Journal of Surgical Oncology 2014;110:976–981

Outcomes After Curative Hepatectomy in Patients with Non-B Non-C Hepatocellular Carcinoma And Hepatitis B Virus Hepatocellular Carcinoma From Non-Cirrhotic Liver JONG MAN KIM, MD, PhD,1 CHOON HYUCK DAVID KWON, MD, PhD,1 JAE-WON JOH, MD, PhD,1* JAE BERM PARK, MD, PhD,1 JOON HYEOK LEE, MD, PhD,2 SUNG JOO KIM, MD, PhD,1 SEUNG WOON PAIK, MD, PhD,2 CHEOL KEUN PARK, MD, PhD,3 AND BYUNG CHUL YOO, MD, PhD2 1

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

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Backgrounds and Objective: There is controversy regarding liver function of non‐B, non‐C hepatocellular carcinoma (NBNC‐HCC) patients, the biological behavior of their tumors, and the outcome after surgical treatment. The aims of the present study were to compare clinicopathologic data and long‐term clinical outcomes between NBNC‐HCC patients and hepatitis B virus HCC (HBV‐HCC) patients from non‐cirrhotic liver after curative hepatectomy. Methods: Data for HBV‐HCC patients (n ¼ 360) and NBNC‐HCC patients (n ¼ 103) were retrospectively reviewed. Results: The median age of patients in the NBNC group was significantly higher than that of the HBV group (63 years vs. 53 years, P < 0.001). Tumor size in the NBNC group was greater than that in the HBV group (5.1 cm vs. 3.8 cm, P < 0.001). Regarding liver histology, the grade of lobular activity, periportal activity, and fibrosis in the HBV group was higher than in the NBNC group (P < 0.001, P < 0.001, and P < 0.001, respectively). There were no statistically significant differences in disease‐free survival and overall survival between the two groups (P ¼ 0.257 and P ¼ 0.579, respectively). Multivariate analysis showed that increased tumor size, microvascular invasion, and intrahepatic metastasis were associated with tumor recurrence after curative liver resection. Conclusion: For patients with non‐cirrhotic liver, clinical outcomes for NBNC‐HCC were comparable to those for HBV‐HCC after curative hepatectomy.

J. Surg. Oncol. 2014;110:976–981. ß 2014 Wiley Periodicals, Inc.

KEY WORDS: hepatocellular carcinoma; hepatectomy; non‐cirrhosis; non B non C; hepatitis B virus; prognosis tumor sizesurvival; tumor recurrence

INTRODUCTION In many Asian countries, the majority cases of hepatocellular carcinoma (HCC) are attributable to hepatitis B virus (HBV)‐related chronic liver disease [1–3]. The oncogenic mechanisms and clinicopathologic characteristics of HCC are strongly influenced by HBV infection [3]. Surgical resection remains the best therapeutic option for HCC patients with early‐stage tumor and well‐preserved liver function [4]. For areas in which HBV infection is prevalent, the incidence of HBV‐ related HCC is decreasing because more than 90% of countries worldwide have introduced HBV vaccine into their national infant immunization schedules, thus dramatically decreasing the incidence of HBV‐related HCC [5]. Although most cases of HCC are still associated with HBV infection, the frequency of HBV surface antigen (HBsAg)‐ negative/HCV antibody (HCVAb)‐negative HCC (NBNC‐HCC) has been reported to be 4–15%, and the number and proportion of cases of NBNC‐HCC have been increasing gradually in Korea and Japan [6–8]. The characteristics and prognosis of HCC in these patients differ from those in patients with chronic hepatitis virus infection. Several studies have reported that patients with NBNC‐HCC have a poorer prognosis than those with HBV‐HCC because tumors in NBNC‐HCC patients are often detected incidentally at an advanced stage without follow‐ up [8–10]. However, HBV might negatively affect HCC recurrence or death rates through enhanced disease progression or liver deterioration after surgical resection.

ß 2014 Wiley Periodicals, Inc.

Although several studies have compared the clinicopathologic features of patients with NBNC‐HCC and HBV‐related HCC [8,11], controversy remains regarding the liver function of NBNC‐HCC patients, the biological behavior of their tumors, and the outcome after surgical treatment. Furthermore, the differences between NBNC‐HCC and HBV‐HCC are poorly defined. In general, HBV‐infected patients have liver cirrhosis caused by viral infection, and cirrhosis is considered a primary risk factor for developing HCC [12]. This study focused on HCC from non‐cirrhotic livers: cirrhotic patients were specifically excluded to eliminate the influence of underlying liver function.

Author’s Contribution: Jong Man Kim: Design, acquisition of data, analysis and interpretation of data. Jae‐Won Joh: Design and interpretation of data. Choon Hyuck David Kwon, Jae Berm Park, Joon‐Hyeok Lee, Sung Joo Kim, Seoung Woon Paik, Cheol Keun Park, Byung Chul Yoo: Acquisition of data and analysis of data. Conflicts of interest: The authors have no conflicts of interest to disclose. *Correspondence to: Jae‐Won Joh, MD, PhD, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Irwon‐Dong Gangnam‐Gu, Seoul 135‐710, Korea. Fax: þ82‐2‐3410‐ 0040. E‐mail: [email protected] Received 10 June 2014; Accepted 5 August 2014 DOI 10.1002/jso.23772 Published online 29 August 2014 in Wiley Online Library (wileyonlinelibrary.com).

NBNC‐HCC and HBV‐HCC in Non‐Cirrhosis The aims of the present study were to compare clinicopathologic data and long‐term clinical outcomes between patients with NBNC‐ HCC and HBV‐HCC from non‐cirrhotic liver after curative hepatectomy and to determine the risk factors for recurrence after hepatectomy in HCC.

MATERIALS AND METHODS Patients This study included 1,158 patients undergoing surgical resection of HCC between January 2005 and December 2010. The exclusion criteria were as follows: mixed HCC and cholangiocarcinoma on pathology; etiologies other than HBV and NBNC;

Outcomes after curative hepatectomy in patients with non-B non-C hepatocellular carcinoma and hepatitis B virus hepatocellular carcinoma from non-cirrhotic liver.

There is controversy regarding liver function of non-B, non-C hepatocellular carcinoma (NBNC-HCC) patients, the biological behavior of their tumors, a...
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