Sustained Virological Response Rates Research Articles

Association of Sofosbuvir and Daclatasvir Plasma Trough Concentrations with Patient-, Treatment-, and Disease-Related Factors Among HIV/HCV-Coinfected Persons.

Sofosbuvir plus daclatasvir achieves high rates of sustained virologic response (SVR), with no differences according to HIV serostatus. However, only limited information is available on the pharmacokinetic variability of sofosbuvir and daclatasvir in HIV/HCV-coinfected patients. The aim of this studywas to identify patient-, treatment-, and disease-related factors that are significantly associated with sofosbuvir and daclatasvir plasma trough concentrations (Ctrough), including liver and renal function, among HIV/HCV-coinfected persons. In this observational cohort pilot study, HIV/HCV-coinfected patients undergoing sofosbuvir plus daclatasvir treatment were prospectively enrolled. Biochemical and viro-immunological parameters were assessed at baseline, week 4 (W4), end of treatment (EOT), and after EOT. The FIB-4 score and CKD-EPI equation were used to estimate liver disease and glomerular filtration rate (eGFR), respectively. For sofosbuvir, sofosbuvir metabolite (GS-331007), and daclatasvir, Ctrough was measured at W4 and week 8 (W8), and the mean of the values at those two time points (mean-Ctrough) was calculated. The Mann-Whitney test and Spearman's rank correlation were used to evaluate the correlations between the mean-Ctrough of each direct-acting antiviral (DAA) and the considered variables. Thirty-five patients were included (SVR 94%). An increased GS-331007 mean-Ctrough was significantly correlated with a decreased eGFR at W4 (rho = -0.36; p = 0.037) and EOT (rho = -0.34; p = 0.048). There was a significant correlation between daclatasvir mean-Ctrough and FIB-4 at all time points: baseline (rho = -0.35; p = 0.037), W4 (rho = -0.44; p = 0.008), EOT (rho = -0.40; p = 0.023), and after EOT (rho = -0.39; p = 0.028). In HIV/HCV-coinfected patients in a real-world setting, exposure to a high GS-331007 Ctrough was associated with a slight decrease in renal function, while advanced hepatic impairment was significantly associated with a lower daclatasvir Ctrough. Though the clinical and therapeutic relevance of these findings may be limited, increasing clinicians' knowledge regarding DAA exposure in difficult-to-treat patients could be relevant in single cases, and further investigations are warranted.

IL28B rs12979860 polymorphism and zinc supplementation affect treatment outcome and liver fibrosis after direct-acting antiviral hepatitis C therapy

BackgroundImpact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis. ResultsThree hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes. ConclusionAbsolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis.

Treatment of hepatitis C virus infection with direct-acting antiviral agent-based regimens in Iranian patients with hereditary bleeding disorders

BackgroundChronic hepatitis C (CHC) is one of the most important comorbidities in patients with hereditary bleeding disorders (HBD). The present study aimed at evaluating the effectiveness of direct-acting antiviral agent (DAA)-based interferon-free HCV antiviral regimens in patients with HBD.Patients and methodsThe present study was performed on the patients with HBD and CHC between 2015 and 2019. Sofosbuvir-based interferon-free regimens with or without ribavirin were prescribed to treat HCV infection. The main endpoint of the study was to determine the sustained virologic response (SVR), assessed 12 weeks after the completion of treatment.ResultsA total of 147 patients with a mean age of 41.1 years were enrolled in the study; 4.1% of them were co-infected with HIV, 25.2% had cirrhosis, and 76.9% of them were diagnosed with hemophilia A. HCV genotype-1 includes the largest number (68.1%) of patients. 46.3% of patients were treatment-naïve and others had a treatment history with interferon-based regimens. Out of 147 patients, 15 patients were lost to follow-up during treatment or for SVR evaluation or discontinued treatment. 132 subjects completed treatment and were evaluated for SVR, 12 weeks after the completion of treatment. All of the patients achieved SVR 12 (SVR rate: 100%, 95% CI 97.2–100%).ConclusionHepatitis C DAA-based regimens are the effective treatments for CHC in patients with HBD, regardless of the treatment modifiers such as previous treatment experience, cirrhosis, HIV co-infection, and HCV genotype.

Epidemiology and treatment status of hepatitis C virus infection among people who have ever injected drugs in Korea: a prospective multicenter cohort study from 2007 to 2019 in comparison with non-PWID.

OBJECTIVESInjection drug use is a major risk factor for hepatitis C virus (HCV) infection; however, limited data on this topic are available in Korea. Thus, this study aimed to investigate the epidemiological and clinical characteristics, treatment uptake, and outcomes of HCV infection among people who inject drugs (PWID).METHODSWe used the data from the Korea HCV cohort, which prospectively enrolled patients with HCV infection between 2007 and 2019. Clinical data and results of a questionnaire survey on lifetime risk factors for HCV infection were analyzed according to a self-reported history of injection drug use (PWID vs. non-PWID group).RESULTSAmong the 2,468 patients, 166 (6.7%) were in the PWID group, which contained younger patients (50.6±8.2 vs. 58.2±13.1 years) and a higher proportion of male (81.9 vs. 48.8%) than the non-PWID group. The distribution of PWID showed significant regional variations. Exposure to other risk factors for HCV infection was different between the groups. The proportion of patients with genotype non-2 infection was higher in the PWID group. Treatment uptake was higher in the PWID group in the interferon era; however, it was comparable between the groups in the direct-acting antiviral era. The rate of sustained virological response did not significantly differ between the groups.CONCLUSIONSAs of 2019, PWID constituted a minority of HCV-infected people in Korea. The epidemiological characteristics, but not treatment uptake and outcomes, were different between the PWID and non-PWID groups. Therefore, active HCV screening and treatment should be offered to PWID in Korea.

Community-Based Assessment and Treatment of Hepatitis C Virus-Related Liver Disease, Injecting Drug and Alcohol Use Amongst People Who Are Homeless: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis addressing community-based assessment and treatment of hepatitis C virus (HCV)-related liver disease, injecting drug use (IDU) and alcohol use amongst people who are homeless (PWAH). Using systematic review methodology, databases were searched (MEDLINE/EMBASE/CINAHL) for studies combining PWAH, HCV-related liver disease and community assessment until December 2019. Studies with a sample size ≥ 30, with PWAH constituting at least 30% of the cohort were included and a quality assessment performed. Pooled estimates of key indicators were analysed using meta-analysis. We identified 39 studies (n=13,918), 37 categorised as poor quality (Newcastle-Ottawa Scale). Prevalence of homelessness ranged between 30%-100% (37 studies). Eight studies provided all of the following: HCV screening, alcohol/substance use/liver fibrosis assessment and HCV treatment. No study provided interventions for alcohol use, with two providing opioid substitution treatment. Alcohol use prevalence (24 studies) was 4%-97%, being 59% (95% CI 20%-92%) in four studies that included only PWAH. Recent IDU prevalence (16 studies) was 7%-73%, being 21% (95% CI 17%-26%) in four studies that included only PWAH. HCV seroprevalence (25 studies) was 2.5% - 58%; in 13 studies that included only PWAH, this was 20% (95% CI 12%-30%). Prevalence of F4 fibrosis (nine studies) was 6%-28%, being 7% and 16% in two studies that included only PWAH. Direct acting antiviral-based intention-to-treat sustained virological response (SVR) rates (five studies) were 82%-92%, being 92% in the one study that included only PWAH. In the only two randomised controlled trials (RCT) identified, community-based interventions (mental health/peer mentor) significantly increased linkage to care (p=0.04), HCV treatment (p=0.005) and SVR rates (p=0.018). The burden from alcohol/IDU and HCV, and consequently liver disease in PWAH needs addressing. RCT trials assessing community-based interventions to improve liver health in PWAH are needed.

S1243 Comparing Racial Disparity in HCV Demographics and Treatment Between 2002-2003 and 2019

Introduction: The recent Direct-Acting Antiviral (DAA) era of HCV treatment has not only increased the sustained viral response (SVR) rate ( >95%), but also eliminated the treatment response disparities between African American (AA) and non-AA patients seen with interferon (IFN) therapy. Issues remain, however, with respect to identification and linkage to care in HCV patients. The aim of our study is to compare 2019 HCV patients in our predominantly AA clinic to patients from 2002-2003. We hypothesize an increase in successfully treated patients due to the advent of DAAs and an increase in the number of patients being treated after their first visit. Methods: Using electronic medical records, we identified 600 HCV patients seen in 2019 and compared them to 398 patients seen between 2002 and 2003. Data collected included demographics, laboratory studies (AST, ALT, HCV genotype, viral load), and treatment history. Fibrosis was assessed directly by FibroScan (2019) or biopsy (2002-2003) and as serum based calculations of the AST Platelet Ratio Index and FIB-4. Results: Only 11 patients were seen in both eras. Of these patients, the majority (9/11) were treated and cured by 2019. More patients were seen per year in the recent era and, with the exception of young non-AA patients, these patients were younger (Fig 1). In both eras, AA patients were older than non-AA patients, with only non-AA females being younger in the recent era (Fig 1). Non-AA patients in both eras were less likely to be infected with genotype 1 compared to AA (95% vs 54%, p< 0.001). In 2019, patients of both races had higher rates of cirrhosis than earlier patients as assessed by ultrasound, but had less significant fibrosis when measured by serum based assays (APRI, FIB-4) (Table 1). When fibrosis by FibroScan and biopsy were directly compared, there was no difference between the two eras. More patients were treated prior to their visit in 2019 compared to 2002-2003 (159/585=27% vs 5/402=1%). For untreated patients, subsequent treatment within 1 year of the initial visit was similar in both eras (35%). Conclusion: Even though current therapies are oral, highly effective, and can be 6-8 weeks in duration, a significant number of patients were not treated within a year of first visit. The increased age of current AA and non-AA male patients suggests an ongoing need to identify older age cohort patients for treatment while the decrease in age of non-AA female patients suggests the need to increase surveillance of younger patients.Figure 1.: Top: Baseline characteristics of the studies population and the percentage of the population with each particular risk factor. Bottom: The predictors of Coronary Artery Diseases in patients with Liver cirrhosis. Figure shows the predictors of coronary artery diseases in the Liver cirrhosis group of patients. Multivariate analysis was performed to address any confounding factors. SPSS was used to calculate the Odds Ratio.Table 1.: EGFR and Creatinine Clearance in different treatments. dF = degrees of freedom; F= F statistics.

Disparities in Treatment with Direct-Acting Hepatitis C Virus Antivirals Persist Among Adults Coinfected with HIV and Hepatitis C Virus in US Clinics, 2010-2018.

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection carries substantial risk for all-cause mortality and liver-related morbidity and mortality, yet many persons coinfected with HIV/HCV remain untreated for HCV. We explored demographic, clinical, and sociodemographic factors among participants in routine HIV care associated with prescription of direct-acting antivirals (DAAs). The HIV Outpatient Study (HOPS) is an ongoing longitudinal cohort study of persons with HIV in care at participating clinics since 1993. There are currently eight study sites in six US cities. We analyzed medical records data of HOPS participants diagnosed with HCV since June 2010. Sustained virological response (SVR) was documented with first undetectable HCV viral load (VL). We assessed factors associated with being prescribed DAAs by multi-variable logistic regression and described the cumulative rate of SVR. Among 306 eligible participants, 131 (43%) were prescribed DAA therapy. Factors associated with greater odds of being prescribed DAA were older age, private health insurance, higher CD4 cell count, being a person who injects drugs, and receiving care at publicly funded sites (p < 0.05). Of 127 (97%) participants with at least 1 follow-up HCV VL, 110 (87%) achieved SVR at 12 weeks. Of the total 131 participants, 123 (94%) eventually achieved SVR. Less than half of HIV/HCV coinfected patients in HOPS have been prescribed DAAs. Interventions are needed to address deficits in DAA prescription, including among patients with public or no health insurance, younger age, and lower CD4 cell count.

Hepatitis C virus treatment failure: Clinical utility for testing resistance-associated substitutions.

The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions (RAS). However, the consequence of resistance selection during new direct-acting antiviral drug (DAA) treatment is not necessarily the therapeutic failure. In fact, DAA treatment has shown a high rate (> 95%) of sustained virological response even when high baseline RAS prevalence has been reported. In the context of RAS emergence and high rates of sustained viral response, the clinical relevance of variants harboring RAS is still controversial. Therefore, in order to summarize the data available in international guidelines, we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.

Genotype-specific versus pangenotypic regimens in patients infected with hepatitis C virus genotype 1b in real-world settings.

Introduction: The introduction of direct-acting antivirals (DAAs) has provided us with hope to eliminate hepatitis C virus (HCV) infection as a significant public health problem in the coming years. Objective: Our study aimed to compare the effectiveness and safety of genotype-specific and pangenotypic regimens in genotype 1b–infected patients treated in real-world settings. Patients and methods: Patients were selected from 990 HCV-infected individuals treated with DAAs in the Department of Infectious Diseases in Kielce, Poland, who had the therapy initiated between July 1, 2015 and December 31, 2020. Results: A total of 795 genotype 1b–infected patients with a median age of 51 years, female predominance (55%), and a 21.1% rate of cirrhosis were included in the analysis. A total of 69.9% of patients were treated with genotype-specific regimens. Those patients were significantly older, more often were treatment experienced, and had advanced liver fibrosis and cirrhosis compared with patients assigned to pangenotypic regimens. An overall sustained virologic response rate of 97.9% in the intention-to-treat (ITT) analysis and 99% after excluding nonvirologic nonresponders was achieved, with no significant difference between patients in the 2 treatment arms. Significantly higher proportions of men (P = 0.001) and DAA-experienced patients (P = 0.049) were documented among virologic nonresponders. Conclusions: We confirmed very high effectiveness and a good safety profile of both genotype-specific and pangenotypic regimens used in patients with genotype 1b HCV infection, and we found no differences between these 2 generations of medications. Male sex and previous treatment with DAAs were identified as negative predictors for therapy effectiveness.

Adherence to Hepatitis C Therapy in a Shelter-Based Education and Treatment Model Among Persons Experiencing Homelessness.

Medication adherence is a common reason for treatment deferment in persons experiencing homelessness. We evaluated adherence to hepatitis C virus (HCV) therapy following HCV education in a shelter-based care model. Prospective study conducted at 4 homeless shelters in Minneapolis, Minnesota and San Francisco, California from November 2018 to January 2021. Sixty-three patients underwent HCV education and treatment. Multivariable modeling evaluated factors associated with (1) medication and (2) overall (composite score of medication, laboratory, and clinic visit) adherence. Median age was 56 years; 73% of participants were male, 43% were Black, 52% had psychiatric illness, and 81% used illicit drugs and 60% used alcohol in the past year. Following education, 52% were extremely confident in their ability to be adherent to HCV therapy. Medication adherence by patient and provider report was 88% and 48%, respectively, and 81% achieved HCV cure. Active alcohol use was associated with less confidence in medication adherence (43% vs 78%, P = .04). Older age was positively (coefficient = 0.3) associated with overall adherence to HCV treatment whereas prior therapy was associated with both medication (odds ratio, 0.08) and overall treatment (coefficient = -0.87) nonadherence. Despite imperfect adherence, sustained virologic response rates were still high. Expanding opportunities to treat persons experiencing homelessness in a structured and supportive setting is critical to HCV elimination efforts.

The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia

Introduction and objectivesHepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. Patients and methodsThe study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. ResultsCompared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years.Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. ConclusionHemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.

Post-treatment serum Wisteria floribunda agglutinin-positive mac-2-binding protein level is a useful predictor of hepatocellular carcinoma development after hepatitis C virus eradication.

AimsRecent advances of direct‐acting antiviral drugs for hepatitis C virus (HCV) have dramatically improved the sustained virologic response (SVR) rate, but hepatocellular carcinoma (HCC) development rarely occurs even in patients who achieve an SVR. Wisteria floribunda agglutinin‐positive mac‐2‐binding protein (WFA+‐M2BP) was recently developed as a noninvasive biomarker of liver fibrosis. However, the association between the WFA+‐M2BP level and HCC development after the achievement of an SVR is unclear.Methods and ResultsWe examined the association between WFA+‐M2BP and HCC development in 522 HCV patients who achieved an SVR (Interferon [IFN]‐based therapy, n = 228; IFN‐free therapy, n = 294). Multivariate analysis revealed that a high WFA+‐M2BP level at SVR week 24 after treatment (SVR24) (hazard ratio [HR] = 1.215, P = 0.020), low platelet counts (HR = 0.876, P = 0.037), and old age (HR = 1.073, P = 0.012) were independent risk factors for HCC development regardless of the treatment regimen. Receiver operator characteristics curve analysis revealed that a WFA+‐M2BP level at SVR24 of ≥1.62 cut‐off index (COI) was the cut‐off value for the prediction of HCC development (adjusted HR = 12.565, 95% CI 3.501–45.092, P < 0.001). The 3‐ and 5‐year cumulative incidences of HCC were 1% and 1.6% in patients with low WFA+‐M2BP at SVR24 (<1.62 COI), and 4.7% and 12.5% in patients with high WFA+‐M2BP (≥1.62 COI) were, respectively (P < 0.001).ConclusionsThe assessment of liver fibrosis using the WFA+‐M2BP level at SVR24 is a useful predictor of HCC development after HCV eradication even in the IFN‐free therapy era.

Nonadherence to Ledipasvir/Sofosbuvir Did Not Predict Sustained Virologic Response in a Randomized Controlled Trial of Human Immunodeficiency Virus/Hepatitis C Virus Coinfected Persons Who Use Drugs.

Eliminating hepatitis C virus (HCV) will require effective treatment delivery to persons with substance use disorders (SUDs). We evaluated the relationship between ledipasvir/sofosbuvir treatment persistence (receiving 84 tablets), adherence, and sustained virologic response (SVR) in persons with human immunodeficiency virus (HIV)/HCV coinfection. Of the 144 participants with HIV/HCV and SUDs, 110 initiated a 12-week treatment course under 1 of 3 conditions (usual care, peer mentors, and cash incentives). We used self-report, pharmacy pill counts, and expected date of refill to examine adherence. Persistent participants were categorized as high adherence (taking ≥90% of doses) or low adherence (taking <90% of doses). Most participants persisted on treatment after initiation (n = 105), with 95% (n = 100) achieving SVR. One third (34%) of participants had moderate/heavy alcohol use by the biomarker phosphatidylethanol ([Peth] ≥50 ng/mL), and 44% had urine toxicology positive for cocaine or heroin at enrollment. The proportion of persons with high adherence was 72% (n = 76), and the proportion of persons with low adherence was 28%. Although low adherence was associated with moderate/heavy alcohol use by PEth (relative risk = 2.77; 95% confidence interval, 1.50-5.12), SVR did not vary according to adherence (P = .702), and most participants (97%) with low adherence achieved SVR. Treatment persistence led to high SVR rates among persons with HIV/HCV, despite imperfect adherence and SUDs.

Effectiveness, tolerability and safety of Direct Acting Antivirals in Mexican individuals with Hepatitis C virus genotype-1 and previous pegylated interferon and ribavirin therapy.

BackgroundDirect Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in <90% sustained virological response (SVR). There are no reports on the real-world DAA response for Mexico and few reports exist for Latin America. The aim of the study was to report SVR, and immediate benefits with the DAA treatments sofosbuvir, ledispavir, with/without ribavirin (SOF/LDV ± RBV) and ombitasvir, paritaprevir, ritonavir, dasabuvir with/without RBV (OBV/PTV/r/DSV ± RBV) in patients with viral genotype 1a or 1b, and who did not respond to previous peginterferon/ribavirin (PegIFNα2a+RBV) therapy.MethodsA descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment.ResultsSVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction.ConclusionsDAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.

Real-Life Experience with Ledipasvir/Sofosbuvir for the Treatment of Chronic Hepatitis C Virus Infection with Genotypes 1 and 4 in Children Aged 12 to 17 Years-Results of the POLAC Project.

Background: Available real-world data on the efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) in pediatric patients are limited. In this prospective, open-label, single-center study, we aimed to present our real-life experience with a fixed dose of LDV/SOF (90/400 mg) for the treatment of chronic hepatitis C (CHC) genotypes 1 and 4 in children aged 12 to 17 years. Methods: We analyzed intention-to-treat (ITT) and per-protocol (PP) rates of sustained virological response (SVR), defined as undetectable HCV viral load at posttreatment week 12, in 37 participants treated with LDV/SOF according to the HCV genotype, baseline liver fibrosis, duration of treatment, and experience of the previous ineffective antiviral treatment. There were 32 patients infected with genotype 1 and 5 with genotype 4. Fourteen (38%) participants were treatment-experienced, two were coinfected with HIV, and three were cirrhotic. Two patients qualified for 24 weeks of therapy, and the remaining 35 received 12 weeks of LDV/SOF treatment. Results: The overall ITT SVR12 rate was 36/37 (97%). One patient was lost to follow-up after week 4 of therapy when his HCV RNA was undetectable. All 36 patients who completed the full protocol achieved SVR (36/36, 100%). PP analyses of SVR12 rates according to the HCV genotype, baseline liver fibrosis, duration of the treatment, and previous ineffective treatment were all 100%. A significant decrease in aminotransferase serum levels was observed in the subsequent weeks of the treatment and at SVR assessment compared to baseline. No serious adverse events were reported. Conclusions: The results of this study confirm previous observations of a suitable efficacy and safety profile of LDV/SOF for the treatment of CHC genotypes 1 and 4 in adolescents.

Sofosbuvir plus velpatasvir combination for the treatment of chronic hepatitis C in patients with end stage renal disease on renal replacement therapy: A systematic review and meta-analysis.

Sofosbuvir (SOF) and velpatasvir (VEL) is a pan-genotypic regimen for the treatment of Hepatitis C virus (HCV) infection. The data on the efficacy and safety of this regimen is end-stage renal disease (ESRD) is scanty. This systematic review and meta-analysis was done to ascertain the efficacy and safety of SOF and VEL in patients with chronic Hepatitis C (CHC) and ESRD on renal replacement therapy (RRT). Systematic search of Pubmed, Embase, Scopus, and Google Scholar was conducted using the search term (end-stage renal disease OR renal replacement therapy OR chronic kidney failure OR severe renal impairment OR chronic kidney disease OR haemodialysis OR dialysis OR peritoneal dialysis) AND (sofosbuvir OR velpatasvir OR NS5A inhibitors OR directly acting antivirals). Pooled sustained virologic response (SVR) and adverse event rates with 95% confidence intervals were estimated. Seven studies (410 patients with CHC and ESRD on RRT) fulfilled our eligibility criteria. The overall pooled SVR rate of SOF and VEL in patients with HCV on RRT was 97.69% (95% CI: 95.71 to 98.92). There was no significant heterogeneity (I2 : 39.3%, p-value of Cochran's Q=0.13) among the studies. The pooled estimate of efficacy of SOF-VEL combination among patients with cirrhosis was 91.94% (95% CI 77.03-98.52). Pooled SVR rates in genotype 3 infection [94.6%, (95%: CI 81.3-99.4)] was comparable to that in those with documented non-genotype 3 infection [94.63%, (95% CI 87.12-98.44)]. No serious adverse event attributable to SOF and VEL was reported in the included studies. The fixed-dose combination of SOF and VEL is effective and safe in CHC patients with ESRD on RRT.

Direct-acting antiviral regimens in Egyptian patients with chronic hepatitis C virus infection: A real-world single-center experience

Background and study aims:Chronic hepatitis C virus (HCV) infection has always been identified as a major health threat and a potential cause of liver cirrhosis, portal hypertension, and other associated problems. The introduction of direct-acting antiviral agents (DAAs) has represented a paradigm shift in HCV management. In this study, we aim to observe the rate of sustained virologic response (SVR12) in a large scale of patients at a single center as well as record the post-treatment changes in the hematologic, hepatic, and renal biochemical profiles. Patients and methodsIn total, 1933 chronic HCV genotype 4 mono-infected non-HCC patients who completed the treatment with six different DAA regimens in the Faculty of Medicine, Ain Shams University Research Institute (MASRI), were retrospectively enrolled in this study. The rate of sustained virologic response after 12 weeks off-therapy (SVR12) was assessed. The baseline characteristics to predict the SVR12 were then analyzed. The post-treatment changes in many profiles were recorded and analyzed. ResultsThe overall SVR12 rate was 96.2% (after excluding 84 cases who were lost to follow-up). It was achieved in 346/375 patients (92.3%), 466/477 patients (97.7%), 60/62 patients (96.8%), 11/11 patients (100%), 532/545 patients (97.6%), and 445/463 patients (96.1%) who received sofosbuvir/daclatasvir (SOF/DCV), sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV), sofosbuvir/ledipasvir (SOF/LDV), sofosbuvir/ledipasvir/ribavirin (SOF/LDV/RBV), sofosbuvir/simeprevir (SOF/SMV), and ombitasvir/paritaprevir/ritonavir/ribavirin (OBV/PTV/r + RBV), respectively. In total, 73 patients (3.8%) failed to achieve SVR12. The baseline aspartate aminotransferase (AST), cirrhotic status, and treatment regimen were determined to have a significant impact on SVR12. In the overall treated population, the levels of serum AST, alanine aminotransferase, albumin, creatinine, bilirubin, and hemoglobin and platelet count improved significantly after treatment. Furthermore, sustained virologic response was strongly related to cirrhosis and its degree. ConclusionThe interferon-free DAA regimens offered high SVR12 rates in Egyptian patients with chronic HCV infection. They were associated with a significant improvement in the hematologic, hepatic, and renal biochemical profiles. The baseline AST, liver cirrhosis, and treatment regimen might have an impact on achieving SVR.

Effect of Daclatasvir and Sofosbuvir Therapy on Serum Levels of Angiogenic Factors: A Prospective Cohort Study

Background: Direct-acting antiviral agents therapy is considered a breakthrough in hepatology due to high rates of sustained virologic response in all patients including those with decompensated cirrhosis. However, impact of Direct-acting antiviral agents-induced sustained virologic response on hepatocellular carcinoma development remains conflicting.&#x0D; Aims: This study aimed at evaluating the change in circulating levels of vascular endothelial growth factor and transforming growth factor-β1, the main angiogenic factors involved in hepatocarcinogenesis process, in cirrhotic patients achieved sustained virologic response after Direct-acting antiviral agents therapy.&#x0D; Study Design: This was a prospective, single-center, cohort study.&#x0D; Place and Duration of Study: Patients were recruited from the outpatient clinic of National Liver Institute, which considered a tertiary referral center in Menoufia University, Egypt (September 2018 to February 2019).&#x0D; Methodology: Forty-five decompensated cirrhotic hepatitis C virus infected patients with no history of hepatocellular carcinoma participated in the study. All patients received 60mg oral daclatasvir and 400mg oral sofosbuvir once daily for 12 or 24 weeks with or without ribavirin. Serum levels of vascular endothelial growth factor and transforming growth factor-β1 were measured at baseline and 12 weeks after the end of therapy.&#x0D; Results: The median serum levels of vascular endothelial growth factor showed a non-statistically significant increase (from 1123 ng/L to 1269 ng/L, P = 0.126). But, transforming growth factor-β1 median serum levels exhibited a non-statistically significant reduction (from 13.22 ng/ml to 12.44 ng/ml, P = 0.163) 12 weeks after treatment.&#x0D; Conclusion: Our findings show direct-acting antiviral agents therapy do not affect vascular endothelial growth factor and transforming growth factor-β1 serum levels. But, a larger scale prospective cohort study on an extended follow-up period is recommended.

O-3 TRENDS IN DECEASED DONOR AND LIVING DONOR LIVER TRANSPLANTATION IN LATIN AMERICAN COUNTRIES DURING A DECADE (2010-2019) . THE ALEH SPECIAL INTEREST GROUP, INTERNATIONAL SURVEY 2020

Brazilian public health system currently provides universal free all oral direct-acting antiviral (DAA) therapy for patients with hepatitis C virus (HCV) infection. Despite high rates of sustained virological response (SVR), patients with cirrhosis remain at risk for hepatocellular carcinoma (HCC). The aim of this study was to investigate incidence, risk factors and tumor pattern at presentation in a cohort of Brazilian HCV-related cirrhotic patients treated with DAAs. This prospective cohort study included patients with HCV-related cirrhosis treated with DAAs and followed for at least 24 weeks after therapy at the Viral Hepatitis Outpatient Clinic of Hospital de Clinicas de Porto Alegre, Brazil, between August 2016 and November 2017. Ultrasound screening was performed within 24 weeks before DAA therapy and patients with presumed past or current HCC were excluded. Primary outcome was HCC incidence. Secondary outcomes were risk factors for HCC ocurrence and tumor pattern at presentation. Multivariate analysis was used to identify independent variables associated with HCC development. A total of 234 patients with HCV cirrhosis were included. Fifty-six percent were males with a mean age of 61.2±10.9 years. Overall SVR was 97.4%. Child-Turcotte-Pugh (CTP) A, B and C at baseline was found, respectively, in 89.3%, 9.4% and 1,3%. Mean Model for End Stage Liver Disease (MELD) score was 9.17 ± 2.82. Esophageal varices were found in 43.6% of the patients. Type 2 diabetes was present in 18.8%. De novo HCC was diagnosed in 9% (21/234) of the patients during follow-up. Tumor pattern at presentation according to BCLC staging was 0, A, B, C and D in 19,1%, 47.6%, 4.8%, 28.6% and 0%, respectively. Multivariate analysis showed significant relative risk (RR) for HCC occurrence associated with the following variables: baseline MELD score ≥10 (RR: 1.8; p =0.05); absence of SVR (RR: 6.9; p =0.04); baseline platelet count <120 × 10 9 /L (RR: 5.0; p =0.04) and baseline albumin level <3.5 mg/dL (RR: 4.6. A high incidence of HCC was found after DAA therapy compared to the literature, particularly among patients with more advanced cirrhosis, particularly those with baseline albumin levels < 3.5 g/dL plus platelets < 120 × 10 9 /L. Absence of SVR was also significantly associated with HCC development. The majority of patients presented with very early (BCLC 0) or early (BCLC A) HCC, although a significant proportion showed advanced stage (BCLC C) at presentation.

O-19 INCIDENCE, PATTERN OF PRESENTATION AND RISK FACTORS FOR HEPATOCELLULAR CARCINOMA AFTER DIRECT ACTING ANTIVIRAL TREATMENT IN PATIENTS WITH HEPATITIS C VIRUS CIRRHOSIS

Brazilian public health system currently provides universal free all oral direct-acting antiviral (DAA) therapy for patients with hepatitis C virus (HCV) infection. Despite high rates of sustained virological response (SVR), patients with cirrhosis remain at risk for hepatocellular carcinoma (HCC). The aim of this study was to investigate incidence, risk factors and tumor pattern at presentation in a cohort of Brazilian HCV-related cirrhotic patients treated with DAAs. This prospective cohort study included patients with HCV-related cirrhosis treated with DAAs and followed for at least 24 weeks after therapy at the Viral Hepatitis Outpatient Clinic of Hospital de Clinicas de Porto Alegre, Brazil, between August 2016 and November 2017. Ultrasound screening was performed within 24 weeks before DAA therapy and patients with presumed past or current HCC were excluded. Primary outcome was HCC incidence. Secondary outcomes were risk factors for HCC ocurrence and tumor pattern at presentation. Multivariate analysis was used to identify independent variables associated with HCC development. A total of 234 patients with HCV cirrhosis were included. Fifty-six percent were males with a mean age of 61.2±10.9 years. Overall SVR was 97.4%. Child-Turcotte-Pugh (CTP) A, B and C at baseline was found, respectively, in 89.3%, 9.4% and 1,3%. Mean Model for End Stage Liver Disease (MELD) score was 9.17 ± 2.82. Esophageal varices were found in 43.6% of the patients. Type 2 diabetes was present in 18.8%. De novo HCC was diagnosed in 9% (21/234) of the patients during follow-up. Tumor pattern at presentation according to BCLC staging was 0, A, B, C and D in 19,1%, 47.6%, 4.8%, 28.6% and 0%, respectively. Multivariate analysis showed significant relative risk (RR) for HCC occurrence associated with the following variables: baseline MELD score ≥10 (RR: 1.8; p =0.05); absence of SVR (RR: 6.9; p =0.04); baseline platelet count <120 × 10 9 /L (RR: 5.0; p =0.04) and baseline albumin level <3.5 mg/dL (RR: 4.6. A high incidence of HCC was found after DAA therapy compared to the literature, particularly among patients with more advanced cirrhosis, particularly those with baseline albumin levels < 3.5 g/dL plus platelets < 120 × 10 9 /L. Absence of SVR was also significantly associated with HCC development. The majority of patients presented with very early (BCLC 0) or early (BCLC A) HCC, although a significant proportion showed advanced stage (BCLC C) at presentation.