently recorded in the EHM group of patients (32% vs. 23.2%), but without statistically significant difference (p=0.532). Serious adverse events of Peg-IFN-alpha-2a and ribavirin were statistically significantly recorded among the patients with EHMs (46.1% vs. 12.9%; p=0.000). Sustained virological response among the patients with and without EHMs rated 56.9% and 70.8% respectively (p=0.125). CONCLUSION: Patients with CHC and EHMs treated with combined Peg-IFN-alpha-2a and ribavirin experience handling difficulties, more often have serious adverse events, while successful outcome is achieved in about 50% of patients.

[Efficacy and safety of peginterferon alfa-2a and ribavirin treatment of chronic hepatitis C in the Republic of Serbia].

INTRODUCTION: Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. Pegylated interferon alfa-2a or 2b (PEG IFN alfa-2a or 2b) and ribavirin (RBV) represent a standard treatment of chronic hepatitis C (CHC). Sustained virological response (SVR), defined as continued undetectable HCV RNA 24 weeks after completion of treatment, is universally considered as an indicator of treatment efficacy. OBJECTIVE: The aim of this study was to determine efficacy and safety of PEG IFN alfa-2a and RBV treatment in patients with CHC in Serbia. METHODS: One hundred seventy-six patients with CHC were included in this multicenter trial from 8 reference centers in Serbia. The patients were treated with standard PEG IFN alfa-2a and RBV protocol. We performed the following virological testing: anti-HCV (ELISA), HCV RNK (quantitative PCR), HCV genotype (type-specific PCR), HBsAg, anti-HBs, anti-HBc and anti-HIV (ELISA). Histological activity and the degree of fibrosis were determined according to the Metavir scoring system. Potential predictors for achieving SVR were evaluated using multivariable logistic regression analysis. RESULTS: Of the treated patients with CHC 65.9% were male, and 60.2% of them aged over 40 years. Of the treated patients 68.2% had infection over 5 years, 63% had HCV RNA >400.000 IU/mL, 76.1% had HCV G1/4, and 60.1% had a mild to moderate liver fibrosis. SVR was achieved in 78.9% of patients (G1/4 79.1%; G2/3 78.1%). The factors that indicated a poorer efficacy of the treatment were age >40 (p<0.05), high basal viremia (p=0.013), and the reduction of PEG IFN alfa-2a and RBV doses, with interruption of therapy (p<0.001). Of the treated patients 45.9% had adverse affects (G1/4 50.8%; G2/3 29.7%). CONCLUSION: Treatment of CHC with PEG IFN alfa-2a and RBV was efficient in 78.9% of patients. The safety profile of therapy was satisfactory. Longer therapy increases the possibility of the development of adverse affects. No life-threatening adverse effects were recorded in our patients.

[Immunomodulatory actions of antibiotics]. / Imunomodulatorna delovanja antibiotika.

INTRODUCTION: Antimicrob drugs and immune system interaction has been studied since the pioneer works of Metchnikoff. After the introduction of antibiotics in clinical practice this area has attracted little attention of investigators, because of the lack of standards. This is the reason that the studying of the influence of antibiotics on immune system is still at its beginning. AIM: To point out the immunomodulatory action of some antibiotics on certain components of immune system. METHODS AND RESULTS: The literature findings show that antibiotics express immunomodulatory action on some components of immune system such as fagocytes (polymorphonucleary, macrophages, monocytes), cytokines, immunoglobulines, and on cellular immunity. The principles of antibiotics action on phagocyte are the inhibition of chemotaxis and oxidants production. Macrolides applied for a short time enhance the phagocytic functions while their long use leads to immunosupression. Some cephalosporines and rifampicin in therapeutic doses inhibit the oxydative metabolism, of macrophages. Tetracyclines, clindamycines, chloramphenicol and tobramycin inhibit the synthesis of superoxyd anione. The action of some antibiotics on cytokine and specific antibodies is also important. Cellular immunity can be affected as well. After administration of certain antibiotics it takes 1-2 weeks to reestablish normal cellular immunity, and for other even more. CONCLUSION: There is still no clear standing on real effects of antibiotics on the immune system. Clinicians should search for more information from this new-old field of investigation in order to give more adequate therapy to patients.

Leptospirosis distribution related to freshwater habitats in the Vojvodina region (Republic of Serbia).

The retrospective study (2002-2007) for human leptospirosis in Vojvodina was undertaken in order to describe the distribution of the disease in relation with some environmental factors. Regarding the presented results, the major detected number of leptospirosis cases concurs with stagnant waters, wetlands, fish pond areas and protected regions, which comprised the basis for mapping of the region in three risk zones: very high risk (incidence rate higher than 5.0), high risk (2.5-5.0) and medium risk of leptospirosis infection (1.0-2.5). During the investigated period, 97 cases were registered with an average of 13.85 cases per year: 2002, 32 cases; 2003, 7; 2004, 22; 2005, 16; 2006, 4 and 2007, 16. Out of these 97 cases only 5 were women. Serovars from 11 presumptive serogroups caused infection, with a predominance of Icterohaemorrhagiae and Bratislava, accounting for 72.72% of cases together. Icterohaemorrhagiae was the commonest infecting serogroup mostly connected with fish ponds. Case fatality ratio was 9.4%.

[Exercise induced rhabdomyolysis]. / Rabdomioliza nakon ekstermnog fizickog napora.

INTRODUCTION: Rhabdomyolysis is a potentially life-threatening disease, characterized by the release of intracellular calcium from skeletal muscles and can result in acute renal failure. CASE REPORT: A nineteen year old boy was admitted to the Clinic for Infective Diseases of Clinical Center Novi Sad. The disease was developing gradually and the symptoms were dizziness, muscle pain and dark color of urine. Due to the pathological level of aminotransferase he was hospitalized on the fourth day of the disease beginning with a suspicious diagnosis of acute viral hepatitis. In the hospital course of the disease, a further elevation of serum aminotransferases, creatine kinase and lactate dehydrogenase were registered. Additional serological analyses were done to exclude other possible causes of acute liver lesion. In the neurological status prolonged decontraction of quadriceps muscle was detected and the electromyography was suspicious on neuromyositis. CONCLUSION: Excessive muscular activity with the strenuous exercise is the leading, but very frequently overlooked, cause of rhabdomyolysis in healthy people. Excessive physical exercise may lead to elevation of the serum activity of aminotransferases and to suspicion of hepatitis.

[On the development of the infectology service in Novi Sad].

INTRODUCTION: Infectious diseases are a part of the history of this region. Devastating epidemics of plague, smallpox, and cholera were frequent during the 18th and the 19th centuries. Other infectious diseases were a serious problem as well: alimentary tract infections, scarlet fever, diphtheria, whooping cough. Geographic position, climate, migrations, as well as the tradition and lack of medical staff and medications, affected the frequency and outcome of infections. THE HISTORY OF THE TREATMENT OF INFECTIOUS DISEASES: Patients with infectious diseases were first treated at home. Later, a hospital in Visarion street was opened as an isolation facility and a hospital for homeless patients. The development of science and the education of medical personnel exerted the greatest influence on the control and later treatment of infectious diseases. These measures resulted in the establishment of the first specialized medical institutions in Novi Sad during the cholera outbreak in 1884. After that, temporary pediatric units were organized for the treatment of scarlet fever, diphtheria and smallpox. A ward for infectious diseases was founded in the The Great City Hospital in the second half of the 19th century (1892). The 20th century was a period of control and eradication of infectious diseases in Vojvodina (smallpox, malaria, diphtheria, polio). MODERN INFECTIOUS DISEASES: Nowdays, major infectious deseases include respiratory, alimentary and parasitic infections. However, new diseases are being registered as well - hemorrhagic fevers, Lyme disease, HIV infection. The Infectologic Service in Novi Sad was developed from an Infectology Departement as part of the Departement of Internal Diseases in the new Provincial Hospital (1909) to the independent Departement for Infectious Diseases (1945). Today, Clinic of lnfectious Diseases is an integral part of the Clinical Center of Vojvodina. DEPARTMENT OF INFECTIOUS DISEASES: The Department of Infectious Diseases of the Faculty of Medicine in Novi Sad was founded in 1960. Undergraduate studies started in 1963/64 for students of medicine and in 1978/79 jor dentistry students. Today. the faculty of the Department takes part in undergraduate studies of medicine, dentistry, health care, as well as in graduate programs. The faculty members are also taking part in specialization programs at the Faculty of Medicine. Infectious disease physicians are involved in the activities of the Infectology Section (founded in 1979) of the Society of Physicians of Vojvodine of the Medical Society of Serbia. The first president of the Infectology Section was Dr. Vera Mudric, professor, infectologists, whereas Dr. Grozdana Canak, professor, was the vice-president from 2000-2004. The Infectology Section collaborates with various national and international societies for infectious diseases.

[Treatment of chronic hepatitis C with PEG-interferon]. / Lecenje hronicnog hepatitisa C peg-interferonom.

INTRODUCTION: Since the discovery of the hepatitis C virus, the etiology of chronic liver diseases has been revealed in great number of patients. However, the treatment of hepatitis C viral infection still hasn't been completely resolved. Antiviral and immunomodulatory effects of interferon, and antiviral effect on the nucleoside analogs were efficient only in small number of patients. Discovery of pegylated interferon brings progress in therapeutic success rates. MATERIAL AND METHODS: Combined therapy with peginterferon alfa-2a (Pegasys) 180 mg once a week plus Ribavirin 800 mg a day during a 24-week period was conducted in 20 patients (13 were previously treated with standard antiviral therapy). The aim of this study was to determine the safety and the efficacy of therapy in our patients. RESULTS AND DISCUSSION: Analysis of safety of the combined therapy was conduced in all 20 patients, and analysis of efficiency in 18 patients. Efficacy of the combined therapy was assessed regarding to biochemical response (normalization of aminotransferase activity at the end of therapy and at the end of 6-month follow-up) and virologic response (disappearance of RNA HCV in serum at the end of 6-month follow-up). 30% of treated patients experienced no troubles during treatment. Influenza-like symptoms, weight loss, depression, hair loss and reaction at the site of injection were mild and did not exclude patients from their usual activities in family, society and work place. Neutropenia, thrombocytopenia and anemia as well as elevated aminotransferase activity demanded periodical dose modification in 20% of patients. Unexpected unwanted effect emerged in one patient after cessation of therapy (pulmonary sarcoidosis). Good effects of combined therapy at the end of follow-up period showed biochemical and virologic response in 66% of patients. CONCLUSION: Combined therapy with Pegasys 180 mg/week and Ribavirin 80 mg/day is safe and well tolerated. Sustained biochemical and virologic response was achieved in 66% of patients.

[Use of antibiotics in general practice and at the Clinic for Infectious Diseases]. / Upotreba antibiotika u opstoj praksi i na klinici za infektivne bolesti.

INTRODUCTION: Optimal pharmacotherapy includes utilization of the right drug, at the right time, right duration of therapy and adequate dosage. This study analyzed utilization of antimicrobial drugs at the Clinic of Infectious Diseases of the Clinical Center Novi Sad and in outpatients of the Outpatient General Service of the Health Center Novi Sad-Liman. MATERIAL AND METHODS: Utilization of anti-infective agents was examined according to Anatomic-Therapeutic-Chemical Classification (group J). Drug utilization data were presented in Defined Daily Doses at the Clinic of Infectious Diseases of the Clinical Center Novi Sad in Defined Daily Doses per 100 bed-days, and in the Outpatient General Service of the Health Center Novi Sad-Liman in Defined Daily Doses/1000 inhabitants per day. RESULTS: At the Clinic of Infectious Diseases of the Clinical Center Novi Sad penicillins susceptible to beta-lactamase were established as most frequently used (39.33%) namely: benzylpenicillin (32.18%), quinolone antibacterial agents, ciprofloxacin (12.44%) and cephalosporins, cephalexin (8.25%). In the Outpatient General Service of the Health Center Novi Sad-Liman most frequently used were extended-spectrum penicillins (24.20%) namely: tetracyclines, doxycycline (18.98%), amoxicillin (18.27%), macrolides, roxithromycin (17.56%). At the Clinic of Infectious Diseases of the Clinical Center Novi Sad the decision on using antibiotics and establishing whether it was bacterial or virus infection in 92.13% cases was made on the basis of following analyses: throat and nasal swabs, urine culture, virus complement-binding reaction. In Outpatient General Service of the Health Center Novi Sad-Liman it was done only in 18.46%. CONCLUSION: Although treatment performed based on clinical picture and experience usually proves to be correct, antibiotic prescription policy should include antibiograms to provide optimal treatment and decrease the degree of resistance. Thus, medicine would be considered an exact science and it should be one of its goals of the 21st century.

[Aminoglycoside antibiotics and post-antibiotic effects]. / Aminoglikozidni antibiotici i postantibiotski efekat.

INTRODUCTION: Man has been fighting diseases for centuries. One of the major battles is against microorganisms and diseases they cause. A health education course was organized on prescribing aminoglycoside antibiotics and postantibiotic effect. The aim of the course was to change the prescription habits in our colleagues. The postantibiotic effect of aminoglycoside antibiotics as well as impact of subinhibiting doses on duration of postantibiotic effect requires modification of previous therapeutic protocols. Single daily dose has the same or even greater effect than multiple daily doses. The toxicity of aminoglycosides is not increased and remains the same or smaller in single daily regimens. RESULTS: The single daily dose regimen of aminoglycosides has been used in 63.6% of cases in Clinic for Infectious Diseases of the Clinical Center of Novi Sad, 41.2% in Outpatient Health Care Center of Novi Sad "Liman" and this regimen has not been used in General Practice Department, Children's Health Care Department and Ear, Nose and Throat Clinic at all. The twice daily regimen has been used instead. CONCLUSION: Doctors are aware of the postantibiotic effect, but vast majority are still bound to their old habits in regard to prescribing antibiotics. Our educational course failed to achieve its goal.