Direct-acting Antivirals Research Articles

Peripheral immune signatures associated with the risk of hepatocarcinogenesis in cirrhotic Egyptian HCV patients before and after treatment with direct-acting antivirals.

Although direct-acting antivirals (DAAs) have revolutionized the management of chronic HCV, the debatable association with hepatocellular carcinoma (HCC) occurrence/recurrence has raised major concerns about their long-term use, especially in cirrhotic cases. The role of epithelial tight junction proteins (TJPs) in hepatocarcinogenesis has been highlighted; however, the association of their expression in peripheral blood mononuclear cells (PBMCs) with HCC has rarely been reported. This study aimed to explore the role of peripheral claudin (Cldn)1 in liver pathogenesis and its crosstalk with soluble immune mediators in HCC prognosis. The study population included six independent subgroups: healthy controls, cirrhotic/non-cirrhotic treatment-naïve HCV patients, DAA-SVR patients, and anticancer treatment-naïve de novo HCC patients. The laboratory tests included serum levels of alpha-fetoprotein (AFP), albumin, liver transaminases, total bilirubin, and CBC profiling. The serum levels of soluble cluster of differentiation (sCD)163, IL-10, and IL-12 were estimated by corresponding ELISA kits, whereas the levels of Cldn1 and transforming growth factor (TGF)-β in PBMCs were quantified using quantitative PCR (qPCR). Serum sCD163, IL-10, and IL-12 levels were significantly higher in the HCC patient group than in the control and non-malignant patient groups (P < 0.0001). No significant difference was detected in the serum levels of the three markers between cirrhotic and non-cirrhotic patients, whereas their levels were significantly different between cirrhotic and non-cirrhotic patients (P < 0.0001). Similarly, the transcriptional levels of peripheral Cldn1 and TGF-β were significantly higher in patients with HCC and non-malignant cirrhosis than in patients without cirrhosis (P = 0.0185-<0.0001 and 0.0089-<0.0001, respectively). Logistic regression analysis revealed a significant association between all the abovementioned markers and HCC (P = 0.0303 to < 0.0001), which was further confirmed by the results of receiver operating characteristic (ROC) analysis, which revealed an area under the curve (AUC) value ranging from 0.883 to 0.996. The calculated cutoff values demonstrated remarkable prognostic capacity, with ranges of 88-99.41% and 82.14-97.92% and positive/negative predictive values ranging from 84.62 to 98.3% and 92-98%, respectively. The proposed HCC predictors are novel non-invasive HCC biomarkers that maintain their predictive power under different pathological conditions and circumvent the drawbacks of conventional prognostic markers in patients with mild cirrhosis and/or normal AFP, albumin, and/or platelet counts.

Clinical factors to predict changes of esophagogastric varices after sustained viral response with direct-acting antiviral therapy.

The clinical course of esophagogastric varices (EGV) after sustained virological response (SVR) with direct-acting antiviral (DAA) therapy has not been clearly elucidated. The predictors for the worsening/improvement of EGV after SVR with DAA therapy were investigated. Of the cirrhosis patients who achieved SVR with DAA therapy, 328 patients who underwent endoscopic examinations both before and after DAA therapy were enrolled. The predictors of EGV worsening or improvement were investigated. Multivariate analysis identified a history of ascites retention, albumin at baseline, and MELD score at baseline as independent factors that contributed to EGV exacerbation. On multivariate analysis, two factors, BMI and platelet count, were related to EGV improvement. An integrated scoring system was created using these risk factors with or without weighting according to each hazard ratio, and the patients were divided into three groups. A scoring system with weighting of each factor appeared to be more useful, with fewer intermediate patients and more cases classified into the low-risk and high-risk groups. Esophagogastric varices after SVR have a varied clinical course. Using this scoring system that can accurately predict EGV outcomes in clinical settings, it may be feasible to establish a risk-based EGV surveillance plan following SVR.

Rate of hepatitis C reinfection after successful direct-acting antivirals treatment among people who inject drugs in Spain: the LIVERate study.

Hepatitis C virus (HCV) reinfection following successful treatment threatens the achievement of HCV elimination. The primary aim of this study is to assess reinfection rate three years after sustained virologic response (SVR) in people who inject drugs (PWID) that are on opioid agonist treatment (OAT) who underwent anti-HCV treatment with interferon-free regimens. Observational, non-interventional, prospective, descriptive study carried out in Spanish tertiary public hospitals between 2017 and 2022. Participants comprised 186 adult HCV infected individuals, 85.5% males with a mean age (Standard Deviation, SD) of 50.1 (5.9). All were enrolled in an OAT program at baseline and had attained SVR 12 weeks after therapy completion with an interferon-free treatment. Baseline data were abstracted from medical chart information collected through the routine clinical practice. The overall rate of HCV reinfection three years after SVR12 among PWID was 1.2 new cases per 100 person-years of follow-up at a median of 15.9 months. In the subgroup analyses, those with injection drug practice and without a stable housing had higher reinfection rates. Although PWID in OAT present a low rate of reinfection by HCV after successful treatment, a closer monitoring in the first year and strengthening inter-consultations with services responsible for monitoring addiction in these patients will be crucial to reduce risky behaviors avoiding HCV reinfection.

An ODEs multiscale model with cell proliferation for hepatitis C virus infection treated with direct acting antiviral agents

In a recent study, a mathematically identical ODE model is derived from a multiscale PDE model of hepatitis C virus infection, which helps to overcome the limitations of the PDE model in the analysis. Here, an extended proposed model is formulated for this transformed ODE model by including the hepatocyte proliferation of both uninfected and infected cells. Unlike the transformed model, the proposed model can predict the triphasic viral decline and the virus level after therapy cessation without oscillations. Numerical simulations are performed to investigate the effect of hepatocyte proliferation and therapy with direct-acting antivirals agents (DAAs). The basic reproduction number is obtained, the equilibrium points are specified, and their stability is analysed. A bifurcation analysis is performed to specify the bifurcation points and to study the effect of varying system parameters. Various viral load profiles generated by the model are confirmed to fit with reported data in the literature.

Externalised nurse-led model for hepatitis C virus microelimination and impact of drug use profile.

Direct-acting antivirals have greatly simplified the treatment of hepatitis C virus (HCV), yet circuits that bring diagnosis and treatment closer to people who inject drugs (PWID) are needed to achieve the elimination targets of the WHO. With this purpose we have established an externalised nurse-driven circuit among former and active PWID in an addiction centre (AC) and a harm reduction centre (HRC). The nursing staff offered HCV screening, diagnosis and treatment to the AC and HRC users, administered medication after the hepatologist's remote prescription to those with an active infection who accepted being treated, and implemented educational and harm reduction interventions. Participants and results: Between October 2018 and March 2021, 566 users accepted screening. 134 (24%) had an active infection, with a higher prevalence among HRC users (42% vs 17%; p<0.001), who were more frequently foreigners, homeless and reported active drug use and syringe sharing. Treatment initiation was similar between groups. Overall sustained viral response (SVR) for intention-to-treat (ITT) and per protocol (PP) was 70% and 88% respectively. Overall adherence was good in both groups; however, SVR was higher in AC users compared to HRC users (ITT-SVR 81% vs 55%). All reinfections (6% by ITT) occurred in the HRC group. Overall loss to follow-up rate was 21%. This patient-centred nurse-driven circuit demonstrates that HCV treatment can be successfully delivered to PWID even with active drug use and socio-economic complexity. User-specific characteristics need to be considered when setting up these interventions to maximise success.

Direct Antivirals Can Achieve a Cure in All Patients With Chronic Hepatitis C due to Genotype 5: A French Multicentre Study.

Hepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%. Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure. HCV-GT-5 patients treated with a DAA regimen had a 99% SVR12 in intention-to-treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real-world HCV-GT-5 patients.

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 &lt; 0.0001). Confirmation of viral infection at first visit was an important factor with respect to treatment (treated 38% vs. not treated 25% p &lt; 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.

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.

The present study aimed to clarify the long-term outcomes after curative resection of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in patients with and without sustained virologic response (SVR) to antiviral therapy. This single-center retrospective cohort study included 216 patients with HCV-related HCC who underwent primary curative resection. Patients were divided into preoperatively achieved SVR, postoperatively achieved SVR through direct-acting antiviral (DAA) therapy and no SVR groups. Associations of SVR and other clinicopathological and surgical variables with overall survival (OS) and recurrence-free survival (RFS) were analyzed. Propensity score (PS) matching was used to reduce selection bias. Patients with pre-SVR (108) and post-SVR (28) had better liver function and less liver fibrosis than those without SVR (80). In multivariate analysis, pre- or post-SVR [hazard ratio (HR), 0.13; 95% confidence interval (CI), 0.03-0.38; P < 0.001] was the only independent predictor of OS. For RFS, pre- or post-SVR (HR, 0.36; 95% CI, 0.18-0.64; P = 0.001) was one of several independent predictors. The study population was divided into the SVR (136 patients) and non-SVR groups. After PS matching, OS and RFS were significantly better in the SVR group (n = 53) than in the non-SVR group (n = 53) (P <0.001 and P = 0.012, respectively). Additionally, OS rates of SVR achieved with DAA were significantly higher than those achieved with interferon (P = 0.019). Achieving SVR by DAA before or after curative resection suppressed recurrence and prevented death in patients with HCV-related HCC.

Non-liver malignancies as main cause of mortality after HCV eradication among people living with HIV.

In people living with HIV (PLWH) with HCV infection, liver and non-liver-related mortality significantly decreased after receiving direct acting antivirals (DAAs). We aimed to assess main causes and predictors of mortality after sustained virological response (SVR) induced by DAAs. Retrospective study in antiretroviral treatment-experienced PLWH with HCV infection, followed at San Raffaele Hospital, Milan, Italy, who achieved SVR after DAAs. Kaplan-Meier analysis and log-rank test were used to estimate cumulative probability of death for any cause. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) of death and the corresponding 95% confidence interval (95%CI); Baseline variables included in the model were: age, diabetes, hepatocellular carcinoma (HCC), α-fetoprotein (AFP), ALBI grade. Among 663 people included with a median follow-up of 4.4 years (IQR=3.5-5.5), 49 died. Overall 5-year cumulative probability of death was 8.0% (95%CI=5.5%-10.4%); 63.2% (n=31/49) died from non-liver-related events [mainly non-liver malignancies (18/49) and cardiovascular events (7/49)].-. At multivariate analysis, death was more likely in older people [aHR (adjusted Hazard Ratio) (5-year older)=1.46, 95%CI=1.16-1.83, p=0.0009], and in people with diabetes [aHR=2.98, 95%CI=1.55-5.71, p=0.001], ALBI grade ≥2 [aHR=2.13, 95%CI=1.17-3.90, p=0.014] and AFP ≥3.4 ng/mL [aHR=1.96, 95%CI=1.01; 3.84, p=0.049]. In our cohort, non-liver-related events and malignancies were the most common cause of death after HCV eradication. Diabetes, ALBI grade ≥2 and AFP≥ 3.4 ng/L were associated with higher risk of death. In PLWH after HCV eradication, regardless of liver disease stage, surveillance of non-liver events, particularly malignancies, should be recommended.

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&lt;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.

The effect of cognitive emotion regulation on direct-acting antivirals adherence in patients with hepatitis C

IntroductionAdherence to direct-acting antivirals (DAAs) could be a predictor of chronic viral hepatitis C (HCV) therapeutic failure. We examined the perceptions of patients receiving DAAs to determine how cognitive factors influence their decision to maintain adherence. Also, we explored the threshold of DAAs adherence for obtaining sustained virologic response (SVR) among patients with HCV, in order to better implement a strategy that improves the DAAs adherence in the future clinical practice.MethodsA single-arm prospective study was performed. Patients with HCV that started and completed DAAs treatment in the County Hospital of Craiova, Dolj, Romania, were enrolled. Patients’ medication adherence was assessed using the HCV-AD10 questionnaire, and the cognitive emotion regulation was measured with CERQ questionnaire (five positive/adaptive cognitive emotion-regulation domains and four negative/maladaptive domains). Spearman correlation analysis was conducted to explore the relationships between adherence and different factors. ROC-curves were used to evaluate the adherence threshold to achieve SVR. A linear regression model was performed to analyze the primary outcome (DAAs adherence) to be the target variable based on given independent variables (age, treatment duration, severity of HCV, the nine adaptive and maladaptive strategies).Results368 patients (mean age: 61 years) with HCV diagnosed 4.05 ± 6.38 (average) years ago were enrolled. Mean (±SD) adherence via HCV-AD10 was 91.51 ± 8.34, and the proportion of the participants achieving SVR was 96%. Patients with an adherence less than 84% (5 patients, 1.36%) was considered nonadherent and they have a high probability of not achieving response (sensitivity and specificity of 83% and 80%, respectively). We obtained significantly higher values of three adaptive strategies between adherent and nonadherent patients following DAAs treatment: in positive refocusing (p-value = 0.044), refocus on planning (p-value = 0.037), and positive reappraisal (p-value = 0.047).DiscussionThe interplay between the three adaptive strategies of the cognitive emotion regulation and the enhancement of DAAs adherence contributes to a more holistic comprehension of patient behavior in the context of HCV treatment. Increasing refocusing and planning using goal setting and assisting patients in establishing specific, achievable goals can be crucial strategies for clinicians aiming to improve adherence among their patients.

New Scenarios in Liver Transplantation for Hepatocellular Carcinoma.

Despite liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC), particularly in patients with impaired liver function, the shortage of donors has forced the application of very restrictive criteria for selecting ideal candidates for whom LT can offer the best outcome. With the evolving LT landscape due to the advent of direct-acting antivirals (DAAs) and the steady increase in donors, major efforts have been made to expand the transplant eligibility criteria for HCC. In addition, the emergence of immune checkpoint inhibitors (ICIs) for the treatment of HCC, with demonstrated efficacy in earlier stages, has revolutionized the therapeutic approach for these patients, and their integration in the setting of LT is challenging. Management of immunological compromise from ICIs, including the wash-out period before LT and post-LT immunosuppression adjustments, is crucial to balance the risk of graft rejection against HCC recurrence. Additionally, the effects of increased immunosuppression on non-hepatic complications must be understood to prevent them from becoming obstacles to long-term OS. In this review, we will evaluate the emerging evidence and its implications for the future of LT in HCC. Addressing these novel challenges and opportunities, while integrating the current clinical evidence with predictive algorithms, would ensure a fair balance between individual patient needs and the overall population benefit in the LT system.

Efficacy of 8-week daclatasvir-sofosbuvir regimen in chronic hepatitis C: a systematic review and meta-analysis

BackgroundThe high rates of the sustained virologic response 12 weeks after treatment (SVR12) in real world settings provoked the adoption of shortened courses of the costly direct-acting antivirals (DAAs) regimens. This study provides, to our knowledge, the first systematic review and meta-analysis for the efficacy of the shortened 8-week course of sofosbuvir (SOF) plus daclatasvir (DCV), the most accessible DAAs in the low-middle income countries (LMICs).MethodsWe performed a proportion meta-analysis to determine a reliable rate of SVR12 by pooling all studies that evaluated the results of the 8-week regimen of DCV + SOF. In addition, we applied sensitivity analyses using two imputation paradigms: a conservative approach, and a pragmatic approach to avoid overestimating the efficacy of the 8-week regimen in studies that followed a response-guided treatment (RGT) approach.ResultsSix studies with a total of 159 patients were included. The pooled SVR12 rate ranged from 91 to 97% in the included scenarios. The pragmatic scenario showed that the pooled SVR12 was 97% (95% confidence interval (CI) 91%; 100%) with lower variability as assessed by the prediction interval. The conservative approach revealed an SVR12 of 93% (95% CI 84%; 95%).ConclusionThe 8-week course of 60 mg DCV with SOF provided a comparable SVR12 to the standard 12-week regimen in treatment-naïve, non-HIV co-infected patients with a minimum estimated efficacy of 90%.

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.

Perceived patient navigator services and characteristics to address barriers to linkage to hepatitis C care among people released from provincial prison in Quebec, Canada

BackgroundPatient navigation increases linkage to hepatitis C virus (HCV) care following release from prison; however, little is known about the services patient navigators should provide to maximize linkage to care. We aimed to identify perceived barriers and facilitators to linkage to HCV care post-release, and to determine patient navigator services and characteristics best suited to address barriers to linkage to care among people released from prison. MethodsTen semi-structured interviews were conducted with adult (age ≥ 18 years) men living with chronic HCV, released from the largest Quebec provincial prison, and linked to HCV care by a patient navigator. Interviews were guided by the Socio-Ecological Model (SEM) and aimed to explore the multi-level barriers and facilitators to linkage to HCV care post-release. Interviews were audio-recorded, transcribed, and analyzed using a deductive, thematic approach. ResultsThe median age of participants was 54 years. Barriers to linkage to HCV care included competing priorities post-release (e.g., substance use, mental health issues, unstable housing), stigma (related to HCV, injection drug use, and incarceration), and lack of transportation. Facilitators included social support, established relationships with existing healthcare providers, prior cure with direct-acting antivirals, and HCV-related health literacy and knowledge. Perceived essential patient navigator services to enhance linkage included pre-release discharge appointments, housing assistance, and facilitated transportation to HCV appointments. Ensuring a consistent, non-judgemental, and empathetic patient navigator were considered important characteristics; lived experiences of incarceration and/or HCV were not felt to be essential for a patient navigator. ConclusionsInterventions that seek to improve linkage to HCV care for people following release from prison should address many levels (individual, interpersonal, and policy) of the SEM. While people experience several competing priorities post-release, having an empathetic and consistent patient navigator, regardless of their lived experiences of HCV and/or incarceration, may improve linkage to HCV care post-release.

Non-acquired immunodeficiency syndrome defining malignancies in people living with haemophilia and human immunodeficiency virus after direct-acting antiviral era.

Non-acquired immunodeficiency syndrome-defining malignancies (NADMs) are the crucial cause of mortality in people living with haemophilia and human immunodeficiency virus (PLWHH). We aimed to analyse the types and characters of NADMs in PLWHH after approval of direct-acting antivirals (DAA), considering that most PLWHH are infected with hepatitis C virus (HCV). We conducted a nationwide questionnaire mail survey across 395 HIV core facilities in Japan between May 2022 and February 2023. Eight-year data from 64 respondent hospitals (n = 328 PLWHH; 2015-2022) were collected; 35 NADM cases were identified and analysed. Standardised cancer incidence ratios (SCIRs) were calculated. The median age of PLWHH with NADMs was 51 years (interquartile range: 47-62 years); the SCIR was 2.08 (95% confidence interval [CI]: 1.48-2.90) for all malignancies (including carcinoma in situ). Liver cancer accounted for most NADMs (43% [15/35]). The SCIRs of liver cancer (23.09 [95% CI: 13.92- 38.30]) and papillary thyroid cancer (9.38 [2.35-37.50]) significantly increased after adjusting for general Japanese male sex and age. Among PLWHH with liver cancers, 73% (11/15) achieved HCV-sustained virological response. Notably, for patients aged ≤ 50 years, 47% (7/15) were affected by liver cancers, and 27% (4/15) succumbed to NADMs. This study presents the largest survey of NADMs in PLWHH after DAA approval. Our findings emphasised the elevated risk of malignancies in PLWHH, underscoring the need for early cancer screening and preventive measures, particularly against liver cancers, even in younger PLWHH.

Cost-effectiveness analysis of emergency department-based hepatitis C screening and linkage-to-care program

BackgroundIn the United States (US), hepatitis C virus (HCV) screening is not covered by payers in settings outside of primary care. A non-traditional, emergency department (ED)-based HCV screening program can be cost-effective and identify infection in vulnerable populations with a high HCV risk. This study examined the long-term cost-effectiveness of routine HCV screening and linkage-to-care for high-risk patients in the ED from the payer’s perspective.MethodsThe University of Illinois Hospital and Health Sciences System (UIH) implemented Project HEAL (HIV & HCV Screening, Education, Awareness, Linkage-to-Care). Under this initiative, patients who presented to the ED received opt-out HCV screening if they were at high risk for HCV infection (birth cohort between 1945 and 1964, persons who inject drugs, and HIV infection) with subsequent linkage-to-care if infected. Using the summary data from Project HEAL, a hybrid decision-analytic Markov model was developed based on the HCV screening procedure in the ED and the natural history of HCV. A 30-year time horizon and 1-year cycle length were used. All patients who received the ED-based HCV screening were referred for treatment with direct-acting antiviral (DAA) regardless of their fibrosis stage.ResultsWhen unscreened/untreated patients received DAA treatment at F1, F2, F3, and compensated cirrhosis stages, the incremental cost-effectiveness ratio (ICER) ranged from $6,084 to $77,063 per quality-adjusted life year (QALY) gained. When unscreened/untreated patients received DAA treatment at the decompensated cirrhosis stage, no HCV screening was dominated.ConclusionED-based HCV screening and linkage-to-care was cost-effective at the willingness-to-pay (WTP) threshold of $100,000/QALY in all scenarios. A reduction in infected persons in the community may provide additional benefits not evaluated in this study.

Understanding Why Metabolic-Dysfunction-Associated Steatohepatitis Lags Behind Hepatitis C in Therapeutic Development and Treatment Advances

Therapeutic development for metabolic-dysfunction-associated steatohepatitis (MASH) trails behind the success seen in hepatitis C virus (HCV) management. HCV, characterized by a viral etiology, benefits from direct-acting antivirals (DAAs) targeting viral proteins, achieving cure rates exceeding 90%. In contrast, MASH involves complex metabolic, genetic, and environmental factors, presenting challenges for drug development. Non-invasive diagnostics like ultrasound, FibroScan, and serum biomarkers, while increasingly used, lack the diagnostic accuracy of liver biopsy, the current gold standard. This review evaluates therapies for MASH, including resmetirom (Rezdiffra) and combinations like pioglitazone and vitamin E, which show potential but offer modest improvements due to MASH’s heterogeneity. The limited efficacy of these treatments highlights the need for multi-targeted strategies addressing metabolic and fibrotic components. Drawing parallels to HCV’s success, this review emphasizes advancing diagnostics and therapies for MASH. Developing effective, patient-specific therapies is crucial to closing the gap between MASH and better-managed liver diseases, optimizing care for this growing health challenge.

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.

Long-term Effect of the HCV Elimination With Direct-acting Antivirals on the Progression of Gastroesophageal Varices.

Gastroesophageal varices (GEV) hemorrhage is a serious complication that can lead to unfavorable outcomes in cirrhotic patients. However, the clinical impact of HCV elimination [sustained viral response (SVR)] by direct-acting antivirals (DAAs), particularly on the long-term effects on the endoscopic findings of GEV have not been sufficiently evaluated. This study aimed to investigate whether HCV elimination with DAA treatment suppresses the progression of GEV. The clinical courses of the endoscopic findings of GEV were retrospectively compared between patients without an SVR (non-SVR group: n=71) and those who achieved an SVR with DAAs (DAA-SVR group: n=38). At 1, 3, 5, and 7 years, the cumulative GEV progression rates were 8.7%, 32.8%, 45.6%, and 66.2%, respectively. At 3 years, the cumulative GEV progression rate in the DAA-SVR group was similar to that in the non-SVR group. Beyond 3 years, cases with GEV progression were found in the non-SVR group, but not in the DAA-SVR group. At 7 years, the cumulative GEV progression rate in the DAA-SVR group was significantly lower than that in the non-SVR group (p<0.05, log-rank test). Variceal hemorrhage occurred in eight patients in the non-SVR group, while no bleeding events were observed in the DAA-SVR group during the observational period [8/71 (11.3%) vs. 0/38 (0.0%), p<0.05]. DAA treatment suppresses the progression of GEV over the long term.