Clinical features of resected hepatocellular carcinoma emerging after sustained virological response against chronic hepatitis C Hepato-biliary-pancreatic Surgery Divion, Department of Surgery, Tokyo Metropolitan Bokutoh Hospital Baongoc Pham, Yasuji Seyama, Junichi Shindoh, Masaki Matsuda, Dai Shida, Tsuyoshi Maeshiro, Sachio Miyamoto, Satoru Inoue, Nobutaka Umekita

Introduction Progress in anti-viral therapy for hepatitis C have markedly improved sustained virological response (SVR) rate and might reduce the risk of carcinogenesis of hepatocellular carcinoma (HCC). However, there still remain sporadic reports of HCC emerging after SVR. By retrospectively studying the clinical courses of resected cases for HCC occurring after obtained SVR, we discuss the clinical factor of SVR in HCC treatment

Materials and Methods 121 HCC resections in this 10 years ⇒ 62 resections (51%) are positive for hepatitis C ⇒ 18 resections with interferon treatment history 7 resections (5 patients) with HCC obtained SVR Analyze the clinical course after resection.

Patients Background 4 men, 1 woman 67 years old in average (range 63-74), All cases were negative for HBsAg, No history of alcoholic abuse, Only 1case complicated with diabetes mellitus.

Clinical course１： SVR⇒hepatectomy Case 1：74 y.o、woman Hepatectomy ①2007 SVR 1996 132 months 48 months No recurrence Alive ICG R15 18.1% Case 2:69 y.o、woman Hepatectomy ①2010 SVR 2004 72 months 12 months No recurrence Alive ICG R15 4.2% Case 3：63 y.o、man SVR 2008 Hepatectomy ①2009 Hepatectomy ② 2010 12 months 12 months 12 months No recurrence Alive ICG R15 7.9% ICG R15 10.4%

Clinical course ２： Hepatectomy⇒SVR⇒hepatectomy Case 4：64y.o、man Hepatectomy ①2001 Hepatectomy ②2008 SVR 2003 60 months 34 months No recurrence Alive ICG R15 8.0% ICG R15 7.8% Case 5：70y.o、man Hepatectomy ①2003 Hepatectomy ②2007 Hepatectomy ③2008 SVR 2005 24 months 12 months ICG R15 25.3% ICG R15 8.3% ICG R15 8.8% 39 months No recurrence Alive

Repeated resections after SVR Case 3 Hepatectomy ①2009 Hepatectomy ②2010 SVR 2008 12 months Partial hepatectomy of S6 Systematic hepatectomy of S6

Repeated resections after SVR Case 5 Hepatectomy ①2003 Hepatectomy ②2007 SVR 2005 Hepatectomy ③2008 12 months Partial hepatectomy of S8 Partial hepatectomy of S8

Pathological findings of tumors (7 resections) Number of tumors single 6, two 1 Average size of tumors 19mm (10-24mm) Vascular invasion 0/7 Histological findings Well differentiated type　 2 cases, Moderately differentiated type 4 cases, Poorly differentiated type　 1case Clinical stage fStage 1 3 cases fStage 2 4 cases

Pathology of resected liver background Case 1：74y.o、woman Hepatectomy ①2007 SVR 1996 F4 A2 Case 2:69y.o、woman Hepatectomy ①2010 F3 A2 SVR 2004 Case 3：63y.o、man Hepatectomy ①2009 F3 A2 Hepatectomy ②2010 F3 A1 SVR 2008

Pathology of resected liver background before and after SVR Case 4： 64y.o、man Hepatectomy ①2001 Hepatectomy ②2008 SVR 2003 F2/3 A2 F2/1 A1 Case 5：70y.o、man Hepatectomy ①2003 Hepatectomy ②2007 Hepatectomy ③2008 SVR 2005 F1 A2 F1 A1 F1 A1

Clinical progress and Prognosis All cases are alive without recurrence since the last hepatectomy. Average observation period 972 days （range 198～1772 days）.

Summary Average time since SVR till carcinogenesis 50.3 months （range 2-132 months）. Liver function is well preserved Average tumor size: 19mm, lesser than fStage2. Grade of fibrosis showed no change, but activity of hepatitis improved. Both recurrent HCCs after SVR emerged within the same segment. All cases are alive without relapse.

Discussion Carcinogenic mechanism after obtained SVR Early HCC existed prior to SVR. Latent infection of HBV. Alcoholic hepatitis. Carcinogenic risk of liver fibrosis itself. Steatohepatitis. Systematic hepatectomy is favorable. Require long term follow up.

Conclusions HCC recurrence may emerge even after hepatectomy in HCV-hepatitis patients obtained SVR. However, with well preserved liver function, prognosis is good. Carcinogenesis in SVR cases suggests the possibility that systematic hepatectomy is effective.