Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323663
Author(s):  
Victor Sapena ◽  
Marco Enea ◽  
Ferran Torres ◽  
Ciro Celsa ◽  
Jose Rios ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Propensity Score ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Recurrence Risk ◽  
Patient Data ◽  
Death Risk ◽  
Significant Difference ◽  
Direct Acting ◽  
Hcc Recurrence

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.ResultsRecurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1).ConclusionEffects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

Impact of Viral Status on Survival in Patients Receiving Sorafenib for Advanced Hepatocellular Cancer: A Meta-Analysis of Randomized Phase III Trials

2017 ◽  
Vol 35 (6) ◽  
pp. 622-628 ◽  
Author(s):  
Richard Jackson ◽  
Eftychia-Eirini Psarelli ◽  
Sarah Berhane ◽  
Harun Khan ◽  
Philip Johnson
Keyword(s):  
Hepatocellular Carcinoma ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Hepatocellular Cancer ◽  
Standard Of Care ◽  
Exponential Model ◽  
Patient Data ◽  
Phase Iii ◽  
Disease Etiology ◽  
Hazard Ratios

Purpose Following the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial, sorafenib has become the standard of care for patients with advanced unresectable hepatocellular carcinoma, but the relation between survival advantage and disease etiology remains unclear. To address this, we undertook an individual patient data meta-analysis of three large prospective randomized trials in which sorafenib was the control arm. Methods Of a total of 3,256 patients, 1,643 (50%) who received sorafenib were available. The primary end point was overall survival (OS). A Bayesian hierarchical approach for individual patient data meta-analyses was applied using a piecewise exponential model. Results are presented in terms of hazard ratios comparing sorafenib with alternative therapies according to hepatitis C virus (HCV) or hepatitis B virus (HBV) status. Results Hazard ratios show improved OS for sorafenib in patients who are both HBV negative and HCV positive (log [hazard ratio], −0.27; 95% CI, −0.46 to −0.06). Median unadjusted survival is 12.6 (11.15 to 13.8) months for sorafenib and 10.2 (8.88 to 12.2) months for “other” treatments in this subgroup. There was no evidence of improvement in OS for any other patient subgroups defined by HBV and HCV. Results were consistent across all trials with heterogeneity assessed using Cochran’s Q statistic. Conclusion There is consistent evidence that the effect of sorafenib on OS is dependent on patients’ hepatitis status. There is an improved OS for patients negative for HBV and positive for HCV when treated with sorafenib. There was no evidence of any improvement in OS attributable to sorafenib for patients positive for HBV and negative for HCV.

scholarly journals Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Therapy with Direct-Acting Antivirals. A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (8) ◽  
pp. 1694
Author(s):  
Leonardo Frazzoni ◽  
Usama Sikandar ◽  
Flavio Metelli ◽  
Sinan Sadalla ◽  
Giuseppe Mazzella ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Meta Analysis ◽  
Random Effect ◽  
Complete Response ◽  
Direct Acting Antivirals ◽  
Direct Acting ◽  
Hcc Recurrence

Background: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality among patients with cirrhosis. The risk of HCC recurrence after a complete response among patients treated with direct-acting antivirals (DAAs) has not been fully elucidated yet. Aim: To assess the risk of HCC recurrence after DAA therapy for hepatitis C virus (HCV). Methods: A systematic review across PubMed, Scopus and Scholar up to November 2020, including full-text studies that assessed the pattern of HCC recurrence after DAA therapy for HCV. Random-effect meta-analysis and univariable metaregression were applied to obtain pooled estimates for proportions and relative risk (RR) and variables influential for the outcome, respectively. Results: Thirty-one studies with 2957 patients were included. Overall, 30% (CI, 26–34%) of the patients with a history of HCC experienced HCC recurrence after DAA therapy, at mean time intervals ranging from 4 to 21 months. This result increased when going from European studies (23%, CI, 17–28%) to US studies (34%, CI, 30–38%), to Egyptian studies (37%, CI, 27–47%), and to Asian studies (33%, CI, 27–40%). Sixty-eight percent (CI, 45–91%) of recurrent HCCs developed within 6 months of follow-up since DAA treatment, among the eight studies providing stratified data. Among the studies providing head-to-head comparisons, the HCC recurrence risk was significantly lower after DAA therapy than IFN (RR, 0.64; CI, 0.51–0.81), and after DAA therapy than no intervention (RR, 0.68; CI, 0.49–0.94). Conclusions: The recurrence of HCC after DAA is not negligible, being higher soon after the end of treatment and among non-European countries. DAA therapy seems to reduce the risk of HCC recurrence compared to an IFN regimen and no intervention.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis

Radiology ◽  
2021 ◽  
Author(s):  
Christian B. van der Pol ◽  
Matthew D. F. McInnes ◽  
Jean-Paul Salameh ◽  
Brooke Levis ◽  
Victoria Chernyak ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data

Development of Hepatocellular Carcinoma in Patients Aged 75–84 Years With Chronic Hepatitis C Treated With Direct-Acting Antivirals

2020 ◽  
Author(s):  
Eiichi Ogawa ◽  
Hideyuki Nomura ◽  
Makoto Nakamuta ◽  
Norihiro Furusyo ◽  
Eiji Kajiwara ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Chronic Hepatitis C ◽  
Multicenter Cohort Study ◽  
Direct Acting Antiviral ◽  
Significant Difference ◽  
Direct Acting

Abstract Background Direct-acting antiviral (DAA) treatment has revolutionized hepatitis C virus (HCV) care. We aimed to evaluate the risk for the development of hepatocellular carcinoma (HCC) in patients aged 75–84 years with chronic hepatitis C after HCV elimination. Methods This multicenter cohort study included 2405 consecutive patients with chronic hepatitis C without a history of HCC who achieved HCV elimination by DAAs. Patients in whom HCC developed within 1 year of DAA initiation were excluded. Propensity score matching analysis was used to evaluate differences in HCC risk between patients aged 75–84 versus 60–74 years. Results The median observational period was 3.5 years. Among patients aged 75–84 years with a high Fibrosis-4 (FIB-4) index (≥3.25 at baseline), there was no significant difference in the annual incidence of HCCs between groups with an FIB-4 index ≥3.25 (2.75 per 100 person-years [PY]) versus &lt;3.25 (2.16 per 100 PY) at 12 weeks after the end of treatment, unlike the results in those aged 60–74 years (3.61 and 1.51 per 100 PY, respectively) (adjusted hazard ratio, 2.20; P = .04). In 495 pairs matched by propensity score matching, in patients without cirrhosis, the cumulative HCC incidence was significantly higher in the 75–84-year than in the 60–74-year age group (P = .04). Conclusions Older patients aged 75–84 years remained at high risk for the development of HCC, even after HCV elimination and the improvement of the FIB-4 index to &lt;3.25.

scholarly journals Evaluating the performance of propensity score matching based approaches in individual patient data meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatema Tuj Johara ◽  
Andrea Benedetti ◽  
Robert Platt ◽  
Dick Menzies ◽  
Piret Viiklepp ◽  
...  
Keyword(s):  
Propensity Score ◽  
Propensity Score Matching ◽  
Propensity Scores ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Random Effect ◽  
Multidrug Resistant ◽  
Patient Data ◽  
Propensity Score Model ◽  
Score Model

Abstract Background Individual-patient data meta-analysis (IPD-MA) is an increasingly popular approach because of its analytical benefits. IPD-MA of observational studies must overcome the problem of confounding, otherwise biased estimates of treatment effect may be obtained. One approach to reducing confounding bias could be the use of propensity score matching (PSM). IPD-MA can be considered as two-stage clustered data (patients within studies) and propensity score matching can be implemented within studies, across studies, and combining both. Methods This article focuses on implementation of four PSM-based approaches for the analysis of data structure that exploit IPD-MA in two ways: (i) estimation of propensity score model using single-level or random-effects logistic regression; and (ii) matching of propensity scores (PS) across studies, within studies or preferential-within studies. We investigated the performance of these approaches through a simulation study, which considers an IPD-MA that examined the success of different treatments for multidrug-resistant tuberculosis (MDR-TB). The simulation parameters were varied according to three treatment prevalences (according to studies, 50% and 30%), three levels of heterogeneity between studies (low, moderate and high) and three levels of pooled odds ratio (1, 1.5, 3). Results All approaches showed greater biases at the higher levels of heterogeneity regardless of the choices of treatment prevalences. However, matching of propensity scores using within-study and preferential-within study reported better performance compared to matching across studies when treatment prevalence varied across-studies. For fixed prevalences, a random-effect propensity score model to estimate propensity scores followed by matching of propensity scores across-studies achieved lower biases compared to other PSM-based approaches. Conclusions Propensity score matching has wide application in health research while only limited literature is available on the implementation of PSM methods in IPD-MA, and until now methodological performance of PSM methods have not been examined. We believe, this work offers an intuition to the applied researcher for the choice of the PSM-based approaches.

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