Effectiveness and safety of ledipasvir/sofosbuvir±ribavirin in the treatment of HCV infection: The real-world HARVEST study.

BACKGROUND: To evaluate the effectiveness and safety of ledipasvir/sofosbuvir (LDV/SOF)±ribavirin (RBV) regimen in a real-world setting. METHODS: Patients received a fixed-dose combination tablet containing LDV and SOF with or without RBV, for 8, 12 or 24 weeks. Patients were assessed at baseline, end of treatment, and 12 weeks after the end of treatment. The primary effectiveness endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: Of the 86 patients, aged 20-80 years, 82.6% were HCV genotype 1b-infected and 50.0% were cirrhotic. More than half (52.3%) had previously followed pegylated interferon-containing (PEG-IFN) treatment regimens, and 38.5% were null-responders. SVR12 was achieved by 94.2% of patients. All non-responders were cirrhotic: two demonstrated virologic breakthrough and the remaining three relapsed. All patients treated with an 8-week regimen achieved SVR12 despite having high viral load at baseline (HCV RNA of >1 million IU/mL in 8/10 patients, including one with a viral load of >6 million IU/mL). Adverse events were generally mild and transient. Most frequently, fatigue (22.1%), headache (15.1%), and arthralgia (7.0%) were observed. Laboratory abnormalities included anemia and hyperbilirubinemia. CONCLUSIONS: Treatment with LDV/SOF±RBV is an effective and safe option for patients with HCV, including those with advanced liver disease or a history of non-response to PEG-IFN-based therapy.

Efficacy of HCV treatment in Poland at the turn of the interferon era - the EpiTer study.

THE AIM OF THE STUDY: Was to analyze the efficacy achieved with regimens available for chronic hepatitis C (CHC) in Poland between 2013 and 2016. MATERIAL AND METHODS: Data were collected from 29 centers and included 6786 patients with available sustained virologic response (SVR) data between 1 January 2013 and 31 March 2016. RESULTS: The sustained virologic response rate for genotypes (G) 1a, 1b, 2, 3 and 4 was 62%, 56%, 92%, 67% and 56% respectively; 71% patients (n = 4832) were treated with pegylated interferon α (Peg-IFNα) and ribavirin (RBV), with SVR rates of 58%, 49%, 92%, 67% and 55% respectively. The sustained virologic response among 5646 G1 infected patients was the lowest with natural interferon α (7%, n = 70) or PegIFN (50%, n = 3779) with RBV, and improved in those receiving triple regimens of Peg-IFN + RBV combined with boceprevir (47%, n = 485), telaprevir (64%, n = 805), simeprevir (73%, n = 132) or sofosbuvir (70%, n = 23). The sustained virologic response with interferon-free regimens of sofosbuvir and RBV (n = 7), sofosbuvir and simeprevir (n = 53), and ledipasvir and sofosbuvir (n = 64) achieved 86%, 89% and 94% respectively. The highest SVR of 98% was observed with ombitasvir/paritaprevir combined with dasabuvir (n = 227). Patients infected with G3 (n = 896) and G4 (n = 220) received mostly Peg-IFN + RBV with SVR of 67% and 56% respectively. Interferon-free regimens were administered in 18 G3/G4 patients and all achieved an SVR. Sofosbuvir combined with Peg-IFN and RBV was administered to 33 patients with an SVR rate of 94%, and a similar rate was achieved among 13 G2 patients treated with interferon and RBV. CONCLUSIONS: We observed significant differences in efficacy of HCV regimens available in Poland at the turn of the interferon era. The data will be useful as a comparison for therapeutic options expected in the next few years.

Prevalence of HCV genotypes in Poland - the EpiTer study.

THE AIM OF THE STUDY: Was to assess current prevalence of hepatitis C virus (HCV) genotypes in Poland, including their geographic distribution and changes in a given period of time. MATERIAL AND METHODS: Data were collected with questionnaires from 29 Polish centers and included data of patients diagnosed with HCV infection between 1 January 2013 and 31 March 2016. RESULTS: In total, data of 9800 patients were reported. The highest prevalence was estimated for genotype 1b (81.7%), followed by 3 (11.3%), 4 (3.5%), 1a (3.2%) and 2 (0.2%). Genotype 5 or 6 was reported in 6 patients only (0.1%). The highest prevalence of genotype 1 was observed in central (lódzkie, mazowieckie, swietokrzyskie), eastern (lubelskie) and southern (malopolskie, slaskie) Poland. The highest rate for genotype 3 was observed in south-western (dolnoslaskie, lubuskie) and eastern (podlaskie, warminsko-mazurskie and podkarpackie) Poland. Compared to historical data, we observed an increasing tendency of G1 prevalence from 72.0% in 2003 to 87.5% in 2016, which was accompanied by a decrease of G3 (17.9% vs. 9.1%) and G4 (9.0% vs. 3.1%). CONCLUSIONS: Almost 85% of patients with HCV in Poland are infected with genotype 1 (almost exclusively subgenotype 1b), and its prevalence shows an increasing tendency, accompanied by a decrease of genotypes 3 and 4.

Effect of Peginterferon or Ribavirin Dosing on Efficacy of Therapy With Telaprevir in Treatment-Experienced Patients With Chronic Hepatitis C and Advanced Liver Fibrosis: A Multicenter Cohort Study.

We investigated the safety, efficacy, and impact of ribavirin and peginterferon dose reduction on complete early virologic response and sustained virologic response (SVR) to triple therapy with telaprevir in treatment-experienced patients with advanced liver fibrosis.Treatment was initiated for 211 patients who failed treatment with peginterferon and ribavirin, with bridging fibrosis (F3, n = 68) or cirrhosis (F4, n = 143), including 103 (49%) null-responders (NR), 30 (14%) partial responders (PR), and 78 (37%) relapsers (REL). Impaired liver function (ILF) platelets <100,000/mm or albumin <35 g/L were present in 40 patients. The distribution of hepatitis C virus subtypes was: 1a, 1b, or 1, with undetermined subtype for 10 (5%), 187 (89%), and 14 (6%) patients, respectively. Treatment was started with peginterferon alpha-2a or alpha-2b, ribavirin, and telaprevir at standard doses.The overall SVR24 rate was 56% and was lower in cirrhotic patients (NR: 35%, PR: 40%, and REL: 63%, respectively) than in patients with bridging fibrosis (NR: 50%, PR: 75%, and REL: 75%, respectively). The lowest probability of SVR24 was in NRs with ILF (26%). The SVR24 rate significantly decreased in NRs receiving <60% vs >60% of the total ribavirin dose (23% vs 44%, respectively) or <80% vs >80% of the total ribavirin dose (33% vs 48%, respectively). A significant SVR24 decrease was noted subsequent to a total peginterferon dose reduction, both when comparing patients who received <60% vs >60% of the total dose (NR: 0% vs 44%; REL: 33% vs 68%) and patients who received <80% vs >80% of the total dose (NR: 17% vs 50%; REL: 46% vs 71%).Serious adverse events were observed in 31 patients (15%). Deaths occurred in 4 patients. All of the deceased subjects were cirrhotic members of the ILF (baseline serum albumin level <35 g/L and/or platelet count <100,000/mm) group.Ribavirin dose reduction did not affect efficacy in REL but did in NR. Peginterferon dose reduction decreased the SVR24 rate for all groups, particularly in prior NR. ILF increased the risk of fatal complications with a low probability to achieve SVR24. One solution might be to provide wide and early access to novel, efficient, and safe interferon-free combinations to treatment-experienced patients, particularly those with liver cirrhosis.

[Polish multicenter study on safety and efficacy of adefovir dipivoxil in the treatment of lamivudine resistant chronic hepatitis B in adults (HEP 2008)]. / Wieloosrodkowe badanie bezpieczenstwa i skutecznosci preparatu dipiwoksyl adefowiru w leczeniu przewleklego wirusowego zapalenia watroby typu B u doroslych z opornoscia na lamiwudyne (HEP 2008).

Initiated in April 2008 Polish multicenter study HEP2008 aimed clinical data concerning safety and efficacy of adefovir dipivoxil (ADV, Hepsera, Gilead Sciences) in adult chronically infected HBV with lamivudine (LAM) resistance after earliest treatment. We examined 38 men (70.4%) and 16 women (29.6%) with chronic hepatitis B in age 23-81 (average 53) mostly HBeAg positive (70.4%). Majority of patients received earlier LAM (72%), but others additional entekawir and\ or pegylated interferon. Average time from discovering infection HBV was 95 +/- 77 (10-307) months. Majority of patients received monotherapy ADV, but physicians decided at 12 (22%) persons about continuation of LAM therapy. Median HBV DNA level decreased from a baseline value 6.73 +/- 1.71 (1.8-9.0) to 3.25 log10 copies/mL. At least HBV DNA drop 1 log10 and 2 log10 get 78.8 and 60.6% in 24 week, 84.8 and 69.7% in 48 week. HBV DNA reduction below level 300 and 50 copies/mL it observed in 15.2 and 6.1% in 24 week, 39.4 and 30.3% in 48 week. Patients with undetectable Mean ALT activity dropped significantly and were below limit norm at 24 week in 40%, and at 48 week in 58% of patients. Patients treated ADV and LAM reached great reduction of ALT activity but was no influence on HBV DNA reduction. Results of research have confirmed efficiency and safety 48-week's therapy ADV in patients with LAM resistance.

[Ehrlichiosis]. / Ehrlichioza.

Ehrlichiosis is a disease caused by Ehrlichiae bacteria. The disease is transmitted by ticks. The disease occurs in the following clinical forms: monocytic ehrlichiosis, granulocytic ehrlichiosis and sennetsu fever. Symptoms of ehrlichiosis are non-specific, and include flu-like symptoms, cutaneous manifestations (erythema), enlargement of the lymphatic nodules, liver and spleen. Involvement of the gastrointestinal tract is common in the patients. Symptoms are accompanied by alteration seen in peripheral blood (leukopenia with lymphocytopenia, thrombocytopenia). Antibiotics are used in management of ehrlichiosis.