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ObjectiveTo assess the cerebral blood flow (CBF) in patients with diabetic neuropathic pain, and its changes after duloxetine therapy.MethodsUsing iodine-123-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (IMP-SPECT), we performed a cross-sectional study of 44 patients with diabetes, and compared CBF in those with (n = 24) and without neuropathic pain (n = 20). In patients with neuropathic pain, we also longitudinally assessed changes in CBF 3 months after treatment with duloxetine.ResultsIMP-SPECT with voxel-based analyses showed a significant increase in cerebral blood flow in the right anterior cingulate cortex and a decrease in the left ventral striatum in patients with neuropathic pain, compared with those without pain. After duloxetine treatment, volume of interest analyses revealed a decrease in cerebral blood flow in the anterior cingulate cortex in patients with significant pain relief but not in non-responders. Furthermore, voxel-based whole brain correlation analyses demonstrated that greater baseline CBF in the anterior cingulate cortex was associated with better pain relief on the numerical rating scale.ConclusionsOur results suggest that the development of neuropathic pain is associated with increased activity in the anterior cingulate cortex, and greater baseline activation of this region may predict treatment responsiveness to pharmacological intervention.Trial registration numberUMIN000017130;Results.

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...