Hepatitis: Saito T

Saito T, Gale M. · Department of Immunology, University of Washington School of Medicine, H578 HSB 1959 N.E. Pacific St, Seattle, WA 98195-7650, USA. · Uirusu. · Pubmed #19374189 links to  free full text

Abstract: Hepatitis C virus (HCV) infection is one of the most serious public health problems in the world. HCV leads patients to develop hepatic cirrhosis and precipitates hepatocellular carcinoma. HCV establishes persistent infection by impairing host innate and adaptive immune responses. HCV infected hepatocytes sense the infection through Pathogen Associated Molecular Patterns (PAMPs). The sensor molecules, Pattern Recognition Receptors (PRRs) contain two distinct categories, toll like receptors (TLR) and cytoplasmic Retinoic Acid inducible Gene I (RIG-I) like helicases (RLHs). In the hepatocyte, the cytoplasmic PRR, Retinoic Acid inducible Gene I (RIG-I) plays the central role of HCV viral genome recognition, resulting in activation of signaling to induce type I interferon and proinflammatory cytokines. Type I IFN induces more than 300 effector molecules known as interferon stimulated genes (ISGs) that establish an antiviral state in infected cells and neighboring cells. The activation of innate immunity is also critical for the mounting of innate and adaptive immunity. However, a variety of viral strategies of HCV disrupt host innate immune signaling and ISG function, resulting in a dysfunctional immune response against HCV and poor responses to the current type I IFN based therapy. Many studies have reported immune dysfunction during HCV infection in cell culture, animal models and patients. This review article focuses on understanding how the hepatic innate immunity sensor, PRR, associates with HCV PAMPs, and how HCV escapes from host immunity.

Saito T, Nishise Y, Ishii R, Watanabe H, Suzuki K, Kawata S. · Department of Gastroenterology, Yamagata University School of Medicine, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19346718 No free full text.

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Saito T, Misawa K, Kawata S. · The Department of Gastroenterology, Yamagata University. · Intern Med. · Pubmed #17220609 links to  free full text

Abstract: Although steatohepatitis can be induced by an excessive intake of alcohol, it can also arise through various other causes, in which case it is known as non-alcoholic fatty liver disease (NAFLD). NAFLD is classified into two categories:simple fatty liver with a favorable clinical outcome, and non-alcoholic steatohepatitis (NASH), which is intractable and progressive. Recently in Japan, there has been an increase in the number of individuals at risk of lifestyle-related diseases, due to increased insulin resistance and visceral fat obesity. The metabolic syndrome (MS) is associated with several risk factors for atherosclerosis, including diabetes mellitus (DM), hypertension, and hyperlipidemia. Visceral fat obesity is the prime cause of NASH in the liver, and is therefore considered to be one of the phenotypic features of MS. Furthermore, most chronic liver diseases are associated with hepatitis C virus (HCV) infection. Fatty degeneration of hepatocytes is often observed in the liver of HCV-infected individuals, and results from viral suppression of mitochondrial beta-oxidation of fatty acid. The natural outcome of HCV infection is worse in patients with lifestyle-related high insulin resistance and visceral fat obesity. In this review, we describe the recent advances in research on progressive liver diseases that are the result of fat accumulation in the liver, with special reference to MS.

Saito T, Misawa K, Kawata S. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #16223146 No free full text.

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Saito T, Watanabe H, Togashi H, Kawata S. · Division of Gastroenterology, Department of Internal Medicine and Molecular Therapeutics, Yamagata University School of Medicine. · Nippon Rinsho. · Pubmed #15453339 No free full text.

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Murakami J, Fukushima N, Ueno H, Saito T, Watanabe T, Tanosaki R, Kobayashi Y, Matsuno Y, Tobinai K. · Hematology Division, National Cancer Center Hospital, Tokyo, Japan. · Int J Hematol. · Pubmed #11843297 No free full text.

Abstract: Primary hepatic lymphoma, mostly diffuse large B-cell lymphoma, is a rare disease. We describe an extremely rare case of low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type occurring in the liver. A 61-year-old man with a history of hepatitis A presented with early gastric cancer and a liver mass. Needle biopsy of the liver tumor suggested low-grade B-cell lymphoma by histology and polymerase chain reaction of the immunoglobulin heavy chain gene. The tumor (3.4 x 2.8 x 2.4 cm) was completely resected from the anterior segment of the right lobe of the liver. Atypical lymphoid cells of small to intermediate size proliferated in the tumor, and lymphoepithelial lesions were recognized. Immunohistochemically, lymphoma cells were positive for CD20 and negative for CD5, CD10, and cyclin D1. Staging procedures showed no lymphoma lesion other than the liver tumor. Thus, the patient was diagnosed with low-grade hepatic marginal zone B-cell lymphoma of the MALT type. The patient has been followed up for 1.5 years since surgical resection with no recurrence. The clinicopathologic characteristics and management of this rare disease are discussed.

Takeda Y, Togashi H, Shinzawa H, Miyano S, Ishii R, Karasawa T, Takeda Y, Saito T, Saito K, Haga H, Matsuo T, Aoki M, Mitsuhashi H, Watanabe H, Takahashi T. · Second Department of Internal Medicine, Yamagata University School of Medicine, Japan. · J Gastroenterol Hepatol. · Pubmed #11059943 No free full text.

Abstract: A 68-year-old man presented with multiple hepatocellular carcinoma, which was considered to be unresectable at the first admission in January 1994. Pathological diagnosis was made by biopsy of the one lesion among them. From January 1994 to December 1997, 10 transarterial chemoembolizations and six percutaneous ethanol injection therapies were performed on the tumours in the cirrhotic liver. In February 1998 the tumour situated in the right lobe began to increase in size. The maximum tumour diameter was 6.3 cm measured by computed tomography (CT). In the beginning of May 1998 moderate ascites was present and mild hepatic encephalopathy was noticed. The patient was in the terminal stage of hepatocellular carcinoma and no further treatment was possible at that time. However, serum alpha-fetoprotein and protein induced by vitamin K absence or antagonist II dramatically decreased in June 1998. The CT scan also showed that the tumour had completely regressed without specific treatment. In February 1999 a new biopsy-proven hepatocellular carcinoma, 2 cm in diameter, developed in the lateral segment of the liver. It was well treated by percutaneous ethanol injection therapy. The patient was alive in good condition without any symptoms or tumour recurrence in June 1999. It was concluded that a rare case of spontaneous regression of hepatocellular carcinoma had occurred.

Saito T, Ji G, Shinzawa H, Okumoto K, Hattori E, Adachi T, Takeda T, Sugahara K, Ito JI, Watanabe H, Saito K, Togashi H, Ishii K, Matsuura T, Inageda K, Muramatsu M, Kawata S. · Division of Gastroenterology, Department of Internal Medicine and Molecular Therapeutics, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan. · Biochem Biophys Res Commun. · Pubmed #15063762 No free full text.

Abstract: The outcome of hepatitis C virus (HCV) infection varies among individuals, but the genetic factors involved remain unknown. We conducted a population-based association study in which 238 Japanese individuals positive for anti-HCV antibody were genotyped for 269 single nucleotide polymorphisms (SNPs) in 103 candidate genes that might influence the course of infection. Altogether, 50 SNPs in 32 genes were listed. Genetic polymorphisms in IL4, IL8RB, IL10RA, PRL, ADA, NFKB1, GRAP2, CABIN1, IFNAR2, IFI27, IFI41, TNFRSF1A, ALDOB, AP1B1, SULT2B1, EGF, EGFR, TGFB1, LTBP2, and CD4 were associated with persistent viremia (P < 0.05), whereas those in IL1B, IL1RL1, IL2RB, IL12RB1, IL18R1, STAT5A, GRAP2, CABIN1, IFNAR1, Mx1, BMP8, FGL1, LTBP2, CD34, and CD80 were associated with different serum alanine aminotransferase levels in HCV carriers (P < 0.05). The sorted genes allow us to draw novel hypotheses for future studies of HCV infection to ultimately identify bona fide genes and their variations.

Moriyama M, Matsumura H, Aoki H, Shimizu T, Nakai K, Saito T, Yamagami H, Shioda A, Kaneko M, Goto I, Tanaka N, Arakawa Y. · Third Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. · Intervirology. · Pubmed #14555850 No free full text.

Abstract: OBJECTIVE: Because the determination of the stage of fibrosis depends on rather subjective judgment, more objective parameters are needed. In this study, we followed the long-term outcome, with monitoring of platelet counts, in patients with chronic hepatitis C or liver cirrhosis (LC) who had undergone interferon (IFN) therapy. METHODS: 596 patients who were diagnosed at our institute from 1987 to 1998 with chronic hepatitis C and LC were treated with IFNs. A further 58 patients were not treated (NT). The annual rate of changes in platelet counts were calculated and compared for IFN-treated and NT patients. RESULTS: The relationship between the efficacy of IFN therapy and the incidence of hepatocellular carcinoma (HCC) showed that the patients who were virologic sustained responders (VSR) had a significantly lower incidence of HCC than the nonresponders (NR) and NT patients. The change in platelet counts was +4,350/microl/year in the VSR, +1,010/microl/year in the biochemical sustained responders (BSR), -4,540/microl/year in the NR and -6,180/microl/year in the NT patients, indicating a significant platelet increase in the VSR, a decrease of the same magnitude in the NR and NT patients, and no change in the BSR. The cumulative probability of developing HCC and liver failure was significantly higher in groups with decreased platelet counts than in groups with increased platelet counts among patients who had undergone IFN therapy. Multivariate analyses revealed that a decrease in platelet counts was the cardinal risk factor for development of HCC and liver failure in chronic hepatitis C or LC patients. CONCLUSION: Investigation of platelet counts was useful for determining the long-term outcome of patients who had undergone IFN therapy and for predicting the development of HCC.

Terui Y, Saito T, Watanabe H, Togashi H, Kawata S, Kamada Y, Sakuta S. · No affiliation provided · Hepatology. · Pubmed #12297856 No free full text.

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Saito T, Nishise Y, Makino N, Haga H, Ishii R, Okumoto K, Ito JI, Watanabe H, Saito K, Takeda H, Togashi H, Kubota I, Daimon M, Kato T, Kawata S. · Department of Gastroenterology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. · Metabolism. · Pubmed #19411086 No free full text.

Abstract: Measurement of the serum alanine aminotransferase (ALT) level is used as an initial test for detection of liver diseases, and recent studies have also highlighted its potential value as a measure of overall health and survival as a marker of an increased risk of metabolic disorder. This study was designed to clarify the prevalence of elevated ALT levels in the Japanese population and to assess factors associated with ALT elevation. The subjects were 2165 individuals aged 40 to 85 years who participated in a Japanese community-based study referred to as the Takahata Study. Serum ALT levels and factors associated with ALT elevation were investigated. Among 2087 subjects who were negative for hepatitis B and C, the rates of elevated ALT greater than 30 U/L in men and greater than 25 U/L in women were 217 (22.7%) of 957 and 239 (21.2%) of 1130, respectively. These ALT cutoff levels had a specificity of more than 80% for exclusion of subjects with none or 1 of 3 metabolic risk factors: hypertension, lipid metabolism abnormality, and hyperglycemia. Multivariate analysis revealed 5 factors with a significant association with ALT elevation in men (n = 957): high gamma-glutamyltranspeptidase, low adiponectin, high low-density lipoprotein cholesterol, high body mass index, and high homeostasis model assessment insulin resistance index. Similarly, 4 factors were significantly associated with ALT elevation in women (n = 1130): high gamma-glutamyltranspeptidase, low adiponectin, high body mass index, and high homeostasis model assessment insulin resistance index. These results suggest that elevated ALT levels in the Japanese population older than 40 years have a strong association with metabolic syndrome-related features including obesity and insulin resistance.

Karasawa T, Togashi H, Tajima K, Suzuki A, Onodera S, Haga H, Ishii R, Misawa K, Sanjo M, Okumoto K, Nishise Y, Ito J, Sugahara K, Saito K, Saito T, Kawata S. · Department of Gastroenterology, Yamagata University Faculty of Medicine, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19262055 No free full text.

Abstract: We report a case of chronic hepatitis C complicated with idiopathic thrombocytopenic purpura (ITP), successfully treated with interferon (IFN) beta. A 65-year-old woman was admitted to our hospital for the treatment of chronic hepatitis C with IFN beta. ITP was also diagnosed because of the presence of platelet associated IgG and the findings of bone marrow examination. We started IFN therapy, which resulted in normalization of transaminases, complete HCV eradication, and increased number of platelet.

Nishi S, Imai N, Saito T, Ueno M, Arakawa M, Oota T, Gejyo F. · Blood Purification Center, Niigata University Medical and Dental Hospital, Niigata, 951-8520, Japan · Clin Exp Nephrol. · Pubmed #18854922 No free full text.

Abstract: We report here unique electron microscopy findings showing clusters of deposition of spherical and tubular microparticles in a glomerular basement membrane (GBM) of a 46-year-old Japanese male with membranous nephropathy. Another distinct feature was the deep infolding of podocyte membranes into the GBM. Light microscopy showed the ladder formation of the GBM suggesting membranous nephropathy, while the immunofluorescent examination was atypical for the absence of the global capillary deposition of IgG and C3. He had mild liver dysfunction with positive hepatitis B antigen. Antibodies to hepatitis B surface antigen reacted weakly on the GBM in the immunohistochemistry. We suspected the unique findings of this case might be related to the hepatitis B viral infection.

Kaibori M, Ha-Kawa SK, Ishizaki M, Matsui K, Saito T, Kwon AH, Kamiyama Y. · Department of Surgery, Hirakata Hospital, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, Osaka, 573-1191, Japan. · World J Surg. · Pubmed #18758848 No free full text.

Abstract: BACKGROUND: Postoperative mortality after hepatectomy remains high compared with other types of surgery in patients who have cirrhosis or chronic hepatitis. Although there are several useful perioperative markers of liver dysfunction, there are no standard markers for predicting postoperative liver failure. This study investigated risk factors for postoperative liver failure after resection of hepatocellular carcinoma to detect markers that could identify candidates for hepatectomy. METHODS: Perioperative risk factors for liver failure after hepatectomy were analyzed in 191 patients with hepatocellular carcinoma. Multivariate logistic regression analysis was done to investigate factors with a significant independent influence among 35 variables. The ratio of serum hyaluronic acid to the maximum removal rate of technetium-99 m diethylenetriaminepentaacetic acid galactosyl human serum albumin (hyaluronate/GSA-Rmax ratio) was calculated. RESULTS: Liver failure occurred postoperatively in 16 patients, 3 of whom died. The hyaluronate/GSA-Rmax ratio was a risk factor for postoperative liver failure by univariate analysis and was the only risk factor according to multivariate analysis. All three patients who died had a hyaluronic acid/GSA-Rmax ratio > or = 500 mg min/dl. This ratio had a sensitivity of 88% and a specificity of 92% for predicting liver failure. CONCLUSIONS: To reduce postoperative liver failure, preoperative planning should employ various measures of the hepatic functional reserve, including tests of both parenchymal and nonparenchymal liver function. The hyaluronate/GSA-Rmax ratio can predict liver failure after hepatectomy, and a ratio > or = 500 mg min/dl is a relative contraindication to liver resection.

Kato M, Ryu T, Miura H, Yamada H, Saito T. · Department of Internal Medicine, Social Insurance Chuo General Hospital, Tokyo. · Nippon Naika Gakkai Zasshi. · Pubmed #18681159 No free full text.

This publication has no abstract.

Saito T, Owen DM, Jiang F, Marcotrigiano J, Gale M. · Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98195-7650, USA. · Nature. · Pubmed #18548002 No free full text.

Abstract: Innate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated molecular patterns (PAMPs). Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide. Infection is regulated by hepatic immune defences triggered by the cellular RIG-I helicase. RIG-I binds PAMP RNA and signals interferon regulatory factor 3 activation to induce the expression of interferon-alpha/beta and antiviral/interferon-stimulated genes (ISGs) that limit infection. Here we identify the polyuridine motif of the HCV genome 3' non-translated region and its replication intermediate as the PAMP substrate of RIG-I, and show that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of RIG-I recognition and immune triggering in human and murine cells. 5' terminal triphosphate on the PAMP RNA was necessary but not sufficient for RIG-I binding, which was primarily dependent on homopolymeric ribonucleotide composition, linear structure and length. The HCV PAMP RNA stimulated RIG-I-dependent signalling to induce a hepatic innate immune response in vivo, and triggered interferon and ISG expression to suppress HCV infection in vitro. These results provide a conceptual advance by defining specific homopolymeric RNA motifs within the genome of HCV and other RNA viruses as the PAMP substrate of RIG-I, and demonstrate immunogenic features of the PAMP-RIG-I interaction that could be used as an immune adjuvant for vaccine and immunotherapy approaches.

Togashi H, Hashimoto C, Yokozawa J, Suzuki A, Sugahara K, Saito T, Yamaguchi I, Badawi H, Kainuma N, Aoyama M, Ohya H, Akatsuka T, Tanaka Y, Mizokami M, Kawata S. · Department of Gastroenterology, Course of Internal Medicine and Therapeutics, Yamagata University Faculty of Medicine, Yamagata University Health Administration Center, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, Japan. · J Hepatol. · Pubmed #18479773 No free full text.

Abstract: BACKGROUND/AIMS: We investigated what can be revealed by extending the sensitivity of HBsAg detection to below the present limit. METHODS: We examined the sensitivity of this immunoassay in comparison with real-time PCR detection of HBV DNA using serially diluted sera from HBV carriers. Low HBsAg was measured in 210 healthy volunteers and 368 patients with non-B chronic liver diseases who were negative for HBsAg by a standard EIA method. RESULTS: The radical immunoassay was able to detect HBsAg at a concentration of 0.025 ng/ml. Low HBsAg was positive in 6 of 210 normal volunteers (2.86%), 5 of 65 non-B, non-C cirrhosis patients (7.69%), 6 of 62 non-B, non-C hepatocellular carcinoma patients (9.68%: p=0.04 vs. volunteers), 12 of 134 chronic hepatitis C patients (8.96%: p<0.02 vs. volunteers), and 11 of 107 hepatocellular carcinoma patients complicated by chronic hepatitis C (10.28%: p<0.008 vs. volunteers). Although no HBV DNA was positive in healthy volunteers, 9 patients with non-B chronic liver diseases were positive for HBV DNA by real-time PCR analysis. CONCLUSIONS: Increasing the sensitivity of HBsAg detection to below the present limit has revealed that infection with HBV, including occult HBV, is far more endemic than suspected previously.

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.

Saito T, Gale M. · University of Washington School of Medicine, Department of Immunology, Washington, USA. · Hepatol Res. · Pubmed #18021225 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is a global public health problem. HCV infection is treated with type I interferon (IFN), a natural product that is produced by cells during virus infection as a result of innate immune signaling events. The secreted IFN alert the surrounding cells to turn on an "antiviral state" that resists infection. In general, the role of innate immune response is to suppress viral replication and to induce cytokines and other factors that promote adaptive immunity and the resolution of infection. The mechanisms by which the innate immune response and IFN actions limit HCV infection are not well defined, but are likely to involve the function of specific IFN-stimulated genes. HCV also copesintensively with immune responses in order to establish persistent infection. Recent studies reveal that a other viruses use similar tactics to regulate the antiviral innate immune response. In the case of HCV, innate immune signaling is strictly controlled by the viral NS3/4A protease, resulting in the disruption of IFN production. Here, we summarize the current understanding of how HCV evades the innate immune system.

Sugahara K, Saito T, Watanabe H, Misawa K, Ishii R, Suzuki A, Haga H, Sanjo M, Okumoto K, Nishise Y, Ito J, Saito K, Togashi H, Kawata S. · Department of Gastroenterology, Yamagata University School of Medicine. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #17917401 No free full text.

Abstract: This report describes our experience with two cases of pyogenic spondylitis with chronic hepatitis C during combination therapy of interferon alfa and ribavirin. The first patient, a 59-year-old man, was treated conservatively and improved, but the second patient, a 69-year-old woman, was not improved by conservative therapy and reconstructive operation was performed. The combination therapy of interferon alfa and ribavirin has a high risk of severe infectious diseases as side effects. CT scan and MRI are recommended immediately to diagnose pyogenic spondylitis, when patients has pyrexia and lumbago with laboratory data suspected inflammation during interferon therapy.

Nishise Y, Saito T, Sugahara K, Ito JI, Saito K, Togashi H, Nagano-Fujii M, Hotta H, Kawata S. · Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan. · J Infect Dis. · Pubmed #17763321 No free full text.

Abstract: We conducted a retrospective study of 65 patients with chronic hepatitis C, to determine whether the secondary structure of the amino-terminal 120 residues of the hepatitis C virus (HCV) NS3 protein is associated with an increased risk of development of hepatocellular carcinoma (HCC). The cumulative incidence of HCC was highest among patients infected with group B HCV-1b, wherein the risk of HCC significantly increased compared with that among patients infected with group A (hazard ratio, 4.95 [95% CI, 1.43-17.11]) after adjustment for age and histological stage. This HCV-1b grouping may be a useful marker for detecting the risk of development of HCC.

Akioka N, Fukuda O, Takaba M, Kameda H, Saito T, Endo S. · Department of Neurosurgery, Saito Memorial Hospital, Niigata, Japan. <> · J Stroke Cerebrovasc Dis. · Pubmed #17689404 No free full text.

Abstract: BACKGROUND: Acute spontaneous subdural hematomas of arterial origin without any traumatic history or vascular anomaly are rarely reported. Here, we report our series of 6 patients with acute spontaneous subdural hematoma. METHODS: All patients with acute spontaneous subdural hematoma were surgically treated at our hospital between January 1994 and December 2003. Each patient's constitution, medical history, clinical findings, intraoperative findings, complications, and outcomes were reviewed. RESULTS: The patients were 5 men and 1 woman with a mean age of 53.0 years (range 32-82). Two of the 6 patients had histories of head injury with onset more than 10 years earlier. Other medical histories included hepatitis C, dementia, alcoholism, and hypertension in one patient each. Initial symptoms were rapidly progressive disturbance of consciousness in 5 patients. Surgical operation was performed in all patients, and the bleeding points were identified as ruptures of cortical arteries located near the sylvian fissure. One patient completely recovered, one had a moderate deficit, two had severe deficits, one fell into a vegetative state, and one died (mortality was 16.7%). CONCLUSION: In many cases, the patients suddenly fell into a serious disturbance of consciousness at the onset, and the outcomes were poor. We emphasize that a very early operation is required for a good outcome.

Okumoto K, Saito T, Onodera M, Sakamoto A, Tanaka M, Hattori E, Haga H, Ito JI, Sugahara K, Saito K, Togashi H, Kawata S. · Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata City, Yamagata, Japan. · J Gastroenterol Hepatol. · Pubmed #17688667 No free full text.

Abstract: BACKGROUND AND AIM: Hematopoietic growth factors including stem cell factor (SCF), thrombopoietin (TPO) and granulocyte colony stimulating factor (G-CSF) have a potential role in inducing bone marrow hematopoietic stem cells to move into the circulation, and the association of these factors with liver regeneration has received a lot of attention recently. The aim of this study was to determine the serum levels of such factors in patients with acute liver injury. METHODS: The subjects were 25 patients with acute hepatitis (AH) who had a favorable prognosis and 26 patients with fulminant hepatitis (FH), of whom 11 were alive and 15 had died. Sixty-six healthy subjects matched for age and sex served as controls. Serum samples were collected before treatment, and the levels of SCF, TPO and G-CSF were measured using enzyme-linked immunosorbant assays. RESULTS: The levels of SCF and TPO were significantly lower in FH patients than in AH patients and the controls, and were also significantly lower in the FH patients who died, compared to the surviving patients. The G-CSF levels did not differ among them. CONCLUSIONS: These results suggest that low serum levels of SCF and TPO may be linked to poor prognosis in patients with severe liver injury.

Endo H, Kawauchi K, Tomimatsu M, Iga D, Ogasawara T, Yasuyama M, Saito T, Otsuka K, Aiba M. · Department of Internal Medicine, Tokyo Women's Medical University Medical Center East, Tokyo, Japan. <> · Intern Med. · Pubmed #17473502 links to  free full text

Abstract: A 70-year-old woman suffering from HCV-related liver cirrhosis was admitted for abnormal bleeding. Laboratory findings included PT at 46.6 sec, APTT at >212 sec, factor V activity of <3%, and factor V inhibitor of 2 BU. Having experienced a persistent bleeding tendency for one month, the patient was started on prednisolone (0.8 mg/kg/day). Within a few days, the inhibitor became undetectable and clinical bleeding disappeared. Although clinical improvement was achieved, she died 6 months after the initial bleeding episode from the progression of a lung cancer. An autopsy revealed squamous cell carcinoma of the lung and hepatocellular carcinoma.

Akatsuka T, Kobayashi N, Ishikawa T, Saito T, Shindo M, Yamauchi M, Kurokohchi K, Miyazawa H, Duan H, Matsunaga T, Komoda T, Morisseau C, Hammock BD. · Department of Microbiology, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan. · J Autoimmun. · Pubmed #17296285 links to  free full text

Abstract: Autoimmune responses were observed in a large proportion of hepatitis C cases and are suspected to be part of viral pathogenesis. The AN6520 antigen (AN-Ag) is a normal cellular protein mainly expressed in liver that was found associated with non-A, non-B hepatitis. To elucidate its pathogenic role in hepatitis C, we developed an IgM capture assay using purified AN-Ag and confirmed that the antibody response to AN-Ag is associated almost exclusively with hepatitis C cases (29%). Screening of a human liver expression library revealed that AN-Ag is mainly the microsomal epoxide hydrolase (mEH), a drug-metabolizing enzyme that plays an important role in the metabolism of some mutagenic and carcinogenic epoxides. Using the purified recombinant human mEH as an antigen, we now found that antibodies against this protein are associated with nearly 82% of hepatitis C virus infections and surprisingly with 46% of patients with hepatitis A. The appearance of AN-Ag/mEH in the incubation period of hepatitis C as previously reported and the antibody responses shown here indicate that this enzyme may be a marker for or even a cause of some of the pathology associated with hepatitis C and A.