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Background: Hepatitis B Virus (HBV) remains a major global health challenge, with significant morbidity and mortality associated with chronic infections. Methods: This study examines the epidemiology, screening, and risk factors associated with HBV in Romania, focusing on a comprehensive national screening program, LIVE(RO)2, involving 320,000 individuals (majority of them considered vulnerable population). A questionnaire was used to collect information on the potential risk factors for HBV transmission. Results: The overall prevalence rate of HBV chronic infection among all the participants tested was 1.67% (confidence interval: 1.63–1.72%), with significant differences (p = 0.0001) between participants from the main geographical regions of residence (North-East 1.89%, South 1.38%, South-East 2.06%, and South-West 1.54%). Male persons aged 30–49 or 60–69 years old, from the rural and Eastern parts of Romania and non-Romanian ethnia, with a low level of education, unvaccinated, not married, unemployed, with family members with hepatitis, with personal histories of blood or blood product transfusion, surgical interventions, tattooing, hospitalizations, imprisonment, haemodialysis, unsafe sexual contacts, or with sexual transmitted infectious diseases were risk factors associated with HBsAg seropositivity. Conclusions: Our findings highlight significant demographic and epidemiological patterns of reduced HBV prevalence even in vulnerable persons, as well as modified risk factors and the impact of socio-economic factors. [ABSTRACT FROM AUTHOR]

Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with an unpredictable course and a remitting–relapsing evolution. Fatigue is a frequent complaint in patients with IBD, affecting approximately half of the newly diagnosed patients with IBD. The aim of this study was to analyze fatigue in patients with IBD in remission. Materials and Methods: One hundred nineteen consecutive outpatients diagnosed with IBD for over 3 months that were in corticosteroid-free clinical and biochemical remission at the time of assessment were included in this cross-sectional study. Out of them, 72 (60.5%) were male; the median age was 39 years (IQR 30–47). Seventy-seven patients (64.7%) were diagnosed with Crohn's disease and forty-two (35.3%) with ulcerative colitis, with a median disease duration of 6 years (IQR 2–10). Fatigue, health-related quality of life (HR-QoL), anxiety and depression were evaluated using the following self-administered questionnaires: FACIT Fatigue, IBDQ 32 and HADS. Results: The mean FACIT-Fatigue score was 41.6 (SD ± 8.62), and 38.7% of patients were revealed as experiencing fatigue when a cut-off value of 40 points was used. The mean IBDQ 32 score was 189.4 (SD ± 24.1). Symptoms of anxiety and depression were detected in 37% and 21% of the patients, respectively. In the multivariate analysis, fatigue was significantly associated with lower HR-QoL (OR 2.21, 95% CI: 1.42–3.44, p < 0.001), symptoms of anxiety (OR 5.04, 95% CI: 1.20–21.22, p = 0.008), female sex (OR 3.32, 95% CI: 1.02–10.76, p = 0.04) and longer disease duration (OR 1.13, 95% CI: 1.01–1.27, p = 0.04). Conclusions: Fatigue is highly prevalent even in patients with inactive IBD and is correlated with lower HR-QoL and anxiety, as well as with clinical factors such as longer disease duration and female sex. [ABSTRACT FROM AUTHOR]

Post liver transplantation (LT) fibrosis has a negative impact on graft function. Cytokine production in the host immune response after LT may contribute to the variable CYP3A-dependent immunosuppressive drug disposition, with subsequent impact on liver fibrogenesis, together with host-related factors. We aimed to investigate whether the cytochrome P4503A5*3 (CYP3A5*3) or TBX21 genotypes impact post-LT liver fibrogenesis. Furthermore, the impact of immunosuppressants on cellular apoptosis has been evaluated using human hepatocytes harvested from cirrhotic explanted livers. We have enrolled 98 LT recipients that were followed for occurrence of liver fibrosis for at least 12 months. There was a statistically significant higher trough level of TAC in patients with homozygous CC-TBX21 genotype (7.83 ± 2.84 ng/ml) vs. 5.66 ± 2.16 ng/ml in patients without this genotype (p = 0.009). The following variables were identified as risk factors for fibrosis ≥2: donor age (p = 0.02), neutrophil to lymphocyte ratio (p = 0.04) and TBX21 genotype CC (p = 0.009). In the cell culture model cytometry analysis has indicated the lowest apoptotic cells percentage in human cirrhotic hepatocytes cultures treated with mycophenolate mofetil (MMF) (5%) and TAC + MMF (2%) whereas the highest apoptosis percentage was registered for the TAC alone (11%). The gene expression results are concordant to cytometry study results, indicating the lowest apoptotic effect for MMF and MMF + TAC immunosuppressive regimens. The allele 1993C of the SNP rs4794067 may predispose to the development of late significant fibrosis of the liver graft. MMFbased regimens have a favourable anti-apoptotic profile in vitro, supporting its use in case of LT recipients at high risk for liver graft fibrosis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with an unpredictable evolution that can have a negative impact on patients' quality of life (QoL). Even though patients in remission have a better QoL compared to patients with active disease, they still have a lower QoL compared to healthy people. The aim of this study is to identify the factors that are associated with a lower QoL in patients with IBD in clinical remission, in a tertiary IBD center in Romania. Materials and Methods: Ninety-seven adult patients with a current diagnosis of IBD for over 3 months who were in clinical remission were enrolled in this study. Pregnant women, patients with ostomy, perianal disease, extraintestinal manifestations or other significant comorbidities were excluded. Out of the 97 patients, 63.9% were men. The median age was 39 years (IQR 29–47), and the median disease duration was 5 years (IQR 2–10). Disease activity was assessed using the SCCAI score for ulcerative colitis and HBI score for Crohn's disease. Remission was defined for SCCAI score ≤ 1 and HBI score ≤ 4. The health-related quality of life (HR-QoL) was assessed using the IBDQ32 score. FACIT-Fatigue was used to evaluate the level of fatigue. Patients with symptoms of anxiety or depression were identified with the HADS score. Symptoms of anxiety were considered when HADS-A >7 points and symptoms of depression when HADS-D >7 points. Results: Sixty-five patients (67%) were diagnosed with CD and the remaining 32 (33%) with UC. Ninety-three patients (95.9%) were on biological therapy. The mean IBDQ score (total score) was 190.54 points (SD +/− 8.2). The mean FACIT Fatigue score was 42.5 (SD +/− 8.2), with 6.2% of patients suffering from severe fatigue (FACIT Fatigue < 30 points). A total of 33% of patients had symptoms of anxiety and 16.5% of depression. Exposure to more than one biologic therapy (p = 0.02), fatigue (p < 0.001) and symptoms of anxiety (p < 0.001) were associated with a lower HR-QoL in the multivariate analysis. Female patients, patients with Crohn's disease, patients with anemia and patients with symptoms of depression also had a lower HR-QoL, but this did not reach statistical significance in our study. Conclusions: Exposure to a higher number of biological agents (patients that switched multiple biologics), the presence of fatigue and symptoms of anxiety impair the HR-QoL of patients with IBD in clinical remission. Further studies should assess in a prospective manner whether early identification of these factors with prompt clinical interventions could lead to a better HR-QoL in these patients. [ABSTRACT FROM AUTHOR]

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Several biologic treatments are available in addition to intravenous also in subcutaneous form for treatment of chronic diseases. Benefits of the subcutaneous application of drugs include self-administration by the patient, shorter time of application process with less infusion related adverse events and consequently lower healthcare costs. With appropriate education and support patients are able to administer their treatments at home. This leads to improvement of quality of life, reduction of time needed to travel to the healthcare institution and consequently also reduces costs also for the patient. Over one million residents in the USA and 2.5 million in Europe are estimated to have inflammatory bowel disease (IBD), with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients. The Virtual Community Meeting, which offered an exchange of experience and opinions from healthcare professionals who are active in treating IBD, and patients with this chronic disease, revealed in-depth arguments and answers to some essential questions: which patients prefer subcutaneous over intravenous dosing; which patients continue to favour intravenous infusions; what are the limitations regarding both applications; what is the patient's role in therapeutical decision-making and how does IBD affect the patient's work, finances and quality of life? The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from the health-economic, scientific, and personal perspectives. The meeting offered strong confirmation that most of the patients and healthcare professionals prefer subcutaneous over intravenous drug administration but emphasise the management of risks associated with treatment compliance. Patient education provided by the IBD team in this regard is mandatory. Quality of life of patients is poorer during active disease, but the findings that it can improve over time, including as a result of home- or self-administration of biologics, may be encouraging for individuals with this chronic disease. [ABSTRACT FROM AUTHOR]

Background and Aims: We assessed the clinical and economic impact of direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV) in England, Italy, Romania and Spain. Methods: An HCV progression Markov model was developed considering DAA eligibility and population data during the years 2015‐2019. The period of time to recover the investment in DAAs was calculated as the cost saved by avoiding estimated clinical events for 1000 standardized treated patients. A delayed treatment scenario because of coronavirus disease (COVID‐19) was also developed. Results: The estimated number of avoided hepatocellular carcinoma, decompensated cirrhosis and liver transplantations over a 20‐year time horizon was: 1,057 in England; 1,221 in Italy; 1,211 in Romania; and 1,103 in Spain for patients treated during 2015‐2016 and 640 in England; 626 in Italy; 739 in Romania; and 643 in Spain for patients treated during 2017‐2019. The cost‐savings ranged from € 45 to € 275 million. The investment needed to expand access to DAAs in 2015‐2019 is estimated to be recovered in 6.5 years in England; 5.4 years in Italy; 6.7 years in Romania; and 4.5 years in Spain. A delay in treatment because of COVID‐19 will increase liver mortality in all countries. Conclusion: Direct‐acting antivirals have significant clinical benefits and can bring substantial cost‐savings over the next 20 years, reaching a Break‐even point in a short period of time. When pursuing an exit strategy from strict lockdown measures for COVID‐19, providing DAAs should remain high on the list of priorities in order to maintain HCV elimination efforts. [ABSTRACT FROM AUTHOR]

Abstract: Background: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real‐life data are still needed in order to confirm this profile. Material and methods: In Romania, through a nationwide government‐funded programme in 2015‐2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post‐treatment (SVR12). Results: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow‐up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro‐inflammation (severity score 3‐Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention‐to‐treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105/mm3(P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). Conclusions: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count. [ABSTRACT FROM AUTHOR]

Aim: to compare the efficacy and safety of Adalimumab(ADA) and Infliximab(IFX), in a large Romanian population and to identify predictors of response. Methods We performed a national retrospective cohort study including 265 patients (136 ADA, 129 IFX) between 2008-2014. Binary logistic regression was performed with the statistical program Minitab. Results: Patients were half women, with a median age of 36, a median disease duration of 2.5 years, 80% received Azathioprine. Mean therapy duration was 20 months in ADA group and 36 months in IFX group. Complete response to Adalimumab respectively Infliximab was recorded in 77%vs.65%, secondary loss of response in 18%vs.28%, statistically comparable. We failed to identify predictors of response. In 79.2%of patients with secondary loss of response to ADA, the dose was escalated, 12.5% were switched to Infliximab. In 70%of patients that lost response to IFX, the dose was increased, 30% were switched to Adalimumab. Conclusions: Adalimumab and Infliximab have similar efficacy, with a complete response rate of~70%. In case of secondary loss of response to IFX, the best solution is to switch to ADA, with 83% response rate, while in case of secondary loss of response to ADA, increasing the dose leads to 84 % response rate. [ABSTRACT FROM AUTHOR]

Aim: We evaluated the influence of the type of needle and the operator's experience on the quality of the specimen obtained at liver biopsy (LB). Material and method: We performed a multicentre, prospective study in four university hospitals, including LBs performed using either 'cutting' (TruCut) or 'suction' (Menghini) needles. According to their experience, we considered the operators as 'junior' (<100 LBs) or 'senior' (>100 LBs). Results: A total number of 745 LBs were evaluated, 413 performed with suction needles and 332 with cutting needles. Of all LBs, 473 where performed by 'senior' and 272 by 'junior' operators. The mean length of the fragment obtained was larger in LBs performed by senior (23.5±11.6 mm) vs. junior operators (15.9±9.8 mm, p<0.001) and also if modified Menghini needles were used (23.7±12.1 mm) vs. TruCut (13.0±5.2 mm, p<0.001). The number of portal tracts (PT) was higher in LBs performed by 'senior' (14.3±8.8 PT) vs. 'junior' operators (8.8±6.8 PT, p<0.001); and with Menghini needles (17.2±9.7 PT) vs. TruCut (8.6±5.0 PT, p<0.001). Conclusion: Our study demonstrates that optimal biopsy samples are obtained by two intrahepatic passages with Menghini needles and that 'senior' operators obtain better tissue samples than 'junior' ones. [ABSTRACT FROM AUTHOR]

A 46-yr-old female with hepatocellular carcinoma and severe hepatitis B-related liver cirrhosis received a domino liver graft from a 25-yr-old female with homozygous familial hypercholesterolemia (HFHC) in September 2001. Hypercholesterolemia occurred in the graft recipient within one yr after transplantation and was partially controlled by atorvastatin. Three yr after transplantation, an autologous CD34+ cell transplantation was performed in order to better control the hypercholesterolemia. Only preliminary results of this domino liver transplantation (DLT) were published in 2003, without a long-term analysis of the hypercholesterolemic effects in recipient. Subsequent to DLT, the average plasma cholesterol level in the domino donor rapidly normalized and seven yr after had a value of 182 mg/dL. After seven-yr follow-up, the domino recipient has no hepatocarcinoma recurrence. Moreover, no signs of cardiovascular or atherosclerotic lesions were noted despite an elevated plasma cholesterol level (339 mg/dL after seven yr of follow-up) resistant to drug therapy and stem cell autotransplantation. In conclusion, DLT using a liver graft from a patient with HFHC provides a viable option for marginal recipients. [ABSTRACT FROM AUTHOR]

The paper is concerned with the determination of blood permittivity and conductivity in Poiseuille and Couette simple shear flows. The experimental procedure, based on dielectric spectroscopy, evidences the sensitivity of blood electric properties to the applied frequency and local shear rate magnitude. The method evidences the possibility to correlate (for well‐defined flow geometry) magnitude of shear rate, and consequently the shear stress level, with spectra permittivity of blood. [ABSTRACT FROM AUTHOR]

Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy. [ABSTRACT FROM AUTHOR]

Background. Bevacizumab (Bev) is approved in Europe and USA in combination with chemotherapy (CTH) based on fluoropirimidine (FP) in the treatment of adult patients with metastatic colorectal cancer (mCRC) in the first line of therapy, as maintenance treatment, postprogression, and in the second line of therapy. It was performed a retrospective analysis on mCRC patients treated with CTH + Bev in succesive lines in the Medical Oncology Department of the Fundeni Clinical Institute, Bucharest. Method. We collected demografic and clinical data: the disease stage at diagnosis, histopathology data, duration and CTH line, grade 3/4 adverse events, response rate (RR), progression-free survival (PFS), and overall survival (OS). Between August 2007 and December 2018 there had been treated with Bev 516 patients. At 3-6 months from the diagnosis, 384 patients (67.4%) presented synchronous metastases and 168 patients (32.6%) presented metachronous metastases. Results. A total of 358 patients (69.2%) received Bev in the first line of the treatment, of which 260 patients (72.6%) received FP + oxaliplatin (OX): FOLFOX/CAPOX, and 86 patients (24%) received FP + irinotecan(IRI): FOLFIRI/ CAPIRI. Four patients received FOLFOXIRI in the first line, and eight patients received only FP. As maintenance therapy, it was administered Bev/Bev+FP in 88 patients (79.3%) in the OX group and in 20 patients (18%) in the IRI group. A total of 128 patients (35.8%) received Bev beyond progression, of which 99 patients (79.8%) in the OX group and 22 patients (17.7%) in the IRI group; 137 patients (38.3%) received subsequent therapy lines after Bev failure. The medium chemotherapy duration for patients who received OX was 9.9 months (95% CI; 8.67-11.18), and 9.2 months (95% CI; 6.72-11.62) for those who received IRI. A total of 219 patients presented a therapy response, with a RR of 75.34% on OX, and a RR of 24.65% on IRI. The median PFS was 8.12 months (95% CI; 6.89-9.35) for OX and 8.35 months (95% CI; 6.6-10.1) for IRI, with p=0.034. The median OS was 17.03 months (95% CI; 14.66-19.40) for OX and 18.87 months (95% CI; 15.28-22.46) for IRI, with p=0.900. Conclusions. In our experience, Bev-OX had a similar efficacy as Bev-IRI regarding both PFS and OS, but with a higher response rate for those treated with OX. [ABSTRACT FROM AUTHOR]