Prediction of risk for hepatocellular carcinoma by response of serum α‐fetoprotein to entecavir therapy

Yang, Sung Mo; Kim, Gi Hyun; Chung, Jung Wha; Sohn, Hyung Rae; Lee, Sang Soo; Hong, Sukho; Chung, Seong Min; Jang, Eun Sun; Jeong, Sook Hyang; Kim, Jin-Wook

doi:10.1111/jgh.12921

Cited by 18 publications

(16 citation statements)

References 29 publications

(62 reference statements)

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“…Contrary to the previous expectations that use of NA may help improve the test performance of AFP [16, 20, 23], rigorous comparisons of C statistics revealed that AFP performance deteriorated with exposure history to NA therapy. The main reason for the deterioration was apparently due to decreased sensitivity (Table 5).…”

Section: Discussioncontrasting

confidence: 86%

“…Similar to chronic hepatitis C virus infection, hepatitis activity and fibrosis stage may influence AFP levels in CHB [21–24]. To make matters more complicated, potent oral nucleos(t)ide analog (NA) therapy may reduce the elevated AFP levels [16, 23, 25, 26], and several reports suggested progressively or persistently elevated AFP as a specific marker for HCC in CHB patients on NA therapy [20, 23, 26]. …”

Section: Introductionmentioning

confidence: 99%

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Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B

et al. 2016

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Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance.

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Section: Discussioncontrasting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B

et al. 2016

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“…Although the majority of patients assessed have been non-cirrhotic, the AFP values have been found to be consistently decreased alongside viral suppression 34–36,39,41,43. Interestingly, the pattern for normalization of AFP varies with different treatment, such as patients treated with entecavir experiencing a smooth, gradual reduction of AFP with a shorter period of AFP normalization (mean follow-up of 11.9 weeks) as compared to patients treated with pegylated-IFN experiencing a more fluctuating pattern with longer time of AFP normalization (mean follow-up of 22.3 weeks) 36.…”

Section: Discussionmentioning

confidence: 99%

“…Unlike HCV, there are several studies which have assessed the impact of HBV non-IFN-based treatment on AFP values 34–36,43. Although the majority of patients assessed have been non-cirrhotic, the AFP values have been found to be consistently decreased alongside viral suppression 34–36,39,41,43.…”

Section: Discussionmentioning

confidence: 99%

Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct-acting Antivirals

Nguyen

Jimenez

Moghadam

et al. 2017

Journal of Clinical and Translational Hepatology

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Background and Aims: The lack of specificity has limited the role of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening among patients with cirrhosis related to hepatitis C virus (HCV) infection. We sought to examine whether AFP may decrease after achieving a sustained virological response (SVR) in patients with HCV-related cirrhosis. Methods: We performed a retrospective study of patients with HCV-related cirrhosis who were cured with direct-acting antiviral (DAA) therapy at the University of California, Los Angeles. Laboratory values, including serum AFP, were measured before and after completing the DAA treatment. Results: Fifty-six patients met the inclusion criteria, with median (interquartile range [IQR]) age of 67 (58-69) years and with 51.8% being male. All patients received DAA therapy without interferon. AFP decreased from median (IQR) 7.2 (4.2-13.4) ng/mL before DAAs to 4.2 (2.7-6.3) ng/mL at the end of treatment and 4.2 (2.9-6.8) ng/mL at 12 weeks after treatment (p < 0.001). Model for end-stage liver disease (MELD), fibrosis-4 (FIB4), and aspartate transaminase (AST) to platelet ratio index (APRI) scores at baseline were not significantly associated with AFP reduction. On multivariate analysis, platelet count, AST and total bilirubin at baseline were significantly correlated to AFP reduction (p = 0.04, 0.009 and 0.04, respectively). The higher the baseline AFP, the greater the reduction in AFP. There was no statistically significant correlation between baseline AFP and MELD, FIB4 or APRI scores. Conclusion: There was a significant decrease in AFP in patients with cirrhosis who achieved a SVR with DAAs. Given a reduction in AFP after DAA treatment, AFP should be further studied as a screening modality for HCC in patients with cirrhosis.

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“…[14] In patients with chronic hepatitis B (CHB), but without HCC, antiviral treatment reduces AFP levels. [17–20] In these studies, HCC developed exclusively in patients with persistently elevated AFP levels after 6 [19] or 12 months [18,20] of antiviral therapy. However, most of the patients in these studies had AFP levels <100 mg/mL, which is a level that can be used to confirm HCC.…”

Section: Introductionmentioning

confidence: 99%

Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma

Kim

Lee

et al. 2017

Medicine

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Prediction of risk for hepatocellular carcinoma by response of serum α‐fetoprotein to entecavir therapy

Abstract: Delayed AFP response to ETV may serve as an indicator of high HCC risk.

Cited by 18 publications

References 29 publications

Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B

Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B

Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct-acting Antivirals

Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma

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