Koji Orii

Investigation of SEN Virus Infection in Patients with Cryptogenic Acute Liver Failure, Hepatitis-Associated Aplastic Anemia, or Acute and Chronic Non–A–E Hepatitis

SEN virus (SENV) has been tentatively linked to transfusion-associated non-A-E hepatitis. We investigated SENVs role in unexplained hepatitis in other settings. Polymerase chain reaction amplification was used to detect 2 SENV variants (SENV-D and SENV-H) in 1706 patients and control subjects. SENV was detected in 54 (22%) of 248 patients with acute or chronic non-A-E hepatitis, 9 (35%) of 26 patients with hepatitis-associated aplastic anemia, and 0 of 17 patients with cryptogenic acute liver failure, compared with 150 (24%) of 621 control subjects with liver disease and 76 (10%) of 794 healthy control subjects. When controlling for geographic region, the prevalence of SENV among case and control subjects was not significantly different. The severity of acute or chronic hepatitis A, B, or C was not influenced by coexisting SENV infection. No etiological role for SENV in the cause of cryptogenic hepatitis could be demonstrated.

Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core‐related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment

Summary. We aimed to assess the clinical performance of a newly developed chemiluminescence enzyme immunoassay (CLEIA) for the detection of hepatitis B virus (HBV) core‐related antigen (HBcrAg) in patients with chronic HBV infection. A total of 82 patients with chronic HBV infection and 167 HBV‐negative controls were studied. HBcrAg was measured by CLEIA with monoclonal antibodies to hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg), and HBV DNA was measured by transcription‐mediated amplification assay (TMA) and in‐house real‐time detection polymerase chain reaction (RTD‐PCR). The HBcrAg assay detected viremia in 189 of 216 samples (88%) collected from 72 patients whilst the TMA assay detected viremia in 178 of the 216 samples (82%) (P = 0.019). The HBcrAg concentration correlated linearly with the HBV DNA concentration (P < 0.001) over a range which varied 100 000‐fold. The accuracy in the measurement of the patients’ HBV load obtained using the HBcrAg assay was not affected by the absence of hepatitis B e antigen from the serum or the presence of precore mutations in the HBV genome. In patients without anti‐viral drugs, changes in their serum HBcrAg concentration over time corresponded to their HBV DNA concentration. In six additional patients who were later treated with lamivudine, HBV DNA concentration declined more rapidly than their HBcrAg concentration. Three months after treatment commenced, the ratio of HBcrAg: HBV DNA had increased in all six patients (P = 0.031). The HBcrAg assay is a sensitive and useful test for the assessment of a patients HBV load. When monitoring the anti‐viral effect of lamivudine, HBcrAg provides a viral marker which is independent of HBV DNA.

Association between SEN Virus Infection and Hepatitis C in Japan

There is a strong association between 2 SEN virus (SENV) variants (SENV-D and SENV-H) and transfusion-associated non-A-E hepatitis. In total, 200 subjects from a Japanese region where hepatitis C virus (HCV) is highly endemic and 194 persons from a contiguous area where HCV is not endemic were tested for SENV-D and SENV-H DNA by polymerase chain reaction. SENV DNA was detected equally in subjects from each area (56% prevalence in the area of high endemicity vs. 61% in the nonendemic area). Age-specific prevalence of SENV was similar to that of TT virus, with equal distribution at all ages in both areas; HCV was predominant in the elderly population. Alanine aminotransferase levels were significantly associated with HCV viremia but not with SENV viremia. SENV is a common infection that appears to have transmission routes and age-related prevalence that are distinct from those of HCV. No evidence was found that SENV caused hepatitis or worsened the course of hepatitis C.

Seroepidemiological study of hepatitis E virus infection in Japan using a newly developed antibody assay

Purpose. A seroepidemiological study of hepatitis E virus (HEV) infection was conducted in Japan, where HEV infection is not considered endemic. Methods. IgG and IgM class antibodies to HEV were measured with a newly developed enzyme-linked immunosorbent assay in which recombinant virus-like particles were used as an antigen. A total of 1253 individuals (401 males and 852 females; age range, 6–89 years) were enrolled from two different areas: area 1 (n = 478), in which hepatitis C was endemic; and area 2 (n = 775), in which it was not endemic. Results. The HEV antibody (IgG class) positive rate was 6.7% in area 1 and 4.6% in area 2. Similarly, the HAV antibody (IgG class) positive rates were 65.3% and 72.3%. The age- and sex-specific prevalence of both HAV and HEV antibodies was quite similar in the two areas, and the HAV antibody positive rate clearly increased with age in both males and females. On the other hand, the HEV antibody positive rate showed a slight tendency to increase with age in males, but not in females. None of the 32 individuals with the HEV antibody who were interviewed had a history of visiting countries in which hepatitis E was endemic. In both areas, the mean age, percentage of males, and HAV antibody positive rate were significantly higher in the group of individuals with the HEV antibody than in the group of those without it, according to conventional statistical analyses. Of the three factors age, male sex, presence of HAV antibody, and the area factor, only male sex was statistically significant (P < 0.001) on multivariate logistic regression analysis. Two (0.2%) of the total of 1253 individuals were positive for the IgM class antibody to HEV. Conclusions. Our results suggest the possibility that HEV infection is circulating in Japan at a low level. HEV infection was associated with male sex, but not with HAV infection.

Transmission of and liver injury by TT virus in patients on maintenance hemodialysis

Abstract: To study the prevalence and clinical significance of TT virus (TTV) infection in hemodialysis patients, we tested for TTV DNA in serum, using the nested polymerase chain reaction. The prevalence of TTV DNA in 352 hemodialysis patients was 32%, significantly higher than that in 50 healthy blood donors (12%). The prevalence increased with age (P = 0.0098); it was 20% (22/110) in patients aged less than 49 years, 37% (69/188) in those aged 50–69 years, and 41% (22/54) in those aged over 70 years. Other clinical features and the prevalence of other hepatitis viral markers tested did not differ between patients with TTV DNA and those without it. The detection rate of hepatitis C virus (HCV) and hepatitis G virus (HGV) viremias increased with duration of hemodialysis and with the number of blood transfusion units, but the prevalence of TTV viremia did not. Twenty-nine of 91 patients followed for 5 years were initially positive for TTV DNA. Of these 29 patients, 17 (59%) carried this viremia for at least 5 years. Fourteen of the 62 patients (23%) who were initially negative for TTV DNA acquired TTV viremia. Serum alanine aminotransferase (ALT) levels were elevated in patients with HCV viremia but not in patients with HGV or TTV viremia. However, the mean ALT level in patients with all three viremias (HCV, HGV, and TTV) was significantly higher than that in patients with one or two of the viremias. More than 30% of the hemodialysis patients had TTV viremia and the carrier state was maintained for years. The hemodialysis procedures, including blood transfusion, did not seem to be crucial for the transmission of TTV. The pathogenic effects of TTV on hepatitis appear to be limited.

Relationship between hepatitis C virus infection and schistosomal liver disease: not simply an additive effect

Background. To study the association, clinical sig-nificance, and impact of hepatitis C virus (HCV) co-infection in patients with schistosomal liver disease (SLD). Methods. A total of 240 patients with chronic liver diseases encountered consecutively were enrolled in the study. Fifty volunteer blood donors were enrolled as controls. HCV antibody determination (enzyme-linked immunosorbent assay), qualitative and quantitative HCV RNA assay (reverse transcriptase polymerase chain reaction), and HCV genotyping (line probe assay) were performed. Results. Twenty-eight patients had SLD alone, 60 had both SLD and chronic hepatitis C (CH-C), 120 had CH-C alone, and 32 had other liver diseases. The positivity rates for HCV antibody (76% vs 20%; P < 0.001) and HCV RNA (59% vs 10%; P < 0.001) were significantly higher in the patients with SLD (n = 88) than in the volunteer blood donors (n = 50). Complications of liver cirrhosis were more common in patients with concomitant SLD and CH-C than in those with either SLD or CH-C alone. The mean levels of alanine aminotransferase (77 ± 42 vs 93 ± 55 IU/l; P = 0.049) and HCV RNA concentrations (3.5 ± 1.0 vs 4.2 ± 1.0 log copy/ml; P < 0.001) were significantly lower in patients with concomitant SLD and CH-C than in those with CH-C alone. HCV genotype 4 predominated in both these groups (93% and 98%). Conclusions. SLD in Egypt is significantly associated with HCV infection, with the predominance of genotype 4. Concurrent HCV infection and SLD result in much more severe liver disease than that seen with either disease alone. However, the activity of HCV infection seems to be partially suppressed in patients with SLD.

Clinical impact of genotype 1 TT virus infection in patients with chronic hepatitis C and response of TT virus to α‐interferon

Background: The relationship between genotype 1 TT virus (TTV) infection and the status of chronic hepatitis C was studied.

Prevalence and disease association of TT virus infection in Japanese patients with viral hepatitis

Abstract Prevalence and disease association of the TT virus (TTV) were studied in Japanese patients with various types of viral hepatitis. A total of 317 patients with viral hepatitis were analyzed, and the results were compared to those of 100 apparently healthy controls. TTV DNA in serum was measured by semi-nested polymerase chain reaction. Prevalence of TTV DNA was significantly higher in patients with hepatitis A (36%, 5/14), hepatitis B (35%, 35/101), hepatitis C (61%, 90/148), and non-A-E hepatitis (41%, 22/54) than in healthy controls (12%, 12/100), respectively. In each type of hepatitis, the prevalence did not differ between acute and chronic liver diseases, and did not increase with the complication of hepatocellular carcinoma. The clinical backgrounds did not differ between TTV DNA positive and negative patients, in patients with acute hepatitis or in those with chronic liver diseases. Similarly, no liver function test showed a significantly higher level of in TTV DNA positive patients than in negative ones. In conclusion, TTV infection was highly prevalent in patients with viral hepatitis, especially in those with hepatitis C. TTV was suggested to have a weak pathogenicity (or no pathogenicity), at least when co-infecting with an established hepatitis virus.

TT virus infection in an area of high-endemicity for hepatitis C

TT virus (TTV) was recently identified as a candidate for a new hepatitis virus. In the present study, the clinical features and transmission routes of TTV infection were analyzed in an area highly endemic for hepatitis C virus (HCV) infection, and compared to those in an area not endemic. In conclusion, the prevalence of TTV infection was as high as 58% in the high-endemicity area for HCV infection. The main transmission route for TTV appeared to be different from that of HCV and HGV. TTV infection showed a reciprocal association with HCV infection, and had limited pathogenetic effect on hepatitis.

Clinical significance of T.T. virus infection in maintenance hemodialysis patients of an endemic area for hepatitis C infection

Clinical significance of TTV infection was analyzed in Egyptian hemodialysis (HD) patients. Forty-seven Egyptian patients on maintenance HD and 50 age-matched volunteer blood donors were investigated. TT virus (TTV) DNA detection and genotyping were performed using a semi-nested polymerase chain reaction with specific primers. The prevalence of TTV DNA in patients on HD (66%) was significantly (P<0.001) higher than in blood donors (24%) with genotype 1b predominance (89%) in both. Clinical background including mean age, sex, history of blood transfusion, and positive markers for either hepatitis B virus (HBV) or hepatitis C virus (HCV) did not differ between TTV DNA positive and negative HD patients. However, the mean duration of HD was significantly (P=0.032) shorter in the TTV positive patients (28+/-19 months) than in the negative ones (45+/-34 months). Mean alanine aminotransferase level in patients with HCV infection alone (41+/-24 IU/l) did not differ from that in patients with both co-infection (33+/-28 IU/l), but was significantly higher than that in patients with TTV infection alone (26+/-10 IU/l). Occurrence of chronic hepatic changes in patients with TTV infection alone (7%) was significantly less common than those with HCV infection alone (100%, P<0.001) or those with both co-infection (100%, P<0.001). Serum level of HCV core protein was similar between patients with HCV infection alone and those with co-infection with TTV. In conclusion, the prevalence of TTV infection is high in Egyptian patients on regular HD, especially with shorter duration on HD. No clinical significance of TTV virus could be elicited in HD Egyptian patients; neither it showed any clinical impact as a co-infection with HCV.