Development of hepatocellular carcinoma in patients with chronic hepatitis C more than 10 years after sustained virological response to interferon therapy

Abstract

Abstract. The risk factors for the development of hepatocellular carcinoma (HCC) in patients who have achieved a long-term sustained viral response (SVR) to interferon (IFN) are not fully understood. This study aimed to investigate the characteristics of patients who developed HCC after 10 years of achieving SVR. We retrospectively studied 5 patients with HCC which developed more than 10 years after the termination of IFN therapy. The clinical characteristics at the induction of IFN therapy were male gender, a mean age of 51.6±9.1 years, while 2 patients were moderate alcohol consumers. None of the 5 patients were positive for either HBs Ag or anti-HBc Ab. A histological examination at the initial IFN therapy showed the activity scores to be A2 in all cases, and the fibrosis scores at least F2. The clinical parameters at the diagnosis of HCC included fluctuating transaminase levels in all cases. These levels scarcely fell below the upper limits even after SVR was achieved. In 3 patients, liver tissues were obtained at the treatment of HCC. These tissues showed marked improvement in both activities and fibroses, but severe steatosis in 1 patient. To conclude, chronic hepatitis C patients who respond to IFN therapy should undergo long-term follow-up, even after the eradication of HCV, with special attention particularly to patients who had elevated transaminase levels and steatosis. IntroductionHepatocellular carcinoma (HCC) is the major cause of cancerrelated death in Japan. Approximately 70-80% of HCCs in Japanese patients are associated with hepatitis C virus (HCV) infection (1). HCV causes chronic infection in more than 70% of cases, and liver disease gradually progresses to liver cirrhosis and finally to HCC.Interferon (IFN) has been used for the treatment of chronic hepatitis C (CHC) patients. Many investigators have reported that IFN treatment is effective in the reduction of the serum alanine amino transferase (ALT) level, eliminating HCV RNA from the circulation and improving liver histology in CHC patients (2-6). In certain patients, IFN therapy normalizes the serum ALT levels and leads to sustained eradication of HCV. These patients are commonly referred to as having achieved a sustained viral response (SVR) (7), and it has been noted that the cumulative incidence of HCC is significantly lower in SVR patients than in those with a non-response (NR) to IFN therapy (8,9), suggesting that the success of treatment for HCV infection is expected to significantly reduce the risk of developing HCC.However, the development of HCC among CHC patients with SVR to IFN therapy has been reported (10-16). In most cases, HCCs occurred within 5 years after the termination of IFN treatment. The risk factors for developing HCC after achieving SVR were suggested in these reports; however, the associated significant factors remain unknown. Moreover, the risk factors for the development of HCC in patients who have achieved SVR for more than 10 years are not fully understood. Therefore, it remains undetermined which patient g...

NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations

“…In experimental models, using transgenic mice, HCV core proteins showed a causative role in the development of steatosis and HCC [ 65 , 66 , 67 , 68 ]. The experimental evidence has been confirmed in the majority of clinical studies performed [ 67 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. Both retrospective and prospective studies, with only a few exceptions, showed that HCV-related steatosis was strictly associated with the development of HCC and that the amount of fatty liver deposition was an important risk factor for HCC [ 67 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ].…”

Hepatocellular Carcinoma in a Non-Cirrhotic Patient With Sustained Virological Response After Hepatitis C Treatment

“…Furthermore, patients with SVR present an important improvement in hepatic inflammation and fibrosis, and consequently a reduction in the risk of developing HCC 3 , 14 , 17 , 18 . However, the presence of HCC in non-cirrhotic patients with SVR is possible and Asia practically monopolizes existing accounts, especially Japan 1 , 12 , 16 . The factors involved in these cases as well as the profile of these patients are still not fully understood.…”

Occurrence of Hepatocellular Carcinoma upon Advanced Liver Fibrosis Thirteen Years After Achieving Sustained Virological Response to Hepatitis C: How Long Surveillance Should Be Maintained?

“…According to the results of a metaanalysis of retrospective studies, risk of HCC halves in patients with C virus infection who achieve sustained viral response (SVR) with interferon and ribavirin [3]. However, there are some reports about the development of HCC after achieving SVR [3][4][5] even 10 years after finishing antiviral treatment. HCC incidence and risk factors in these patients are not well established.…”

“…Morgan et al [10] found that in patients with SVR, risk of HCC was 7, 2, and 3 times higher in relation to age ([50 years), advanced histological stage (fibrosis score CF3), and male gender, respectively. High ALT level in relation to the presence of alcoholic steatosis, diabetes mellitus, or obesity [4] has been suggested in different studies as another risk factor for HCC. In addition, occult HBV infection has also been associated as another risk factor for HCC.…”