Title: Hepatocellular carcinoma in patients without advanced fibrosis after eradication of HCV with antiviral treatment

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Title: Hepatocellular carcinoma in patients without advanced fibrosis after eradication of HCV with antiviral treatment Authors: Yolanda Sánchez-Torrijos, Jara Eloísa Ternero Vega, Carmen Cepeda Franco DOI: 10.17235/reed.2017.4677/2016 Link: PubMed (Epub ahead of print) Please cite this article as: Sánchez-Torrijos Yolanda, Ternero Vega Jara Eloísa, Cepeda Franco Carmen. Hepatocellular carcinoma in patients without advanced fibrosis after eradication of HCV with antiviral treatment. Rev Esp Enferm Dig 2017. doi: 10.17235/reed.2017.4677/2016. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

CE 4677 inglés Hepatocellular carcinoma in patients without advanced fibrosis after eradication of HCV with antiviral treatment Yolanda Sánchez-Torrijos 1, Jara Eloísa Ternero-Vega 2 and Carmen Cepeda-Franco 1 1 Clinical Management Unit of Digestive Diseases. Hospital Universitario Virgen del Rocío. Sevilla, Spain. 2 Internal Medicine Unit. Hospital Universitario Virgen del Rocío. Sevilla, Spain Correspondence: Yolanda Sánchez-Torrijos e-mail: yolandas_st@hotmail.com Dear Editor, This study was performed to demonstrate the difficulties recently found with regard to screening for hepatocellular carcinoma (HCC) in patients treated with the hepatitis C virus (HCV). The new antiviral resources will result in a larger number of patients with a sustained virological response (SVR) and low fibrosis in the future. This creates uncertainty concerning the monitoring of these patients. Case report We present the case of a 49-year-old male with hepatopathy HCV (genotype 1b). A biopsy was performed in 2006 which showed chronic active hepatitis, METAVIR A2, F2, and a viral load (VL) of 117,342 Ul/ml. The patient received IFN-α and ribavirin with SVR, and underwent annual blood tests which were normal. In January 2014, the patient experienced abdominal pain and the blood parameters were as follows: GOT 105 U/l, GPT 38 U/l, GGT 105 U/l and α-fp 45,232 ng/ml. The VL remained negative. An ultrasound scan detected a lesion suspicious of HCC (14 x 12.5 cm) that was confirmed by triphasic CT. The extension study was negative. A hepatectomy was performed and the histological study identified HCC (23 cm) with angioinvasion that did not reach the resection margins. There was no inflammatory activity in the rest of liver and there

was expansive portal fibrosis (METAVIR A0, F2). One month later, the α-fp levels were 433 ng/ml and tumor relapse was found on CT. The patient was treated with sorafenib. Discussion The annual risk of HCC with HCV is about 3.4%. Alcohol, metabolic syndrome, age > 50, α-fp > 8 ng/ml and GPT > 40 U/l (1) are risk factors in patients with SVR. In this case, these factors were absent. The current guidelines recommend screening for HCC in chronic hepatitis HCV stage F3 (2,3). Furthermore, SVR is associated with the regression of fibrosis (4) and the reduction of HCC incidence (5). A study identified controversial outcomes related to the development of HCC in patients with SVR, and there was a significant amount of HCC in the lower-intermediate stages of fibrosis. According to the European Association for the Study of the Liver (EASL) (3), monitoring is not required for patients without advanced fibrosis with SVR. This case could represent an exception as the histological section from the hepatectomy procedure showed grade 2 fibrosis. SVR rates of 90-95% are being reached due to the new therapies. However, the screening protocol after treatment has not yet been established (3). Cases such as the one described here highlight the need to keep monitoring lower-intermediate fibrosis. References 1. Yamashita N, Ohho A, Yamasaki A, et al. Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained virological response to interferon: Significance of lifelong periodic cancer screening for improving outcomes. J Gastroenterol 2014;49:1504-13. DOI: 10.1007/s00535-013-0921-z 2. Bruix J, Sherman M. Management of hepatocellular carcinoma: An update. AASLD Practice guideline. Hepatol 2011;53(3):1020-2. DOI: 10.1002/hep.24199 3. European Association for the Study of the Liver. European Organization for Research and Treatment of Cancer Clinical Practice Guidelines: Management of Hepatocellular Carcinoma. J Hepatol 2012;56:908-43. DOI: 10.1016/j.jhep.2011.12.001 4. Poynard T, Yuen M-F, Ratziu V, Lai CL. Viral hepatitis C. Lancet 2003;362:2095-100. DOI: 10.1016/S0140-6736(03)15109-4

5. Van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA 2012;308(24):258. DOI: 10.1001/jama.2012.144878 Fig. 1. Hepatectomy.