Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

Hepatitis C screening in Lithuania: first-year results and scenarios for achieving WHO elimination targets.

BACKGROUND: The World Health Organization (WHO) has outlined a set of targets to achieve eliminating hepatitis C by 2030. In May 2022, Lithuanian health authorities initiated a hepatitis C virus (HCV) screening program to start working towards elimination. In the program, bonus was given to general practitioners (GPs) to promote and conduct anti-HCV tests for two situations: (1) one time testing for individuals born in 1945-1994 and (2) annual HCV testing for persons who inject drugs or are living with human immunodeficiency virus (HIV) regardless of age. This study aimed to model the current viral hepatitis C epidemiological status in Lithuania and to outline the requirements for WHO elimination targets using the first-year HCV screening results. METHODS: Individuals were invited to participate in the anti-HCV screening by GPs during routine visits. Patients who tested positive were then referred to a gastroenterologist or infectious disease doctor for further confirmatory testing. If a patient received a positive RNA test and a fibrosis staging result of ≥ F2, the doctor prescribed direct-acting antivirals. Information on the patients screened, diagnosed, and treated was obtained from the National Health Insurance Fund. The Markov disease progression model, developed by the CDA Foundation, was used to evaluate the screening program results and HCV elimination progress in Lithuania. RESULTS: Between May 2022 and April 2023, 790,070 individuals underwent anti-HCV testing, with 11,943 individuals (1.5%) receiving positive results. Anti-HCV seroprevalence was found to be higher among males than females, 1.9% and 1.2%, respectively. Within the risk population tested, 2087 (31.1%) seropositive individuals were identified. When comparing the screening program results to WHO elimination targets through modelling, 2180 patients still need to be treated annually until 2030, along with expanding fibrosis restrictions. If an elimination approach was implemented, 1000 new infections would be prevented, while saving 150 lives and averting 90 decompensated cirrhosis cases and 110 hepatocellular carcinoma cases. CONCLUSIONS: During the first year of the Lithuanian screening program, GPs were able to screen 44% of the target population. However, the country will not meet elimination targets as it currently stands without increasing treatment levels and lifting fibrosis restrictions.

Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Elevated Cardiac Troponin I as a Mortality Predictor in Hospitalised COVID-19 Patients.

Background and Objectives: SARS-CoV-2 affects multiple organ systems, including the cardiovascular system, leading to immediate and long-term cardiovascular complications. Acute myocardial injury is one of the earliest and most common cardiac issues in the acute phase of COVID-19. This study aimed to evaluate the prognostic value of cardiac troponin I (cTnI) levels in predicting in-hospital mortality among hospitalised COVID-19 patients. Materials and Methods: A retrospective observational cohort study included 2019 adult patients hospitalised with a confirmed COVID-19 infection stratified by cTnI levels on admission into three groups: <19 ng/L (1416 patients), 19-100 ng/L (431 patients), and >100 ng/L (172 patients). Myocardial injury was defined as blood serum cTnI levels increased above the 99th percentile upper reference limit. Depersonalised datasets were extracted from digital health records. Statistical analysis included multivariable binary logistic and Cox proportional hazards regressions. Results: Overall, 29.87% of patients experienced acute myocardial injury, which development was associated with age, male sex, chronic heart failure, arterial hypertension, obesity, and chronic kidney disease. Among patients with cTnI levels of 19-100 ng/L, the odds ratio for requiring invasive mechanical ventilation was 3.18 (95% CI 2.11-4.79) and, for those with cTnI > 100 ng/L, 5.38 (95% CI 3.26-8.88). The hazard ratio for in-hospital mortality for patients with cTnI levels of 19-100 ng/L was 2.58 (95% CI 1.83-3.62) and, for those with cTnI > 100 ng/L, 2.97 (95% CI 2.01-4.39) compared to patients with normal cTnI levels. Conclusions: Increased cardiac troponin I, indicating myocardial injury, on admission is associated with a more adverse clinical disease course, including a higher likelihood of requiring invasive mechanical ventilation and increased risk of in-hospital mortality. This indicates cardiac troponin I to be a beneficial biomarker for clinicians trying to identify high-risk COVID-19 patients, choosing the optimal monitoring and treatment strategy for these patients.

Characteristics of COVID-19 Disease in Renal Transplant Recipients.

Background and Objectives: Kidney transplant recipients are at risk of developing more severe forms of COVID-19 infection. The aim of this study was to compare the clinical course of COVID-19 infection among kidney transplant patients and a control group. Materials and Methods: We examined 150 patients hospitalized with COVID-19 infection. Patients were divided into study (kidney transplant recipients, n = 53) and control (without a history of kidney transplantation, n = 97) groups. Demographics, clinical characteristics, treatment data, and clinical outcomes were assessed. Results: The median patient age was 56.0 (46.0-64.0) years, and seventy-seven patients (51.3%) were men. The median Charlson comorbidity index was higher in the study group (3.0 vs. 2.0, p < 0.001). There was a higher incidence of hypoxemia in the control group upon arrival (52.6% vs. 22.6%, p = 0.001) and a higher NEWS index median (2.0 vs. 1.0 points, p = 0.009) and incidence of pneumonia during hospitalization (88.7% vs. 73.6%, p = 0.023). In the study group, there were more cases of mild (26.4% vs. 11.3%, p = 0.023) and critically severe forms of COVID-19 infection (26.4% vs. 3.1%, p < 0.001), kidney failure was more prevalent (34.0% vs. 1.0%, p < 0.001), and a greater number of patients were transferred to the intensive care unit (22.6% vs. 3.1%, p < 0.001) and died (18.9% vs. 1.0%, p < 0.001). Multivariable analysis revealed that treatment in the intensive care unit correlated with a higher mortality rate than transplantation itself (HR = 20.71, 95% CI 2.01-213.33, p = 0.011). Conclusions: The course of the COVID-19 disease in kidney transplant recipients is heterogeneous and can be more severe than in the general population. Even though patients may be hospitalized with fewer symptoms, complications and death are more likely to occur.

Influenza vaccine effectiveness in patients hospitalized with severe acute respiratory infection in Lithuania during the 2019-2020 influenza season: a test negative case - control study.

BACKGROUND: Influenza is a contagious viral airborne disease that adds to the clinical and economic burden on the healthcare system. It could be prevented substantially by seasonal influenza vaccination. Seasonal influenza vaccine effectiveness (SIVE) varies a lot and should therefore be monitored. This report aims to update age-stratified SIVE estimates among patients hospitalized due to severe acute respiratory infection (SARI) during the 2019-2020 influenza season. METHODS: We performed a test-negative case-control study between December 2019 and April 2020 influenza season. We estimated SIVE and its 95% confidence intervals (95% CI) with logistic regression as (1-odds ratio)*100%. The models were adjusted for covariates that changed the unadjusted SIVE by ≥ 10%. RESULTS: Among 84 participants, 32 (38.1%) were influenza positive, mostly with A(H1N1)pdm09 (25 cases; 78.1%). SIVE against any influenza adjusted for age and heart disease was 39.2% (95% CI: -119.3%, 83.1%). Age-stratified point estimates adjusted for heart diseases indicated different SIVE, and were 64.0% (95% CI: -309.2%, 96.8%) and 21.6% (95% CI: -252.2%, 82.6%) for 18-64 and ≥ 65 year-old participants, respectively. CONCLUSIONS: The point estimates suggested low to moderate SIVE against any influenza among hospitalized 18-64-year-old SARI participants, while low estimates were found in the ≥ 65-year-old group. Although broad SIVE confidence intervals indicate a small sample size and therefore the results can serve only as indicatory, they are in line with the estimates reported by other studies during the 2019-2020 season.

The Association between COVID-19 Infection and Kidney Damage in a Regional University Hospital.

Background and Objectives: Kidneys are one of the main targets for SARS-CoV-2. Early recognition and precautionary management are essential in COVID-19 patients due to the multiple origins of acute kidney injury and the complexity of chronic kidney disease management. The aims of this research were to investigate the association between COVID-19 infection and renal injury in a regional hospital. Materials and Methods: The data of 601 patients from the Vilnius regional university hospital between 1 January 2020 and 31 March 2021 were collected for this cross-sectional study. Demographic data (gender, age), clinical outcomes (discharge, transfer to another hospital, death), length of stay, diagnoses (chronic kidney disease, acute kidney injury), and laboratory test data (creatinine, urea, C-reactive protein, potassium concentrations) were collected and analyzed statistically. Results: Patients discharged from the hospital were younger (63.18 ± 16.02) than those from the emergency room (75.35 ± 12.41, p < 0.001), transferred to another hospital (72.89 ± 12.06, p = 0.002), or who died (70.87 ± 12.83, p < 0.001). Subsequently, patients who died had lower creatinine levels on the first day than those who survived (185.00 vs. 311.17 µmol/L, p < 0.001), and their hospital stay was longer (Spearman's correlation coefficient = -0.304, p < 0.001). Patients with chronic kidney disease had higher first-day creatinine concentration than patients with acute kidney injury (365.72 ± 311.93 vs. 137.58 ± 93.75, p < 0.001). Patients with acute kidney injury and chronic kidney disease complicated by acute kidney injury died 7.81 and 3.66 times (p < 0.001) more often than patients with chronic kidney disease alone. The mortality rate among patients with acute kidney injury was 7.79 (p < 0.001) times higher than among patients without these diseases. Conclusions: COVID-19 patients who developed acute kidney injury and whose chronic kidney disease was complicated by acute kidney injury had a longer hospital stay and were more likely to die.

Genotype Distribution and Characteristics of Chronic Hepatitis C Infection in Estonia, Latvia, Lithuania, and Ukraine: The RESPOND-C Study.

Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode of viral transmission was blood transfusions (17.8%), followed by intravenous substance use (15.7%); however, in 50.9% of patients, the exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%), transmission by intravenous substance use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1-66.4%; GT3-28.1; and GT2-4.1%. The prevalence of GT1 was the highest in Latvia (84%) and the lowest in Ukraine (63%, p < 0.001). Liver fibrosis stages were distributed as follows: F0-12.2%, F1-26.3%, F2-23.5%, F3-17.1%, and F4-20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p < 0.001). Conclusions: This study contributes to the knowledge of epidemiologic characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

Kinetics of SuPAR hemoadsorption in critical COVID-19 patients on renal replacement therapy.

BACKGROUND: SARS-CoV-2 viral infection is associated with a rapid and vigorous systemic inflammatory response syndrome. Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker, both indicative of inflammation and propagating it. Hemoadsorption has been proposed as a potential therapy in COVID-19 patients, therefore the aim of this study is to determine suPAR kinetics during hemoadsoprtion. METHODS: This was a prospective observational study of critical COVID-19 patients, enrolled when hemoperfusion therapy was initiated. Hemoadsorber was integrated into the continuous renal replacement therapy circuit. The first series of suPAR measurements was performed 10 minutes after the start of the session, sampling both incoming and outgoing lines of the adsorber. A second series of the measurements was performed beforefinishing the session with the same adsorber. Statistical significance level was set < 0.05. RESULTS: This study included 18 patients. In the beginning of the session the fraction of suPAR cleared across the adsorber was 29.5% [16-41], and in the end of the session it decreased to 7.2% [4-22], 4 times lower, p = 0.003. The median length of session was 21 hours, with minimal duration of 16 hours and maximal duration of 24 hours. The median suPAR before the procedure was 8.71 [7.18-10.78] and after the session was 7.35 [6.53-11.28] ng/ml. There was no statistically significant difference in suPAR concentrations before and after the session (p = 0.831). CONCLUSIONS: This study concluded that in the beginning of the hemoadsorption procedure significant amount of suPAR is removed from the circulation. However, in the end of the procedure there is a substantial drop in adsorbed capacity. Furthermore, despite a substantial amount of suPAR cleared there is no significant difference in systemic suPAR concentrations before and after the hemoadsorption procedure.

Pulmonary Coccidioidomycosis: A Case Report and Literature Review.

Coccidioidomycosis is an infectious disease caused by Coccidioides immitis or C. posadasii fungus. Humans usually get infected by inhaling spores risen from the soil. Although in 60 percent of cases symptoms are absent, remaining patients can develop various manifestations of the disease, from flu-like symptoms to severe dissemination or meningitis. In endemic regions (California, Arizona, Mexico, Central, and South America), pulmonary coccidioidomycosis causes 25% of community-acquired cases of pneumonia. We present the first registered case of pulmonary coccidioidomycosis in Lithuania. Clinical presentation, pathogenesis, treatment options, and diagnostic alternatives are discussed.

Determinants of Increased Effort of Breathing in Non-Intubated Critical COVID-19 Patients.

Background and objectives: Acute respiratory distress syndrome (ARDS) is the most common complication occurring in COVID-19 patients admitted to the ICU. Given the increased respiratory work of these patients, it is necessary to evaluate their actual breathing efforts. The aim of this study is to report the incidence and determinants of increased effort of breathing (EOB) in critical COVID-19 patients. Materials and Methods: This was a retrospective study of COVID-19 patients admitted to the ICU during the year of 2020. Respiratory rate (RR) was chosen as an indicator of EOB. The cut-off value was set at more than 20 breaths per minute. ROC-AUC analysis was performed to identify the accuracy of the PaO2 and PaCO2 to determine increased EOB. Furthermore, multivariate regression analysis was performed to reveal the determinants of increased EOB. Results: 213 patients were included in the study. Mean RR in the population was 24.20 ± 6.28. 138 (64.8%) of the patients had increased EOB. The ROC-AUC analysis revealed the PaO2 (0.656 (CI 95%: 0.579−0.734, p < 0.001) as more accurate predictor of EOB than PaCO2 (0.584 (CI 95%: 0.505−0.662, p = 0.043). In the final multivariate model, the SpO2 (exp(B) = 0.922, CI 95%: 0.874−0.97 p = 0.033), PaO2/FiO2 ratio (exp(B) = 0.996, CI 95%: 0.922−1.000, p = 0.003) and PaO2 (exp(B) = 0.989 CI 95%: 0.982−0.996 p = 0.003) prevailed as independent predictors of increased EOB. Conclusions: To conclude, PaO2 was revealed as a more accurate predictor of increased EOB than PaCO2. Further investigation revealed the independent determinants of EOB: blood oxygen saturation, PaO2 and PaO2/FiO2 ratio.

Comparison of mortality risk evaluation tools efficacy in critically ill COVID-19 patients.

BACKGROUND: As the COVID-19 pandemic continues, the number of patients admitted to the intensive care unit (ICU) is still increasing. The aim of our article is to estimate which of the conventional ICU mortality risk scores is the most accurate at predicting mortality in COVID-19 patients and to determine how these scores can be used in combination with the 4C Mortality Score. METHODS: This was a retrospective study of critically ill COVID-19 patients treated in tertiary reference COVID-19 hospitals during the year 2020. The 4C Mortality Score was calculated upon admission to the hospital. The Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II, and Sequential Organ Failure Assessment (SOFA) scores were calculated upon admission to the ICU. Patients were divided into two groups: ICU survivors and ICU non-survivors. RESULTS: A total of 249 patients were included in the study, of which 63.1% were male. The average age of all patients was 61.32 ± 13.3 years. The all-cause ICU mortality ratio was 41.4% (n = 103). To determine the accuracy of the ICU mortality risk scores a ROC-AUC analysis was performed. The most accurate scale was the APACHE II, with an AUC value of 0.772 (95% CI 0.714-0.830; p < 0.001). All of the ICU risk scores and 4C Mortality Score were significant mortality predictors in the univariate regression analysis. The multivariate regression analysis was completed to elucidate which of the scores can be used in combination with the independent predictive value. In the final model, the APACHE II and 4C Mortality Score prevailed. For each point increase in the APACHE II, mortality risk increased by 1.155 (OR 1.155, 95% CI 1.085-1.229; p < 0.001), and for each point increase in the 4C Mortality Score, mortality risk increased by 1.191 (OR 1.191, 95% CI 1.086-1.306; p < 0.001), demonstrating the best overall calibration of the model. CONCLUSIONS: The study demonstrated that the APACHE II had the best discrimination of mortality in ICU patients. Both the APACHE II and 4C Mortality Score independently predict mortality risk and can be used concomitantly.

Kidney transplantation from a SARS-CoV-2-positive donor for the recipients with immunity after COVID-19.

The coronavirus (COVID-19) pandemic is evolving very quickly and has affected healthcare systems worldwide. Many uncertainties remain about transplantation from a SARS-CoV-2-positive donor as only a few cases have been reported. Here, we present the successful transplantation of 2 kidneys from a 52-year-old male donor with active (2 weeks of COVID-19-like symptoms and positive nasopharyngeal swab SARS-CoV-2 polymerase chain reaction on the day of organ recovery) SARS-CoV-2 disease. The immediate postoperative course of both recipients was uneventful. This case emphasizes that patients with SARS-CoV-2 may be safe organ donors.

The Epidemiological Patterns of Hepatitis C in Lithuania: Changes in Surveillance from 2005 to 2018.

Background and Objectives: Viral hepatitis C infection is an important public health concern worldwide because it is one of the major global causes of death and morbidity. The early identifi-cation of infected people, together with the provision of proper treatment, are the key strategies used in preventing HCV infection. However, data regarding the epidemiological patterns of hep-atitis C in Lithuania are limited. The aim of this research was to evaluate trends in acute HCV cases registered via the national surveillance system in Lithuania during 2005-2018. Materials and Methods: Incidence rates were calculated for data, stratified by gender, age group (0-24, 25-54, 55-74, and 75+), place of residence (urban or rural), and the Lithuanian county where the case was recorded. The crude incidence rate of hepatitis C was defined as the number of new infec-tions per 100,000 people during a one-year time period. A linear regression was applied to evalu-ate IR trends during the period of 2005-2018. Results: From 2005 to 2018, 572 cases of acute hepa-titis C were registered, and the incidence rate ranged from 2.03 cases per 100,000 people in 2005 to 0.55 in 2016. A statistically significant decreasing trend in the incidence rate was found during the study period (p < 0.0001). Almost 63% of the acute HCV infections recorded via the national surveillance system were in individuals aged from 25 to 54 years. Conclusions: Being male, aged between 25 and 34 years, and living in the city might be important factors for understanding the epidemiological patterns of HCV in Lithuania. Although the number of HCV cases recorded in Lithuania is decreasing, our country has one of the highest IRs compared to other European countries. This shows that a new approach to hepatitis C virus screening strategies is needed.

A Rare Case of Tularemia Complicated by Rhabdomyolysis with a Successful Outcome.

We present a case of tularemia complicated by rhabdomyolysis in a 43-year-old male who presented with fever, swelling, and pain of the right groin and a history of a week-old tick bite. Empirical parenteral amoxicillin/clavulanic acid treatment was initiated. Suspecting tularemia, parenteral gentamycin was added. Later, the patient started to complain of muscle pain, weakness, and difficulties in breathing and walking. Heightened levels of creatine kinase and myoglobin concentration (42,670 IU/L and >12,000 µg/L, respectively) were found. Due to rhabdomyolysis, large amounts of intravenous fluid therapy were initiated to prevent kidney damage, continuing intravenous antibiotic therapy. Francisella tularensis IgG in serum was found to be positive only on the sixteenth day of hospitalization. Upon discharge, the laboratory analyses returned to normal levels, and the patient was in good condition. The successful outcome could be associated with the early appropriate therapy of tularemia and its rare complication of rhabdomyolysis.

Assessment of Liver Stiffness Regression and Hepatocellular Carcinoma Risk in Chronic Hepatitis C Patients after Treatment with Direct-Acting Antiviral Drugs.

Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023-0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.

Follow-Up Analysis of Pulmonary Function, Exercise Capacity, Radiological Changes, and Quality of Life Two Months after Recovery from SARS-CoV-2 Pneumonia.

Background and objective: According to the World Health Organization (WHO), more than 100 million people have already recovered from SARS-CoV-2 infection. Therefore, it is imperative to understand the possible outcomes of COVID-19. The aim of our study was to evaluate pulmonary function, exercise capacity, residual radiological changes, and health-related quality of life (HRQoL) at follow-up in a cohort of SARS-CoV-2 pneumonia survivors. Materials and Methods: Patients with SARS-CoV-2 infection and radiologically confirmed lung injury, with no chronic lung disease prior to this infection, were included in the study. Patients' evaluation 2 months after their discharge from hospital included spirometry (FVC, FEV1, FEV1/FVC), determination of lung volume (TLC, VC, RV) and diffusing capacity of lung for carbon monoxide (DLCO, adjusted for hemoglobin), 6-Minute Walk Test (6MWT), chest CT scan, and 36-Item Short Form General Health Survey (SF-36). Results: Fifty-one patients (25 men, 26 women) were included. The mean age was 56 years (SD-11,72). Eighteen patients (35.3%) had experienced moderate COVID-19, 21 (41.2%) severe COVID-19, and 12 (23.5%) were critically ill. The mean follow-up visit time after the discharge from hospital was 60 days (SD-17). Pulmonary function at follow-up was impaired in 24 (47.2%) patients. Reduced lung volume was observed in 15 (29.4%) patients, DLCO reduction in 15 (29.4%) patients, and only one patient displayed obstruction. Twelve patients out of 51 (12/51, 27.3%) showed reduced physical capacity in the 6 MWT, and 3/51 (9.1%) showed desaturation, with SO2 < 90%. Different levels of abnormality were found in 49/51 (96,1%) patients on follow-up chest CT; the median radiological score was 10.9 (SD ± 8.87, possible maximal score, 25). Ground-glass opacity was the most common radiological feature, found in 45 (88.2%) patients. The SF-36 scores demonstrated a reduction in health status across all domains, with the lowest scores for limitations in social activities because of physical problems, vitality, and general health. Conclusion: In the group of COVID-19 pneumonia survivors 2 months after hospital discharge, residual changes in the lungs on chest CT and in lung function and reduced physical and HRQoL status were found in a significant number of patients. To evaluate COVID-19 long-term consequences, a longer follow-up period is needed.

Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial.

BACKGROUND & AIMS: Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus (HCV) infection; however, head-to-head comparisons are limited. The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) with sofosbuvir plus pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection. METHODS: This was a randomized, open-label, phase III trial. Two hundred fifty-seven patients with HCV genotype (GT)1 or 4 infection and baseline viral load >10,000IU/ml were randomized to receive 12weeks of EBR/GZR 50mg/100mg once daily (n=129) or sofosbuvir (400mg once daily) plus PR (n=128). Primary efficacy objective was sustained virologic response 12weeks after the end of therapy (SVR12, HCV RNA <15IU/ml). The primary safety objective was the proportion of patients experiencing a tier 1 safety event. RESULTS: The majority of patients were non-cirrhotic (83.1%), treatment-naïve (74.9%) and had HCV GT1b infection (82.0%). SVR12 rates were 99.2% (128/129) and 90.5% (114/126) in the EBR/GZR and SOF/PR groups, respectively. The estimated adjusted difference in SVR12 was 8.8% (95% confidence interval [CI], 3.6-15.3%). Because the lower bound of the 1-sided 1-sample exact test was greater than -10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference, 27.0% [95% CI, -35.5% to -19.6%; p<0.001]). CONCLUSIONS: EBR/GZR has a superior efficacy and safety profile in patients with HCV GT1 or 4 infection compared with SOF/PR. LAY SUMMARY: The combination of elbasvir/grazoprevir for 12weeks was highly effective in treating patients with chronic hepatitis C, genotypes 1 or 4 infection. This regimen was more effective than sofosbuvir/pegylated interferon/ribavirin for 12weeks, and was notably superior in patients regarded as difficult to treat, including those with previous treatment failure, cirrhosis, or a high baseline viral load. The combination of elbasvir/grazoprevir also demonstrated a superior safety and tolerability profile based on fewer serious adverse events, no serious drug-related adverse events, and no treatment discontinuations. CLINICAL TRIAL REGISTRATION: Clinical trials.gov Identifier: NCT02358044.