Dynamic noninvasive markers predict hepatocellular carcinoma in chronic hepatitis C patients without sustained virological response after interferon-based therapy

Abstract

Some patients with hepatitis C virus (HCV) infections who fail to achieve sustained virological responses (SVRs) after interferon (IFN) therapy do not develop hepatocellular carcinoma (HCC). Risk stratification of these patients may help identify those who would benefit most from treatment with direct-acting antivirals (DAAs).A total of 552 HCV-infected patients with non-SVR status were enrolled. Laboratory data before and after IFN treatment were analyzed to determine the relationship of changes in serum markers with development of HCC during the 7-year study period.HCC developed in 93 patients. The risk factors for HCC were pre-existing liver cirrhosis, low hemoglobin level at baseline, low pretreatment platelet count, high post-treatment alpha-fetoprotein (AFP) level (≥15 ng/mL), and high post-treatment Fibrosis 4 (FIB4) index (>3.25). For patients without pre-existing cirrhosis, those with high post-treatment AFP level and FIB4 index had the highest risk of HCC (1 year: 6.7%; 3 years: 10.9%; 5 years: 29.7%), followed by those with high post-treatment AFP level and low post-treatment FIB4 index (5 years: 25%), and those with low post-treatment AFP level and high post-treatment FIB4 index (1 year: 3.7%; 3 years: 5.2%; 5 years: 10.6%). The risk was even lower for patients with low post-treatment AFP level and FIB4 index (1 year: 0%; 3 years: 0.4%; 5 years: 2.5%). None of the patients with FIB4 indexes consistently below 1.45 developed HCC.The combined use of post-treatment AFP level and FIB4 index was useful for risk stratification of HCV-infected patients with non-SVR status after IFN therapy. These data may help clinicians to identify patients who most urgently need DAA treatment.

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

“…Therefore, we gave one point each for male gender, elevated FIB‐4 index (> 3.25), and elevated AFP (> 5.0 ng/mL) at SVR24 simply, with the sum used as ADRES score. Although only AFP level (> 5.0 ng/mL) at SVR24 was not significant factor in the validation cohort by Cox hazard multivariate analysis, elevated serum AFP level has also been recognized as one of common risk factors for HCC, and the c‐index for prediction ability for HCC development of the present simple ADRES score of the validation set was better than that of the training set. As a result, the incidence of HCC in each ADRES score with the present training set (ChuShikoku‐group) was similar to that noted in the validation set (Chubu‐group), and good stratification ability for prediction of HCC development was obtained in all cohort.…”

“…In patients able to obtain SVR24 with IFN‐based treatments, an elevated FIB‐4 index has been reported to be a risk factor for HCC (risk ratio 1.73; P = 0.0198); thus, a high FIB‐4 index is considered to be an independent risk factor for prognosis in patients with a history of HCV infection. On the other hand, elevated serum AFP level has also been reported as a risk factor for HCC in HCV‐infected patients with or without attaining SVR following IFN therapy . With Fisher's exact test and logistic regression analysis, male gender, and FIB‐4 index (> 3.25) and AFP level (> 5.0 ng/mL) at SVR24 were extracted for predictive prognostic factor for HCC development.…”

“…On the other hand, elevated serum AFP level has also been reported as a risk factor for HCC in HCV-infected patients with or without attaining SVR following IFN therapy. [22][23][24] With Fisher's exact test and logistic regression analysis, male gender, and FIB-4 index (> 3.25) and AFP level (> 5.0 ng/mL) at SVR24 were extracted for predictive prognostic factor for HCC development. It was thought that the prognostic weight of the predictive factor for HCC development might change, because the distributions of patients, who were treated with DAAs, regarding AFP level and FIB-4 index were different in each area of the present study.…”

Predictors of hepatocellular carcinoma recurrence associated with the use of direct‐acting antiviral agent therapy for hepatitis C virus after curative treatment: A prospective multicenter cohort study

“…In general, the AFP level and frequency of HCC recurrence are suggested to be closely related to malignancy of HCC. An elevated serum AFP level has been reported as a risk factor for HCC in HCV‐infected patients with or without attaining SVR following the IFN therapy . An elevated serum AFP level before the DAA therapy has also been recognized as one of the common risk factors for HCC .…”

Factors predicting hepatocellular carcinoma in hepatitis C infection

“…HCC develops in hepatitis C patients mostly in the setting of advanced fibrosis and liver cirrhosis [13] . For patients without pre-existing cirrhosis, a higher Fibrosis-4 (FIB-4) index translates to a higher risk of HCC [39] . Untreated patients with cirrhosis have a significantly higher HCC incidence rate (45.3 per 1000 person-years) compared to those treated with either IFN or DAAs [40,41] .…”