Lower Sustained Virological Response Research Articles

Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir.

Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct-acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first-line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/VOX among patients failing sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). Retrospective multicentre study (26 Spanish hospitals), including chronic hepatitis C patients unsuccessfully treated with SOF/VEL or GLE/PIB, and retreated with SOF/VEL/VOX ± ribavirin for 12 weeks between December 2017 and December 2022. In total, 142 patients included: 100 (70.4%) had failed SOF/VEL and 42 (29.6%) GLE/PIB. Patients were mainly men (84.5%), White (93.9%), with hepatitis C virus genotype (GT) 3 (49.6%) and 47.2% had liver cirrhosis. Sustained virological response (SVR) was evaluated in 132 patients who completed SOF/VEL/VOX and were followed 12 weeks after end of treatment; 117 (88.6%) achieved SVR. There were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs. GLE/PIB 90.2%, p = 0.8), cirrhosis (no cirrhosis 90% vs. cirrhosis 87.1%, p = 0.6) or GT3 infection (non-GT3 91.9% vs. GT3 85.5%, p = 0.3). However, when considering the concurrent presence of SOF/VEL treatment, cirrhosis and GT3 infection, SVR rates dropped to 82.8%. Ribavirin was added in 8 (6%) patients, all achieved SVR. SOF/VEL/VOX is an effective rescue therapy for failures to SOF/VEL or GLE/PIB, with an SVR of 88.6%. Factors previously linked to lower SVR rates, such as GT3 infection, cirrhosis and first-line therapy with SOF/VEL were not associated with lower SVRs.

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

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

Real-world treatment outcomes of sofosbuvir-based regimens for treatment of chronic hepatitis C with and without human immunodeficiency virus co-infection.

The efficacy of sofosbuvir (SOF)-based regimens in the treatment of chronic hepatitis C (HCV) patients with and without human immunodeficiency virus (HIV) co-infected patients in real-world setting is limited. This was a retrospective cohort study, conducted between 1 January 2017 and 31 December 2021 at Bamrasnaradura Infectious Disease Institute, Thailand. All HCV patients received 12 weeks of SOF-based regimens and had follow-up for at least 12 weeks after therapy discontinuation. The primary outcome was sustained virological response (SVR) at 12 weeks after the end of treatment. Treatment outcomes were compared between HCV patients with and without HIV co-infection. A total of 163 patients were included in the study, 130 (79.8%) were HCV/HIV co-infected, and 33 (20.2%) were HCV mono-infected. Of all, 106 (64%) patients received SOF and ledipasvir. Genotype 1 (GT1) was predominant at 66.4%, followed by GT3 at 22.2%, and GT6 at 11.4%. Overall SVR was 96.9%. SVR in HCV mono-infected was 96.9% and SVR in HIV-HCV co-infected patients was 96.9%. The factor associated with SVR was HCV genotype (P=0.001). Patients with HCV GT6 had lower SVR rates compared with GT1 and GT3 patients (83.3%, 100%, and 97.1% [P=0.000] respectively). There was no association between SVR and other factors such as gender, age, BMI, underlying cirrhosis, baseline HCV viral load, or prior treatment history (all P > 0.05). All patients completed 12-week SOF-based treatment. In real-world setting, HCV treatment with SOF-based regimens between patients with and without HIV co-infection showed high rates of SVR. SOF-based regimens were highly efficacious and tolerated.

Effectiveness of direct-acting antiviral therapy among Aboriginal and Torres Strait Islander peoples with HCV infection in Australia: A national real-world cohort (REACH-C).

Aboriginal and Torres Strait Islander peoples experience a disproportionate burden of hepatitis C virus (HCV) infection. This study assessed the effectiveness of direct-acting antiviral (DAA) therapy among Aboriginal peoples in the three years following universal access in Australia. REACH-C, a national multicentre prospective cohort study, evaluated HCV treatment outcomes from sequential DAA initiations across 33 health services between March 2016 and June 2019. DAA effectiveness was assessed by sustained virological response (SVR) in the total (full analysis set) and effectiveness (modified analysis set excluding those lost to follow-up) populations. Overall, 915 (10%) Aboriginal and 8095 (90%) non-Indigenous people commenced DAA therapy, of whom 30% and 16% reported current injecting drug use and 73% and 42% were treated in primary care, respectively. SVR in the total and effectiveness populations was 74% and 94% among Aboriginal people and 82% and 94% among non-Indigenous people, with loss to follow-up contributing to lower SVR in the total population analysis (22% Aboriginal, 13% non-Indigenous). Among Aboriginal people, returning for follow-up was positively associated with older age (aOR 1.20; 95% CI 1.04, 1.39) and SVR was negatively associated with cirrhosis (aOR 0.39; 95% CI 0.19, 0.80) and prior DAA treatment (aOR 0.14; 95% CI 0.04, 0.49). Factors reflecting higher vulnerability or inequity were not associated with returning for testing or SVR. DAA therapy was highly effective among Aboriginal peoples with HCV treated through primary and tertiary services. Tailored community-led interventions are necessary to optimize follow-up and engagement. Sustained DAA uptake and equitable access to care, treatment and prevention are required for HCV elimination.

Pangenotypic triple versus double therapy in HCV-infected patients after prior failure of direct-acting antivirals.

Despite the excellent effectiveness of direct-acting antivirals (DAA) in the treatment of hepatitis C virus (HCV) infection, still a few percent of patients fail therapy. The study aimed to determine the effectiveness of triple vs double rescue treatment in such a population. The study included all consecutive DAA-experienced patients retreated with pangenotypic options from the EpiTer-2 database, a retrospective national multicenter real-world project evaluating antiviral treatment in HCV-infected patients in 2015-2023. The studied population consisted of 269 patients, of whom 208 were treated with the double (P2) and 61 with the triple (P3) pangenotypic option. No statistically significant differences were found between these subpopulations, except a significantly more frequent history of liver transplantation in the P3 group (6.6% vs. 0.5%, p = 0.01). In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. Virological response at the end of therapy was comparable in both analyzed subpopulations, but the sustained virologic response (SVR) rate was significantly higher in triple retherapy, 98.3% vs. 88.7%, p = 0.02, calculated after exclusion of patients lost to follow-up. Lower SVR was achieved in genotype 3-infected men with cirrhosis, 88.9% and 80% in P3 and P2, respectively. A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender.

S1370 Delayed Clinical Follow Is Not Associated With Lower SVR Rates in an HCV-Infected Cohort in Mumbai, India

Introduction: Hepatitis C Virus (HCV) has a prevalence of 71 million cases worldwide. Regular follow-up can be challenging for patients in low middle income countries (LMIC) due to lack of access to healthcare facilities and transportation difficulties. Our aim was to determine if delayed vs regular follow up for patients being treated for HCV with direct acting antivirals (DAA) resulted in a difference in sustained virologic response (SVR). Methods: We conducted a retrospective cohort study of 149 patients in Mumbai, India who had received treatment for Hepatitis C from 2015 to 2021. All patients had confirmed HCV by PCR and were treated with direct acting antivirals (DAA) approved by the FDA equivalent in India. Patients were asked to present for follow up 12 weeks after end of treatment for SVR12 (sustained virologic response) testing. Results: 149 patients were included. 81 followed up on time (54%) and 68 did not (46%). The mean age at treatment in both groups was similar (51 vs 52, p = 0.29) while male/female distribution showed a significant difference (40% vs 54% male, 60% vs 46% female, p = 0.027). The most common genotype in the cohort was genotype 3 (52% vs 49%) and the second most common was genotype 1 (32% vs 20%). There was not a significant difference in genotypes between both groups (p = 1.0). History of hyperlipidemia (p = 0.12), thyroid disease (p = 0.20), and CKD (p = 0.16) did not show significant difference across both groups. On the other hand, diabetes (p = 0.026) and HTN (p < 0.01) were more prevalent in those who had delayed follow up. There was no significant difference in prior treatment experience between the two groups (p = 0.13). Change in AST and ALT from the initiation of treatment until SVR also did not show significant difference across both groups (p = 0.58, 0.38). Patients with advanced liver disease were more commonly seen in the group which did not have on-time follow up (p < 0.01). SVR was seen more in the group which did not follow up on time (94% vs 79%, p < 0.01). (Table) Conclusion: The likelihood of SVR was not impeded by delayed follow-up compared to regular follow-up in this cohort of infected patients. Further research is needed to determine if this is generalizable across different genotypes and geographic locations. Table 1. - Patients’ baseline clinical characteristics stratified against delayed vs regular follow-up Variable Overall (n=149) Delayed FU (n=68) Regular FU (n=81) P-value Age (mean ± SD) 52 ± 13 53 ± 13 51 ± 13 0.29 Sex (n, %) 0.10 Male 71 (48) 27 (40) 44 (54) Female 78 (52) 41 (60) 37 (46) Genotype (n, %) 1.0 1 46 (31) 20 (20) 26 (32) 2 1 (0.6) 0 (0) 1 (1.2) 3 75 (50) 33 (49) 42 (52) 4 4 (2.7) 2 (2.9) 2 (2.5) 5 1 (0.6) 0 (0) 1 (1.2) Not collected 22 (15) 13 (19) 9 (11) DM (n, %) 0.06 No 120 (81) 50 (74) 69 (85) Yes 29 (19) 18 (26) 12 (15) HTN (n, %) 0.03 No 96 (64) 37 (54) 59 (73) Yes 53 (36) 31 (46) 22 (27) HLD (n, %) 0.18 No 144 (97) 64 (94) 80 (99) Yes 5 (3) 4 (6) 1 (1) Thyroid Disease (n, %) 1.0 No 131 (88) 60 (88) 71 (88) Yes 18 (12) 8 (12) 10 (12) CKD (n, %) 0.38 No 137 (92) 61 (90) 76 (94) Yes 12 (8) 7 (10) 5 (6.2) Treatment Experience (n, %) 0.73 Naive 101 (68) 45 (66) 56 (69) Experienced 48 (32) 23 (34) 25 (31) Liver Status (n, %) 0.03 No Cirrhosis 56 (38) 26 (38) 30 (37) Comp Cirrhosis 68 (46) 25 (37) 43 (53) Decomp Cirrhosis 25 (17) 17 (25) 8 (10) SVR (n, %) < 0.01 No 21 (14) 4 (5.8) 17 (21) Yes 128 (86) 64 (94) 64 (79) Change in AST (mean ± SD) 35 ± 39 37 ± 38 33 ± 41 0.58 Change in ALT (mean ± SD) 42 ± 55 46 ± 64 37 ± 47 0.38

High efficacy of glecaprevir/pibrentasvir for HCV-infected individuals with active drug use

Real world data on glecaprevir/pibrentasvir (G/P) among active drug users are scarce. We evaluated the sustained virological response (SVR) rates of G/P among individuals with and without active drug use in routine clinical practice. Two ongoing prospective multicenter cohorts of individuals starting G/P were analyzed. Overall SVR intention-to-treat (ITT), discontinuations due to adverse effects and dropouts were evaluated. Results in patients with active, past and without active drug use were compared. Overall, 644 individuals started G/P and have reached the date of SVR evaluation. Of them, 613 (95.2%) individuals achieved SVR. There were two (0.3%) relapses, one (0.2%) discontinuation due to side effects and 35 (5.4%) dropouts. SVR rates for patients with active drug use, past drug use and those who never used drugs were 85.4%(n/N=70/82), 96.1%(n/N=320/333) and 97.4%(n/N=223/229) respectively (p<0.001). After adjustment by sex, age, HCV genotype and opioid agonist therapy, active drug use was the only factor independently associated with SVR (ITT) [adjusted OR (95%confidence interval): 0.29(0.09-0.99),p=0.048]. Active drug use was independently associated with lower SVR rates to G/P, mainly due to voluntary dropout. G/P could be particularly beneficial in this scenario but specific strategies designed to increase the retention in care are needed.

Impact of proton pump inhibitors on sustained virologic response in veterans treated with sofosbuvir/velpatasvir for chronic hepatitis C virus: A retrospective cohort study.

The objective of this study was to determine the clinical relationship between proton pump inhibitor (PPI) use and sustained virologic response (SVR) in patients treated with sofosbuvir/velpatasvir (SOF/VEL) for chronic hepatitis C virus (HCV) infection. This was a multicenter retrospective cohort study. Data was collected on patients from 128 Veterans Affairs Medical Centers throughout the United States. This study included veterans aged 18-89 years with viremic HCV who received a full course of SOF/VEL treatment from June 2016 - July 2017. Sustained viral response was compared in patients taking SOF/VEL with or without concurrent PPI prescriptions. Analysis of the primary outcome was completed utilizing logistic regression. The relationship between SVR and PPI use was adjusted for African-American race, presence of cirrhosis, prior treatment, BMI greater than 30 kg/m2, and HCV genotype. The final analysis included 4,008 veterans, 830 with concomitant PPI use and 3,178 without PPI use. After adjustment for other variables in the logistic model, there was no statistically significant association between PPI use and lower SVR (odds ratio 0.67; 95%CI: 0.42, 1.06; p=0.087). Concomitant PPI treatment adjusted for other variables did not significantly impact success or failure of SOF/VEL treatment of chronic HCV. Despite the lack of significant association identified in this study, in efforts to provide the best care possible, it remains prudent to proceed with caution in patients desiring to use PPI therapy while receiving SOF/VEL, and ensure prescribing instructions are closely followed in regard to concomitant PPI use, especially in patients with other risk factors for decreased SVR.

Identification of NS5B Resistance-Associated Mutations in Hepatitis C Virus Circulating in Treatment Naïve Vietnamese Patients.

IntroductionTreatment of HCV infection with peginterferon and ribavirin results in a low sustained virologic response rate, but has a number of undesirable adverse effects. Direct-acting antivirals (DAAs) offer a high efficacy, low risk, and a short treatment time. However, the existence of resistance-associated mutations, particularly in the NS5B polymerase, can attenuate the efficacy of DAAs. The objective of this study was to identify amino acid changes in the NS5B gene linked to DAA resistance in treatment-naive Vietnamese chronic hepatitis C patients.MethodsBlood samples and treatment data were collected from 100 HCV-infected patients hospitalized at the National Hospital for Tropical Diseases between January and December 2020; the plasma was then isolated and stored at –80°C for molecular analysis. The NS5B gene fragments of 100 samples were amplified with specified primers and the nucleotide sequences were obtained using the Sanger sequencing system. The nucleotide sequences were then analyzed and compared to identify substitutions in the NS5B region.ResultsA total of 100 HCV isolates from patients were classified into three genotypes, including genotypes 1, 3, and 6. The NS5B sequence analysis revealed many amino acid mutations in all genotypes, although these mutations were not strongly associated with resistance to DAAs like S282T. Analytical data on ribavirin–resistance mutations revealed that Q309R was predominantly found in genotype 1a, D310N was mostly found in genotype 1b, and N244I, T329I, A333E were not observed. The following mutations were shown to be related with DAAs resistance: E237G, S282R, L320F, V321A, and V321I. Furthermore, NS5B-resistance mutations were not associated with clinical characteristics, long-term virological response, or improvements in clinical parameters (liver enzymes or liver fibrosis index).ConclusionAlthough NS5B mutations were found in treatment-naive Vietnamese patients, changes in the NS5B gene did not appear to be highly correlated with HCV ribavirin and DAA antiviral resistance.

Comparison of the Efficacies of Direct-Acting Antiviral Treatment for HCV Infection in People Who Inject Drugs and Non-Drug Users.

Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users.

What Is the Optimal Bridging Therapy for Patients with Hepatitis C-associated Hepatocellular Carcinoma Awaiting Liver Transplant? An Analysis of the United States HCC Liver Transplantation Consortium

Introduction: Patients with hepatitis C (HCV)-associated hepatocellular carcinoma (HCC) often receive bridging therapy in the form of liver-directed therapy (LDT) while awaiting liver transplant (LT). The optimal modality of LDT, with respect to both cancer outcomes and response to direct-acting antiviral (DAA) therapy, remains unknown. Methods: The United States HCC Liver Transplantation Consortium was queried for patients with primary HCV-associated HCC within Milan criteria who completed DAA therapy and underwent LT. Primary outcomes were HCC recurrence-free survival (RFS) and overall survival (OS). Secondary outcome was sustained virologic response (SVR) as indicator of efficacy of DAA therapy. Results: Of 857 patients, 753 met inclusion criteria. LDT consisted of radiofrequency ablation (RFA,13.3%,N=100), transarterial chemoembolization (TACE,44.1%,N=332), yttrium-90 (Y90,4.8%,N=36), and stereotactic body radiation therapy (SBRT,2.9%,N=22). Eighty-one(10.8%) patients received no LDT and 182(24.2%) received multiple modalities. SBRT patients had the highest 5-year RFS(100%) followed by those receiving TACE(94%), Y90(91.4%), RFA(89.9%), and multiple therapies(88.2%) (p=0.048, Figure 1A). OS was higher among patients who received SBRT, but not statistically significant (p=0.685, Figure 1B). SVR rate was lower among radiation-based therapy groups (Y90 73.5%, SBRT 78.9%, others≥88%; p=0.046). Conclusions: In a homogeneous population of HCV-associated HCC patients within Milan criteria who received bridging therapy while awaiting LT, SBRT was associated with increased RFS and trended towards increased OS. However, radiation-based therapy was associated with decreased efficacy of DAA as measured by lower SVR rates. The optimal choice of bridging therapy to liver transplant must balance oncologic and virologic outcomes, but these findings seem to favor SBRT.

Acute reversible rhabdomyolysis during direct-acting antiviral hepatitis C virus treatment: a case report

IntroductionTreatment of hepatitis C infection has evolved dramatically since 2011. Previous conventional therapy with interferon and ribavirin used to have a low sustained virological response rate of less than 40%. In the new direct-acting antiviral therapy era, a sustained virological response can be achieved in more than 90% of cases.Case presentationWe report a rare case of severe reversible acute rhabdomyolysis in a 31-year-old Saudi male patient with very long-chain acyl-coenzyme A dehydrogenase deficiency and chronic hepatitis C infection. The patient was clinically asymptomatic with no signs of decompensated liver disease.The patient received new direct-acting antiviral agents: sofosbuvir and daclatasvir. Fourteen days after initiation of direct-acting antiviral agents, the patient was found to have asymptomatic rhabdomyolysis. His creatine kinase peaked at 2572 IU/l, and he was treated conservatively; the direct-acting antiviral agents were discontinued and within 7 days, the patient’s creatine kinase levels normalized.ConclusionThis case highlights possible direct-acting antiviral agent-induced rhabdomyolysis in a patient with very-long-chain acyl-CoA dehydrogenase deficiency, presumably through alteration of mitochondrial membrane potential. Further studies are required to assess the possible impact and associations.

Schistosoma mansoni infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade

ABSTRACT Schistosoma mansoni infection (SMI) is suspected to be directly and indirectly involved in hepato-carcinogenesis. This study evaluated the association of a previous SMI with hepatocellular carcinoma (HCC) development, patients, tumor characteristics, treatment outcomes, and survival. This observational study included patients with HCC with and without previous SMI who presented to the multidisciplinary HCC clinic, Kasr-Alainy hospital (November 2009 to December 2019). It also included 313 patients with liver cirrhosis without HCC. Clinical and laboratory features of the patients (complete blood count, liver/renal functions , alpha-fetoprotein, and hepatitis B/C status), tumor characteristics (Triphasic CT and/or dynamic MRI), liver stiffness (transient elastography), HCC treatment outcome, and overall survival were studied. This study included 1446 patients with HCC; 688(47.6%) composed group-1, defined by patients having a history of SMI, and 758(52.4%) were in group-2 and without history of SMI. Male sex, smoking, diabetes mellitus, splenomegaly, deteriorated performance status, synthetic liver functions, and platelet count were significantly higher in group-1. The groups did not differ with regard to liver stiffness, tumor characteristics, or the occurrence of post-HCC treatment hepatic decompensation or recurrence. HCC treatment response was better in group-2. Group-1 showed lower sustained virological response to hepatitis C direct-acting antivirals (DAAs) compared with group-2 (60% versus 84.3%, respectively, P = 0.027). Prior SMI was associated with HCC (adjusted odds ratio = 1.589, 95% confidence interval = 1.187–2.127), and it was concluded that it increases the risk of HCC. In addition, it significantly affects the performance status, laboratory characteristics, response to DAAs, and overall survival.

Hepatitis C direct-acting antiviral outcomes in patients 75 years and older.

Background and AimElderly patients with hepatitis C virus (HCV) infection have worse interferon‐based treatment outcomes than young patients. Direct‐acting antiviral (DAA) regimens have enabled the treatment of previously difficult‐to‐cure populations. There are few studies that specifically assess DAA treatment outcomes in patients over 75 years of age.MethodsDesign: This was a cohort study. Setting: The setting was three Canadian HCV specialty sites. Participants: Patients aged 75 years and older and treated with DAA without interferon were enrolled. Measurements: Patient demographics, liver fibrosis by transient elastography, treatment regimen, and treatment outcome data were collected.ResultsThe mean age of 78 patients in our analysis was 78.6 years (SD 3.5; range: 75–88 years). The most common genotype was 1b (35%). The most frequently utilized regimens included sofosbuvir‐velpatasvir (33%) and ledipasvir‐sofosbuvir (32%). Ribavirin was included for 17% of recipients. Sustained virological response (SVR) was achieved in 94% of patients (69% of those receiving ribavirin and 98% of patients on ribavirin‐free regimens). Ribavirin toxicity contributed to the lower SVR rates in ribavirin‐exposed patients. Ribavirin dosage was decreased in three patients and ultimately discontinued in two of these patients. All treatment was discontinued in another two patients.ConclusionRibavirin‐free DAA therapy is safe and achieves SVR rates in older adults comparable to those described in the general population. RBV inclusion frequently results in complications, often leads to treatment modification or interruption, and does not improve SVR rates in those with advanced age.

Real-world effectiveness of direct-acting antiviral agents for chronic hepatitis C patients with genotype-2 infection after completed treatment.

Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long-term outcomes. Several direct-acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non-SOF-based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype-2 (GT-2) patients in Taiwan. However, there is limited real-world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real-world efficacy in CHC GT-2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT-2 patients who were treated with SOF-based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non-SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT-2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations.

Effect of baseline resistance-associated substitutions on the efficiency of glecaprevir/pibrentasvir in chronic hepatitis C subjects: A meta-analysis.

The effect of baseline resistance-associated substitutions on the sustained virologic response at 12weeks in chronic hepatitis C subjects has drawn considerable attention. However, it has been reported that the relationship between such substitutions and sustained virologic response at 12weeks in chronic hepatitis C subjects is variable in different treatments. This meta-analysis was performed to evaluate this relationship in subjects treated with glecaprevir/pibrentasvir. A systematic literature search up to May 2020 was done, and 17 studies were identified with 6501 chronic hepatitis C subjects. They were reporting relationships between baseline resistance-associated substitutions and sustained virologic response at 12weeks in chronic hepatitis C subjects treated with glecaprevir/pibrentasvir. The odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of baseline resistance-associated substitutions on the sustained virologic response at 12weeks in chronic hepatitis C subjects treated with glecaprevir/pibrentasvir using the dichotomous method with a random or fixed-effect model. Lower sustained virologic response at 12weeks post-treatment in chronic hepatitis C subjects was significantly related to baseline resistance-associated substitutions in overall genotypes (OR, 0.03; 95% CI, 0.15-0.61, P<.001), baseline NS5a resistance-associated substitutions in genotype-1 (OR, 0.16; 95% CI, 0.04-0.57, P=.005), baseline resistance-associated substitutions in genotype-3 (OR, 0.14; 95% CI, 0.05-0.38, P<.001), and baseline NS5a resistance-associated substitutions in genotype-3 (OR, 0.21; 95% CI, 0.09-0.49, P<.001). Sustained virologic response at 12weeks in chronic hepatitis C subjects was not significantly related to the baseline NS5a resistance-associated substitutions (OR, 0.61; 95% CI, 0.17-2.22, P=.45), and baseline resistance-associated substitutions in genotype-1 (OR, 0.35; 95% CI, 0.12-1.088, P=.07). In conclusion, the impact of baseline resistance-associated substitutions on the sustained virologic response at 12weeks in chronic hepatitis C subjects treated with glecaprevir/pibrentasvir may have a great prognostic effect, especially in genotype-3 as a tool to improve treatment prediction. Chronic hepatitis C subjects with baseline resistance-associated substitutions may have an independent risk relationship with poor treatment outcomes. This relationship forces us to recommend testing prior to treatment selection to avoid any possible treatment failure.

Sofosbuvir and daclatasvir are safe and effective in treatment of recurrent hepatitis C virus in Egyptian patients underwent living donor liver transplantation

BackgroundLiver transplant population has been considered as a special population in the treatment of hepatitis C virus infection, not only because of lower sustained virological response (SVR) rates in comparison with pretransplant setting, but also for other aspects (i.e., immunosuppressive therapy, renal function, drug–drug interactions). We aimed to evaluate the efficacy and safety of the combined treatment with sofosbuvir and daclatasvir with or without ribavirin in liver transplant recipients with recurrent hepatitis C following transplantation and screening for the development of hepatocellular carcinoma during treatment, after the end of treatment, or during follow-up. This multicenteric prospective study was conducted in Egypt. This study included 40 patients who underwent living donor liver transplantation that started treatment at least 3 months following transplantation. All participants received 400 mg sofosbuvir once daily plus daclatasvir 60 mg daily ± ribavirin. Treatment lasted for up to 24 weeks, and participants were followed up as outpatients monthly for 12 and 24 weeks and 36 weeks post-treatment to determine sustained virological response (SVR12 and SVR24), considered to be a cure and detection of any changes in tumor markers or radiological imaging during follow-up.ResultsIn the current study, 40 patients (100%) have good response to treatment during treatment and during follow-up (SVR 12 was 100%). No abnormal side effects to treatment were detected; also, no drug–drug interactions were noted during the treatment.ConclusionsTreatment of HCV after living donor liver transplantation with combined sofosbuvir and daclatasvir is safe and well-tolerated and provides high rates of SVR.

Major mutations in the NS3 gene region of hepatitis C virus related to the resistance to direct acting antiviral drugs: a systematic review.

Hepatitis C virus (HCV) remains a global public health problem with high prevalence rates and chronicity of infection. Present work aimed to describe the main mutations in the NS3 region of the HCV genome related to the resistance of patients to the currently available direct-acting antivirals (DAAs). To guide the study description, the preferred items in the PRISMA protocol for systematic review were used. The data collected were HCV genotypes and subtypes and mutations in HCV NS3, general and stratified by continent. The 10 papers selected for this systematic review reported studies in seven countries, on three continents, and generated data of 2937 patients. The most frequent HCV subtype was 1a. Prevalence of genotypes suggested that there were few demographic regions reached by the studies, since there were regional variations in the type of genotypes reported in the available bibliographies. Of the total study population, 35.3% (n = 1037) had mutations in the NS3 gene region of HCV, suggesting a high rate of resistance to DAAs and a low sustained virologic response among those who used some therapeutic option. Ten major mutations were identified: Q80K, V170I, S122G, V36L, T54S, D168Q, A156S, Q80G, S122R, and V55A. The Q80K mutation was the highlight of the study, appearing not only with greater representativity (61.6%) but also as the only one described in the three continents analyzed. This systematic review reinforces the need to carry out more studies of detection of these mutations to fill in all information gaps that might help in optimization of treatment.

Sofosbuvir-based regimens in the treatment of patients with chronic hepatitis C virus infection: Real-world efficacy in Thailand.

AimsTo analyze the efficacy and safety of sofosbuvir (SOF)-based regimens in Thai patients with chronic hepatitis C virus infection who had pre-existing significant liver fibrosis.Patients and methodsThis was a retrospective cohort study, conducted between 1 June 2018 and 31 May 2019 at Rajavithi Hospital, Bangkok, Thailand. All patients completed 12 weeks of SOF-based regimens and had follow-up for at least 12 weeks after therapy discontinuation. The primary outcome was sustained virological response (SVR) 12 weeks after the end of therapy.ResultA total of 185 patients were included, with 52, 63 and 70 taking SOF+Ledipasvir (SOF+LDV), SOF+LDV+ribavirin (RBV) and SOF+Pegylated interferon (Peg-IFN)+RBV (SOF+Peg-IFN+RBV) respectively. Genotype (GT) 1 was predominant at 40.0%, followed by GT3 at 37.8%, and GT6 at 22.2%. Overall 95.1% of patients in this study achieved SVR (n = 176/185), and the only factor associated with SVR was HCV genotype (p = 0.001). GT6 patients had lower SVR rates compared to GT1 and GT3 patients (82.9%, 98.6%, and 98.6% respectively) while there was no association between SVR and other factors (p >0.05) such as gender, age, BMI, underlying cirrhosis, baseline HCV viral load, or prior treatment history. No serious adverse events were reported in the present study.ConclusionSofosbuvir-based regimens in the treatment of patients with chronic HCV infection were highly efficacious with excellent safety and tolerability profiles in a real-world setting; however, further research is required to establish whether or not such a regimen is an adequate treatment for all genotype 6 patients.

Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs.

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.