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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: Since delay in recognition and effective treatment of necrotizing fasciitis (NF) caused by invasive group A streptococcus increases the mortality and disability, the early diagnosis and management of this disease are essential for a better outcome. We presented a patient with a severe form of streptococcal NF of the left upper limb in whom amputation was performed as a life saving procedure., Case Report: A 65-year-old man, previously healthy, suffered an injury to his left hand by sting on a fish bone. Two days after that the patient got fever, redness, swelling and pain in his left hand. Clinical examination of the patient after admission indicated NF that spread quickly to the entire left upper limb, left armpit, and the left side of the chest and abdomen. Despite the use of aggressive antibiotic and surgical therapy severe destruction of the skin and subcutaneous tissues developed with the development of gangrene of the left upper limb. In this situation, the team of specialists decided that the patient must be operated on submitted to amputation of the left arm, at the shoulder. After amputation and aggressive debridement of soft tissue on the left side of the trunk, the patient completely recovered. beta-hemolytic streptococcus group A was isolated from the skin and tissue obtained during the surgery., Conclusion: In the most severe forms of streptococcal NF of the extremities, adequate multidisciplinary treatment, including limb amputation, can save the life of a patient.

Introduction: Streptococcal necrotizing fasciitis (NF) is a serious soft tissue infection with rapid progression of inflammatory process among superficial or deep fascia, systemic host response to infection leading to toxic shock syndrome (TSS), and multiple organ failure. Lethality is high., Case Outline: A 46-year-old male without co-morbidities was admitted to the Emergency Department with redness, swelling and pain on his right lower leg. He became sick two days earlier with malaise, chills and shivering. On admission he was hypotensive, anuric, with erythematous rash on his face, neck and chest, with acute renal failure and elevated creatine phosphokinase level. During the next several hours, the changes on his right lower leg rapidly spread to the whole leg, followed by skin destruction and subcutaneous bleeding, indicating NF. Aggressive antimicrobial, supportive and symptomatic therapy was initiated immediately and on the same evening surgical intervention was performed. Despite these measures, a rapid development of severe TSS, with lethal outcome, occurred in less than 40 hours after the admission. Streptococcus pyogenes (group A β-hemolytic Streptococcus) was isolated from the throat, skin and tissue obtained during the surgery., Conclusion: Necrotizing fasciitis is a very serious disease with unpredictable course. For that reason doctors must devote a great deal of attention to early, i.e. timely diagnosis of this disease, whose treatment with a multidisciplinary approach is very important.

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.

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.