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Direct acting antiviral-induced dynamic reduction of serum α fetoprotein in hepatitis C patients without hepatocellular carcinoma

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Abstract

Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12–213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (> 5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP > 5.5 was associated with the presence of cirrhosis (P =0.001), coexisting non-alcoholic steatohepatitis (NASH) (P = 0.035), and GT 1 (P = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis (P = 0.003), Child—Pugh score < 6 (P = 0.015), and baseline AFP < 10 (P = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child—Pugh score < 6, and baseline AFP < 10.

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References

  1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385(9963): 117–171

    Article  Google Scholar 

  2. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014; 61(1 Suppl): S45–S57

    Article  Google Scholar 

  3. Koretz RL, Lin KW, Ioannidis JP, Lenzer J. Is widespread screening for hepatitis C justified? BMJ 2015; 350: g7809

    Article  Google Scholar 

  4. Ermis F, Senocak Tasci E. New treatment strategies for hepatitis C infection. World J Hepatol 2015; 7(17): 2100–2109

    Article  Google Scholar 

  5. Lazarevich NL. Molecular mechanisms of α-fetoprotein gene expression. Biochemistry (Mosc) 2000; 65(1): 117–133

    CAS  Google Scholar 

  6. Ball D, Rose E, Alpert E. α-fetoprotein levels in normal adults. Am J Med Sci 1992; 303(3): 157–159

    Article  CAS  Google Scholar 

  7. Matsui H, Rimal N, Kamakura K, Uesugi S, Yamamoto H, Ikeda S, Taketa K. Serum α-fetoprotein levels in healthy Japanese adults. Acta Med Okayama 1998; 52(3): 149–154

    CAS  PubMed  Google Scholar 

  8. Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M, Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata M. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and non-cirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 1999; 131(3): 174–181

    Article  CAS  Google Scholar 

  9. Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 2005; 25(2): 143–154

    Article  Google Scholar 

  10. Di Bisceglie AM, Hoofnagle JH. Elevations in serum a-fetoprotein levels in patients with chronic hepatitis B. Cancer 1989; 64(10): 2117–2120

    Article  CAS  Google Scholar 

  11. Liaw YF, Tai DI, Chen TJ, Chu CM, Huang MJ. α-fetoprotein changes in the course of chronic hepatitis: relation to bridging hepatic necrosis and hepatocellular carcinoma. Liver 1986; 6(3): 133–137

    Article  CAS  Google Scholar 

  12. Bayati N, Silverman AL, Gordon SC. Serum α-fetoprotein levels and liver histology in patients with chronic hepatitis C. Am J Gastroenterol 1998; 93(12): 2452–2456

    Article  CAS  Google Scholar 

  13. Goldstein NS, Blue DE, Hankin R, Hunter S, Bayati N, Silverman AL, Gordon SC. Serum α-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores. Am J Clin Pathol 1999; 111(6): 811–816

    Article  CAS  Google Scholar 

  14. Chu CW, Hwang SJ, Luo JC, Lai CR, Tsay SH, Li CP, Wu JC, Chang FY, Lee SD. Clinical, virologic, and pathologic significance of elevated serum α-fetoprotein levels in patients with chronic hepatitis C. J Clin Gastroenterol 2001; 32(3): 240–244

    Article  CAS  Google Scholar 

  15. Hu KQ, Kyulo NL, Lim N, Elhazin B, Hillebrand DJ, Bock T. Clinical significance of elevated α-fetoprotein (AFP) in patients with chronic hepatitis C, but not hepatocellular carcinoma. Am J Gastroenterol 2004; 99(5): 860–865

    Article  CAS  Google Scholar 

  16. Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, Nevens F, Solinas A, Mura D, Brouwer JT, Thomas H, Njapoum C, Casarin C, Bonetti P, Fuschi P, Basho J, Tocco A, Bhalla A, Galassini R, Noventa F, Schalm SW, Realdi G. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 1997; 112(2): 463–472

    Article  CAS  Google Scholar 

  17. Sato Y, Nakata K, Kato Y, Shima M, Ishii N, Koji T, Taketa K, Endo Y, Nagataki S. Early recognition of hepatocellular carcinoma based on altered profiles of α-fetoprotein. N Engl J Med 1993; 328(25): 1802–1806

    Article  CAS  Google Scholar 

  18. Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995; 332(22): 1463–1466

    Article  CAS  Google Scholar 

  19. Chen TM, Huang PT, Tsai MH, Lin LF, Liu CC, Ho KS, Siauw CP, Chao PL, Tung JN. Predictors of a-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon α 2a-ribavirin combination therapy. J Gastroenterol Hepatol 2007; 22(5): 669–675

    Article  CAS  Google Scholar 

  20. Murashima S, Tanaka M, Haramaki M, Yutani S, Nakashima Y, Harada K, Ide T, Kumashiro R, Sata M. A decrease in AFP level related to administration of interferon in patients with chronic hepatitis C and a high level of AFP. Dig Dis Sci 2006; 51(4): 808–812

    Article  CAS  Google Scholar 

  21. Tamura Y, Yamagiwa S, Aoki Y, Kurita S, Suda T, Ohkoshi S, Nomoto M, Aoyagi Y; Niigata Liver Disease Study Group. Serum α-fetoprotein levels during and after interferon therapy and the development of hepatocellular carcinoma in patients with chronic hepatitis C. Dig Dis Sci 2009; 54(11): 2530–2537

    Article  CAS  Google Scholar 

  22. Arase Y, Ikeda K, Suzuki F, Suzuki Y, Kobayashi M, Akuta N, Hosaka T, Sezaki H, Yatsuji H, Kawamura Y, Kobayashi M, Kumada H. Prolonged-interferon therapy reduces hepatocarcino-genesis in aged-patients with chronic hepatitis C. J Med Virol 2007; 79(8): 1095–1102

    Article  CAS  Google Scholar 

  23. Asahina Y, Tsuchiya K, Tamaki N, Hirayama I, Tanaka T, Sato M, Yasui Y, Hosokawa T, Ueda K, Kuzuya T, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N, Izumi N. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology 2010; 52(2): 518–527

    Article  CAS  Google Scholar 

  24. Asahina Y, Tsuchiya K, Nishimura T, Muraoka M, Suzuki Y, Tamaki N, Yasui Y, Hosokawa T, Ueda K, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N, Nakagawa M, Kakinuma S, Watanabe M, Izumi N. α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C. Hepatology 2013; 58(4): 1253–1262

    Article  CAS  Google Scholar 

  25. Tachi Y, Hirai T, Ishizu Y, Honda T, Kuzuya T, Hayashi K, Ishigami M, Goto H. α-fetoprotein levels after interferon therapy predict regression of liver fibrosis in patients with sustained virological response. J Gastroenterol Hepatol 2016; 31(5): 1001–1008

    Article  CAS  Google Scholar 

  26. Osaki Y, Ueda Y, Marusawa H, Nakajima J, Kimura T, Kita R, Nishikawa H, Saito S, Henmi S, Sakamoto A, Eso Y, Chiba T. Decrease in α-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study. J Gastroenterol 2012; 47(4): 444–451

    Article  CAS  Google Scholar 

  27. El-Serag HB, Kramer J, Duan Z, Kanwal F. Epidemiology and outcomes of hepatitis C infection in elderly US Veterans. J Viral Hepat 2016; 23(9): 687–696

    Article  CAS  Google Scholar 

  28. El-Serag HB, Kanwal F, Richardson P, Kramer J. Risk of hepatocellular carcinoma after sustained virological response in Veterans with hepatitis C virus infection. Hepatology 2016; 64(1): 130–137

    Article  CAS  Google Scholar 

  29. Takayama K, Furusyo N, Ogawa E, Ikezaki H, Shimizu M, Murata M, Hayashi J. Direct-acting antiviral-based triple therapy on α-fetoprotein level in chronic hepatitis C patients. World J Gastroenterol 2015; 21(15): 4696–4706

    Article  CAS  Google Scholar 

  30. Oze T, Hiramatsu N, Yakushijin T, Miyazaki M, Yamada A, Oshita M, Hagiwara H, Mita E, Ito T, Fukui H, Inui Y, Hijioka T, Inada M, Katayama K, Tamura S, Yoshihara H, Inoue A, Imai Y, Hayashi E, Kato M, Miyagi T, Yoshida Y, Tatsumi T, Kasahara A, Hamasaki T, Hayashi N, Takehara T; Osaka Liver Forum. Post-treatment levels of α-fetoprotein predict incidence of hepatocellular carcinoma after interferon therapy. Clin Gastroenterol Hepatol 2014; 12(7): 1186–1195

    Article  CAS  Google Scholar 

  31. Nguyen K, Jimenez M, Moghadam N, Wu C, Farid A, Grotts J, Elashoff D, Choi G, Durazo FA, El-Kabany MM, Han SB, Saab S. Decrease of α-fetoprotein in patients with cirrhosis treated with direct acting agents. J Clin Transl Hepatol 2017; 5(1): 43–49

    PubMed  PubMed Central  Google Scholar 

  32. Miyaki E, Imamura M, Hiraga N, Murakami E, Kawaoka T, Tsuge M, Hiramatsu A, Kawakami Y, Aikata H, Hayes CN, Chayama K. Daclatasvir and asunaprevir treatment improves liver function parameters and reduces liver fibrosis markers in chronic hepatitis C patients. Hepatol Res 2016; 46(8): 758–764

    Article  CAS  Google Scholar 

  33. Fouad R, Elsharkawy, A, Alem SA, EL, Kassas, M, Alboraie M, Sweedy A, Afify S, Abdellatif Z, Khairy M, Esmat G. Clinical impact of serum α-fetoprotein and its relation on changes in liver fibrosis in hepatitis C virus patients receiving direct-acting antivirals. Eur J Gastroenterol Hepatol 2019 Mar 20. [Epub ahead of print] doi:https://doi.org/10.1097/MEG.0000000000001400

    Article  CAS  Google Scholar 

  34. Huynh T, Zhang J, Hu KQ. Hepatitis C virus clearance by direct acting antiviral results in rapid resolution of hepatocytic injury as indicated by both alanine aminotransferase and aspartate aminos-transferase normalization. J Clin Transl Hepatol 2018; 6(3): 258–263

    PubMed  PubMed Central  Google Scholar 

  35. Di Bisceglie AM, Sterling RK, Chung RT, Everhart JE, Dienstag JL, Bonkovsky HL, Wright EC, Everson GT, Lindsay KL, Lok AS, Lee WM, Morgan TR, Ghany MG, Gretch DR; HALT-C Trial Group. Serum α-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C Trial. J Hepatol 2005; 43(3): 434–441

    Article  CAS  Google Scholar 

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Acknowledgements

The authors want to thank Drs. Johnathan Zhang and Mohit Mittal for their contribution on data collection.

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Authors and Affiliations

  1. Department of Pharmacy, University of California, Irvine, School of Medicine, Orange, CA, 92868, USA

    Tung Huynh

  2. Division of Gastroenterology and Hepatology, University of California, Irvine, School of Medicine, Orange, CA, 92868, USA

    Ke-Qin Hu

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Correspondence to Ke-Qin Hu.

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Tung Huynh and Ke-Qin Hu declare that they have no conflict of interest related to this study. This retrospective study included human subjects and was conducted after approval by our IRB. This study was an investigator-initiated study, and no external funding in any source has been obtained. Tung Huynh has nothing to disclose. Dr. Hu is on speaker bureau for Gilead Sciences.

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Huynh, T., Hu, KQ. Direct acting antiviral-induced dynamic reduction of serum α fetoprotein in hepatitis C patients without hepatocellular carcinoma. Front. Med. 13, 658–666 (2019). https://doi.org/10.1007/s11684-019-0707-7

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