Shigenobu Takayama

Prevalence and persistence of a novel DNA TT virus (TTV) infection in Japanese haemophiliacs.

To clarify the clinical implication of a newly discovered ‘TT virus (TTV)’, we assayed TTV DNA in sera from 50 haemophiliacs by a seminested‐PCR. TTV DNA was detected in 75% (35/50), which was a much higher prevalence than for HBV (HBc‐Ab), HCV RNA, or HGV RNA. In particular, TTV DNA was found in 44.4% (4/8) of patients who had been treated only with virally inactivated factor VIII concentrates. Elevated ALT levels were observed in patients with HCV RNA and TTV DNA; however, the elevation in TTV DNA was obtained from patients co‐infected with HCV RNA (62.9%, 22/35). There was no significant difference in ALT levels between TTV DNA‐positive and DNA‐negative in patients without HCV RNA. 85.3% (35/41) of TTV DNA‐positive sera in 1990 were again positive for TTV DNA in 1995. These findings suggest that many haemophiliacs have been infected with TTV. Although TTV infection was not associated with serum ALT elevation, persistent TTV infection may contribute to cryptogenic hepatic failure in haemophiliacs.

An application of apo(a) isoforms for the clinical assessment of Lp(a).

To examine whether or not Lp(a) is applicable as a diagnostic marker for atherosclerosis, we studied the correlation between Lp(a) levels and molecular weights of apo(a) isoforms in sera from both normal healthy adults and diabetic patients. Serum Lp(a) level was measured by turbidimetric immunoassay (TIA) and the molecular weight of apo(a) isoform was determined by Western blotting analysis. The serum Lp(a) levels of the diabetic patients (25.0 mg/dl ± 2.2 [mean ± SE], n = 54) were significantly higher than those of the normal subjects (14.4 mg/dl ± 0.57, n = 500). With respect to the correlation between serum Lp(a) levels and the molecular weights of apo(a) isoforms, there was an inverse correlation in sera from normal subjects (n = 298), whereas there was no correlation in sera from the diabetic patients. Statistical significant inverse correlation (r = –0.91, y = 224.25 – 3.07×) was especially observed in 50 representative apo(a) isotypes from the normal subjects. By applying a standardized curve based on the significant inverse correlation to serum Lp(a) levels, 40.7% (22/54) of the diabetic patients were revealed to have an abnormally high value of serum Lp(a). Moreover, it was found that the significantly higher mean value of serum Lp(a) in the diabetic group was caused by the 22 patients with higher value of Lp(a). The present findings suggest that determination of apo(a) isoform size provides estimation of the serum Lp(a) value and that the inverse correlation curve between serum Lp(a) level and the molecular weight of apo(a) isoform may be applicable to the clinical use of Lp(a). J. Clin. Lab. Anal. 14:53–58, 2000.

Interferon therapy for Japanese hemophiliacs with chronic hepatitis C

Eight Japanese hemophiliacs with chronic hepatitis C (CHC) received interferon (IFN) therapy and four of them (50%) responded completely. Non‐responders included 3 double‐infected patients: I with hepatitis B virus (HBV) and 2 with human immunodeficiency virus‐1 (HIV‐1). In one of the patients with HIV‐1 double infection, the absolute number of CD4* lymphocytes decreased during IFN therapy. These findings suggest that hemophiliac patients with CHC can respond well to IFN therapy, but in patients who are double‐infected with HBV and HIV‐1, the indication of IFN therapy should be considered seriously.

Investigation of hepatitis C antibody in hemophilia patients.

Twenty-one hemophilia patients followed at St. Marianna University Hospital were investigated for the detection of antibody against hepatitis C virus (HCV). All patients had been received at least three years. We examined HCV antibody serially for those patients. The relation between titer of HCV antibody and the levels of alanine aminotransferase (ALT) was studied.The overall prevalence of HCV antibody positivity was 85.7% (18/21 patients). Four patients went from seropositive to seronegative, however, fourteen patients were repeatedly seropositive. In these four patients, three of them showed normalized ALT levels accompanied with decreased levels of HCV antibody.Furthermore, six repeatedly seropositive patients and three seroconverted (from seropositive to seronegative) patients were investigated to detect HCV genome by reverse transcription-polymerase chain reaction (RT-PCR) technique using NS-5 region primers diverted from the HCV nucleotide sequence (Houghton et al. European patent 0318216. 1989).In five of the former six patients HCV genome were detected, but in the latter three patients HCV genome could not be detected.