Direct-acting Antiviral Drugs Research Articles

Real-life Data of Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients: A Single-center Study

Background: Glecaprevir/pibrentasvir (G/P) is a pangenotypic direct-acting antiviral (DAA) drug with a high resistance barrier. It has been used in patients with chronic hepatitis C in Turkey since March 2019. This drug's efficacy and safety data in Turkey are very limited, and there are not enough studies on real-life data. Objectives: In this study, we aim to present real-life data, efficacy, and safety for our patients. Methods: In this retrospective, observational, single-center study, 116 patients who were started on G/P (100mg/40mg) oral therapy at the infectious diseases clinic between March 2019 and December 2021 due to HCV were included. Of the 116 patients included in the study, 92 were analyzed. Demographic data of the patients, previous treatment experience, drug use, viral load (HCV RNA levels at the 4th week of treatment and 12th week after treatment), and viral genotype data were obtained retrospectively from the automation system. Statistical analysis IBM SPSS version 21.0 statistical package program was used. Results: Seventy-one (77.2%) of the patients were male, and 21 (22.8%) were female, with a mean age of 47.4 (18 - 89). Genotype distribution of patients 8.7% (n = 8) type 1a, 31.5% (n = 29) type 1b, 26.1% (n = 24) type 2, 22.9% (n = 21) type 3, 10.9% (n = 10) were type 4, 8.7% (n = 8) of the patients were treatment-experienced. In our study, there were no patients with cirrhosis. SVR-12 could not be obtained from a patient infected with only genotype 1a. In addition, this patient was co-infected with Hepatitis B. No side effects were observed in any of the patients that required treatment discontinuation. The SVR-12 rate was 98.6% with patients per protocol analysis (PP), but the SVR-12 rate was 77.2% with intention to treat analysis (ITT). Conclusions: In conclusion, this study suggested that G/P therapy in Turkey is used in real life with very high efficacy and tolerability. In addition, a significant change was observed in the genotype distribution previously reported in Turkey in the patient group we treated.

Antiviral properties of verdazyls and leucoverdazyls and their activity against group B enteroviruses

Enteroviruses are non-enveloped viruses of Enterovirus genus, Picornaviridae family, causing a variety of human diseases: from acute respiratory and intestinal infections to more severe pathologies including poliomyelitis, encephalitis, myocarditis, pancreatitis. Currently, no approved direct-acting antiviral drugs for treatment of enterovirus infections exists, whereas vaccination is available only for prevention of poliomyelitis and enterovirus 71 infection. Therefore, it is promising to conduct a search for inhibitors of enteroviruses life cycle in drug development to treat enterovirus infections. Here, antiviral properties of stable free radicals, verdazyls, and their precursors, leucoverdazyls, were investigated. It has been shown that leucoverdazyls vs verdazyls increased the survival of permissive cell culture infected with coxsackievirus. The activity range of the lead leucoverdazyl against RNA-containing and DNA-containing human viruses (in the viral yield reduction assay) and its proposed mechanism of action (time of addition assay) was studied. The lead compound suppressed reproduction of group B enteroviruses in vitro, with modest activity against influenza A virus and no activity against herpes virus type 1 and adenovirus type 5. The maximum decrease in viral titers was observed upon its addition to infected cells during early and middle stages of the virus life cycle. Thus, we concluded that the studied compound has a pronounced inhibitory activity against group B enteroviruses not belonging to the class of capsid binder inhibitors, without virucidal properties. Previously, we described antioxidant properties of leucoverdazyls. It is known that many viral infections are accompanied by production of reactive oxygen species and oxidative stress, and some compounds with antioxidant properties exhibit antiviral potential. Targeted chemical modifications of leucoverdazyls and further studies of leucoverdazyl mechanism of action as well as in vivo animal studies are needed. However, the results obtained may be useful for future development of new antiviral drugs to treat enteroviral infections.

Serum retinol-binding protein 4 as a predictor of fibrosis regression and response to direct-acting antiviral drugs in chronic hepatitis C virus patients

BackgroundHepatitis C virus is the underlying cause of chronic hepatitis which frequently progresses to cirrhosis and hepatocellular carcinoma. In addition, HCV is thought to cause steatosis, dyslipidemia, insulin resistance, diabetes, obesity, and cardiovascular events. The aim of this study is to evaluate the role of serum RBP-4 in the prediction of fibrosis regression and the response of treatment among chronic HCV patients receiving direct-acting antiviral agents.MethodsThis study included 40 chronic HCV Egyptian patients, divided into two groups: Naive cases, 20 chronic HCV patients before starting first line of treatment; Relapser cases, 20 chronic HCV patients who were non-responders before starting second line treatment; and 10 healthy subjects as control. Laboratory investigations including complete blood count, full hepatic profile, fibroscan assessment, and retinol-binding protein-4 level at baseline and re-assessed 12 weeks after the end of treatment [sustained virological response SVR12]. Student T test, analysis of variance, chi-square, Tukey’s test, and Pearson correlation coefficient tests were used for statistical analysis.ResultsBaseline retinol-binding protein-4 level was significantly higher in the naïve case group than in the relapser and control groups with a P value of P value of < 0.001. All the naïve patients had 100% SVR12, only 90% of the relapser group achieved SVR12. A significant reduction in retinol-binding protein-4 and fibrosis staging and measurements by fibroscan among all studied patients were noted after receiving direct acting antivirals (P value < 0.001). Retinol-binding protein-4 levels before and after treatment were significantly lower among F4 patients in comparison to those of F1–F3 patients (P value 0.002, 0.009, respectively). The best cutoff value of retinol-binding protein-4 in the prediction of liver cirrhosis (F4) was ≤ 46 pg/ml with sensitivity of 100% and specificity of 66.67%.ConclusionSerum retinol-binding protein-4 was found to be higher in chronic HCV infection with a significant reduction after successful eradication. Its level is much lower in cirrhotic patients [F4]. As a result, retinol-binding protein-4 may have a promising role in assessing direct acting antivirals response, as well as a prognostic value in predicting liver cirrhosis.

Prevention of malignant digestive system tumors should focus on the control of chronic inflammation.

Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.

Impact of COVID-19 fear on Hepatitis C management

Background/Aim: Hepatitis C virus (HCV) infection, a major cause of cirrhosis worldwide, is the most common cause of cirrhosis and hepatocellular carcinoma in Turkey. Today, HCV infection can be treated effectively and safely using direct-acting antiviral drugs, and therefore, the World Health Organization has announced elimination targets by 2030. During the pandemic, many social and personal restrictions were applied for fear of increasing the prevalence of coronavirus disease 2019 (COVID-19) infection. Here we investigate the effects of these restrictions on managing HCV infection in internal medicine departments that deal with both infections. Methods: Patients who applied to the internal medicine departments of our hospital and tested for anti-HCV between 11 March 2020 and 09 April 2022, which was the time interval when official restrictions were applied in Turkey during the COVID-19 pandemic, were included in the study. Patients who were not tested for anti-HCV were excluded from the study. The study was planned as a retrospective cohort study, and patients’ files tested for anti-HCV were scanned. Anti-HCV positivity, HCV RNA PCR testing, and treatment status in HCV RNA-positive patients were evaluated. Results: During the official pandemic period when social restrictions were applied, anti-HCV positivity was revealed in 400 (1.9%) of 21,501 patients for whom anti-HCV tests were performed in internal medicine departments. HCV RNA was not tested in 64 of 400 patients with positive anti-HCV test (16%), and 83 (24.7%) of 336 patients tested for HCV RNA were found to be positive. It was determined that 17 (20.5%) of the HCV RNA-positive patients did not receive antiviral treatment. Conclusion: In studies conducted in Turkey in the pre-pandemic period, it was determined that HCV RNA was not tested in approximately half of the anti-HCV-positive patients, while this rate was found to be only 16% during the pandemic period. This can be explained by the fact that patients infected with the COVID-19 virus were mostly followed-up by internal medicine clinics, where the awareness of viral hepatitis was high. It was determined that 20.5% of the patients with positive HCV RNA PCR tests remained untreated. This finding suggested that the social and personal restrictions applied during the pandemic led to patient follow-up and treatment disruptions.

Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C.

Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.

Global reporting of progress towards elimination of hepatitis B and hepatitis C

The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving and measuring the 2030 targets requires a substantial increase in the capacity to test and treat viral hepatitis infections and a mechanism to monitor the progress of hepatitis elimination. This study aimed to identify the gaps in data availability or quality and create a new mechanism to monitor the progress of hepatitis elimination. In 2020, using a questionnaire, we collected empirical, systematic, modelled, or surveyed data-reported by WHO country and WHO regional offices-on indicators of progress towards elimination of viral hepatitis, including burden of infection, incidence, mortality, and the cascade of care, and validated these data. WHO received officially validated country-provided data from 130 countries or territories, and used partner-provided data for 70 countries or territories. We estimated that in 2019, globally, 295·9 million (3·8%) people were living with chronic hepatitis B virus (HBV) infection and 57·8 million (0·8%) people were living with chronic hepatitis C virus (HCV) infection. Globally, there were more than 3·0 million new infections with HBV and HCV and more than 1·1 million deaths due to the viruses in 2019. In 2019, 30·4 million (95% CI 24·3-38·0) individuals living with hepatitis B knew their infection status and 6·6 million (5·3-8·3) people diagnosed with hepatitis B received treatment. Among people with HCV infection, 15·2 million (95% CI 12·1-19·0) had been diagnosed between 2015 and 2019, and 9·4 million (7·5-11·7) people diagnosed with hepatitis C infection were treated with direct-acting antiviral drugs between 2015 and 2019. There has been notable global progress towards hepatitis elimination. In 2019, 30·4 million (10·3%) people living with hepatitis B knew their infection status, which was slightly higher than in 2015 (22·0 million; 9·0%), and 6·6 million (22·7%) of those diagnosed with hepatitis B received treatment, compared with 1·7 million (8·0%) in 2015. Mortality from hepatitis C has declined since 2019, driven by an increase in HCV treatment ten times that of the strategy baseline. However, an estimated 89·7% of HBV infections and 78·6% of HCV infections remain undiagnosed. A new global strategy for 2022-30, based on these new estimates, should be implemented urgently to scale up the screening and treatment of viral hepatitis. World Health Organization.

Efficacy and safety of glecaprevir/pibrentasvir treatment in Koreans with chronic hepatitis C: A retrospective study

Background and study aimsThe introduction of direct-acting antiviral (DAA) drugs has dramatically improved chronic hepatitis C (CHC) treatment. The pangenotype DAA therapy glecaprevir/pibrentasvir (G/P) was recently recommended for treating CHC in Korea. Unfortunately, given its recent introduction, little real-world data from a Korean population exists. We examined the effectiveness and safety of G/P treatment in Koreans with CHC. Patients and methodsWe analyzed CHC patients at Samsung Changwon Hospital from June 2018 to December 2020. Sustained virologic response at 12 weeks posttreatment (SVR 12) was evaluated after treatment, and the associated factors were analyzed. Furthermore, the degree of liver fibrosis before and after treatment was compared to determine whether liver fibrosis improved. ResultsIn total, 102 patients were enrolled; 35.3 % had compensated liver cirrhosis (LC), and 11.8 % had received previous treatment. Of the 102 patients, 99 (97.1 %) reached SVR 12. Of the 81 patients who completed 8 weeks of G/P treatment, 80 (98.8 %) reached SVR 12, while 19 of the 21 (90.5 %) patients in the 12- or 16-week group reached SVR 12, with no significant difference between the two groups (P = 0.107). As a secondary endpoint, liver fibrosis before and after treatment was also compared. The Fibrosis-4 index (FIB-4) (3.3 vs 2.8, P = 0.010), aspartate transaminase (AST)-platelet ratio index (APRI) (1.3 vs 1.0, P < 0.001), and liver stiffness measurements (LSM) (9.5 vs 4.6, P < 0.001) were significantly different after G/P treatment. ConclusionsRegardless of genotype, G/P treatment for Koreans with CHC is safe, highly effective, and can improve liver fibrosis.

Genotypes of Hepatitis C Virus and Efficacy of Direct-Acting Antiviral Drugs among Chronic Hepatitis C Patients in a Tertiary Care Hospital.

Hepatitis C virus (HCV) chronic infection is a major causative factor for several chronic liver diseases, including liver cirrhosis, liver cell failure, and hepatocellular carcinoma. The HCV has seven major genotypes. Genotype 4 is the most prevalent genotype in the Middle East, including Saudi Arabia, followed by genotype 1. The HCV genotype affects the response to different HCV treatments and the progression of liver disease. Currently, combinations of direct-acting antiviral drugs (DAAs) approved for the treatment of HCV achieve high cure rates with minimal adverse effects. Because real-world data from Saudi Arabia about the efficacy of DAAs are still limited, this study was conducted to assess the effectiveness of DAAs in treating patients with chronic hepatitis C and to identify the variables related to a sustained virologic response (SVR) in a real-world setting in Saudi Arabia. This prospective cohort study included 200 Saudi patients with chronic HCV who were 18 years of age or older and had been treated with DAAs at King Abdul-Aziz Specialized Hospital in Taif, Saudi Arabia, between September 2018 and March 2021. The response to treatment was assessed by whether or not an SVR had been achieved at week 12 post treatment (SVR12). An SVR12 was reached in 97.5% of patients. SVR12 rates were comparable for patients of different ages, between men and women, and between patients with and without cirrhosis. In addition, the SVR12 rates did not differ according to the infecting HCV genotype. In this study, the presence of cirrhosis and the patient's gender were independent predictors of who would not reach an SVR12 (known here as the non-SVR12 group) according to the results of univariate and multivariate binary logistic regression analyses based on the determinants of SVR12. In this population of patients with chronic HCV infection, all DAA regimens achieved very high SVR12 rates. The patients' gender and the presence of cirrhosis were independent factors of a poor response.

Discovery of Polyphenolic Natural Products as SARS-CoV-2 Mpro Inhibitors for COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chemical phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 Mpro. Several compounds were discovered to inhibit Mpro at low micromolar concentrations. It was possible to crystallize robinetin together with SARS-CoV-2 Mpro, and the X-ray structure revealed covalent interaction with the protease's catalytic Cys145 site. Selected potent molecules also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for future COVID-19 research.

Diagnostic value of novel hepatic fibrosis markers in assessing cirrhosis in patients with chronic hepatitis C

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.

Hepatitis C Virus Infection Upregulates Plasma Phosphosphingolipids and Endocannabinoids and Downregulates Lysophosphoinositols.

A mass spectrometry-based lipidomic investigation of 30 patients with chronic hepatitis C virus (HCV) infection and 30 age- and sex-matched healthy blood donor controls was undertaken. The clustering and complete separation of these two groups was found by both unsupervised and supervised multivariate data analyses. Three patients who had spontaneously cleared the virus and three who were successfully treated with direct-acting antiviral drugs remained within the HCV-positive metabotype, suggesting that the metabolic effects of HCV may be longer-lived. We identified 21 metabolites that were upregulated in plasma and 34 that were downregulated (p &lt; 1 × 10-16 to 0.0002). Eleven members of the endocannabinoidome were elevated, including anandamide and eight fatty acid amides (FAAs). These likely activated the cannabinoid receptor GPR55, which is a pivotal host factor for HCV replication. FAAH1, which catabolizes FAAs, reduced mRNA expression. Four phosphosphingolipids, d16:1, d18:1, d19:1 sphingosine 1-phosphate, and d18:0 sphinganine 1-phosphate, were increased, together with the mRNA expression for their synthetic enzyme SPHK1. Among the most profoundly downregulated plasma lipids were several lysophosphatidylinositols (LPIs) from 3- to 3000-fold. LPIs are required for the synthesis of phosphatidylinositol 4-phosphate (PI4P) pools that are required for HCV replication, and LPIs can also activate the GPR55 receptor. Our plasma lipidomic findings shed new light on the pathobiology of HCV infection and show that a subset of bioactive lipids that may contribute to liver pathology is altered by HCV infection.

Frequency of Hepatocellular Carcinoma in HCV Patients Treated with Direct-Acting Antiviral Drugs

Frequency of Hepatocellular Carcinoma in HCV Patients Treated with Direct-Acting Antiviral Drugs

Correlation of NF-kB Serum Level with the Expression Pattern of Microrna-221 in a Sample of Hcv-Exposed Iraqi Patients

Background: Hepatitis C virus (HCV) has the ability to change cellular messenger RNA transcription and translation by stimulating the synthesis of cellular microRNAs (miRNAs) that impair immune response and facilitate viral reproduction. One of the most important members of the immune response against HCV is nuclear factor-kappa B (NF-κB), which is regulated by cellular miRNAs. Aims: we aimed to investigate the correlation of NF-κB serum level with circulatory miRNA-221 (miR-221) fold change in HCV-exposed individuals. Materials and Methods: Serum level of NF-κB in 88 samples (22 patients with persistent HCV infection, 22 individuals with spontaneous HCV virus clearance, 22 individuals treated with direct-acting antivirals (DAAs) drugs, and 22 uninfected apparently healthy blood donors as control) was measured by enzyme-linked immunosorbent assay. Reverse transcriptase–polymerase chain reaction was used to quantify the expression fold of circulatory miR-221. Results: The results showed that there was a significant decrease in the mean level of NF-κB at P &lt; 0.000 among HCV-exposed patients (2.0058 ng/ml) as compared to the control group (2.9841 ng/ml). The mean fold change of miR-221 was significantly upregulated about six more times among HCV-exposed patients (mean = 6.3545) compared to the control group (mean = 1.1864). Furthermore, the mean ± standard deviation of miR-221 fold change in patients with persistent HCV infection was significantly higher compared to patients cured after DAA therapy (P = 0.048), there was a weak negative correlation (r = −0.246, P = 0.021) between NF-κB serum level and miR-221 folding level. Conclusion: HCV infection disrupts NF-κB activation, resulting in dysregulation of miR-221 that persists long after the virus has been cleared. Thus, quantification of serum NF-κB and miR-221in HCV-exposed patients could be used as noninvasive prognostic marker during long-term follow-up. Furthermore, a miRNAs profile analysis can help distinguish HCV-exposed from healthy individuals.

Sociodemographic Profile, Genotype, and Response to Therapy in Hepatitis C Virus Infection: A Brief Report from Himachal Pradesh

Introduction Hepatitis C virus (HCV) infection is a major cause of liver disease worldwide. There is no data on sociodemographic profile, risk factors, genotype, and response to therapy of HCV infection from Himachal Pradesh. Methods In this single-center study, we retrospectively analyzed data from HCV-infected patients treated with new oral direct-acting antiviral drugs from September 2019 to March 2022. Data on the sociodemographic profile of HCV-infected patients, along with risk factors for its transmission, HCV genotype, and response to therapy, was analyzed. Results A total of 189 patients were included, with a mean age of 30.9 ± 13.8 years. Most were males and were students. Predominant risk factor for HCV transmission was intravenous drug use (61.4%), tattooing (11.7%), and hemodialysis (11.1%). A majority of the patients were students (72%). The predominant genotype was GT 3. Most (95.2%) patients were without cirrhosis, so sofosbuvir plus daclatasvir for 12 weeks was the most common regimen used. Sustained virological response was achieved in 94.7% of patients. Conclusion This study, alarmingly, shows that intravenous drug users and tattooing are important risk factors for HCV infection in Himachal Pradesh. Further, students were the most frequently infected group.

Early post-liver transplant use of direct-acting antivirals in naive and NS5A inhibitor-experienced HCV patients.

Direct-acting antiviral drugs (DAA) are safe and effective in the HCV population. However, in patients with decompensated cirrhosis and/or active hepatocellular carcinoma or relapse to NS5A inhibitors, response rates are lower and DAA therapy must be postponed until after liver transplant in an era of organ shortage and suboptimal donors. We aimed to assess the prevalence of patients still HCV infected at time of transplantation over the last 3 years in our Center and describe the safety and efficacy of DAA therapy started as soon as possible after surgery. We enrolled all HCV viraemic patients transplanted in our Centre from January 2019 to March 2022. The follow-up was closed in July 2022. Among 490 liver transplants, 49 (10%) patients were still HCV viraemic at operation, 43 naive to DAA and 6 were NS5A-experienced. Median donor age was 64 years; donor risk index was 1.8. In naive patients, sofosbuvir/velpatasvir was started after a median time of 1 day from surgery, while in NS5A-experienced sofosbuvir/velpatasvir/voxilaprevir after 14.5 days (p= .001). Response rate was 98%. 1 NS5A-experienced patient experienced acute cholestatic hepatitis which promptly reverted after permanent DAA discontinuation. Hence, very early post-liver transplant HCV eradication was safe and effective thanks to a close teamwork which involved anaesthesiologists, transplant surgeons and hepatologists.

1250. Screening for Hepatitis C as Part of an Opioid Stewardship Initiative: Identifying Infected Patients and Analyzing Linkage to Care

Abstract Background Hepatitis C (HCV) remains a major cause of liver-related morbidity and mortality even though direct-acting antiviral drugs (DAAs) are increasingly accessible and have cure rates approaching 100%. The demographics of HCV have shifted to younger patients, primarily due to the opioid epidemic and associated increased numbers of people who inject drugs (PWID). A robust screening program targeting patients with opioid use disorder (OUD) can identify patients with HCV and present opportunities for linkage to care, cure, and disease prevention by breaking the chain of transmission in high-risk groups. Methods As part of an organizational opioid stewardship long-term goal (2018-2020), Novant Health screened patients with OUD for HCV. A best practice alert (BPA) in the electronic health record (EHR) prompted providers to order HCV antibody. Management of positive tests was left to the discretion of the ordering provider. The disposition of patients with a positive HCV antibody was evaluated by retrospective chart review with patients categorized as: (a) known spontaneous virus clearance (b) linked to care with HCV specialist (c) previous treatment (d) not appropriately linked to care (e) not linked to care due to patient-directed discharge or nonadherence. Results Of 5560 patients encountered (average age 40.9, 49% female, 73.7% White, 21.8% AA/Black), 4405 patients were tested. Of those screened, 33.9% were positive. Among those with a positive HCV antibody, 24% had known spontaneous viral clearance and 73.9% needed linkage to care or follow up bloodwork, with 301 linked to care and 804 not successfully linked. Of eligible patients, 27.2% were linked to care. Conclusion There is a need for ongoing screening efforts in patients with OUD. Despite a BPA intervention, a large percentage of positive patients were not appropriately linked to care. Barriers to linkage include lack of provider education on HCV referral and treatment concurrent to the BPA rollout, as well as psychiatric comorbidities and social vulnerabilities more prevalent in patients with OUD. Disclosures All Authors: No reported disclosures.

A comprehensive review on pharmacologic agents, immunotherapies and supportive therapeutics for COVID-19.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

Evaluation of Direct-acting Antiviral Drugs for Hepatitis C patients below 30 years age in Sialkot, Pakistan

Background: Infection of Hepatitis C virus (HCV) is major contributor in liver problems, affecting nearly more than 70 million people all over the world. Top ten countries which are affected by Hepatitis, also include Pakistan. Medical science has entered a new era of HCV therapy in elimination of infection and disease is a real possibility. In Asia, Genotype 3 is chronic hepatitis C genotype as compared to other genotypes. Direct-acting antiviral drugs are famous for their high efficacy rate, but less work has done in Asia. Methods: A follow up research was performed to evaluate 3 months treatment outcome of some direct acting antiviral drugs in 35 patients (26 patients of HCV genotype 3) below 30 years of age using some relevant biological parameters. Results: A total of 30 patients yielded a pooled SVR of more than 85% after twelve weeks outcome of commonly used antiviral drugs evaluation. Conclusion: Commonly used antiviral drugs in Sialkot, Pakistan showed effectiveness in HCV patients having genotypes 1, 2, 3 and 5. Keywords: Hepatitis C virus, genotype 3, direct acting antiviral drugs, liver function tests, renal function tests

Evolution of clinical outcomes following hepatitis C virus clearance

As hepatitis C treatment entered the era of direct-acting antiviral drugs, an increasing number of patients received treatment and achieved virus clearance, but virus clearance is merely a relative endpoint. Future emphasis will be placed on post-treatment benefits and the evolution of clinical outcomes. This article aims to describe the improvement in all-cause mortality and hepatic and extrahepatic-related diseases following virus clearance, particularly in patients treated with direct-acting antiviral drugs.