Miyuki Taniguchi

Epidemiology of hepatitis E in Northeastern China, South Korea and Japan.

OBJECTIVES The seroprevalence of hepatitis E virus (HEV) infection in Northeastern Asia is unknown. This study was conducted to gain insight into the epidemiology of HEV that has been obscure in Northeastern China, South Korea and Japan. METHODS A total of 1500 samples of serum were collected (300 each) from 5 groups of inhabitants over 40 years of age (Korean Chinese, indigenous Chinese, South Koreans, Koreans living in Japan, and indigenous Japanese) and screened for antibodies to HEV by the antigen-antibody-antigen sandwich Enzyme Linked Immunosorbent Assay system. RESULTS The positivity for HEV antibodies was 50.7% (95%CI: 45.0-56.3) in Korean Chinese, 47.7% (95%CI: 42.1-53.3) in indigenous Chinese, 34% (95%CI: 28.9-39.5) in South Koreans, 14.3% (95%CI: 10.8-18.8) in Koreans living in Japan, and 6.0% (95%CI: 3.8-9.3) in indigenous Japanese. CONCLUSIONS This result emphasizes that HEV is endemic in Northeastern Asia and tends to accumulate in developing countries. Further studies are needed to elucidate the genotype of HEV circulating in these areas and its transmission route-water-borne outbreaks, smaller outbreaks or sporadic forms attributed to zoonosis-with reference to past epidemics, food culture, and sanitary conditions.

TTV positivity and transfusion history in non-B, non-C hepatocellular carcinoma compared with HBV- and HCV-positive cases.

The prevalence of TT virus (TTV) and its rate of transmission through transfusion were investigated to determine its possible hepatocarcinogenic role in non-B, non-C hepatocellular carcinoma (HCC) as compared with that in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-positive HCC. Its transfection route in TTV-positive cases was also studied. Serum was positive for TTV in 77.8% (7/9) of HBV-positive, 36.4% (12/33) of HCV-positive, and 63.6% (7/11) of non-B, non-C cases of HCC. The rate of transmission through transfusion was 52.4% (11/21) in HBV-positive, 40.1% (61/152) in HCV-positive, 33.3% (2/6) in HBV+HCV-positive, and 40% (8/20) in non-B, non-C HCCs, while it was 48.3% (14/29) in TTV-positive and 39.3% (11/28) in TTV-negative cases. The association between TTV and HCC was limited, and the main route of infection of TTV was not through transfusion.

Prediction of efficacy of interferon treatment of chronic hepatitis C by multivariate analysis and a new classification

One hundred and fifteen patients with chronic hepatitis C were administered interferon (IFN) and classed into two groups: (i) complete responders (CR), HCV‐RNA continuously negative 1 year after treatment; and (ii) non‐responders (NR), positive 1 year after treatment. Multivariate analysis comprised eight variables: age, sex, transfusion history, alanine aminotransferase level, viral genotype, level of viremia, type of IFN, and total amount of IFN. The HCV‐RNA level was correlated with complete response (P = 0.0175). Liver biopsy specimens were classified into four grades and stages according to the measure of severity and the extent of fibrosis, respectively. There was no correlation between the efficacy rate and grading. However, in staging there was a difference in the efficacy of IFN between stages 1 or 2, and stage 3 (0.05

Acute Pancreatitis Associated with Pegylated Interferon and Ribavirin Treatment of Chronic Hepatitis C, Genotype 1b with High Viral Load.

Acute pancreatitis, an uncommon side effect of pegylated interferon α (PEG-IFN α) and ribavirin (RBV) combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN α (60, 80, and 90 μg) plus a daily oral dose of RBV (600 mg). The therapy was discontinued, however, because of the onset of acute pancreatitis (after 15 weeks, 48 weeks, and 3 weeks respectively). The drug-induced pancreatitis was diagnosed on the basis of elevated levels of amylase and lipase and the absence of other identifiable causes. High tumor necrosis factor-α was found in one patient and high interleukin-6 in the other two. The immune system stimulated by PEG-IFN and RBV combination therapy might have caused the acute pancreatitis. Further study is needed to clarify the mechanism of the onset of drug-induced pancreatitis by PEG-IFN and RBV combination therapy.

Usefulness of a new immunoradiometric assay of HCV core antigen to predict virological response during PEG-IFN/RBV combination therapy for chronic hepatitis with high viral load of serum HCV RNA genotype 1b.

We investigated the clinical usefulness of a new immunoradiometric (IRM) assay of hepatitis C virus (HCV) core antigen in predicting virological response during pegylated interferon plus ribavirin (PEG-IFN/RBV) combination therapy for chronic hepatitis with high viral loads of serum HCV RNA genotype 1b. Thirty-nine patients received a regimen of PEG-IFNα-2b (1.5 µg/kg/week s.c.) in combination with RBV (600–1,000 mg/day). Of the 39 patients, 18 (46.2%) achieved sustained virological response (SVR), 11 (28.2%) attained partial response (PR) and 10 (25.6%) showed no response (NR). Four weeks after the start of therapy, 1- and 2-log reductions in the amount of HCV core antigen were observed in 20 (2/10) and 0% (0/10) showing NR, 91 (10/11) and 63.6% (7/11) with PRs, and 88.9 (16/18) and 55.6% (10/18) of patients with SVR, respectively. The 1- and 2-log reductions 4 weeks after the start of therapy were not a definingcondition for PR and SVR. The amount of HCV core antigen was significantly different between SVR and PR patients on days 1 and 7, and between patients with NR and SVR at all points of time. In conclusion, this new IRM assay is useful in predicting virological response during PEG-IFN/RBV therapy.

Outcome and early viral dynamics with viral mutation in PEG-IFN/RBV therapy for chronic hepatitis in patients with high viral loads of serum HCV RNA genotype 1b.

We investigated whether sustained virological response (SVR) and non-SVR by chronic hepatitis C patients to pegylated interferon plus ribavirin (PEG-IFN/RBV) combination therapy are distinguishable by viral factors such as the IFN/RBV resistance-determining region (IRRDR) and by on-treatment factors through new indices such as the rebound index (RI). The first RI (RI-1st; the viral load at week 1 divided by the viral load at 24 h) and the second RI (RI-2nd; the viral load at week 2 divided by the viral load at 24 h) were calculated. The subject patients were divided into 3 groups based on RI-1st and RI-2nd: an RI-A group (RI-1st ≤1.0), an RI-B group (RI-1st >1.0 and RI-2nd <0.7) and an RI-C group (RI-1st >1.0 and RI-2nd ≧0.7). The SVR rate was 71.4% (10/14) in the RI-A group, 46.2% (6/13) in the RI-B group and 20.0% (3/15) in the RI-C group (p = 0.005 between the RI-A group and the RI-C group). In IRRDR ≧6 and IRRDR ≤5 the SVR rate was 81.3% (13/16) and 23.1% (6/26) (p = 0.0002), respectively. By combining RI and IRRDR as a predicting factor, the SVR rate was 87.5% (7/8) in the RI-A group (≧6 mutations in the IRRDR) and 7.7% (1/13) in the RI-C group (≤5 IRRDR mutations) (p = 0.0003).

Comparison of prevalence of metabolic syndrome between korean emigrants and host country residents in Japan and china-the korean emigrant study.

OBJECTIVES This study aims to compare the prevalence of metabolic syndrome between Korean emigrants (KEs) and their host country residents in Japan and China. METHODS The Korean Emigrant Study (KES) is a cohort study initiated in 2005 to elucidate the effect of genetic susceptibility and environmental change on hypertension, diabetes, and metabolic syndrome. Equal numbers of KEs and host country residents, aged 30 or over, were recruited from three regions; Kobe-Osaka in Japan (total number=965), Yanbian in China (n=1,019), and Changchun in China (n=949). RESULTS The age-adjusted prevalences of metabolic syndrome among KEs in Kobe-Osaka were significantly higher than those among Japanese (in men 24.0% vs. 15.6%, p=0.04, in women 8.4% vs. 2.7%, p=0.01), while the age-adjusted prevalences among KEs in Changchun were similar to those among Chinese (in men 11.7% vs. 16.1%, p=0.37, in women 28.3% vs. 30.1%, p=0.91). The age-adjusted prevalences were generally higher in Yanbian than other regions, and KEs had higher prevalence than Chinese in men but not in women (in men 37.9% vs. 28.3%, p=0.03, women 46.0% vs. 50.6%, p=0.44). The components with significant ethnic differences in prevalence were high blood pressure and abdominal obesity in Japan, and triglyceride in China. The most influential component in diagnosing metabolic syndrome was abdominal obesity in men and triglyceride in women. CONCLUSION The prevalence of metabolic syndrome was higher in KEs than in host country residents in Japan but not in China. Abdominal obesity and triglyceride are both discriminating and influential components in metabolic syndrome.

Prevalence of hepatitis B and C virus infection among adults in Korea

Abstract To compare the prevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in three populations (urban, island, and rural areas), a seroepidemiologic study of HBV and HCV was conducted in Korea, where an HBV is endemic. The study population comprised 1733 adults at least 20 years of age: 532 (male 459, female 73) health examinees (Korean Medical Insurance Corporation [KMIC] beneficiaries) were from Pusan City (urban); 646 (male 531, female 115) health examinees (KMIC beneficiaries) were from Cheju Island (island); and 555 (male 247, female 308) volunteers were from Haman, a rural area in Kyongsangnam Province (rural). A structured questionnaire was completed for each individual by trained interviewers at the time of the health survey of the rural population. A self-administered questionnaire was completed by the health examinees in the urban and island populations. The prevalence of HBsAg in the three populations (age- and sex standardized) was 5.1% in the urban, 6.9% in the island, and 6.1% in the rural populations. These values were not significantly different from each other or from the national population. In contrast, the prevalence of anti-HCV in the rural population (age- and sex-standardized) was 5.4%. This value was higher than that of the urban (0.8%) and island (0.6%) rates. A history of transfusion was not associated with the HCV infection. This study suggests that the rural area is highly endemic for HCV infection and the route of HCV infection is other than blood transfusion in Korea.

Double-Filtration Plasmapheresis plus IFN for HCV-1b Patients with Non-Sustained Virological Response to Previous Combination Therapy: Early Viral Dynamics

Double-filtration plasmapheresis (DFPP) was approved in Japan in April 2008 for the retreatment of chronic hepatitis C patients with genotype 1b and high viral loads, whose hepatitis C virus was not eradicated by earlier IFN therapy or by pegylated IFN plus ribavirin (PEG-IFN/RBV) combination therapy. In this study, we assessed the early viral dynamics of 9 patients with non-sustained virological response to the combination therapy. The overall viral dynamics of DFPP plus IFN treatment with or without RBV for 4 weeks showed a reduction of ≧1 log in the viral load in 22% (2 of 9 patients), 55.6% (5/9), 77.8% (7/9) and 77.8% (7/9) at 24 h, 1, 2 and 4 weeks after the start of treatment. By contrast, DFPP plus consecutive intravenous IFN-β for 4 weeks reduced the viral load by ≧1 log in 33% (2/6), 50% (3/6), 83.3% (5/6) and 83.3% (5/6) at 24 h, 1, 2 and 4 weeks. The viral load declined by ≧2 log in 50% (3/6) at 4 weeks after the start of treatment. DFPP plus consecutive intravenous IFN-β for 4 weeks is a promising treatment for non-sustained virolgical response patients.

Pegylated Interferon plus Ribavirin Combination Therapy for Chronic Hepatitis C with High Viral Load of Serum Hepatitis C Virus RNA, Genotype 1b, Discontinued on Attaining Sustained Virological Response at Week 16 after Onset of Acute Pancreatitis

Recent clinical trials have shown that pegylated interferon-α (PEG-IFN-α) in combination with ribavirin (RBV) improves the rate of sustained virological response (SVR), with over 50% of patients demonstrating a positive response to treatment. However, no SVR has been reported when PEG-IFN/RBV combination therapy is discontinued by week 16, especially in cases of chronic hepatitis with a high viral load of serum hepatitis C virus (HCV) RNA, genotype 1b. Here, we describe SVR in a 67-year-old woman whose PEG-IFN/RBV combination therapy for chronic hepatitis C with a high viral load of serum HCV RNA, genotype 1b, was discontinued after 16 weeks because of the onset of PEG-IFN plus RBV-induced acute pancreatitis. Among viral factors, substitution of amino acid 70 (Arg) and 91 (Leu) in the core region and HCV RNA negativity were observed after 8 weeks. Host factors including low body weight, no alcohol consumption, no coinfection with hepatitis B virus, slight fibrosis, and viral factors including early viral clearance, double wild type in the core region, may have contributed to the SVR irrespective of the discontinuation of the combination therapy at week 16. Moreover, PEG-IFN plus RBV-induced acute pancreatitis might have been related to the SVR.