(1) Background: Treatment of hepatitis C virus (HCV) infections with direct-acting antivirals (DAA) has demonstrated high efficacy and an excellent safety profile. The cured patients showed a sustained virological response and improved liver function, but also a continued risk of hepatocellular carcinoma (HCC) during the 2–3 years of follow-up after treatment; (2) Methods: A total of 192 patients out of 209 of the primary AMBER study were analyzed five years after treatment with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin. Results: We confirmed that HCV clearance after DAA treatment is stable regardless of baseline liver fibrosis. We found that sustained virologic response is associated with a gradual but significant reduction in liver stiffness over 5 years. Liver function improved during the first 2 years of follow-up and remained stable thereafter. The risk of death due to HCC as well as death due to HCV persists through 5 years of follow-up after successful DAA treatment. However, in non-cirrhotic patients, it appears to clear up 3 years after treatment; (3) Conclusions: Monitoring for more than 5 years after curing HCV infection is necessary to assess the long-term risk of possible development of HCC, especially in patients with cirrhosis of the liver.

Hypervariable region 1 (HVR1) contained within envelope protein 2 (E2) gene is the most variable part of HCV genome and its translation product is a major target for the host immune response. Variability within HVR1 may facilitate evasion of the immune response and could affect treatment outcome. The aim of the study was to analyze the impact of HVR1 heterogeneity employing sensitive ultra-deep sequencing, on the outcome of PEG-IFN-α (pegylated interferon α) and ribavirin treatment.

In chronic hepatitis C (CHC), characterized by exhaustion of T-cell function, increased frequencies of double-positive (DP) (CD4⁺CD8⁺) cells are present in peripheral blood. We compared the exhaustion phenotype between DP and single positive (SP) T-cells, including HCV-specific cells, and assessed the effect of successful HCV treatment on inhibitory receptors expression. Blood samples from 97 CHC patients were collected before and six months post-treatment. PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing molecule-3) expression was assessed by flow cytometry. DP T-cells displayed significantly higher PD-1 expression, lower Tim-3 expression than CD8⁺ SP T-cells and lower percentages of PD-1⁻Tim-3⁻ cells than CD4⁺ SP T-cells, both before and after treatment. PD-1⁺Tim-3⁺ DP T-cells decreased following treatment. HCV-specific cells were more frequent among DP than SP T-cells, both before and after treatment. HCV-specific DP T-cells were characterized by lower PD-1 expression, higher PD-1 and Tim-3 co-expression, and lower percentages of PD-1⁻Tim-3⁻ cells (both before and after treatment) and higher post-treatment Tim-3 than HCV-specific SP T-cells. Their percentages decreased following treatment, but the exhaustion phenotype remained unchanged. DP T-cells in CHC exhibit a distinct exhaustion phenotype from SP T-cells, and these changes mostly persist following successful treatment.

The study aimed to assess the phenomenon of achieving sustained virologic response (SVR) in patients with detectable ribonucleic acid (RNA) of hepatitis C virus (HCV) at the end of treatment (ET) with direct-acting antivirals (DAA), find how this is affected by the type of regimen, and how patients experiencing this differed from non-responders with detectable HCV RNA at the ET. The study included all consecutive patients with detectable HCV RNA at the ET selected from the EpiTer-2 database, a retrospective national multicentre project evaluating antiviral treatment in HCV-infected patients in 2015-2023. Of the 16106 patients treated with IFN-free regimens with available HCV RNA assessment at the ET and at follow-up 12 weeks after treatment completion (FU), 1253 (7.8%) had detectable HCV RNA at the ET, and 1120 of them (89%) finally achieved SVR. This phenomenon was significantly more frequent in pangenotypic regimens, 10.3% vs. 4.7% in genotype-specific options (p < 0.001), and the highest proportion was documented for glecaprevir/pibrentasvir (13.7%), and velpatasvir/sofosbuvir ± ribavirin (6.9%). Patients ET + FU- treated with these two pangenotypic regimens (n = 668) had less advanced liver disease, were less frequently infected with genotype (GT) 3, and were significantly more likely to be treatment-naïve than 61 non-responders. We documented 7.8% rate of patients with detectable HCV RNA at the ET, of whom 89% subsequently achieved SVR, significantly more frequently in the population treated with pangenotypic regimens. Less severe liver disease, more often GT3 infection, and a higher percentage of treatment-naive patients distinguished this group from non-responders.

Background: The wave of wartime migration from Ukraine has raised a number of concerns about infectious diseases, the prevalence of which is higher in Ukraine than in host countries, with hepatitis C virus (HCV) infection being one of them. Our analysis aimed to assess the percentage of HCV-infected Ukrainian refugees under care in Polish centers providing antiviral diagnosis and therapy, to evaluate their characteristics and the effectiveness of treatment with direct-acting antiviral drugs (DAAs). Methods: The analysis included patients of Polish and Ukrainian nationality treated for HCV infection between 2022 and 2024 in Polish hepatology centers. Data were collected retrospectively and completed online. Results: In the population of 3911 patients with chronic hepatitis C treated with DAAs in 16 Polish centers in 2022–2024, there were 429 war refugees from Ukraine, accounting for 11% of the total treated. The Ukrainian population was significantly younger (45.7 vs. 51 years, p < 0.001) and had a higher percentage of women (50.3% vs. 45.3%, p = 0.048) compared to Polish patients. Patients of Ukrainian origin had less advanced liver disease and were significantly less likely to have comorbidities and the need for comedications. Coinfection with human immunodeficiency virus was significantly more common in Ukrainians than in Polish patients, 16.1% vs. 5.9% (p < 0.001). The distribution of HCV genotypes (GTs) also differed; although GT1b predominated in both populations, its frequency was significantly higher in the Polish population (62.3% vs. 44.5%, p < 0.001), while the second most common GT3 was significantly more common in Ukrainian patients (30.5% vs. 16.2%, p < 0.001). Conclusions: Documented differences in patient characteristics did not affect the effectiveness of antiviral therapy, which exceeded 97% in both populations, but there was a higher rate of those lost to follow-up among Ukrainian patients.