Hepatitis: Saito H

Ishii H, Saito H. · No affiliation provided · J Gastroenterol Hepatol. · Pubmed #10937671 No free full text.

This publication has no abstract.

Nakamura M, Saito H, Hibi T. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. · Keio J Med. · Pubmed #18677087 links to  free full text

Abstract: The research for hepatitis C virus (HCV) has long delayed by missing of in vitro culture system. Since the development of replicon system, a replication system of subgenomic HCV RNAs in a hepatoma cell line, has been reported, many virological and clinical findings have been discovered. Recently, in addition of subgenomic replication system, hepatitis C virus full-length RNA replication has been possible, and a few cell culture systems producing viral particles have been produced. These developments enabled us to investigate the life cycle or intracellular circumstance of HCV production. By screening of newly synthesized drugs with this replicon system, several possible medicines have been established and clinical researches are now running. Among them, VX950 and SCH503034 are nearest to clinical use. Other possible agents for reducing viral replication such as cyclophyllin inhibitors, inhibitors of sphingomyelin synthesis, HMG-CoA reductase inhibitors, or RNA-dependent RNA polymerase inhibitors have been also investigated. Furthermore the mechanism for development of hepatocellular carcinoma in the HCV infected liver has been vigorously studied using the HCV replicon system.

Saito H. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #18360976 No free full text.

This publication has no abstract.

Abe K, Saito H, Takahashi A, Rai T, Takiguchi J, Kanno Y, Monoe K, Ohira H. · Second Department of Internal Medicine, Fukushima Medical University School of Medicine, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #17230007 No free full text.

Abstract: A 20-year-old woman given a diagnosis of hyperthyroidism (Basedow's disease) had been subsequently treated with methimazole since 1999. As she could not be made euthyroid, surgery was planned to relieve the symptoms. Because of liver dysfunction after discontinuation of methimazole and administration of iodine, she was admitted to the hospital. She was negative for hepatitis A, B and C virus serologies, but positive for anti-nuclear antibodies. A liver biopsy, which showed features of chronic active hepatitis, led to the diagnosis of autoimmune hepatitis (AIH). Interestingly, normalization of serum T4 correlated with improvement of serum aminotransferases. This leads us to speculate that this patient's liver dysfunction may have been AIH exacerbated by the liver dysfunction of hyperthyroidism rather than acute deterioration of AIH itself.

Yamagishi Y, Ebinuma H, Saito H, Ishii H. · Department of Internal Medicine, School of Medicine, Keio University. · Nippon Rinsho. · Pubmed #11761992 No free full text.

This publication has no abstract.

Ebinuma H, Saito H, Tada S, Nakamoto N, Kurita S, Kitamaura K, Horikawa H, Kumagai N, Tsuchimoto K, Ishii H, Hibi T, Anonymous00373. · Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. · Hepatogastroenterology. · Pubmed #16506384 No free full text.

Abstract: BACKGROUND/AIMS: Two distinct natural interferon-alpha (BALL-1 and Namalwa) are available for patients with chronic hepatitis C in Japan, but the efficacy has not been well documented. We investigated two studies using a natural BALL-1 interferon-alpha treatment for chronic hepatitis C and assessed its efficacy. METHODOLOGY: In interferon-alpha monotherapy (Study I), 42 patients with chronic hepatitis C received 10 mega units of BALL-1 interferon-alpha intramuscularly consecutively for an initial 2 weeks followed by three times a week for 6 months totally. In a combination therapy of natural interferon-alpha and interferon-beta (Study II), 24 patients received intravenous 3 mega units of interferon-beta twice daily for the initial 2 weeks followed by 10 mega units of natural BALL-1 interferon-alpha consecutively for 2 weeks and three times a week for 6 months totally. Efficacy and predictive factors for sustained viral response was investigated. RESULTS: Study II included significant younger patients than study I. Sustained virological response was obtained in 31.0% in Study I and 56.5% in Study II by intention-to-treat analysis. Sustained viral response in the group of genotype 1b and viral load more than 100 KIU/mL was 3/23 (13.0%) and 8/18 (44.4%) in Study I and II, respectively. The response rate in Study II was higher than that of Study I especially among the patients with high pretreatment viral load or genotype 1b (p<0.05). Multivariate analysis showed that pre-treatment HCV-RNA levels, HCV-genotype, and histological staging before the interferon treatment were significant predictive factors of sustained viral response. CONCLUSIONS: These studies suggest that natural BALL-1 interferon-alpha is useful for inducing sustained viral response in patients with chronic hepatitis C, even in those possessing genotype 1b and high viral load. In addition, the combination therapy with a starting regimen with twice-daily interferon-beta administration for 2 weeks may be more effective than monotherapy.

Uchida M, Hamada A, Yamasaki M, Fujiyama S, Sasaki Y, Saito H. · Department of Pharmacy, Kumamoto University Hospital, Kumamoto, Japan. · Drug Metab Pharmacokinet. · Pubmed #15681898 links to  free full text

Abstract: Ribavirin has recently been demonstrated to be efficacious in combination with interferon (IFN) alpha-2b for the treatment of relapsed hepatitis C infections. The aim of this study was to evaluate the relationship between the pharmacokinetics and adverse reactions of ribavirin when ribavirin plus IFN alpha-2b were administered to patients affected with chronic hepatitis C. Nineteen patients received intramuscular IFN alpha-2b at a dose of 6 or 10 million units and oral ribavirin at 600 mg or 800 mg daily for 24 weeks. The pharmacokinetic profiles of ribavirin were assessed by the measurement of plasma concentrations. Twelve patients were continuously given both ribavirin and IFN alpha-2b, whereas in 7 patients the therapy was discontinued due to severe adverse drug reactions such as skin eruption, anemia and depression. There were no significant differences in ribavirin dose, Hb, ALT and AST values between the continued and the discontinued therapy groups. In contrast, the pretreatment platelet level and patient age of the discontinued therapy group were significantly different to the continued group. The trough plasma concentration of ribavirin in the discontinued therapy group was significantly higher than that in the continued group at week 1. These results suggest that the monitoring of plasma ribavirin concentrations may be valid for predicting the early phase of adverse drug reactions, thereby providing useful information for the adjustment of the ribavirin dosing for each patient.

Takahashi M, Saito H, Higashimoto M, Atsukawa K, Ishii H. · Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. · J Clin Microbiol. · Pubmed #15634970 links to  free full text

Abstract: A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.0%, accuracy = 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity = 100%, specificity = 87.2%, accuracy = 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity = 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay.

Ebinuma H, Saito H, Tada S, Masuda T, Kamiya T, Nishida J, Yoshioka M, Ishii H, Anonymous00376. · Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. · Hepatogastroenterology. · Pubmed #15239256 No free full text.

Abstract: BACKGROUND/AIMS: We previously reported that intravenous interferon-beta administration was effective in treating patients with chronic hepatitis C and that there was no significant correlation between the response to therapy and host in vitro immunoglobulin production. The aims of this study were to evaluate the additive effect of a liver extract preparation and flavin adenine dinucleotide mixture and to reevaluate the correlation. METHODOLOGY: 65 patients with chronic hepatitis C received intravenously 6 million units of interferon-beta and 2 mL of a liver extract preparation and flavin adenine dinucleotide mixture. The results of this study were compared with those of our previous study, on interferon-beta monotherapy in 91 patients with chronic hepatitis C. In addition, peripheral blood mononuclear cells were obtained before interferon-beta administration and cultured. Immunoglobulin concentrations in their supernatants were measured and the correlation with the interferon response was evaluated. RESULTS: The virological end-of-treatment or sustained response occurred in 49 of 58 cases (84.5%), and 16 of 58 cases (27.6%), respectively. Biochemical end-of-treatment or sustained responses occurred in 22 of 58 cases (37.9%), and 30 of 58 cases (51.7%), respectively. These response rates were higher than those reported in our previous study of interferon monotherapy. Monovariate analysis indicated that the use of the liver extract preparation and flavin adenine dinucleotide mixture was a significant predictor of the virological end-of-treatment response and the sustained biochemical response, but by multivariate analysis these relationships were not significant. Immunoglobulin production was not correlated with the virological and biochemical responses. CONCLUSIONS: This study indicated that combination therapy with intravenous interferon-beta and the liver extract preparation and flavin adenine dinucleotide mixture was more effective than intravenous interferon-beta monotherapy. However, no correlation between the interferon response and in vitro immunoglobulin production was observed.

Yano M, Hayashi H, Yoshioka K, Kohgo Y, Saito H, Niitsu Y, Kato J, Iino S, Yotsuyanagi H, Kobayashi Y, Kawamura K, Kakumu S, Kaito M, Ikoma J, Wakusawa S, Okanoue T, Sumida Y, Kimura F, Kajiwara E, Sata M, Ogata K. · Third Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, 466-8550, Nagoya, Japan. · J Gastroenterol. · Pubmed #15235875 No free full text.

Abstract: BACKGROUND: Increasing evidence indicates that iron cytotoxicity plays an important role in the pathogenesis of chronic hepatitis C (CHC). However, the biochemical effects of iron reduction therapy on CHC remain to be confirmed in a controlled study. This study aimed to test whether iron removal by repeated phlebotomy improves serum alanine aminotransferase (ALT) levels in patients with CHC. METHODS: Patients were randomly assigned to an iron reduction therapy or control group. The patients in the treatment group received 3-month iron reduction therapy by biweekly phlebotomy, while the patients in the control group were followed up for 3 months with regular blood tests alone. RESULTS: Thirty-three patients completed the 3-month treatment, while 29 patients received the complete follow-up. The serum ALT levels were reduced from 118 +/- 79 to 73 +/- 39 IU/L in the treatment group, but did not change in the control group (106 +/- 45 versus 107 +/- 48 IU/L). Posttreatment enzyme activity was decreased significantly from the baseline. Furthermore, it was significantly lower than the 3-month control level. Although 5 patients withdrew from the study, none was affected by any side effects of repeated phlebotomy that required them to discontinue the treatment. CONCLUSIONS: This short-term controlled trial demonstrated the biochemical efficacy and safety of iron reduction therapy for patients with CHC.

Ishii H, Yamagishi Y, Okamoto S, Saito H, Kikuchi H, Kodama T. · Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. · Keio J Med. · Pubmed #12713021 links to  free full text

Abstract: A 37-year-old man had a sore throat and pyrexia since January 1999. He was treated at a nearby hospital, but not improved. Jaundice was indicated there, and the patient was referred transferred to our hospital, where he was admitted for treatment with a diagnosis of severe acute hepatitis with acute renal failure. Thereafter the patient was revealed to have had a past history of heavy drinking, and he underwent the treatment with a diagnosis of acute fulminant hepatitis due to hepatitis A virus (HAV). He showed a tendency toward improvement. During the course, however, viral associated hemophagocytic syndrome (VAHS) developed. Various treatments were conducted, but it was not improved, and the patient died on Hospital Day 66. On pathologic autopsy, remarkable hepatosplenomegaly associated with marked bone marrow abnormalities compatible with VAHS was observed. Aspergillus abscesses were also observed in many organs, and they were considered as an adverse reaction to potent immunosuppressive therapy. Since there have been only a few reports on HAV-related VAHS, discussing VAHS related to HAV, the present case was considered valuable.

Miyaguchi S, Watanabe T, Takahashi H, Nakamura M, Saito H, Ishii H. · Department of Internal Medicine, Tokyo Metropolitan Otsuka Hospital, Minami-Otsuka 2-8-1, Toshima-ku, Tokyo, Japan. · Hepatogastroenterology. · Pubmed #12063979 No free full text.

Abstract: BACKGROUND/AIMS: Interferon-alfa is widely used for the treatment of chronic hepatitis C, and has been thought to have a preventive effect on the development of hepatocellular carcinoma. Hepatocellular carcinoma develops from chronic liver diseases such as chronic hepatitis C or liver cirrhosis. We studied the effect of interferon for liver cirrhosis with hepatocellular carcinoma after treating hepatocellular carcinoma itself. METHODOLOGY: To evaluate the preventive effect of this drug on local recurrence and/or new development of primary tumor after clearance of hepatitis C virus, 46 patients with hepatocellular carcinoma with low HCV-RNA level were randomized to receive recombinant interferon-alfa 2b (n = 22) or not (n = 24) after being treated by transcatheter arterial chemoembolization and percutaneous ethanol injection therapy. In the interferon-treated group, patients received 3 million international units of interferon-alfa 2b intramuscularly three times a week for 4 months. In both groups, transcatheter arterial chemoembolization followed by percutaneous ethanol injection therapy was performed as an initial treatment and these therapies were repeated every 4-6 months. Serum HCV-RNA levels of all 46 patients were under 0.5 Meq/mL by branched DNA probe assay. RESULTS: In the interferon-treated group, 11 of the 22 (50%) patients were HCV-RNA negative at the 6 months after completing the course of interferon therapy. HCV-RNA was undetectable during the observation period in 2 of the 24 (9.5%) patients in the untreated group. The survival rate in the interferon-treated group was significantly higher than that in the untreated group (P = 0.01 by the log-rank test). Though there was no significant difference in the incidence of local recurrence in both groups, the incidence of secondary hepatocellular carcinoma was significantly lower in the interferon-treated group than that in the untreated group. Cox proportional hazards regression analysis validated interferon treatment as an independent predictor of hepatocellular carcinoma prognosis. CONCLUSIONS: We concluded that, if HCV-RNA level is low, interferon may be a therapy of choice in combination with transcatheter arterial chemoembolization and percutaneous ethanol injection therapy for the treatment of hepatocellular carcinoma.

Atsukawa K, Saito H, Ebinuma H, Morizane T, Takahashi M, Ohishi T, Kumagai N, Tsuchimoto K, Ishii H. · Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. · Hepatogastroenterology. · Pubmed #11149032 No free full text.

Abstract: BACKGROUND/AIMS: Immunological status has been considered to correlate to the response to interferon therapy for chronic hepatitis C. The aim of this study was to evaluate the correlation between humoral immunity and long-term response to interferon treatment for chronic hepatitis C. METHODOLOGY: Seventy-one patients with chronic hepatitis C received 10 million units of interferon-alpha 2b three times a week for 24 weeks. Peripheral blood mononuclear cells were obtained before interferon-alpha 2b was administered and were cultured for 7 days. Immunoglobulin concentration in the culture supernatants was measured by enzyme-linked immunosorbent assay and correlation with the response to the therapy was evaluated. RESULTS: Serum ALT levels normalized in 51.4% and hepatitis C virus RNA disappeared in 35.7% six months after the end of therapy. Immunoglobulin production was significantly lower in the patients in whom serum ALT levels normalized than those in whom serum ALT levels remained elevated. The similar result was obtained when efficacy was evaluated on the basis of hepatitis C virus RNA disappearance. CONCLUSIONS: These results suggest that the less humoral immunity, the better response to interferon will be obtained in patients with chronic hepatitis C, meaning that the balance in T-helper function is one of key factors in the response to interferon treatment.

Saito H, Ebinuma H, Satoh I, Miyaguchi S, Tada S, Iwabuchi N, Kumagai N, Tsuchimoto K, Morizane T, Ishii H. · Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. · J Viral Hepat. · Pubmed #10718945 No free full text.

Abstract: Results from a multicentre, clinical trial of interferon-alpha2a (IFN-alpha2a) for the treatment of chronic hepatitis C are reported. Serum hepatitis C virus (HCV) RNA levels were monitored as follows: before, and 2 days after, the first administration of IFN-alpha2a; during and at the end of treatment; and 6 months after completion of therapy. Peripheral blood lymphocyte subpopulations were measured, by two-colour flow cytometry, before and 3 h after the first intramuscular (i.m.) administration of 9 mega units (MU) of IFN-alpha2a. Virological responders had a significantly lower pretreatment level of CD11+ CD8- lymphocytes. Biochemical responders had significantly lower pretreatment levels of CD11- CD8+, human leucocyte antigen (HLA) DR- CD4- and HLA DR- CD8+ populations, and a higher pretreatment HLA DR+ CD4- population. These pretreatment differences disappeared 3 h after the first i.m. administration of IFN-alpha2a. CD11- CD8+ and HLA DR+ CD8+ cell populations became significantly lower in virological responders 3 h after the first i. m. administration of IFN-alpha2a. HLA DR+ CD4+ cell populations were increased less in biochemical responders. Thus, T-lymphocyte subpopulations were different between responders and non-responders to IFN therapy and IFN-modulated host immunity. Multivariate analysis showed that the pretreatment CD11+ CD8- cell population was an independent predictive factor of response to therapy. On the other hand, patients whose serum HCV RNA cleared or decreased within the first 2 days of IFN-alpha2a therapy were more likely to achieve a virological response. This predictive factor, however, was not an independent factor by multivariate analysis. These results suggest that host immunity is an important factor in response to IFN therapy, and HCV clearance within the first 2 days is a good predictive factor of response.

Toyoda H, Fukuda Y, Nakano I, Katano Y, Takamatsu J, Saito H, Hayakawa T. · Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan. · Haemophilia. · Pubmed #10215959 No free full text.

Abstract: We observed six cases of haemophiliacs with HIV-induced immunodeficiency who died from fatal liver failure despite the absence of evident cirrhosis. They all had the infection with hepatitis viruses (two patients with hepatitis B and D viruses and four patients with hepatitis C virus) and their CD4 counts were severely decreased. They were much younger than cirrhotic haemophiliacs without HIV. Their serum levels of hyaluronic acid and type IV collagen were lower than those in haemophiliacs with cirrhosis, and were normal. No patients had experienced symptoms or concomitant diseases characteristic of cirrhosis, such as ascites, jaundice, oesophageal/gastric varices or hepatocellular carcinoma, except for one case who had a history of mild ascites. The characteristics of this liver failure were different from liver failure resulting from cirrhosis caused by chronic hepatitis, which suggests liver failure that is specific to patients with immunodeficiency. This kind of liver failure can be a factor threatening survival in patients with HIV infection and with hepatitis virus co-infection in an immunodeficient state.

Horie Y, Yamagishi Y, Kikuchi M, Saito H, Kato S, Ishii H, Hibi T. · Eiju General Hospital, 2-23-16 Higashiueno Taito-ku, Tokyo 110-8645, Japan. · Nihon Arukoru Yakubutsu Igakkai Zasshi. · Pubmed #19348160 No free full text.

Abstract: Recently prevalence of alcoholic liver disease has been increasing in Japan associated with an increase in alcoholic beverage consumption. In the present study, we addressed the recent trend in the etiology of liver cirrhosis (LC) in Japan, and investigated the influence of habitual drinking and viral hepatitis type C in the progression of LC. We carried out nation-wide survey by asking for the hospitals that are approved by the Japanese Society of Gastroenterology for the etiology of in-patients with LC, and compared to that in our hospital. Regarding the cases in nation-wide survey, 1274 cases (14%) of 9126 patients with LC were pure (without any markers of hepatitis virus) heavy drinkers, and 580 cases (6%) were heavy drinkers with any markers of hepatitis virus. However, in our general hospital, 24 cases of 101 patients with LC (24%) were pure heavy drinker, and 31 cases (30%) were heavy drinkers with any markers of hepatitis virus. In conclusion, although influence of hepatitis virus infection in alcoholic LC has been decreasing, it still plays an important role in the progression of alcoholic LC, especially in the general hospitals. Education of abstinence or low risk drinking is important not only heavy drinkers but also habitual drinkers with hepatitis virus infection.

Tada S, Saito H, Ebinuma H, Ojiro K, Yamagishi Y, Kumagai N, Inagaki Y, Masuda T, Nishida J, Takahashi M, Nagata H, Hibi T. · Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. · Hepatol Res. · Pubmed #19054155 No free full text.

Abstract: Aim: We investigated lipid metabolism in patients with chronic hepatitis C virus (HCV), serotype 1, undergoing combination therapy with PEG-IFN alpha-2b (PEG-IFN) and ribavirin (RBV). Methods: A total of 185 patients with chronic HCV (HCV serotype 1; HCV RNA levels >/= 100 KIU/mL) who received a combination of PEG-IFN and RBV were enrolled. Results: Sustained virological response (SVR) was obtained in 82 cases (44.3%). The median age, red blood cell and platelet counts differed significantly between the SVR and non-SVR groups before treatment. However there was no significant difference between total cholesterol (TC), LDL-cholesterol (LDL-C) and triglyceride (TG) levels before treatment. TC and LDL-C levels decreased during the treatment in both groups. In the SVR group, TC and LDL-C levels increased quickly after the end of the treatment and were higher than those before treatment. On the other hand, TC and LDL-C levels returned to pretreatment levels in the non-SVR group and were significantly lower than in the SVR group. TG levels were elevated in both groups after the beginning of treatment. After the end of treatment, this elevation persisted in the SVR group, while TG levels returned to pre-treatment levels in the non-SVR group. There was a significant difference in TG levels at 24 weeks after the end of the treatment between the 2 groups. In the non-SVR group some patients achieved normalization of ALT (alanine aminotransferase) but persistence of normal ALT levels did not contribute to the increase of TC and TG. Conclusion: TC, LDL-C and TG levels increase only in patients with HCV, serotype 1, undergoing combination therapy when a SVR is achieved.

Takahashi A, Kanno Y, Takahashi Y, Sakamoto N, Monoe K, Saito H, Abe K, Yokokawa J, Irisawa A, Ohira H. · Department of Internal Medicine II, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Japan. · World J Gastroenterol. · Pubmed #18803363 links to  free full text

Abstract: A 43-year-old woman with multiple sclerosis (MS) was treated with pulsed methylprednisolone and interferon beta at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and admitted to our hospital. Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis, but not for autoimmune hepatitis (AIH). She was successfully treated with corticosteroids. As ataxia developed after 1 year, she was treated with pulsed methylprednisolone for 3 d, then readmitted to our hospital when liver dysfunction occurred. Clinical and laboratory findings led to the diagnosis of AIH. To the best of our knowledge, this is the second case of AIH developed after pulsed methylprednisolone for MS.

Ojiro K, Naganuma M, Ebinuma H, Kunimoto H, Tada S, Ogata H, Iwao Y, Saito H, Hibi T. · Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. · J Gastroenterol. · Pubmed #18592158 No free full text.

Abstract: We encountered a case of reactivation of hepatitis B virus after administration of infliximab for Crohn's disease. The use of infliximab was considered because the patient displayed abdominal symptoms and perianal lesions. Transaminases were normal, and hepatitis B virus (HBV) DNA was undetectable before treatment, so no antiviral treatment was used, and infliximab and low-dose 6-mercaptopurine were administered. This treatment was effective, but liver dysfunction and reactivation of HBV were observed after the fourth injection of infliximab. This is the first report of Crohn's disease for which infliximab use was continued even after reactivation of HBV was observed. However, liver dysfunction was not improved by lamivudine. Antiviral treatment should be considered before administration of infliximab for patients with HBV.

Abe K, Ohira H, Kobayashi H, Saito H, Takahashi A, Rai T, Kanno Y, Monoe K, Watanabe H, Irisawa A, Sato Y. · Department of Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan. · Fukushima J Med Sci. · Pubmed #18402289 No free full text.

Abstract: Reportedly, bacterial DNA containing unmethylated cytosine-guanosine dinucleotide motif-containing oligodeoxynucleotides (CpG-ODNs) can induce Th1-type adjuvant effects. We produced autoantibodies and induced hepatitis in mice using extracted proteins from human hepatocytes with CpG-ODNs as adjuvant. Western blot analysis was performed of sera from immunized mice and two patients with autoimmune hepatitis (AIH). When a common band was detected, N-terminal amino acid sequencing was performed to determine its site. For detection of antibodies against the identified protein (calreticulin), ELISA was performed of sera of 50 patients with AIH: 45 with primary biliary cirrhosis (PBC), 24 with chronic hepatitis C (CH), and 24 healthy controls. Mice were immunized with calreticulin protein with CpG-ODNs as adjuvant. Several reacted bands were detected in their sera; in addition, a common band to the sera of patients with AIH was detected at 60 kDa. Subsequent N-terminal amino acid sequencing revealed that the protein was human calreticulin. ELISA showed that, of patients with AIH, PBC, and CH, 30.0% (15/50), 17.8% (8/45), and 12.5% (3/24), respectively, were positive for anti calreticulin antibodies. Splenocytes from immunized mice produced IFN-gamma after they were pulsed with calreticulin protein. Histological analyses of liver specimens taken from mice immunized with calreticulin protein together with CpG-ODNs showed spotty and focal necrosis. Immunofluorescence analysis showed increased expression of calreticulin in the liver treated with CpG-ODNs. These results suggest that a breakthrough of immune self tolerance to calreticulin is induced with CpG-ODNs as adjuvant and that calreticulin protein might be a target antigen in this model.

Nakamura M, Saito H, Ikeda M, Tada S, Kumagai N, Kato N, Shimotohno K, Hibi T. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Shinanomachi, Shinjuku-ku, Tokyo, Japan. · J Med Virol. · Pubmed #18297719 No free full text.

Abstract: We previously reported the relationship between viral polymerase polymorphisms and the initial decline in viral load induced by interferon-alpha and ribavirin therapy in genotype 1b-related chronic hepatitis C patients. The presence of E124K and I85V of NS5B was closely associated with viral clearance at 8 weeks of treatment. The aim of this study was to investigate the mechanisms by which this polymorphism of NS5B protein affects early viral clearance. We used a replicon system derived from strain O, genotype 1b virus. Three mutants (V85I), (K124E), and (V85I/K124E) were introduced to the replicon. OR6c, a derivative of HuH7 cells, was transfected with the replicon including a luciferase reporter gene. Luciferase activities were measured 72 hr post-transfection. All three mutants showed higher luciferase activity than that of the wild type, and the V85I mutant showed the highest activity. This result was also confirmed by neomycin gene-containing replicons with same mutations. All replicons were down-regulated by ribavirin, but the level of reduction in the V85I mutant was the lowest. Our results suggested that this mutation at least partly contributes to resistance to early viral clearance during interferon and ribavirin combination therapy.

Khan A, Tanaka Y, Saito H, Ebinuma H, Sekiguchi H, Iwama H, Wakabayashi G, Kamiya T, Kurbanov F, Elkady A, Mizokami M. · Department of Clinical Molecular Informative Medicine, Nagoya City University, Mizuho, Nagoya 467-8601, Japan. · Virus Res. · Pubmed #18207274 No free full text.

Abstract: Hepatitis B virus genotypes are associated with transmission pattern, virological and clinical features and outcome of the chronic infection course. HBV genotypes other than Genotype F (HBV/F) are considered a reflection of human migration into South America. A total of 487 individuals in Bolivia, including Japanese immigrants (n=287) and natives (n=200), were screened for HBV serological markers. Overall 22/487 (4.5%) of the subjects were positive for HBsAg, 217/487 (44.5%) for anti-HBc and 162/487 (33.3%) for anti-HBs. Genotypes were determinable in 22 cases by EIA, followed by sequencing and phylogenetic analysis in 17 cases. HBV genotype distribution in Japanese and Bolivians was HBV/F (4 and 8); HBV/C (5 and 3); and HBV/B (1 and 1), respectively. Phylogenetic analyses of nine complete and eight partial (HBsAg/pre-core/core region) genomes, revealed that HBV/F strains cluster with previously reported regional strains, whereas HBV/B and HBV/C strains belonged to Asian subgenotype B2 (Ba) and C2 (Ce), respectively. Japanese immigrants might have introduced HBV/B and HBV/C to natives in Bolivia, conversely, exposed to the indigenous HBV/F. This report provides evidence of an inter-communities transmission of HBV revealed by its genotypes. Further study is required to investigate peculiarities of the genotypes in different ethnic groups in Bolivia.

Takahashi A, Saito H, Kanno Y, Abe K, Yokokawa J, Irisawa A, Kenjo A, Saito T, Gotoh M, Ohira H. · Department of Internal Medicine II, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan. · World J Gastroenterol. · Pubmed #18176975 links to  free full text

Abstract: A 36-year-old woman was admitted to our department for close examination of a liver tumor that was found during a medical checkup. Abdominal US, CT and MRI showed a tumor in segment 7 (S7) of the liver. Although imaging suggested hepatocellular carcinoma, laboratory tests showed no abnormality in liver function, hepatitis virus markers were negative, and tumor markers including protein induced by vitamin K absence or antagonist II (PIVKA-II), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) were all within normal ranges. Upon aspiration biopsy of the liver, the histopathological diagnosis was moderately differentiated hepatocellular carcinoma. Therefore, right hepatectomy was performed. Although a part of the tumor was necrotic, about 60% of the viable part showed a clear-cell variant. Consequently, it was diagnosed as clear-cell hepatocellular carcinoma. It was noted that the background liver tissue was normal. This case is worthy of reporting because development of clear-cell hepatocellular carcinoma in the normal liver of a middle-aged woman is rarely seen.

Higashimoto M, Takahashi M, Jokyu R, Syundou H, Saito H. · Clinical Laboratory, Tokyo Metropolitan Hiroo Hospital, Shibuya-ku, Tokyo. · Rinsho Byori. · Pubmed #18154032 No free full text.

Abstract: A HCV core antigen (Ag) detection assay system, Lumipulse Ortho HCV Ag has been developed and is commercially available in Japan with a lower detection level limit of 50 fmol/l, which is equivalent to 20 KIU/ml in PCR quantitative assay. HCV core Ag assay has an advantage of broader dynamic range compared with PCR assay, however the sensitivity is lower than PCR. We developed a novel HCV core Ag concentration method using polyethylene glycol (PEG), which can improve the sensitivity five times better than the original assay. The reproducibility was examined by consecutive five-time measurement of HCV patients serum, in which the results of HCV core Ag original and concentrated method were 56.8 +/- 8.1 fmol/l (mean +/- SD), CV 14.2% and 322.9 +/- 45.5 fmol/l CV 14.0%, respectively. The assay results of HCV negative samples in original HCV core Ag were all 0.1 fmol/l and the results were same even in the concentration method. The results of concentration method were 5.7 times higher than original assay, which was almost equal to theoretical rate as expected. The assay results of serially diluted samples were also as same as expected data in both original and concentration assay. We confirmed that the sensitivity of HCV core Ag concentration method had almost as same sensitivity as PCR high range assay in the competitive assay study using the serially monitored samples of five HCV patients during interferon therapy. A novel concentration method using PEG in HCV core Ag assay system seems to be useful for assessing and monitoring interferon treatment for HCV.

Kumagai N, Kaneko F, Tsunematsu S, Tsuchimoto K, Tada S, Saito H, Hibi T. · Research Center for Liver Disaeases, Kitasato Institute Hospital, Tokyo, Japan. · Eur J Clin Invest. · Pubmed #17576208 No free full text.

Abstract: BACKGROUND: Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N-terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR-1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels. MATERIALS AND METHODS: Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2.5 years by fluorescence single-strand conformation polymorphism and sequence analysis. RESULTS: There was no significant difference in the changes in the number of quasispecies during the follow-up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR-1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression. CONCLUSION: Our results suggested that the disease activity is not always related to the generation of the HVR-1 quasispecies complexity.