A tool for selecting patients with a high probability of sustained virological response to peginterferon alfa-2a (40kD)/ribavirin.

BACKGROUND & AIMS: Pretreatment identification of patients likely to achieve a sustained virological response (SVR) with peginterferon alfa-2a/ribavirin would be useful for individualizing treatment choices. The aim of this analysis was to devise a simple scoring system to identify patients with high probability of achieving an SVR with peginterferon alfa-2a/ribavirin. METHODS: Using data from 2109 Caucasian treatment-naive hepatitis C virus (HCV) genotype 1 mono-infected patients from the PROPHESYS cohorts, the relationship between favourable baseline characteristics and SVR was explored using generalized additive model analysis, and a scoring system was devised to predict SVR. RESULTS: Points were assigned for: age (years) (≤35: 2; >35, ≤45: 1; >45: 0); body mass index (kg/m(2)) (≤20: 2; >20, ≤22: 1; >22: 0); HCV RNA (IU/ml) (≤100,000: 3; >100,000-400,000: 2; >400,000-800,000: 1; >800,000: 0); platelets (>150 ×10(9)/l: 1; ≤150 ×10(9)/l: 0); alanine aminotransferase [×upper limit of normal (ULN)] (>3: 1; ≤3: 0); serum aspartate aminotransferase (×ULN) (≤1: 1; >1: 0). 1029, 698 and 382 patients had scores of 0-2, 3-4 and ≥5, respectively, among whom SVR rates were 35.0, 54.9 and 76.7%. SVR in patients with scores ≥5 and undetectable HCV RNA by week 4 was 86.7%. The score was tested against two databases of patients who received peginterferon alfa-2a/ribavirin in other clinical trials; similar high SVR rates in patients with scores ≥5 were reported. CONCLUSIONS: The scoring system can reliably identify treatment-naive HCV genotype 1 mono-infected Caucasian patients who have a high probability of achieving an SVR with peginterferon alfa-2a/ribavirin and will be particularly useful where protease inhibitors are not readily available.

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.

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

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

[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.

[Antiviral/immunomodulatory combination therapy: pegylated interferon alpha 2a and ribavirin in patients with chronic hepatitis C virus infection].

INTRODUCTION: Chronic hepatitis C virus (HCV) infection can progress to liver cirrhosis that causes bleeding from the gastrointestinal tract, liver failure and primary hepatocellular carcinoma. Use of standard therapeutic option consists of recombinant pegylated interferon alpha 2a/b with ribavirin in order to eradicate virus and prevent complications. OBJECTIVE: The aim of investigation was to evaluate efficiency of combination therapy (pegylated interferon alpha 2a/b plus ribavirin) in patients with chronic HCV infection and to estimate predictive factors for successful treatment. METHODS: A total of 387 patients with confirmed diagnosis of hepatitis C were evaluated (aged 18-65 years of both genders). Patients were treated with pegylated interferon alpha 2a/b and ribavirin according to a standard regimen lasting 24 or 48 weeks, dependent on virus genotype. RESULTS: Negative HCV RNA (PCR assay) was recorded in 79.7% of patients at the end of treatment. Six months after completed therapy, negative HCV RNA, i.e. stained virologic response (SVR) was assessed in 70.5% of patients. Statistical summary of our results concerning SVR confirmed better efficiency of combination therapy for the following parameters compared to other investigated variables: age < or = 40 (84.3% vs. 59.1%; p < 0.0005), absence of cirrhosis (75.6% vs. 58.3%; p = 0.003), lack of genotype 1 (86.6% vs. 61.8%; p < 0.0005), and in patients who received full doses of pegylated interferon alpha 2a (78.3% vs. 63.3%; p = 0.002). CONCLUSION: Combination therapy of recombinant pegylated interferon alpha 2a with ribavirin leads to SVR in the majority of treated patients (70.5%). Successful treatment depends on a variety of host and virus factors.

Epidemiological characteristics and clinical manifestations of acute non-A-E hepatitis.

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 U-test, 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.

[Efficacy and safety of peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C virus infection].

INTRODUCTION: Chronic hepatitis C remains a formidable threat to world health. Progression of chronic hepatitis C is associated with significant morbidity: cirrhosis, hepatic failure and hepatocellular carcinoma. The introduction of combined therapy with pegylated interferons and ribavirin has increased the sustained virologic response (SVR) in the much higher percentage than with previous treatment options, while the level of adverse effects has not changed significantely. The aim of this study was to assess the efficacy and safety of combined therapy (peginterferon alfa-2a + ribavirin) in Serbian population. MATERIAL AND METHODS: Patients with genotypes 1 and 4 received a 48-week course of therapy of peginterferon alfa-2a (180 microg/week) and ribavirin (1000-1200 mg/day). Patients with genotypes 2 and 3 received the same doses of both drugs, but during 24 weeks. All patients were scheduled for follow-up visit 24 weeks after the end of treatment. Physicians were instructed to adjust the dose of both drugs if adverse events occurred. Standard PCR tests were used for qualitative and quantitative detection of viral RNA, as well as for determination of patients' genotypes. RESULTS AND DISCUSSION: A total of 95 patients were enrolled in the sutdy. The majority of patients were male (65.26%), aged 40 or under (52.63%), with genotype 1 (63.15%). The average duration of infection was 2.81 + 4.89 years, but still, the majority of patients (51.58%) had HCV infection for less than 2 years. Fibrosis was present in 69.47 % of patients, and cirrhosis in 21.06%. The most common mode of infection was through i.v. drug use (29.48%), but it was unknown in 32.63% of patients. The mean ALT value was 100.44 + 70.26, with the total of 93.68% of patients having elevated ALT level. At the end of treatment (EoT) time point, data were collected from 66 patients (69.47%), while at the end of follow-up (EoFU), data were collected from 68 patients (71.58%). This unusuall drop-out rate of 28.42% was mainly caused by losing contact with patients (14.74%) and premature termination of therapy (13.68%). The primary parameter of efficacy SVR at the EoFU was achieved in 59 out of 68 patients (86.76%), while the secondary efficacy parameter (SVR at the EoT) was achieved in 77.27% of patients. Multiple regression anlysis has established the initial level of ALT, patient's age and fibrosis level as main parameters statistically significantely impacting the outcome of treatment. Although without statistical significance, the trend of better outcomes was associated with early therapy (within 2 years from infection), and while the disease has not progressed (patients with fibrosis achieved SVR at the EoFU in 89.19% vs. 75.00% in patients with cirrhosis). The safety record was good, the most common adverse effects including cytopenia, rash and local reactions at the site of administration. CONCLUSION: Combination therapy with peginterferon alfa-2a and ribavirin is safe and well tolerated, with SVR achieved in 86.76% of patients.

Treatment of anicteric acute hepatitis C with peginterferon alpha-2a plus ribavirin.

BACKGROUND: Hepatitis C virus (HCV) infection is the most frequent cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world. Acute hepatitis C is the most commonly asymptomatic liver disease with the development of chronic HCV infection in the majority of infected patients. Studies of the natural history of HCV infection suggest that only 15-30% of patients with acute infection recover spontaneously. Others, up to 85% of the infected patients develop chronic hepatitis C. Acute hepatitis C is so uncommon and with the unpredictable occurrence, and of the low frequency, that it is difficult to determine the optimal treatment of this disease. There have been many randomized, controlled trials of the therapy in patients with chronic hepatitis C, but none of an adequate size or rigor in patients with acute hepatitis C. Therefore, the causal treatment of patients with acute hepatitis C aimed at the prevention of chronic liver disease is necessary. CASE REPORT: We have treated a patient with anicteric form of acute hepatitis C after a three-month outpatient follow-up using a combined therapy: pegylated interferon-alpha 2a, 180 microg, subcutaneously, once a week plus ribavirin 1000 mg orally once a day. The treatment lasted 24 weeks. Stable biochemical and virological response was achieved both at the end of the treatment and 6 months after the completion of the therapy. CONCLUSION: We believe that the above mentioned might be one of the approaches to the treatment of acute hepatitis C. However, further prospective studies with significantly larger number of patients are necessary for the definite conclusions about the treatment of HCV infections.

[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.