Abstract
An 82-year-old man presented with hepatocellular carcinomas (HCCs) 24 years after achieving a sustained virological response (SVR) to an interferon for hepatitis C. His hepatic fibrosis stage was F1 when he was treated at 58 years. He was followed-up by annual blood tests and abdominal ultrasonography or computed tomography. After the IFN treatment, he had drunk approximately 100 g of ethanol. Serum aspartate aminotransferase and gamma-glutamyl transpeptidase levels had been elevated since 2012. To investigate the possible factors that affect hepatocarcinogenesis over 10 years after achieving an SVR, we reviewed the literature. Of 39 reported patients, 26, as well as ours, had one or more lifestyle-related factors, including body mass index ≥ 25 kg/m2, diabetes mellitus, impaired glucose tolerance, hepatosteatosis, or alcohol consumption. In our patient, aging and daily alcohol consumption might have triggered the development of HCCs.
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Abbreviations
- HCV:
-
Hepatitis C virus
- HCC:
-
Hepatocellular carcinoma
- IFNs:
-
Interferons
- SVR:
-
Sustained virological response
- DEB-TACE:
-
Drug-eluting beads transcatheter arterial chemoembolization
- CT:
-
Computed tomography
- BMI:
-
Body mass index
- HBsAg:
-
Hepatitis B surface antigen
- HBcAb:
-
Hepatitis B core antibody
- AST:
-
Aspartate aminotransferase
- ALT:
-
Alanine aminotransferase
- GGT:
-
Gamma-glutamyl transpeptidase
- AFP:
-
Alpha-fetoprotein
- BCLC:
-
Barcelona clinic liver cancer
- M2BPGi:
-
Mac-2 binding protein glycosylation isomer
- AUROC:
-
Area under the receiver-operating characteristic curve
- COI:
-
Cut-off index
References
Tada T, Kumada T, Toyoda H, et al. Viral eradication reduces all-cause mortality, including non-liver-related disease, in patients with progressive hepatitis C virus-related fibrosis. J Gastroenterol Hepatol. 2017;32:687–94.
Makiyama A, Itoh Y, Kasahara A, et al. Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy. Cancer. 2004;101:1616–22.
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;64:130–37.
Iwasaki Y, Takaguchi K, Ikeda H, et al. Risk factors for hepatocellular carcinoma in hepatitis C patients with sustained virologic response to interferon therapy. Liver Int. 2004;24:603–10.
Igarashi G, Endo T, Sawada N, et al. Development of hepatocellular carcinoma in chronic hepatitis c patients 20 years after achieving a sustained virological response with interferon therapy: a report of two cases. J Gen Fam Med. 2015;16:199–203.
Okabe J, Fukuda K, Iwamoto T, et al. A case of cirrhosis with hepatitis C virus infection developing hepatocellular carcinoma 20 years after achieving sustained virological response to interferon therapy. Kanzo (Acta Hepatol Jpn). 2016;57:27–33 (in Japanese, abstract in English).
Nakayama H, Iketani S, Okamoto D, et al. Long-term prognosis of patients with chronic hepatitis C who developed hepatocellular carcinoma after a sustained response to interferon therapy. Iwaki Kyoritsu Byoin Ihou (J Iwaki Kyoritsu Gen Hosp). 2013;34:12–21 (in Japanese).
Harai S, Kuratomi N, Fukazawa Y, et al. A case of hepatocellular carcinoma with portal vein tumor thrombosis and bone metastasis developed 20 years after successful interferon therapy to hepatitis C. Yamanashi Kenritsu Chuo Byoin Nenpo (J Yamanashi-ken Central Hosp. 2015; 41:68–70 (in Japanese).
Hirohata Y, Yoh Y, Nakamura Y, Kato T, Okamura R. Surgical treatment for hepatocellular carcinoma in a chronic hepatitis C patient 20 years after achieving a sustained virological response. Nippon Shokaki Geka Gakkai Zasshi (Jpn J Gastroenterol Surg). 2017;50:528–34 (in Japanese, abstract in English).
Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–93.
Kuno A, Ikehara Y, Tanaka Y, et al. A serum “sweet-doughnut” protein facilitates fibrosis evaluation and therapy assessment in patients with viral hepatitis. Sci Rep. 2013;3:1065.
Nagata H, Nakagawa M, Nishimura-Sakurai Y, et al. Serial measurement of Wisteria floribunda agglutinin positive Mac-2-binding protein is useful for predicting liver fibrosis and the development of hepatocellular carcinoma in chronic hepatitis C patients treated with IFN-based and IFN-free therapy. Hepatol Int. 2016;10:956–64.
Sato T, Okada M, Masumoto A, Takeda N. A case of surgical treatment for hepatocellular carcinoma occurred 10 years after a successful interferon therapy in a patient with chronic hepatitis C. Rinsho to Kenkyu (Jpn J Clin Exp). 2005;82:342–43. (in Japanese).
Kobayashi M, Suzuki M, Yamada N, et al. A case of hepatocellular carcinoma developed ten years after successful interferon therapy for chronic hepatitis C. Sei Marianna Ika Daigaku Zasshi (St Marianna Med J). 2006;34:115–23 (in Japanese, abstract in English).
Sugunami F, Tomiyama Y, Ohmoto K, et al. Hepatocellular carcinoma occurring after 11 year-long sustained viral response to interferon therapy for chronic hepatitis C. Nippon Shokakibyo Gakkai Zasshi (Jpn J Soc Gastroenterol). 2007;104:809–14. (in Japanese, abstract in English).
Kimura Y, Tsuji K, Matsui T, et al. A case of synchronous double cancer of liver metastasis of thymoma and hepatocellular carcinomas, 10 years after achieving sustained virological response treated with peginterferon/ribavirin in chronic hepatitis C virus infection. Kanzo (Acta Hepatol Jpn). 2016;57:252–59 (in Japanese, abstract in English).
Hanaoka J, Shimada M, Ikegami T, et al. A case of surgical treatment for hepatocellular carcinoma that developed in a chronic hepatitis C patient who had shown sustained virological response to interferon 11 years before. Kanzo (Acta Hepatol Jpn). 2008;49:248–54 (in Japanese, abstract in English).
Nojiri K, Sugimoto K, Shiraki K, et al. Development of hepatocellular carcinoma in patients with chronic hepatitis C more than 10 years after sustained virological response to interferon therapy. Oncol Lett. 2010;1:427–30.
Ito Y, Yamamoto N, Nakata R, et al. Delayed development of hepatocellular carcinoma during long-term follow-up after eradication of hepatitis C virus by interferon therapy. World J Gastroenterol. 2005;11:7218–21.
Kawano Y, Egami K, Sasajima K, et al. A hepatocellular carcinoma developed following 12 years from sustained virologic response to interferon therapy in a patient with hepatitis C. Kanzo (Acta Hepatol Jpn). 2007;48:48–56 (in Japanese, abstract in English).
Hayashi T, Tamori A, Nishikawa M, et al. Differences in molecular alterations of hepatocellular carcinoma between patients with a sustained virological response and those with hepatitis C virus infection. Liver Int. 2009;29:126–32.
Sanefuji K, Kayashima H, Iguchi T, et al. Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C. J Surg Oncol. 2009;99:32–7.
Tsumura T, Takaki S, Aikata H, et al. A case of double cancer of the liver, cholangiocarcinoma and hepatocellular carcinoma detected in a patient with hepatitis C 13 years after diminution of HCV-RNA by interferon treatment. Nippon Shokakibyo Gakkai Zasshi (Jpn J Soc Gastroenterol). 2009;106:674–583 (in Japanese, abstract in English).
Yagura M, Tanaka A, Kamitsukasa H. A case of hepatocellular carcinoma who cleared hepatitis C virus with interferon therapy 13 years ago. Kanzo (Acta Hepatol Jpn). 2009;50:238–43 (in Japanese, abstract in English).
Mashitani T, Yoshiji H, Yamazaki M, et al. Development of hepatocellular carcinoma in a patient 13 years after sustained virological response to interferon against chronic hepatitis C: a case report. Cases J. 2009;2:18.
Bertolini E, Bassi F, Fornaciari G. Deveopment of hepatocellular carcinoma in a non-cirrhotic, long-term responder to antiviral therapy, chronic hepatitis C patient: what kind of surveillance? Ann Gastroenterol. 2013;26:80–3.
Watanabe E, Koizumi Y, Hirooka M, et al. Hepatocellular carcinoma in a chronic hepatitis C patient 15 years after achieving a sustained virological response. Kanzo (Acta Hepatol Jpn). 2012;53:763–68 (in Japanese, abstract in English).
Higuchi R, Yasuda H, Koda K, et al. Hepatocellular Carcinoma Development in Hepatitis-C-Sustained Virological Response to Interferon-Based Therapy After 15-Year Follow-Up. Nippon Gekakei Rengo Gakkaishi (J Jpn Coll Surgeons). 2011;36:66–71 (in Japanese, abstract in English).
Takeuchi N, Tada H, Nishida Y, et al. Rapid growing hepatocellular carcinoma in a patient with chronic hepatitis C after 16 years of a sustained and complete response to interferon therapy. Kan Tan Sui. 2011;63:699–705 (in Japanese).
Saito M, Seo Y, Yano Y, et al. Development of a hepatocellular carcinoma in a chronic hepatitis C patient 18 years after achieving a sustained virological response to interferon therapy: case report and literature review. Clin J Gastroenterol. 2012;5:119–26.
Ohshima K, Oba N, Kyoden Y, Iseki J, et al. A case of surgical treatment for hepatocellular carcinoma detected in a patient with chronic hepatitis C who had shown sustained virological response (SVR) to interferon 19 years before. Liver Cancer (Tokyo). 2012;18:23–35 (in Japanese, abstract in English).
Toyoda H, Tada T, Takaguchi K, et al. Differences in background characteristics of patients with chronic hepatitis C who achieved sustained virologic response with interferon-free versus interferon-based therapy and the risk of developing hepatocellular carcinoma after eradication of hepatitis C virus in Japan. J Viral Hepat. 2017;24:472–76.
Asahina Y, Tsuchiya K, Nishimura T, et al. alpha-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C. Hepatology. 2013;58:1253–62.
Nirei K, Matsumura H, Kumakawa M, et al. Steatosis influences the clinical profiles and long-term outcomes of interferon-treated chronic hepatitis C and liver cirrhosis patients. Int J Med Sci. 2017;14:45–52.
Nanba S, Ikeda F, Baba N, et al. Association of hepatic oxidative stress and iron dysregulation with HCC development after interferon therapy in chronic hepatitis C. J Clin Pathol. 2016;69:226–33.
Whitfield JB, Zhu G, Heath AC, et al. Effects of alcohol consumption on indices of iron stores and of iron stores on alcohol intake markers. Alcohol Clin Exp Res. 2001;25:1037–45.
Ikeda K, Marusawa H, Osaki Y, et al. Antibody to hepatitis B core antigen and risk for hepatitis C–related hepatocellular carcinoma: a prospective study. Ann Int Med. 2007;146:649–56.
Kusumoto S, Tanaka Y, Mizokami M, et al. Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma. Int J Hematol. 2009;90:13–23.
Acknowledgements
This study was supported by a Grant from the Ministry of Health, Labour and Welfare, Japan (H28-kansei-ippan-001).
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Yoshida, Y., Yonezawa, M., Okamoto, T. et al. Occurrence of hepatocellular carcinoma 24 years after successful interferon therapy in a patient with chronic hepatitis C: a case report. Clin J Gastroenterol 12, 120–127 (2019). https://doi.org/10.1007/s12328-018-0915-8
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DOI: https://doi.org/10.1007/s12328-018-0915-8