BACKGROUND: NK cells phenotype and functional state in different genotypes of chronic viral hepatitis C (CVHC), depending on liver fibrosis severity, have not been sufficiently studied, which limits the possibilities for the development of pathology therapy.
METHODS: The CVHC diagnosis was based on the EASL recommendations (2018). Clinical examination with liver elastometry was performed in 297 patients with genotype 1 and in 231 patients with genotype 3 CVHC. The blood NK cells phenotype was determined by flow cytometry in 74 individuals with genotype 1 and in 69 individuals with genotype 3 CVHC.
RESULTS: The frequency of METAVIR liver fibrosis stages F3-F4 was 32.5% in individuals with genotype 3, and 20.5% in individuals with genotype 1 CVHC (p = 0.003). In patients with both genotype 1 and genotype 3 CVHC, a decrease in the total number of blood NK cells, CD56brightCD16+ NK cells and an increase in the proportion of CD56dimCD16+ NK cells, CD94+ and CD38 + CD73+ NK cells were registered in patients with fibrosis stage F3-F4 by METAVIR in comparison with persons with METAVIR fibrosis stage F0-F1.
CONCLUSIONS: In patients with both genotype 1 and genotype 3 CVHC, an imbalance in the ratio between cytokine-producing and cytotoxic NK cells and an increase in the content of NK cells that express inhibitory molecules were determined in patients with severe liver fibrosis.

UNASSIGNED: To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with nonalcoholic fatty liver disease (NAFLD) versus other risk factors.
UNASSIGNED: Different clinical and tumor characteristics are associated with HCC in the setting of NAFLD in comparison to other risk factors. It is still unclear whether these differences impact patient survival after radical hepatectomies.
UNASSIGNED: Randomized controlled trials and observational studies published in the English literature between July 1980 and June 2020 were searched using multiple databases. Patients\' baseline characteristics and the hazard ratios (HRs) of the OS and DFS were extracted and meta-analyses were performed.
UNASSIGNED: Fifteen retrospective cohort studies with a total of 7226 patients were included. Among them, 1412 patients (19.5%) had NAFLD and 5814 (80.4%) had other risk factors (eg, viral hepatitis B or C, alcoholic cirrhosis, or cryptogenic cirrhosis). Summary statistics showed that patients with NAFLD had better DFS (HR = 0.81; 95% CI: 0.70-0.94; P = 0.006) and OS (HR = 0.78; 95% CI: 0.67-0.90; P = 0.001) than the control group. Subgroups analyses also indicated that the OS favored NAFLD patients versus patients with viral hepatitis B or C (HR = 0.80; 95% CI: 0.67-0.96; P = 0.017) or alcoholic and cryptogenic cirrhosis (HR = 0.68; 95% CI: 0.47-1.0; P = 0.05).
UNASSIGNED: After hepatic resections for HCC, NAFLD patients have better DFS and OS than patients with other risk factors. Subgroup analysis and meta-regression suggested that the survival advantage of NAFLD patients was more pronounced in studies published after 2015 and from Asian centers.

The World Health Organization (WHO) aims to reduce HCV mortality, but estimates are difficult to obtain. We aimed to identify electronic health records of individuals with HCV infection, and assess mortality and morbidity. We applied electronic phenotyping strategies on routinely collected data from patients hospitalized at a tertiary referral hospital in Switzerland between 2009 and 2017. Individuals with HCV infection were identified using International Classification of Disease (ICD)-10 codes, prescribed medications and laboratory results (antibody, PCR, antigen or genotype test). Controls were selected using propensity score methods (matching by age, sex, intravenous drug use, alcohol abuse and HIV co-infection). Main outcomes were in-hospital mortality and attributable mortality (in HCV cases and study population). The non-matched dataset included records from 165,972 individuals (287,255 hospital stays). Electronic phenotyping identified 2285 stays with evidence of HCV infection (1677 individuals). Propensity score matching yielded 6855 stays (2285 with HCV, 4570 controls). In-hospital mortality was higher in HCV cases (RR 2.10, 95%CI 1.64 to 2.70). Among those infected, 52.5% of the deaths were attributable to HCV (95%CI 38.9 to 63.1). When cases were matched, the fraction of deaths attributable to HCV was 26.9% (HCV prevalence: 33%), whilst in the non-matched dataset, it was 0.92% (HCV prevalence: 0.8%). In this study, HCV infection was strongly associated with increased mortality. Our methodology may be used to monitor the efforts towards meeting the WHO elimination targets and underline the importance of electronic cohorts as a basis for national longitudinal surveillance.

The global effort to eliminate HCV infection requires new approaches to accessing and testing the affected population in a setting with as low of a threshold as possible. The focus should be on socially marginalized people who inject drugs (PWIDs) and who are not willing or able to visit standard medical services. With this vision, we established an outreach service-a testing point in an ambulance in the park in front of the Main Railway Station of the capital city of Prague-to provide bloodborne disease testing and treatment. The service was available every week on Wednesday afternoon. Over the initial two years of our experience, 168 unique people were tested. Of them, 82 (49%) were diagnosed with chronic HCV infection and were eligible for treatment with antivirals. Of these, 24 (29%) initiated antiviral treatment over the study period, and 17 (71%) of these individuals achieved a documented sustained virological response. Offering medical services in PWIDs\' neighborhoods helps overcome barriers and increase the chances that they will become patients and begin HCV treatment. The described outcomes appear promising for reaching the vision of linkage to the care of such a hard-to-reach population and can serve as a feasible model of care for further expansion.

BACKGROUND: To monitor Sweden\'s progress towards the WHO goal of eliminating viral hepatitis, we estimated the prevalence, notification rate, and liver-related morbidity and mortality for diagnosed hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in 2015 and 2018.
METHODS: We identified cases of hepatitis B and C within the National System for Notifiable Diseases and obtained data on treatment and whether the case was deceased or not. We calculated prevalence, notification rates per 100,000, and proportion of newly diagnosed cases of hepatitis with liver disease at the time of diagnosis, and proportion of all deceased cases who died from liver disease. We calculated Poisson 95% confidence intervals (CIs) around the notification rates and Wilson 95% CIs around prevalence and mortality estimates.
RESULTS: In 2015 and 2018, the prevalence of diagnosed HBV infections was 0.20% [95% CI: 0.19-0.20] and 0.21% [0.20-0.21]. Notification rates per 100,000 for HBV infections were 13.02 [12.32-13.76] and 7.71 [7.18-8.27]. HBV liver-related morbidity was 2.65% [1.90-3.68] and 2.16% [1.35-3.43]. HBV liver-related mortality was 20.00% [14.81-26.44] and 17.95% [13.20-23.94]. In 2015 and 2018, the prevalence of diagnosed HCV-infections was 0.24% [0.24-0.25] and 0.18% [0.18-0.19]. Notification rates per 100,000 for HCV infections were 15.92 [15.14-16.73] and 13.05 [12.36-13.77]. HCV liver-related morbidity was 8.14% [6.89-9.60] and 3.90% [2.99-5.08]. HCV liver-related mortality was 27.08% [24.54-29.77] and 26.90% [24.12-29.88].
CONCLUSIONS: All indicators decreased or remained stable between 2015 and 2018, indicating progress in the elimination of viral hepatitis, especially for HCV infection.

Background: The objective was to reveal the most typical changes in oral mucosa in HCV patients and compare them with those in HCV negative patients. Methods: The study involved 96 HCV patients and 100 patients without HCV who applied to a dental clinic. The content of cytokines IL-2, IL-4, IL-10 and ɤ-INF in the oral fluid was determined by ELISA. Buccal mucosa and gums biopsies passed histological examination. An immunohistochemical study of mucous membrane biopsies was performed using monoclonal mouse antibodies to CD3+ and CD20+. Results: The HCV patients group included 96 (63.5% males), and the non-HCV group included 100 subjects (62.0% males) with lesions of the oral mucous membrane. The lesions of lips and oral mucosa were more frequent in HCV than in the non-HCV group-e.g., erosion (13.5% vs. 1%), cracks in the mouth corners (42.7% vs. 0%), changes in the oral mucosa surface (89.6% vs. 3.0%), hemorrhages (78.1% vs. 0%), etc. The pro-inflammatory IL-2 level was higher and anti-inflammatory IL-4 level was lower in HCV patients compared with those in the non-HCV group. Conclusions: Morphological changes developed in the microvasculature both worsen the tissue trophism and accelerate the healing with differentiation into coarse-fibrous connective tissue. Immunohistochemical findings indicated a decrease in local humoral immune response.

Our work aimed to assess the efficacy and safety of direct-acting antiviral drugs in the treatment of hepatitis C in Madagascar.
This retrospective clinical study was carried out from March 2018 to February 2020 in the hepato-gastro-enterology department of the University Hospital Center Joseph Raseta de Befelatanana.
A total of 35 patients were included, out of which 24 received sofosbuvir/ledipasvir ± ribavirin, 10 sofosbuvir/ribavirin and one sofosbuvir/velpatasvir. Thirty-three patients were naïve to the treatment and 2 patients were initially treated with the sofosbuvir/ledipasvir combination. The sustained virologic response was 94% (33/35) in the general population, 23/25 in cirrhotic patients and 10/10 in non-cirrhotic patients. The sustained virologic response was 22/24 for sofosbuvir/ledipasvir ± ribavirin, 10/10 for sofosbuvir/ribavirin and 1/1 for sofosbuvir/velpatasvir. Adverse effects were observed in 13 patients, mainly asthenia and insomnia.
The small number of patients with hepatitis C treatments and their limited financial resources are the main limits of this survey.
Direct-acting antivirals are effective and characterized by good tolerance in these Malagasy hepatitis C patients.

The elimination of HCV (hepatitis C virus) infection is, according to WHO (World Health Organization), of international interest. With new diagnostic tools and treatment possibilities, one major challenge for the elimination is to involve infected patients, especially those from socially excluded subpopulations, into HCV infection-treatment programs. The key question is how to help people who inject drugs (PWID) to engage in HCV infection-treatment programs and improve communication between PWID and hepatologists or other medical professionals involved in the treatment of chronic HCV infection. Furthermore, the medical professionals have to accept the changing spectrum of patients with chronic viral hepatitis. Without close interdisciplinary cooperation, it would be extremely difficult to achieve the WHO goal of global viral hepatitis C elimination. Here, we try to encourage our colleagues as well as addictologists and social workers to play their crucial part in the viral hepatitis C eradication process. It is extremely important for the healthcare providers to be able to communicate with addicted clients, inform PWID about the latest developments in the diagnosis and HCV infection treatment, and get them motivated to engage with specialized treatment programs.

Hepatitis C virus (HCV)-induced liver disease contributes to chronic hepatitis. The immune factors identified in HCV include changes in the innate and adaptive immune system. The inflammatory mediators, known as \"inflammasome\", are a consequence of the metabolic products of cells and commensal or pathogenic bacteria and viruses. The only effective strategy to prevent disease progression is eradication of the viral infection. Immune cells play a pivotal role during liver inflammation, triggering fibrogenesis. The present paper discusses the potential role of markers in cell death and the inflammatory cascade leading to the severity of liver damage. We aim to present the clinical parameters and laboratory data in a cohort of 88 HCV-infected non-cirrhotic and 25 HCV cirrhotic patients, to determine the characteristic light microscopic (LM) and transmission electron microscopic (TEM) changes in their liver biopsies and to present the link between the severity of liver damage and the serum levels of cytokines and caspases. A matched HCV non-infected cohort was used for the comparison of serum inflammatory markers. We compared the inflammation in HCV individuals with a control group of 280 healthy individuals. We correlated the changes in inflammatory markers in different stages of the disease and the histology. We concluded that the serum levels of cytokine, chemokine, and cleaved caspase markers reveal the inflammatory status in HCV. Based upon the information provided by the changes in biomarkers the clinician can monitor the severity of HCV-induced liver damage. New oral well-tolerated treatment regimens for chronic hepatitis C patients can achieve cure rates of over 90%. Therefore, using the noninvasive biomarkers to monitor the evolution of the liver damage is an effective personalized medicine procedure to establish the severity of liver injury and its repair.

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.