Cost-Effectiveness Analysis of Pan-Genotypic Sofosbuvir-Based Regimens for Treatment of Chronic Hepatitis C Genotype 1 Infection in China

Background: Hepatitis C virus (HCV) genotype 1 is the most prevalent HCV infection in China. Sofosbuvir-based direct antiviral agent (DAA) regimens are the current mainstays of treatment. Sofosbuvir/velpatasvir (SOF/VEL) and sofosbuvir/ledipasvir (SOF/LDV) regimens became reimbursable in China in 2020. Thus, this study aimed to identify the optimal SOF-based regimen and to inform efficient use of healthcare resources by optimizing DAA use in treating HCV genotype 1.Methods and Models: A modeling-based cost-utility analysis was conducted from the payer's perspective targeting adult Chinese patients with chronic HCV genotype 1 infection. Direct medical costs and health utilities were inputted into a Markov model to simulate lifetime experiences of chronically infected HCV patients after receiving SOF/LDV, SOF/VEL or the traditional strategy of pegylated interferon (pegIFN) + ribavirin (RBV). Discounted lifetime cost and quality adjusted life years (QALYs) were computed and compared to generate the incremental cost utility ratio (ICUR). An ICUR below the threshold of 31,500 $/QALY suggests cost-effectiveness. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of model findings.Results: Both SOF/LDV and SOF/VEL regimens were dominant to the pegIFN + RBV regimen by creating more QALYs and incurring less cost. SOF/LDV produced 0.542 more QALYs but cost $10,390 less than pegIFN + RBV. Relative to SOF/LDV, SOF/VEL had an ICUR of 168,239 $/QALY which did not meet the cost-effectiveness standard. Therefore SOF/LDV was the optimal strategy. These findings were robust to linear and random variations of model parameters. However, reducing the SOF/VEL price by 40% would make this regimen the most cost-effective option.Conclusions: SOF/LDV was found to be the most cost-effective treatment, and SOF/VEL was also economically dominant to pegIFN + RBV. These findings indicated that replacing pegIFN + RBV with DAA regimens could be a promising strategy.

Cost-utility Analysis of Second-generation Direct-acting Antivirals for Hepatitis C

Background: Hepatitis C virus (HCV) can lead to increased mortality, disability, and liver transplantation if left untreated, and it is associated with a possible increase in disease burden in the future, all of which would surely have a significant impact on the health system. New antiviral regimens are effective in the treatment of the disease yet expensive. Objectives: The purpose of the present study was to assess the cost-effectiveness of three medication regimens, namely, ledipasvir/sofosbuvir (LDV/SOF), velpatasvir/sofosbuvir, and daclatasvir/sofosbuvir (DCV/SOF) for HCV patients with genotype 1 in Iran. Methods: A Markov model with a lifetime horizon was developed to predict the costs and outcomes of the three mentioned medication therapy strategies. The final outcome of the study was quality-adjusted life-years (QALYs), which was obtained using the previously published studies. The study was conducted from the perspective of the Health Ministry; therefore, only direct medical costs were estimated. The results were provided as the incremental cost-effectiveness ratio (ICER) per QALY. Ultimately, the one-way and probabilistic sensitivity analyses were used to measure the strength of study results. Results: The results showed that the QALYs for LDV/SOF, DCV/SOF, and VEL/SOF were 13.25, 13.94, and 14.61, and the costs were 4,807, 7,716, and 4,546$, respectively. The VEL/SOF regimen had lower costs and higher effectiveness than the LDV/SOF and DCV/SOF regimens, making it a dominant strategy. The tornado diagram results showed that the study results had the highest sensitivity to chronic hepatitis C (CHC) and compensated cirrhosis (CC) state costs. Moreover, the scatter plots showed that the VEL/SOF was the dominant therapeutic strategy in 73% of the simulations compared to LDV/SOF and 66% of the simulations compared to DCV/SOF; moreover, it was in the acceptable region in 92% of the simulations and below the threshold. Therefore, it was considered the most cost-effective strategy. Moreover, the results showed that DCV/SOF was in the acceptable region below the threshold in 69% of the simulations compared to LDV/SOF. Therefore, the DCV/SOF regimen was more cost-effective than LDV/SOF. Conclusions: According to the present study results, it is suggested that the VEL/SOF regimen be used as the first line of therapy in patients with HCV genotype 1. Moreover, DCV/SOF can be the second-line medication regimen.

A Novel Subtype of Bovine Hepacivirus Identified in Ticks Reveals the Genetic Diversity and Evolution of Bovine Hepacivirus

Hepaciviruses represent a group of viruses that pose a significant threat to the health of humans and animals. New members of the genus Hepacivirus in the family Flaviviridae have recently been identified in a wide variety of host species worldwide. Similar to the Hepatitis C virus (HCV), bovine hepacivirus (BovHepV) is hepatotropic and causes acute or persistent infections in cattle. BovHepVs are distributed worldwide and classified into two genotypes with seven subtypes in genotype 1. In this study, three BovHepV strains were identified in the samples of ticks sucking blood on cattle in the Guangdong province of China, through unbiased high-throughput sequencing. Genetic analysis revealed the polyprotein-coding gene of these viral sequences herein shared 67.7–84.8% nt identity and 76.1–95.6% aa identity with other BovHepVs identified worldwide. As per the demarcation criteria adopted for the genotyping and subtyping of HCV, these three BovHepV strains belonged to a novel subtype within the genotype 1. Additionally, purifying selection was the dominant evolutionary pressure acting on the genomes of BovHepV, and genetic recombination was not common among BovHepVs. These results expand the knowledge about the genetic diversity and evolution of BovHepV distributed globally, and also indicate genetically divergent BovHepV strains were co-circulating in cattle populations in China.

Consumption and use of the main nutrients of the ration when crossbreeding cattle of Kazakh White-headed and Hereford breeds

Crossbreeding in cattle contributes to the production of crossbred young animals, which due to enriched heredity have the potential for intensive growth and achieving a high level of beef productivity. The purpose of the work was to study the infl uence of crossbreeding of cattle of Kazakh White-headed and Hereford breeds on the efficiency of consumption and use of the main nutrients of the ration by steers, heifers and castrated steers. For the experiment, 3 groups of heifers and 6 groups of steers of the following genotypes have been formed: the 1st Kazakh White-headed, the 2nd – 1/2 Hereford×1/2 Kazakh White-headed, the 3rd – 3/4 Kazakh White-headed×3/4 Hereford. At the age of 3 months half of the steers were castrated. It has been found that purebred animals were inferior to crossbreds from the crossbreeding of cattle of Kazakh White-headed and Hereford breeds. For example, during the rearing period, purebred animals of Kazakh White-headed breed consumed 2638,8– 3272,1 feed units and 2674,8–3549,2 EFU, crossbreds of the genotype 1/2 Hereford×1/2 Kazakh White–headed – 2811,6–3389,2 feed units and 2836,4–3640,1 EFU, crossbreds of the genotype 3/4 Kazakh White-headed×3/4 Hereford – 2749,2–3332,1 feed units and 2764,3–3332,0 EFU, metabolic energy, respectively, by genotypes – 26 748,1–35 492,1 MJ, 28 364,2 – 36 401,2 MJ and 27 643,1–35 941,9 MJ, digestible protein – 246,0–344,2 kg, 296,1–356,9 kg and 289,2–350,5 kg, crude protein-350,9–451,4 kg, 365,2–466,8 kg and 362,1–460,5 kg. The crossbreeding of cattle of Kazakh White-headed and Hereford breeds had a certain influence on the studied indicators. Thus, the best indicators of the efficiency of consumption and use of the main nutrients of the ration among steers, heifers and castrated steers were distinguished by half-blood crossbreds. At the same time, the largest amount of consumption of all nutrients in the ration was distinguished by steers, the smallest – heifers, castrated steers occupied an intermediate position.

Prevalence and Genotyping of Pneumocystis jirovecii Pneumonia in Patients with Previously Untreated Acute Myeloid Leukemia

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection affecting immunocompromised patients. Patients with acute myeloid leukemia (AML) are not considered at high risk of PJP, thus, prophylaxis is not recommended. Between 2010 and 2020 we retrospectively analyzed 251 AML patients. We performed molecular diagnosis and genotyping of Pneumocystis jirovecii in 67 bronchoalveolar lavage samples. Eleven cases of PJP were diagnosed, with a prevalence of 4.3%. Our study confirms that the most widespread genotype in Europe is genotype 1; in our patients, 70% presented with genotype 1 and 30% the genotype 3.

Characterization of a Novel Hepatitis C Virus Genotype 1 Subtype from a Patient Failing 4 Weeks of Glecaprevir-Pibrentasvir Treatment

Limited information is available in relation to surveillance, genotyping, genome sequences, and treatment outcomes for rare hepatitis C virus variants. Here, we have characterized a novel subtype of major hepatitis C virus genotype 1, which was deep sequenced before and after treatment failure with 4 weeks of glecaprevir and pibrentasvir.