Decreased risk of hepatocellular carcinoma recurrence with directacting antivirals compared with no treatment for hepatitis C: a meta-analysis (original) (raw)
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Hepatoma Research, 2019
Aim: Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma (HCC) in the United States. Achieving sustained viral response with interferon (IFN) treatment reduces the risk from 3%-5% to 0.5%-1% annually. Several studies reported unexpectedly high rates of HCC after treatment with direct-acting antivirals (DAAs). The aim of our study was to compare HCC rates in DAA-, IFN-treated and untreated populations. Methods: A literature search was conducted using ScienceDirect, Ovid®, Web of Science and MEDLINE through January 2019. Studies were included if they measured rates of de novo or recurrent HCC (following curative treatment) in HCV-infected persons. We included 138 studies (n = 177,512). Simple pooling of data and meta-analysis were performed, using the random effects method. Results: Mean age was higher in the DAA-treated vs. IFN-treated group (58.4 years vs. 52.6 years; P = 0.0073), as were diabetes prevalence (34.5% vs. 11.7%; P ≤ 0.001) and incident cirrhosis (47.8% vs. 34.2%, P = 0.0017). The incidence rate of de novo HCC was 2.01/100 person-years (py) (95%CI: 1.38, 2.67) in the DAA group and 1.45/100py (95%CI: 0.98, 1.94) in the IFN-treated group. HCC recurred at 16.76/100py (95%CI: 10.75, 22.91) in the DAA-treated group vs. 20.04/100py (95%CI: 2.58, 45.21) after IFN. After adjusting for factors such as age and cirrhosis, the hazard ratio was 0.58 (95%CI: 0.20, 1.07) for HCC occurrence and 0.59 (95%CI: 0.24, 1.03) for HCC recurrence after DAA treatment compared to IFN-based treatment. Conclusion: We did not find evidence for increased rates of HCC in DAA-treated compared with IFN-treated patients. Compared to those treated with IFN, older patients with additional risk factors for HCC were treated with DAAs. This imbalance appears to explain the higher numerical incidence of HCC among DAA-treated patients.
HCC incidence and recurrence after DAAs: new insights
Hepatoma Research, 2019
Hepatit C virus (HCV) infection is a global health and economic problem in the world. It is the cause of chronic active hepatitis, liver cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC) and extrahepatic manifestations. Before 2013, standard care of HCV infection was the combination of Pegylated Interferon (PEG IFN) and Ribavirin. Sustained Virologic Response (SVR) rate of this combination was approximately 50% after 48 weeks of therapy. One fifth of patients who had this combination had to stop treatment because of severe side effects. Adding of Telaprevir or Boceprevir (first generation of protease inhibitors) to PEG IFN and Ribavirin therapy for 24 or 48 weeks result in a SVR rate around 70%. However, because of severe adverse events, these combinations are not recommended.
Clinics and Research in Hepatology and Gastroenterology, 2020
Background: Although it has now been excluded that direct-acting antivirals (DAA) are associated with a significant risk of hepatocellular carcinoma (HCC) in HCV-infected patients, a possible effect of DAA on tumor growth is still a subject of debate. We performed a blind comparison of the kinetics of HCC recurrence in patients after HCV treatment with or without DAA to evaluate the potential aggressiveness of HCC after DAA treatment. Basic procedures: Thirty-nine HCV-infected patients from the AFEF/ANRS CO22 Hepather cohort who experienced HCC recurrence after so-called curative treatment were evaluated. Contrastenhanced CT and/or MR images were read blindly 6 months before HCC recurrence and during the follow-up period. Seventeen patients who received DAA (DAA +) before HCC recurrence were compared to the 22 who did not receive (DAA−), according to the LiRads and mRECIST criteria. Main findings: There were 28 men and 11 women, median age 62 years old, 37 (95%) with cirrhosis. DAA+ patients had a lower median MELD score (8 ± 2 vs. 10 ± 4, P = 0.0286) than DAA− patients. The median time to HCC recurrence (time from the date of curative treatment to the diagnosis of recurrence) was not different (20 vs. 18 months) (P = 0.73) between the two groups. There was no difference between the 2 groups in the overall survival and/or transplantation-free survival (P = 0.71) and for the mRECIST time to progression (P = 0.25). Conclusion: This blinded analysis of HCC recurrence after HCC treatment does not support any negative impact of DAA therapy on the severity or progression of recurrent HCC.
Liver International, 2019
Background & Aims: Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. Methods: This was a prospective multicenter cohort study from Latin America including 1,400 F1-F4 treated patients with DAAs (F3-F4 n=1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. Results: During a median follow-up of 16 months (IQR 8.9-23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01;0.03) at 12 months and 0.04 (CI 0.03;0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n=784) was 0.03 (CI 0.02-0.05) at 12 months and 0.06 (CI 0.04-0.08) at 24 months of follow-up. Failure to achieve SVR was independently Accepted Article This article is protected by copyright. All rights reserved. associated with de novo HCC with a HR of 4.9 (CI 1.44;17.32), after adjusting for diabetes mellitus, previous interferon non-responder, Child Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%-91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. Conclusions: Achieving SVR with DAAs regimens was associated with a significant risk reduction of HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.
Hepatoma Research, 2020
Aim: Despite the high cure rate of interferon-free directly acting antivirals (DAAs) for chronic hepatitis C (CHC) patients, the treatment efficacy for patients with preexisting hepatocellular carcinoma (HCC) remains undefined. We aimed in the present study to address the issue by using novel DAAs in treating CHC patients who were adherent to treatment in Taiwan. Methods: CHC patients with or without HCC were consecutively enrolled. The primary objective was sustained virological response (SVR) defined as undetectable HCV RNA throughout 12 weeks of a post-treatment follow-up period (SVR12). Only patients with available SVR12 were enrolled for final analysis. Results: A total of 1237 patients (1113 non-HCC, 101 inactive HCC and 23 active HCC) were enrolled. The overall SVR12 rate was 98.9%, and was similar between HCV patients with and without pre-existing HCC (98.4% vs. 98.9%, P = 0.64). While HCC patients were classified as those who had active or inactive HCC, the SVR12 was also similar between patients with and without active HCC (95.7% vs. 99.0%, P = 0.34). Among the 101 patients without viable HCC at the time of DAA initiation, eighty-four patients exhibited curative therapy and the other 17 patients experienced HCC recurrence before DAAs. Among the 23 patients with viable HCC at the time of DAA treatment, 10 patients had received curative therapy for HCC whereas the remaining 13 patients had HCC that was never cured. The SVR12 rates were also similar among the four subpopulations, being 98.8% (83/84), 100% (17/17), 90% (9/10) and 100% (13/13) respectively. Conclusion: CHC patients with HCC who were adherent to potent DAAs achieved similar SVR12 rate compared to those without HCC and could be effectively treated.
Journal of Hepatocellular Carcinoma, 2021
Background: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood. Patients and Methods: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis. Results: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5-4.7) for DAA and 9.3 years (IQR: 6.6-12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20-18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤0.001, depending on covariates). A HR of 6.62 (CI: 2.01-21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups. Conclusion: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.
Hepatoma Research, 2019
Aim: The increased risk of hepatocellular carcinoma (HCC) recurrence in hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAAs) after curative treatment for HCC is controversial. The purpose of this study was to examine the risk of HCC recurrence after DAA therapy. Methods: We conducted a retrospective cohort study of 312 consecutive patients with HCV-related HCC who received DAA therapy in participating institutions between September 2014 and July 2016. All patients received curative hepatectomy or radio-frequency ablation. We calculated the annual incidence of HCC recurrence after DAA therapy and identified the risk factors for HCC recurrence using Cox regression models. Results: The median age was 74 years old, and a sustained virological response was achieved by 288 patients. The 3-year-overall survival rate was 95.4% in a median follow-up period of 855 days. HCC recurred in 135 patients. The 1-, 2- and 3-year recurrence rates were 18.3%, 38.8% and 55.4%, respectively. A multivariate analysis revealed that the following factors were associated with HCC recurrence: multiple tumors at the first HCC treatment [hazard ratio (HR) = 2.21; 95%CI: 1.41-3.49], a history of multiple treatments for HCC (HR = 1.97; 95%CI: 1.28-3.02), and α-fetoprotein (AFP-L3) ≥ 10% at the initiation of DAA therapy (HR = 4.74; 95%CI: 2.10-10.7). Conclusion: Among patients treated with DAAs after the curative treatment of HCC, multiple tumors at the first HCC treatment, multiple prior HCC treatments and a high AFP-L3 level before DAA therapy were associated with recurrence, and the rate of recurrence was comparable to that before the DAA era.
Journal of viral hepatitis, 2017
In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV infected population from one Egyptian specialized HCC management center starting from the time of successful HCC intervention. The incidence rates of HCC recurrence between DAA exposed and non-exposed patients were compared, starting from date of HCC complete radiological response and censoring after two years. DAA exposure was treated as time-varying. Two Poisson regressions models were used to control for potential differences in the exposed and non-exposed group; multivariable adjustment and balancing using inverse probability of treatment weighting. We included 116 patien...