Real-life effectiveness of antiviral therapy for HCV infection with pangenotypic regimens in HIV coinfected patients.

BACKGROUND: The aim of this study was to evaluate the real-life efficacy of pangenotypic antivirals in HIV-HCV-positive patients. RESEARCH DESIGN AND METHODS: The analysis included 5650 subjects who were treated with pangenotypic anti-HCV drugs: 5142 were HCV-positive and 508 were HIV-HCV-positive. RESULTS: Patients with HCV-monoinfection were older (p < 0.0001), however patients with HCV-monoinfection had a higher proportion of advanced fibrosis F4 (p < 0.0001). There were no differences between the study groups in the rate of SVR12 in ITT-analysis (87,6% versus 93,9% in coinfection and monoinfection group, respectively; p > 0.05). However, there was a difference between study groups in PP-analysis, HIV/HCV and HCV, respectively 95.9% vs 97.9%, p = 0.0323. Additionally, there were a higher rate of patients who did not apply for follow-up (SVR12) in coinfected patients (7,9% vs 3,6% respectively p = 0.0001). In multivariante analysis, factors associated with worse response to the pangenotypic anti-HCV therapy included male sex, HCV genotype 3, stage of fibrosis and decompensation of liver function and HIV coinfection. CONCLUSIONS: The real-life results of pangenotypic anti-HCV treatment are veryeffective in the group of HIV-HCV-coinfected patients. However, the finaleffectiveness is slightly lower than that obtained in HCV monoinfectedpatients.

Analysis of the prevalence of anti-SARS-CoV-2 antibodies in groups of medical and non-medical professions.

OBJECTIVES: The assessment of the prevalence of anti-SARS-CoV-2 antibodies in various professional groups is very important. Hence, the purpose of the following study was to analyze the seroprevalence of anti-SARS-CoV-2 antibodies among employees performing both medical and nonmedical professions before the launch of SARS-CoV-2 vaccination. MATERIAL AND METHODS: The study was conducted among employers of 1 of the institutions: The Provincial Specialist Hospital of Wladyslaw Bieganski in Lódz, Poland, Radio Lódz and the Border Guards of Lódz Airport. Blood samples were collected in December 2020-February 2021. Patients were screened for the presence of SARS-CoV-2 antibodies. Simultaneously respondents were asked to complete a self-designed questionnaire including demographic data, detailed profession, history of SARS-CoV-2 infection and willingness to be vaccinated against COVID-19. RESULTS: Seroprevalence was significantly higher in the group of rural residents (p < 0.012), participants who declared previous COVID-19 infection (p < 0.001) and healthcare workers (HCWs) (p = 0.002), especially nurses (35.5%, p = 0.003) and medics worked in areas dedicated to COVID-19 than in other specialties (38.7% vs. 26.8%, respectively, p = 0.017). There was no association between the presence of antibodies and the gender (p = 0.118), age (p = 0.559) or BMI (p = 0.998). CONCLUSIONS: Healthcare workers, in particular nurses, are at high risk of contracting COVID-19 in the workplace. Occupational infections can occur during occur not only during contact with the patient, but also with members of the medical team who do not show typical symptoms of the disease. Shortages in medical staff may also increase the number of infections among HCWs. Medical and hospital staff providing health services during the COVID-19 epidemic in Poland, may seek compensation in the event of consequences related to SARS-CoV-2 infection. The effectiveness of education and self-discipline in complying to safety rules among HCWs should also be constantly monitored. Int J Occup Med Environ Health. 2023;36(5):643-55.

Inflammatory and thrombotic parameters associated with the COVID-19 course in Poland (SARSTer study).

PURPOSE: The aim of the study was to assess the coagulation and inflammatory markers connected with severe course of COVID-19 and no clinical improvement. MATERIAL AND METHODS: The study population included 2590 adult patients, diagnosed with COVID-19, selected from the SARSTer national database - an ongoing project led by the Polish Association of Epidemiologists and Infectiologists and supported by the Medical Research Agency. Clinical and laboratory parameters, such as C-reactive protein (CRP), white blood cells (WBCs), neutrophil and lymphocyte count, procalcitonin, ferritin, interleukin-6 (IL-6), D-dimer concentration and platelet (PLT) count were analyzed before and after treatment (remdesivir, tocilizumab, dexamethasone, anticoagulants). RESULTS: Significant differences between patients with mild and severe course of the disease were observed in all examined parameters before treatment (p â€‹< â€‹0.05). After treatment only ferritin concentration did not differ significantly. In patients with pulmonary embolism, CRP concentration, neutrophil count, D-dimer and IL-6 concentration were significantly higher than in patients without embolism (p â€‹< â€‹0.05). The significant differences between the groups with and without fatal outcome were observed within all analyzed parameters. Significant differences in all examined parameters before treatment were observed between patients with and without clinical improvement (p â€‹< â€‹0.05). Multivariate logistic regression showed that no clinical improvement was associated with: IL-6>100 â€‹pg/ml (OR-2.14), D-dimer concentration over 1000 â€‹ng/ml (OR-1.62) and PLT count below 150,000/µl (OR-1.57). CONCLUSIONS: Severe course of the disease is associated with lower PLT and lymphocyte count, higher D-dimer, CRP, neutrophil count and IL-6 concentration. The best predictors of no clinical improvement in COVID-19 are: IL-6>100 â€‹pg/ml, D-dimer>1000 â€‹ng/ml and PLT<150,000/µl.

Effectiveness of Tocilizumab with and without Dexamethasone in Patients with Severe COVID-19: A Retrospective Study.

PURPOSE: The pathogenesis of coronavirus disease 2019 (COVID-19) is complicated, and in addition to antiviral therapy and combating coagulopathy, treatment should also include inhibition of the proinflammatory cytokines overproduction. The purpose of this study is to compare the effectiveness of tocilizumab (TCZ) and dexamethasone (DEX) administered alone or in combination in patients with severe COVID-19. PATIENTS AND METHODS: Patients were selected from the SARSTer database, containing 3330 individuals with COVID-19 treated between 1 March 2020 and 10 March 2021. The current study included adult patients with baseline oxygen saturation (SpO2) ≤90%, requiring regular or non-invasive high-flow oxygen supplementation. RESULTS: Among included 460 patients, 59 were treated with TCZ, 125 with TCZ and DEX, 169 with DEX, and 107 did not receive TCZ nor DEX. The groups were balanced regarding demographics, coexisting diseases, baseline SpO2, and comedications with remdesivir or low-molecular-weight heparin. The death rate of 6.8% was significantly lower in patients receiving TCZ alone than each arm (19.6%-23.1%), particularly in patients with interleukin-6 concentration exceeding 100pg/mL (5% vs 22.9%-51.7%, respectively). Analysis of clinical improvement demonstrated doubled, significantly higher rate after 21 and 28 days in patients treated with TCZ alone (60% and 75%, respectively) compared to DEX (27.6% and 37.9%, respectively). The need for mechanical ventilation was similar in all arms. CONCLUSION: In patients with severe course of COVID-19, particularly those developing cytokine storm, administration of TCZ provides a significantly better effect than DEX regarding survival, clinical improvement, and hospital discharge rate. The combination of TCZ and DEX does not improve therapy effectiveness in patients with severe COVID-19 compared to the administration of TCZ alone.

Impact of Kidney Failure on the Severity of COVID-19.

BACKGROUND: Patients with kidney failure are at an increased risk of progression to a severe form of coronavirus disease 2019 (COVID-19) with high mortality. The current analysis was aimed to assess the impact of renal failure on the severity of COVID-19 and identify the risk factors of the fatal outcome in this population. METHODS: The analysis included patients from the SARSTer database, a national real-world study evaluating treatment for COVID-19 in 30 Polish centers. Data were completed retrospectively and submitted online. RESULTS: A total of 2322 patients were included in the analysis. Kidney failure was diagnosed in 455 individuals (19.65%), of whom 373 presented moderate stage and 82 patients, including 14 dialysis individuals, presented severe renal failure. Patients with kidney failure were significantly older and demonstrated a more severe course of COVID-19. The age, baseline SpO2, the ordinal scale of 4 and 5, neutrophil and platelet count, estimated glomerular filtration rate, and C-reactive protein concentration as well as malignancy and arterial hypertension were the independent predictors of 28-day mortality in logistic regression analysis. CONCLUSIONS: Underlying kidney disease in patients with COVID-19 is among the leading factors associated with a higher risk of severe clinical presentation and increased mortality rate.

Tocilizumab Improves the Prognosis of COVID-19 in Patients with High IL-6.

Despite direct viral effect, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore, tocilizumab (TOC), a monoclonal antibody against IL-6 receptors, was considered as a possible therapeutic option. Patients were selected from the SARSTer database, containing 2332 individuals with COVID-19. Current study included 825 adult patients with moderate to severe course. Analysis was performed in 170 patients treated with TOC and 655 with an alternative medication. The end-points of treatment effectiveness were death rate, need for mechanical ventilation, and clinical improvement. Patients treated with TOC were balanced compared to non-TOC regarding gender, age, BMI, and prevalence of coexisting conditions. Significant effect of TOC on death was demonstrated in patients with baseline IL-6 > 100 pg/mL (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.08-0.57). The best effectiveness of TOC was achieved in patients with a combination of baseline IL-6 > 100 pg/mL and either SpO2 ≤ 90% (HR: 0.07) or requiring oxygen supplementation (HR: 0.18). Tocilizumab administration in COVID-19 reduces mortality and speeds up clinical improvement in patients with a baseline concentration of IL-6 > 100 pg/mL, particularly if they need oxygen supplementation owing to the lower value of SpO2 ≤ 90%.

Real-world effectiveness and safety of direct-acting antivirals in patients with cirrhosis and history of hepatic decompensation: Epi-Ter2 Study.

BACKGROUND AND AIMS: The aim of this study was to assess the real-life effectiveness and safety of direct acting antivirals (DAAs) in patients with cirrhosis and history of hepatic decompensation compared to those with compensated cirrhosis. METHOD: Data of patients treated with DAAs and included in the EpiTer-2 database (N = 10 152) were collected retrospectively. The primary endpoint was sustained viral response (SVR) at 12 weeks posttreatment. Patients were also evaluated in terms of liver-related adverse events and treatment modification/discontinuation. RESULTS: The overall SVR rate was 91.4% in the intent to treat (ITT) analysis and 95.2% in the per-protocol (PP) analysis (P < .001). Patients with decompensated cirrhosis had lower SVR rates compared to those with compensated cirrhosis in ITT analysis (86.4% vs 92.0%, P < .001), while not in PP analysis (92.9% vs 95.5%, P > .05). Adverse events (AE) occurred 45.6% and 29.3% of patients with decompensated and compensated cirrhosis (P < .001). Patients with decompensated cirrhosis were at higher risk of death (5.4% vs 0.9%; P < .0001) or liver decompensation (21.5% vs 1.3%; P < .0001). Treatment with protease inhibitors was not associated with hepatic decompensation (P = .3). Only 82.6% of patients with decompensated cirrhosis completed DAA treatment (vs 92.8% in compensated cirrhotics; P < .0001). CONCLUSION: Despite higher frequency of AE and treatment modifications, once completed, DAAs yield comparable results for patients with decompensated and compensated cirrhosis. High rate of serious adverse events in patients with advanced liver disease treated with PI may not be related to the detrimental effect of the medications, but rather to the disease itself.

Sofosbuvir/velpatasvir in treatment-experienced HCV-infected patients - short report.

AIM OF THE STUDY: The aim of this overview was to evaluate the efficacy of sofosbuvir/velpatasvir (SOF/VEL) combination in a real-life setting, with particular regard to treatment-experienced individuals. MATERIAL AND METHODS: Seventy-five consecutive patients who were treated with SOF/VEL, completed the 12-week follow-up and had sustained virologic response (SVR) evaluated were included in the analysis. Out of them, 60 (80%) patients were treatment-naïve and 15 (20%) were treatment-experienced. RESULTS: SVR rates reached 89.4% (66/75) in the whole study group and were comparable irrespective of the fibrosis stage or HCV genotype. However, a significant difference in treatment efficacy between treatment-naïve and treatment-experienced individuals was observed, with SVR rates of 98.3% (59/60) and 46.7% (7/15), respectively (p < 0.0001). CONCLUSIONS: Further studies including large real-life cohorts of treatment-experienced patients treated with SOF/VEL are warranted to elucidate the real efficacy of this regimen as a retreatment option.

Hepatocellular carcinoma in non-alcohol fatty liver disease - changing trends and specific challenges.

Background and Aims: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. The etiology of this disease is known in 90% of the patients, and it is viral in most of the cases. According to recent predictions, nearly half of the world population will be suffering from obesity by 2030. Consequently, non-alcoholic fatty liver disease (NAFLD) may play a growing role in HCC epidemiology. In this review, we sought to explore the relationship between liver steatosis and HCC.Methods: A narrative review was conducted using the PubMed MeSH search. The eligible papers were identified using a standard PubMed search with relevant key terms and various synonyms.Results: According to the results, patients with NAFLD-HCC tended to be older than those with hepatitis C virus (HCV)-HCC, and they were more often obese and had concomitant diseases, such as diabetes. On the other hand, the synthetic liver function was better preserved in NAFLD-HCC patients, who also obtained lower scores on the Model for End-stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP). However, it has to be noted that HCC in patients with non-alcoholic steatohepatitis (NASH) may develop without underlying cirrhosis. Although NASH-HCC is usually smaller and well-differentiated compared to HCV-HCC, the prognosis is similar in both groups. Efficient HCC screening in NASH cirrhosis poses a challenge because it is difficult to perform ultrasound examination in obese patients and alfa-fetoprotein level is no longer considered reliable.Conclusions: The constantly increasing prevalence of NAFLD in the general population can contribute to a growing role of NAFLD/NASH in HCC epidemiology. Moreover, some particular challenges specific for patients with liver steatosis may impede proper HCC diagnosis, treatment and follow-up.

Prevalence of hepatitis C virus infection in patients hospitalised for ischemic heart disease versus controls - PRO-CARDIO-C study.

AIM OF THE STUDY: Ongoing national screening programmes suggest that the prevalence of chronic hepatitis C (CHC) in Poland ranges between 0.5% and 1%. It has been recently noted that patients with confirmed coronary artery disease may be at higher risk for hepatitis C virus (HCV) infection. MATERIAL AND METHODS: Testing for the presence of anti-HCV antibodies was performed in a group of patients admitted to the Cardiology Department with symptomatic ischemic heart disease (IHD) and in patients hospitalised in the Dermatology Department. RESULTS: A total of 1171 patients underwent anti-HCV testing: 672 patients in the Cardiology Department (K group) and 499 patients in the Dermatology Department (D group). Twenty-eight (2.4%) positive anti-HCV results were detected. The prevalence of positive anti-HCV antibodies in groups K and D was 2.23% and 2.61%, respectively (p > 0.05). Presence of HCV RNA was confirmed in 15 cases (1.28%) - 7 patients in group K and 8 patients in group D (1.04% and 1.6%, respectively; p > 0.05). CONCLUSIONS: Our findings suggest that this patient cohort has increased risk of HCV infection, which may influence screening strategies.

Prevalence of anti-HCV antibodies in the population of young women and general medicine patients

BACKGROUND: Comparison of the estimated prevalence of HCV infection and number of detected chronic hepatitis C (CHC) cases shows that most infections in Polish population remain undetected. Until now we have probably diagnosed and treated only approximately 20% of the whole HCV-infected population in Poland. METHODS: We performed anti-HCV antibodies testing in the groups of patients with arterial hypertension or diabetes mellitus and compared proportions of positive results with rates obtained in the group of young, healthy women aged < 35 years. All patients had positive history of at least one hospitalisation. RESULTS: The analysis of patient subgroups according to study inclusion criteria revealed the highest ratio of positive anti-HCV results in the group of young women aged < 35 years with positive history of at least one hospitalisation (5/91, 5.5%). Among patients with arterial hypertension and diabetes 6/505 (1.2%) and 1/94 (1.06%) positive anti-HCV results were detected, respectively. The difference in the proportion of positive anti-HCV results between the group of young women and subgroups of patients with arterial hypertension and diabetes was statistically significant (p=0.00327). CONCLUSION: In view of obtained results it seems reasonable to look for new risk groups of HCV infection in order to increase efficacy of screening tests.

Epidemiology of hepatitis C virus infections in Lódzkie voivodeship / Epidemiologia zakazen HCV w województwie lódzkim

INTRODUCTION: Epidemiology of HCV subtypes plays an increasing role in treatment decision making in the era of direct acting antivirals. Data on incidence of HCV subtypes in Poland are sparse and equivocal. AIM OF THE STUDY: The aim of this study was to assess the distribution of HCV subtypes basing on data collected in Lodzkie province in 2015. MATERIALS AND METHODS: Patients with chronic hepatitis C were evaluated for antiviral treatment in one of the three infectious diseases departments in Lodzkie province in 2015 and had HCV genotype/subtype determined. The exclusion criteria were as follows: HBV and/or HIV coinfection and age under 18 years old. RESULTS: The study included 555 patients aged from 18 to 87 years. The rate of women was 52.8%, mean age was 47.4 years and treatment-experienced patients comprised 22.7% of study group. Genotypes 1, 3 and 4 were detected in 512 (92.25%), 34 (6.13%) and 7 (1.26%) patients, respectively. Subtype determination was performed in 464 patients infected with HCV genotype 1. The frequency of subtype 1a and 1b was 18.8% and 81%, respectively. Mean age in patients with HCV 1a infection was 28.6 years and was significantly lower than in patients infected with HCV 1b (52.5 years, p<0.05). A significant correlation between age and HCV subtype was observed. CONCLUSIONS: Prevalence of subtype 1a in patients with chronic hepatitis C in Lodzkie province is high, moreover, this subtype dominates in population of young adults (18-29 years).

Efficacy and direct costs of chronic hepatitis C treatment with first generation NS3/4A protease inhibitors in a real life population.

INTRODUCTION: Recent years have brought a significant advance in chronic hepatitis C (CHC) treatment that includes development of direct acting antivirals (DAA). Two of them, boceprevir (BOC) and telaprevir (TVR), were first approved for treatment of patients infected with CHC genotype 1 in combination with pegylated interferon (P) and ribavirin (R). Our aim was to evaluate the efficacy and direct costs of BOC/PR and TVR/PR in a real life population. MATERIAL AND METHODS: The study included adult patients qualified for the CHC Therapeutic Programme treated with TVR/PR or BOC/PR. Treatment was continued for 24 or 48 weeks. Sustained virological response, treatment discontinuation due to adverse events and lack of virological response rates were compared. RESULTS: A total of 243 adult patients with CHC were included. TVR/PR and BOC/PR were administered in respectively 122 and 121 patients. Thirty-two patients (13%) were treatment-naïve, whereas liver cirrhosis/advanced fibrosis was observed in 138 patients (56.7%). Overall, 43.6% of patients achieved a sustained virologic response (SVR). In the BOC/PR group the SVR rate was significantly lower than in the TVR/PR group (33.1% vs. 54.1%; p = 0.00094). Lack of response to therapy was observed in 41.3% and 12.3% of patients receiving BOC and TVR, respectively (p < 0.00001). The direct cost of achieving SVR in one patient was 285 450 PLN with BOC and 185 757 PLN with TVR. CONCLUSIONS: The very low treatment efficacy may be the result of inclusion criteria that allowed treatment of patients with advanced liver fibrosis/liver cirrhosis or previous treatment failure. Telaprevir seems to be significantly more potent against hepatitis C virus, with similar safety and tolerance.

The prevalence and severity of 25-(OH)-vitamin D insufficiency in HCV infected and in HBV infected patients: a prospective study.

AIM OF THE STUDY: To assess the prevalence and severity of vitamin D insufficiency in patients with hepatitis C virus (HCV) infection and in patients with hepatitis B virus (HBV) infection. MATERIAL AND METHODS: This prospective study included 90 patients with chronic hepatitis C and 35 patients with chronic hepatitis B admitted to the Infectious Diseases Department between March 2013 and May 2014. Patients with chronic liver disease other than viral hepatitis, HIV co-infection, advanced liver disease and a history of diseases influencing vitamin D status were excluded. Serum vitamin D measurement as well as liver function, viral load, HCV genotype, interleukin 28 and liver fibrosis assessments were performed. RESULTS: In all patients, the mean vitamin D serum concentration was 18.8 (± 8.9) ng/ml. The mean vitamin D level in HBV infected patients was lower than in HCV infected patients (17.6 ng/ml vs. 19.3 ng/ml; p = 0.43). Vitamin D status was assessed in relation to viral load, HCV genotype, interleukin 28 and sex, but the differences were not significant. In both groups, serum vitamin D levels were significantly lower in winter compared to summer (14.2 ng/ml vs. 23.9 ng/ml in patients infected with HCV [p < 0.000001] and 14.7 ng/ml vs. 23.8 ng/ml in patients infected with HBV [p < 0.001]). CONCLUSIONS: Our study showed that in patients with chronic hepatitis C or chronic hepatitis B, insufficient 25(OH)D concentrations occur very often, but are not associated with poor virological characteristics. The only factor influencing the vitamin D level was the season.