Akira Ohbayashi

Familial Clustering of Asymptomatic Carriers of Australia Antigen and Patients with Chronic Liver a Disease or Primary Liver Cancer

From sera from 54 persons from three families with the clustering of chronic liver disease and primary liver cancer, Australia antigen (Au antigen) and the antibodies against Au antigen (anti-Au) were tested by means of the immune adherence hemagglutination method. Au antigen was positive in 14 (93%) out of 15 of the affected members and their siblings, and also positive in 20 (83%) out of the 24 children of the female siblings. In contrast, Au antigen was negative in seven out of the eight children of the male siblings, and also negative in six spouses of the siblings so far tested. Anti-Au was detected only in one of the wives of the Au antigen-positive males. From these findings and from a review of familial cirrhosis in the-Japanese literature, it is suggested that, in certain kindreds, Au antigen or an Au antigenrelated infective agent is transmitted from mother to child, and is also responsible for the development of the carrier state, chronic hepatitis, cirrhosis of the liver, and eventual primary liver cancer.

Hepatitis C viral cDNA clones isolated from a healthy carrier donor implicated in post-transfusion non-A, non-B hepatitis

Using a specific hepatitis C virus (HCV) antibody assay, positive blood donors responsible for the transmission of post-transfusion non-A, non-B hepatitis (PT-NANBH) were identified. cDNA fragments were isolated from one of the plasma samples of such healthy HCV carriers by using polymerase chain reactions. Nucleotide (nt) sequence analyses of the cDNA from three different regions of the viral genome revealed that they were derived from a Japanese HCV isolate that was similar but not identical to the prototype HCV previously isolated from a chronically infected chimpanzee. Homology at the nt and amino acid levels was comparatively lower in the presumed structural region than in putative nonstructural regions. This result not only confirms that HCV antibody-positive blood contains infectious HCV, but suggests the existence of different type(s) of HCV.

INTRAFAMILIAL TRANSMISSION OF HEPATITIS C VIRUS

SiR,—Using an enzyme immunoassay for antibody to hepatitis C virus (HCV)1 we have investigated the sexual transmission of this virus in 191 sera of heterosexual patients with syphilis, gonorrhoea, condylomata accuminata, and genital herpes. We also looked for antibody to hepatitis B core antigen (anti-HBc). We used commercial tests for HCV (Ortho) and HBc antibody (Abbott). Sera from 390 age and sex matched blood donors were assessed for comparison.

Late liver-related mortality from complications of transfusion-acquired hepatitis C†

Although several cohort studies have been reported in individuals with chronic hepatitis C virus (HCV) infection, little is known about liver‐related mortality among the elderly. We conducted a cohort study in 302 patients with tuberculosis sequelae who had received a blood transfusion at a young age and had subsequently been treated at a chest clinic. The cohort consisted of 147 patients with antibody to HCV (anti‐HCV), of whom 81% were positive for HCV RNA, and 155 without anti‐HCV. The cohort was followed for a mean duration of 5.7 years. There were no differences between the two groups in the mean age of the patients at the time of transfusion (31 vs. 34 years) or at the time of entry into the study (65 vs. 66 years). The outcome of 143 patients with, and 145 without, anti‐HCV could be traced; 92 (64%) and 82 (57%) had died, respectively. The main cause of death was tuberculosis sequelae in 61 (42%) and 66 (46%) patients, respectively. Eight (6%) of the 143 patients with anti‐HCV died of liver disease (hepatocellular carcinoma: seven; rupture of varices: one). The average annual mortality from liver disease from study entry in the patients with anti‐HCV was 9.8 per 1,000 person‐years. The patients with anti‐HCV had a significantly lower cause‐specific survival probability for liver disease (92% vs. 100% at 10 years, P < .005). In conclusion, in our study, liver‐related mortality appeared to be high among elderly HCV‐infected individuals. (HEPATOLOGY 2005;41:819–825.)

A Comparative Study of Urinary Xanthopterin and Neopterin in Liver Diseases

By adsorption to activated charcoal, various pteridine derivatives in human urine are oxidized to xanthopterin. Following this oxidation, xanthopterin in urine from healthy subjects and from patients with liver diseases was assayed by high performance liquid chromatography. The mean values for xanthopterin in healthy subjects were 532 +/- 116 mumol/mol creatinine (mean +/- SD) in males and 585 +/- 153 mumol/mol creatinine in females; the difference was statistically significant (p < 0.01). Xanthopterin concentrations in patients with liver disease were significantly higher than those in normal subjects. When compared with urinary neopterin, which is a marker of activated cell immunity, xanthopterin was significantly increased even in fatty liver disease. These findings suggest that increased concentrations of urinary xanthopterin in liver diseases reflect not only the status of activated cell-mediated immunity, but also injury to liver cells.

Comparative studies on immunogenicity of Chinese hamster ovary cell derived HB vaccine and plasma derived HB vaccine

Chinese Hamster Ovary Cell derived HB vaccine (CDV) and plasma derived HB vaccine (PDV) were separately given to two groups of 131 and 112 medical stuff subjected, and both the anti-HBs responses were observed for 24 months from the time of first injection. The anti-HBs positive rate at the 7th month was 97% (mean geometric anti-HBs concentration 588 IU/L) in CDV group and 78% (83 IV/L) in PDV group, and the positive rate and mean titer of anti-HBs were always higher for 24 months in CDV group. The differences were remarkable between both the subjects aged over 40 years. The decreasing curves of the anti-HBs titer in the two groups were almost parallel; accordingly, the protective efficacy was estimated to be far longer in CDV. Also, the rate of non-responder was less lower (2.8%) in CDV group than that (15.2%) in PDV group. Above results show that CDV has a higher immunogenicity than PDV.

A case of benign postoperative intrahepatic cholestasis

腹部腫瘍のため開腹手術を受けた73歳の女性に肝内胆汁うっ滞症を認めた.手術はG.O.F.麻酔で行われ,この際5単位の保存血が輸血された.手術は約2時間で終ったが,翌日急速に黄疸を発症した.皮膚掻痒感や肝脾腫は認めなかった.血清ビリルビン値は9.7mg/dl(直接型70%)まで増加したのに対して,血清トランスアミナーゼの強い上昇は認めなかった.手術後17日目の肝生検像では,肝細胞内にビリルビンのうっ滞,毛細胆管に胆汁栓を認めたが,肝細胞の変性・壊死はなく,また細胞浸潤もみられなかった.経過は良好で黄疸および検査所見は1カ月後には正常化した.本症例はSchmidの記載にみられる良性術後肝内胆汁うっ滞症に該当しており,おそらく手術侵襲により術後一過性に肝細胞レベルでの胆汁分泌障害を起したと推測されるが,さらに今後詳細な検討が必要であろう.

Carrier state and infectivity of HBs-Ag

It has recently been clarified by Magnius and others that e antigen and antibody system is closely related to HBV infectivity, i.e., HBsAg-positive sera detected e antigen (e-Ag) have an intensive infectivity, and those detected e antibody are no infective. Therefore, the authors tested e-Ag and e-Ab by the Micro-Ochteronys method in sera from 127 carriers, and, from the data, discussed as to intrafamilial infections with HBV and the clustering of the carriers. The results are as follows. 1. In eleven children of 6 e-Ag-positive carrier mothers, 10 children were positive for HBsAg, and 3 out of 6 children of 2 e-Ag-positive carrier fathers also were HBsAg-positive. Moreover, in one of 3 children living with their e-Ag-positive grandfather, HBsAg was detected in the serum. Accordingly, it can be said that an e-Ag-positive carrier produces new carriers at a high rate in the following generations, and the rate is extremely high in mother-to-child transmission. 2. In 103 asymptomatic carriers, the frequency of e-Ag-positive result was higher in the younger ages (75% in ages of below 10 years and 12% in ages of more than 41 years). On the contrary, the rate of e-Ab-positive carriers was higher in the older ages (17% in ages of below 10 years and 44% in ages of more than 41 years). This result implies that, in the majority of HBsAg carriers, although there are wide differences in the individuals, HBV infectivity declines with years and finally vanishes.

Clinical observation on asymptomatic carriers of Australia antigen in families with clustering of chronic liver disease

High incidence of hepatitis in hospital personnels has been frequently reported. Of patients with acute hepatitis admitted to this Depar tment during the past 8 years, 25.7% were hospital staffs, and similarly, 24.7% of patients registered at the Hepatology Out-pat ient Clinic were medical and paramedical staffs. In view of the possible close connection between Australia antigen (Au) and hepatitis virus, an epidemiologic study of Au was carried out, with stress laid on the incidence of Au in personnels of medical institutions. Serum samples were obtained from 435 9 volunteers who were medical and paramedical staffs in Hokkaido district, and who had no history of hepatitis. Of a total of 64 subjects who work in hemodialysis units in 5 institutions, 6 were found to have Au, and 2 were found to have antibody (Ab) against Au, so that a total of 8 subjects (12.5%) showed contamination with Au. In one of the 5 institutions, Au was detected in 10 of 154 personnels tested, and 3 out of the 10 were hemodialysis unit personnels. In another of the 5 institutions, Ab was detected in 3 of 57 nurses, and 2 of the 3 Ab-carriers were hemodialysis unit personnels. The over-all incidence of Au and Ab in medical and paramedical staffs in these 5 institutions was approximately 5%, which was significantly higher than the estimated incidence of approximately 1% in the general population of the district. O f 200 laboratory technicians working in a number of hospitals in Hokkaido, Au was detected in 11 subjects, and Ab was found in 1, so that a total of 12 subjects (6.0%) were contaminated with Au. I t is concluded that the incidence of Au and Ab in medical and paramedical staffs are significantly higher than the incidence in general population, and hemodialysis unit personnels and laboratory technicians are especially subject to contamination. Countermeasure to this problem appears urgent.

The effects of 10% oxygen gas inhalation on lipids metabolism in several diseases, especially in liver diseases

1. In normal subjects the re la t ionship between blood ammonium and sugar levels was not obvious because ammonium levels show no deviation when glucose is administered. 2. In pa t ien ts with acute hepat i t is and chronic active hepat i t is , mild diabetic-type glucose tolerance tes t curve together with elevation of IRI and ammonium levels were observed. Blood urea n i t rogen presented no remarkable deviation. 3. The major i ty cases with c i r rhos is revealed mild diabetic-type curve with slightly elevated IRI levels. However, no definite elevation of blood ammonium and urea ni trogen levels was recognized.