Milotka Fabri

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.

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.

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%.

368 REDUCED BONE MINERAL DENSITY DERIVED FROM DUAL X-RAY ABSORPTIOMETRY ASSESSMENTS IN PATIENTS WITH CHRONIC HEPATITIS B (CHB)

1Toronto General Hospital,University Health Network, Toronto, ONT Canada; 2Clinical Centre Vojvodina, Clinic of Infectious Diseases, Novi Sad, Serbia; Clinical Centre of Serbia, 3Uludag University Medical Faculty Hospital, Bursa Turkey; 4Hepatitis Program, Vancouver Hospital, Vancovuer BC; 6Faculty Hospital Brno and Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic 7Clinical Department of Infectious Diseases Silesian Medical School, Chorzow, Poland 5Prof. Dr. Matei Bals Institute for Infectious Diseases, Bucharest Romania; 8Clinic for Infectious and Tropical Diseases, Belgrade, Serbia; 9Auckland City Hospital, Auckland New Zealand, 10Gilead Sciences Inc, Foster City, CA.

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

Abstract 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.

Exercise induced rhabdomyolysis

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.

The occurrence of liver steatosis in patients with chronic hepatitis C - the experience of the Clinical Center of Vojvodina

Background/Aim. Hepatic steatosis in patients with chronic hepatitis C occurs in about half of the cases. Its occurrence is influenced by factors of the host and viral factors and its importance lies in the fact that it reduces the success of antiviral therapy based on interferon in the treatment of chronic hepatitis C and that, associated with other factors, exacerbates liver disease. The aim of this study was to determine the prevalence and severity of steatosis in patients with chronic hepatitis C and to determine the factors that affect its occurrence. Methods. The study included 123 patients with chronic hepatitis C with diagnosis of liver steatosis made by liver biopsy and histopathological examination according to which ≥ 5% of hepatocytes was affected by fatty change. Based on the presence of steatosis, the patients were divided into two groups: 43 patients with steatosis and 80 patients without steatosis. The influence of certain factors on the occurrence of steatosis was examined using standard statistical methods. Results. Liver steatosis was found in 34.96% of patients with chronic hepatitis C, and a majority of patients (76.74%) had mild steatosis. Of the examined predictive factors for the occurrence of steatosis, statistical significance in its occurrence was connected to elevated body mass index (BMI), genotype 3 hepatitis C virus (HCV) and HCV viremia. Conclusion. Hepatic steatosis often occurs in people with chronic hepatitis C, and most often it is mild. The occurrence of hepatic steatosis in our sample was most often affected by genotype 3 HCV and HCV viremia level. Hepatic steatosis can reduce the success of antiviral therapy based on interferon and negatively affect chronic liver disease course. Therefore, we need to recognize it, treat it and make it withdraw.

Autoimmune thyroid diseases in patients with chronic hepatitis C treated by pegylated interferon-alpha and ribavirin: A prospective study

Maja Ružić1, Milotka Fabri1, Milica Medić-Stojanoska2, Ivana Bajkin2, Vesna Turkulov1, Ludovico Abenavoli3 1University of Novi Sad, Medical Faculty, Clinical Centre of Vojvodina, Clinic for Infectious Diseases, Novi Sad, Serbia; 2University of Novi Sad, Medical Faculty, Clinical Centre of Vojvodina, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Novi Sad, Serbia; 3University “Magna Græcia”, Department of Health Sciences, Catanzaro, Italy

Visceral leishmaniasis as a cause of postpartum pyrexia — case report

IntroductionVisceral leishmaniasis, caused by protozoan parasites of the Leishmania genus, is very rare cause of postpartum pyrexia. It is also known as kala-azar, black fever, and Dumdum fever. Signs and symptoms include fever, weight loss, mucosal ulcers, fatigue, anemia, and substantial swelling of the liver and spleen.Case reportWe represent a very rare case of the septic form of visceral leishmaniasis in a thirty-year-old woman during puerperium, 31 days after vaginal delivery. Her continuously febrile state, splenomegaly, and laboratory findings characteristic of a febrile state meant that the disease at the beginning was understood and treated as a puerperal sepsis. The patient’s condition worsened continuously, despite treatment with wide spectrum antimicrobial agents. Expert advice at the Clinic decided that hysterectomy was necessary. After a short remission, her febrile state returned; we decided to transfer the patient to the Clinic for Infectious Diseases for further evaluation and diagnosis. Microscopic analyses of a sternal biopsy showed polymorphic forms of Leishmania chagasi, confirming the diagnosis of visceral leishmaniasis. After adequate the patient recovered completely.ConclusionOnly careful examination, close observation, and prompt treatment performed by a multidisciplinary team of specialists can lead to a good outcome for the patient. Bone marrow biopsy remains the gold standard in the diagnosis of Visceral leishmaniasis.

Hepatitis B reactivation after therapy for non-Hodgkin lymphoma: A case report with review of literature

The natural course of hepatitis B virus (HBV) infection depends on the immune status of the host. In cancer patients, as the consequence of immune suppression due to chemotherapy and malignant disease itself, the balance between replicative potential of the virus and immune response of the host is disrupted leading to acute HBV infection or reactivation. We present a case of HBsAg positive, diffuse large B cell gastric lymphoma patient CD20+ staged IB, treated with six cycles of R-CHOP protocol and two cycles with rituximab monotherapy. Five months after the successful anticancer treatment, patient developed reactivation of chronic HBV infection (ten-fold increase in liver enzymes, HBsAg+, IgM antiHBc+, HBeAg(-), and HBV DNA 5×10 copies/ml). Antiviral therapy with lamivudine was started. Four weeks after the antiviral therapy initiation liver enzymes were in normal ranges. One year after the start of antiviral treatment HBV DNA PCR test did not detect any viral particles. The patient is in complete remission of malignant disease, and still receiving therapy with lamivudine. HBV screening in cancer patients is necessary in order to provide a prompt antiviral therapy and to prevent postponement or even cessation of planned anticancer treatment. HBsAg positive patients should start prophylactic antiviral treatment before the start of immunosuppressive treatment. Chemotherapy protocols consisting rituximab and corticosteroids significantly increase the risk of reactivation. If reactivation is diagnosed in course of chemotherapy, the therapy should be stopped and antiviral treatment should be applied as soon as possible. Treatment with lamivudine is continued at least 6 months after the chemotherapy end.