Identification of two novel subtypes of hepatitis C virus genotype 8 and a potential new genotype successfully treated with direct acting antivirals.

BACKGROUND: Hepatitis C virus (HCV) has a high genetic diversity and is classified into 8 genotypes and over 90 subtypes with some endemic to specific world regions. This could compromise direct-acting antiviral (DAA) efficacy and global HCV elimination. METHODS: We characterised HCV subtypes 'rare' to the UK (non-1a/1b/2b/3a/4d) by whole genome sequencing via a national surveillance programme. Genetic analyses to determine the genotype of samples with unresolved genotypes were undertaken by comparison with ICTV HCV reference sequences. RESULTS: Two HCV variants were characterised as being closely related to the recently identified genotype 8 (GT8), with >85% pairwise genetic distance similarity to GT8 sequences and within the typical inter-subtype genetic distance range. The individuals infected by the variants were UK residents originally from Pakistan and India. In contrast, a third variant was only confidently identified to be more similar to GT6 compared to other genotypes across 6% of the genome and was isolated from a UK resident originally from Guyana. All three were cured with pangenotypic DAAs (Sofosbuvir + Velpatasvir or Glecaprevir + Pibrentasvir) despite the presence of resistance polymorphisms in NS3 (80 K/168E), NS5A (28 V/30S/62L/92S/93S) and NS5B (159F). CONCLUSIONS: This study expands our knowledge of HCV diversity by identifying two new GT8 subtypes and potentially a new genotype.

Outcomes of early vs late treatment initiation in solid organ transplantation from hepatitis C virus nucleic acid test-positive donors to hepatitis C virus-uninfected recipients: Results from the HCV-TARGET study.

Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients (D+/R-). We evaluated outcomes of early and late HCV treatment among D+/R- nonliver organ transplants. Patients received HCV regimens per local standard (n = 10 sites). Outcomes were compared between early and late treatments. Early treatment regimens (ETR) (n = 56) were initiated pretransplantation to day 7 posttransplant. Late treatment regimens (LTRs) (n = 102) began median 31 (range, 8-114) days posttransplant. There were 79 kidney, 50 lung, 23 heart, and 6 mixed transplants, similar between groups. HCV RNA was quantifiable in 98% of LTR versus 44.6% of ETR recipients (P < .001). Mean (range) days on treatment were 28 (7-93) ETR and 81 (51-111) LTR (P < .0001). There were no virological failures with ETR, but relapse (n = 3) and nonresponse (n = 2) in LTR (P = .16), including fibrosing cholestatic hepatitis postrelapse (n = 1). Sustained virological response was 100% (95% confidence interval, 93.4-100.0) in ETR (n = 54) and 94.9% (95% confidence interval, 88.5-98.3) in LTR (n = 98). Acute rejection occurred in 11 (19.6%) ETR and 25 (24.5%) LTR. In total, 11 HCV-unrelated deaths occurred: 8 ETR and 3 LTR. Organ transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients was safe. ETR led to fewer virological failures with shorter treatment duration, supporting recommendations to initiate treatment promptly posttransplant.

Optimal hepatitis C treatment adherence patterns and sustained virologic response among people who inject drugs: The HERO study.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are highly effective for treating HCV infection even among people who inject drugs (PWID). Yet, little is known about patients' adherence patterns and their association with sustained virologic response (SVR) rates. We aimed to summarize various adherence patterns and determine their associations with SVR. METHODS: Electronic blister packs were used to measure daily adherence to once-a-day sofosbuvir/velpatasvir during the 12-week treatment period among active PWIDs. Blister pack data were available for 496 participants who initiated DAAs for whom SVR status was known. Adherence was summarized in multiple patterns, such as total adherent days, consecutive missed days, and early discontinuations. Thresholds for adherence patterns associated with >90% SVR rates were also determined. RESULTS: The overall SVR rate was 92.7%, with a median adherence rate of 75%. All adherence patterns indicating greater adherence were significantly associated with achieving SVR. Participant groups with ≥50% (>42/84) adherent days or <26 consecutive missed days achieved an SVR rate of >90%. Greater total adherent days during 9-12 weeks and no early discontinuation were significantly associated with higher SVR rates only in those with <50% adherence. Participants with first month discontinuation and ≥2 weeks of treatment interruption had low SVR rates, 25% and 85%, respectively. However, greater adherent days were significantly associated with SVR (adjusted odds ratio 1.10; 95% CI 1.04-1.16; p <0.001) even among participants with ≥14 consecutive missed days. CONCLUSIONS: High SVR rates can be achieved in the PWID population despite suboptimal adherence. Encouraging patients to take as much medication as possible, with <2 weeks consecutive missed days and without early discontinuation, was found to be important for achieving SVR. IMPACT AND IMPLICATIONS: People who inject drugs can be cured of HCV in >90% of cases, even with relatively low adherence to direct-acting antivirals, but early discontinuations and long treatment interruptions can significantly reduce the likelihood of achieving cure. Clinicians should encourage people who inject drugs who are living with HCV to adhere daily to direct-acting antivirals as consistently as possible, but if any days are interrupted, to continue and complete treatment. These results from the HERO study are important for patients living with HCV, clinicians, experts writing clinical guidelines, and payers. CLINICAL TRIAL NUMBER: NCT02824640.

Recently acquired HCV infection in men who have sex with men in Germany in the direct-acting antivirals era and during the COVID-19 pandemic.

INTRODUCTION: Direct-acting antivirals (DAAs) are key to eliminating hepatitis C virus (HCV). In men who have sex with men (MSM) with HIV co-infection, recently acquired HCV infection is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates. METHODS: The cohort included MSM with recently acquired HCV infection from 2014 to 2021. The patients' demographic, clinical, behavioural, and laboratory data and treatment and reinfection outcomes were documented. RESULTS: A total of 237 men with recently acquired HCV infection were included: 216 (91%) had HIV. The median age was 46 years (interquartile range [IQR] 39-52), and the median CD4 count was 660/mm3 (IQR 527-835). The annual incidence of recently acquired HCV remained between 0.28% and 0.43% but dropped to 0.02% in 2021 during the COVID pandemic, almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95% confidence interval 12.6-18.8), and reinfection was associated with the use of crystal methamphetamine (p = 0.032) and ketamine (p = 0.042). In total, 31.3% had multiple reinfections, and four reinfections occurred in users of pre-exposure prophylaxis. CONCLUSIONS: High treatment and cure rates did not lead to HCV elimination. A change in sexual behaviour, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As recently acquired HCV is prevalent in MSM with and without HIV, surveillance is necessary to consolidate elimination goals.

Sex-related difference analyses of efficacy and safety in clinical trials of direct-acting antivirals to treat chronic HCV genotype 1 and 3 infections.

This study aims to identify clinically meaningful sex differences in efficacy and selected safety adverse events for the treatment of chronic hepatitis C virus infection (HCV) or HIV/HCV co-infection in those receiving combination direct-acting antiviral (DAA) regimens. Our assessment was based on adult trial participants treated at the approved DAA dosage and treatment duration from 40 phase 3 clinical trials submitted to the FDA. Female enrollment ranged from 11% to 54% (overall mean 38%). Females with HCV genotype (GT) 1 or 3 infection had statistically significant higher unadjusted or covariant-adjusted odds of achieving sustained virologic response at post-treatment Week 12 (SVR12) compared with males. Odds ratios favouring females were observed among Whites and those ≥40 years of age with HCV GT1 or 3 infections, and among those ≥50 years of age, non-cirrhotic and those with HCV GT3 infection who were treatment-experienced. These differences were not clinically relevant due to the high SVR12 rate achieved by females and males, overall or in subgroups. No differences were observed in SVR12 rates between HCV GT1 mono-infected and HCV GT1/ HIV-1 co-infected participants. Numerically, more females reported headache, fatigue and nausea compared to males, but the differences were small and predominately Grade 1 or 2 severity. Discontinuation rates for any reason or due to an adverse event were low and similar between the sexes. Our study demonstrated females successfully complete DAA regimens and achieve high SVR12 rates despite numerically higher adverse events for certain commonly reported events.

Hepatitis C epidemiology and treatment outcomes in Italy: Impact of the DAA era and the COVID-19 pandemic.

HCV infection poses a global health threat, with significant morbidity and mortality. This study examines HCV trends in a large Italian region from 2015 to 2022, considering demographic changes, evolving clinical profiles, treatment regimens and outcomes, including the impact of the COVID-19 pandemic. This multicentre retrospective study analysed demographics, clinical histories and risk factors in 6882 HCV patients. The study spanned before and after the direct-acting antiviral (DAA) era, and the COVID-19 period, focusing on treatment outcomes (SVR12, non-SVR12 and patients lost to follow-up). Statistical methods included ANOVA, multinomial logistic regression, Kruskal-Wallis test and chi-square analysis, and were conducted adhering to the intention-to-treat (ITT) principle. The cohort, mainly Italian males (average age 58.88), showed Genotype 1 dominance (56.6%) and a high SVR12 rate (97.5%). The pandemic increased follow-up losses, yet SVR12 rates remained stable, influenced by factors like age, gender, cirrhosis and comorbidities. Despite COVID-19 challenges, the region sustained high SVR12 rates in HCV care, emphasising the importance of sustained efforts in HCV care. Continuous screening and targeted interventions in high-risk populations are crucial for achieving WHO elimination targets. The study highlights the resilience of HCV care during the pandemic and provides insights for future public health strategies.

A Programme of Hepatitis C Surveillance With Active Linkage to Care (HEAL) for Inpatients in Two Tertiary Hospitals in Jiangsu, China.

Hepatitis C virus (HCV) infection is a major public health burden in China, affecting more than 10 million individuals. We aimed to evaluate the effectiveness of a hospital-based intervention programme for HCV Surveillance with linkage to care (HEAL) in a prospective cohort. The HEAL programme was carried out targeting inpatients from non-infectious departments of two tertiary hospitals in Jiangsu, China. It consisted of an educational campaign to raise awareness of physicians from non-IDs to promote HCV surveillance, a patient-navigator-centred clinical algorithm responsible for the efficient follow-up of patients with positive HCV antibody, including comprehensive testing, diagnosis and treatment. We characterised the rate of linkage to HCV diagnosis, care and treatment during the pre-intervention period (from 1 July 2016 and June 30, 2018) and after the intervention (from March 2019 to May 2021). During the pre-intervention period, 89,303 (45.3%) out of 196,780 non-ID inpatients were screened for anti-HCV, and 631 patients were tested positive. One hundred and fifty-six (24.7%) patients was followed up for HCV RNA confirmatory testing, and 58 (37.1%) of patients further were diagnosed with chronic HCV infection (CHC). Only 18 (31.3%) of the diagnosed patients with CHC were linked to hepatitis C clinics for treatment, 10 (55.6%) patients received antiviral regimen. Among them, two (11.1%) received DAA treatment, while eight (44.4%) adopted peginterferon/ribavirin regimen. During the intervention period, 232,275 patients were hospitalised in non-infectious department and 151,203 (65.1%) were screened for anti-HCV. Of these, 960 patients tested positive for HCV antibodies, resulting in a prevalence of anti-HCV positivity of 0.63%. Six hundred and seventy (69.8%) patients were enrolled, and 100% were followed up for HCV RNA confirmatory testing. Two hundred and ninety-one (43.4%) individuals with active HCV were identified. Two hundred and thirty-eight (81.8%) of HCV-infected individuals were linked to HCV care, and 157 (65.9%) were linked to treatment. Compared to the pre-intervention period, there was a 2.61-fold increase in the percentage of patients linked to care and a 5.94-fold increase in the proportion of patients who started DAAs therapy. This HEAL programme achieved enhanced HCV Surveillance with linkage to care, which has been demonstrated as an effective strategy in the hospital setting to improve the hepatitis C care continuum by identifying inpatients unaware of their HCV status and facilitating their access to HCV treatment.

Community Pop-Up Clinic: Cascade of Care and HCV Treatment of Vancouver's Inner-City PWID Populations.

Elimination of HCV infection as a public health concern by the end of this decade will require a concerted effort in all target populations, including drug-users in the inner-city. Several strategies have been proposed to identify, engage and provide HCV-infected residents with antiviral therapy and maximise treatment and cure achievement. This study aims to assess the effectiveness of a multidisciplinary approach in delivering HCV treatment to people who inject drugs (PWID) within Vancouver's inner city. We have evaluated a novel approach, the Community Pop-Up Clinic, for its ability to promote access to care and uptake of HCV therapy, with additional analyses of HCV reinfection and opioid-related mortality. From January 2021 to August 2023, we evaluated 1968 individuals. 620 (31.5%) were found to carry HCV antibodies and of these, 474 (76.5%) were found to be viremic. Treatment engagement has been secured in 387 (81.6%). 326 (84.2%) have started treatment, 60 in the pre-treatment phase and 1 died of an overdose in pre-treatment. Of 326, 302 completed treatments, 18 are currently on treatment and 1 died of an overdose. Of 302 who completed treatment, 286 confirmed as cured (SVR 12), 16 are awaiting SVR 4, 2 had documented virologic relapse and 1 was reinfected. Three patients withdrew from treatment. By mITT, the cure rate is 286/288 (99.3%). We documented 2 overdose deaths over 326 PY. The data presented validates multidisciplinary programs such as ours aimed at treating HCV in inner-cities and highlights societal benefits that could be achieved including lower overdose death rates.

A systematic PCR record-based re-call of HCV-RNA-positive people enables re-linkage to care and HCV elimination in Austria - The ELIMINATE project.

BACKGROUND AND AIMS: Identification of people living with hepatitis C virus (HCV) via readily available laboratory records could be a key strategy for macro-elimination, aligning with the WHO elimination goal. Therefore, the ELIMINATE(ELIMINation of HCV in AusTria East) project aimed to systematically re-link people with a 'last-positive' HCV-RNA PCR record to care. METHODS: In 10 major liver centres in Eastern Austria, a systematic readout of 'last-positive' HCV-RNA PCR test records obtained between 2008 and 2020 were conducted and linked to available patient contact data. Between 2020 and 2023, individuals were contacted first by phone, then by letter, to inform them about the availability of effective direct-acting antiviral (DAA) treatment and invite them for pre-treatment evaluation. RESULTS: The overall cohort of last-positive HCV+ individuals included 5695 subjects (62.5% males, mean age 57.3 ± 17.3 years); of note, 1931 (34%) of them had died and 759 (13%) individuals had no valid contact information. Of the remaining 3005 individuals, 1171 (40.0%) had already achieved sustained virological response (SVR) at the time of re-call. We successfully reached 617 (20.5%), of whom 417 (67.6%) attended their pre-treatment visit, and 397 (64.3%) commenced DAA-therapy. HCV cure has been confirmed in 326 individuals, corresponding to an SVR rate of 82.1%. CONCLUSION: The ELIMINATE project identified 5695 people living with HCV who were 'lost to care' despite documented HCV viraemia. While invalid contact data were an evident barrier to HCV elimination, premature deaths among the cohort underscored the severity of untreated HCV. The implementation of a systematic HCV-RNA PCR recorded-based re-call workflow represents an effective strategy supporting the WHO goal of HCV elimination.

Persistent pruritus associated with worse quality of life in patients with chronic hepatitis.

INTRODUCTION: Prevalence and severity of pruritus among US patients with chronic hepatitis B and C (HBV, HCV) are not well-documented. Chronic Hepatitis Cohort Study (CHeCS) patients were surveyed to examine pruritus prevalence and impact on quality of life (QoL). METHODS: Patients who reported experiencing pruritus ≥3 on a Numeric Rating Scale (NRS) within the past 30 days were invited to participate in a 6-month study using the SF-36 questionnaire. General regression (univariate followed by multivariable modelling) was used to analyse pruritus intensity and eight QoL dimensions. RESULTS: Among 1654 patients (HBV = 358, HCV = 1296, HBV/HCV = 6), pruritus prevalence was significantly higher among patients with HCV than those with HBV (44% vs. 35%; p < .05). One hundred and twenty-three patients (21 HBV and 102 HCV) participated in the QoL study (72% ≥60 years; 50% men; 25% Black; 37% with cirrhosis; 66% had BMI > 25). Mean NRS was 4.9-5.3. QoL responses for social functioning and emotional well-being were higher (70-72 points) than responses for energy/fatigue (50-51). Antiviral treatment rates were higher in HCV (92%, SVR 99%) than HBV (71% ever, 43% ongoing). Multivariable analyses showed no significant effect of hepatitis type or antiviral treatments on itch. Antihistamines were associated with severe itch. Higher NRS was associated with significantly reduced QoL. Each unit increase in NRS was associated with a 2-3 unit decline in emotional well-being, general health, physical function, energy/fatigue, social functioning and emotional health. CONCLUSION: Pruritus negatively affects many viral hepatitis patients, regardless of antiviral treatment status. Improved treatment options are needed to address its impact on QoL.

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study.

BACKGROUND AND AIMS: Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS: We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS: Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS: The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C.

Designing cities for everyday nature.

The motivations for incorporating nature into the design of cities have never been more compelling. Creating experiences with nature that occur every day (everyday nature) in cities could help reverse the fate of many threatened species and connect people with nature and living cultural traditions. However, this requires more than just urban greening; it involves ensuring daily doses of nature in a way that also supports nonhuman organisms. A major shift in the way nature is conceived of and is made part of the design of cities is required. Principles include reconsidering nature as a development opportunity rather than a constraint and eliminating offsetting of biodiversity site values. Processes include using biodiversity-sensitive design frameworks and establishing meaningful professional engagement among ecologists, planners, and designers. Challenges include design obstacles, conflicts between nature and people (e.g., safety, disease, and noise) that require careful management, and socioeconomic and political considerations (e.g., Global North vs. Global South). Research to interrogate the multiple benefits of nature in cities can complement experimental interventions, ultimately supporting better urban design and creating much more resiliently built environments for people and nature.

Diseño de ciudades para la naturaleza cotidiana Resumen Los motivos para incorporar a la naturaleza dentro del diseño urbano jamás habían sido tan convincentes. La creación en las ciudades de experiencias con la naturaleza que ocurren a diario (naturaleza cotidiana) podría ayudar a cambiar el destino de muchas especies amenazadas y conectar a las personas con la naturaleza y las tradiciones culturales vivientes. Lo anterior requiere más que reverdecimiento urbano ya que involucra dosis diarias de naturaleza de manera que también mantengan a los organismos no humanos. Se necesita de un cambio mayor en la manera en la que se concibe a la naturaleza y cómo se le hace parte del diseño urbano. Los principios incluyen reconsiderar a la naturaleza como una oportunidad de desarrollo en lugar de una limitación y eliminar la compensación del valor de los sitios de biodiversidad. Los procesos incluyen el uso de marcos de diseños sensibles con la biodiversidad y el establecimiento de una participación profesional significativa entre los ecologistas, los planeadores y los diseñadores. Los retos incluyen los obstáculos del diseño, conflictos entre la naturaleza y las personas (seguridad, enfermedades y ruido) que requieren de un manejo cuidadoso y consideraciones políticas (Norte Global versus Sur Global). La investigación para interrogar los múltiples beneficios de la naturaleza en las ciudades puede complementar a las intervenciones, a la larga respaldando un mejor diseño urbano y creando ambientes para las personas y la naturaleza construidos con mayor resiliencia.

Evaluating hepatitis C cascade of care surveillance system in Tuscany, Italy, through a population retrospective data-linkage study, 2015-2021.

This comprehensive retrospective data-linkage study aimed at evaluating the impact of Direct-Acting Antivirals (DAAs) on Hepatitis C Virus (HCV) testing, treatment trends, and access to care in Tuscany over six years following their introduction. Utilizing administrative healthcare records, our work reveals a substantial increase in HCV tests in 2017, attributed to the decision to provide universal access to treatment. However, despite efforts to eradicate chronic HCV through a government-led plan, the target of treating 6,221 patients annually was not met, and services contracted after 2018, exacerbated by the COVID-19 pandemic. Key findings indicate a higher prevalence of HCV screening among females in the 33-53 age group, influenced by pregnancy-related recommendations, while diagnostic tests and treatment uptake were more common among males. Problematic substance users constituted a significant proportion of those tested and treated, emphasizing their priority in HCV screening. Our paper underscores the need for decentralized HCV models and alternative testing strategies, such as point-of-care assays, especially in populations accessing harm reduction services, communities, and prisons. The study acknowledges limitations in relying solely on administrative records, advocating for improved data access and timely linkages to accurately monitor HCV care cascades and inform regional plans. Despite challenges, the paper demonstrates the value of administrative record linkages in understanding the access to care pathway for hard-to-reach populations. The findings emphasize the importance of the national HCV elimination strategy and the need for enhanced data collection to assess progress accurately, providing insights for future regional and national interventions.

Overreporting of adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs in the HERO study.

BACKGROUND: Self-reported adherence to direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) among persons who inject drugs (PWID) is often an overreport of objectively measured adherence. The association of such overreporting with sustained virologic response (SVR) is understudied. This study among PWID aimed to determine a threshold of overreporting adherence that optimally predicts lower SVR rates, and to explore correlates of the optimal overreporting threshold. METHODS: This study analyzed per-protocol data of participants with adherence data (N = 493) from the HERO (Hepatitis C Real Options) study. Self-reported and objective adherence to a 12-week DAA regimen were measured using visual analogue scales and electronic blister packs, respectively. The difference (Δ) between self-reported and objectively measured adherence was calculated. We used the Youden index based on receiver operating characteristic (ROC) curve analysis to identify an optimal threshold of overreporting for predicting lower SVR rates. Factors associated with the optimal threshold of overreporting were identified by comparing baseline characteristics between participants at/above versus those below the threshold. RESULTS: The self-reported, objective, and Δ adherence averages were 95.1% (SD = 8.9), 75.9% (SD = 16.3), and 19.2% (SD = 15.2), respectively. The ≥ 25% overreporting threshold was determined to be optimal. The SVR rate was lower for ≥ 25% vs. < 25% overreporting (86.7% vs. 95.8%, p <.001). The factors associated with ≥ 25% Δ adherence were unemployment; higher number of days and times/day of injecting drugs; higher proportion of positive urine drug screening for amphetamine, methamphetamine, and oxycodone, and negative urine screening for THC (tetrahydrocannabinol)/cannabis. CONCLUSIONS: Self-reported DAA adherence was significantly greater than objectively measured adherence among PWID by 19.2%. Having ≥ 25% overreported adherence was associated with optimal prediction of lower SVR rates. PWID with risk factors for high overreporting may need to be more intensively managed to promote actual adherence.

High prevalence of hepatitis C virus among criminals in rehabilitation facilities in Japan.

OBJECTIVE: There is a high prevalence of hepatitis C virus (HCV) carriers in prison in several developed countries, but the situation in Japan has not been well reported. This study aimed to determine the state of HCV infection among criminals in Japan. METHODS: We enrolled 533 criminals in rehabilitation facilities (354 men and 179 women) who underwent a medical check-up from April 2014 to March 2022. Their records of blood tests, medical history, and drug injection use were retrospectively analyzed. RESULTS: The HCV-antibody positive rate was 11.1 % (59/533), with rates of 8.2 % (29/354) in men and 16.8 % (30/179 in women. Approximately half of the HCV-infected residents had a history of drug injection, and this rate did not vary by age or by sex. Although an opportunity to treat HCV infection with medical assistance from government was provided to all residents who were positive for HCV RNA, 26.5 % of them abandoned the treatment. CONCLUSION: In spite of the generous economical support to treat HCV infection by the government and the free access system in Japan, eliminating HCV in criminals appears to be difficult. The reason for this problem might be the criminals' negligent attitude to life.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

Simultaneous Bilateral Total Hip Arthroplasty With Either the Direct Anterior or Posterior Approaches: A Propensity Score Match Study.

BACKGROUND: Bilateral hip osteoarthritis is evident in approximately 20% of patients who present to the clinic for evaluation of hip pain, and for those undergoing total hip arthroplasty (THA), 22% will end up needing a contralateral THA. The risk and benefits of simultaneous bilateral total hip arthroplasty (SBTHA) versus staged bilateral THA procedures have been well studied, demonstrating equivalent safety profiles comparable to unilateral and SBTHA. However, the influence of the surgical approach on SBTHA on postoperative outcomes remains unclear. We sought to compare perioperative outcomes and complication rates between the direct anterior approach (DAA) and posterior approach (PA) in patients undergoing SBTHA. METHODS: We performed a 1:1 propensity score match based on age, sex, and body mass index. A total of 252 patients were available after matching, 126 patients in the DAA group and 126 in the PA group. Perioperative outcomes as well as surgical complications at the latest follow-up were retrospectively collected for each group. The mean follow-up was 36.7 months (range, 12.5 to 74.4). RESULTS: A SBTHA with DAA had significantly shorter surgical time (P < 0.001), anesthesia time (P < 0.001), and length of stay (P < 0.001), compared to the PA. A greater percentage of patients in the DAA group (91%) were discharged home compared to the PA group (57%) (P < 0.001). There were no differences in in-hospital complications (P = 0.617), 90-day complications (P = 0.605), or reoperation rates (P = 0.309) between surgical approaches. CONCLUSIONS: A SBTHA, either through the DAA or PA, can be safely performed with low complication rates. The DAA in the setting of SBTHA provides shorter surgical times, a shorter length of stay, and a greater percentage of patients discharged home.

After the Storm: Persistent Molecular Alterations Following HCV Cure.

The development of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has revolutionized the management of this pathology, as their use allows viral elimination in a large majority of patients. Nonetheless, HCV remains a major public health problem due to the multiple challenges associated with its diagnosis, treatment availability and development of a prophylactic vaccine. Moreover, HCV-cured patients still present an increased risk of developing hepatic complications such as hepatocellular carcinoma. In the present review, we aim to summarize the impact that HCV infection has on a wide variety of peripheral and intrahepatic cell populations, the alterations that remain following DAA treatment and the potential molecular mechanisms implicated in their long-term persistence. Finally, we consider how recent developments in single-cell multiomics could refine our understanding of this disease in each specific intrahepatic cell population and drive the field to explore new directions for the development of chemo-preventive strategies.

The Effect of Conjugated Nitrile Structures as Acceptor Moieties on the Photovoltaic Properties of Dye-Sensitized Solar Cells: DFT and TD-DFT Investigation.

A major challenge in improving the overall efficiency of dye-sensitized solar cells is improving the optoelectronic properties of small molecule acceptors. This work primarily investigated the effects of conjugation in nitriles incorporated as acceptor moieties into a newly designed series of D-A-A dyes. Density functional theory was employed to specifically study how single-double and single-triple conjugation in nitriles alters the optical and electronic properties of these dyes. The Cy-4c dye with a highly conjugated nitrile unit attained the smallest band gap (1.80 eV), even smaller than that of the strong cyanacrylic anchor group (2.07 eV). The dyes lacking conjugation in nitrile groups did not contribute to the LUMO, while LUMOs extended from donors to conjugated nitrile components, facilitating intramolecular charge transfer and causing a strong bind to the film surface. Density of state analysis revealed a considerable impact of conjugated nitrile on the electronic properties of dyes through an effective contribution in the LUMO, exceeding the role of the well-known strong 2,1,3-benzothiadiazole acceptor unit. The excited state properties and the absorption spectra were investigated using time-dependent density functional theory (TD-DFT). Conjugation in the nitrile unit caused the absorption band to broaden, strengthen, and shift toward the near-infrared region. The proposed dyes also showed optimum photovoltaic properties; all dyes possess high light-harvesting efficiency (LHE) values, specifically 96% for the dyes Cy-3b and Cy-4c, which had the most conjugated nitrile moieties. The dyes with higher degrees of conjugation had longer excitation lifetime values, which promote charge transfer by causing steady charge recombination at the interface. These findings may provide new insights into the structure of conjugated nitriles and their function as acceptor moieties in DSSCS, which may lead to the development of extremely effective photosensitizers for solar cells.

"Heterotopic ossification after total hip arthroplasty through direct anterior approach without a dedicated orthopaedic table or direct lateral approach: a quasi-randomized single-center study".

INTRODUCTION: Heterotopic ossifications (HO) are common after total hip arthroplasty (THA). The invasiveness of surgical approaches plays a relevant role in HO development. The aims of this study were to assess the development of HO 6 months after THA through direct lateral approach (DLA) or direct anterior approach (DAA) without a dedicated orthopaedic table and to assess the clinical impact of HO. METHODS: This is a single-center IRB-approved, quasi-randomized prospective cohort, observational imaging study. Fifty patients underwent primary THA through DLA and 50 through DAA. Age, sex, BMI and side of the affected hip were collected. At the 6 post-operative month the Harris Hip Score (HHS) and the presence of HO (scored through the Brooker classification system) were assessed. RESULTS: There was no significant difference in the demographic data between groups. Operative time was significantly higher in the DAA group (72 ± 10 min vs. 58 ± 8 min: p < 0.03). At 6 post-operative months the incidence of HO was 14% in the DAA group and 32% in the DLA group (p = 0.02). Severe HO (Brooker 3-4) were significantly more common in the DLA group (p = 0.04). There was no significant difference in the HHS of patients with HO between the DAA and DLA groups. There was no association between poorer clinical outcomes and the severity of HO. CONCLUSION: The DAA without a dedicated orthopaedic table is associated with a significant lower incidence of HO than the DLA 6 months after elective THA. Except for the surgical approach, no other factors correlated with the occurrence of HO. Even though a lower HHS was found with severe HO, the correlation between severity of HO and clinical outcomes did not reach statistical significance.