Elsevier

Hepatology Research

Volume 20, Issue 3, July 2001, Pages 301-311
Hepatology Research

Interferon alpha inhibits intrahepatic recurrence in hepatocellular carcinoma with chronic hepatitis C: a pilot study

https://doi.org/10.1016/S1386-6346(00)00148-0Get rights and content

Abstract

The aim of the present study is to evaluate whether interferon alpha (IFNα) therapy can inhibit intrahepatic recurrence after the curative treatment of small HCC with underlying chronic hepatitis C. Forty patients were enrolled in this study. They had solitary, small HCC≤3 cm in diameter, underlying chronic hepatitis C, and were ≤70 years old. Of the patients, 18 were treated with IFNα for 6 months after the treatment of HCC, and 22 patients who did not receive IFNα therapy were used as controls. Six (33%) patients in the IFN group showed sustained response. The incidence of local recurrence was not different in the IFN and non-IFN groups (6 vs. 9%). The cumulative incidences of distant recurrence in the non-IFN and IFN groups were 9 and 6% at 1 year, 27 and 11% at 2 years, 63 and 18% at 3 years, 76 and 28% at 4 years, and 82 and 28% at 5 years; they were significantly different (P<0.01). Six (27%) patients in the non-IFN group died from the progression of HCC, but all IFN-treated patients were alive (P<0.05). The pilot study demonstrates that IFNα therapy after the curative treatment of small HCC can inhibit intrahepatic recurrence in the remnant liver and improve the prognosis of hepatitis C virus-related HCC.

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignant neoplasms, and its incidence is increasing world-wide, especially in Japan [1], [2], [3]. Recent progress in diagnostic and therapeutic modalities has made it possible to detect small HCCs and to treat them curatively with hepatic resection or percutaneous ethanol injection therapy (PEIT). However, the long-term survival of patients after curative treatment of small hepatocellular carcinoma (HCC) is far from satisfactory because of the high incidence of intrahepatic recurrence [4], [5], [6], [7], [8], [9], [10]. Intrahepatic recurrence occurs in one of three patterns: (1) local recurrence occurring in or adjacent to the treated lesion, (2) intrahepatic metastasis from the main tumor via the portal system, or (3) new HCC of multicentric origin occurring in the remnant liver. Local recurrence and intrahepatic metastasis are related to tumor factors, including tumor size, tumor number, portal venous invasion, and histological degree of tumor cell differentiation [4], [5], [7], [9], [10]. Intrahepatic recurrence after the curative treatment of small HCC without distinct tumor factors is considered to be a multicentric occurrence in the remnant liver with persistent infection of hepatitis B virus or hepatitis C virus (HCV).

Treatment with interferon alpha (IFNα) is effective in decreasing serum alanine aminotransferase (ALT) levels, improving hepatic necroinflammation and fibrosis, and further removing serum HCV RNA in chronic hepatitis C [11], [12], [13], [14], [15], [16]. Also, IFNα therapy can inhibit the development of HCC in patients with chronic hepatitis C and HCV-related liver cirrhosis [17], [18], [19], [20], [21], [22]. These findings suggest that IFNα therapy after the treatment of small HCV-related HCC can inhibit multicentric occurrence. In the present study, we evaluated whether IFNα therapy can inhibit intrahepatic recurrence after the curative treatment of small HCC with underlying chronic hepatitis C.

Section snippets

Patients

Between October 1990 and March 1998, a total of 988 Japanese patients with HCV-related HCC (positive for HCV antibody and negative for hepatitis B surface antigen) were admitted to the Second Department of Internal Medicine, Tottori University Hospital and its affiliated hospitals. Of these patients, 264 had solitary, small HCC≤3 cm in diameter without portal venous invasion, and were curatively treated with hepatic resection or PEIT. Fifty-four patients had underlying chronic hepatitis without

Response to IFN therapy

All IFN treated patients tolerated IFNα therapy. Of the 18 patients, six (33%) were sustained responders, seven (39%) were transient responders, and five (28%) were non-responders. All sustained responders had HCV genotype 1b, and five of these patients had serum HCV RNA levels <106 equiv./ml. On the other hand, all non-IFN treated patients had abnormal ALT levels and positive HCV RNA during the observation period.

Incidence of intrahepatic recurrence

The incidences of intrahepatic recurrence and death in the patients are shown in

Discussion

Previous reports have shown that intrahepatic recurrence after the curative treatment of small HCC was very frequent, ranging from 12 to 27% after 1 year, 38 to 58% after 2 years, 57 to 74% after 3 years, 65 to 87% after 4 years, and 68 to 96% after 5 years [5], [6], [8], [9], [10]. It is known that tumor factors, such as tumor size, tumor number, histological degree of tumor cell differentiation, or serum α-fetoprotein level, are risk factors for intrahepatic recurrence after the treatment of

Acknowledgements

This study was partially supported by the special research fund of Tottori Prefecture Health Promoting Council.

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