Kazuhiko Miyake

Epstein-Barr virus infection resembling autoimmune hepatitis with lactate dehydrogenase and alkaline phosphatase anomaly

Abstract: A 73-year-old man had fever, lymphadenopathy, granulocytopenia, thrombocytopenia, ascites, pleural effusion, liver injury, and an allergic-like skin rash. Autoantibodies, such as anti-nuclear antibody, were shown, and there were lactate dehydrogenase and alkaline phosphatase anomalies and platelet-associated IgG. His liver injury resembled that in autoimmune hepatitis. He was diagnosed with Epstein-Barr virus (EBV) infection associated with autoimmunization because of his clinical course, fluctuation of anti EBV antibodies and positive EBV genome in circulating lymphocytes and serum. This case suggests a close relationship between EBV infection and autoimmunization or autoimmune-like hepatitis.

Naturally occurring anti-interferon-α2a antibodies in patients with acute viral hepatitis

The occurrence of antibodies against recombinant human interferon‐α2a (IFN‐α2a) in patients with acute viral hepatitis (AVH) was examined by ELISA. Naturally occurring IgG anti‐IFN‐α2a were found in 50% of patients with type A, 50% of those with type B and in 8.3% of those with non‐A, non‐B AVH. The corresponding frequencies of IgM antibodies were 80%, 30% and 33.3%, respectively. IgM anti‐IFN‐α2a were found more frequently in patients with AVH type A than in normal control subjects (P < 0.01). Anti‐IFN‐α2a were detectable at the highest frequency 3 weeks after acute onset and then became negative. An absorption experiment revealed that IgM anti‐IFN‐α2a did not cross‐react with recombinant human IFN‐α2b. Immunoblotting analysis confirmed the binding of antibodies to IFN‐α2a. Sera positive for IgG and/or IgM anti‐IFN‐α2a were unable to neutralize IFN‐α2a. The appearance of anti‐IFN‐α2a was not correlated with disease severity. There was no evidence to suggest that anti‐IFN‐α2a impaired the elimination of hepatitis virus. This is the first study to demonstrate the occurrence of anti‐IFN‐α2a in patients with AVH. Detection of anti‐IFN‐α2a may be useful for clarifying any underlying immune events in various diseases.

Effect of interferon on GB virus C and hepatitis C virus in hepatitis patients with the co‐infection

Of 74 patients who were infected with hepatitis C virus (HCV) and received interferon, 12 (16%) were positive for RNA of GB virus C (GBV‐C). RNA of GBV‐C was determined in sera from the co‐infected patients retrospectively, and the effect of interferon on GBV‐C was compared with that on HCV in them. Titers of both GBV‐C and HCV RNAs decreased during interferon in all of them. Two patients lost both GBV‐C and HCV RNAs and remained clear until 6 months after treatment with interferon, while 2 lost RNA for GBV‐C only and 2 for HCV RNA alone. Low pre‐treatment RNA titers of GBV‐C and HCV correlated with the efficacy of interferon in clearing. Alanine aminotransferase returned to normal only in the patients who lost HCV RNA, regardless of the persistence or loss GBV‐C RNA. These results indicate that the response to interferon of GBV‐C is comparable to but independent of that of HCV and that the persistence of GBV‐C would not prevent the normalization of aminotransferases in response to interferon in patients with chronic hepatitis C. J. Med. Virol. 52:156–160, 1997.

Ursodeoxycholic acid therapy for chronic type C hepatitis: A multicenter, dose-finding trial

Abstract Ursodeoxycholic acid (UDCA) was administered orally for 12 weeks to 40 patients with chronic type C hepatitis. Patients were randomly assigned to receive UDCA 150 mg/day (n = 20) or 450 mg/day (n = 20). In the 450-mg group, alanine aminotransferase (ALT) decreased significantly ( P P P P

Improvement of the sandwich ELISA for the determination of basement membrane collagen complex in sera of patients with chronic liver diseases by utilizing the chaotropic ion, NaSCN

Abstract The sandwich ELISA for the determination of basement membrane collagen complex (BCC), which is composed of type IV collagen and basement membrane-associated collagen (BAC), in sera of patients with chronic liver diseases was improved by using the chaotropic ion, NaSCN. NaSCN activated the immunoreactivity of endogenous BCC in sera in a concentration-dependent manner and showed the maximum effect at 400 mM. Intra- and inter-assay coefficients of variation were below 6.9% and below 11.9%, respectively. Recovery of standard BCC added to a normal or a pathological serum was 102.4 to 108.0%. The BCC levels in sera of patients with chronic hepatitis and liver cirrhosis showed significantly higher values than those in serum of healthy volunteers, which was consistent with the immunohistochemical analysis in which the staining of BAC of the liver cirrhotic tissue was much increased as compared with that of normal liver tissue.

Involvement of GBV-C/HGV in liver diseases in Japan

Abstract A questionnaire survey was conducted of members of the NANB Hepatitis Research Group of the Japanese Ministry of Health and Welfare on the incidence of GBV-C/HGV RNA-positivity among HCV, HBV, and non-B-C infected patients to clarify the involvement of the newly discovered GBV-C/HGV in hepatic diseases in Japan. As a result, GBV-C/HGV RNA was detected in about 10% of HCV-infected patients, 5% of HBV-infected patients, and 5% of patients with non-B non-C hepatitis. With HBs antigen-positive patients, the GBV-C/HGV positivity rate increased with the progression of liver disease from 3.9% with chronic hepatitis, 5.4% with liver cirrhosis, and 9.1% with hepatocellular carcinoma. This increase was not observed with HCV RNA-positive and non-B, non-C patients. Also no GBV-C/HGV RNA-positive patients were seen among HCV RNA-positive fulminant hepatitis patients having no history of use of blood or blood products. These results suggest that although GBV-C/HGV may possibly be involved as a causative virus in some non-A-E hepatitis in Japan, it is not a main cause. If HBV-infected patients are excluded, it is almost possible to conclude that GBV-C/HGV is not involved in the progression of chronic liver disease. Although a very slight possibility exists that GBV-C/HGV infection may be a cause of fulminant hepatitis, the data suggest that it is not a major cause.

Efficacy of interferon retreatment in chronic hepatitis C patients whose hepatitis had relapsed after initial treatment.

初回IFN治療で無効と判定され, IFN再治療を受けたC型慢性肝炎例30例についてその治療効果を検討した. 初回治療のIFN投与量が400MIU以上であった17例中再治療著効例は3例 (18%) であったのに対し, 初回400MIU未満の13例では5例 (38%) が再治療で著効となった. 再治療著効例のうち初回IFN投与量が400MIU以上の3例全例は初回治療終了時にはHCVRNAが陰性化していたが, 初回投与量が400MIU未満の5例中3例は初回治療終了時にもHCVRNAが残存していた. 初回IFN投与量が400MIU未満であった症例は6カ月のIFN再治療でも初回治療例に近い著効率が得られる可能性が示唆された. HCV genotype 2aないし2b型は著効例中では63%, 無効例中では18%であり著効群で有意に高率であった. HCV genotypeは再治療でも有効な効果予測因子であった.

Phenotypes of α1-antitrypsin in liver diseases

肝疾患患者761名の血清α1-アンチトリプシン表現型の分布を正常者648名を対照として新しい方法であるpolyacrylamide gel slab isoelectric focusingを用いて検討した.正常者群で,MMが99.2%, rare variants 0.8%,肝疾患患者群で,MMが98.8%, rare variants 1.2%であった.欧米と比較しMMが圧倒的に多く,また欠乏症を呈するZ遣伝子が検出されなかった.このようにα1-アンチトリプシン表現型の分布には民族差が認められた.慢性肝疾患患者中に欧米では稀であり,α1-アンチトリプシン濃度が低値を示すPのheterozygotesが4名認められた.この患者の肝生検組織にはα1-アンチトリプシンの蓄積は認められなかった.Isoelectric focusingによりMMがさらに3つの亜型,M1M1, M1M2, M2M2に分類され,3群間に血中濃度差(M1M1＞M1M2＞M2M2)が認められた.低値群のM2M2の出現頻度が正常者群で4.9%であるのに対し,慢性肝疾患患者群に10.8%と有意に高頻度に観察された(p＜0.001).