Akira Kanamori

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

BACKGROUND & AIMSnSome 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.nnnMETHODSnTherefore, we compared chronic hepatitis B patients who received NA therapy to those who did not, using a propensity analysis.nnnRESULTSnOf 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).nnnCONCLUSIONSnNA 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.

Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection: a propensity score analysis

Eradication of hepatitis C virus (HCV) by interferon (IFN)‐based therapy has been reported to reduce all‐cause mortality rates in patients with chronic HCV infection. However, the impact of HCV eradication on non–liver‐related mortality including the causes of death has not been sufficiently investigated in patients with chronic HCV infection.

HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics

BACKGROUND & AIMSnSeveral hepatitis B virus (HBV) markers have been identified as factors associated with the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We clarified the predictive power of HBV markers for the development of HCC using receiver operating characteristic (ROC) analysis with a consideration of time dependence.nnnMETHODSnA total of 1031 CHB patients who were not treated with nucleos(t)ide analogue therapy were enrolled. Univariate, multivariate, and time-dependent ROC curves for HBV markers associated with the development of HCC were analyzed.nnnRESULTSnSeventy-eight patients developed HCC during the follow-up period (median duration 10.7years). Different levels or statuses of several HBV markers (HBV genotype, HBV DNA, HBV core-related antigen (HBcrAg), hepatitis B e antigen (HBeAg), and basal core promoter (BCP)), but not hepatitis B surface antigen, were significantly associated with the incidence of HCC by univariate analysis using the log-rank test. Cox proportional hazards models using the covariates of HBV genotype status, HBV DNA levels, HBcrAg levels, HBeAg status, and BCP status indicated that HBcrAg >2.9logU/ml (hazard ratio (HR), 5.05; 95% confidence interval (CI), 2.40-10.63) and BCP mutation (HR, 28.85; 95% CI, 4.00-208.20) were independently associated with the incidence of HCC. Additionally, time-dependent ROC analysis showed that HBcrAg was superior to HBV DNA in terms of predictive power for HCC development throughout the follow-up period.nnnCONCLUSIONSnElevation of HBcrAg levels in CHB patients is associated with the development of HCC. HBcrAg is an excellent predictor of HCC development.nnnLAY SUMMARYnHepatitis B virus (HBV) core-related antigen (HBcrAg) is an excellent predictor of hepatocellular carcinoma (HCC) development in chronic hepatitis B patients without nucleos(t)ide analogue therapy. HBcrAg was superior to HBV DNA in terms of predictive power for HCC development by time-dependent receiver operating characteristic analysis.

High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma

BackgroundPrognosis of patients with hepatocellular carcinoma (HCC) remains poor because HCC is frequently diagnosed late. Therefore, regular surveillance has been recommended to detect HCC at the early stage when curative treatments can be applied. HCC biomarkers, including Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), are widely used for surveillance in Japan. A newly developed immunoassay system measures AFP-L3xa0% with high sensitivity. This retrospective study aimed to evaluate clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) as a predictor of early stage HCC in surveillance at a single site.MethodsOf consecutive 2830 patients in the surveillance between 2000 and 2009, 104 HCC-developed and 104 non-HCC patients were selected by eligibility criteria and propensity score matching. Samples were obtained from the HCC patients who had blood drawn annually for 3xa0years prior to HCC diagnosis.ResultsIn the present study, hs-AFP-L3 was elevated 1xa0year prior to diagnosis in 34.3xa0% of patients. The survival rate of patients with the hs-AFP-L3xa0≥xa07xa0% at 1xa0year prior to diagnosis was significantly lower than that of patients with hs-AFP-L3xa0<xa07xa0%.ConclusionsElevation of hs-AFP-L3 was early predictive of development of HCC even at low AFP levels and in absence of ultrasound findings of suspicious HCC. The hs-AFP-L3 should be added to surveillance programs with US because elevated hs-AFP-L3 may be a trigger to perform enhanced imaging modalities for confirmation of HCC.

Predictive value of tumor markers for hepatocarcinogenesis in patients with hepatitis C virus

BackgroundIncreases in tumor markers are sometimes seen in patients with chronic liver disease without hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between the levels of three tumor markers [alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3%), and des-γ-carboxy prothrombin (DCP)] and hepatic carcinogenesis to identify hepatitis C virus (HCV) carriers at high risk for cancer development.MethodsA total of 623 consecutive HCV carriers with follow-up periods of >3xa0years were included. The average integration values were calculated from biochemical tests, and tumor markers, including AFP, AFP-L3%, and DCP, and factors associated with the cumulative incidence of HCC were analyzed.ResultsHCC developed in 120 (19.3%) of the 623 patients. Age >65xa0years [adjusted relative risk, 2.303 (95% confidence interval, 1.551–3.418), Pxa0<xa00.001], low platelet count [3.086 (1.997–4.768), Pxa0<xa00.001], high aspartate aminotransferase value [3.001 (1.373–6.562), Pxa0<xa00.001], high AFP level [≥10, <20xa0ng/mL: 2.814 (1.686–4.697), Pxa0<xa00.001; ≥20xa0ng/mL: 3.405 (2.087–5.557), Pxa0<xa00.001] compared to <10xa0ng/mL, and high AFP-L3% level [≥5, <10%: 2.494 (1.291–4.816), Pxa0=xa00.007; ≥10%: 3.555 (1.609–7.858), Pxa0<xa00.001] compared to <5% were significantly associated with an increased incidence of HCC on multivariate analysis.ConclusionsIncreased AFP or AFP-L3% levels were significantly associated with an increased incidence of HCC. Among HCV carriers, patients with ≥10xa0ng/mL AFP or patients with ≥5% AFP-L3% are at very high risk for the development of HCC even if AFP is less than 20xa0ng/mL or AFP-L3% is less than 10%, which are the most commonly reported cutoff values.

Prevalence of Low-Level Hepatitis B Viremia in Patients with HBV Surface Antigen-Negative Hepatocellular Carcinoma with and without Hepatitis C Virus Infection in Japan: Analysis by COBAS TaqMan Real-Time PCR

Objectives: The effect of circulating low-level hepatitis B virus (HBV), defined as one of the states of ‘occult HBV infection’, on the development of hepatocellular carcinoma (HCC) in HBV surface antigen (HBsAg)-negative patients is controversial. In addition, the prevalence of occult HBV infection strongly depends on the sensitivity of the HBV detection method. We investigated the prevalence of low-level HBV in the serum of HBsAg-negative patients with HCC using a newly developed, sensitive method based on real-time polymerase chain reaction. Methods: Serum was examined for HBV DNA in 132 patients with HBsAg-negative HCC (95 with hepatitis C virus [HCV] infection and 37 without detectable hepatitis virus infection) with the COBAS TaqMan HBV test, of which the 95% hit rate is 35 copies/ml (6.7 IU/ml). Results: Low-level HBV DNA was detected in 2 of 95 (2.1%) patients with HCV-related HCC and 1 of 37 (2.7%) patients with non-viral HCC. Conclusion: The prevalence of the detection of circulating low-level HBV was low in both HBsAg-negative HCC patients with HCV infection and those without detectable hepatitis virus, even with the use of the most sensitive method for the detection of HBV. Circulating low-level HBV does not appear to play an important role in hepatocarcinogenesis in HBsAg-negative HCC.

Higher hepatic gene expression and serum levels of matrix metalloproteinase-2 are associated with steatohepatitis in non-alcoholic fatty liver diseases

We investigated the gene expression of tissue inhibitor metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) and serum levels of TIMPs, MMPs, and hyaluronic acid that are associated with liver fibrosis in 64 patients with nonalcoholic fatty liver diseases (NAFLD). Whereas, no differences were found between patients with and without nonalcoholic steatohepatitis (NASH) in serum levels of hyaluronic acid when excluding NASH patients with advanced fibrosis, the quantity of MMP2 mRNA in liver tissue and serum MMP2 levels were significantly higher in patients with NASH than those without, even focusing on patients with less advanced fibrosis, indicating the initiation of liver fibrosis.

Relation between incidence of hepatic carcinogenesis and integration value of alanine aminotransferase in patients with hepatitis C virus infection

Alanine aminotransferase (ALT) activity is the most widely used laboratory parameter in the evaluation of necroinflammatory activity in liver disease.1–3 However, it is incorrect to evaluate the arithmetic or the annual mean values. If the ALT level is high, the measurement interval decreases, whereas if the ALT level is low, the interval increases. As a result, the arithmetic mean value increases in patients with increased ALT levels. We performed a more accurate evaluation by using the integration value of ALT. The aim of this study was to determine the utility of the integration value of ALT in predicting hepatic carcinogenesis in patients with the hepatitis C virus (HCV) infection.nnA total of 1704 consecutive patients with follow-up periods of ⩾3 years, with no evidence of hepatocellular carcinoma (HCC) for ⩾3 years before the observation period, and interferon treatment completed ⩾3 year before the detection of HCC during …

Characteristics of elderly hepatitis C virus-associated hepatocellular carcinoma patients.

The average age of hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC) patients has been rising in Japan. We evaluate characteristics of HCV‐positive patients who develop HCC in older age to determine an optimal surveillance strategy.

Viral Eradication reduces all-Cause Mortality, Including non-Liver-Related Disease, in Patients With Progressive Hepatitis C Virus-Related Fibrosis.

Eradication of hepatitis C virus (HCV) with interferon (IFN)‐based therapy has been reported to reduce all‐cause mortality in patients with chronic HCV infection. However, the impact of HCV eradication on non–liver‐related mortality and causes of death has not been sufficiently investigated in patients with progressive HCV‐related fibrosis.