α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C

Asahina, Yasuhiro; Tsuchiya, Kaoru; Nishimura, Takashi; Muraoka, Masaru; Suzuki, Yuichiro; Tamaki, Nobuharu; Yasui, Yutaka; Hosokawa, Takanori; Ueda, Ken; Nakanishi, Hiroyuki; Itakura, Jun; Takahashi, Yuka; Kurosaki, Masayuki; Enomoto, Nobuyuki; Nakagawa, Mina; Kakinuma, Sei; Watanabe, Mamoru; Izumi, Namiki

doi:10.1002/hep.26442

Cited by 242 publications

(281 citation statements)

References 44 publications

Supporting

Mentioning

264

Contrasting

Order By: Relevance

“…Previous studies have reported that advanced fibrosis, advanced age, lower albumin levels, lower platelet counts, and higher α‐fetoprotein (AFP) levels before and after treatment are important predictors of HCC in patients who achieve SVR with interferon‐based treatment 14, 15, 16. However, the risk factors for the development of HCC in patients who achieve SVR after DAA treatment have not been adequately clarified in a prospective study.…”

Section: Introductionmentioning

confidence: 99%

Liver stiffness measurement predicts hepatocellular carcinoma development in patients treated with direct‐acting antivirals

et al. 2017

View full text Add to dashboard Cite

Background and AimPredictive factors for hepatocarcinogenesis following eradication of hepatitis C virus by direct‐acting antivirals (DAAs) are unknown. The aim of the study was to investigate the relationships between liver stiffness (LS) using acoustic radiation force impulse (ARFI) erastograghy and the development of hepatocellular carcinoma (HCC) in patients who achieved sustained virological response (SVR) treated with DAA.MethodsIn this prospective study, we enrolled 263 hepatitis C patients with SVR who underwent ARFI before DAA treatment. Thirty patients had previous HCC.ResultsThe median LS value according to ARFI measurements was 1.34 m/s (range: 0.67–4.35). During the follow‐up period (median: 18.1 months), development of HCC occurred in 19 patients (7.2%; HCC occurrence in 7 patients and HCC recurrence in 12 patients). By multivariate Cox regression analysis, HCC history (hazard ratio [HR]: 10.634; 95% confidence interval [CI]: 4.13–27.37; P = 0.001), older age (HR: 4.638; 95% CI: 1.63–13.61; P = 0.004) and higher total bilirubin levels (HR: 4.189; 95% CI: 1.66–10.60; P = 0.002) were independent predictors for the development of HCC, and higher LS value (≥1.73 m/s) at baseline was an independent predictor for HCC occurrence (HR: 8.350; 95% CI: 1.62–43.09; P = 0.011). The cumulative recurrence of HCC was statistically similar according to the degree of LS in patients who were previously treated for HCC.ConclusionThe LS value at baseline is useful for predicting HCC occurrence. Thus, even if SVR is achieved, patients with higher LS at baseline must be followed carefully for HCC occurrence.

show abstract

Section: Introductionmentioning

confidence: 99%

Liver stiffness measurement predicts hepatocellular carcinoma development in patients treated with direct‐acting antivirals

et al. 2017

View full text Add to dashboard Cite

show abstract

“…1,6 Therefore, future studies are needed to determine whether our results are in agreement with long-term, large cohort studies that include various population subgroups. Nevertheless, we believe that our results have important clinical implications for clinicians considering an individual patient's HCC surveillance and/or treatment strategy.…”

mentioning

confidence: 58%

Reply

Asahina

Tsuchiya²,

Izumi³

2014

Hepatology

Self Cite

View full text Add to dashboard Cite

We appreciate the valuable comments made by Dr. Lo. We agree that serum a-fetoprotein (AFP) levels sometime fluctuate during serial observations. Therefore, we used the average AFP integration value in our study, 1 as previously described, 2,3 and an AFP fluctuation that may have occurred during our observation period was not likely to affect the average AFP result. We also agree that a 1-month interval between AFP measurements for lowrisk patients is too frequent. In our study, the AFP measurement interval depended on an individual patient's risk for hepatocellular carcinoma (HCC), and in accordance with the Japanese Evidencebased Clinical Guidelines for the Diagnosis and Treatment of HCC, 4 our AFP measurement interval was every 6 months for low-risk patients.Unlike other cross-sectional studies that examined AFP values as a tumor marker to detect current HCC, 5 our longitudinal cohort study determined the clinical significance of posttreatment AFP values and evaluated whether AFP values could be used as a predictive risk factor for "future" HCC development. We hypothesized that the AFP values during the observation period associate with the risk for "future" HCC development because elevated serum AFP is sometimes observed in patients with advanced chronic hepatitis C virus (CHC) in the absence of HCC.The positive predictive value of AFP was low. However, the extremely high negative predictive AFP value (0.960) suggested that the postinterferon (post-IFN) treatment AFP value <6.0 ng/mL predicted a decreased likelihood of "future" HCC development. In the HALT-C study, 6 the AFP was 20 ng/mL in 50% of patients who developed HCC, suggesting that the AFP predictive criterion of 20 ng/mL is insufficient to predict a low risk for HCC development. Therefore, post-IFN treatment predictive AFP levels should be <6.0 ng/mL to suppress the risk for "future" HCC development.The HCC incidence is largely different between Western countries and Japan (Western < Japan). 1,6 Therefore, future studies are needed to determine whether our results are in agreement with long-term, large cohort studies that include various population subgroups. Nevertheless, we believe that our results have important clinical implications for clinicians considering an individual patient's HCC surveillance and/or treatment strategy.We also appreciate the valuable comments made by Drs. Toyoda, Kumada, and Tada. We are also aware that there are two distinct patterns of HCC development after sustained virological response (SVR) has been achieved. Although we carefully ruled out the existence of HCC by imaging modalities, 1 we agree that the limit of detection of our imaging apparatus did not allow us to detect and completely exclude minute HCC. However, this raises the question as to whether incidences of minute HCC are capable of producing detectable AFP. We agree with Dr. Toyoda et al. that an AFP fucosylated fraction (AFP-L3) may be useful to address this question. 7 Unfortunately, pre-IFN treatment AFP-L3 levels were not available in our patients who...

show abstract

“…Nevertheless, SVR patients remain at risk of HCC development, especially those with old age, high baseline gamma-glutamyltransferase levels, advanced liver fibrosis or comorbidity such as diabetes [206][207][208]. High APRI 6 months after the end of treatment [209] and high posttreatment ALT or AFP levels [210] were independent factors significantly associated with HCC development. These data indicate that regular monitoring for HCC screening and good control of comorbidities after achieving a SVR are mandatory for HCV patients.…”

Section: Laboratory Testing After Hcv Curementioning

confidence: 99%

“…These data indicate that regular monitoring for HCC screening and good control of comorbidities after achieving a SVR are mandatory for HCV patients. Older age, male gender, advanced fibrosis, severe steatosis, lower serum albumin levels, non-SVR, and higher post-interferon-treatment ALT or AFP levels are identified as independent factors significantly associated with HCC development [210]. Occurrence of HCC is not a rare event during and after antiviral treatment in older HCV patients [211] or HCV patients with advanced fibrosis [210].…”

Section: Laboratory Testing After Hcv Curementioning

confidence: 99%

“…Older age, male gender, advanced fibrosis, severe steatosis, lower serum albumin levels, non-SVR, and higher post-interferon-treatment ALT or AFP levels are identified as independent factors significantly associated with HCC development [210]. Occurrence of HCC is not a rare event during and after antiviral treatment in older HCV patients [211] or HCV patients with advanced fibrosis [210]. Further studies will be needed regarding this point after interferon-free treatment [212][213][214][215][216].…”

Section: Laboratory Testing After Hcv Curementioning

confidence: 99%

See 1 more Smart Citation

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

et al. 2016

View full text Add to dashboard Cite

The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on ''APASL consensus statements and recommendations for management of hepatitis C'' in March 2015 to revise the ''APASL consensus statements and management algorithms for hepatitis C virus infection'' (Hepatol Int 6:409-435, 2012). The working party consisted of expert hepatologists from the Asian-Pacific region gathered at the Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed, and debated during the course of drafting a revision. Participants of the consensus meeting assessed the quality of the cited studies. The finalized recommendations for hepatitis C prevention, epidemiology, and laboratory testing are presented in this review.

show abstract

α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C

Abstract: Post-IFN treatment ALT and AFP levels are significantly associated with hepatocarcinogenesis. Measurement of these values is useful for predicting future HCC risk after IFN treatment. Suppression of these values after IFN therapy reduces HCC risk even in patients without HCV eradication.

Cited by 242 publications

References 44 publications

Liver stiffness measurement predicts hepatocellular carcinoma development in patients treated with direct‐acting antivirals

Liver stiffness measurement predicts hepatocellular carcinoma development in patients treated with direct‐acting antivirals

Reply

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

Contact Info

Product

Resources

About