Treatment-naive Noncirrhotic Patients Research Articles

Pre-Existing and New-Onset Metabolic Dysfunctions Increase Cirrhosis and Its Complication Risks in Chronic Hepatitis B.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing among the chronic hepatitis B (CHB) population. This study aimed to explore the impact of metabolic dysfunction (MD) on cirrhosis and cirrhotic complication risks in CHB. Patients with CHB were consecutively recruited between 2006 and 2021. The presence of MD was based on the 5 cardiometabolic criteria specified in the MASLD definition. Patients were categorized into MD/non-MD groups based on these criteria. Eleven thousand five hundred two treatment-naive noncirrhotic patients with CHB were included with a median follow-up of 5.3 years. Patients in the MD group (n = 7,314) were older and had lower hepatitis B virus DNA levels than non-MD patients (n = 4,188). After adjustment for clinical and viral factors, MD patients had significantly higher risks of cirrhosis (adjusted hazard ratio [aHR]: 1.82, 95% confidence interval [CI]: 1.40-2.37, P < 0.001) and cirrhotic complications (aHR: 1.30 per MD, 95% CI: 1.03-1.63, P = 0.025) in a dose-dependent manner. Furthermore, new-onset diabetes mellitus during the follow-up aggravated the risk of cirrhotic complications (aHR: 2.87, 95% CI: 1.34-6.11, P = 0.006). Hepatic steatosis was associated with lower risks of cirrhosis (aHR: 0.57 within 5 years, 95% CI: 0.44-0.74, P < 0.001) and cirrhotic complications (aHR: 0.45, 95% CI 0.23-0.88, P = 0.020). Among individuals with hepatic steatosis, patients with MASLD exhibited a higher cirrhosis risk than non-MD patients. Concurrent and new-onset MDs increase the risks of cirrhosis and cirrhotic complications in patients with CHB, independent of hepatic steatosis. Proactively investigating metabolic comorbidities in CHB is critical to stratify the risk of liver disease progression.

Cost-effectiveness of sofosbuvir in hepatitis C genotype 1 infection in Germany: A reanalysis of published results.

ObjectivesRecently, the results of two economic evaluations were published both of which seemingly demonstrate the cost-effectiveness of sofosbuvir-based regimens for the treatment of chronic hepatitis C genotype 1 infection in Germany. Both analyses were sponsored by the manufacturer of sofosbuvir and use a different methodology: Whereas one evaluation is based on a conventional cost-utility analysis, the other rests upon the efficiency-frontier method used by the German Institute for Quality and Efficiency in Health Care (IQWiG). The purpose of this study is to reanalysis the results of both economic evaluations in combination.DesignReanalysis of published decision modelling results.SettingPrimary care in Germany.ParticipantsPatients with chronic hepatitis C genotype 1 infection (treatment-naïve and -experienced, cirrhotic and non-cirrhotic).InterventionsSofosbuvir, other anti-hepatitis C virus drugs, and no treatment.Primary and secondary outcome measuresCost per unit of health benefit and cost per quality-adjusted life year.ResultsReanalysis of the results of both economic evaluations in combination reveals an unclear rationale for choosing the selected cost-effectiveness methods as well as a potential publication bias, favoring the product of the manufacturer. Based on the reanalysis, sofosbuvir is not cost-effective in treatment-experienced non-cirrhotic patients, potentially lacks cost-effectiveness in treatment-experienced cirrhotic patients, and is only partially cost-effective in treatment-naïve non-cirrhotic patients. Taken together, these results indicate a lack of cost-effectiveness in three quarters of the German patient population.ConclusionsTwo economic evaluations on sofosbuvir suggest, in combination, that sofosbuvir cannot be considered a cost-effective treatment in three quarters of the German patient population.

Efficacy of Sofosbuvir plus Daclatasvir in Treatment of Chronic HCV Infection in Egyptian Patients: A Prospective Cohort Study

Background and study aim: Chronic hepatitis C virus infection is a massive health challenge in Egypt. New DAAs in the past few years have proven to be extremely effective in treatment of HCV infection. The aim of this study was to evaluate the efficacy of a sofosbuvir-based treatment protocol composed of sofosbuvir and daclatasvir with or without the addition of ribavirin in Egyptian patients infected with HCV genotype 4 in Sharkia governorate. Patients and Methods: One hundred patients were included in the study. Patients were divided into three groups, group I: 48 treatment-naive non-cirrhotic patients who were assigned to receive dual therapy (Daclatasvir+Sofosbuvir) for a duration of 12 weeks, group II: 32 treatment-naive cirrhotic patients who were assigned to receive triple therapy (Daclatasvir + Sofosbuvir + Ribavirin) for a duration of 12 weeks, and group III: A control group composed of 20 chronic HCV patients, not receiving antiviral therapy. Patients were followed up thoroughly by clinical and laboratory evaluation monthly throughout treatment and for 3 months after the end of treatment (EOT). In addition, the virological response for each patient was recorded. Results: No statistically significant difference was found between both groups that received treatment regarding virological response, since 100% of patients achieved SVR12 rates in both groups. Conclusion: The combination of Daclatasvir plus Sofosbuvir with or without the addition of ribavirin for a duration of 12 weeks has proven to possess high efficacy in the treatment of cirrhotic and non-cirrhotic naive Egyptian patients with chronic infection with HCV genotype4 in Sharkia governorate.

Glecaprevir/pibrentasvir expands reach while reducing cost and duration of hepatitis C virus therapy.

Hepatitis C virus (HCV) treatments have dramatically progressed from poorly tolerated, moderately successful interferon-based therapies to highly effective all-oral interferon-free regimens. While sustained virologic responses have significantly improved with fixed-dose combinations (FDC) of these direct-acting antivirals (DAA), cost remains high and certain populations of patients remain difficult to treat. Glecaprevir (GLE, an NS3/4A protease inhibitor) and pibrentasvir (PIB, NS5A inhibitor) were recently approved as a FDC therapy for HCV, and have expanded reach, reduced cost, and in certain populations, reduced HCV treatment duration. GLE/PIB is effective across all genotypes, and has been shown to be effective in HIV-infected patients, patients with chronic kidney disease, and Child-Pugh A-compensated cirrhosis. GLE/PIB is also effective for a shortened duration of 8weeks in treatment-naive non-cirrhotic patients.

Eight-Week Outcomes of Ledipasvir/Sofosbuvir in Noncirrhotic Treatment-Naive Patients with Hepatitis C: Analysis of Pharmacy-Based Data.

Clinical trials have demonstrated that 8 weeks of ledipasvir and sofosbuvir (LDV/SOF) achieved high rates of sustained virologic response at 12 weeks (SVR12) in patients with hepatitis C viral (HCV) genotype 1 infection. The effectiveness of this combination was noted to be robust in treatment-naive noncirrhotic patients and in patients with an HCV viral load of < 6 million IU/mL before treatment. Generalizability of these results to community clinical practice, however, was advised with caution due to the variability of staging methods, fluctuating nature of viral loads, lack of prospective trials, and real-life confirmation. To evaluate the efficacy, defined as SVR12, of LDV/SOF in a real-world setting. Patients met inclusion criteria if given 8 weeks of LDV/SOF by a specialty pharmacy from October 2014 to October 2015 and if SVR12 was assessed after therapy completion. Clinical outcomes data were obtained from the pharmacy database. Of the 6,391 prescriptions of LDV/SOF received by the pharmacy, 3,648 (57%) were covered by insurance, and among them, only 511 (14%) were for an 8-week regimen. SVR12 data were available for 380 (74%) patients who completed an 8-week regimen. 230 different prescribers wrote prescriptions, and 57 different insurance plans approved the 8-week regimen. The majority (74%) of patients were followed by gastroenterology clinics. The 380 patients included in the analysis were all treatment-naive HCV genotype 1 patients. Overall, SVR12 was achieved in 97% of patients, while 10 patients relapsed. The SVR12 rates were lower (93%) in patients with stage 3 fibrosis, particularly in African Americans (29 of 35: 83%). Outcomes were favorable for the 8-week use of LDV/SOF in a noncontrolled real-world setting in treatment-naive noncirrhotic patients with a baseline viral load < 6 million IU/mL. Use of this approach in African Americans with evidence of advanced fibrosis should be avoided. No outside funding supported this study. Lott is an employee of Diplomat Pharmacy. Andres and Qureshi have nothing to disclose. Study concept and design were contributed by Lott and Qureshi, who also collected the data. All authors contributed equally to data interpretation and manuscript preparation. Andres revised the manuscript, along with Lott and Qureshi. This work was presented in part as a poster at the 2016 International Liver Conference; Barcelona, Spain; April 13-17, 2016.

Eight Weeks of Ledipasvir/Sofosbuvir in Kidney Transplant Recipients With Hepatitis C Genotype 1 Infection.

Short treatment duration of ledipasvir/sofosbuvir (LDV/SOF) has been successfully used to treat hepatitis C virus (HCV) genotype 1 infection in treatment-naive noncirrhotic patients with viral loads (VLs) under 6 million IU/mL. However, this short duration has not been studied in renal transplant recipients (RTRs), a patient population on lifelong immunosuppression. Here, we describe 3 RTRs who received 8 weeks of LDV/SOF, meeting the standard criteria for shortened treatment duration. All 3 patients tolerated treatment well and achieved sustained virologic response at 12 weeks (SVR 12).

Cost-Effectiveness of Treating Hepatitis C with Sofosbuvir/Ledipasvir in Germany.

BackgroundInfections with the hepatitis C virus (HCV) are a global public health problem. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. Newly introduced direct acting antivirals, especially interferon-free regimens, have improved rates of sustained viral response above 90% in most patient groups and allow treating patients who were ineligible for treatment in the past. These new regimens have replaced former treatment and are recommended by current guidelines. However, there is an ongoing discussion on high pharmaceutical prices. Our aim was to assess the long-term cost-effectiveness of treating hepatitis C genotype 1 patients with sofosbuvir/ledipasvir (SOF/LDV) treatment in Germany.Material and MethodsWe used a Markov cohort model to simulate disease progression and assess cost-effectiveness. The model calculates lifetime costs and outcomes (quality-adjusted life years, QALYs) of SOF/LDV and other strategies. Patients were stratified by treatment status (treatment-naive and treatment-experienced) and absence/presence of cirrhosis. Different treatment strategies were compared to prior standard of care. Sensitivity analyses were performed to evaluate model robustness.ResultsBase-case analyses results show that in treatment-naive non-cirrhotic patients treatment with SOF/LDV dominates the prior standard of care (is more effective and less costly). In cirrhotic patients an incremental cost-effectiveness ratio (ICER) of 3,383 €/QALY was estimated. In treatment-experienced patients ICERs were 26,426 €/QALY and 1,397 €/QALY for treatment-naive and treatment-experienced patients, respectively. Robustness of results was confirmed in sensitivity analyses.ConclusionsOur analysis shows that treatment with SOF/LDV is cost-effective compared to prior standard of care in all patient groups considering international costs per QALY thresholds.

Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection: A Randomized Trial.

Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. To assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6. Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766). 48 U.S. sites. 377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks. Sustained virologic response at 12 weeks (SVR12). In part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with velpatasvir, 25 mg; 83% (25 of 30) with velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with velpatasvir, 100 mg; and 81% (25 of 31) with velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with velpatasvir, 25 mg; 88% (22 of 25) with velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with velpatasvir, 100 mg; and 88% (23 of 26) with velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide. The study was open-label, no inferential statistics were planned, and sample sizes were small. Twelve weeks of sofosbuvir, 400 mg, and velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6. Gilead Sciences.

The cost-effectiveness of sofosbuvir-based regimens for treatment of hepatitis C virus genotype 2 or 3 infection.

Chronic infection with hepatitis C virus (HCV) genotype 2 or 3 can be treated with sofosbuvir without interferon. Because sofosbuvir is costly, its benefits should be compared with the additional resources used. To estimate the cost-effectiveness of sofosbuvir-based treatments for HCV genotype 2 or 3 infection in the United States. Monte Carlo simulation, including deterministic and probabilistic sensitivity analyses. Randomized trials, observational cohorts, and national health care spending surveys. 8 patient types defined by HCV genotype (2 vs. 3), treatment history (naive vs. experienced), and cirrhosis status (noncirrhotic vs. cirrhotic). Lifetime. Payer. Sofosbuvir-based therapies, pegylated interferon-ribavirin, and no therapy. Discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). The ICER of sofosbuvir-based treatment was less than $100,000 per QALY in cirrhotic patients (genotype 2 or 3 and treatment-naive or treatment-experienced) and in treatment-experienced noncirrhotic patients but was greater than $200,000 per QALY in treatment-naive noncirrhotic patients. The ICER of sofosbuvir-based therapy for treatment-naive noncirrhotic patients with genotype 2 or 3 infection was less than $100,000 per QALY when the cost of sofosbuvir was reduced by approximately 40% and 60%, respectively. In probabilistic sensitivity analyses, cost-effectiveness conclusions were robust to uncertainty in treatment efficacy. The analysis did not consider possible benefits of preventing HCV transmission. Sofosbuvir provides good value for money for treatment-experienced patients with HCV genotype 2 or 3 infection and those with cirrhosis. At their current cost, sofosbuvir-based regimens for treatment-naive noncirrhotic patients exceed willingness-to-pay thresholds commonly cited in the United States. National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.