Knowledge of, and attitude towards, the treatment of hepatitis C in people who inject drugs.

BACKGROUND: Direct acting antivirals (DAAs) as a curative treatment of hepatitis C have been available for several years and have replaced interferon-containing therapies. However, treatment rates of people who inject drugs (PWID) are declining in Germany, putting the elimination of hepatitis C by 2030 at risk. This study aimed at elucidating the knowledge of, and attitude towards, hepatitis C treatment in a clinical sample of PWID. METHODS: Participants were recruited between February 2019 and October 2020 at two opioid agonist therapy (OAT) clinics and two in-patient drug detoxification wards. Based on the European Addiction Severity Index (Europ-ASI), a standardized interview focusing on: sociodemographic data, drug history, risky behavior, infection with hepatitis C virus (HCV) and HIV, and previous experience with HCV treatment was carried out. In addition, participants filled in a questionnaire evaluating 13 statements relating to HCV treatment (right/wrong) and 15 statements on their personal 'pros and cons' views to start such a treatment assessed with the means of a 6-point Likert scale. RESULTS: A total of 153 patients (average age 45 years, male 78%; 106 (69.3%) currently in opioid maintenance treatment, 47 (30.7%) currently admitted to an inpatient detoxification) with an opioid use disorder were investigated. All of them reported having injected drugs at least once in their lives; 97 participants (63.3%) stated that they had been previously diagnosed with HCV infection. Among them, 27/97 patients (27.8%) reported a previous treatment with interferon; 27/97 (27.8%) with DAAs; and 32/97 (33.0%) reported a currently active hepatitis C. Most patients knew about the availability and efficacy of DAAs. However, DAAs' low rate of side effects, their short treatment duration, and their replacement of interferon, were not correctly evaluated by up to 50.3% of patients. 25-40% of 32 patients with currently active hepatitis C prioritized handling of social and other medical issues, e.g., reduction of heroin use, over treatment of hepatitis C. CONCLUSIONS: Although current levels of risky behavior have reportedly been reduced by active PWID over the past few years, educational and motivational interventions to increase hepatitis C treatment uptake should address the gaps in patients' knowledge.

Assessment of Liver Stiffness Regression and Hepatocellular Carcinoma Risk in Chronic Hepatitis C Patients after Treatment with Direct-Acting Antiviral Drugs.

Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023-0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.

Safety and Efficacy of 8 Weeks Ledipasvir/Sofosbuvir for Chronic Hepatitis C Genotype 4 in Children Aged 4-10 Years.

OBJECTIVE: To evaluate the safety and efficacy of shortened 8-week regimen of ledipasvir/sofosbuvir (LED/SOF) combination therapy in treatment-naïve children without cirrhosis aged 4-10 years of age with chronic hepatitis C virus (HCV) infection. STUDY DESIGN: This observational single arm prospective study included 30 treatment-naïve children (20 males) with proved chronic HCV fulfilling inclusion criteria. Their body weights ranged from 17 to 26 kg. Four patients were excluded from the study. All the included children received a single oral dose of LED/SOF 45/200 mg for 8 weeks. Body weight, HCV-RNA, complete blood count, and liver function tests were monitored at 0, 2, 4, and 8 weeks and sustained virologic response was evaluated after 12 weeks after treatment (SVR12). The emergence of any side effects was also monitored. RESULTS: The most common risk factor (53.3%) was an parent or sibling with HCV infection. Twenty-nine patients (96.7%) were negative for HCV-RNA by week 2 of treatment and 1 patient became negative by week 4. The end of treatment response and SVR12 were 100%. Transaminases levels declined and returned to normal levels by week 2. Major side effects were fatigue in 90% (27/30) and headache in 76.7% (23/30). Side effects were minimal, tolerable, and did not interfere with daily activity or necessitate treatment discontinuation. CONCLUSIONS: A shortened 8-week regimen of LED/SOF (45/200 mg) is safe and effective with 100% SVR12 in treatment-naïve children with cirrhosis aged 4-10 years with chronic HCV infection genotype 4.

Hepatitis C cure improved patient-reported outcomes in patients with and without liver fibrosis in a prospective study at a large urban medical center.

Patient-reported outcomes (PROs) are important measures of quality of life. Direct-acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA-based HCV cure on PROs and liver-related outcomes in real-world patients at a large urban medical center. The short form (SF)-36 and three additional validated instruments were used. F3-4 fibrosis was defined as > 9.6 kPa by transient elastography (TE); S2-3 steatosis was defined as > 270 dB/m by TE-controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n = 16) who did not achieve a sustained virologic response at 12 weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF-36 vitality score, measured baseline to SVR12: 63 versus 82, P < .001 (n = 111). Scores in 24 of 25 PRO domains improved at SVR12 (P < .05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (P < .005), but steatosis was unchanged (P = .58). Patients with baseline F0-2 fibrosis and those with F3-F4 fibrosis both improved in 22 domains. Patients with baseline S0-S1 steatosis improved in more domains (23) than patients with S2-S3 steatosis (19). At baseline, patients with F3-F4 fibrosis and patients with S2-3 steatosis had worse scores in certain PRO domains than patients with F0-2 fibrosis or S0-S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment.

[Price analyses on direct-acting antiviral drugs of hepatitis C].

The oral direct-acting antiviral drug (DAA) offers tremendous opportunities to eliminate hepatitis C. We analyzed the market trends, price trends and global treatment progress of DAA drugs by reviewing the guidelines recommended by the World Health Organization for the treatment of hepatitis C, and discusses the current accessibility of DAA treatment and its influencing factors. The results show that WHO recommends the use of DAA for treatment of hepatitis C, but the price of DAA is expensive. Although some countries have taken measures to lower prices and improve accessibility, the advancement of DAA treatment has been unsatisfactory and coverage is still not high. In addition to price, factors such as strategy, health system, accessibility and service provision need to be considered, and public health methods should be adopted to promote DAA treatment to achieve the elimination of hepatitis C.

[Effects of direct antiviral agent on the frequency of peripheral blood mononuclear cells and their activating factors sCD14s and CD163 in patients with chronic hepatitis C].

Objective: To explore the effects of direct antiviral agent (DAAs) on the frequency of peripheral blood mononuclear cells and their activating factors sCD14s and CD163 in patients with chronic hepatitis C. Methods: Data of 15 treatment-naive chronic hepatitis C patients and 10 healthy controls were collected. Patients with chronic hepatitis C were treated with DAAs for 12 weeks. Blood samples were collected at 0, 4 and 12 weeks respectively, and blood samples of healthy controls were used as controls. Flow cytometry was used to detect the frequency of classical CD14(++)CD16(-) mononuclear cells and pro-inflammatory CD14(+)CD16(+) mononuclear cells in peripheral blood. Serum sCD14s and sCD163 were detected by enzyme-linked immunosorbent assay. The comparison between the two groups was performed by t-test. The comparison between multiple groups was performed by analysis of variance, and further pairwise comparison was performed by LSD-t test. Results: Prior DAAs treatment, peripheral blood CD14(+)CD16(+) mononuclear cell frequency (18.49% ± 1.54% vs. 10.65% ± 0.83%), serum sCD14s [(64 407.38 ± 5778.49) pg/ml vs. (28 370.76 ± 2 357.68 ) pg/ml] and sCD163 [(22 853.80 ± 4 137.61) pg/ml vs. (2 934.41 ± 223.31) pg/ml] were all higher than healthy controls (P < 0.05), while the frequency of CD14(++)CD16(-) mononuclear cells in peripheral blood was lower than healthy controls (59.14%±0.54% vs. 72.75%±1.31%, P < 0.01). During DAAs treatment, CD14(+)CD16(+) mononuclear cells frequency, serum sCD14 and sCD163 were all decreased significantly. After 12 weeks of treatment, CD14(+)CD16(+) mononuclear cells had decreased to nearly normal level (12.42% ± 1.60% vs. 10.65% ± 0.83%, P > 0.05), and serum sCD14 and scd163 were still higher than those of healthy controls [sCD14: (44 390.06 ± 3 330.17) pg / ml vs. (28 370.76 ± 2 357.68) pg/ml, Scd163: (11 494.79 ± 1 836.97) pg / ml vs. (2 934.41 ± 223.31) pg / ml, P < 0.01], while the frequency of CD14(++)CD16(-)mononuclear cells had gradually increased during the course of treatment and neared healthy control level after 12 weeks of treatment. There was no statistically significant difference between the two groups (71.54) % ± 2.99% vs. 72.75% ± 1.31%, P > 0.05). Conclusion: DAAs therapy can reduce the activation of peripheral blood mononuclear cells in patients with chronic hepatitis C.

Review on chemogenomic approaches towards hepatitis C viral targets.

Hepatitis C virus (HCV) is the most prevalent viral pathogen that infects more than 185 million people worldwide. HCV infection leads to chronic liver diseases such as liver cirrhosis and hepatocellular carcinoma. Direct-acting antivirals (DAAs) are the recent combination therapy for HCV infection with reduced side effects than prior therapies. Sustained virological response (SVR) acts as a gold standard marker to monitor the success of antiviral treatment. Older treatment therapies attain 50-55% of SVR compared with DAAs which attain around 90-95%. The current review emphasizes the recent chemogenomic updates that have been unfolded through structure-based drug design of HCV drug target proteins (NS3/4A, NS5A, and NS5B) and ligand-based drug design of DAAs in achieving a stable HCV viral treatment strategies.

Hepatitis C virus infection in Australian psychiatric inpatients: A multicenter study of seroprevalence, risk factors and treatment experience.

Screening and treatment for hepatitis C virus (HCV) infection were not prioritised in psychiatric patients due to adverse neuropsychiatric effects of interferon therapy despite reports of high prevalence. However, with the safe new antiviral drugs, HCV eradication has become a reality in these patients. The aim of this study was to report HCV seroprevalence, risk factors and treatment model in an Australian cohort. This prospective study involved patients admitted to four inpatient psychiatric units, from December 2016 to December 2017. After pretest counselling and consent, HCV testing was done; information on risk factors collected. A total of 260 patients (70% male), median age 44 years (IQR 24), were studied. The HCV seroprevalence was 10.8% (28/260) with 95% CI 7-15. Independent predictors of HCV positivity were injection drug use (P < 0.001, OR 44.05, 95% CI 7.9-245.5), exposure to custodial stay (P = 0.011, OR 7.34, 95% CI 1.6-33.9) and age (P = 0.011, OR 1.09, 95% CI 1.02-1.16). Eight of the 16 HCV RNA-positive patients were treated. Hepatitis nurses liaised with community mental health teams for treatment initiation and follow-up under supervision of hepatologists. Seven patients achieved sustained viral response, one achieved end of treatment response. The remaining eight patients were difficult to engage with. In conclusion, HCV prevalence was high in our cohort of psychiatric inpatients. Although treatment uptake was achieved only in 50% patients, it was successfully completed in all, with innovative models of care. These findings highlight the need to integrate HCV screening with treatment linkage in psychiatry practice.

Male Sexual Dysfunction Among Egyptian Patients with Chronic Hepatitis C Virus Infection Before and After Direct-Acting Antiviral Drugs.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a global health burden that affects quality of life, with a negative impact on sexual functioning (SF). AIM: To study male sexual dysfunction (MSD) among Egyptian men with chronic HCV infection and the impact of therapy with direct-acting antiviral drugs (DAAs) on their sexual health. METHODS: The self-administered International Index of Erectile Function (IIEF) questionnaire was completed by 400 sexually active male patients with chronic HCV infection without liver cirrhosis before the initiation of therapy with DAAs and then again at the completion of therapy. We compared these baseline questionnaires with those completed by a similar number of age-matched and socioeconomic status-matched controls. In the patients with HCV infection, we also compared IIEF questionnaires completed before and after DAA therapy. MAIN OUTCOME MEASURE: We determined the proportions of patients and controls who were dissatisfied with their sexual life and the impact of clearing HCV infection on MSD and evaluated the impact of DAA therapy on the total IIEF score and scores in all IIEF domains. RESULTS: Men with chronic HCV infection before DAA treatment had significantly higher erectile dysfunction (ED) scores compared with controls, and scores increased with age (P < .0001). The average scores in all IIEF domains was significantly lower in the patients compared with controls in all age groups. Men with chronic HCV infection had significantly higher ED scores before cure than after cure (P < .0001). CLINICAL IMPLICATIONS: Given the high prevalence of MSD in patients with chronic HCV infection, and given that curing the HCV virus can improve the MSD associated with HCV infection, it is recommended that sexual quality of life in men with HCV be addressed as part of the evaluation protocol before initiation of DAA treatment and again after cure in an effort to improve this particular aspect of quality of life. STRENGTHS & LIMITATIONS: This is the first study to report on MSD in the era of DAA therapy in Egyptian men with chronic HCV infection before the development of cirrhosis, with a relatively large study population. The use of a detailed version of the IIEF questionnaire reinforces the validity of our study. CONCLUSION: Chronic HCV infection negatively impacts MSD, affecting all domains of the IIEF, and effects increase with age. The MSD associated with HCV infection is significantly improved in patients who are cleared of the virus. These findings require further confirmation and need to be addressed as part of a comprehensive therapeutic plan to improve patients' quality of life. Elshimi E, Morad W, Mohamad NE. Male Sexual Dysfunction Among Egyptian Patients with Chronic Hepatitis C Virus Infection Before and After Direct-Acting Antiviral Drugs. J Sex Rev 2019;16:402-409.

A systematic review and meta-analysis of community and primary-care-based hepatitis C testing and treatment services that employ direct acting antiviral drug treatments.

BACKGROUND: Direct Acting Antiviral (DAAs) drugs have a much lower burden of treatment and monitoring requirements than regimens containing interferon and ribavirin, and a much higher efficacy in treating hepatitis C (HCV). These characteristics mean that initiating treatment and obtaining a virological cure (Sustained Viral response, SVR) on completion of treatment, in non-specialist environments should be feasible. We investigated the English-language literature evaluating community and primary care-based pathways using DAAs to treat HCV infection. METHODS: Databases (Cinahl; Embase; Medline; PsycINFO; PubMed) were searched for studies of treatment with DAAs in non-specialist settings to achieve SVR. Relevant studies were identified including those containing a comparison between a community and specialist services where available. A narrative synthesis and linked meta-analysis were performed on suitable studies with a strength of evidence assessment (GRADE). RESULTS: Seventeen studies fulfilled the inclusion criteria: five from Australia; two from Canada; two from UK and eight from USA. Seven studies demonstrated use of DAAs in primary care environments; four studies evaluated integrated systems linking specialists with primary care providers; three studies evaluated services in locations providing care to people who inject drugs; two studies evaluated delivery in pharmacies; and one evaluated delivery through telemedicine. Sixteen studies recorded treatment uptake. Patient numbers varied from around 60 participants with pathway studies to several thousand in two large database studies. Most studies recruited less than 500 patients. Five studies reported reduced SVR rates from an intention-to-treat analysis perspective because of loss to follow-up before the final confirmatory SVR test. GRADE assessments were made for uptake of HCV treatment (medium); completion of HCV treatment (low) and achievement of SVR at 12 weeks (medium). CONCLUSION: Services sited in community settings are feasible and can deliver increased uptake of treatment. Such clinics are able to demonstrate similar SVR rates to published studies and real-world clinics in secondary care. Stronger study designs are needed to confirm the precision of effect size seen in current studies. Prospero: CRD42017069873.

Accepting hepatitis C virus-infected donor hearts for transplantation: Multistep consent, unrealized opportunity, and the Stanford experience.

The current mismatch between supply and demand of organs has prompted transplant clinicians to consider innovative solutions to broaden the donor pool. Advancements of direct-acting antiviral agent (DAA) therapy for hepatitis C virus (HCV) have allowed entertaining the use of viremic donor organs in nonviremic recipients. In this report, we describe the evolution of HCV treatment, ethics and informed consent, cost-effectiveness of HCV medications in treating acute HCV post-transplantation, and the Stanford experience with two HCV-viremic donor heart transplantations. We describe excellent short-term outcomes post-heart transplantation with HCV NAT-positive organs. The availability of this therapy may expand the donor pool. While we await larger-scale clinical data on the effectiveness and safety of DAA therapy in patients after heart transplantation, many transplant centers have already started accepting organs from HCV-infected donors, balancing the unknown long-term risks versus the benefits of shorter wait times and expansion of the donor pool. Protocols and multidisciplinary teams are needed to effectively communicate risk to potential recipients, to ensure timely DAA access, and to implement appropriate clinical follow-up in order to achieve excellent clinical outcomes and to maximize the donor pool by utilizing HCV-infected organs for heart transplantation.

Outcomes of treatment with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation.

AIM: The development of direct-acting oral agents has dramatically changed the treatment strategy of hepatitis C virus (HCV) infection. Here we aimed to reveal the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) for recurrent HCV genotype 1 infection after liver transplantation (LT). METHODS: A retrospective study was undertaken on nine patients who underwent a 24-week DCV/ASV treatment regimen for recurrent HCV genotype 1 infection. Five of the patients were men; four had failed treatment with pegylated interferon (Peg-IFN)/ribavirin, two had failed simeprevir/Peg-IFN/ribavirin, one had the resistance-associated variant Y93H in the NS5A region, and one underwent maintenance dialysis. RESULTS: Median time to treatment initiation following LT was 70 months. Of the nine patients treated with DCV/ASV, eight (88.9%) achieved a sustained viral response 12 weeks after completion of therapy (SVR12). The patient with virologic failure had failed simeprevir/Peg-interferon/ribavirin therapy 4 months before undergoing the DCV/ASV treatment regimen. In addition, a resistance-associated variant D168E in the NS3 region was detected in the patient after discontinuation of the DCV/ASV regimen. The trough level of tacrolimus tended to decrease, and renal function showed no significant changes during treatment. Adverse events occurred in two patients (22.2%), but no severe adverse events occurred during treatment. CONCLUSIONS: The DCV/ASV regimen was well tolerated, resulting in high rates of sustained viral response 12 weeks after completion of therapy for LT patients with recurrent HCV genotype 1 infection.

Severe liver disease related to chronic hepatitis C virus infection in treatment-naive patients: epidemiological characteristics and associated factors at first expert centre visit, France, 2000 to 2007 and 2010 to 2014.

Given recent profound improvements in the effectiveness of antiviral treatment for chronic Hepatitis C virus (HCV) infection, we aimed to describe the characteristics of patients referred to hepatology expert centres in France from 2000 to 2007 and from 2010 to 2014, and to identify factors associated with severe liver disease at their first visit for evaluation. We analysed data from two sources covering all of France: the former hepatitis C surveillance network, which included patients between 2000 and 2007, and the ANRS CO22 HEPATHER multi-centre cohort, which included patients between 2012 and 2014. Severe liver disease (SLD) was defined as the presence of either cirrhosis (histological, biochemical or clinical) or hepatocellular carcinoma. Multivariable Poisson regression models were used to identify the factors associated with SLD in complete-case analysis and after multiple imputation. Overall, 16,851 patients were included in the analysis and SLD was diagnosed in 11.6%. SLD at first visit was significantly associated with known risk factors (male sex, history of excessive alcohol intake, HCV genotype 3), late referral to hepatologists after diagnosis and HCV diagnosis at an older age. Providing earlier specialised care and treatment may be an important target for public health action.

Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial.

UNLABELLED: Grazoprevir (MK-5172, Merck & Co., Inc.) is a selective inhibitor of the hepatitis C virus (HCV) NS3/4a protease. The aim of this study was to evaluate the safety and efficacy of grazoprevir at doses of 25-100 mg/day in combination with peginterferon and ribavirin (PEG-IFN/RBV). In this randomized, dose-ranging, multicentre trial, treatment-naive adults with chronic HCV genotype 1 infection received once-daily grazoprevir 25 mg, 50 mg or 100 mg plus PEG-IFN/RBV for 12 weeks. Patients with quantifiable HCV RNA (≥25 IU/mL) at week 4 received an additional 12 weeks of PEG-IFN/RBV. The primary endpoint was sustained virologic response (HCV RNA <25 IU/mL 12 weeks after completing therapy [SVR12]). Eighty-seven patients were randomly assigned and received ≥1 dose of therapy. Median time to undetectable HCV RNA was 16 days in the 100-mg arm and 22 days in the 25- and 50-mg arms. All patients except one had HCV RNA undetectable or unquantifiable at week 4 and received 12 weeks of therapy. SVR12 was achieved by 13 of 24 (54.2%), 21 of 25 (84.0%) and 23 of 26 (88.5%) patients in the 25-, 50- and 100-mg arms, respectively (per-protocol analysis). Three patients discontinued as a result of nonserious adverse events (AEs) and three patients experienced serious AEs. Transaminase elevations occurred in two patients (one each in the 25- and 100-mg arms). CONCLUSION: These data support further study of the grazoprevir 100-mg dose. Phase 3 studies of grazoprevir 100 mg in combination with elbasvir are currently ongoing (NCT01710501; protocol P038).

Safety and effectiveness of direct-acting antiviral drugs in the treatment of hepatitis C in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) management in Inflammatory Bowel Disease (IBD) is uncertain. The ECCO guidelines 2021 recommended HCV treatment but warn about the risk of IBD reactivation. We aimed to evaluate 1) the effectiveness and safety of direct-acting antivirals (DAAs) in IBD; 2) the interaction of DAAs with IBD drugs. METHODS: Multicentre study of IBD patients and HCV treated with DAAs. Variables related to liver diseases and IBD, as well as adverse events (AEs) and drug interactions, were recorded. McNemar's test was used to assess differences in the proportion of active IBD during the study period. RESULTS: We included 79 patients with IBD and HCV treated with DAAs from 25,998 IBD patients of the ENEIDA registry. Thirty-one (39.2 %) received immunomodulators/biologics. There were no significant differences in the percentage of active IBD at the beginning (n = 11, 13.9 %) or at the 12-week follow-up after DAAs (n = 15, 19 %) (p = 0.424). Sustained viral response occurred in 96.2 % (n = 76). A total of 8 (10.1 %) AEs occurred and these were unrelated to activity, type of IBD, liver fibrosis, immunosuppressants/biologics, and DAAs. CONCLUSIONS: We demonstrate a high efficacy and safety of DAAs in patients with IBD and HCV irrespective of activity and treatment of IBD.

A deep learning drug screening framework for integrating local-global characteristics: A novel attempt for limited data.

At the beginning of the "Disease X" outbreak, drug discovery and development are often challenged by insufficient and unbalanced data. To address this problem and maximize the information value of limited data, we propose a drug screening model, LGCNN, based on convolutional neural network (CNN), which enables rapid drug screening by integrating features of drug molecular structures and drug-target interactions at both local and global (LG) levels. Experimental results show that LGCNN exhibits better performance compared to other state-of-the-art classification methods under limited data. In addition, LGCNN was applied to anti-SARS-CoV-2 drug screening to realize therapeutic drug mining against COVID-19. LGCNN transcends the limitations of traditional models for predicting interactions between single drug targets and shows new advantages in predicting multi-target drug-target interactions. Notably, the cross-coronavirus generalizability of the model is also implied by the analysis of targets, drugs, and mechanisms in the prediction results. In conclusion, LGCNN provides new ideas and methods for rapid drug screening in emergency situations where data are scarce.

Surveillance for Hepatocellular Carcinoma in Patients with Successfully Treated Viral Disease of the Liver: A Systematic Review.

Background: Surveillance for hepatocellular carcinoma (HCC) has been proven to increase the proportion of tumors detected at early stages and the chance of receiving curative therapies, reducing mortality by about 30%. Summary: Current recommendations consist of a semi-annual abdominal ultrasound with or without serum alpha-fetoprotein measurement in patients with cirrhosis and specific subgroups of populations with chronic viral hepatitis. Antiviral therapies, such as nucleot(s)ide analogs that efficiently suppress the replication of hepatitis B virus (HBV) and direct-acting antiviral drugs able to eliminate the hepatitis C virus (HCV) in >90% of patients, have radically changed the outcomes of viral liver disease and decreased, but not eliminated, the risk of HCC in both cirrhotic and non-cirrhotic patients. HCC risk is a key starting point for implementing a cost-effective surveillance and should also guide the decision-making process concerning its modality. As the global number of effectively treated viral patients continues to rise, there is a pressing need to identify those for whom the benefit-to-harm ratio of surveillance is favorable and to determine how to conduct cost-effective screening on such patients. Key Messages: This article addresses this topic and attempts to determine which patients should continue HCC surveillance after HBV suppression or HCV eradication, based on cost-effectiveness principles and the fact that HCC risk declines over time. We also formulate a proposal for a surveillance algorithm that switches the use of surveillance for HCC from the "one-size-fits-all" approach to individualized programs based on oncologic risk (precision surveillance).

Occult hepatitis C virus infection in hemodialysis patients who achieved a sustained virological response to directly acting antiviral drugs: is it a concern?

PURPOSE: Hepatitis C virus infection is a major health problem in hemodialysis patients. Occult HCV infection is defined as the presence of HCV-RNA in hepatocytes or peripheral blood mononuclear cells without the detection of HCV-RNA in the serum. We aimed to evaluate the prevalence and predictors of occult HCV infection among hemodialysis patients after treatment with direct-acting antiviral agents. METHODS: This research is a cross-sectional study that included 60 HCV patients maintained on regular HD patients who achieved 24 weeks of sustained virological response after treatment with direct-acting antiviral agents. Real-time PCR was performed to detect HCV-RNA in peripheral blood mononuclear cells. RESULTS: HCV-RNA was detected in peripheral blood mononuclear cells of three patients (5%). Occult HCV infection cases were treated by Interferon/ribavirin before direct-acting antiviral agents and two of them had raised pre-treatment alanine aminotransferase levels. Logistic regression analyses revealed that high pre-treatment viral load and raised pre-treatment alanine aminotransferase were associated with an increased risk of occult HCV infection with p value of 0.041 and 0.029, respectively. CONCLUSIONS: Occult HCV infection in hemodialysis patients who achieved sustained virological response after treatment with direct-acting antiviral agents may occur, and this may necessitate dual testing for HCV in both serum and peripheral blood mononuclear cells to ensure viral clearance. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT04719338.

Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus Retreatment in Difficult-to-treat Patients: A Real-life Observational Study from India.

Background and aim: Hepatitis C virus (HCV) treatment fails to achieve sustained virological response at 12 weeks (SVR12) in 5-10 % and requires retreatment with second-line drugs. We report our experience of sofosbuvir/velpatasvir/voxilaprevir use for HCV retreatment in a small cohort of difficult-to-treat Indian patients. Methods: We reviewed our HCV databases to identify the patients who had failed to achieve SVR12 after treatment with sofosbuvir in combination with either daclatasvir, ledipasvir, or velpatasvir with/without ribavirin on one or more occasions. Participants were excluded if they had (i) decompensated cirrhosis, (ii) HIV coinfection or (iii) chronic kidney disease, or (iv) prior organ transplantation. All the participants were treated with sofosbuvir/velpatasvir/voxilaprevir plus ribavirin for 12 weeks. Treatment outcome was categorized as successful or failure if HCV RNA was undetectable or detectable at SVR12, respectively. Results: Fifteen patients (male 67 %; genotype-3 80 %) were included in the analysis. Ten (67 %) had cirrhosis. Five, eight, and two participants had previously failed one, two, and three courses of pegylated-interferon free, sofosbuvir containing direct acting antiviral (DAA) regimens respectively. Fourteen participants had failed to at least one course of the sofosbuvir/velpatasvir combination. Fourteen patients achieved SVR12, and one patient was lost to follow-up. Treatment was successful in 100 % and 93.3 % of per-protocol (PP) and intention to treat (ITT) analyses, respectively. Conclusion: Sofosbuvir/velpatasvir/voxilaprevir combination is an effective second-line therapy in India for difficult-to-treat HCV patients.