Interferon-free therapy as the cause of white matter tracts and cerebral perfusion recovery in patients with chronic hepatitis C.

The purpose of this study was to assess cerebral microstructural and perfusion changes in patients with chronic hepatitis C virus (HCV) infection before and after interferon-free therapy, using advanced magnetic resonance (MR) techniques. Eleven HCV-positive patients underwent diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) using a 1.5T MR unit, before and 24 weeks after completion of interferon-free therapy. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts. PWI values of relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were assessed from 8 areas, including basal ganglia, and cortical and white matter locations. In HCV-positive patients therapy with ombitasvir, paritaprevir boosted with ritonavir and dasabuvir, with or without ribavirin, was scheduled. Cognitive tests were used to assess cognitive function. We found increased FA values after interferon-free therapy compared to values obtained before treatment in HCV patients in almost all white matter tracts. We also observed elevated rCBV values in basal ganglia after therapy. There were significant correlations between improvement in the score of cognitive tests and increased FA values in both inferior fronto-occipital fascicles and left posterior cingulum after treatment. Liver fibrosis regression in elastography, APRI and improvement in cognitive tests were observed. This is the first report of interferon-free therapy as the cause of white matter tracts recovery as well as cerebral perfusion improvement in HCV-infected patients, indicating better functioning of frontal lobes after interferon-free treatment.

Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial.

BACKGROUND: Hepatitis C virus (HCV) genotype 4 accounts for about 13% of global HCV infections. Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability, an unmet need exists for effective all-oral regimens. We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir, an NS5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (ombitasvir plus paritaprevir plus ritonavir), given with or without ribavirin. METHODS: In this multicentre ongoing phase 2b, randomised, open-label combination trial (PEARL-I), patients were recruited from academic, public, and private hospitals and clinics in France, Hungary, Italy, Poland, Romania, Spain, Turkey, and the USA. Eligible participants were aged 18-70 years with non-cirrhotic, chronic HCV genotype 4 infection (documented ≥6 months before screening) and plasma HCV RNA levels higher than 10,000 IU/mL. Previously untreated (treatment-naive) patients were randomly assigned (1:1) by computer-generated randomisation lists to receive once-daily ombitasvir (25 mg) plus paritaprevir (150 mg) plus ritonavir (100 mg) with or without weight-based ribavirin for 12 weeks. Previously treated (treatment-experienced) patients who had received pegylated interferon plus ribavirin all received the ribavirin-containing regimen. The primary endpoint was a sustained virological response (HCV RNA <25 IU/mL) 12 weeks after the end of treatment (SVR12). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01685203. FINDINGS: Between Aug 14, 2012, and Nov 19, 2013, 467 patients with HCV infection were screened, of whom 174 were infected with genotype 4. 135 patients were randomly assigned to treatment and received at least one dose of study medication; 86 patients were treatment-naive, of whom 44 received ombitasvir plus paritaprevir plus ritonavir and 42 received ombitasvir plus paritaprevir plus ritonavir with ribavirin, and 49 treatment-experienced patients received the ribavirin-containing regimen. In previously untreated patients, SVR12 rates were 100% (42/42 [95% CI 91·6-100]) in the ribavirin-containing regimen and 90·9% (40/44 [95% CI 78·3-97·5]) in the ribavirin-free regimen. No statistically significant differences in SVR12 rates were noted between the treatment-naive groups (mean difference -9·16% [95% CI -19·61 to 1·29]; p=0·086). All treatment-experienced patients achieved SVR12 (49/49; 100% [95% CI 92·7-100]). In the ribavirin-free group, two (5%) of 42 treatment-naive patients had virological relapse, and one (2%) of 44 had virological breakthrough; no virological failures were recorded in the ribavirin-containing regimen. The most common adverse event was headache (14 [29%] of 49 treatment-experienced patients and 14 [33%] of 42 treatment-naive patients). No adverse event-related discontinuations or dose interruptions of study medications, including ribavirin, were noted, and only four patients (4%) of 91 receiving ribavirin required dose modification for haemoglobin less than 100 g/L or anaemia. INTERPRETATION: An interferon-free regimen of ombitasvir plus paritaprevir plus ritonavir with or without ribavirin achieved high sustained virological response rates at 12 weeks after the end of treatment and was generally well tolerated, with low rates of anaemia and treatment discontinuation in non-cirrhotic previously untreated and previously treated patients with HCV genotype 4 infection. FUNDING: AbbVie.

Before and After: Attitude and Adverse Effects Induced by the First and Second Doses of mRNA BNT162b2 Vaccine among Healthcare Professionals in the First Weeks after Their Introduction in Poland.

BACKGROUND: In the last days of December 2020, the SARS-CoV-2 virus vaccine BNT162b2 (Comirnaty, Pfizer-BioNTech) was introduced, for the first time, for wide use in Poland. According to the vaccination schedule, healthcare workers were the first to receive the vaccine. The aim of this study was to analyse the attitudes of those who were determined to be vaccinated, with particular reference to their concerns, attitudes towards vaccination advocacy and sources of knowledge on vaccination, as well as the incidence of adverse reactions. METHODS: The study had a three-stage design. Respondents completed a self-administered questionnaire before receiving the 1st and 2nd vaccine doses and 2 weeks after receiving the 2nd dose. A total of 2247 responses were obtained (1340 responses in the first stage, 769 in the second and 138 in the third). RESULTS: The main source of knowledge on vaccination was the Internet (32%; n = 428). Of the respondents, 6% (n = 86) reported anxiety before the 1st dose of the vaccine, which increased to 20% (n = 157) before the 2nd dose. A declaration of willingness to promote vaccination among their families was made by 87% (n = 1165). Among adverse reactions after the 1st dose of the vaccine, respondents most frequently observed pain at the injection site (n = 584; 71%), fatigue (n = 126; 16%) and malaise (n = 86; 11%). The mean duration of symptoms was 2.38 days (SD 1.88). After the 2nd dose of vaccine, similar adverse reactions-pain at the injection site (n = 103; 75%), fatigue (n = 28; 20%), malaise (n = 22; 16%)-predominated among respondents. Those who declared having had a SARS-CoV-2 virus infection (p = 0.00484) and with a history of adverse vaccination reactions (p = 0.00374) were statistically more likely to observe adverse symptoms after vaccination. CONCLUSIONS: Adverse postvaccinal reactions are relatively common after Comirnaty vaccination but are usually mild and transient in nature. It is in the interest of public health to increase the knowledge of vaccine safety.

Tubo-ovarian abscess during therapy of chronic hepatitis C with pegylated interferon and ribavirin.

BACKGROUND: Serious infections are rare complications of standard treatment in chronic hepatitis C with pegylated interferon alpha (Peg IFN) and ribavirin. CASE: We report two cases of life-threatening tubo-ovarian abscess (TOA) in women older than 40 year of age. No casual risk factors of TOA could be identified in them. In one case septic shock and acute renal failure occured. TOA was caused by endogenic bacteria (Porphyromonas asaccharolytica in the first case and Streptococcus intermedius in the latter). Surgical treatment and interruption of IFN therapy was necessary in both cases. CONCLUSIONS: Serious gynecological infections may have the significant negative influence on chronic hepatitis C therapy outcome. Because of the risk of TOA developing during IFN therapy gynecological care is needed in chronic hepatitis C management.

[Renaissance of infectious diseases]. / Renesans chorób zakaznych.

According to the report of the National Institutes of Health (NIH) in Bethesda, Maryland, USA, infectious diseases are one of the eight most common causes of illness since 1990. Due to breaking down barriers of interspecies, the state of immunosuppression, widespread use of antibiotics, there are still new threats, and earlier known to cause disease of a different course, resistant to previously effective therapies. The evolution of infectious diseases directs our attention primarily on the validity of the principles of rational antibiotic use to the increasing resistance of microorganisms. The movements of the opponents of vaccination appear to be more effective than the planned education of doctors and their patients, and the absence of sufficient administrative control performance of vaccination, raises a serious problem in contemporary clinical researcher. Infectious diseases will continue to exist as long as host organisms. It is important to the fight against them, making the best use of expertise and funds. In such a situation, the balance may move to benefit us--humans.

Evaluation of brain volume alterations in HCV-infected patients after interferon-free therapy: A pilot study.

The study was performed to evaluate cerebral volume changes in HCV-infected subjects before and after interferon-free therapy with direct-acting antiviral agents (DAA). We aimed also to estimate the impact of successful DAA therapy on the neuropsychological state of patients. Eleven HCV genotype 1 (GT1) patients treated with ombitasvir/paritaprevir (boosted with ritonavir) and dasabuvir, with or without ribavirin underwent brain magnetic resonance (MR) before and 24 weeks after completion of therapy. All patients achieved sustained viral response. Precise automatic parcellation was made using the fully-available software FreeSurfer 6.0. Statistically significant volume deceleration six months after treatment was found in the subcallosal cingulate gyrus, transverse frontopolar gyri and sulci, anterior segment of the circular sulcus of the insula and horizontal ramus of the anterior segment of the lateral sulcus. After DAA therapy we found statistically significant improvement in the performance of all three tasks of the Rey Complex Figure Test that permits the evaluation of different functions (attention, planning, working,memory). Additionally, significant amelioration in Percentage Conceptual Level Responses in The Wisconsin Card Sorting Test (a neurocognitive test for assessing intellectual functioning) was also discovered. Successful interferon-free therapy may lead to transient cerebral atrophy, probably by reducing neuroinflammation and oedema. This is the first pilot study of the alterations in brain volume after successful interferon-free therapy in chronic HCV patients. Longitudinal follow-up study is needed to observe further effects of therapy on cerebral structures volume changes.

Visual and brainstem auditory evoked potentials in HCV-infected patients before and after interferon-free therapy - A pilot study.

INTRODUCTION: The aim of this study was to investigate brain bioelectrical activity disturbances in HCV-positive patients before and 24 weeks after interferon-free therapy (DAA), using visual (VEP) and brainstem (BAEP) evoked potentials and advanced magnetic resonance techniques. MATERIALS AND METHODS: 11 HCV-infected patients (6 women, 5 men, mean age 51 years old) and 30 healthy controls, sex and age-matched, were studied. Clinical neurological examinations, VEP, BAEP, diffusion tensor imaging (DTI) and perfusion weighted imaging (PWI) were performed. RESULTS: 11 patients achieved a sustained viral response, and liver fibrosis regression in APRI and in elastography were observed. The mean P100 latency was significantly shorter in HCV-patients after therapy compared to the values before treatment (p<0.05). The mean wave BAEP V latency and I-V interpeak latency were significantly longer in the HCV-infected patients before therapy compared to HCV-patients after therapy. CONCLUSIONS: This study confirms that treatment with DAA in patients with chronic HCV infection positively affects the bioelectrical activity of the brain. An increase in the amplitude of EP after treatment indicates an improvement in the activity of the cerebral cortex. EP examination may be a useful method of assessing the function of the nervous system before and after antiviral treatment.

Effect of comedication on ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin therapy in chronic hepatitis C - a real-world study.

AIM OF THE STUDY: This multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy. MATERIAL AND METHODS: Concomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool (http://www.hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used. RESULTS: Among the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic. CONCLUSIONS: Although most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions.