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

ABSTRACT: 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.

SUBMITTER: Abe K

PROVIDER: S-EPMC7721183 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Abe Kazumichi K Wakabayashi Hiroto H Nakayama Haruo H Suzuki Tomohiro T Kuroda Masahito M Yoshida Naoe N Tojo Jun J Kogure Atsuko A Rai Tsuyoshi T Saito Hironobu H Mukai Shinji S Fujita Masashi M Hayashi Manabu M Takahashi Atsushi A Ohira Hiromasa H

PloS one 20201207 12

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 = 18 ...[more]

PMID: 33284844

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Project description:Background & aimsIt is unclear if hepatocellular carcinoma (HCC) risk declines over time after hepatitis C virus (HCV) eradication. We analyzed changes in HCC annual incidence over time following HCV eradication and identified dynamic markers of HCC risk.MethodsWe identified 48,135 patients who initiated HCV antiviral treatment from 2000 through 2015 and achieved a sustained virologic response (SVR) in the Veterans Health Administration (29,033 treated with direct-acting antiviral [DAA] agents and 19,102 treated with interferon-based regimens). Patients were followed after treatment until February 14, 2019 (average 5.4 years), during which 1509 incident HCCs were identified.ResultsAmong patients with cirrhosis before treatment with DAAs (n = 9784), those with pre-SVR fibrosis-4 (FIB-4) scores ≥3.25 had a higher annual incidence of HCC (3.66%/year) than those with FIB-4 scores <3.25 (1.16%/year) (adjusted hazard ratio 2.14; 95% confidence interval 1.66-2.75). In DAA-treated patients with cirrhosis and FIB-4 scores ≥3.25, annual HCC risk decreased from 3.8%/year in the first year after SVR to 2.4%/year by the fourth year (P=.01). In interferon-treated patients with FIB-4 scores ≥3.25, annual HCC risk remained above 2%/year, even 10 years after SVR. A decrease in FIB-4 scores from ≥3.25 pre-SVR to <3.25 post-SVR was associated with an approximately 50% lower risk of HCC, but the absolute annual risk remained above 2%/year. Patients without cirrhosis before treatment (n = 38,351) had a low risk of HCC, except for those with pre-SVR FIB-4 scores ≥3.25 (HCC risk 1.22%/year) and post-SVR FIB-4 scores ≥3.25 (HCC risk 2.39%/year); risk remained high for many years after SVR.ConclusionsPatients with cirrhosis before an SVR to treatment for HCV infection continue to have a high risk for HCC (>2%/year) for many years, even if their FIB-4 score decreases, and should continue surveillance. Patients without cirrhosis but with FIB-4 scores ≥3.25 have a high enough risk to merit HCC surveillance, especially if FIB-4 remains ≥3.25 post-SVR.

Project description:BACKGROUND & AIMS:It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with HCV infection. Therefore, in the current study, our aim was to determine the impact of DAA-induced SVR on HCC risk. METHODS:We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1 January 1999 to 31 December 2015, including 35,871 (58%) interferon (IFN)-only regimens, 4,535 (7.2%) DAA?+?IFN regimens, and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 15 June 2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs. DAA?+?IFN vs. IFN-only) and HCC risk. RESULTS:We identified 3,271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87), and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio [AHR] 0.29; 95% CI 0.23-0.37), DAA?+?IFN (AHR 0.48; 95% CI 0.32-0.73) or IFN-only (AHR 0.32; 95% CI 0.28-0.37). Receipt of a DAA-only or DAA?+?IFN regimen was not associated with increased HCC risk compared with receipt of an IFN-only regimen. CONCLUSIONS:DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared with treatment with IFN. LAY SUMMARY:It was unclear whether direct-acting antiviral treatment-induced sustained virologic response reduces the risk of liver cancer in patients with HCV infection. We demonstrated that eradication of HCV infection with direct-acting antiviral agents reduces the risk of liver cancer by 71%.

Project description:(1) Background: The pursuit of finding biomarkers for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has never been so paramount in the days of personalized medicine. The main objective of our study is to identify new biomarkers for diagnosing HCC, and to identify which patients are at risk of developing tumor recurrence, decompensation, or even possesses the risk of cancer-related death. (2) Methods: We have conducted an untargeted metabolomics study from the serum of 69 European patients-32 compensated cirrhotic patients without HCC (controls), and 37 cirrhotic patients with HCC with compensated underlying liver disease (cases), that underwent curative treatment (surgery or ablation), performing ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF- (ESI+)-MS) with an emphasis on lipid metabolites. (3) Results: 1,25-dihydroxy cholesterol (m/z = 419.281), myristyl palmitate (m/z = 453.165), 25-hydroxy vitamin D2 (m/z = 413.265), 12-ketodeoxycholic acid (m/z = 391.283), lysoPC (21:4) (m/z = 558.291), and lysoPE (22:2) (m/z = 534.286) represent notable biomarkers that differentiate compensated cirrhosis from early HCC, and ceramide species are depleted in the serum of HCC patients. Regarding prognosis, no metabolite identified in our study could determine tumor relapse. To distinguish between the HCC patients that survived curative treatment and those at risk that developed tumor burden, we have identified two notable phosphocholines (PC (30:2); PC (30:1)) with AUROCs of 0.820 and 0.807, respectively, that seem to increase when patients are at risk. In a univariate analysis, arachidonic acid was the only metabolite to predict decompensation (OR = 0.1, 95% CI: 0-0.16, p < 0.005), while in the multivariate analysis, dismally, no variable was associated with decompensation. Furthermore, in the multivariate analysis, we have found out for the first time that the increased expression of 1,25-dihydroxy cholesterol, myristyl palmitate, 12-keto deoxycholic acid, lysoPC (21:4), and lysoPE (22:2) are independent markers of survival. (4) Conclusions: Our study reveals that lipids play a crucial role in discriminating compensated cirrhosis and early hepatocellular carcinoma, and might represent markers of survival and prognosis in personalized and minimally invasive medicine.

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

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

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