Yasuhiro Hisanaga

Prognostic Significance of Simultaneous Measurement of Three Tumor Markers in Patients With Hepatocellular Carcinoma

BACKGROUND & AIMS We conducted a prospective study to evaluate the significance of simultaneous measurement of 3 currently used tumor markers in the evaluation of tumor progression and prognosis of patients with hepatocellular carcinoma (HCC). METHODS Three tumor markers for HCC, alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), were measured in the same serum samples obtained from 685 patients at the time of initial diagnosis of HCC. Positivity for AFP >20 ng/dL, AFP-L3 >10% of total AFP, and/or DCP >40 mAU/mL was determined. In addition, tumor markers were measured after treatment of HCC. RESULTS Of the 685 patients, 337 (55.8%) were positive for AFP, 206 (34.1%) were positive for AFP-L3, and 371 (54.2%) were positive for DCP. In a comparison of patients positive for only 1 tumor marker, patients positive for AFP-L3 alone had a greater number of tumors, whereas patients positive for DCP alone had larger tumors and a higher prevalence of portal vein invasion. When patients were compared according to the number of tumor markers present, the number of markers present clearly reflected the extent of HCC and patient outcomes. The number of markers present significantly decreased after treatment. CONCLUSIONS Tumor markers AFP-L3 and DCP appear to represent different features of tumor progression in patients with HCC. The number of tumor markers present could be useful for the evaluation of tumor progression, prediction of patient outcome, and treatment efficacy.

Comparison of the usefulness of three staging systems for hepatocellular carcinoma (CLIP, BCLC, and JIS) in Japan.

OBJECTIVES:We retrospectively compared the usefulness of three different staging systems for hepatocellular carcinoma (HCC), the Cancer of the Liver Italian Program (CLIP) scoring system, the Barcelona Clinic Liver Cancer (BCLC) classification system, and the Japan Integrated Staging (JIS) system, in terms of patient distribution and survival rates.METHODS:Subjects were 1,508 patients diagnosed as having initial HCC during the period of 1976–2003. The disease was staged in all patients by means of the three staging systems, and the distribution of patients across stages and associated survival rates were compared between systems. In addition, comparisons were made on the basis of the time of diagnosis: 1976–1990 (n = 497) and 1991–2003 (n = 1,011).RESULTS:Patients were evenly distributed across stages within each staging system, and survival rates differed between stages except for BCLC C and D. During the period 1991–2003, when HCCs were smaller at diagnosis, JIS system is in particular yielded even distribution of patient across stages and marked differences in survival rates.CONCLUSIONS:Overall, the CLIP and the JIS scoring systems proved to be suitable for patients in Japan with HCC. The CLIP staging systems proved to be more suitable before 1991. In contrast, the JIS system was the most suitable after 1990, when early detection and early treatment of HCC became common. The JIS system is, therefore, the appropriate system in this era of early detection and treatment of HCC.

Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic hepatitis B patients: A propensity score analysis

BACKGROUND & AIMS Some patients with chronic hepatitis B virus (HBV) infection progress to hepatocellular carcinoma (HCC). However, the long-term effect of nucleos(t)ide analogue (NA) therapy on progression to HCC is unclear. METHODS Therefore, we compared chronic hepatitis B patients who received NA therapy to those who did not, using a propensity analysis. RESULTS Of 785 consecutive HBV carriers between 1998 and 2008, 117 patients who received NA therapy and 117 patients who did not, were selected by eligibility criteria and propensity score matching. Factors associated with the development of HCC were analyzed. In the follow-up period, HCC developed in 57 of 234 patients (24.4%). Factors significantly associated with the incidence of HCC, as determined by Cox proportional hazards models, include higher age (hazard ratio, 4.36 [95% confidence interval, 1.33-14.29], p=0.015), NA treatment (0.28 [0.13-0.62], p=0.002), basal core promoter (BCP) mutations (12.74 [1.74-93.11], p=0.012), high HBV core-related antigen (HBcrAg) (2.77 [1.07-7.17], p=0.036), and high gamma glutamyl transpeptidase levels (2.76 [1.49-5.12], p=0.001). CONCLUSIONS NA therapy reduced the risk of HCC compared with untreated controls. Higher serum levels of HBcrAg and BCP mutations are associated with progression to HCC, independent of NA therapy.

Impact of Diabetes Mellitus on the Prognosis of Patients with Hepatocellular Carcinoma

The majority of patients with hepatocellular carcinoma (HCC) have coexisting cirrhosis or chronic hepatitis, often complicated by diabetes mellitus. In the current study, the authors evaluated the impact of diabetes mellitus on the prognosis of patients with HCC.

Relationship between Lens culinaris agglutinin-reactive alpha-fetoprotein and pathologic features of hepatocellular carcinoma

Abstract: Aim: We investigated pathological features of Lens culinaris agglutinin‐reactive α‐fetoprotein (AFP‐L3)‐positive hepatocellular carcinoma (HCC) in order to seek a pathological basis of poor prognosis of HCC patients with elevated AFP‐L3.

The effect of retreatment with interferon‐α on the incidence of hepatocellular carcinoma in patients with chronic hepatitis C

Interferon (IFN) has been reported to have beneficial long term effects that reduce the occurrence of hepatocellular carcinoma (HCC), even in patients who do not have complete responses to IFN. The authors evaluated the effect of retreatment with IFN‐α on the long term prognoses of those with incomplete responses to their initial IFN‐α treatment.

Incidence of hepatocellular carcinoma in hepatitis C carriers with normal alanine aminotransferase levels

BACKGROUND/AIMS This study sought to identify the independent risk factors involved in the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection who have normal alanine aminotransferase (ALT) levels. METHODS A total of 519 patients with average ALT integration values less than or equal to 40 IU/L over 10 years were included. Baseline ultrasound was done in all patients and 68 patients underwent liver biopsy at the start of this study. Factors associated with the cumulative incidence of HCC were determined. RESULTS HCC occurred in 48 of 519 patients (9.2%). The following factors were significantly associated with the incidence of HCC: age>65 years (adjusted hazard ratio: 2.006 [95% confidence interval: 1.078-3.733]), ALT>20 IU/L (6.242 [1.499-25.987]), platelet count<15.0x10(4)/m(3) (2.675 [1.407-5.085]), total bilirubin>1.2mg/dL (2.798 [1.257-6.228]), ALP>338 IU/L (2.486 [1.327-4.657]), and total albumin<3.5g/dl (2.707 [1.177-6.223]). The 5- and 10-year cumulative incidences of HCC were 4.4% and 26.5% in patients with ALT>20 IU/L and platelet count<15.0x10(4)/m(3), respectively. CONCLUSIONS High ALT level and low platelet count are closely associated with the development of hepatocarcinogenesis. Therefore, individuals within this group are candidates for antiviral therapy.

Changes in the Characteristics and Survival Rate of Hepatocellular Carcinoma from 1976 to 2000 Analysis of 1365 Patients in a Single Institution in Japan

The authors analyzed changes in the characteristics and survival rate of patients with hepatocellular carcinoma (HCC) in the past 25 years.

Risk factors of hepatocellular carcinoma development in non-cirrhotic patients with sustained virologic response for chronic hepatitis C virus infection

Hepatocellular carcinoma (HCC) can develop in patients with chronic hepatitis C after they have achieved a sustained virologic response (SVR) to antiviral therapy, that is eradication of hepatitis C virus (HCV). Thus, surveillance for HCC remains necessary after SVR. We investigated factors that are predictive of HCC in HCV‐infected patients who achieved SVR.

Changes in Hepatitis C Virus (HCV) Antibody Status in Patients with Chronic Hepatitis C after Eradication of HCV Infection by Interferon Therapy

BACKGROUND Changes in hepatitis C virus (HCV) antibody status were followed for 10 years after the eradication of HCV by interferon (IFN) therapy in 30 patients with chronic hepatitis C who showed a sustained virological response. METHODS HCV core antibody titer, third-generation HCV recombinant immunoblot assay (RIBA) grade (measuring the presence of antibodies for core, NS3, NS4, and NS5 antigens), and genotype-specific antibodies to the HCV NS4 region were measured annually with commercially available kits for these antibodies. RESULTS For grade of HCV antibody determined by RIBA, the most significant decrease was observed with anti-NS5 antibody, followed by anti-NS4, anti-NS3, and anti-core antibodies, in that order. Tests for anti-NS5 and anti-NS4 antibodies had negative results in almost 50% of patients 10 years after eradication of HCV. In contrast, the results of tests for anti-core antibody were still markedly positive in most patients. However, anti-core antibody titer decreased continuously during the 10-year follow-up period. Antibodies to the NS4 region specific for HCV genotypes 1 and 2 also decreased during the follow-up period. Differences in the rate at which antibody titers decreased were observed between antibodies for genotypes 1 and 2; as a consequence, the serological type of HCV changed during the follow-up period in some patients. CONCLUSIONS HCV antibody titer appears to continue to decrease during the 10 years after eradication of HCV by IFN therapy.