Achievement Of Sustained Virological Response Research Articles

Prognostic Factors for Overall Survival in Patients with HCV-Related HCC Undergoing Molecular Targeted Therapies: Beyond a Sustained Virological Response.

Simple SummaryThe eradication of the hepatitis C virus (HCV) has had a significant impact on the management of patients with HCV-related hepatocellular carcinoma (HCC). However, its eradication has not completely resolved survival issues in patients with HCV-related HCC. Therefore, the present study investigated prognostic factors for survival in patients with HCV-related HCC undergoing molecular targeted therapies. In total, 359 HCC patients treated with first-line chemotherapy were enrolled. The median follow-up duration was 16.0 months (range, 1.0–115.7) and the median duration of first-line systemic therapy was 3.7 months (range, 0.7–86.9). The achievement of a sustained virological response (SVR) (p < 0.001), albumin-bilirubin (ALBI) grade II/III (p < 0.001), Barcelona Clinic Liver Cancer (BCLC) stage C (p = 0.005), extrahepatic spread (p < 0.001), baseline AFP level ≥ 90 (p = 0.038), baseline DCP level ≥ 500 (p < 0.001), and a fibrosis-4 (FIB-4) index ≥ 4 (p = 0.003) were identified as independent prognostic factors for overall survival.Background: The treatment of the hepatitis C virus (HCV) has reduced the risk of hepatocellular carcinoma (HCC)-related mortality. Many patients with advanced HCC have achieved longer survival through systemic chemotherapy. However, survivors of HCC may develop liver cancer during and after treatment. Therefore, the present study investigated prognostic factors for survival in patients with HCV-related HCC in the new era of molecular targeted therapy. Methods: A total of 359 patients with HCV-related HCC treated with first-line chemotherapy were reviewed. A Cox proportional hazards model and Kaplan–Meier curve were used to identify prognostic factors associated with survival outcomes. Results: The median follow-up duration was 16.0 months (range, 1.0–115.7) and the median duration of first-line systemic therapy was 3.73 months (range, 0.7–86.9). The achievement of a sustained virological response (SVR) (p < 0.001), albumin–bilirubin (ALBI) grade II/III (p < 0.001), Barcelona Clinic Liver Cancer (BCLC) stage C (p = 0.005), extrahepatic spread (p < 0.001), baseline AFP (alpha-fetoprotein) level ≥ 90 (p = 0.038), baseline DCP (des-γ-carboxy prothrombin) level ≥ 500 (p < 0.001), and a fibrosis-4 (FIB-4) index ≥ 4 (p = 0.003) were identified as prognostic factors for overall survival. Conclusions: The achievement of SVR was most strongly associated with overall survival. Other factors, such as the BCLC stage, extrahepatic spread, baseline tumor marker (AFP/DCP) levels, ALBI grade, and FIB-4 index need to be considered in the management of patients with HCV-related HCC.

Factors Associated with Sustained Virologic Response to Hepatitis C Treatment in a Homeless-Experienced Cohort in Boston, 2014-2020.

Engaging people experiencing homelessness or unstable housing in hepatitis C virus (HCV) treatment is critical to achieving HCV elimination. To describe HCV treatment outcomes, including factors associated with retention through the treatment cascade, for a cohort of individuals treated in a homeless health center in Boston. Retrospective cohort study. All individuals who initiated HCV treatment with Boston Health Care for the Homeless Program's HCV treatment program between January 2014 and March 2020 (N = 867). The primary outcome was sustained virologic response (SVR), defined as an HCV ribonucleic acid (RNA) level ≤ 15 IU/mL at least 12 weeks after treatment completion. We used multivariable logistic regression to examine the association between baseline variables and SVR. Process-oriented outcomes included treatment completion, assessment for SVR, and achievement of SVR. Of 867 individuals who started HCV treatment, 796 (91.8%) completed treatment, 678 (78.2%) were assessed for SVR, and 607 (70.0%) achieved SVR. In adjusted analysis, residing in stable housing (OR 3.83, 95% CI 1.85-7.90) and age > 45 years old (OR 1.53, 95% CI 1.04-2.26) were associated with a greater likelihood of achieving SVR. Recent drug use (OR 0.63, 95% CI 0.41-0.95) was associated with a lower likelihood of SVR. Age, housing status, and drug use status impacted retention at every step in the treatment cascade. A large proportion of homeless-experienced individuals engaging in HCV treatment in a homeless health center achieved SVR, but enhanced approaches are needed to engage and retain younger individuals, those with recent or ongoing substance use, or those experiencing homelessness or unstable housing. Efforts to achieve HCV elimination in this population should consider the complex and overlapping challenges experienced by this population and aim to address the fundamental harm of homelessness itself.

The analysis of immunoreactivity of individual B-cell epitopes of hepatitis C virus (Flaviviridae: Hepacivirus: Hepatitis С virus) NS4a antigen

Chronic viral hepatitis C (CHC) is a ubiquitous infectious disease, a significant limitation of which WHO attributes to the use of a new highly effective antiviral therapy. Previously, two B-cell epitopes were identified in NS4a antigen of the hepatitis C virus (HCV). It was shown that certain titers of antibodies (ABs) to the extended C-terminal epitope (1687-1718 a.a.) can predict a high probability of achieving a sustained virological response (SVR) to standard therapy with pegylated interferon-α and ribavirin.The aim of the work was to determine immunoreactivity of two B-cell epitopes (middle and C-terminal) of NS4a antigen, and to estimate a possible association of ABs to them with the achievement of SVR after standard interferon therapy and treatment with direct antiviral drugs (DAAs) daclatasvir and sofosbuvir (velpanat). Blood serum samples of patients with CHC (n = 113), of which 55 participants received standard interferon therapy, 50 received velpanate treatment, the remaining 8 received no therapy were examined. The middle B-cell epitope (positions 24-34 a.a.) of NS4a was synthesized by the solid-phase method, while the C-terminal epitope (34-54 a.a.) was obtained using genetically engineered techniques. Enzyme immunoassay (ELISA) testing of the sera collected before treatment was performed for the two selected epitopes according to the conventional methods. The antibodies to the C-terminal epitope were detected significantly more frequently than those to the middle one (p = 0.01) when analyzing the blood sera of patients (n = 113). The presence of ABs to the C-terminal epitope in the serum samples of participants who completed standard interferon therapy was associated with the achievement of SVR (p = 0.0245). In the blood sera of participants who completed therapy with velpanate, an association of the presence of ABs to the C-terminal epitope with the achievement of SVR was also established (p &lt; 0.0001). The presence of ABs to the middle B epitope was not associated with the achievement of SVR, regardless of the therapy used. The observed difference in the immunoreactivity of the two B-cell determinants may be associated with the localization of the nearest Th-epitopes, the sensitivity of NS4a antigen to proteolytic enzymes, and the peculiarities of epitope presentation by antigen-presenting cells. However, it should be noted that the immunoreactivity of the middle B-epitope is poorly studied. Although the association of ABs to the C-terminal epitope with the achievement of SVR has been shown by several scientific teams, the detailed molecular mechanism of their influence on the effectiveness of therapy is unclear. In CHC, ABs to the C-terminal epitope of NS4a are produced more frequently than those to the median epitope. The presence of ABs to the C-terminal epitope is a predictive marker of a high probability of achieving SVR, regardless of the type of therapy and antibody titer.

No increased risk of hepatocellular carcinoma after eradication of hepatitis C virus by direct-acting antivirals, compared with interferon-based therapy

It is well-known that sustained virological response (SVR) by interferon (IFN)-based therapy against hepatitis C virus (HCV) infection reduced the incidence of hepatocellular carcinoma (HCC). However, whether IFN-free direct-acting antivirals reduce the risk of HCC is controversial. Therefore, this study aims to compare the incidence of HCC after the achievement of SVR between sofosbuvir combined with ledipasvir (SOF/LDV) and simeprevir with pegylated interferon plus ribavirin (Sim+IFN). Japanese patients with HCV infection (genotype 1) who achieved SVR between January 2013 and December 2014 by SOF/LDV (NCT01975675, n = 320) or Sim+IFN (000015933, n = 289) therapy in two nationwide, multicenter, phase III studies were prospectively monitored for the development of HCC by ultrasonography for 5 years after the end of treatment (EOT). No HCC was detected before the treatment. HCC was detected in 9 and 7 patients in the SOF/LDV and the Sim+IFN group in 5 years, respectively. The cumulative incidences of HCC rates 1, 3, and 5 years after EOT were similar between the two groups (1.5%, 2.7%, and 3.2% for the SOF/LDV and 1.8%, 2.8%, and 3.0% for the Sim+IFN group, respectively). No HCC was developed 3.5 years after EOT. Interestingly, a retrospective careful review of imaging taken before therapy revealed hepatic nodules in 50% of HCC patients, suggesting HCC was pre-existed before therapy. In conclusion, we could not find any differences in the incidence of HCC after the HCV eradication between the two therapeutic regimens, suggesting no enhancement of HCC development by DAA.

SVR achievement in triple therapy treated hepatitis C induced cirrhosis: A dual center retrospective cohort study

Background and objectiveMultiple prospective and retrospective cohort studies from the West have demonstrated the conflicting results about the efficacy of direct-acting antivirals (DAAs) by sustained virologic response (SVR) achievement rate in hepatitis C virus (HCV) infected patients. But there is limited to no data about the effectiveness of triple therapy ribavirin-sofosbuvir-daclatasvir in cirrhotic hepatitis C infected patients from Pakistan. MethodsWe conducted a retrospective cohort study by retrieving records of 359 hepatitis C infected patients treated with triple therapy from two tertiary care hospitals in Pakistan [Cirrhotic = 187 (53%); non-cirrhotic = 172 (47%)] from February 18, 2018, to June 29, 2019. We lost the follow-up of 158 (44.1%) patients due to death (n = 24, 6.68%), non-responding/wrong contact number (n = 43, 9.63%), and whom consented to study but didn't complete follow-up/refused to participate in the study (n = 91, 25.34%). Only 201 (45.9%) completed follow up, and of these 87 (43.2%) were cirrhotic patients based on Liver Stiffness Index. Analysis was run by dividing groups into subgroups; who achieved SVR/who didn't achieve SVR. ResultsWe analyzed the data of 201 (45.9%) who completed follow-up including cirrhotic patients (n = 87, 43.2%). Mean age was 50.6 + 10.65 years. 81 (94.18%) did achieve SVR while 5 (5.81%) did not achieve SVR. Achievement of SVR was statistically associated with low platelet count, higher total bilirubin, and lower albumin (p < 0.05) while other demographic and disease-related characteristics of patients were not statistically significant (p > 0.05). ConclusionTriple therapy (ribavirin-sofosbuvir-daclatasvir) achieves over 94% SVR in the Pakistani population, so proved to be highly effective against hepatitis C infection.

Sustained Virological Response Is the Most Effective in Preventing Hepatocellular Carcinoma Recurrence after Curative Treatment in Hepatitis C Virus-Positive Patients: A Study Using Decision Tree Analysis

This study evaluated the factors that affect the recurrence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients, who had received curative treatment for initial HCC, using decision tree analysis in 111 curative cases. The enrolled patients were divided into three groups by the decision tree analysis as follows: Patients who achieved sustained virological response (SVR) after curative treatment belonged to Group 1 (n = 33), those who did not achieve SVR and with alpha-fetoprotein (AFP) levels &lt; 11 ng/mL belonged to Group 2 (n = 30), and those who did not achieve SVR and with AFP levels ≥ 11 ng/mL belonged to Group 3 (n = 48). The Kaplan–Meier method revealed that Group 1 had significantly longer recurrence-free survival than Group 2 or 3 (p = 0.004). Moreover, there was no significant difference between patients achieving SVR with direct-acting antivirals and interferon therapy (p = 0.251). Group 3 had significantly poorer recurrence-free survival than Group 2 (p &lt; 0.001). The Cox proportional hazards model demonstrated that SVR achievement was the only independent factor associated with low HCC recurrence (p = 0.005). In conclusion, patients who achieved SVR were the least prone to HCC recurrence, whereas those who did not achieve SVR and had AFP levels ≥ 11 ng/mL were the most prone to HCC recurrence.

Impact of the PNPLA3 genotype on the risk of hepatocellular carcinoma after hepatitis C virus eradication.

Almost all chronic hepatitis C (CHC) patients can achieve sustained virological response (SVR) with direct-acting antivirals. However, the development of hepatocellular carcinoma (HCC), even after the achievement of SVR, continues to be a serious problem. The aim of this study was to assess the association between host genetic factors and de novo HCC after SVR. This single-center, retrospective study consisted of 442 consecutive CHC patients without a history of HCC who achieved SVR through interferon (IFN)-based and IFN-free therapy. Predictive factors associated with the development of HCC were determined by the Cox proportional hazards model. The single-nucleotide polymorphism (SNP) genotyping data of 223 patients were available for analysis. Of the seven SNPs analyzed in this study, only the patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 GG genotype was significantly, positively associated with the development of de novo HCC after adjusting for age, sex, and fibrosis status (adjusted hazard ratio [aHR] 5.66, p = 0.003). In multivariable analysis, age (aHR 1.05, p = 0.007), advanced fibrosis (aHR 2.69, p = 0.019), α-fetoprotein at post-12 weeks of treatment ≥7.0 ng/ml (aHR 3.85, p = 0.001), and PNPLA3 GG genotype (aHR 3.02, p = 0.004) were extracted as independent predictors of the development of de novo HCC. In conclusion, the PNPLA3 genotype was independently associated with the de novo HCC of CHC patients who achieved SVR. Such detailed knowledge of host genetic factors will be useful for HCC surveillance after HCV elimination.

Hepatocellular carcinoma incidence in chronic hepatitis C patients according to sustained virological response (SVR) with interferon‐based therapies and baseline characteristics

AbstractIntroductionHepatocellular carcinoma (HCC) is the second most common cause of cancer‐related death worldwide with increasing incidence. Effective antiviral treatment for chronic hepatitis C (CHC) became available in the last 7 years but despite the WHO Hepatitis elimination targets, they are not universally available today in all regions for all the patients, indicating still a bleak outlook for CHC‐associated HCC in the next decades.AimTo assess the HCC incidence in relation to interferon (IFN)‐based antiviral treatment response and baseline characteristics of a large cohort of chronic hepatitis C (CHC) patients from a single institution.MethodsWe retrospectively collected data of CHC patients, who were diagnosed between 1989 and 2011 and treated at the AKH‐University Hospital of Vienna before the introduction of direct‐acting antiviral (DAA) only therapy. We analysed the HCC incidence in patients with a sustained virological response (SVR) and without SVR according to the patients' baseline characteristics.ResultsOur study included 2134 patients, who were treated or not treated with IFN‐based antiviral treatment and had long‐term follow‐up available. The overall HCC incidence in this cohort was 6.2% (132 HCC cases over a median follow‐up period of 9 years). According to the baseline fibrosis stage, the overall HCC incidence was: 1.1% in patients with baseline fibrosis stage F0‐2, 8.2% in F3 and 20.6% in F4 patients. The HCC incidence was significantly higher in non‐SVR and no‐treatment group as compared with SVR patients: 12.4% vs 1.9%, P &lt; .0001, 7.3% vs 1.9%, P &lt; .0001. In multivariate analysis, lower platelet count (odds ratio‐OR = ‐0.1, 95% CI: 0.15‐0.63), for the SVR group and presence of cirrhosis (OR = 3.6, 95% CI: 1.59‐8.17), ALBI grade &gt;=2 (OR = 2.3, 95% CI: 1.0‐5.3) for the non‐SVR group were independently associated with HCC occurrence. For the group of patients with no treatment, the only predictor for HCC was high baseline alpha‐fetoprotein values (OR = 10.2, 95% CI: 2.2‐47.9).ConclusionThe achievement of SVR significantly reduces the risk for HCC occurrence during long‐term follow‐up. However, the risk remains high in successfully treated patients with low platelet count and in patients who did not achieve SVR with more advanced liver disease. These risk factors should be considered in decision‐making of HCC surveillance in this settling.

Does Hepatitis C Virus Treatment by Directly Acting Antivirals Obligate Shifting Patients with Type 2 Diabetes from Oral Hypoglycemic Drugs to Insulin Therapy?

PurposeThe aim of the present work was to investigate whether hepatitis C virus treatment by directly acting antivirals obligate shifting patients with type 2 diabetes from oral hypoglycemic drugs to insulin therapy.MethodsThis was a prospective study including 92 treatment-naïve patients with chronic hepatitis C virus infection and type 2 diabetes who were eligible for treatment with directly acting antivirals (sofosbuvir + daclatasvir ± ribavirin). Patients in the study were divided into two groups; group 1 included 22 patients on insulin therapy and group 2 included 70 patients on oral antidiabetic medications. Patients were advised to keep on their anti-diabetic treatment.ResultsAll our patients achieved sustained virologic response with significantly lower HbA1c 12 weeks after the end of therapy (p. values 0.001 for group 1 and group 2). There was no statistically significant difference in HbA1c level post-treatment between both groups (p. value 0.352).ConclusionAchievement of sustained virologic response using interferon free, directly acting antivirals-based regimen was associated with significantly lower HbA1c 12 weeks after the end of therapy. The type of treatment used for type 2 diabetes (oral drugs or insulin) did not affect improved glycemic control observed after achieving sustained virologic response.

The wide spectrum of cryoglobulinemic vasculitis and an overview of therapeutic advancements.

Immunoglobulins that reversibly precipitate at temperatures below 37 °C are called cryoglobulins (CGs). Cryoglobulinemia often manifests as cryoglobulinemic vasculitis (CV), whose symptoms range in severity from purpuric eruptions to life-threatening features. The majority of CV patients are infected with hepatitis C virus (HCV), whereas lymphoproliferative disorders or connective tissue diseases (CTD) are commonly diagnosed among patients with CV of non-infectious origin. In the absence of detectable associated disease, cryoglobulinemia is classified as “essential” (EMC). All HCV-positive CV patients should be given direct-acting antiviral agents (DAAs) that are consistently able to induce a sustained virologic response (SVR). Glucocorticoids (GCs) can mitigate CV-associated vasculitis, but they have no role as maintenance therapy. Cyclophosphamide restrains the hyperactive phase(s) of the disease and the post-apheresis rebound of newly synthesized CGs. Its use has been largely replaced by rituximab (RTX) in patients unresponsive to DAAs, patients progressing to B-cell non-Hodgkin lymphoma (B-NHL) and patients in whom CV persists or reappears after clearance of HCV. Therapeutic apheresis is an emergency treatment for CV patients with hyperviscosity syndrome. HCV-positive CV patients are at an increased risk of developing NHL, but the achievement of SVR can effectively prevent HCV-related NHL or induce the remission of an already established lymphoma, even without chemotherapy. The treatment of patients with IgM or IgG monoclonal cryoglobulins and an underlying immunoproliferative disorder is based on the regimens adopted for patients with the same B-cell malignancies but without circulating CGs. For patients with CTD, GCs plus alkylating agents or RTX are similarly effective as first-line therapy and in the relapse/refractory setting. In patients with EMC, treatment should consist of GCs plus RTX, with the dose of GCs tapered as soon as possible to reduce the risk of infectious complications.

Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

BackgroundIn HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort.MethodsWe identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits.Results559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7–51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24–0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08–0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15–0.54, p < 0.0001), liver-related mortality (HR 0.40, 95% CI 0.17–0.96, p = 0.04), non-liver-related mortality (HR 0.17, 95% CI 0.06–0.49, p = 0.001), liver transplantation (HR 0.17, 95% CI 0.05–0.54, p = 0.003), and hepatocellular carcinoma (HR 0.52, 95% CI 0.29–0.93, p = 0.03).ConclusionTreatment with direct antiviral agents is associated with reduced risk for mortality. The sustained virological response was 88%. Thus, direct antiviral agents treatment should be considered for any patient with HCV-related decompensated cirrhosis.Trial registration: ClinicalTrials.gov registry number: NCT01953458.

Long term immunological perturbations post DAA therapy in chronic HCV/HIV co-infected patients

Direct-acting antiviral (DAA) therapies are efficacious for the achievement of sustained virologic response (SVR) in almost all treated hepatitis C virus (HCV)-infected patients. However, the impacts of HCV eradication on immune function and chronic immune activation in the long-term remain controversial and limited, especially in patients co-infected with human immunodeficiency virus (HIV). Indeed, although restoration of many immune responses clearly can be observed, several features of immune perturbations persist over time after HCV clearance. Understanding the degree and reasons of the partial recovery of the immune system in chronic HCV/HIV co-infection after HCV elimination is pivotal to avoid disease progression and possible long-term clinical outcomes in cured patients, as well as contributing to the development of immunotherapy drug design.

Utilizing Telemedicine and Modified Fibrosis Staging Protocols to Maintain Treatment Initiation and Adherence Among Hepatitis C Patients During the COVID-19 Pandemic.

The COVID-19 pandemic exacerbated the decline in Hepatitis C Virus (HCV) screening and treatment globally in part due to lockdowns and restrictions at healthcare centers. The goal of this retrospective cohort study was to assess the effectiveness of an updated workflow implemented at Boston Medical Center (BMC) HCV clinics. Revised workflow incorporated appointments via telemedicine, transitioning to blood test-based fibrosis scoring, and delivering medication by mail to mitigate the lack of in-person services. We compared 2 cohorts of patients who attended at least the initial intake appointment at BMCHCV clinics: 170 before the pandemic and 133 after the pandemic. Outcome variables included treatment starts, fibrosis lab tests completed, appointment attendance, and SVR achievement. Proportions for outcome variables were compared between groups by use of χ2 and 2-sample t-tests where appropriate. Our results showed a 14.43% decrease in completing fibrosis scoring tests (P-value: <.001) and a 15.21% decrease in medication initiation (P-value: <.001) among the patients who initiated care during the pandemic (modified workflow group). Furthermore, we found a 18.56% decrease in sustained virologic response (SVR) among the modified workflow group when compared to the controls. Overall, these results align with current trends of patients’ decreasing engagement in HCV care but show higher retention than other published data. Furthermore, these figures support how appointments via telemedicine, transitioning to blood test-based fibrosis scoring, and medication delivery by mail can serve as tools to increase access to HCV care and successful HCV treatment completion even after COVID restrictions are lifted.

HCV eradication with DAAs differently affects HIV males and females: A whole miRNA sequencing characterization.

Gender-specific consequences after HCV eradication are unexplored. MicroRNAs (miRNAs) play a crucial role in the immune response against viral infections. However, few have highlighted miRNA role in sex-biased disease or therapy response. We aim to assess gender differences reflected in the miRNA expression of HIV/HCV-coinfected patients who achieve sustained virological response (SVR) with direct acting antivirals (DAAs). We conducted a prospective study of miRNA expression in PBMCs from 28 chronic HIV/HCV-coinfected patients (HIV/HCV) at baseline and after achieving SVR with DAAs. Sixteen HIV-monoinfected patients (HIV) and 36 healthy controls (HC) were used as controls. Identification of significant differentially expressed (SDE) miRNAs was performed with generalized linear model and mixed GLMs. We also explored putative dysregulated biological pathways. At baseline, the HIV/HCV patients showed differences in the miRNA profile concerning the HIV group (165 and 102 SDE miRNAs for males and females, respectively). Gender-stratified analysis of HIV/HCV group at baseline versus at SVR achievement showed higher differences in males (80 SDE miRNAs) than in females (55 SDE miRNAs). After SVR, HIV/HCV group showed similar values to HIV individuals, especially in females (1 SDE miRNA). However, ten miRNAs in males remained dysregulated, which were mainly involved in cancer, fatty acid, and inflammatory pathways. Taken together, our results show gender-biased dysregulation in the miRNA expression profile of PBMCs after HCV eradication with DAAs. These differences were normalized in females, while miRNA profile and their target-related pathways in males lack of normalization, which may be related to a high-risk of developing liver-related complications.

Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis.

Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48weeks post-treatment. The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4mg/dl for total bilirubin, 2.9g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12weeks post-treatment and maintained the stable effects until 48weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48weeks post-treatment.

917. Accessible HCV Care for People Who Inject Drugs: Randomized Clinical Trial Comparing Low-Threshold Treatment at a Syringe Service Program Versus Facilitated Referral

BackgroundTo achieve hepatitis C virus (HCV) elimination, treatment programs need to be developed to engage, treat, and cure people who inject drugs (PWID).MethodsWe present final data from the Accessible Care Trial for curing HCV in PWID. The randomized clinical trial compared on-site, low-threshold HCV treatment with care-coordination at a NYC syringe service program (Accessible Care) with facilitated referral to local providers through a patient navigation program (Usual Care). Eligible participants were HCV RNA+ and had injected drugs in the past 90 days. Participants were randomized 1:1 to the Accessible Care or Usual Care arm. The primary endpoint was achievement of sustained virologic response (SVR12) within 12 months of enrollment. Secondary endpoints examined rates HCV care cascade step completion from referral to clinician, attending clinical visit, baseline lab testing, treatment initiation, and cure.ResultsAmong the 572 participants screened, 167 met eligibility criteria and were enrolled, with two excluded post-randomization (N=165). Demographics were similar with a median age of 41 years; 22% women; 59% Hispanic and 5% non-Hispanic black. At baseline, 84% of participants had injected drugs in the past 30 days with those averaging 22 injections/month, 70% were receiving either methadone or buprenorphine, 57% were recently homeless, 7% were HIV+, and 11% were HCV treatment experienced. In the intention-to-treat analysis, 55/82 (67.1%) of the Accessible Care arm and 19/83 (22.9%) of the Usual Care arm achieved SVR12 (p< 0.001). The SVR12 rates of those starting therapy were 55/64 (85.9%) and 19/22 (86.3%) in the two arms (p=0.96). Loss to follow-up (12.2% and 16.9%, p=0.51) was similar in the two arms. Significantly more participants in the Accessible Care arm achieved all steps in the care cascade with the greatest attrition in the Usual Care arm seen in referral to clinician and attending clinical visit. ConclusionAmong HCV RNA+ PWID significantly higher rates of cure were achieved using the Accessible Care model focused on low-threshold, destigmatized, flexible HCV care compared to facilitated referral. To achieve HCV elimination, expansion of treatment programs specifically geared toward engaging PWID is paramount. Disclosures Benjamin Eckhardt, MD, MS, Gilead Sciences (Grant/Research Support) Shashi Kapadia, MD, Gilead Sciences Inc (Grant/Research Support) Kristen Marks, MD, Gilead Sciences (Grant/Research Support)

Elastography as a predictor of liver cirrhosis complications after hepatitis C virus eradication in the era of direct-acting antivirals.

Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Adherence and sustained virologic response among vulnerable people initiating an hepatitis C treatment at a nurse-led clinic: A non-experimental prospective cohort study based on clinical records.

There is a need to develop specific care route for vulnerable people with hepatitis C virus. At a nurse-led clinic, we aimed to: (1) report the prevalence of patients initiating an hepatitis C treatment who (a) achieved sustained virologic response and (b) were adherent to their treatment; and (2) explore factors associated with adherence and sustained virologic response. A clinical record-based prospective cohort study. A community-based nurse-led clinic coordinating outreach services for people with hepatitis C virus in Québec City, Québec, Canada. All patients initiating an hepatitis C treatment at the nurse-led clinic from January 1, 2012 to December 31, 2017 (end of data collection). Patients were followed from the day they initiated their hepatitis C treatment, up to 24 weeks after the end of the treatment. Sustained virologic response was achieved if hepatitis C virus ribonucleic acid (RNA) was undetectable or below the lower limit of quantification at week 12 or later. Patients who reported hepatitis C treatment completion without missing any doses were considered adherent. Factors associated with adherence and sustained virologic response were identified using adjusted prevalence ratios. A total of 171 patients infected with hepatitis C virus (women: n=51, 30%; criminal record: n=102, 60%; substance addiction: n=99, 58%) initiated an hepatitis C treatment at the nurse-led clinic. Overall, 126/171 (74%) patients were adherent. Patients using illicit drugs were less likely to be adherent (adjusted prevalence ratio 0.77, 95% confidence interval 0.67-0.89). Among 156/171 (91%) patients with an hepatitis C virus RNA test post-treatment, 96% (n=149) achieved sustained virologic response. Patients who were less likely to achieve sustained virologic response were those who were non-adherent (adjusted prevalence ratio 0.81, 95% confidence interval 0.68-0.98) or who had a criminal record (adjusted prevalence ratio 0.87, 95% confidence interval 0.79-0.97). A nurse-led clinic could fill an important gap in hepatitis C health services targeted at vulnerable people in a community setting, to drive adherence and achievement of sustained virologic response.

Epidemiology and Clinical Characteristics of Individuals with Hepatitis C Virus Infection in the United States, 2017-2019.

IntroductionHepatitis C virus (HCV) is the most common bloodborne chronic infection in the US. Following approval of highly effective, direct-acting antivirals in 2014, the diagnostic and treatment rates for HCV infection in the US have evolved. This study assessed the number of individuals with HCV screening or diagnostic testing and the clinical characteristics and treatment of HCV-infected individuals between 2017 and 2019.MethodsIndividuals screened for HCV antibody and/or tested for HCV ribonucleic acid (RNA) from 2017 to 2019 by two large US laboratory companies were included in this analysis. Clinical characteristics, such as HCV genotype, fibrosis stage, HIV coinfection and demographics, were assessed in HCV RNA-positive individuals. HCV treatment and subsequent achievement of sustained virologic response were imputed using data-driven algorithms based on successive viral load decline and negativity.ResultsFrom 2017 to 2019, the number of individuals tested for HCV antibody increased by 5.7%, from 7,580,303 in 2017 to 8,009,081 in 2019. The percentage of individuals tested who were HCV antibody positive was stable, ranging from 5.0% in 2017 to 4.9% in 2018 and 2019. The number of HCV RNA-positive individuals decreased by 5.0% from 382,500 in 2017 to 363,532 in 2019. Of HCV RNA-positive individuals, the proportions with genotype (GT) 3 and minimal fibrosis increased over time; proportions of individuals aged < 40 years increased, while the proportion aged 50 to 59 years decreased. Treatment rates increased from 23.4% in 2017 to 26.8% in 2019.ConclusionsThe percentage of HCV antibody-positive individuals remained stable from 2017 to 2019. The number of individuals tested HCV RNA positive decreased over the years. Demographics shifted toward a younger population with less fibrosis and higher rates of GT3. More than 70% of diagnosed individuals were not treated during this interval, highlighting a need for unfettered access to treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01928-y.