Hepatitis: Japan

Li T, Takeda N. · Department of Virology 2, National Institute of Infectious Diseases, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19194092 No free full text.

This publication has no abstract.

Okamoto H. · Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19194090 No free full text.

This publication has no abstract.

Masuzaki R, Yoshida H, Tateishi R, Shiina S, Omata M. · Department of Gastroenterology, University of Tokyo, Bunkyo-ku, Tokyo, Japan. · Best Pract Res Clin Gastroenterol. · Pubmed #19187872 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is a common malignancy worldwide, and its incidence is increasing in the United States and elsewhere. The prognosis of HCC patients depends not only on tumour stage but also on the background liver function reservoir. Current options for the treatment of HCC are surgical resection, liver transplantation, transcatheter arterial embolization, chemotherapy, and percutaneous ablation therapy. The choice of optimal treatment for individual patients, especially those at an earlier cancer stage, is sometimes controversial. Short-term prognosis of HCC patients has been much improved recently due to advances in early diagnosis and treatment, although long-term prognosis is as yet far from satisfactory as indicated by the overall survival at 10 years after apparently curative treatment of only 22-35%. Prevention of HCC recurrence, or tertiary prevention, is one of the most challenging tasks in current hepatology.

Usui M, Minoda H. · Department of Ophthalmology, Tokyo Medical University. · Nippon Rinsho. · Pubmed #19177759 No free full text.

Abstract: In this paper, we review sexually transmitted diseases (STD) involving the eye. Recently conjunctivitis due to Chlamydia trachomatis in children and adults is increasing, and that of Neisseria gonorrhoeae resistant to multiple antibiotics has attracted special attention in our country. Syphilis has many ocular manifestations such as keratitis, iridocyclitis, retinochorioiditis, and neuritis, etc. Ocular complications related to HIV infection, including HIV retinopathy, cytomegalovirus retinitis, zoster ophthalmics, and Kaposi s sarcoma in conjunctiva are increasing in Japan. Phthirus pubis infection of the eye lid, and human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis are occasionally reported. Furthermore conjunctival tumor associated with human papilloma virus (HPV) infection, acute retinal necrosis(ARN) due to herpes simplex virus type 2 (HSV-2), as well as hepatitis B virus (HVB) and hepatitis C virus (HVC) retinopathy are also mentioned in this review.

Akari H, Iwasaki Y, Yoshida T, Iijima S. · Laboratory of Disease Control, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan. · Microbiol Immunol. · Pubmed #19161559 No free full text.

Abstract: More than 170 million people worldwide are chronically infected by HCV, which is the causative agent of chronic hepatitis C, cirrhosis, and finally liver cancer. Although animal models of viral hepatitis are a prerequisite for the evaluation of antiviral and vaccine efficacy, the restricted host range of HCV has hampered the development of a suitable small animal model of HCV infection. Use of the chimpanzee, the only animal known to be susceptible to HCV infection, is limited by ethical and financial restrictions. In this regard GBV-B, being closely related to HCV, appears to be a promising non-human surrogate model for the study of HCV infection. This review describes the characteristic of GBV-B infection of New World monkeys, and discusses current issues concerning the GBV-B model and its future directions.

Watanabe T, Soga K, Hirono H, Hasegawa K, Shibasaki K, Kawai H, Aoyagi Y. · Department of Internal Medicine and Gastroenterology, Medical Hospital, The Nippon Dental University School of Life Dentistry at Niigata, 1-8 Hamauracho, Chu-o-ku, Niigata 951-8580, Japan. · World J Gastroenterol. · Pubmed #19132775 links to  free full text

Abstract: AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)]. Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 +/- 12 mo in AIH patients and 8.4 +/- 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC.

Ebihara T, Matsumoto M, Seya T. · Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. · Uirusu. · Pubmed #19122385 links to  free full text

Abstract: Hepatitis C virus (HCV) is a single-strand, positive sense RNA virus belonging to the flaviviridae family. HCV develops persistent infection in >70% of infected patients, and eventually causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma in some patients. Once chronic infection is established in patients with HCV, spontaneous viral clearance fails, although how HCV remains persistently infecting the liver is largely unknown. Insufficient immune response, involving antiviral innate immune response including dendritic cells (DCs), has been focused. A number of controversial studies have been reported as to HCV genome replication and HCV-mediated immune responses in human DCs. A tantalizing point of these earlier studies is the lack of the system for viral propagation in HCV. Recently, an in vitro system was exploited to propagate HCV particles using the JFH1 strain. In this review, we review the previous reports about the subversion of innate immunity by HCV and show the innate response of monocyte-derived dendritic cells (MoDCs) against the JFH1 strain. We could not observe HCV direct interaction with MoDC maturation. MoDCs maturated by phagocytosing HCV-infected apoptotic cells containing virus-derived dsRNA, which interacted with TLR3 in the phagosomes. All of these data suggests the importance of TLR3 signal for the induction of anti-HCV innate immunity.

Kudo M. · Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. · Oncology. · Pubmed #19092266 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is a malignant tumor which is becoming more prevalent worldwide. Patients at high risk of developing HCC, namely hepatitis B- and C-related liver cirrhosis patients, should be entered into surveillance programs, which should be performed using both ultrasonography and 3 tumor markers (AFP, PIVKA-II, AFP-L3). The surveillance interval needs to be shortened for patients at higher risk of HCC. Therefore, super-high-risk patients should be screened at 3- to 4-month intervals based on their risk of developing HCC. Sonazoid-enhanced US is extremely useful to characterize hepatic tumors when compared with multidetector-row computed tomography (MDCT). Moreover, Sonazoid-enhanced US with defect reperfusion imaging is a breakthrough approach in the treatment of HCC. This technique will markedly change the therapeutic strategy for liver cancer. Furthermore, diagnostic capability using the new imaging technique Gd-EOB-DTPA MRI is promising. A reduced uptake (low intensity) in the hepatobiliary phase of Gd-EOB-DTPA MRI strongly suggests HCC (including early-stage HCC) or a high-grade dysplastic nodule with high malignant potential. Empirically, intrahepatic arterial infusion chemotherapy using implanted reservoir port is known to be effective for advanced HCC with vascular invasion; however, no randomized study exists to prove its efficacy. Further controlled study is necessary to establish this treatment option as a standard of care in a treatment algorithm for HCC. In contrast, sorafenib was established as the first choice of treatment as a standard of care in advanced HCC patients with preserved liver function and vascular invasion/extrahepatic spread. Furthermore, global clinical trials are now ongoing using sorafenib as an adjuvant setting after resection, ablation or TACE. Efficacy of combined use of sorafenib with TACE or intra-arterial infusion chemotherapy is not clear. In order to clarify this issue a randomized clinical trial for intermediate and advanced HCC comparing sorafenib alone versus sorafenib combined with maintenance TACE/intra-arterial infusion chemotherapy and/or intra-arterial infusion chemotherapy is scheduled to be initiated in Japan in 2009. If positive results are obtained by these trials, its impact on treatment strategy for HCC will be drastically changed.

Suzuki F. · Department of Hepatology, Toranomon Hospital, Tokyo 105-8470, Japan. · Rinsho Byori. · Pubmed #19086457 No free full text.

Abstract: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major viruses known to cause viral hepatitis. Serological markers are commonly used as diagnostic and/or prognostic indicators of acute or chronic HBV or HCV infection. The ability to detect HBV DNA in serum has been reported to have prognostic value for the outcome of chronic HBV infection. A rapid and sustained drop in HBV DNA or HCV RNA levels in patients under therapy has been shown to be a predictive factor for a favourable treatment outcome. Various techniques for detecting HBV DNA or HCV RNA have already been described; however, there are various problems with the sensitivity or detection range of those methods. New virus measuring methods have recently been reported and used. The Cobas Taq Man HCV Test is a new method to detect HBV DNA and HCV RNA with higher sensitivity and a broader range of quantitation than conventional methods. Some reports have shown that these methods improve therapy monitoring and the management of HBV or HCV infection. Moreover, hepatitis E virus (HEV) infection has been reported in Japan. The clinical features and viral markers of HEV have also been described.

Teranishi M, Manabe S. · · Nippon Yakurigaku Zasshi. · Pubmed #19075530 No free full text.

This publication has no abstract.

Takedai M, Takatani A, Funato T, Ino K, Nakayama T, Nomura F, Miyachi H, Noboru T, Ueda K. · Division of Healthcare Economics and Quality Management, Tohoku Fukushi University, Sendai, 981-8522, Japan. · Rinsho Byori. · Pubmed #19068783 No free full text.

Abstract: Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. The severity of disease varies widely from mild illness to cirrhosis and hepatocellular carcinoma. The routine diagnostic test for HCV infection is performed using anti-HCV antibodies and an enzyme immunoassay (EIA) for serologic identification and HCV-RNA assay employing the polymerase chain reaction(PCR) for genetic identification. This study assessed the sensitivity and specificity of HCV-RNA diagnostic tests on analysis of the literature. A literature search was performed using the criteria from The standards for Reporting of Diagnostic Accuracy (STARD) steering committee for the assessment of diagnostic tests. The selected studies were searched for identifying publications on the appropriate conducting and reporting of diagnostic studies, and we extracted potential items to generate an extensive list. Out of 409 studies, 38 were selected. Further studies are necessary to accurately access HCV-RNA in various populations compared with reference tests.

Kimura T, Noguchi Y, Shikata N, Takahashi M. · Quality Assurance and External Scientific Affairs Department, Ajinomoto Co., Inc, Tokyo, Japan. · Curr Opin Clin Nutr Metab Care. · Pubmed #19057187 No free full text.

Abstract: PURPOSE OF REVIEW: To highlight the usefulness of amino acid profiling in clinical diagnosis and current developments in analysis revealing underlying metabolic relationships. RECENT FINDINGS: Recent innovations in metabolomics and systems biology enable high throughput measurement of diverse amino acids and the subsequent data mining for various uses. Recent studies show new possibilities of using plasma amino acid analysis as biomarker discovery tools by generating diagnostic indices through systematic computation. Such studies show that amino acid-based clinical diagnostic indices for hepatic fibrosis in type C hepatitis patients can be generated. In addition, several studies show the potential of treating amino acid profile data as a metabolomic subset, which can be integrated through the analysis of correlation with different types of 'omics' data for describing metabolite-to-metabolite or metabolite-to-gene interaction networks. CONCLUSION: Amino acid profiling of biological samples could be used to generate indices that could be used for clinical diagnosis and is a useful tool for understanding metabolic implications under various physiological conditions. Although further improvements in analytical methods are needed, amino acids could be useful indicators for facilitating nutritional management of specific physiological and pathological states.

Otsubo H, Yamaguchi K. · Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan. · Jpn J Infect Dis. · Pubmed #19050347 links to  free full text

Abstract: Over the past decades, the incidence of transfusion-transmitted diseases has been dramatically reduced. These reductions have been due to a multifocal approach to the collection, processing, and release of blood components. The estimated risks of transfusion-transmitted hepatitis viruses are now extremely small, but the possibility of infections with emerging pathogens always exists because preventive measures may not be available for all cases. Thus, some patients may be harmed before preventive measures are introduced. Beside transfusion-transmitted infections (TTI), unsolved residual risks such as transfusion-related acute lung injury or incompatible blood components transfusion still exist as major concerns. Continuous efforts toward research on and the prevention of adverse reaction-related blood components must be made to ensure blood safety. The purpose of this article is to introduce the concept of the current risks of transfusion including TTI, review the preventive measures already implemented, and discuss future visions for transfusion safety in Japan.

Toyokuni S. · Department of Pathology and Biological Responses, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan. · Cancer Sci. · Pubmed #19018762 No free full text.

Abstract: Iron is abundant universally. During the evolutionary processes, humans have selected iron as a carrier of oxygen inside the body. However, iron works as a double-edged sword, and its excess is a risk for cancer, presumably via generation of reactive oxygen species. Thus far, pathological conditions such as hemochromatosis, chronic viral hepatitis B and C, exposure to asbestos fibers, as well as endometriosis have been recognized as iron overload-associated risks for human cancer. Indeed, iron is carcinogenic in animal experiments. These reports unexpectedly revealed that there are target genes in iron-induced carcinogenesis and that iron-catalyzed oxidative DNA damage is not random in vivo. Several iron transporters and hepcidin, a peptide hormone regulating iron metabolism, were discovered in the past decade. Furthermore, a recent epidemiological study reported that iron reduction by phlebotomy decreased cancer risk in the apparently normal population. These results warrant reconsideration of the role of iron in carcinogenesis and suggest that fine control of body iron stores would be a wise strategy for cancer prevention.

Kamada Y, Takehara T, Hayashi N. · Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka 565-0871, Japan. · J Gastroenterol. · Pubmed #19012034 No free full text.

Abstract: Adipose tissue is a massive source of bioactive substances known as adipocytokines, including tumor necrosis factor (TNF)-alpha, resistin, leptin, and adiponectin. Recent advances in medical research view obesity as a chronic low-grade inflammatory state. Hypertrophied adipocytes in obesity release chemokines that induce macrophage accumulation in adipose tissue. Accumulated macrophages in obese adipose tissue produce proinflammatory cytokines and nitric oxide, and these inflammatory changes induce adipocytokine dysregulation. The latter is characterized by a decrease in insulinsensitizing and anti-inflammatory adipocytokines, and an increase in proinflammatory adipocytokines. Adipocytokine dysregulation induces obesity-related metabolic disorders, the so-called metabolic syndrome. Metabolic syndrome is a cluster of metabolic abnormalities, including diabetes mellitus, hypertension, hyperlipidemia, and nonalcoholic steatohepatitis (NASH). Recent studies have revealed that obesity is an independent risk factor for chronic liver diseases, such as NASH, alcoholic liver disease, chronic hepatitis C, and hepatocellular carcinoma. A common mechanism underlying these hepatic clinical states is thought to be adipocytokine dysregulation. In this review, we discuss the association of adipocytokines, especially leptin, adiponectin, TNF-alpha, and resistin, with liver diseases.

Nagai H, Sumino Y. · Division of Gastroenterology and Hepatology, Toho University Medical Center, Omori Hospital, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan. · Recent Pat Anticancer Drug Discov. · Pubmed #18991790 No free full text.

Abstract: The majority of primary liver cancer is hepatocellular carcinoma (HCC). HCC has increased in many countries, particularly where hepatitis C virus infection is more common than hepatitis B virus infection. Several non-surgical treatment options, including transcatheter arterial embolization, percutaneous ethanol injection, microwave coagulation, and radiofrequency ablation have been developed and are widely used for unresectable HCC. However, these modalities are not indicated for patients with multifocal disease, invasion or thrombosis of major blood vessels, and poor liver function. The majority of patients with advanced hepatocellular carcinoma (aHCC) do not survive for longer than 6 months from the time of diagnosis. Combined intra-arterial chemotherapy is one of the few remaining options for patients with aHCC. Continuous local arterial infusion of 5-fluorouracil (5-FU) and cisplatin (CDDP) via an infuser pump and implanted reservoir has been shown to prolong the survival of patients with aHCC. When LC patients with aHCC undergo chemotherapy, we should consider the influence of both tumor factors and host immunity. This review focuses on therapeutic strategy of patients with aHCC by using combined intra-arterial chemotherapy and the influence of host immunity on the response to such chemotherapy based on our results. The present article shows some recent patents related to the field.

Ishikawa T. · Department of Gastroenterology and Hepatology, Saiseikai Niigata Second Hospital, Teraji 280-7, Niigata 950-1104, Japan. · World J Gastroenterol. · Pubmed #18985803 links to  free full text

Abstract: Chronic hepatitis C is a leading cause of hepatocellular carcinoma (HCC) worldwide. Interferon (IFN) therapy decreases the incidence of HCC in patients with chronic hepatitis C. Prevention of chronic-hepatitis-C-related HCC is one of the most important issues in current hepatology. We have previously reported that male gender and high titer of hepatitis C virus (HCV) RNA are predictive factors for the development of HCC in HCV-related cirrhosis. Clinical efforts at eradicating or reducing the viral load may reduce the risk for HCC. Furthermore, because HCC often recurs after ablation therapy, we performed a trial of IFN in patients with chronic liver disease caused by HCV to see whether IFN therapy decreases recurrence after ablation therapy of HCV-related HCC. By using IFN therapy as a secondary prevention, patients with HCC who had received complete tumor ablation showed better survival, primarily as a result of the preservation of liver function and also probably prevention of recurrence. Postoperative IFN therapy appears to decrease recurrence after ablation therapy such as radiofrequency ablation (RFA) therapy of HCV-related HCC. We believe that there is a survival benefit in secondary prevention using IFN therapy. However, a controlled study is essential to obtain conclusive evidence of the efficacy of this strategy.

Tanaka K, Tsuji I, Wakai K, Nagata C, Mizoue T, Inoue M, Tsugane S, Anonymous00029. · Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan. · Jpn J Clin Oncol. · Pubmed #18945722 links to  free full text

Abstract: BACKGROUND: Although alcohol consumption has been recognized as a risk factor for primary liver cancer, it will be informative to summarize relevant epidemiologic data in the Japanese who have characteristic environmental determinants (e.g. hepatitis C virus infection) and genetic traits (e.g. presence of poor acetaldehyde metabolizers). METHODS: We systematically reviewed epidemiologic studies on alcohol drinking and liver cancer among Japanese populations. Original data were obtained through searches of the MEDLINE (PubMed) and Ichushi databases, complemented with manual searches. The evaluation was performed in terms of the magnitude of association ('strong', 'moderate', 'weak' or 'no association') in each study and the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient'), together with biological plausibility as previously assessed by the International Agency for Research on Cancer. RESULTS: Among 22 cohort studies identified, 14 (64%) reported weak to strong positive associations between alcohol and liver cancer risk, 3 (14%) reported no association and five (23%) reported weak to moderate inverse associations; such inverse associations were found mostly in follow-up studies of patients with chronic liver disease (particularly, cirrhotic patients), yet recent studies on patients with chronic hepatitis C presented fairly consistent positive associations. Of 24 case-control studies identified, 19 (79%) showed weak to strong positive associations, whereas the remainder demonstrated no association (n = 4) or a moderate inverse association (n = 1). CONCLUSION: We conclude that there is 'convincing' evidence that alcohol drinking increases the risk of primary liver cancer among the Japanese population.

Nishino H, Murakoshi M, Tokuda H, Satomi Y. · Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, Nojihigashi 1-1-1, Kusatsu, Shiga 525-8577, Japan. · Arch Biochem Biophys. · Pubmed #18848517 No free full text.

Abstract: Various natural carotenoids seem to be valuable for cancer prevention, and these carotenoids may be more suitable in combinational use, rather than in single use. In fact, we have proven that combinational use of natural carotenoids resulted in significant suppression of liver cancer. Patients of viral hepatitis with cirrhosis were administered with beta-cryptoxanthin-enriched Mandarin orange juice, in addition to capsules of carotenoids mixture. Cumulative incidence of hepatocellular carcinoma development was compared with that in the group treated with carotenoids mixture capsules alone, or in the group without treatment (control group). In the data analysis at year 2.5, cumulative incidence of liver cancer in beta-cryptoxanthin-enriched orange juice with carotenoids mixture capsules-treated group was lower than that in the control group (p=0.05). Cumulative incidence of liver cancer in the group treated with carotenoids mixture capsules alone was also lower than that in the control group, but not statistically significant.

Pachera S, Nishio H, Takahashi Y, Yokoyama Y, Oda K, Ebata T, Igami T, Nagino M. · Division of Surgical Oncology, Department of Surgery, University of Nagoya Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan. · J Hepatobiliary Pancreat Surg. · Pubmed #18836810 No free full text.

Abstract: Undifferentiated embryonal sarcoma (UES) of the liver was first identified as an independent clinicopathologic type of sarcoma in 1978. It is an uncommon hepatic tumor, of mesenchymal origin, usually observed in children, and cases in adults are rare: to our best knowledge, reports of only 51 cases have been published in the past 50 years. We present a case of UES of the liver in a previously healthy 22 year-old woman, admitted to our hospital due to a palpable mass in the right upper abdomen. On admission, laboratory studies showed mildly elevated aspartate aminotransferase, alkaline phosphatase, and gamma-GPT. Hepatitis and tumor markers were negative. Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) showed a large mass involving the right lobe and the medial segment of the liver, with compression of the bile duct. Right trisectionectomy with bile duct resection and reconstruction was performed. Microscopically, the tumor was composed of pleomorphic spindle cells in a myxoid stroma with focal staining of S-100 by immunohistochemistry. The histologic diagnosis was UES. Adjuvant therapy with vincristine, actinomycin-D, and cyclophosphamide was performed, and at 14 months of follow-up, the patient is alive without any evidence of recurrence. The clinical and histopathological features, as well as the therapeutic choices for adult UES, are described for this patient and in the literature of the past 50 years.

Doi H, Horiike N, Hiraoka A, Koizumi Y, Yamamoto Y, Hasebe A, Ichikawa S, Yano M, Miyamoto Y, Ninomiya T, Ishimaru Y, Miyagawa M, Takamura K, Kawasaki H, Kozuka T, Maeda T, Yoshino T. · Department of Gastroenterology, Ehime Prefectural Central Hospital, Ehime, Japan. · Int J Hematol. · Pubmed #18807227 No free full text.

Abstract: A primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) is very rare. We found a solitary mass 27 mm in size in the left lobe of the liver of a 58-year-old Japanese man with a history of hepatitis-C infection. Based on the results of imaging studies, the tumor was diagnosed as a hepatocellular carcinoma (HCC). The left lobe of the liver was lobectomized and microscopic findings showed that the tumor was a hepatic MALT lymphoma, while immunohistochemistry showed it to be positive for CD20 and CD79a. In a fluorodeoxyglucose-positron emission tomography examination integrated with computed tomography scanning (FDG-PET CT) before surgery, the tumor was revealed to have a high standardized uptake value (SUV) for FDG. The patient received chemotherapy after surgery. To the best of our knowledge, 45 cases had been reported with a mean age for all patients of 61.4 years. The pathogenesis remains unclear, although half of the patients had a past history of chronic inflammatory liver disease. Surgical resection was performed in most cases and some patients received postoperative chemotherapy or radiotherapy. The clinicopathologic characteristics and management of this extremely rare disease are also discussed.

Miyake Y, Yamamoto K. · Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. · Acta Med Okayama. · Pubmed #18766204 links to  free full text

Abstract: Autoimmune hepatitis (AIH) is a chronic and progressive disease characterized by histological interface hepatitis, hypergammaglobulinemia, and circulating autoantibodies. Multiple factors, including molecular mimicry, a genetic background including major histocompatibility complex class II, and defective function of regulatory T-cells, are involved in the pathogenesis. The diagnosis is made based on the scoring system of the International Autoimmune Hepatitis Group, the sensitivity and specificity of which are > 90%, respectively. AIH is classified into 3 sub-types based on the profiles of circulating autoantibodies: anti-nuclear antibody and/or smooth muscle antibody-positive (type 1), anti-liver-kidney microsomal antibody-positive (type 2), and anti-soluble liver antigen/liver-pancreas antigen antibody- positive (type 3). Recently, however, the number of atypical cases lacking the usual features has increased--for example, patients with acute-onset or fulminant-type AIH, autoantibody-negative patients, male patients, and patients with bile duct injury--and thus the clinical features of AIH have been diversified. AIH is responsive to immunosuppressive treatment in most cases; however, relapse occurs in more than 80% of patients within 1 year after immunosuppressive treatment withdrawal. The 10-year survival rate and the 10-year hepatocellular carcinoma-free rate are > 90%, respectively, indicating that some patients reach liver failure or develop hepatocellular carcinoma. To improve the prognosis of these patients, persistent normalization of transaminase is required.

Hiroishi K, Ito T, Imawari M. · Department of Gastroenterology, Showa University School of Medicine, Tokyo, Japan. · J Gastroenterol Hepatol. · Pubmed #18761560 No free full text.

Abstract: Immune responses against hepatitis C virus (HCV) play a crucial role in the pathogenesis of chronic hepatitis C. HCV infection often persists and leads to chronic hepatitis and eventually cirrhosis. Accumulated data suggest that HCV proteins suppress host immune responses through the suppression of functions of immune cells, such as cytotoxic T lymphocytes, natural killer cells, and dendritic cells. They also suppress the type 1 interferon signaling system. The resulting insufficient immune responses against HCV lead to the sustained infection. The appropriate control of immune responses would contribute to the eradication of HCV and the improvement of hepatitis, but there are still many issues to be clarified. This review describes the scientific evidence to support these emerging concepts, and will touch on the implications for improving antiviral therapy.

Motoyama H, Enomoto M, Yasuda T, Fujii H, Kobayashi S, Iwai S, Morikawa H, Takeda T, Tamori A, Sakaguchi H, Kawada N. · Department of Hepatology, Graduate School of Medicine, Osaka City University, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #18679001 No free full text.

Abstract: A 37-year-old woman was admitted to a hospital with jaundice. Within a couple of weeks, her liver function improved with only symptomatic therapy. About 30 to 60 days before admission, she had taken a herbal medicine, bofu-tsu-sho-san. A diagnosis of drug-induced liver injury was made according to the diagnostic scale proposed at the Digestive Disease Week-Japan 2004. A drug-lymphocyte stimulation test for each ingredient of bofu-tsu-sho-san; the results were positive for Cnidii Rhizoma, Angelicae Radix and Menthae Herba. The liver biopsy specimen revealed features of acute hepatitis. Physicians should be aware that bofu-tsu-sho-san can cause liver injury, as this drug is commonly used as an over-the-counter medicine.

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.