Direct-acting Antiviral Therapy Research Articles

Hepatitis C Infection Confirmation and Fewer Visits Contribute to Improving Treatment Rates in a Predominantly African American Health Center

Background/Objectives: The approval of direct-acting antiviral (DAA) therapy for hepatitis C (HCV) resulted in a highly effective oral treatment for patients. The primary objective of this study was to identify reasons that patients were not treated versus why patients were treated. Identifying potential reasons for the failure to treat can provide a pathway to interventions using evidence-based data. Methods: The electronic medical records in an urban predominately African American (AA) population were searched for all patients with HCV seen at least once in a Gastroenterology or Infectious Disease clinic in 2019. Data collected included demographics, treatment visits, laboratory data, insurance and ZIP codes for median income. Results: Of the 441 patients who were not yet treated at the first 2019 visit, only 43% were treated by July 2020. Insurance and median income were not factors in failure to treat. Patients with an average of four visits were more likely to be treated than those with two or less, suggesting that failure to follow up was a significant factor for patient treatment (42% vs. 8% p < 0.0001). Confirmation of viral infection at first visit was an important factor with respect to treatment (treated 38% vs. not treated 25% p < 0.02). Conclusions: Significant numbers of our patients (57%) failed to be treated after at least one clinic visit. The two critical factors were PCR confirmation prior to the initial visit and the requirement for multiple visits before the initiation of treatment. Since the degree of fibrosis had no impact on treatment, initiating treatment immediately after confirming infection with HCV should improve patient treatment rates and outcomes.

Real-life data of hepatitis C treatment with direct acting antiviral therapy in persons injecting drugs or on opioid substitution therapy

Abstract Purpose HCV treatment has been revolutionized by introduction of direct-acting antiviral therapy (DAA). Short treatment duration of eight to twelve weeks combined with significantly improved tolerability opened the opportunity to reach out to difficult-to-treat populations. Here, we retrospectively analyzed real life data on HCV treatment adherence and outcome in people who inject drugs (PWID) or on opioid substitution therapy (OST). Methods All PWID or on OST receiving DAA therapy between 3/2021–11/2022 at an infectious disease clinic in Bonn were retrospectively analyzed. Patients received either 8 weeks glecaprevir/pibrentasvir or 12 weeks sofosbuvir/velpatasvir (+ ribavirin in genotype 3 cirrhotic patients). Sustained virological response (SVR) was measured 4 and 12 weeks after HCV therapy. Results In our cohort 47 patients (68%) received treatment with glecaprevir/pibrentasvir and 22 patients (32%) sofosbuvir/velpatasvir. All 47 (100%) patients started on glecaprevir/pibrentasvir received prescriptions for the full length of therapy, while patients on sofosbuvir/velpatasvir completed 12 weeks therapy in 86% and 8 weeks in 14% (p = 0.029). Of 69 patients 74% were found to achieve SVR. In 20% no information is available as they were lost to follow-up. Re-infection was documented in 3 patients and one relapse in a gt3 patient with cirrhosis. Conclusion High adherence and response rates to HCV treatment were found following DAA based therapy in PWID supporting the call to include difficult-to-treat populations into HCV treatment efforts on the way to HCV elimination. Treatment of OST and HCV at one institution supporting patients by a multidisciplinary team may further facilitate adherence to follow up visits enabling documentation of treatment outcomes more easily.

Impact of Sustained Virological Response on Long-Term Outcomes After Curative Resection in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma in the Era of Direct-Acting Antiviral Therapy

Impact of Sustained Virological Response on Long-Term Outcomes After Curative Resection in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma in the Era of Direct-Acting Antiviral Therapy

English

Objectives: Direct-acting antivirals (DAAs) share pharmacokinetic pathways with many comedications commonly administered to patients living with chronic hepatitis C virus (HCV) infection (PLWHCV). International guidelines recommend a thorough drug-drug interaction (DDI) risk assessment prior to starting DAA therapy and before starting comedications. This study aims to evaluate the impact of potential multiple DDIs in the real-life adverse event (AE) profile of PLWHCV treated with DAAs. Material and method: This is a retrospective, observational study using electronic medical records. Patients included were PLWHCV and were treated with either the protease inhibitor (PI) free DAA sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) between 2017 and 2020. Potential (single and multiple) DDIs were identified using the Liverpool HEP Interaction Checker. AEs potentially associated to DDIs were identified during DAA treatment period. Results: 1620 patients with DAA prescriptions (SOF/VEL or GLE/PIB) were included. Of these, 123 were predicted to have multiple DDIs (multi-DDI). About 10% (123/1256) of the patients receiving ≥2 comedications were at risk of multi-DDI with DAA. Most comedication-associated AEs were recorded in this multi-DDI population (88.9%, 16/18), meaning that 13% (16/123) of the multi-DDI population suffered AEs. According to DAA regimen, more comedication-associated AEs were reported in GLE/PIB-treated as compared with SOF/VEL-treated patients (18.3% [13/71] vs 5.8% [3/52] p<0.05). These AEs were mainly reported by primary care physicians (62.5%). Discussion: PLWHCV predicted to have multiple DDIs are at high risk of AEs. Moreover, fewer comedication-associated AEs were identified with the PI-free DAA SOF/VEL as compared with GLE/PIB.

Real-World Effectiveness of All-Oral Direct-Acting Antivirals in Patients With Hepatitis C Virus-Related HCC.

The association between direct-acting antiviral (DAA) treatment and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is currently unclear. Hence, we aim to assess the association between DAA treatment and mortality rate among Medicare beneficiaries with HCV-related HCC. This retrospective cohort study screened 19,813 adults in 2013-2019 Surveillance, Epidemiology, and End Results data linked with Medicare data. Patients with HCV-related HCC initiating DAA therapy after their first HCC diagnosis were compared with patients with HCV-related HCC who received no HCV treatment. After inverse probability treatment weighting, multivariable Cox proportional hazards models compared mortality rates between the groups. Subgroup and sensitivity analyses were based on HCC stage (early vs. advanced), type of HCC treatment (curative, palliative, none), and DAA treatment duration. In total 3,777 patients with HCV-related HCC were identified (mean age: 68.2 years, 75.2% male, 61.8% White), of whom 19% initiated DAA therapy. Crude incidence mortality rates were 17.9 and 90.7 deaths per 100 person-years in the DAA and HCV-untreated groups, respectively. Cox regression models indicated that DAA therapy was associated with decreased risk of all-cause mortality (adjusted hazard ratio, 0.33; 95% CI 0.31-0.36). Median survival time was 45.7 (95% CI 40.9-57.9) months in the DAA group and 7.7 (95% CI 7.3-8.2) months in the HCV-untreated group (P < 0.001). All subgroup and sensitivity analyses were consistent with the main analyses. DAA therapy was associated with survival benefits for patients with HCV-related HCC regardless of the stage or type of HCC treatment and should not be withheld from this population of Medicare beneficiaries.

Use of Hepatitis C Viremic Donors to Expand the Pediatric Donor Pool

The use of hepatitis C virus (HCV)-positive donors in organ transplantation has become increasingly viable due to advancements in direct-acting antiviral (DAA) therapies, which offer high cure rates. This review aims to evaluate the current practices, benefits, and challenges of utilizing HCV-positive donors for organ transplantation. The recent data show that transplant centers are progressively accepting HCV-positive donors for various organs, including kidneys, livers, and hearts, given the efficacy of post-transplant antiviral treatment. Using these donors has helped mitigate the organ shortage crisis, increasing the donor pool and reducing waitlist times. Despite these advantages, the approach raises concerns about viral transmission, long-term outcomes, and the cost-effectiveness of post-transplant DAA therapy. Furthermore, this review highlights the ethical implications of informed consent and the monitoring of HCV-negative recipients following transplantation. The outcomes from recent studies suggest that with proper management, transplantations from HCV-positive donors to HCV-negative recipients can be safe and effective, leading to excellent graft function and patient survival. This review synthesizes existing research and offers insights into optimizing protocols for future transplants involving HCV-positive donors.

Factors involved in gastroesophageal varix-related events in patients with hepatitisC virus-related compensated and decompensated cirrhosis after direct-acting antiviral therapy.

The incidence of and factors involved in gastroesophageal varix-related events in hepatitisC virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear. We conducted a multicenter study using prospective data from 478 hepatitisC virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria. Patients without varix or with F1 without red color signs were defined as low-risk varix, and patients with ≥F2 or red color signs or a history of rupture were defined as high-risk varix. Varix-related events were defined as prophylactic treatment or rupture of gastroesophageal varix. The median age was 70years, 43% of patients had decompensated cirrhosis, and 16% had high-risk varices (13% in compensated and 33% in decompensated, p<0.001). Sustained virologic response rates were 94.9% for compensated cirrhosis and 91.3% for decompensated cirrhosis (p=0.120). Across 35.7months, 25 patients received prophylactic treatment, and four experienced varix rupture. The 3-year incidence rate of varix-related events was 6.2% (3.5% in compensated and 9.9% in decompensated, p=0.001). In the multivariate analysis, high-risk varix (p<0.001), high baseline gamma-glutamyl transpeptidase levels (p<0.001), and virologic failure (p=0.004) were significantly involved in varix-related events. The cumulative incidence rate of varix-related events was significantly higher in decompensated cirrhosis than in compensated cirrhosis. Baseline varix status, baseline gamma-glutamyl transpeptidase levels, and virologic response were related to varix-related events after direct-acting antiviral therapy.

Loss to follow-up of patients after antiviral treatment as an additional barrier to HCV elimination

BackgroundEliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it.MethodsPatients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study.ResultsIn the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy.ConclusionsIn a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.

Elevated intestinal fatty acid-binding protein levels as a marker of portal hypertension and gastroesophageal varices in cirrhosis

We measured intestinal fatty acid-binding protein (I-FABP) levels, a useful marker of small intestinal mucosal injury, in patients with cirrhosis to determine their relationship with liver function and complications. This cross-sectional study included 71 patients with cirrhosis admitted for treatment of cirrhotic complications or hepatocellular carcinoma (cohort A) and 104 patients with cirrhosis who received direct-acting antiviral therapy for HCV (cohort B). I-FABP levels, measured by ELISA, were evaluated relative to hepatic reserve and compared with non-invasive scoring systems for diagnostic performance in cirrhotic complications. The median I-FABP level in both cohorts were significantly elevated in patients with reduced hepatic reserve (CTP grade A/BC cohort A, 2.33/3.17 ng/mL, p = 0.032; cohort B, 2.46/3.64 ng/mL, p = 0.008) and complications with gastroesophageal varices (GEV; GEV (-)/(+) cohort A, 1.66/3.67 ng/mL, p < 0.001; cohort B, 2.32/3.36 ng/mL; p = 0.003). Further, multiple logistic regression analysis identified I-FABP as the only factor contributing to GEV presence in both cohorts, which outperformed non-invasive scoring systems for GEV diagnosis (sensitivity 84.6%; specificity 84.2%; sensitivity 69.6%; specificity 63.8%, respectively). In conclusion, elevated small-intestinal mucosal injury in patients with cirrhosis was related to reduced hepatic reserve and GEV presence. I-FABP levels reflect portal hypertension and may be useful in cirrhosis management.

A case of hepatocellular carcinoma arising from the intraductal hepatic bile duct without parenchymal lesion.

Hepatocellular carcinoma (HCC) rarely presents as an intraductal tumor with no parenchymal lesions. Here, we present a case of HCC arising from an intrahepatic bile duct. A 74-year-old man who had been treated with direct-acting antiviral therapy for hepatitis C virus infection was referred to our hospital because of elevated serum prothrombin levels induced by vitamin K absence II (PIVKA-II). Initial imaging revealed no findings suspicious of HCC; however, repeat CT six months later revealed dilation of the intrahepatic bile ducts in the lateral segment of the liver. Cholangiography revealed a significant stricture of B3, and biopsy suggested adenocarcinoma. A left hepatectomy was performed with a preoperative diagnosis of intrahepatic cholangiocarcinoma. Although a surface nodule on the lateral segment of the liver, suspicious for intrahepatic metastasis, was found intraoperatively, radical resection was performed. Histopathological examination revealed a tumor filling the intrahepatic bile duct from the stump to the peripheral bile duct, with no infiltration into the liver parenchyma. The surface nodule is a dilated peripheral bile duct filled with a tumor with no extrabiliary invasion. Immunohistochemistry suggested HCC. No tumor lesions were observed in the hepatic parenchyma, and the tumor was finally diagnosed as HCC stemming from the biliary epithelium.

Racial Disparities in Liver Transplant for Hepatitis C-Associated Hepatocellular Carcinoma.

In the United States, hepatitis C virus-associated hepatocellular carcinoma incidence and mortality are highest among minorities. Socioeconomic constraints play a major role in inequitable treatment. We evaluated the association between race/ethnicity and outcomes in a population that overcame treatment barriers. We report a retrospective cohort study of 666 patients across 20 institutions in the United States Hepatocellular Carcinoma Liver Transplantation Consortium from 2015 to 2019 with hepatitis C virus-associated hepatocellular carcinoma who completed direct-acting antiviral therapy and underwent liver transplantation. Patients were excluded if they had a prior liver transplantation, hepatocellular carcinoma recurrence, no prior liver-directed therapy, or if race/ethnicity data were unavailable. Patients were stratified by race/ethnicity. Primary outcomes were recurrence-free survival and overall survival, and secondary outcome was major postoperative complication. Race/ethnicity was not associated with differences in 5-year recurrence-free survival (White 90%, Black 88%, Hispanic 92%, Other 87%; p = 0.85), overall survival (White 85%, Black 84%, Hispanic 84%, Other 93%; p = 0.70), or major postoperative complication. Race/ethnicity was not associated with worse oncologic or postoperative outcomes among those who completed direct-acting antiviral therapy and underwent liver transplantation, suggesting that overcoming socioeconomic constraints equalizes outcomes across racial/ethnic groups. Eliminating barriers that prohibit care access among minorities must be a priority.

Thrombospondin 2 as a Predictive Biomarker for HCC inHepatitis C Patients: A Longitudinal Study Following DAA Therapy.

This multicentre study investigated the dynamics of thrombospondin 2 (TSP2) levels during direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV) infected patients and evaluated TSP2's potential as a predictive marker for hepatocellular carcinoma (HCC). All 134 participants achieved sustained virological response at 12 weeks (SVR12) with DAA therapy, and serum TSP2 levels significantly decreased from before and after treatment (p < 0.001). During the median follow-up period of 6.0 years, HCC after DAA therapy was observed in 16 patients (11.9%). Patients with serum TSP2 High (≥ 32 ng/mL) at SVR12 had a significantly higher cumulative occurrence of HCC than did those without (26.5% vs. 7.0%, p = 0.0033). A multivariate Cox proportional hazards model identified male gender (HR 4.84, p = 0.005), HCC history (HR 4.61, p = 0.017) and TSP2 High (HR 3.93, p = 0.009) as significant independent predictors of HCC occurrence after DAA therapy. The model had a high concordance index of 0.878. Additionally, combining TSP2 High and FIB-4 High (≥ 3.538) at SVR12 yielded high specificity and negative predictive value (0.941 and 0.917, respectively) for predicting HCC. Kaplan-Meier analysis showed a higher HCC incidence in the TSP2 High + FIB-4 High group (log-rank p < 0.0001). In conclusion, TSP2 may be a promising biomarker for personalised HCC surveillance in DAA-treated hepatitis C patients.

DAA treatment for HCV reduce risk of hepatocellular carcinoma: a 10-years follow-up study based on Chinese patients with hepatitis C

The long-term benefits of direct-acting antiviral (DAA) therapy after achieving sustained virological response (SVR) remain uncertain in the Chinese population. This study evaluates the incidence of hepatocellular carcinoma (HCC), hepatic decompensation, and all-cause mortality among Chinese hepatitis C patients treated with DAAs. We included patients diagnosed since 2011 and followed them until November 1, 2022. The primary outcomes were HCC, hepatic decompensation, and mortality. Multivariable proportional hazards model was used to assess the impact of SVR and cirrhosis status. The cohort consisted of 1272 patients with SVR (92.1%) and 109 without SVR (7.9%), with a median follow-up of 61 months. The incidence of HCC was significantly lower in the SVR group (5.1 per 1000 person-years) compared to the no-SVR group (15.0 per 1000 person-years). Achieving SVR was associated with a significantly reduced risk of HCC (adjusted hazard ratio: 0.32; 95% CI 0.16–0.67). Cirrhosis was linked to an increased risk of developing HCC and hepatic decompensation. These findings highlight the importance of early DAA treatment, particularly for patients with cirrhosis.

Prevalence of and Risk Factors for Liver Enzyme Elevation After Hepatitis C Virologic Cure.

A subset of patients with chronic hepatitis C virus (HCV) infection demonstrate liver enzyme elevation (LEE) after achieving sustained virologic response (SVR). Risk factors for LEE are not well characterised. We conducted a single-centre retrospective cohort study of adults with HCV infection in the Duke University Health System who received direct-acting antiviral therapy and achieved SVR. We performed multivariable logistic regression to assess the relationship between potential risk factors and LEE. We used generalised linear mixed-effects models to explore longitudinal relationships between HIV and LEE. Among 1356 patients, 556 (41.0%) had LEE after achieving SVR. Higher pretreatment alanine aminotransferase (ALT) (adjusted odds ratio [aOR] 1.08 per 10 IU/L increase; 95% confidence interval [CI] 1.05-1.11) and pretreatment cirrhosis (aOR 2.26, 95% CI 1.60-3.21) were associated with higher odds of LEE; male sex was associated with lower odds of LEE (aOR 0.28, 95% CI 0.21-0.38). There was insufficient evidence of an association between HIV and LEE (aOR 0.83, 95% CI 0.47-1.44). Pretreatment ALT, cirrhosis and female sex predicted LEE in this cohort of patients with HCV infection who achieved SVR. These findings can help to identify patients at greatest risk of post-SVR liver injury.

A-242 Assessing the efficacy of the one-step diagnostic algorithm for Hepatitis C

Abstract Background Hepatitis C virus (HCV) infection can be asymptomatic and may go into spontaneous remission. However, in 60-80% of cases, it becomes chronic and progresses into cirrhosis or hepatocarcinoma. The virus is mainly transmitted parenterally, although cases of sexual and transplacental transmission have also been found. Since the development of direct-acting antiviral (DAA) therapy that can achieve a complete cure in 95% of patients, eradication strategies based on rapid diagnosis and treatment have been promoted. Therefore, the World Health Organization (WHO) has set a goal to eliminate HCV infection as public health threat by 2030. This is a retrospective study on the usefulness and effectiveness of the one-step HCV diagnostic algorithm application from May 2022 to December 2023 in our hospital. Methods The current HCV testing algorithm consists in a reflex HCV RNA testing, in which anti-HCV antibody-positive samples are automatically referred for HCV RNA testing on the same specimen. We used a serological electrochemiluminescence (ECLIA) assay for the detection of anti-HCV antibodies (Cobas e801, Roche Diagnostics®) in serum samples; and then a confirmation of HCV viremia by nucleic acid testing of HCV RNA in plasma samples (Cobas 4800, Roche Diagnostics®). Results A total of 22713 HCV serologies were performed with a total of 221 positive results (1%). Of the HCV cases, 21 patients had a newly diagnosis of active infection (10%) for whom we recommended derivation to the Digestive Service to initiate elimination treatment. 71% were men, with a mean age of 53 years and a standard deviation of 17. The mean age of women was 56 years with a standard deviation of 18. Coinfection with HIV or hepatitis B virus (HBV) was also assessed. Patients with HIV-HCV coinfection represented 9% of cases and were on average 12 years younger than HCV-monoinfected individuals. We did not identify any case of HBV-HCV co-infection. Conclusions The pattern we observed in terms of incidence by age and sex is similar to that reported in the literature, as well as the incidence of new HCV cases. One-step diagnosis enables the laboratory to identify the need for referring to a specialist, reducing the time to treatment for new and known but untreated cases. Therefore, global access to HCV diagnostics will be a keystone to success.

Single-center retrospective review of standard versus minimal monitoring for hepatitis C direct-acting antiviral therapy

BackgroundHighly effective direct-acting antiviral (DAA) therapies have transformed the landscape of hepatitis C virus (HCV) treatment. However, there continues to be limited data regarding the efficacy and safety of required in-person clinic visits (standard monitoring) versus completely telehealth clinic visits (minimal monitoring) during HCV therapy, which could delay practice adoption. ObjectivesThis study aimed to assess the rates of undetectable HCV ribonucleic acid (RNA) in sustained viral load 12 weeks after therapy (SVR12) in standard versus minimal monitoring approaches during DAA. MethodsA 12-month, single-center retrospective cohort study was conducted in treatment-naïve HCV-infected adults who received DAA therapy between May 1, 2020, and April 30, 2021. The standard monitoring group had ≥1 in-person clinic visit with HCV RNA laboratory monitoring during DAA treatment. The minimal monitoring group had entirely telehealth visits without HCV RNA laboratory monitoring during treatment. Both groups received telephonic touchpoints throughout DAA treatment from a clinical pharmacist practitioner and a nurse care coordinator. The primary outcome was SVR12. ResultsFrom May 2020 to April 2021, 133 patients with HCV met inclusion criteria and were treated with DAA (standard, n = 56; minimal, n = 77), with no differences in baseline demographics. Overall, total encounters during DAA treatment remained significantly higher in the standard than minimal monitoring group (standard, 2.1 ± 0.8, vs. minimal, 1.7 ± 0.9; P < .01). Although minimal monitoring had higher loss to follow-up rates (standard, 7.1%, vs. minimal, 18.2%; P = 0.06), the modified intention-to-treat analysis showed no differences in sustained virologic response (SVR) between standard and minimal monitoring approaches (standard, 98.1%, n = 51, vs. minimal, 95.3%, n = 60; P = 0.41). ConclusionsThis single-center retrospective cohort study demonstrated that minimal monitoring during HCV treatment was as effective in achieving SVR cure rates as standard monitoring. Eliminating required in-person clinic visits during DAA therapy alongside a collaborative approach may play a major role in overcoming barriers to HCV care in select patients.

Hepatitis C in Children-An Asia-Pacific Concise Perspective.

Since the discovery of hepatitis C virus (HCV) in 1989, we now have curative treatment options with direct-acting antiviral therapies. By increasing the rate of treatment and reducing transmission, the eradication of HCV is potentially achievable. Nonetheless, the feasibility and implementation of this goal remains challenging. This article sums up the approach to managing children with HCV in the Asia-Pacific region and lists some of the difficulties and complexities surrounding this issue.

Hepatitis C Virus Infection in Europe.

The Hepatitis C Virus (HCV) is a significant public health challenge in European countries. Historically, healthcare-related procedures were the primary source of HCV infection in Europe. However, with the implementation of blood safety programs, injection drug use has become the main transmission route. The infection's distribution and genotype prevalence vary widely across the continent. Even with the availability of highly effective direct-acting antiviral (DAA) therapies, HCV infection is far from being controlled. A significant proportion of patients remain undiagnosed, contributing to the ongoing transmission of the virus. Additionally, several barriers hinder the widespread use of DAAs, including high treatment costs, stigma, poor linkage to care, and considerable geographical variations in prevalence and transmission routes. The World Health Organization has set ambitious targets to reduce liver-related deaths, decrease new viral hepatitis infections, and ensure that 90% of infected individuals are diagnosed by 2030. However, most European countries face challenges, highlighting the need for screening programs, funding mechanisms, and public health strategies to effectively control HCV infection in Europe.

Extrahepatic Cancer Risk in Patients with Hepatitis C Virus Infection Treated with Direct-Acting Antivirals.

Chronic hepatitis C virus (HCV) infection is associated with an increased risk of extrahepatic cancers, particularly non-Hodgkin lymphoma. The introduction of direct-acting antivirals (DAAs) has revolutionized HCV therapy, resulting in high cure rates. However, concerns have been raised about potential effects on cancer risk. This review summarizes the current evidence on extrahepatic cancer risk in HCV-infected patients treated with DAAs. We examined epidemiologic data on HCV-associated extrahepatic cancers and explored potential mechanisms linking HCV to carcinogenesis outside the liver. Studies evaluating cancer outcomes after DAA therapy were critically reviewed while considering methodological challenges. While some studies suggested a reduced risk of extrahepatic cancers after DAA therapy, others showed no significant change. Limitations included short follow-up periods and confounding variables. Immunological changes following rapid HCV clearance may have complex effects on cancer risk. Long-term prospective studies and mechanistic investigations are needed to fully elucidate the relationship between DAA therapy and extrahepatic cancer risk in HCV patients. Clinicians should remain vigilant for extrahepatic malignancies in this population.

In vitro study on efficacy of SKF7®, a Malaysian medicinal plant product against SARS-CoV-2

BackgroundIn early 2020, COVID-19 pandemic has mobilized researchers in finding new remedies including repurposing of medicinal plant products focusing on direct-acting antiviral and host-directed therapies. In this study, we performed an in vitro investigation on the standardized Marantodes pumilum extract (SKF7®) focusing on anti-SARS-CoV-2 and anti-inflammatory activities.MethodsAnti-SARS-CoV-2 potential of the SKF7® was evaluated in SARS-CoV-2-infected Vero E6 cells and SARS-CoV-2-infected A549 cells by cytopathic effect-based assay and RT-qPCR, respectively. Target based assays were performed on the SKF7® against the S1-ACE2 interaction and 3CL protease activities. Anti-inflammatory activity of the SKF7® was evaluated by nitric oxide inhibitory and TLR2/TLR4 receptor blocker assays.ResultsThe SKF7® inhibited wild-type Wuhan (EC50 of 21.99 µg/mL) and omicron (EC50 of 16.29 µg/mL) SARS-CoV-2 infections in Vero-E6 cells. The SKF7® also inhibited the wild-type SARS-CoV-2 infection in A549 cells (EC50 value of 6.31 µg/mL). The SKF7® prominently inhibited 3CL protease activity. The SKF7® inhibited the LPS induced-TLR4 response with the EC50 of 16.19 µg/mL.ConclusionsIn conclusion, our in vitro study highlighted anti-SARS-CoV-2 and anti-inflammatory potentials of the SKF7®. Future pre-clinical in vivo studies focusing on antiviral and immunomodulatory potentials of the SKF7® in affecting the COVID-19 pathogenesis are warranted.