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Liver Resection for Hepatocellular Carcinoma on Cirrhosis: Univariate and Multivariate Analysis of Risk Factors for Intrahepatic Recurrence

Ercolani, Giorgio MD*; Grazi, Gian Luca MD*; Ravaioli, Matteo MD*; Del Gaudio, Massimo MD*; Gardini, Andrea MD*; Cescon, Matteo MD*; Varotti, Giovanni MD*; Cetta, Francesco MD†; Cavallari, Antonino MD*

Original Articles

Objective: To evaluate prognostic factors that could affect disease-free survival and recurrence after liver resection for hepatocellular carcinoma (HCC) on cirrhosis.

Summary Background Data: Tumor recurrence is the main cause of poor survival after liver resection for HCC on cirrhosis.

Methods: Two hundred twenty-four liver resections for HCC on cirrhosis were retrospectively reviewed. Univariate and multivariate analyses were performed on several clinicopathologic variables to analyze factors affecting long-term outcome and intrahepatic recurrence. The relation between preoperative aminotransferase level and recurrence rate was evaluated in the overall group, and separately in HCV-positive and in HBsAg-positive patients. Median follow-up was 35.6 months.

Results: The 1-, 3-, and 5-year overall survival rates were 83%, 62.8%, and 42.5%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 70.3%, 43%, and 27.4%, respectively. The 1-, 3-, and 5-year recurrence rates were 20.8%, 38.6%, and 54.4% respectively. Tumor recurrence appeared in 93 patients (41.5%) and was the main cause of death in 51 patients (56%). Number of nodules, tumor capsule, microvascular portal vein thrombosis, and preoperative serum aspartate aminotransferase (AST) level significantly affected disease-free survival and recurrence rates. On multivariate analysis, single nodules and preoperative AST level less than twice normal (2N) were related to a better 5-year disease-free survival and lower tumor recurrence. In particular, among HCV-positive patients the recurrence rate was strongly affected by the preoperative AST level.

Conclusions: Child A patients with single nodules are the best candidates for liver resection. Tumor recurrence is strictly linked to the status of the underlying liver disease, and a preoperative AST level equal to 2N seems to be a sensitive cutoff among patients with different risks of recurrence. HCV-positive patients with AST levels above 2N have the highest risk for intrahepatic recurrence and should be monitored carefully or offered alternative treatments.

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world 1 and is related to hepatitis B or C virus infection in 80% of cases. 1,2 Because of recent progress in early diagnosis and operative technique, results after liver resection have improved, with a 5-year survival rate of up to 50% and a mortality rate of less than 2%. 3,4 However, long-term survival remains unsatisfactory because of the high incidence of tumor recurrence (the main cause of poor prognosis), which ranges from 60% to 100% at 5 years. 5–8 To improve the surgical result for HCC and to evaluate whether any adjuvant treatment might be useful and prolong disease-free survival, it is of paramount importance to elucidate the presence of possible risk factors for recurrence.

It has been already shown that patients with high preoperative serum aminotransferase levels are at increased risk for postoperative morbidity and mortality after liver resection. 9,10 Recently, Japanese authors have reported that cirrhotic patients with serum aminotransferase levels persistently greater than twice the normal levels (2N) are at high risk for HCC. 11 However, the role of preoperative aminotransferase levels as an index of long-term prognosis in resected patients is still unknown.

We retrospectively reviewed our experience with 224 liver resections for HCC on cirrhosis to evaluate prognostic factors that might affect disease-free survival and recurrence rates. Special care was taken to analyze the relationship between preoperative aminotransferase levels, as an index of chronic active hepatitis and liver inflammation, and tumor recurrence in the global series and separately in HCV-positive and in HBsAg-positive patients.

From the *Department of Surgery and Transplantation, Surgical Unit, S. Orsola Hospital, University of Bologna, Italy, and the

†Department of Surgery, University of Siena, Italy

Correspondence: Gian Luca Grazi, MD, Department of Surgery and Transplantation, Surgical Unit, S. Orsola Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.


Accepted for publication September 11, 2002.

© 2003 Lippincott Williams & Wilkins, Inc.