Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Early HCV viral kinetics under DAAs may optimize duration of therapy in patients with compensated cirrhosis.

ABSTRACT: BACKGROUND & AIMS:Detailed hepatitis C virus (HCV) kinetics modelling is scarce in patients with advanced liver disease receiving direct-acting antivirals (DAAs). Due to budget restrictions, patients and health systems would benefit from the shortest possible treatment course. We investigated whether modelling very early HCV kinetics in cirrhotic patients under DAAs therapy could be used to individualize care and reduce treatment duration to achieve cure. METHODS:We included 74 patients with HCV-related cirrhosis who received interferon-free treatments for 12-24 weeks. HCV genotype, liver disease stage and treatment regimen were recorded. Viral load was determined prospectively at very frequent intervals until target not detected (TND, <15 IU/mL). A viral kinetic model was used to predict time to cure based on HCV clearance in extracellular body fluid (CL-EF). RESULTS:Sixty-eight patients (92%) achieved cure. Thirteen (18%) had MELD ?15, 35 (47%) were Child-Pugh (CTP) ?7. Median time to reach TND was 2 weeks (IQR: 1-4 weeks). Modelling indicated an average DAAs efficacy in blocking viral production of ? = 99.1%. HCV half-life (t1/2 ) was significantly shorter in patients with CTP <7, LSM <21 kPa or MELD <15 (1.5 vs 2.5 hours; P = 0.0057). The overall median CL-EF was 5.6 weeks (4.1-7.8). A CTP >7 and a LSM ?21 kPa were significantly (P = 0.016) associated with longer CL-EF. CONCLUSIONS:The study provides insights into HCV dynamics during DAAs therapy in patients with compensated and decompensated cirrhosis. Viral kinetics modelling suggests that treatment duration may be optimized in patients with compensated cirrhosis.

SUBMITTER: Gambato M

PROVIDER: S-EPMC6483833 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Factors associated with hepatocellular carcinoma occurrence after HCV eradication in patients without cirrhosis or with compensated cirrhosis.

Project description:The present study aimed to investigate the incidence of hepatocellular carcinoma (HCC) and factors related to HCC occurrence after direct-acting antiviral (DAA) treatment in the Fukushima Liver Academic Group (FLAG). We conducted a multicenter retrospective cohort study of 1068 patients without cirrhosis (NC) or with compensated liver cirrhosis (LC) who achieved a sustained virologic response (SVR). First, we compared the cumulative HCC incidence and survival rates in NC (n = 880) and LC (n = 188) patients without a history of HCC treatment. Second, we performed multivariate analysis of factors related to HCC occurrence after DAA treatment. Overall, the average age was 65 years, and the male/female ratio was 511/557. Thirty-nine (4%) patients developed HCC. The cumulative 4-year HCC incidence and survival rates were 3.0% and 99.8% in NC patients and 11.5% and 98.5% in LC patients, respectively. The independent factors affecting HCC occurrence identified by multivariate analysis were the serum albumin (ALB) level before SVR for NC patients and the ALBI score, platelet count, and diabetes before SVR for LC patients. The factors related to HCC occurrence differed between NC and LC patients. Careful surveillance of post-SVR patients with these risk factors is needed.

| S-EPMC7721183 | biostudies-literature

Arterial blood pressure is closely related to ascites development in compensated HCV-related cirrhosis.

Project description:BACKGROUND: Arterial blood pressure (BP) is a reliable marker of circulatory dysfunction in cirrhotic patients. There are no prospective studies evaluating the association between different levels of arterial BP and ascites development in compensated cirrhotic patients. Therefore, we evaluated the relationship between arterial BP and ascites development in compensated cirrhotic patients. MATERIALS AND METHODS: A total of 402 patients with compensated HCV-related cirrhosis were prospectively followed during 6 years to identify ascites development. At baseline, patients underwent systolic, diastolic and mean arterial pressure (MAP) measurements. Any history of arterial hypertension was also recorded. The occurrence of events such as bleeding, hepatocellular carcinoma, death and liver transplantation prior to ascites development were considered as competing risk events. RESULTS: Over a median of 156 weeks, ascites occurred in 54 patients (13%). At baseline, MAP was significantly lower in patients with ascites development (75.9 mm/Hg [95%CI, 70.3-84.3]) than those without ascites (93.6 mm/Hg [95% CI: 86.6-102.3]). After adjusting for covariates, the 6-year cumulative incidence of ascites was 40% (95%CI, 34%-48%) for patients with MAP<83.32 mm/Hg. In contrast, cumulative incidences of ascites were almost similar among patients with MAP values between 83.32 mm/Hg and 93.32 mm/Hg (7% [95% CI: 4%-12%]), between 93.32 mm/Hg and 100.31 mm/Hg (5% [95% CI: 4%-11%]) or higher than 100.31 mm/Hg (3% [95% CI: 1%-6%]). The MAP was an independent predictor of ascites development. CONCLUSIONS: The MAP is closely related to the development of ascites in compensated HCV-related cirrhosis. The risk of ascites development increases in 4.4 fold for subjects with MAP values <83.32 mm/Hg.

| S-EPMC3995756 | biostudies-literature

Longitudinal assessment of HCV core antigen kinetics to monitor therapeutic response in the age of DAAs.

Project description:BackgroundIn the economy of therapeutic monitoring, an affordable viral marker is essential in the era of direct-acting antivirals (DAAs). We elucidated the kinetics of HCVcAg to delineate its precise role in monitoring therapeutic response.MethodsIn this longitudinal study, 3208 patients were tested for HCV RNA. A total of 423 patients were started on DAAs. Treatment response and kinetics of HCVcAg/RNA were assessed in treatment-naïve (n = 383) and previously treated (n = 40) patients with follow-up for 2 years.ResultsAfter the initiation of DAAs, the rate of relapse was significantly higher in the previously treated group than naive group [12.5% (5/40) Vs 2% (7/383), p<0.0001]. The response rate at RVR was significantly higher with HCVcAg than RNA in both groups (p<0.02). The kinetics of HCVcAg and RNA were significantly different at ETR and SVR12 in the naïve (p<0.04), but similar at all therapeutic points in the previously treated group. The correlation between HCVcAg and RNA was good at baseline, ETR and SVR, except RVR in both groups (r>0.6; p<0.0001). Furthermore, HCV genotypes, treatment regimen, CTP (<7/≥7) and MELD (<15/≥15) did not influence the therapeutic response and the viral replication kinetics (p>0.05).ConclusionsIt is the first longitudinal study from India shows that the response rate and kinetics of HCVcAg are comparable to HCV RNA for an extended duration, except at RVR, irrespective of the HCV genotypes, treatment regimen, and liver disease severity. Hence, HCVcAg can be considered as a pragmatic marker to monitor therapeutic response and predict relapse in the era of DAAs.

| S-EPMC9937470 | biostudies-literature

Effectiveness and safety of 8-week glecaprevir/pibrentasvir in HCV treatment-naive patients with compensated cirrhosis: real-world experience from Taiwan nationwide HCV registry.

Project description:BackgroundLarge-scale real-world data of the 8-week glecaprevir/pibrentasvir (GLE/PIB) therapy for treatment-naïve patients of chronic hepatitis C virus (HCV) infection with compensated cirrhosis is scarce.MethodsThe TASL HCV Registry (TACR) is an ongoing nationwide registry program that aims to set up a database and biobank of patients with chronic HCV infection in Taiwan. In this study, data were analyzed as of 31 October 2021 for treatment-naïve HCV patients with compensated cirrhosis receiving 8-week GLE/PIB therapy. Effectiveness reported as sustained virologic response at off-therapy week 12 (SVR12) and safety profiles were assessed. Patient characteristics potentially related to SVR12 were also evaluated.ResultsOf the 301 patients enrolled, 275 had available SVR12 data. The SVR12 rate was 98.2% (270/275) in the modified intention-to-treat (mITT) population and 89.7% (270/301) in the ITT population. For those mITT patients with genotype 3, FibroScan > 20 kPa, platelet < 150,000/µl, and FibroScan > 20 kPa and platelet < 150,000/µl, the SVR12 rates were 100% (6/6), 100% (12/12), 98.0% (144/147), 100% (7/7), respectively. Overall, 24.9% (75/301) patients experienced adverse events (AEs). The most frequent AEs (> 5%) included fatigue (9.0%) and pruritus (7.0%). Seven (2.3%) patients experienced serious AEs and two (0.7%) resulted in permanent drug discontinuation. None of them were considered as GLE/PIB-related.ConclusionsIn this large-scale real-world Taiwanese cohort, 8-week GLE/PIB therapy was efficacious and well tolerated for treatment-naïve compensated cirrhosis patients. SVR12 rates were similarly high as in the clinical trials, including those with characteristics of advanced liver disease.

| S-EPMC10042416 | biostudies-literature

Baseline and Breakthrough Resistance Mutations in HCV Patients Failing DAAs.

Project description:Sustained virologic response rates have increased dramatically following direct acting antiviral (DAA) therapy in chronic HCV infection. However, resistance-associated substitutions (RASs) may occur either prior to DAA or following drug exposure. The aim of this study was to determine RASs in DAA treatment-failing patients and the role of RASs in failure treatment. Six hundred and twenty HCV patients were evaluated. Direct sequencing of HCV genes was performed at breakthrough in all 31 patients failing DAAs, and in 19 baseline patients. Deep sequencing analysis was performed in 15/19 baseline patients. RASs were detected at breakthrough in 17/31 patients and at baseline in 11/19 patients, although, only 8/19 patients carried RASs associated with the prescribed regimen. Deep sequencing analysis showed RASs at baseline in 10/15 treatment-failing patients. No significant difference was observed with the Sanger sequencing. Treatment failure in the 14/31 patients without RASs was associated with suboptimal treatment. In 54.8% of treatment-failing patients one of the causes of failure might be the presence of RASs. In the majority of patients with RASs, mutations were present at baseline. Direct resistance test is advocated before treatment and at breakthrough in order to optimize retreatment regimens.

| S-EPMC5700050 | biostudies-literature

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance.

Project description:BackgroundAlthough human immunodeficiency virus type 1 (HIV-1) reservoir size is very stable under antiretroviral therapy (ART), individuals exposed to the Hepatitis C virus (HCV) (chronically coinfected and spontaneous clarifiers) show an increase in HIV reservoir size and in spliced viral RNA, which could indicate that the viral protein regulator Tat is being more actively synthesized and, thus, could lead to a higher yield of new HIV. However, it is still unknown whether the effect of HCV elimination with direct-acting antivirals (DAAs) could modify the HIV reservoir and splicing.MethodsThis longitudinal study (48 weeks' follow-up after sustained virological response) involves 22 HIV+-monoinfected individuals, 17 HIV+/HCV- spontaneous clarifiers, and 24 HIV+/HCV+ chronically infected subjects who eliminated HCV with DAAs (all of them aviremic, viral load < 50). Viral-spliced RNA transcripts and proviral DNA copies were quantified by qPCR. Paired samples were analyzed using a mixed generalized linear model.ResultsA decrease in HIV proviral DNA was observed in HIV+/HCV- subjects, but no significant differences were found for the other study groups. An increased production of multiple spliced transcripts was found in HIV+ and HIV+/HCV+ individuals.ConclusionsWe conclude that elimination of HCV by DAAs was unable to revert the consequences derived from chronic HCV infection for the reservoir size and viral splicing, which could indicate an increased risk of rapid HIV-reservoir reactivation. Moreover, spontaneous clarifiers showed a significant decrease in the HIV reservoir, likely due to an enhanced immune response in these individuals.

| S-EPMC9267476 | biostudies-literature

Ombitasvir/paritaprevir/ritonavir plus ribavirin for 24 weeks in patients with HCV GT4 and compensated cirrhosis (AGATE-I Part II).

Project description:Background and Aims:AGATE-I Part I previously reported high sustained virologic response rates in hepatitis C genotype 4 patients with cirrhosis, with 12 and 16 weeks' treatment with a combination of two direct-acting antivirals, ombitasvir and paritaprevir (codosed with ritonavir), plus ribavirin. Part II, reported here, extended the trial to include a 24-week treatment arm to fully assess treatment duration in patients with chronic hepatitis C genotype 4 infection and compensated cirrhosis. Methods:Enrollment took place between June and November of 2015. Treatment-naive and interferon-experienced patients with chronic hepatitis C genotype 4 infection and compensated cirrhosis were enrolled into Arm C; patients previously treated with a sofosbuvir-based regimen were enrolled into Arm D. All patients received a 24-week treatment with ombitasvir, paritaprevir, and ritonavir plus ribavirin. The primary outcome was the proportion of patients with a sustained virologic response (hepatitis C virus RNA < 25 IU/mL) at posttreatment week 12 in the intention-to-treat population. The safety population included all patients who received at least one dose of study drug. Results:In total, 64 patients were enrolled into AGATE-I Part II. Sustained virologic response at posttreatment week 12 was achieved in 57 of 61 patients (93.4%; 97.5% confidence interval, 92.6-97.7) in Arm C and 3 of 3 patients (100%) in Arm D. Two patients were missing SVR12 data, and two prematurely discontinued treatment. The most common adverse events for Arm C were fatigue (16 [26%]) and asthenia (15 [25%]). Results were comparable with those reported in Part I. Conclusions:AGATE-I Part II indicates that extending treatment beyond 12 weeks in genotype 4-infected patients with compensated cirrhosis does not offer additional benefit.

| S-EPMC6427060 | biostudies-literature

Liver Remodeling on CT Examination in Patients with HCV Compensated Cirrhosis Who Achieved Sustained Virological Response after Direct-Acting Antivirals Treatment.

Project description:Aims: The purpose of this study was to assess the changes in hepatic morphology evaluated by computed tomography (CT) examination in patients with hepatitis C virus (HCV)-related compensated cirrhosis who achieved sustained virologic response (SVR) after direct-acting antivirals (DAAs) treatment. Methods: CT examination was performed in 56 patients with HCV-related compensated cirrhosis before and within 6-18 months after the treatment with Ombitasvir/Paritaprevir/ritonavir + Dasabuvir. The liver CT changes were assessed by measuring liver volume, caudate-right lobe ratio (C/RL), hepatic vessels diameters, periportal widening space, and right posterior notch. Portal trunk, splenic and superior mesenteric vein diameters, as well as spleen volume were assessed as part of portal hypertension. Results: Right hepatic vein diameter was significantly wider after treatment (median: 8.12 mm; IQR: 4.20) than before treatment (median: 6.36 mm; IQR: 3.94) z = -3.894; p < 0.001. The liver volume was significantly higher prior to the treatment (median: 1786.77 mm3; IQR: 879.23) than after treatment (median: 1716.44 mm3; IQR: 840.50), z = -1.970; p = 0.049. Splenic volume was considerably higher before treatment (median: 564.79 mm3; IQR: 342.54) than after (median: 474.45 mm3; IQR: 330.00), z = -2.500; p = 0.012. The other parameters, such as C/RL, periportal space widening, and right hepatic notch showed no significant changes. Conclusions: SVR in patients with HCV-related compensated cirrhosis treated with DAAs is associated with some improvements of hepatic morphology detectable by CT, the most constant being the increase of right hepatic vein diameter.

| S-EPMC7231305 | biostudies-literature

Liver stiffness and thrombin generation in compensated cirrhosis.

Project description:BackgroundDecompensated cirrhosis is associated with coagulation abnormalities that can increase the risk of thrombosis and bleeding. It is unclear precisely when these abnormalities arise and whether they are exacerbated as compensated cirrhosis progresses. Transient elastography using FibroScan generates liver stiffness measurements (LSM) that associate with portal hypertension, clinical outcomes and provides prognostic information at an earlier stage than traditional liver function scores eg, MELD score.ObjectiveTo characterize thrombin generation in patients with compensated cirrhosis and to determine whether parameters of coagulation change throughout compensated cirrhosis, staged using LSM.Patients/methodsBlood samples were collected from well-compensated cirrhotic patients n = 61, All Child Pugh A stage) attending the Mater Misericordiae University Hospital, Ireland. Comprehensive clinical staging of liver disease, including LSM, was performed. Tissue Factor-stimulated thrombin generation was measured by calibrated automated thrombography.ResultsUsing LSM to stage well-compensated cirrhotic patients, we demonstrate a significant decrease in the rate of propagation, the rate of attenuation, and total thrombin generation as LSM increase. LSM correlated with endogenous thrombin potential, peak thrombin generation, the rate of propagation, and the rate of attenuation. This association between thrombin generation and LSM was still evident in sub-analyses excluding patients with ongoing alcohol use, active HCV infection, or a history of decompensation. In contrast, there was no significant correlation between thrombin generation, prothrombin times, Child-Pugh scores, or MELD scores.ConclusionLiver stiffness measurements identify differences in parameters of thrombin generation within a cohort of compensated cirrhotic patients before changes in clotting times occur.

| S-EPMC6462746 | biostudies-literature

Daclatasvir-based regimens in HCV cirrhosis: experience from the Italian early access program.

Project description:We reported the efficacy and safety data for daclatasvir (DCV)-based all-oral antiviral therapy in patients treated in the Italian compassionate-use program. 275 patients were included (202 male-73.5%, mean age: 57.4 years, 62 HIV-coinfected, 94 with recurrence of hepatitis C post-OLT). Forty-nine patients (17.8%) had Child-Pugh B, Genotype(G) distribution was: G1a:72 patients (26.2%), G1b:137 (49.8%); G3:40 (14.5%) and G4:26 (9.5%). Patients received DCV with sofosbuvir(SOF) (n?=?221, 129 with ribavirin(RBV) or with simeprevir (SMV) or asunaprevir (ASU) (n?=?54, 19 with RBV) for up to 24 weeks. Logistic regression was used to identify baseline characteristics associated with sustained virological response at week 12 post-treatment (SVR12). Liver function changes between baseline and follow up were assessed in 228 patients. 240 patients achieved SVR12 (87.3%), post transplant and HIV co-infected patients were equally distributed among SVR and no SVR (35% vs 34.3%; p?=?0.56 and 24.2% vs 11.4%, p?=?0.13, respectively). SVR rate was significantly higher with the combination DCV?+?SOF compared with DCV?+?SIM or ASU (93.2% vs 63.0%, p?<?0.0001). Bilirubin value (OR: 0.69, CI95%: 0.54-0.87, p?=?0.002) and regimen containing SOF (OR: 9.99, CI95%: 4.09-24.40; p?<?0.001) were independently related with SVR. Mean albumin and bilirubin values significantly improved between baseline and follow-up week 12. DCV-based antiviral therapy was well tolerated and resulted in a high SVR when combined with SOF either in pre-transplant and in OLT patients and in "difficult to treat" HCV genotypes. Regimens containing DCV in combination with NS3 protease inhibitors obtained suboptimal results.

| S-EPMC6345835 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data