Real life results of direct acting antiviral therapy for HCV infection in HIV-HCV-coinfected patients: Epi-Ter2 study.

The aim of this study was to evaluate the baseline demographics and real-life efficacy of direct acting antivirals (DAAs) in HIV-HCV-positive patients as compared to patients with HCV monoinfection. The analysis included 5690 subjects who were treated with DAAs: 5533 were HCV-positive and 157 were HIV-HCV-positive. Patients with HCV-monoinfection were older (p < .0001) and in HIV-HCV group there were more men (p < .0001). Prevalence of genotype 1a (p = .002), as well as of genotypes 3 and 4 (p < .0001) was higher in HIV-HCV-coinfected patients. Genotype 1b was more frequent (p < .0001) in the HCV-mono-infection group. Patients with HCV-monoinfection had a higher proportion of fibrosis F4 (p = .0004) and lower proportion of fibrosis F2 (p < .0001). HIV-HCV-coinfected individuals were more often treatment-naïve (p < .0001). Rates of sustained viral response after 12 weeks did not differ significantly between both groups (95.9% versus 97.3% in coinfection and monoinfection group, respectively; p > .05). They were, however, influenced by HCV genotype (p < .0001), stage of hepatic fibrosis (p < .0001), male sex (p < .0001), BMI (p = .0001) and treatment regimen modifications (p < .0001). Although factors associated with worse response to therapy (male sex, genotype 3) occurred more often in the HIV coinfection group, real-life results of DAAs did not differ significantly between both populations.

Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness 2 years after treatment with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in the AMBER, real-world experience study.

We followed for 2 years patients treated with direct-acting agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator-initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2-year follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post-treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2-year follow-up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2-year monitoring for possible disease progression.

Treatment of HCV infection in Poland at the beginning of the interferon-free era-the EpiTer-2 study.

The aim of the EpiTer-2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon-free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon-free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two-third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir-based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3-infected patients. Efficacy of treatment in the whole study population measured as intent-to-treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer-2 study confirmed the excellent efficacy and safety profile of the real-world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections.

Hepatitis C virus (HCV) genotype 1 NS5A resistance-associated variants are associated with advanced liver fibrosis independently of HCV-transmission clusters.

OBJECTIVES: The aim of the study was to characterize the differences in the frequencies of NS3 and NS5A resistance-associated variants (RAVs) among Polish therapy-naive genotype 1 (G1) hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients including clustering patterns and association of RAV frequency with liver fibrosis. METHODS: NS3/NS5A RAVs were identified by population sequencing in 387 directly acting antiviral treatment-naive G1-infected individuals (54 with genotype 1a (G1a) and 333 with genotype 1b (G1b)). Liver fibrosis was assessed based on histopathology or ultrasound elastography. Phylogenetic clusters were identified using maximum likelihood models. For statistics, chi-squared or two-sided Fisher's exact tests and multivariate logistic regression models were used, as appropriate. RESULTS: NS3 RAVs were found in 33.33% (18/54) for G1a and 2.62% (8/297) for G1b whereas NS5A variants were present in 5.55% (3/54) G1a and 9.31% (31/333) G1b sequences. Variations in NS5A 31 and 93 codon positions were found only in G1b (4.2% (14/333) for L31I/F/M and 5.39% (17/333) for Y93H). NS5A RAVs were more frequent among patients with advanced liver fibrosis (17.17% (17/99) for F3-F4 versus 6.94% (17/245) for F0-F2; p 0.004) or liver cirrhosis (20.34% (12/59) for F4 versus 7.72% (22/285) for F0-F3; p 0.003). Liver cirrhosis (F4) was associated with higher odds ratio of the NS5A RAVs among HCV-infected patients (odds ratio 2.34, 95% CI 1.004-5.291; p 0.049). NS5A RAVs were less frequent among sequences forming clusters and pairs (5.16% (8/155) versus 11.21% (26/232); p 0.039). CONCLUSIONS: Presence of NS5A RAVs correlated with progression of liver fibrosis and represents de novo selection of variants rather than transmission of drug resistance. Hence, the presence of NS5A RAVs may be a predictor for a long-lasting HCV infection.

Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study.

BACKGROUND: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. AIM: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. METHODS: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. RESULTS: A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients. CONCLUSIONS: The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting.

What we can really expect from telemedicine in intensive diabetes treatment: results from 3-year study on type 1 pregnant diabetic women.

Existing standards of the management of the diabetic patients are not efficient enough, and further improvement is needed. The major objective of this paper is to present and discuss the therapeutic effectiveness of an intensive care telematic system designed and applied for intensive treatment of pregnant type 1 diabetic women. The developed system operates automatically, every night transferring all the data recorded during the day in the patient's glucometer memory to a central clinical unit. In order to assess the efficiency of the designed and developed system, a 3-year randomized prospective clinical trial was conducted, using the study group and the control group, each consisting of 15 pregnant type 1 diabetic women. All patients were treated by the same diabetologist. In the presented analysis, two indices calculated weekly were used for the assessment of glycemic control: MBG represents mean blood glucose level, and the universal J-index is sensitive to the glycemic level and glycemic variations. The most important results from the study concern: (a) better glycemic control in the study group in comparison with the control group during the course of treatment, as assessed by the average differences of the MBG and J indices calculated weekly (n = 24) (deltaMBG = -3.2 +/- 4.3 mg/dL, p = 0.0016, deltaJ = -1.4 +/- 2.3, p = 0.0065); (b) much more similar results in glycemic control among members of the study group compared to each other, than among members of the control group compared to each other, as indicated by significantly lower variations of the applied glycemic control indices (SDMBG: 11.9 vs. 18.7 mg/dL, p = 0.0498; SDJ: 6.5 vs. 10.9, p = 0.0318); (c) the observed tendency of a better glycemic control for patients with a lower level of intelligence (IQ < 100) supported by the telematic system in comparison with all other assessed groups of patients. The last result was not statistically significant (p > 0.05). This telematic intensive care system improved the effectiveness of diabetes treatment during pregnancy. It also allows the diabetologist's strategy to be much more precise than if it were conducted without telematic support. This telematic system is inexpensive and simple in use.

Teletransmission system supporting intensive insulin treatment of out-clinic type 1 diabetic pregnant women. Technical assessment during 3 years' application.

A telematic system supporting intensive insulin treatment of pregnant type 1 diabetic out-clinic patients was implemented and technical efficiency of the system was evaluated over long-term ambulatory application. The system consists of a patient teletransmission module (PTM) and a central clinical control unit (CCU). The PTM contains a one-box blood glucose meter and electronic logbook, a modem and a dial-up or cellular phone set. The CCU consists of a PC computer with a modem and DIAPRET - an original program designed to monitor the intensive insulin treatment. The system was installed in the Clinic of Gastroenterology and Metabolic Disease, MA Warsaw and was tested for 166 +/- 24 days on 15 pregnant type 1 diabetic women. Telemonitoring of the patient data was done automatically. No major technical problems with proper operation or handling of the system was noted. Total effectiveness was 69.3 +/- 13.0% and technical effectiveness 91.5 +/- 6.1%. The efficacy of the system was not significantly influenced by patient intelligence level, education level or place of residence (p < 0.05). Significant improvement of metabolic control was noted during application of the system. In conclusion, the telematic system we developed and implemented should have a positive influence on the quality of diabetes treatment during pregnancy.

[Pregnancy in women with diabetes complicated by nephropathy and proliferative retinopathy]. / Ciaza u kobiet chorych na cukrzyce powiklana nefropatia i retinopatia proliferacyjna.

Nephropathy and proliferative retinopathy are widely known as the most serious complications of diabetes. In the paper the analysis of the course of pregnancy, labour and neonatal complications among mothers with White class F, R, FR and T was made. The study group consisted of 44 patients. Primary hypertension was observed in 17 (38.6%) patients. The percentage of complications both maternal and neonatal was very high. Among maternal complications were pregnancy induced hypertension (43.2%), urinary tract infections (36%), anaemia (22.7%), threatened preterm labor (13.6%). Nearly 50% of patients has diurnal proteinuria in nearly 50% of patients exceed 3 g. In the opinion of the authors there is a strong need to establish the national supraregional centers designed specially to deal with the problems of pregnant women with diabetic nephropathy and retinopathy.

[Results of screening tests for gestational diabetes mellitus at Medical University in Warsaw]. / Badania przesiewowe w kierunku rozpoznawania cukrzycy ciezarnych na materiale I i II Kliniki Poloznictwa i Ginekologii Akademii Medycznej w Warszawie.

Our purpose was to determine the incidence of screening for gestational diabetes among the population of women delivering at I and II Departments of the First Faculty of Medical University in Warsaw. A retrospective review of 647 pregnancies was performed. The incidence of gestational diabetes mellitus screening was determined and the rate of occurrence of GDM analyzed. 310 (48%) pregnancies were screened for gestational diabetes mellitus with a 1-hour, 50 gm oral glucose challenge test. 49 (16.07%) of the screens had positive results at a plasma glucose level of > 139 mg/dl. Two-hour 75 gm oral glucose tolerance tests (according to the 1994 World Health Organization panel recommendations) were performed on screen-positive women, eleven of whom (22.45%) were diagnosed with gestational diabetes mellitus. Despite of positive oral 50 gm glucose test, (plasma glucose level 140-179 mg/l) 15 women (30%) haven't had the 75 gm oral glucose test. The incidence of GDM among analyzed population is 4% and when GDM screening is carried out, exceeds 7%. Early gestational glucose screening, if performed, may be beneficial in detecting gestational diabetes. Consideration should be given to fulfill it more frequently and for sure, repeat glucose testing in patients with positive one-hour screening tests.

[Risk factors for gestational diabetes mellitus and results of glucose tolerance tests]. / Czynniki ryzyka cukrzycy ciazowej a wyniki testów obciazenia glukoza.

The authors made an effort to verify the connection between the presence of risk factors for GDM and results of screening and diagnostic tests. Study group consisted 302 patients. Gestational diabetes was more frequently diagnosed when an excessive maternal weight and family history of diabetes occurred. Among women with gestational diabetes recognised on the basis of the tests results (screening or diagnostic), 1/3 of patients had no evidence of any risk factor. There is no correlation between the number of risk factors and the occurrence of gestational diabetes. The risk factors were present in half of the investigated patients.

[The effect of selected factors on the birthweight of the newborns in gestational diabetes]. / Wplyw wybranych czynników na mase urodzeniowa noworodków matek z cukrzyca ciezarnych.

Fetal macrosomia is commonly associated with gestational diabetes mellitus (GDM) which may lead to various complications. We attended to establish maternal constitutional and metabolic risk factors responsible for the genesis of macrosomia. 219 GDM mothers were divided into two groups treated by diet or insulin. This study shows that maternal glycemic status and maternal nutritional status before pregnancy are important determinants of fetal macrosomia.

[Factors affecting birthweight in insulin-dependent diabetes mellitus pregnancy]. / Wplyw wybranych czynników na mase urodzeniowa noworodków matek z przedciazowa cukrzyca insulinozalezna.

Fetal growth is affected by various maternal factors. Metabolic disturbances often present in pregnancy complicated by insulin-dependent diabetes mellitus may have important effect on birthweight. The aim of this study was to evaluate the influence of maternal morphometric and metabolic factors on birthweight parameters in women with IDDM. Data were analyzed from 124 diabetic women who delivered in I Department of Obstetrics and Gynaecology University Medical School in Warsaw between 1989-1998. Maternal morphometric factors, glycemic control, insulin requirement, glycosylated hemoglobin and fructosamine levels were correlated with birthweight and birthweight ratios. Glycemic control in first weeks of second part of pregnancy as well as maternal height and weight gain during pregnancy affected birthweight in women with insulin-dependent diabetes mellitus.

[Influence of intelligence level of the type I diabetic patients handling hi-tech glycemia monitoring system on the effectiveness of intensive insulin treatment]. / Wplyw poziomu inteligencji pacjentów z cukrzyca typu 1 stosujacych wysokospecjalistyczny system monitorujacy glikemie na wyniki intensywnej insulinoterapii podczas ciazy.

An intensive care system designed and developed in IBBE PAS allows for electronic storage and automatic transmission of BG values and other parameters directly from a patient's BG meter and electronic logbook (Glucometer M+ Bayer) to central clinical computer by telematic connection. Despite effort made to keep the system as simple as possible, its proper handling still requires some additional skills from the patient. Thus, effectiveness of the intensive insulin treatment supported by the system may be influenced by the patient's intelligence level. The aim of this work was to evaluate influence of the intelligence level of type 1 diabetic patients equipped with designed system on effectiveness of a long-term intensive insulin treatment. The study group consisted of 17 type 1 diabetic pregnant women randomly divided in two sub-groups. Eight patients used the transmission system and the remaining 9 patients were treated classically. Patient's intelligence level was assessed according Wechsler scale. Analysis of variance indicated that intelligence level did not influence significantly on average result of the treatment (p > 0.05) in whole study group and in both subgroups. Generally, in patients with lower (93 +/- 2.0) and higher (114.1 +/- 1.2) intelligence level glycemic control indices were found to be similar and did not differ significantly. Performed analysis indicated that the designed system could be properly handled by diabetic patients within wide range of intelligence level. However, despite not statistically significant influence of the patients intelligence level on obtained glycemic control, tendency was observed to obtain better average long-term glycemic control in patients with lower intelligence level using telematic data transmission in comparison with the patients treated in classical way (SDWG = 7.0 +/- 0.4 vs. 8.1 +/- 1.0 mmol/l and J = 30.3 +/- 4.4 vs. 39.0 +/- 12.2).

[The effectiveness of prenatal steroid and ambroxol therapy for the prevention of respiratory distress syndrome in newborns of diabetic mothers]. / Profilaktyka zaburzen oddychania noworodków u ciezarnych z przedciazowa cukrzyca insulinozalezna.

The aim of the study was to determine the effectiveness of antenatal steroids and ambroxol in reduction of respiratory distress syndrome (RDS) in newborns of diabetic mothers. A retrospective chart review was done on 101 diabetic gravidas who were hospitalised at 1st Department of Obstetrics and Gynaecology Medical University in Warsaw between January 1989 and December 1999. We studied the neonatal outcomes for women with diabetes mellitus who delivered before 37 gestational weeks depend on exposition to antenatal steroids or ambroxol. Both groups were compared with unexposed neonates for respiratory distress syndrome. Frequency of occurrence and severity of RDS were similar in all study subgroups. We did not found reduction of respiratory distress syndrome in newborns of diabetic mothers exposed to antenatal steroids or ambroxol.

[The influence of prenatal glucocorticoids on glycemic control among pregnant women with type I diabetes]. / Wplyw sterydoterapii stosowanej w profilaktyce zaburzen oddychania na gospodarke weglowodanowa ciezarnych z cukrzyca przedciazowa insulinozalezna.

The purpose of this study was to determine the impact of glucocorticoids treatment, administered for a severe risk of premature delivery. The study material consisted of 30 diabetic mothers treated with intensive insulin therapy. The effects of steroid treatment on glucose level two days prior, one day prior, during 1-, or 2-, or 3-days therapy and the first 2 days following treatment were determined. No case of ketoacidosis was reported.