Dataset Information

Differential Effect of HCV Eradication and Fibrosis Grade on Hepatocellular Carcinoma and All-cause Mortality.

ABSTRACT: Whether a sustained virological response (SVR) improves long-term outcomes in chronic hepatitis C patients with earlier-stage fibrosis has not been established. We investigated the differential effect of SVR on the risk of outcomes according to hepatic fibrosis grade. Fibrosis grade was categorised using FIB-4: <1.45, low-probability of significant fibrosis; 1.45-3.25, intermediate-probability; and ≥3.25, high-probability. Primary and secondary endpoints were hepatocellular carcinoma (HCC) occurrence and death, respectively. Among 1,373 included chronic hepatitis C patients, 744 patients were treated with interferon-based or -free regimens and 622 (83.6%) achieved SVR. SVR was independently associated with lower risk of HCC (vs. untreated: adjusted hazard ratio [aHR], 0.165; 95% confidence interval [CI], 0.077-0.350; P < 0.001) and overall death (vs. untreated; aHR, 0.146; 95% CI, 0.050-0.424; P < 0.001) during the median observation of 3.5 (interquartile range, 1.9-6.6) years. The SVR group had significantly lower risk of HCC than the untreated group among patients with intermediate-probability (n = 492: aHR, 0.171; 95% CI, 0.051-0.578; P = 0.004) and high-probability (n = 446: aHR, 0.243; 95% CI, 0.107-0.551; P < 0.001) of significant fibrosis. HRs were maintained after balancing with inverse probability weighting. SVR was associated with reduced risk of HCC development and all-cause mortality in patients with chronic hepatitis C.

SUBMITTER: Lee YB

PROVIDER: S-EPMC6135856 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Differential Effect of HCV Eradication and Fibrosis Grade on Hepatocellular Carcinoma and All-cause Mortality.

Lee Yun Bin YB Nam Joon Yeul JY Lee Jeong-Hoon JH Chang Young Y Cho Hyeki H Cho Young Youn YY Cho Eun Ju EJ Yu Su Jong SJ Kim Hwi Young HY Lee Dong Ho DH Lee Jeong Min JM Hwang Seong Gyu SG Kim Yoon Jun YJ Yoon Jung-Hwan JH

Scientific reports 20180912 1

Whether a sustained virological response (SVR) improves long-term outcomes in chronic hepatitis C patients with earlier-stage fibrosis has not been established. We investigated the differential effect of SVR on the risk of outcomes according to hepatic fibrosis grade. Fibrosis grade was categorised using FIB-4: <1.45, low-probability of significant fibrosis; 1.45-3.25, intermediate-probability; and ≥3.25, high-probability. Primary and secondary endpoints were hepatocellular carcinoma (HCC) occur ...[more]

PMID: 30209336

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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: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.

Dataset Information

Differential Effect of HCV Eradication and Fibrosis Grade on Hepatocellular Carcinoma and All-cause Mortality.

Publications

Differential Effect of HCV Eradication and Fibrosis Grade on Hepatocellular Carcinoma and All-cause Mortality.

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