Efficacy Of Direct-acting Antivirals Research Articles

Hepatitis C virus eradication in people living with human immunodeficiency virus: Where are we now?

Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV).

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

The host-targeted antiviral drug Zapnometinib exhibits a high barrier to the development of SARS-CoV-2 resistance

Host targeting antiviral drugs (HTA) are directed against cellular mechanisms which can be exploited by viruses. These mechanisms are essential for viral replication, because missing functions cannot be compensated by the virus. However, this assumption needs experimental proof. Here we compared the HTA Zapnometinib (ZMN), with direct acting antivirals (DAA) (Remdesivir (RDV), Molnupiravir (MPV), Nirmatrelvir (NTV), Ritonavir (RTV), Paxlovid PAX)), in terms of their potency to induce reduced drug susceptibilities in SARS-CoV-2. During serial passage of δ-B1.617.2 adaptation to all DAAs occurred, while the inhibitory capacity of ZMN was not altered. Known single nucleotide polymorphisms (SNPs) responsible for partial resistances were found for RDV, NTV and PAX. Additionally, the high mutagenic potential of MPV was confirmed and decreased drug efficacies were found for the first time. Reduced DAA efficacy did not alter the inhibitory potential of ZMN. These results show that ZMN confers a high barrier towards the development of viral resistance and has the potential to act against partially DAA-insensitive viruses.

Efficacy of direct-acting antivirals in hemodialysis patients with chronic hepatitis C: A real clinical experience

Efficacy of direct-acting antivirals in hemodialysis patients with chronic hepatitis C: A real clinical experience

Assessing the impact of direct-acting antivirals on hepatitis C complications: a systematic review and meta-analysis.

Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.

Planning a clinical trial programme for direct-acting antivirals for chronic viral hepatitis C

Scientific relevance. Direct-acting antivirals have significantly improved the effectiveness of treatment for hepatitis C. However, Russia and the Eurasian Economic Union lack recommendations for the clinical development of medicinal products from this pharmacotherapeutic group.Aim. The study aimed to analyse the requirements and recommendations for planning safety and efficacy clinical trials of direct-acting antivirals for chronic viral hepatitis C, outlined in the regulatory documents of the European Union and the United States.Discussion. Upon analysing the requirements and recommendations, the authors explained the reasons behind choosing the target population and the design for the efficacy and confirmatory studies. The article covers the clinical development of direct-acting antivirals in special populations, including patients with hepatitis C and HIV co-infection, a liver transplant, and prior treatment experience. According to the authors, patients who achieved a sustained virological response should be followed up for a full year after the end of treatment in order to confirm the durability of their response. A dose-finding study should first identify a suitable dose range for monotherapy and, subsequently, for combined therapy. Current treatment regimens should be optimised, and studies should be conducted to reduce treatment duration.Conclusions. The authors outlined the main approaches and a methodology for clinical trial programmes that should take into account the degree of correlation between the efficacy of direct-acting antivirals and the genotype/subtype of hepatitis C virus.

THU-221 - Efficacy of direct-acting antivirals in patients with hepatitis C virus-associated cryoglobulinemia and monoclonal gammopathy

THU-221 - Efficacy of direct-acting antivirals in patients with hepatitis C virus-associated cryoglobulinemia and monoclonal gammopathy

Efficacy of direct-acting antivirals in patients with HCV-associated cryoglobulinemia and monoclonal gammapathy

Efficacy of direct-acting antivirals in patients with HCV-associated cryoglobulinemia and monoclonal gammapathy

Efficacy and Safety of Sofosbuvir and Ledipasvir for Hepatitis C in Kidney Transplant Recipients: A Single-center Retrospective Observational Study.

Treatment using direct-acting antivirals provides high rates of sustained virologic response and a favorable safety profile for patients with chronic hepatitis C virus infection. However, data on the efficacy of direct-acting antivirals in kidney transplant recipients are still limited. We evaluated the safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination in kidney transplant recipients. Retrospective, observational, single-center study. Data of 29 kidney transplant recipients who received a fixed-dose safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination for 12 or 24 weeks with or without ribavirin were analyzed. The primary outcome was SVR12, which was defined as undetectable HCV-RNA levels 12 weeks after the treatment. Secondary outcomes were graft function, proteinuria, and calcineurin inhibitor trough level variability. The predominant hepatitis C virus genotype was 1b (n = 19, 65.6%). All patients achieved SVR12. No graft failures nor deaths were reported during the study period. Throughout and after the treatment, the levels of aspartate aminotransferase [21 (range: 18-29.5) to 16 (range: 14-20) U/l, p < 0.001] and alanine aminotransferase [22 (range: 15-34) to 14 (range: 12-17.5) U/l, p < 0.001] improved significantly, unlike bilirubin, hemoglobin, and platelet levels. Renal function remained stable. Dose adjustments for calcineurin inhibitors were required. Serious adverse events were not observed. Safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination was effective and safe in kidney transplant recipients with hepatitis C virus. However, cautious monitoring of trough levels of calcineurin inhibitorss is needed due to potential drug-drug interactions during the treatment episode.

Efficacy of direct-acting antivirals in patients with hepatitis C virus-associated cryoglobulinemic vasculitis: Results of a long-term follow-up

Objective – to evaluate the long-term outcomes of HCV eradication with direct-acting antivirals (DAAs) in patients with hepatitis C-associated cryoglobulinemic vasculitis (HCV-CV)Materials and methods. We retrospectively assessed 48 patients with HCV-CV treated with DAAs. The activity of HCV-CV was assessed by using Birmingham Vasculitis Activity Score version 3 (BVAS v. 3). In patients with HCV-CV the rate of sustained virologic (defined as undetectable HCV-RNA levels 12 weeks after treatment cessation) and immunological (defined as absence of circulating cryoglobulins, rheumatoid factor and normal C4 level) response; and the rate of complete (defined by a BVAS v. 3 score of 0) and partial (defined as BVAS v. 3 score &lt;50% of the baseline score) clinical response were evaluated. Immunosupressants were given before or after DAAs therapy if clinically needed.Results. Median time of follow-up from treatment cessation were 26,5 (11,5–62,3) months. All 48 (100%) patients achieved sustained virologic response. Elimination of cryoglobulins were reported in 20 (41,7%) patients, complete immunological response-in 4 (8,3%) cases. Complete and partial clinical responses were observed in 13 (27,1%) and 19 (39,6%) patients, respectively. BVAS v. 3 score &lt;4 at baseline was independently associated with complete clinical response (ОR=7,58; 95% CI: 1,42–40,48; р=0,018). 3 (6,3%) patients demonstrated HCV-CV relapse.Conclusion. Patients with HCV-CV require a long-term follow-up period even after reaching the SVR. The use of BVAS v. 3 score before the DAAs therapy can facilitate the planning of therapeutic approach, particularly, when identifying the patients in whom the immunosupressive therapy should be considered after viral eradication.

Hepatitis C care cascade in a large academic healthcare system, 2012 to 2018.

To determine the hepatitis C virus (HCV) care cascade among persons who were born during 1945 to 1965 and received outpatient care on or after January 2014 at a large academic healthcare system. Deidentified electronic health record data in an existing research database were analyzed for this study. Laboratory test results for HCV antibody and HCV ribonucleic acid (RNA) indicated seropositivity and confirmatory testing. HCV genotyping was used as a proxy for linkage to care. A direct-acting antiviral (DAA) prescription indicated treatment initiation, an undetectable HCV RNA at least 20 weeks after initiation of antiviral treatment indicated a sustained virologic response. Of the 121,807 patients in the 1945 to 1965 birth cohort who received outpatient care between January 1, 2014 and June 30, 2017, 3399 (3%) patients were screened for HCV; 540 (16%) were seropositive. Among the seropositive, 442 (82%) had detectable HCV RNA, 68 (13%) had undetectable HCV RNA, and 30 (6%) lacked HCV RNA testing. Of the 442 viremic patients, 237 (54%) were linked to care, 65 (15%) initiated DAA treatment, and 32 (7%) achieved sustained virologic response. While only 3% were screened for HCV, the seroprevalence was high in the screened sample. Despite the established safety and efficacy of DAAs, only 15% initiated treatment during the study period. To achieve HCV elimination, improved HCV screening and linkage to HCV care and DAA treatment are needed.

Modelling the potential effectiveness of hepatitis C screening and treatment strategies during pregnancy in Egypt and Ukraine

HCV test and treat campaigns currently exclude pregnant women. Pregnancy offers a unique opportunity for HCV screening and to potentially initiate direct-acting antiviral treatment. We explored HCV screening and treatment strategies in two lower middle-income countries with high HCV prevalence, Egypt and Ukraine. Country-specific probabilistic decision models were developed to simulate a cohort of pregnant women. We compared five strategies: S0, targeted risk-based screening and deferred treatment (DT) to after pregnancy/breastfeeding; S1, World Health Organization (WHO) risk-based screening and DT; S2, WHO risk-based screening and targeted treatment (treat women with risk factors for HCV vertical transmission [VT]); S3, universal screening and targeted treatment during pregnancy; S4, universal screening and treatment. Maternal and infant HCV outcomes were projected. S0 resulted in the highest proportion of women undiagnosed: 59% and 20% in Egypt and Ukraine, respectively, with 0% maternal cure by delivery and VT estimated at 6.5% and 7.9%, respectively. WHO risk-based screening and DT (S1) increased the proportion of women diagnosed with no change in maternal cure or VT. Universal screening and treatment during pregnancy (S4) resulted in the highest proportion of women diagnosed and cured by delivery (65% and 70%, respectively), and lower levels of VT (3.4% and 3.6%, respectively). This is one of the first models to explore HCV screening and treatment strategies in pregnancy, which will be critical in informing future care and policy as more safety/efficacy data emerge. Universal screening and treatment in pregnancy could potentially improve both maternal and infant outcomes. In the context of two lower middle-income countries with high HCV burdens (Egypt and Ukraine), we designed a decision analytic model to explore five different HCV testing and treatment strategies for pregnant women, with the assumption that treatment was safe and efficacious for use in pregnancy. Assuming direct-acting antiviral treatment during pregnancy would reduce vertical transmission, our findings indicate that the provision of universal (rather than risk-based targeted) screening and treatment would provide the greatest maternal and infant benefits. While future trials are needed to assess the safety and efficacy of direct-acting antivirals in pregnancy and their impact on vertical transmission, there is increasing recognition that the elimination of HCV cannot leave entire subpopulations of pregnant women and young children behind. Our findings will be critical for policymakers when developing improved screening and treatment recommendations for pregnant women.

Direct-Acting Antiviral Treatment in Albanian Patients With Chronic Hepatitis C and Advanced Liver Fibrosis.

Background Treating chronic hepatitis C (CHC) with direct-acting antiviral (DAA) is very effective at clearing the infection. In Albania treatment with DAA is limited to patients with liver stiffness F3-F4, and with other co-infections. The objective of this study was to evaluate the efficacy of DAA in Albanian patients with genotypes 1-5, who mostly suffer from advanced liver fibrosis. Material and Methods This is a retrospective study carried out at the University Hospital Center "Mother Teresa", Tirana, during 2014-2019, including treatment-naïve and treatment-experienced patients with genotypes 1-5. All patients were evaluated with elastography and most of them were F3-F4. The primary endpoint involved the patients achieving SVR-12, or undetectablehepatitis C virus/ribonucleic acid (HCV RNA) 12 weeks after the end of treatment. In patients without a genotype, we have used a pangenotypic regimen. Results This study included 207 patients with a mean age of 48.9 ± 13.1 years, 56% male and 44% female; 152 (73%) were genotype 1, 24 were (11.5%) genotype 2, nine were (4.3%) genotype 3, 14 were (6.7%) genotype 4, one was (0.4%) genotype 5, and seven (3.8%) unassigned genotypes. The sustained virologic response (SVR) percentage according to genotype is discussed in the article. The overall SVR score of all the patients in our study was>93%. According to elastography, 127 (66%) were F3-F4, and 80 (38.6%) were F1-F2. Conclusion Treatment with DAA proved to be very effective in our patients; most of them had advanced liver fibrosisas well as compensatedor decompensated liver cirrhosis. The overall SVR score ofthe patients in our study was>93%. Our country needs to treat all patients with chronic hepatitis C without limitations to attain the WHO objectiveof eradicating this disease by 2030.

Low Risk of Failing Direct-Acting Antivirals in People With Human Immunodeficiency Virus/Hepatitis C Virus From Sub-Saharan Africa or Southeastern Asia: A European Cross-Sectional Study.

Several studies have reported suboptimal efficacy of direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) subtypes endemic to sub-Saharan Africa (SSA) and Southeastern Asia (SEA). The extent of this issue in individuals with human immunodeficiency virus (HIV)/HCV from SSA or SEA residing in Europe is unknown. We retrospectively analyzed data from several prospective European cohorts of people living with HIV. We included individuals with HIV/HCV who originated from SSA or SEA, were treated with interferon-free DAAs, and had an available HCV RNA result ≥12 weeks after the end of treatment. The primary outcome was sustained virological response at least 12 weeks after the end of treatment (SVR12). Of the 3293 individuals with HIV/HCV treated with DAA and with available SVR12 data, 142 were from SSA (n = 64) and SEA (n = 78). SVR12 was achieved by 60 (94% [95% confidence interval {CI}, 86%-98%]) individuals from SSA and 76 (97% [95% CI, 92%-99%]) from SEA. The genotypes of the 6 individuals failing DAA treatment were 2, 3a, 3h, 4a, 4c, and 6j. For 2 of the 4 unsuccessfully treated individuals with available sequence data at treatment failure, NS5A resistance-associated substitutions were present (30R/93S in an individual with genotype 4c and 31M in an individual with genotype 6j). SVR12 rates were high in individuals with HIV/HCV residing in Europe and originating from regions where intrinsically NS5A-resistant HCV strains are endemic. HCV elimination for this population in Europe is unlikely to be hampered by suboptimal DAA efficacy.

Meta-analysis: diagnostic accuracy of hepatitis C core antigen detection during therapy with direct-acting antivirals.

Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) is monitored by assessing plasma HCV-RNA load. However, detection of HCV core antigen (HCVcAg) may be an alternative. To evaluate the diagnostic performance of the HCVcAg assay to monitor the efficacy of DAAs in HCV-infected patients METHODS: We performed searches in multiple electronic databases until 6 July 2022, of studies evaluating the HCVcAg detection in plasma or serum compared with the HCV-RNA test (gold standard). We calculated pooled measurement at 2 and 4 weeks of treatment, and at end-of-treatment (EOT), as well as sustained virological response (SVR; 12 weeks after EOT). We selected 16 studies from 2016 to 2022, with 3237 patients and 8958 samples. Overall, the diagnostic performance and clinical utility of the HCVcAg assay were poor at week 2 (sensitivity=0.40, specificity=0.96, positive likelihood ratio (PLR)=9.16, negative likelihood ratio (NLR)=0.63, and area under the summary receiver operating curve (SROC)=0.57), fair at week 4 (sensitivity=0.30, specificity=0.90, PLR=3.18, NLR=0.77, and AUC=0.79), acceptable at EOT (sensitivity=0.40, specificity =0.98, PLR=16.54, NLR=0.62, and AUC=0.97) and excellent for SVR (sensitivity=0.94, specificity=0.99, PLR=107.54, NLR=0.06, and AUC=0.99). The HCVcAg assay may be helpful for monitoring the efficacy of HCV treatment with DAAs in HCV-infected patients at EOT and for documenting SVR, but not at weeks 2 and 4 of treatment due to poor diagnostic performance.

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.

Impact of utilization of hepatitis C positive organs in liver transplant: Analysis of united network for organ sharing database.

BACKGROUNDThe utility of hepatitis C virus (HCV) organs has increased after the Food and Drug Administration approval of direct acting anti-viral (DAA) medications for the HCV treatment. The efficacy of DAA in treating HCV is nearly 100%. AIMTo analyze the United Network for Organ Sharing (UNOS) database to compare the survival rates between the hepatitis C positive donors and negative recipients and hepatitis C negative donors and recipients. METHODSWe analyzed the adult patients in UNOS database who underwent deceased donor liver transplant from January 2014 to December 2017. The primary endpoint was to compare the survival rates among the four groups with different hepatitis C donor and recipient status: (Group 1) Both donor and recipient negative for HCV (Group 2) Negative donor and positive recipient for HCV (Group 3) Positive donor and negative recipient for HCV (Group 4) Both positive donor and recipient for HCV. SAS 9.4 software was used for the data analysis. Kaplan Meier log rank test was used to analyze the estimated survival rates among the four groups. RESULTSA total of 24512 patients were included: Group 1: 16436, Group 2: 6174, Group 3: 253 and Group 4: 1649. The 1-year (Group 1: 91.8%, Group 2: 92.12%, Group 3: 87%, Group 4: 92.8%), 2-year (Group 1: 88.4%, Group 2: 88.1%, Group 3: 84.3%, Group 4: 87.5%), 3-year (Group 1: 84.9%, Group 2: 84.3%, Group 3: 75.9%, Group 4: 83.2%) survival rates showed no statistical significance among the four groups. Kaplan Meier log rank test did not show any statistical significance difference in the estimated survival rates between Group 3 vs all the other groups. CONCLUSIONThe survival rates in hepatitis C positive donors and negative recipients are similar as compared to both hepatitis C negative donors and recipients. This could be due to the use of DAA therapy with cure rates of nearly 100%. This study supports the use of hepatitis C positive organs in the selected group of recipients with and without HCV infection. Further long-term studies are needed to further validate these findings.

Geographic Distribution of HCV Genotypes and Efficacy of Direct-Acting Antivirals in Chronic HCV-Infected Patients in North and Northeast China: A Real-World Multicenter Study.

Objective To assess the geographic distribution of HCV genotypes, effectiveness, and safety of DAA treatment for HCV-infected patients in North and Northeast China. Methods The geographic distribution of HCV genotypes was analyzed in 2162 patients recruited from April 2018 to February 2021. Sustained virologic response rates at 12 (SVR12) or 24 (SVR24) weeks posttreatment and safety were analyzed in 405 patients who completed DAA treatment according to patient baseline characteristics and treatment. Results Four genotypes and six subtypes were identified as follows: 1b (1187, 54.90%), 2a (790, 36.54%), 3a/b (134, 6.20%), 6a/n (44, 2.04%), mixed genotypes (2a-6a or 2a-3a) (7, 0.32%). Overall, 99.01% patients achieved SVR12, while 98.43% achieved SVR24. All patients treated with elbasvir/grazoprevir (EBR/GZR), sofosbuvir/velpatasvir ± ribavirin (SOF/VEL ± RBV), and SOF/ledipasvir (LDV) achieved SVR12 or SVR24; 92.86% SVR12 and 95.83% SVR24 were observed in patients using SOF + RBV. SVR12 was higher in noncirrhosis versus compensated cirrhosis patients (100% vs. 97.09%, p=0.022). No severe drug-related adverse event was observed. Conclusions Genotypes 1b and 2a were dominant subtypes in North and Northeast China. The approved drug regimens EBR/GZR and SOF/LDV for subtype 1b and SOF/VEL for nongenotype 1b are the optimal effective and safety profile.

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.

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.