A validation study of after direct-acting antivirals recommendation for surveillance score for the development of hepatocellular carcinoma in patients with hepatitis C virus infection who had received direct-acting antiviral therapy and achieved sustained

The pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with hepatitis C virus (HCV) who have received direct-acting antiviral (DAA) therapy and achieved sustained virological response (SVR). This study validated a composite predictive model for HCC in these patients. This study included 3058 patients in whom HCV was eradicated with DAA therapy. After DAAs recommendation for surveillance (ADRES) score, which is based on sex, FIB-4 index, and α-fetoprotein, was used as a composite predictive model for HCC development. The 1-, 3-, and 5-year cumulative incidence rates of HCC were 0.9, 4.5, and 15.2%, respectively. Multivariate analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 2.646; 95% confidence interval [CI], 1.790-3.911), FIB-4 index >3.25 (HR, 2.891; 95% CI, 1.947-4.293), and α-fetoprotein >5 ng/mL (HR, 2.835; 95% CI, 1.914-4.200) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES score (P < 0.001). Cox proportional hazards models showed that compared to the ADRES score 0 group, the HR for HCC development was 2.947 (95% CI, 1.367-6.354) in the ADRES score 1 group, 9.171 (95% CI, 4.339-19.380) in the ADRES score 2 group, and 20.630 (95% CI, 8.641-49.230) in the ADRES score 3 group. ADRES score had superior predictive power for HCC development compared with the FIB-4 index and α-fetoprotein according to time-dependent receiver operating characteristic analysis. The ADRES score is useful for predicting HCC development after SVR.

Tada T ，Kurosaki M ，Tamaki N ，Yasui Y ，Mori N ，Tsuji K ，Hasebe C ，Joko K ，Akahane T ，Furuta K ，Kobashi H ，Kimura H ，Yagisawa H ，Marusawa H ，Kondo M ，Kojima Y ，Yoshida H ，Uchida Y ，Nakamura S ，Izumi N ... -  《JGH Open》

mADRES predicts hepatocellular carcinoma development in patients with hepatitis C virus who achieved sustained virological response.

The study aims to develop a novel predictive model including the fibrosis (FIB)-3 index for hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C virus (HCV) who achieved sustained virological response (SVR) with direct-acting antiviral (DAA) therapy. This study included 2529 patients in whom HCV was eradicated with DAA therapy. The after DAA recommendation for surveillance (ADRES) score, which is based on sex, FIB-4 index, and α-fetoprotein, was used to predict HCC development. We developed a modified ADRES (mADRES) score, in which the FIB-4 index was replaced by the FIB-3 index, and evaluated its usefulness in predicting HCC development compared with the ADRES score. In the training set (n = 1770), multivariate analysis with Cox proportional hazards modeling showed that male sex (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.48-3.01), FIB-3 index (HR, 1.36; 95% CI, 1.28-1.45), and α-fetoprotein (HR, 1.05; 95% CI, 1.03-1.07) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES or mADRES score in multiple comparisons. Univariate Cox proportional hazards models showed that compared with the mADRES score 0 group, the HR for HCC development was 2.07 (95% CI, 1.02-4.19) for the mADRES score 1 group, 11.37 (95% CI, 5.80-22.27) for the mADRES score 2 group, and 21.95 (95% CI, 10.17-47.38) for the mADRES score 3 group. Similar results were obtained for mADRES score but not for ADRES score in the validation set (n = 759). The mADRES score is useful for predicting HCC development after SVR.

Tada T ，Kumada T ，Hiraoka A ，Kariyama K ，Yasuda S ，Tada F ，Ohama H ，Nouso K ，Matono T ，Nakamura S ，Toyoda H ，Real‐life Practice Experts for HCC (RELPEC) Study Group ... -  《-》

Proposed a simple score for recommendation of scheduled ultrasonography surveillance for hepatocellular carcinoma after Direct Acting Antivirals: multicenter analysis.

To develop a scoring method using with common clinical data for predicting hepatocellular carcinoma (HCC) development after sustained virological response at 24 weeks (SVR24) after treatment with direct acting antivirals (DAAs), we retrospectively evaluated clinical features of patients who obtained SVR24. From October 2014 to December 2017, 1069 hepatitis C virus patients without a past history of HCC, who obtained SVR24 by DAAs at two different areas, were enrolled (the training [n = 484, ChuShikoku-group] and validation [n = 585, Chubu-group] sets). All were examined by ultrasonography as surveillance for HCC at the time of starting DAAs and twice a year after SVR24. We identified three parameters at SVR24, male gender, FIB-4 index > 3.25, and α-fetoprotein level > 5.0 ng/mL, as risk factors for HCC development and gave them point values, with the sum used as After DAAs Recommendation for Surveillance (ADRES) score. In the ChuShikoku-group, the respective 1-/2-year rates for HCC incidence rates ADRES score 0 were 0.0%/0.0%, for a score 1 were 1.1%/2.1%, score 2 were 8.8%/15.9%, and score 3 were 17.1%/28.1%. On the other hand, those respective scores for the Chubu-group were 0.0%/0.0%, 0.0%/0.7%, 7.9%/10.6%, and 19.5%/not available. The c-index of the predictive value for HCC development in the training set after SVR24 was 0.835 while 0.899 in the validation set. Finally, those of the entire cohort were 0.0%/0.0%, 0.5%/1.6%, 8.4%/13.4%, and 18.0%/32.8%. The present ADRES score was simple and easy to use and may be useful for predicting risk of HCC development in short term after reaching SVR24 by DAAs.

Hiraoka A ，Kumada T ，Ogawa C ，Kariyama K ，Morita M ，Nouso K ，Toyoda H ，Tada T ，Ochi M ，Murakami T ，Izumoto H ，Ueki H ，Kitahata S ，Aibiki T ，Okudaira T ，Yamago H ，Iwasaki R ，Tomida H ，Miyamoto Y ，Mori K ，Miyata H ，Tsubouchi E ，Kishida M ，Ninomiya T ，Michitaka K ... -  《-》

Characteristics of hepatocellular carcinoma in patients with hepatitis C virus who received direct-acting antiviral therapy and achieved sustained virological response: The impact of a hepatologist on surveillance.

The relationship between the characteristics of hepatocellular carcinoma (HCC) diagnosed after sustained virological response (SVR) with direct-acting antiviral (DAA) therapy and surveillance status has not been sufficiently investigated. This study investigated the clinical risk factors for HCC development and HCC characteristics according to which type of physician performed follow-up after SVR. A total of 1070 patients in whom hepatitis C virus (HCV) was eradicated with DAA therapy were evaluated. There were 458 patients followed by hepatologists (specialist group) and 612 followed by non-hepatologists (non-specialist group) after SVR. During the follow-up period, 54 patients developed HCC. The 1-, 2-, 3-, 4-, and 5-year cumulative incidence rates of HCC were 1.8, 4.1, 6.9, 10.5, and 17.2%, respectively. Multivariate Cox proportional hazards analysis showed that male sex (hazard ratio [HR], 3.139; 95% confidence interval [CI], 1.732-5.690), α-fetoprotein level (HR, 1.056; 95% CI, 1.035-1.077), and fibrosis-4 (FIB-4) index (HR, 1.051; 95% CI, 1.017-1.085) were significantly associated with HCC development, while the follow-up physician type after SVR was not. There were 25 patients with stage I HCC, 17 with stage II, 9 with stage III, and 3 with stage IV. Multivariate ordinal logistic regression showed that follow-up physician type (non-specialist) (HR, 39.100; 95% CI, 9.350-224.00) was independently associated with HCC stage, while α-fetoprotein level and FIB-4 index were not. When patients have more risk factors for HCC development after SVR (i.e., male sex, elevated α-fetoprotein, or elevated FIB-4 index), they should be followed by a hepatologist for HCC surveillance.

Tada T ，Kumada T ，Matono T ，Nakamura S ，Sue M ，Matsuo Y ，Takatani M ，Iijima H ，Tanaka J ... -  《-》

General evaluation score for predicting the development of hepatocellular carcinoma in patients with advanced liver fibrosis associated with hepatitis C virus genotype 1 or 2 after direct-acting antiviral therapy.

To validate a composite predictive model for hepatocellular carcinoma (HCC) development in patients with advanced liver fibrosis associated with chronic hepatitis C virus (HCV) who have received direct-acting antiviral (DAA) therapy and achieved sustained virologic response (SVR). This study included 1258 patients with advanced liver fibrosis associated with HCV genotype 1, 2, or both. General evaluation score (GES), which is based on sex, age, fibrosis stage, albumin, and α-fetoprotein, was used as a composite predictive model. There were 645 (51.3%) patients in the low-risk group, 228 (18.1%) in the intermediate-risk group, and 385 (30.6%) in the high-risk group based on GES categories. The 12-, 36-, and 60-month cumulative incidence of HCC was 0.7%, 5.3%, and 13.0%, respectively. Multivariable analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 1.863; 95% confidence interval [CI], 1.204-2.883), F4 fibrosis stage (HR, 3.199; 95% CI, 1.696-6.036), and albumin (HR, 0.489; 95% CI, 0.288-0.828) are independently associated with HCC development. The incidence of HCC differed significantly by GES-based risk category (P < 0.001). Cox proportional hazards models showed that, with the low-risk group as the referent, the HR for HCC development was 1.875 (95% CI, 1.000-3.514) in the intermediate-risk group and 2.819 (95% CI, 1.716-4.630) in the high-risk group. GES had better predictive ability for HCC development than fibrosis-4 index according to time-dependent receiver operating characteristic analysis. GES is useful for predicting HCC development in patients with advanced liver fibrosis after SVR.

Tada T ，Kurosaki M ，Tamaki N ，Yasui Y ，Mori N ，Tsuji K ，Hasebe C ，Joko K ，Akahane T ，Furuta K ，Kobashi H ，Fujii H ，Ishii T ，Marusawa H ，Kondo M ，Kojima Y ，Yoshida H ，Uchida Y ，Nakamura S ，Izumi N ... -  《-》