Atsuhiko Kusakabe

Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus.

Background: To examine the relationship between hepatitis C virus (HCV) infection and diabetes mellitus (DM) in Japanese populations, a retrospective study was done in 866 patients with chronic viral disease. Methods: The present study included 707 HCV-infected and 159 hepatitis B virus (HBV)-infected patients. The prevalences of HBV- and HCV-related cirrhosis were 32% and 33%, respectively. A case-control study was also conducted to determine the seroprevalence of HCV infection in a cohort of 459 diabetics. Results: The prevalence of DM was higher in HCV-infected patients (20.9%; P < 0.02) than in HBV-infected subjects (11.9%). In the cirrhotic patients, DM was observed in 30.8% of the subjects with HCV compared with 11.8% of those with HBV (P < 0.01). Multivariate analysis revealed that the major independent variables associated with type II DM were male sex (odds ratio, 1.54; p = 0.020) and cirrhosis (odds ratio, 1.97; P = 0.0007). The relative odds of the development of DM were calculated to be 3.2 times higher in HCV-infected cirrhotic patients than in HBV-infected ones. In the case-control study of the diabetic cohort, 10.5% of patients were infected with HCV compared with 1.1% with HBV (P < 0.0001). The results indicate that HCV infection is closely associated with DM, compared with HBV infection. Cirrhosis was an independent risk factor for DM. Conclusions: Taken together, the findings indicate that cirrhosis appears to be a more important predictor of glucose intolerance than HCV infection, and the combination of both factors increases the risk of DM in our populations.

Changes in serum hepatitis C virus RNA titer and response to interferon therapy in patients with chronic hepatitis C

Response to interferon (IFN) therapy for chronic hepatitis C has been determined by the alteration of serum alanine aminotransferase (ALT) values. However, eradication of hepatitis C virus (HCV) could be another aim of the therapy. Thus, we serially measured serum HCV RNA levels during therapy and for at least 12 months after cessation of therapy in 65 patients with chronic hepatitis C who received IFN-α (49 cases) or -β (16 cases). The presence of HCV and its amount were measured by the combination of nested and competitive PCR. Twenty-seven patients, who were categorized as complete responders, showed sustained normalization of ALT values for more than six months posttreatment. The viral RNA titers at pretreatment were significantly lower in complete responders (logarithmic copy numbers/ml: 5.4±1.3,P<0.001) than in partial and nonresponders. Complete response rate was significantly higher in patients with HCV genotype III (68.4%,P<0.01) than those with type II (23.6%). Among 27 complete responders, HCV RNA became undetectable in only 13 patients six months after completion of therapy, and 11 still had low levels of viremia; however, none experienced relapse of the disease during follow-up of 12–24 months. Three complete responders showed lasting high-titered viremia, and their ALT values rose again during follow-up. Our data suggest that IFN treatment of chronic hepatitis C is often ineffective in eradicating HCV infection even in responders, and long-term follow-up study is necessary to determine the sustained beneficial effect of IFN.

Isolation of a large glycopeptide from cartilage procollagen by collagenase digestion and evidence indicating the presence of glucose, galactose and mannose in the peptide

Abstract Digestion of cartilage procollagen, pro-α1(II), with bacterial collagenase followed by fractionation of Sephadex G-150 yielded a large glycopeptide (molecular weight 13,200) which could not be demonstrated in a similarly prepared digest of α1(II) chain. Isotopic studies suggested that this glycopeptide contained, in addition to glucose and galactose, mannose, a sugar that is not found in the authentic α-chain of cartilage. The results imply that in pro-α1(II) there is a glycopeptide region differing from the α1(II) chain in amino acid composition and also in the type of carbohydrates attached.

Copper- and Iron-rich Matrices in Hepatocellular Lipofuscin Particles of a Young Male Patient: Diagnostic Ultrastructures for Wilson Disease

A 17-year-old male patient appeared with the biochemical liver damage associated with hypoceruloplasminemia and mild iron overload. Genetic analysis identified a compound heterozygosity of ATP7B responsible for the primary copper toxicosis of Wilson disease without mutations in HFE. A liver specimen consisted of cirrhotic nodules of large-sized hepatocytes with fatty change and those of fat-free small-sized hepatocytes. Histochemically, iron was distributed diffusely in the small-sized hepatocytes, while copper grains appeared in a few of the hepatocytes near the fibrous bands. X-ray microanalysis on the liver tissue fixed with a 0.1% osmium tetroxide solution and embedded in epoxy resin disclosed (1) complex formation of copper with sulfur, and iron with phosphorus in the hepatocyte lipofuscin particles, (2) intraparticle localization of the cuprothionein in the less dense matrix and ferric proteins in the dense matrix, and (3) high affinity of the cuprothionein to lead staining. Considering the fact that ceruloplasmin is the major ferroxidase essential for iron efflux, iron deposits in the hypoceruloplasminemic patients with Wilson disease are not a complication, but a natural event. This study disclosed for the first time the diagnostic ultrastructures of Wilson disease, which might represent different detoxification processes to the reactive metals of copper and iron.

Randomized controlled trial of twice-a-day administration of natural interferon β for chronic hepatitis C

Abstract We conducted a randomized controlled trial to assess the efficacy of twice-a-day administration of natural interferon β (IFNβ) as an induction of IFN therapy for chronic hepatitis C. Seventy-one patients with chronic hepatitis C were enrolled into the trial and randomly assigned into three treatment groups. Six million units (MU) of IFNβ were administered once-a-day for the first 4 weeks, and then thrice weekly for 12 weeks in 20 patients (once-a-day group). Three milion units of IFNβ were administered twice-a-day for the first 2 weeks, 6 MU once-a-day for the next 2 weeks, and then thrice weekly for 12 weeks in 23 patients (twice-a-day+β group), or 6 MU of lymphoblastoid IFNα were administered thrice weekly for the last 12 weeks instead of IFNβ in 28 patients (twice-a-day+α group). Four patients in once-a-day group (20%), 9 in twice-a-day+β group (39%), and 12 in twice-a-day+α group (43%) obtained sustained response. Sustained response rate in twice-a-day groups was higher than in once-a-day group, although there was no statistical significance. The present study suggested the possible superiority of twice-a-day administration of IFNβ as an induction therapy to once-a-day administration, but further studies are needed to confirm this regimen.

Randomized controlled trial of lymphoblastoid interferon α for chronic hepatitis C (comparison of 9-MU and 6-MU doses)

Abstract Objective: We conducted a randomized controlled trial to compare the efficacy of two different dosages of lymphoblastoid interferon α (IFN) for the treatment of chronic hepatitis C. Methods: Eighty-four patients with chronic hepatitis C were enrolled and randomly assigned into the two groups; group A was treated with 6 million units (MU) and group B with 9 MU daily for the first 2 wk, and then thrice weekly for an additional 14 or 22 wk. Results: Eighty patients were evaluated (39 patients in group A and 41 in group B); 14 patients in group A (35.9%) and 15 in group B (36.6%) obtained sustained response. The percentages of patients who became negative for HCV RNA at the end of the second wk differed slightly between the groups, without statistical significance (56.4% and 68.3%). When assessed in detail, patients with genotype 1 and

Clinical significance of mitochondrial glutamic-oxaloacetic transaminase in serum of patients with liver disease

SummarySerum mitochondrial glutamic-oxaloacetic transaminase activity was determined in 83 patients with various liver diseases and 10 healthy adults.1)The average of mitochondrial glutamic-oxaloacetic transaminase value was 1.2 mU in healthy adults, 8.3 mU in patients with acute hepatitis, 13.7 mU in patients with post-transfusion hepatitis, 5.0mU in patients with persistent hepatitis, 4.5mU in patients with chronic inactive hepatitis, 9.6mU in patients with chronic active hepatitis, 5.6 mU in liver cirrhosis, and 295 mU in a patient with fulminant hepatitis.2)While one patient with acute hepatitis showed the highest value in the group of 29 mU, one patient with fulminant hepatitis showed an extremely high value of 295 mU, revealing an obvious difference between them.3)One patient with fresh myocardial infarction also showed an extremely high value of 110 mU.

Acute Graft‐Versus‐Host Disease of the Large Intestine after Bone Marrow Transplantation

Abstract: A 13‐year old male with acute lymphocytic leukemia was admitted to our hospital for bone marrow transplantation (BMT). Lower abdominal pain and bloody diarrhea developed during the fourth post‐BMT week. Colonoscopy revealed edematous mucosa, erosions and multiple irregular ulcers in the rectum and sigmoid colon. Histologically, multiple apoptotic lesions were recognizable in the crypt basement membrane. Most infiltrating lymphoid cells were mature memory T lymphocytes bearing LFA‐la‐, CD43 and CD45RO antigens. HLA‐DR and ICAM‐1 immunostaining was seen on the vascular endothelium and the epithelium stained positively for HLA‐DR antigens.

Peptic Ulcer in Infants: Three Case Reports and a Review of the Japanese Literature

Abstract: Three cases of peptic ulcer in children under two years of age are reported, and 33 cases of infants with peptic ulcer reported in Japan between 1955 and March, 1989 are reviewed.