Search

Hepatitis B virus (HBV), with a G-to-A point mutation at nucleotide 83 in the precore region (mutant HBV83), accounts for most cases of hepatitis B e antigen (HBeAg)-defective HBV. However, it is still not clear how mutant HBV83 is associated with HBe seroconversion. Twenty-six HBeAgpositive patients with chronic hepatitis B who received oral prednisolone (30 mg/day) for 3 weeks were studied to clarify the prevalence of mutant HBV83 during the treatment using polymerase chain reaction with a restriction fragment length polymorphism assay. Twelve (46%) patients seroconverted to anti-HBe 1 year after treatment, whereas 14 (54%) did not. The proportion of mutant HBV83 to whole HBV remained unchanged in both groups during an acute exacerbation induced by withdrawal of corticosteroids. Among 12 anti-HBe-0seroconverted patients, five (56%) of nine patients with only wild-type HBV at baseline developed detectable levels of mutant HBV83 while all three patients with a mixed viral population of wild-type HBV and mu tant HBV83 at baseline developed a higher pro portion of mutant HBV83 one year after treat ment. In contrast, these changes were observed in only one (14%) of seven who failed to seroconvert. The results indicate that a flare-up of hepa titis precedes emergence or selection of mutant HBV83, followed by HBe seroconversion in patients with chronic hepatitis B. © 1995 WiIey-Liss, Inc.

Propagermanium (PPG), an organic germanium compound, is thought to inhibit hepatitis B virus (HBV) replication and eliminate it from the system through immunostimulation and protection from viral infection by increased interferon (IFN) production at the infected area. In a double blind comparative study with an inactive placebo, PPG significantly decreased alanine aminotransferase (ALT) levels and HBV e antigen (HBeAg) titers, and increased anti-HBe antibody (HBeAb) inhibition rates. Comparison with the placebo group revealed that these changes were significantly larger in the PPG group. Seroconversion was found in 27% of PPG-treated patients after treatment, and HBeAg was undetectable in 41%. These results were comparable to those of various IFN treatments. In liver histology, improvement was found mainly in necrosis and inflammation in the lobule. The low frequency of adverse effects (4.9%), none serious, indicated that PPG is quite safe. It is thought that PPG, administered orally, is a clinically useful drug as a remedy for chronic hepatitis.

Hepatitis B virus (HBV) carriers and patients with acute hepatitis B living in the Kamigoto islands, a part of Japan with a high incidence of HBV carriage, were retrospectively tested for serum anti-hepatitis D virus (anti-HDV) and they were compared with the inhabitants of Oita City (an area with an average HBV carriage rate). The prevalence of anti-HDV in HBV-infected individuals was 8.3% (42/507) in Kamigoto and 0% (0/101) in Oita City. With one exception, all of the positive serum samples in Kamigoto were collected before 1986, and the mean age of the positive individuals was significantly younger than that of the negative individuals (P < 0.005). Among the 42 anti-HDV-positive patients, nine (21%) had definite liver disease. The route of infection was uncertain in most cases (i.e. sporadic), but two pairs of mothers and children were detected. Although the prevalence of anti-HDV positivity in Japan has been reported to be very low (about 1% or less), the present investigation showed that the local spread of HDV infection in Kamigoto occurred on a minor scale up to 1986. The infections presumably resulted from the closed environment and the high incidence of HBV carriage in these islands. Accordingly, there could be a considerable risk of the outbreak of HDV infection in the future under similar conditions, even in countries where the disease has never been detected previously.

In order to analyze the clinical significance of the various HCV epitopes, we compared the results of different HCV specific assays with HCV-RNA, determined in serum by RT-PCR method using primers to the 5' untranslated region of HCV-RNA. Among 73 patients with chronic NANB liver disease, 93% were positive for C22-3, 96% for C33C, 81% for C100-3 and 91% for RT-PCR. Positivity rates for 537 healthy subjects were 1.7% for C100-3 and 2.9% for second generation anti-HCV. A total of 6 persons were positive for C22-3 but not C100-3; all were negative for HCV-RNA. In 11 of 30 patients treated with interferon and HCV-RNA became negative and remained so for more than 24 months. In these 11 sustained responders, C100-3 and C33C antibody declined progressively, but C22-3 antibody showed a little change after treatment by quantitative analysis. The discrepancy of changes to NS region and core region after interferon treatment is consistent with a different clinical significance of reactivities to these HCV epitopes. Thus negative reactivity to NS region but positive for core region among healthy subjects may indicate past infection with HCV. Presence of antibodies to NS epitopes is implicated in HCV replication, while core epitopes indicate both present and past HCV infection.

We report a 42-year-old Japanese woman with Recklinghausen's neurofibromatosis 1 (NF1) who developed mixed connective tissue disease (MCTD). Previously experiencing good health without an increase in subcutaneous nodules, she presented with Raynaud's phenomenon, swollen hands and polyarthralgia Clinical examination revealed a high titer of anti-RNP antibody, and she was thus diagnosed as having MCTD. She was treated with oral prednisolone (10 mg/day) and her symptoms improved rapidly. Since the association of MCTD and NF1 has not been reported previously, we concluded that this association is rare. We also discussed the association of NF1 and autoimmune diseases including MCTD.

Seven smaller than 2 cm in diameter hepatocellular carcinomas (HCC) undetectable by hepatic arteriography and computed tomography (CT) after intraarterial injection of iodized oil (Lipiodol CT) were diagnosed by ultrasonography-guided fine-needle biopsy in 6 patients. All lesions were treated by percutaneous ethanol injection (PEI) in 1-3 weekly intervals. No recurrences have been demonstrated after 7-15 months. The treatment of HCCs undetectable by angiography and Lipiodol CT presents a problem as transcatheter arterial embolization is considered ineffective due to poor vascularity. PEI appears to be an excellent treatment for these small HCCs.

10 different HCV-specific assays and RT-PCR of the 5' untranslated region of HCV RNA were used to analyze sixty-four patients with chronic NANB liver disease. Po, CP-9 and C22 antigens are located in the putative core; C33c in the putative NS3; C100-3 in the putative NS3/4; KCL in the putative NS4/5 and C825 is located in the putative NS5. GOR protein is not part of the HCV genome, but antibodies to it appear to be present in response to a hepatitis C infection. Positive rates were 91% for Po, 89% for CP-9, 94% for C22, 97% for C33c, 88% for C100-3 (Ortho, EIA), 86% for C100-3 (Abbott, EIA), 84% for C100-3 (Ohtsuka, RIA), 88% for KCL, 59% for C825, 58% for GOR, and 83% for RT-PCR. There were 8 cases which were negative by all anti-C100 tests. 7 of these cases were positive by other anti-HCV markers and/or PCR suggesting the need for improved blood screening assays. There is a variation in the relative reactivity for different markers with different samples. Of the tests employed, anti C33c shows the highest positivity rate.

— In a 6-month follow-up study of acute hepatitis in Japan, 31 out of 41 (75.6%) cases of post-transfusion non-A and non-B hepatitis (NANB-PTH) and 14 out of 40 (35.0%) cases of sporadic non-A non-B hepatitis (NANB-SPO) were found to be positive for antibody to the hepatitis C virus (HCVAb). After 12 months of follow-up, 30 cases (81.1%) became chronic among 37 HCVAb positive acute NANB hepatitis cases. This figure shows a significantly higher rate of chronicity as compared with HCVAb negative acute NANB hepatitis. The prevalences of HCVAb in hepatitis B surface antigen (HBsAg) negative cases of chronic hepatitis and liver cirrhosis were 76.3% (200/262) and 66.7% (106/159), respectively, which were significantly different from the values of 5.1% (13/255) and 10.6% (13/123) observed in HBsAg positive cases. Of chronic liver disease cases positive for HCVAb, 45.8% (152/332) had a history of blood transfusion, in contrast to the value of 3.7% (13/352) observed in HBsAg positive cases of chronic liver disease that were negative for HCVAb.

肝細胞癌の早期診断はきわめて難しい.著者らは細小肝細胞癌7例を経験したので,その臨床病理学的特徴につき述べる.7例中6例は診断時自覚症状は軽微であった.臨床所見中変形し増大する肝腫に注目する必要がある.血中AFPは5例が陽性で診断に役立ち,とくに経時的な追跡測定が重要である.特異的診断法ではないが,HBs抗原,アルカリホスファターゼ,総コレステロール,LDH, LAP,トランスアミナーゼ解離が有用な例があった.肝動脈造影は有力な診断法で5例にTumor stainがみられた.AFP陰性,肝動脈造影でTumor stainがみられない2例中1例は腫瘤の吸引細胞診で診断がついた.組織型は全例索状型であった.非癌部組織は全例肝硬変または肝線維症で,肝細胞癌の治療上の問題点につき述べた.術後4年生存している1例では,肝シンチグラム,肝動脈造影で切除部は修復されており,肝硬変でも再生するこ とを示していると考えられた.

In Japan, the national counterplan for prevention of mother-infant hepatitis B virus (HBV) transmission with HB vaccine was established in 1985 after 10 years of clinical trials with human hepatitis B immunoglobulin (HBIG). The preventing method is based on passive-active prophylaxis with HBIG and HB vaccine, and only infants from HBe antigen-positive mothers can receive this administration. We compared the effectiveness of several methods of administration of HBIG and HB vaccine for 1199 infants. The rate of infants who became HBV carrier state was 6% out of all the subjects. The prophylaxis in which infants were injected with HBIG just after delivery and with HB vaccine as soon as possible after birth was superior to the others in protective efficacy. The infants injected just after delivery showed no harmful effects. These results suggest the possibility and necessity of improved administration methods which will reduce the stress for infants and economic burden for their parents.

HBe抗原陽性HBVキャリアー妊婦127例を対象にHBV感染に及ぼす妊娠・分娩の影響を調べた.全例妊娠後半には肝機能は正常化する傾向があり, 101例は分娩後3カ月以内にGPTの異常が見られ, 1年以内に25例(24.8%)でHBe抗原が陰性化した.分娩後に肝機能の異常が見られなかった26例は全例HBe抗原陽性のままであった.分娩1カ月前のHBe抗原がcut off値で3.0未満では66.7%でHBe抗原が陰性化しており,希釈後測定した成績でもHBe抗原の値が低い例で分娩後早期にHBe抗原が陰性化していた.妊娠中に分泌されるステロイドホルモンがHBe抗原に影響していると思われる.

A型急性肝炎41例の発症後経時的に得られた血清につき,RIA (HAVAB)法およびIAHA法によりHA抗体の動態を検索すると共に病初期one point血清での診断法を検討した.IAHA法では発症後もしばらくHA抗体活性が検出されず,発症4週ないし10週よりようやく検出された.従って病初期と10週以後のペア血清があれば診断可能であるがretrospectiveにしか診断されない難点がある.RIA法では病初期からHA抗体活性が検出された.発症時の主な抗体活性はIgM抗体であり,回復期のものはIgG抗体であった.2mercaptoethanol処理血清と非処理対照のHA抗体活性を測定し両者の比M-indexを算出するとA型肝炎初期の血清では1.5以上の値が得られone point血清のみによるA型肝炎の診断が可能であることが分った.発症期と回復期のペア血清を用いRIA法でHA抗体を検出する場合も血清の2ME処理を行った方がより確実に診断出来ることが分った.

Recently Irgasan DP 300 (DP) has been widely used as an inactivator of HBs antigen. Although some literatue reports negative opinions on the effect of the agent, it must be practically used as an antiseptic in HBs antigen positive patients, because there is no other suitable inactivator which may directly contact the skin. In Nagasaki Chuo Hospital, it was suspected that many inpatients had dermatitis after use of 0.5% DP in 70% ethanol. Hence, the investigation was held in the liver disease ward, and the following three kinds of alcohol solutions were used as antiseptics for 50 inpatients for 2 weeks to replace 30 % isopropanol: a) 70% ethanol, b) 0.3% DP alcohol, c) 0.5% DP alcohol. DP was studied in terms of thin-layer chromatography (TLC), pH and UV spectrum. The results were as follows: 1) The usage of 0.3% DP in the ward caused dermatitis in 8 patients and 0.5% DP in 4 patients. The patch test revealed 1 positive patienst DP. But it was impossible to distinguish the irritation potential of 0.3% DP alcohol from that of 0.5%. 2) The pH value of 0.5% DP alcohol showed not a remarkable change after exposure to sunlight. The TLC and UV spectrum also produced no change. It is reported that DP does not cause severe irritation in the skin, but the results of these studies do not support such view so far as alcohol solution of DP is concerned. Hence, the application of DP alcohol must be carefully controlled; particularly it should not be applied to the skin for a long period.

大動脈瘤が胸腔内に直接破裂しながら34日間も生存したまれな例を経験したので,報告した. 51才,男.高血圧,狭心症の既往あり.講演後,突然左胸部の激痛後ショック状態に陥つたが,約10時間後に回復.以後増悪軽快をくり返しながら,発作後26日目に当科へ担送入院.左全血胸を呈し,縦隔を右方へ圧排す.血管造影で左肺血管系は造影されず,胸部大動賑は拡大蛇行し,壁の著明な不整を認めた.対症治療中,第34病日に死亡す.剖検で胸腹部大動脈にアテローム硬化性真性大動脈瘤があり,胸部大動脈瘤の一つが左側胸腔内へ直接破裂し,左胸腔は5000ml以上の血液および血塊で満たされていた.

A new enzyme‐linked immunosorbent assay (ELISA) for detecting the antibody to a human T‐lymphotropic virus type I (HTLV‐I) tax gene product, p40tax, has been developed. By this ELISA method, we have investigated the relationship between the presence of p40tax antibody in HTLV‐I‐infected mothers and the virus transmission rate from mothers to their children. The rate of mother‐to‐child transmission of HTLV‐I was higher in P40tax antibody‐positive mothers than in antibody‐negative ones. Thus, the presence of P40tax antibody may indicate an increased risk of vertical transmission of HTLV‐I.

The efficacy of Shosaiko-to (SST) on 222 patients with chronic active hepatitis was studied in a double-blind multicenter clinical study. One hundred and sixteen patients received SST in a daily oral dose of 5.4 g for 12 weeks, followed by the same dose for a further 12 weeks. One hundred and six patients received a placebo containing 0.5 g of SST for 12 weeks, followed by a cross-over to SST for a further 12 weeks. Among the liver tests, serum AST and ALT values decreased significantly with the administration of SST. The difference of the mean value between the SST group and the placebo group was significant after 12 weeks. In patients with chronic active type B hepatitis, a tendency towards a decrease of HBeAg and an increase of Anti-HBe antibodies was also observed. No remarkable side effects were noticed.

In order to estimate age specific prevalence of Anti HA in Japan, 1757 serum samples from healthy subjects or patients with nonhepatic disease taken in 6 different districts of Japan were tested for Anti HA using HAVAB Kit. Very low prevalence, less than 10%, was observed in young adults or children. These facts indicate the young Japanese are quite susceptible to HAV infection and the effective preventive measures are urgently needed. Over all prevalence of Anti HA was 56.2%. Comparing the age specific prevalence of Anti HA in Japan with those in other countries, the situation in Japan was in intermediate between highly endemic South-East region and developed European countries.

Hepatitis C virus RNA (HCV-RNA) and serological markers of HCV infection were measured in 30 patients with chronic hepatitis C who had been treated with interferon (IFN). Patients were classified into four groups according to serum alanine aminotransferase (ALT) levels after treatment. These were: as complete responders (CR); partial responders (PR); transient responders (TR); and non-responders (NR). In all 11 patients in the CR group, HCV-RNA disappeared from serum for at least 24 months and anti-c100-3 decreased progressively during this time. In the PR group, four of five patients were positive for HCV-RNA in spite of the improvement of ALT levels and decline of anti-c100-3. In the TR and NR groups, HCV-RNA disappeared transiently or remained persistently positive. The results indicate that IFN-mediated improvement of ALT and decrease of anti-HCV (anti-c100-3) were not always related to the disappearance of HCV-RNA from serum. On the other hand, sustained disappearance of HCV-RNA from serum was demonstrated in the patients who did not have post-treatment ALT relapse. This indicates that IFN can eradicate HCV from serum in some patients and provide a clinical remission of chronic hepatitis C.

In this study the morphological changes in the livers of marmosets inoculated with stool extracts from epidemic non-A, non-B hepatitis patients in India were examined. The histologic changes of epidemic non-A, non-B hepatitis in marmosets consisted mainly of round cell infiltration in the portal tracts, spotty liver cell necrosis, sinusoidal lymphocyte infiltration, and Kupffer cell mobilization. By electron microscopy, liver cells from infected marmosets showed cisternal dilation of the endoplasmic reticulum, irregularly-shaped nucleus, and disorganization of the mitochondrial cristae. In some areas interaction of lymphocytes with hepatocytes was observed. Similar observations have been made in type B hepatitis infection, presumably due to liver cell damage mediated by immune mechanisms. The result of our study is also compatible with the interpretation that the liver cell damage in this experimental model may be mediated by immune mechanisms.