Norihiro Imai

Large-Scale Long-Term Follow-Up Study of Japanese Patients With Non-Alcoholic Fatty Liver Disease for the Onset of Hepatocellular Carcinoma

OBJECTIVES:The aim of this study was to determine the incidence and risk factors of hepatocellular carcinoma (HCC), and to elucidate the utility of two non-invasive predictive procedures for liver fibrosis: the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the BARD score (which includes the following three variables: body mass index, AST/alanine aminotransferase ratio, and diabetes) in the prediction of HCC in a large population of Japanese patients with non-alcoholic fatty liver disease (NAFLD).METHODS:This was a retrospective cohort study conducted at a public hospital. Study subjects included 6,508 patients with NAFLD diagnosed by ultrasonography. The median follow-up period was 5.6 years. The primary end point was the onset of HCC. Evaluation was performed using Kaplan–Meier methodology and Coxs proportional hazards analysis.RESULTS:In all, 16 (0.25%) new cases with HCC were diagnosed during the study. The cumulative rates of NAFLD-related HCC were 0.02% at year 4, 0.19% at year 8, and 0.51% at year 12. The annual rate of new HCC was 0.043%. Multivariate analysis identified serum AST level ≥40 IU/L (hazard ratio (HR): 8.20; 95% confidence interval (95% CI): 2.56–26.26; P<0.001), platelet count <150 × 103/μl (HR: 7.19; 95% CI: 2.26–23.26; P=0.001), age ≥60 years (HR: 4.27; 95% CI: 1.30–14.01; P=0.017), and diabetes (HR: 3.21; 95% CI: 1.09–9.50; P=0.035) as independent risk factors for HCC. With regard to the APRI, 184 patients (2.83%) were considered to have significant fibrosis (equivalent to non-alcoholic steatohepatitis (NASH) stage 3–4). The cumulative rate of HCC was significantly higher in this group (HR: 25.03; 95% CI: 9.02–69.52; P<0.001). In contrast, regarding the BARD score, 3,841 (59%) patients were considered to have advanced fibrosis (NASH stage 3–4). However, no significant associations between the BARD score and the incidence of HCC were observed (HR: 1.16; 95% CI: 0.40–3.37; P=0.780).CONCLUSIONS:This retrospective study indicates that the annual incidence rate of HCC among Japanese NAFLD patients is low. Elderly NAFLD patients with diabetes, elevated serum AST, and especially thrombocytopenia (suggested to be associated with advanced liver fibrosis) should be monitored carefully during follow-up that includes using the APRI to ensure early diagnosis and treatment of HCC.

Difference in malignancies of chronic liver disease due to non-alcoholic fatty liver disease or hepatitis C in Japanese elderly patients

Aim:  Malignancies that include hepatocellular carcinoma often occurred in patients with chronic liver disease. The aim of this retrospective match control study was to assess the cumulative development incidence and predictive factors for total malignancies in elderly Japanese patients with non‐alcoholic hepatic diseases (NAFLD) or hepatitis C virus (HCV).

Development rate of chronic kidney disease in hepatitis C virus patients with advanced fibrosis after interferon therapy

Aim:  The aim of this retrospective cohort study is to assess the development incidence and predictive factors for chronic kidney disease (CKD) after the termination of interferon therapy in hepatitis C virus (HCV) positive Japanese patients with liver cirrhosis.

Transcatheter Arterial Chemotherapy Using Miriplatin–Lipiodol Suspension with or without Embolization for Unresectable Hepatocellular Carcinoma

OBJECTIVE The purpose of this retrospective study was to compare the anti-tumor and adverse effects of transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy using miriplatin-lipiodol suspension in patients with unresectable hepatocellular carcinoma. METHODS From 2007 to 2010, 162 consecutive patients with unresectable hepatocellular carcinoma were treated using miriplatin. Of these, 122 patients were treated by transcatheter arterial chemoembolization and 40 were treated by transcatheter arterial infusion chemotherapy. There were no significant differences in baseline characteristics between the two groups, except for prothrombin activity. Assessments were performed 1-3 months after treatment. RESULTS Objective responses were achieved in 13 patients undergoing transcatheter arterial infusion chemotherapy and 70 patients undergoing transcatheter arterial chemoembolization (33 versus 57%, P = 0.003). By multivariate logistic regression analysis, objective response was significantly associated with (i) a Lens culinaris agglutinin-reactive fraction of α-fetoprotein ≤10% (P = 0.004; risk ratio = 3.09; 95% confidence interval = 1.42-6.70), (ii) no previous transcatheter arterial chemoembolization (P = 0.007; risk ratio = 4.41; 95% confidence interval = 1.49-13.07) and (iii) transcatheter arterial chemoembolization using gelatin sponge 1 mm particles (P = 0.021; risk ratio = 2.97; 95% confidence interval = 1.17-7.49). Fever, anorexia and elevated serum transaminase levels were observed in most patients after miriplatin administration; there were no significant differences in the number of adverse effects between the two groups. CONCLUSIONS These results suggest that the addition of embolizing agents to a treatment regimen using miriplatin-lipiodol suspension can be safely used for patients with unresectable hepatocellular carcinoma. Objective response was achieved in a significantly higher number of transcatheter arterial chemoembolization patients than transcatheter arterial infusion chemotherapy patients.

Stage progression of small hepatocellular carcinoma after radical therapy: comparisons of radiofrequency ablation and surgery using the Markov model

Background: Stage progression of 374 small hepatocellular carcinomas (HCC) was retrospectively analysed.

Previous Chemoembolization Response after Transcatheter Arterial Chemoembolization (TACE) Can Predict the Anti-Tumor Effect of Subsequent TACE with Miriplatin in Patients with Recurrent Hepatocellular Carcinoma

Aim: The purpose of this retrospective study was to evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) with miriplatin in patients with unresectable hepatocellular carcinoma (HCC). Methods: From 2007 to 2010, 122 consecutive patients with unresectable HCC were treated by TACE with miriplatin-lipiodol suspension in our institute. Twenty-two patients (18%) had a solitary nodule and 100 patients (82%) had multiple nodules. Ninety-eight patients (80%) had a history of TACE. Results: Thirty-five of the 122 treated patients (29%) showed complete response (CR). And no serious complications were observed. Patients who had shown CR after previous TACE (pre-CR) were significantly more likely to show CR in the current study compared with patients who had shown less successful responses after previous TACE (56 vs. 20%, p = 0.003). Multivariate analysis revealed that response after previous TACE (pre-CR, risk ratio: 4.76; p = 0.035), tumor multiplicity (solitary, risk ratio: 9.69; p = 0.003), and injection artery (peripheral to segmental hepatic artery, risk ratio: 5.28;p = 0.040) were significant independent predictors associated with CR after TACE using miriplatin. Conclusion: In repetition of TACE treatment, switching the TACE agent from epirubicin or cisplatin to miriplatin offered a favorable treatment effect, especially in patients who had shown a CR after previous TACE.

Administration of interferon for two or more years decreases early stage hepatocellular carcinoma recurrence rate after radical ablation: a retrospective study of hepatitis C virus-related liver cancer.

Background:  Since hepatocellular carcinoma often recurs after surgical resection or radiofrequency ablation, we analyzed a retrospective large cohort of patients with small hepatocellular carcinoma caused by hepatitis C virus (HCV).

Prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhosis with fasting plasma glucose level of <126 mg/dL.

Aim:  The aim of this study was to evaluate the prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhotic patients with fasting plasma glucose (FPG) level of <126 mg/dL.

Efficacy of reduction therapy of natural human β-interferon and ribavirin in elderly patients with chronic hepatitis C, genotype 2 and high virus load: Efficacy of β-interferon/ribavirin therapy

Aim:  To evaluate the efficacy of natural human interferon (IFN)‐β and ribavirin in elderly patients infected with hepatitis C virus (HCV) genotype 2 and high virus load.

Transcatheter Arterial Chemotherapy with Miriplatin for Hepatocellular Carcinoma Patients with Chronic Renal Failure: Report of Three Cases

Miriplatin is a novel lipophilic platinum complex that was developed to treat hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting chronic renal failure, little prospective data are available regarding the clinical toxicity of chemotherapeutic agents used to treat HCC patients with chronic renal failure. In a phase II study, the plasma concentration of total platinum in patients who received miriplatin was very low, and no severe renal toxicity caused by miriplatin injection was reported. Here, we present three cases of HCC with stage 4 chronic renal failure who received transcatheter arterial chemotherapy with miriplatin. All cases were male, ages 72, 84, and 83 years, and had serum creatinine levels of 2.3, 1.6, and 1.9 mg/dL, respectively. Their estimated glomerular filtration rates were 21.9, 20.3, and 22.2 mL/min, respectively. All cases were treated for unresectable HCC with transcatheter arterial chemotherapy with miriplatin. No serious adverse events were observed, and serum creatinine levels did not elevate, even in the patient who experienced renal failure caused by cisplatin administration. These results might suggest that transcatheter arterial chemotherapy with miriplatin can be safely used in HCC patients with chronic renal failure.