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Background/Aim. In Serbia, pegylated interferon (PEGIFN) alpha-2a has been registered since 2013 for the treatment of patients with chronic hepatitis B (CHB). Numerous advantages, new experiences during the past five years and lack of any published data in our specific population, have initiated this study, with the aim to examine efficacy and safety of PEG-IFN in patients in a Serbian referral center. Methods. This prospective study included 36 patients with CHB who were treated in the Hepatology Department of the Clinic for Infectious and Tropical Diseases, Clinical Center of Serbia in Belgrade, during 2012–2017. Patients had a standard 48-week treatment protocol with PEG-IFN, with measurements of liver enzymes, serology and viraemia before, during, at the end of the treatment and follow-up 6 months afterwards. Treatment outcome was determined using serology (clearance of HBeAg), biochemical [normalization of alanine aminotransferase (ALT)] and virological response [hepatitis B virus (HBV) DNA < 2,000 IU/mL]. Results. Virological success in patients with HBeAg positive CHB was achieved in 50% of patients, HBeAg clearance in 62.5%, and normalization of ALT in 37.5% of patients. In patients with HBeAg negative CHB, 38% of the patients achieved virologic success, biochemical success was obtained in 47.6% of the patients and only one (4.7%) patient had HBsAg clearance. Conclusion. PEG-IFN is important for treatment of patients with CHB in well-defined situations, and in our population success rates are similar to other published studies. Although safety and tolerability are satisfactory, there is a possibility of more serious side-effects so it is necessary to monitor patients regularly during the treatment.

Background/Aim. The era of direct-acting antiviral (DAA) regimen in the treatment of chronic hepatitis C virus (HCV) started in 2011. The aim of this study was to assess the antiviral efficacy and safety of DAA regimen, ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) + dasabuvir (DSV) + ribavirin (RBV), in patients with chronic HCV infection, genotype 1. Methods. The real-life data were collected. The study was multicentric and included seven infectious diseases and hepatology departments in Serbia. A total of 21 patients were enrolled in the OBV/PTV/r + DSV + RBV early access program, 20 of which were previously treated with pegylated interferon + RBV, while 1 was treatment-naive. All patients received the adequate doses of these antiviral drugs. RBV was not given to the patients with HCV genotype 1b infection according to the therapeutic protocol. For the majority of patient, the treatment duration lasted for 12 weeks. For the patients with liver cirrhosis, who were infected with HCV genotype 1a, the duration of treatment was 24 weeks. Viremia was assessed at four points in time: at baseline, 4 weeks after the treatment beginning (rapid viral response, RVR), 12 or 24 weeks after the treatment beginning (end of treatment response – ETR) and 12 weeks after the end of treatment (sustained viral response – SVR). SVR, as a confirmation of the absence of HCV was considered as endpoint of successful treatment. Results. Complete RVR, ETR and SVR were achieved in 64.71%, 85.71% and 95.24% of the patients, respectively. Only 3 patients had mild adverse effects which did not required dose reduction. Conclusion. The treatment of the patients with a chronic HCV infection with OBV/PTV/r + DSV + RBV resulted in excellent antiviral activity and tolerability.

Background/Aim. The reactivation of the varicella zoster virus results in herpes zoster. Acyclovir is currently recommended over 7 to 10 days for herpes zoster treatment and should be started within 72 hours of rash eruption. This study analyses whether a therapy delay and/or shorter courses of treatment are associated with adverse outcomes. Methods. We identified 292 patients treated at the Clinic for Infectious and Tropical Diseases in Belgrade for herpes zoster in a five-years period. The data on these patients were analyzed using the descriptive statistics, the χ2 test, the Mann-Whitney U-test and the multiple logistic regression analysis. Results. The average time from rash eruption to the first dose of acyclovir was 4.07 ± 2.64 days. The patients received acyclovir for 6.83 ± 2.45 days. Seventy-one patients had disseminated herpes zoster, 100 had cranial nerve involvement, 86 had complications other than postherpetic neuralgia and one patient died. In cases where therapy was delayed there was no significant association with complications (χ2 = 0.031; p = 0.86). Our logistic regression model was not able to predict who was treated less than 7 days. An association between the HZ complications and abbreviated acyclovir regimens was not demonstrated (χ2 = 1.109; p = 0.326). We conducted the PubMed search on February 1st, 2017 and found no proof for the need to apply at least 7 days of acyclovir therapy for herpes zoster in the studies that have been published so far. Conclusion. We were unable to prove an association between therapy delay and unfavorable outcomes. The same was true for shorter than recommended acyclovir courses.

Background: Chronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations in UGT1A1 gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome. This is the first study investigating the association of UGT1A1 TA repeats promoter genotypes with the degree of liver injury, viremia and biochemical markers in CHC patients with advanced liver injury and late virological relapse. Methods: Genetic testing of UGT1A1 TA repeats promoter genotypes was performed in 42 CHC patients with advanced fibrosis and cirrhosis who achieved sustained virological response and 42 healthy blood donors. CHC patients were evaluated for clinical findings, laboratory tests and imaging. Results: UGT1A1*28 genotype (7/7 TA repeats) was observed in 23.8% CHC patients and 16.7% healthy controls with no significant difference in genotype frequencies (p= 0.49). Pretreatment levels of ferritin and bilirubin were associated with the presence of U G T1A1*28 genotype, indicating its potential as a predictive marker. However, in our study, there was no correlation of U G T1A 1*28 genotype with the degree of fibrosis or viremia. During antiviral treatment, dose reductions and treatment interruptions, as well as treatment success and occurrence of late virological relapse were not related to the presence of U G T1A 1*28 genotype in CHC patients with severe liver injury. Conclusions: Frequencies of U G T1A 1*28 genotype are high in both Serbian CHC patients and healthy subjects. The presence of U G T1A 1*28 genotype was not associated with ribavirin-related adverse effects and had no effect on long term outcome in CHC patients.

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-naпve 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 period 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

Introduction. Reactivation of chronic hepatitis B virus (HBV) infection often occurs in hepatitis B surface antigen (HBsAg) positive patients undergoing immunosuppressive or chemotherapy, but can also occur in HBsAg negative, anti-HB core positive patients. Treatment of HBV reactivation with lamivudin results in favourable outcome in the majority of patients. The aim of the authors was to show the effect of lamivudin therapy to HBV reactivation caused by immunosuppressive therapy. Outline of Cases. The first patient was a 35-year-old woman with chronic hepatitis B virus infection who underwent prednisolone therapy for pulmonal sarcoidosis. Four months after the beginning of the therapy she presented with jaundice and a significant increase in serum aminotransferase level. Liver biopsy showed chronic viral B hepatitis of strong activity in the stage of rapidly developed cirrhosis. The patient was treated with lamivudine with slow reduction of prednisolone doses, which resulted in full clinical and biochemical recovery. The second patient was a 40-year-old HBsAg negative female with a previous history of resolved acute B hepatitis who received chemotherapy for non-Hodgkin lymphoma. After the third cycle of chemotherapy a significant increase in aminotransferase level occurred, chemotherapy was discontinued, but aminotransferase level still increased. At that moment she was found to be HBsAg positive, and PCR analysis detected a high viral load. Lamivudine treatment resulted in the patient’s recovery and allowed further chemotherapy. Conclusion. In case of the reactivation of chronic HBV infection during immunosuppressive therapy, it should be stopped and antiviral therapy should be immediately initiated. The use of lamivudine results in rapid suppression of serum HBV DNA, improves the outcome and enables the continuation of immunosuppressive and chemotherapy.

Background/Aim. Acute non-A, non-B, non-C, non-D, non-E hepatitis (non-A-E AH) is an acute disease of the liver of unknown etiology for which one or more new, so far undetected, hepatotropic viruses may be responsible. The frequency of non-A-E AH ranges from 3.8% to 33.9%, and therefore it has a significant place within current infectology and hepatology. The aim of our study was to establish the frequency, clinical and biochemical characteristics, natural course and outcome of non-A-E AH and compare them with control groups affected by acute viral hepatitis A, B and C. Methods. This descriptive-analytic prospective study included 31 patients with non-A-E AH treated at the Institute of Infectious and Tropical Diseases, Clinical Center of Serbia, Belgrade, from 2003 to 2008. They were followed up during the period not less than 6 months. The controls involved randomly selected patients, treated at the same time with a definite diagnosis of acute viral hepatitis A, B and C. Statistical data analysis used Mann-Whitney Utest, Student's t-test and variance analysis. The value of p < 0.05 was considered statistically significant. Results. The frequency of non-A-E AH was 7.6%. Almost no difference was found between sexes (male/female ratio was 1 : 1.07); it was developed in all age groups, with the highest incidence in the middle age (mean age was 38.32 ± 15.3 years). It appeared equally throughout the whole year. Out of risk factors, inoculation risk was predominant (before all, dental interventions), mostly involving urban population living in comfortable conditions. The duration of incubation varied much ranging from 20 to 180 days (median 60 days). By clinical course, moderate and icteric forms were most common, mostly corresponding to acute hepatitis A and C. On the other hand, by duration of the disease (mean duration was 67.1 ± 27.1) and chronic transformation, non-A-E AH resembled to acute hepatitis B. Progression to chronicity was recorded in 9.68% of the patients. There was no fulminant neither cholestatic form of the disease. Conclusion. Based on the results obtained in this study, it is probable that there are some so far undetected primary hepatotropic viruses in our environment.

Different types of interferon are widely used to treat hepatitis C virus (HCV) infection. Results obtained in vitro suggest that interferon inhibits internal ribosome entry site (IRES)-mediated translation of the HCV genome. To elucidate the possible effect of the nucleotide sequence of IRES on therapy outcome, we compared HCV isolates from patients with sustained response and non-response to interferon/ribavirin combination therapy. In 56 analyzed HCV isolates, nucleotide changes appeared strictly in the stem-loop IIIb region, the stem part from 243 nt to 248 nt, and the polypyrimidine-II region. The natural sequence variability of IRES in isolates of genotype 3a was significantly higher than in isolates of genotype 1b (p < 0.05). The average number of nucleotide changes in genotype 3a correlated with response to therapy (p < 0.05).

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 of treatment with pegylated interferon plus ribavirin in correctional settings. The aim of this 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 800mg 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 1 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. [ABSTRACT FROM AUTHOR]

Introduction: Progression from acute to chronic HCV infection occurs in 50% to 84% of cases. Even the latest approach - combination therapy with pegilated interferon alfa 2-a or 2b and ribavirin - eliminates the virus in only 54% to 56 % of cases with chronic infection. The aim of this study is to determine whether treatment during the acute phase prevents the development of chronic infection. Material and methods: Between 2001 and 2004, 27 patients with diagnosis of acute hepatitis C were treated at the hepatology Department of Institute of Infectious and Tropical Diseases. Among them, 19 were treated with recombinant interferon alfa 2-a. Acute hepatitis C was defined by clinical and laboratory test results and by exclusion of other causes of acute liver disease. Results: The mean age of our patients was 32.7 years, whereas the mean incubation time was 61.7 days. The mean serum aminotransferase levels were 1119 U/I and the mean total bilirubin levels were 106 mmol/l. At the end of therapy, 81.8% of patients had undetectable levels of HCV RNA, but 94.7% of patients had normal serum alanine aminotransferase levels. At the end of follow up, 84.6% of patients had normal alanine aminotransferase levels and 83.3% of patients had undetectable levels of HCV RNA. One patient had undetectable antibody to HCV at the end of follow-up. Conclusions: The results reported here demonstrate that in the acute phase of HCV infection, interferon treatment is associated with a high rate of virological and biochemical response. We concluded that early treatment of acute hepatitis C may prevent chronic hepatitis C. [ABSTRACT FROM AUTHOR]

Total of 153 patients with chronic Hepatitis C Virus infection was investigated. Patients were classified into three groups: with histologic confirmed liver cirrhosis, clinical advanced cirrhosis, and chronic hepatitis without fibrosis. Acitivity of aminotransferases (AST, ALT), value of INR and platelet counts were analyzed by SPSS for Windows (version 10.0). Probability of cirrhosis was calculated by HALT-C formula and expressed in percent (http://www.haltctrial.org). Thrombocytopenia was the most important predictive factor for progression/exclusion of cirrhosis. Probability of cirrhosis in patients with histologic cirrhosis, clinical cirrhosis and chronic hepatitis without fibrosis was from 23-93%, 41-98% and 4-65%, respectively. Probability equal/more than 50% had 60%, 90% and 14% of patients from the same groups. In conclusion, liver cirrhosis can be predicted based on standard laboratory parameters in more than half of patients with chronic hepatitis C virus infection. [ABSTRACT FROM AUTHOR]

Objectives: Survey was conducted to assess state of viral hepatitis care in Central and Eastern Europe (CEE).Methods: Representatives of 16 CEE countries completed on-line survey in April-May 2017 that collected information on basic epidemiology and availability of key services for HCV and HBV infections. Sources of information provided ranged from national surveillance data to expert opinion.Results: The burden of viral hepatitis varied between countries, ranging from 6,500 to 2 million for HCV and from 10,000 to 3 million for HBV. Access to routine HCV RNA testing and genotyping was reported by 11 and 9 countries, respectively. HCV resistance testing was available in 7 countries. Direct acting antivirals (DAAs) were available in 13 countries, most frequently Sofosbuvir and Ledipasvir/Sofosbuvir (12 countries apiece) and Ombitasvir/Paritaprevir/Dasabuvir (9 countries). HBV DNA testing and HBV genotyping were routinely available in 10 and 7 countries, respectively. Eleven countries reported available treatment with Tenofovir.Conclusions: There are gaps in viral hepatitis care in CEE. Despite the availability of registered modern drugs for HCV and HBV, the access to treatment is limited. Ensuring quality health care is essential to reduce the epidemic and achieve the WHO's goal of eliminating viral hepatitis as a major public health challenge. [ABSTRACT FROM AUTHOR]

Introduction: Reactivation of chronic hepatitis B virus (HBV) infection often occurs in hepatitis B surface antigen (HBsAg) positive patients undergoing immunosuppressive or chemotherapy, but can also occur in HBsAg negative, anti-HB core positive patients. Treatment of HBV reactivation with lamivudin results in favourable outcome in the majority of patients. The aim of the authors was to show the effect of lamivudin therapy to HBV reactivation caused by immunosuppressive therapy., Outline of Cases: The first patient was a 35-year-old woman with chronic hepatitis B virus infection who underwent prednisolone therapy for pulmonal sarcoidosis. Four months after the beginning of the therapy she presented with jaundice and a significant increase in serum aminotransferase level. Liver biopsy showed chronic viral B hepatitis of strong activity in the stage of rapidly developed cirrhosis. The patient was treated with lamivudine with slow reduction of prednisolone doses, which resulted in full clinical and biochemical recovery. The second patient was a 40-year-old HBsAg negative female with a previous history of resolved acute B hepatitis who received chemotherapy for non-Hodgkin lymphoma. After the third cycle of chemotherapy a significant increase in aminotransferase level occurred, chemotherapy was discontinued, but aminotransferase level still increased. At that moment she was found to be HBsAg positive, and PCR analysis detected a high viral load. Lamivudine treatment resulted in the patient's recovery and allowed further chemotherapy., Conclusion: In case of the reactivation of chronic HBV infection during immunosuppressive therapy, it should be stopped and antiviral therapy should be immediately initiated. The use of lamivudine results in rapid suppression of serum HBV DNA, improves the outcome and enables the continuation of immunosuppressive and chemotherapy.

Introduction: Progression from acute to chronic HCV infection occurs in 50% to 84% of cases. Even the latest approach--combination therapy with pegilated interferon alfa 2-a or 2b and ribavirin--eliminates the virus in only 54% to 56% of cases with chronic infection. The aim of this study is to determine whether treatment during the acute phase prevents the development of chronic infection., Material and Methods: Between 2001 and 2004, 27 patients with the diagnosis of acute hepatitis C were treated at the hepatology Department of Institute of Infectious and Tropical Diseases. Among them, 19 were treated with recombinant interferon alfa 2-a. Acute hepatitis C was defined by clinical and laboratory test results and by exclusion of other causes of acute liver disease., Results: The mean age of our patients was 32.7 years, whereas the mean incubation time was 61.7 days. The mean serum aminotransferase levels were 1119 U/l and the mean total bilirubin levels were 106 mmol/l. At the end of therapy, 81.8% of patients had undetectable levels of HCV RNA, but 94.7% of patients had normal serum alanine aminotransferase levels. At the end of folow up, 84.6% of patients had normal alanine antimiransferase levels and 83.3% of patients had undetectable levels of HCV RNA. One patient had undetectable antibody to HCV the end of follow-up., Conclusion: The results reported here demonstrate that in the acute phase of HCV infection, interferon treatment is associated with a high rate of virological and biochemical response. We concluded that early treatment of acute heptitis C may prevent chronic hepatitis C.

Introduction: Lamivudine is effective in suppressing hepatitis B virus replication and hepatic necroinflammatory activity. Patients with HBV-related chronic liver disease often present with hepatic decompensation and are not eligible for interferon therapy. The effectiveness of antiviral therapy in preventing disease progression in patients with hepatitis B cirrhosis is unknown. The aim of this study was to evaluate the effectiveness of lamivudine treatment in patients with cirrhosis due to chronic hepatitis B., Material and Methods: The study included 24 patients with cirrhosis B. During one year, all of them were treated with Lamivudine (100 mg/day). All patients underwent routine laboratory tests and abdominal ultrasound. After that, they were followed-up from 1-15 months., Results and Discussion: Most patients presented with improved general condition. We also noticed a reduction in SBP, ALT level, bilirubin level, hepatic encephalopathy and ascites. Five patients died, due to HCC, and two due to variceal bleeding. There was no significant improvement in liver synthetic function., Conclusion: Lamivudine is highly effective in reducing viral load in HBeAg-negative patients significantly improving the clinical and biochemical status of liver functions.

Introduction: Aminotransferase levels are a sensitive indicator of liver cell injury and is frequently used to identify patients with liver diseases such as hepatitis. Both aminotransferases are normally present in serum at low levels, usually less than 30 U per liter. Although these enzymes are present in tissues throughout the body, they are most often elevated in patients with liver diseases and may reflect liver injury. Raised aminotransferase levels of unknown origin are common problem in clinical practice. Serum alanine aminotransferase (ALT) activity, the variable most commonly measured to assess hepatic disease, fails to identify many patients with hepatic injury. On the other hand, elevated ALT level doesn't always confirm liver disease. The aim of this study was to show the most common reasons for elevated aminotransferase levels., Material and Methods: The study included 27 patients with elevated ALT. All of them were followed-up for six months before liver biopsy was performed. All patients underwent routine laboratory tests and ultrasound of the abdomen., Results: We found that four patients had a nonalcoholic steatohepatitis (NASH), four patients had chronic hepatitis of unknown etiology, two of them had autoimmune hepatitis, four had mild lobular hepatitis (three of them unresolved acute hepatitis, one of them had nodular regenerative hyperplasia), six patients had normal results, and three had no specific changes., Conclusion: Elevated ALT level doesn't always mean that there is a liver disease. If aminotransferase levels are persistently more than twice the normal value, a biopsy is recommended. Although results of biopsy are unlikely to lead to a diagnosis or to changes in management, they often provide reassurance to the patient and the physician to exclude serious pathology.