Yoichi Yano

Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan.

OBJECTIVE:We determined the prevalence of patients with hepatocellular carcinoma (HCC) who were positive for only anti-hepatitis B core (anti-HBc) antibody among 284 Japanese patients and compared their clinical features to those who were hepatitis B surface antigen positive [HBsAg (+)].METHODS:Serum HBsAg and anti-hepatitis C virus (anti-HCV) antibody were examined for all HCC patients. Testing for anti-HBc antibody was performed in the HBsAg(−)/anti-HCV(−) patients. The clinical factors and the survival rate were compared between the HBsAg(+) patients (HCC-B) and those positive for anti-HBc alone (HCC-PB).RESULTS:There were 19 (6.7%) HBsAg(+), 236 (83.1%) anti-HCV(+), seven (2.5%) HBsAg(+)/anti-HCV(+), and 22 (7.7%) HBsAg(−)/anti-HCV(−) among the 284 patients tested. Sixteen (72.7%) of the 22 HBsAg(−)/anti-HCV(−) patients were assigned to the HCC-PB group. The prevalence of positivity for anti-HBc alone among all 284 HCC patients was 5.6%. Significant differences between the HCC-PB and HCC-B groups were that age at diagnosis was higher in the HCC-PB group (72.1 yr) than in the HCC-B group (56.2 yr) (p < 0.001), the serum α-fetoprotein concentrations were lower in the HCC-PB group (8.2 ng/ml) than in the HCC-B group (43 ng/ml) (p = 0.0488), and a higher familial history of liver disease was observed in the HCC-B group (p = 0.0373). However, there was no significant difference in the cumulative survival rate.CONCLUSIONS:Positivity for anti-HBc alone is not rare compared to HBsAg(+), and the clinical features of positivity for anti-HBc alone are similar to those of HBsAg(+). Some differences in the clinical features between the two groups may be explained by differences in the time of first exposure to hepatitis B virus. Therefore, the natural course of acute hepatitis B may be reconsidered.

Clinical features of hepatitis C virus-related hepatocellular carcinoma and their association with α-fetoprotein and protein induced by vitamin K absence or antagonist-II

Abstract: Purpose: We investigated the differences in clinical features between α‐fetoprotein (AFP)‐predominant hepatocellular carcinoma (HCC) and protein induced by vitamin K absence or antagonist‐II (PIVKA‐II)‐predominant HCC, especially regarding host factors thought to contribute to hepatocarcinogenesis in chronic hepatitis C virus (HCV) infection.

Efficacy, Safety, and Survival Factors for Sorafenib Treatment in Japanese Patients with Advanced Hepatocellular Carcinoma

Background: Sorafenib, an oral multikinase inhibitor, was approved for the treatment of advanced hepatocellular carcinoma (HCC), but has not been adequately evaluated for safety and effectiveness in Japanese patients with advanced HCC. Aims: The purpose of this study was to prospectively assess the efficacy, safety, and risk factors for survival in patients with advanced HCC treated with sorafenib. Methods: Between May 2009 and December 2010, 96 Japanese patients with advanced HCC (76 male, 20 female, mean age: 70.4 years) were treated with sorafenib. Eighty-eight patients had Child-Pugh class A, and 8 patients had Child-Pugh class B liver cirrhosis. Barcelona Clinic Liver Cancer stage B and C were found in 64 and 32 patients, respectively. Results: Twelve patients demonstrated partial response to sorafenib therapy, 43 patients had stable disease, and 33 patients had progressive disease at the first radiologic assessment. The most frequent adverse events leading to discontinuation of sorafenib treatment were liver dysfunction (n = 8), hand-foot skin reaction (n = 7), and diarrhea (n = 4). The median survival time and time to progression were 11.6 and 3.2 months, respectively. By multivariate analysis, des-γ-carboxy prothrombin serum levels and duration of treatment were identified as independent risk factors for survival. Conclusions: This study showed that sorafenib was safe and useful in Japanese patients with advanced HCC. In addition, this study demonstrated that sorafenib should be administered as a long-term treatment for advanced HCC regardless of therapeutic effect and dosage.

Chemotherapy for Hepatocellular Carcinoma with Portal Hypertension Due to Tumor Thrombus

A case of hepatocellular carcinoma (HCC) complicated by tumor thrombosis of the main trunk is presented. Four courses of hepatic arterial infusion therapy, via a subcutaneously implanted injection port, were performed using cisplatin (10 mg for 1 hour on days 1-5) and 5-fluorouracil (250 mg for 5 hours on days 1-5). After four courses of the chemotherapy, marked reduction in size of HCC and the tumor markers were noted. The esophageal varices and ascites were improved after the chemotherapy with a recanalization of the left branch of the portal vein. The patient was doing well with a survival period of 28 months after the chemotherapy. These encouraging results suggested that the present therapy, based on the biochemical modulation, was a useful option for advanced HCC with portal hypertension due to tumor thrombosis of the main portal vein.

Evaluation of Resistance-Associated Substitutions in NS5A Using Direct Sequence and Cycleave Method and Treatment Outcome with Daclatasvir and Asunaprevir for Chronic Hepatitis C Genotype 1.

Background The aim of this study was to evaluate the efficacy of daclatasvir plus asunaprevir therapy in patients infected with hepatitis C virus and determine its relevance to resistant variants. Methods A total of 629 consecutive patients infected with hepatitis C virus genotype 1 were assessed. Daclatasvir (60 mg/day) plus asunaprevir (200 mg/day) was given for 24 weeks. The virological responses and resistance-associated substitutions of hepatitis C virus mutants were examined by the direct sequence and cycleave methods were evaluated. Results Overall, 89.4% (555/621) of patients exhibited a sustained virological response (SVR). The SVR rates in the patients with wild type, mixed, and mutant type Y93 by direct sequencing were 92.5% (520/562), 70.3% (26/37), and 42.9% (9/21), respectively. The SVR rates in the patients with 100%, 90%, 80%-30%, and 20%-0% Y93 wild by the cycleave method were 93.4% (456/488), 88.2%(30/34), 56.0%(14/25), and 36.8%(7/19), respectively. In contrast, the SVR rates for the wild type and mixed/mutant type L31 by direct sequencing were 90.2% (534/592) and 72.4% (21/29), respectively. In the multivariate analyses, the wild type Y93, no history of simeprevir therapy, the wild type L31, and low HCV RNA level were independent factors of SVR. Conclusion NS5A resistance-associated substitutions, especially Y93H, were major factors predicting the SVR. Although direct sequencing can predict the SVR rate, the cycleave method is considered to be more useful for predicting the SVR when used in combination.

Clinical significance of antibody against hepatitis B virus core antigen in patients with hepatitis C virus-related hepatocellular carcinoma

Purpose: We investigated the unsettled issue of whether seropositivity for antibody to hepatitis B core antigen (anti‐HBc) affects characteristics of hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC).

A crossover study of oral administration of UFT in chronic liver disease: comparison of continuous and intermittent schedules.

This study was aimed at evaluating the tolerance to an intermittently administered oral UFT for hepatocellular carcinoma (HCC) with chronic liver disease (CLD). Ten patients who had received curative therapy for HCC with CLD (Childs classification A or B) were randomly assigned either an intermittent schedule (IS), oral administration of UFT (130 mg/m2/b.i.d.) with 2 days rest a week, or a continuous schedule (CS), consecutive administration of UFT with the same dose. On day 12, the serum concentration of 5-fluorouracil (5-FU) was measured. After 2 weeks rest, the patients were switched to the other schedule for 10 weeks and the concentration of 5-FU was measured on day 12. The median values of the area under the curve (AUC) and maximum concentration (Cmax) of 5-FU in IS and CS were 187.7 and 263.2 ng/ml/h, 57.1 and 93.0 ng/ml, respectively. Both the AUC and Cmax for IS were significantly lower than those for CS. One IS patient had tolerable diarrhea, while three of the CS patients had intolerable nausea and one had hemorrhagic gastritis. IS seemed to be a suitable measure for CLD.