Hepatitis: Osaka

Moriishi K, Mori Y, Matsuura Y. · Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan. · Uirusu. · Pubmed #19374196 links to  free full text

Abstract: Hepatitis C virus (HCV) is a major causative agent of blood-borne hepatitis. Most of the HCV-positive individuals have been chronically infected with the virus for decades, leading to development of steatosis, cirrhosis and ultimately hepatocellular carcinoma. In addition, cryoglobulinemia and type 2 diabetes mellitus are associated with a chronic infection with HCV. Hepatocellular carcinoma induced by HCV infection is not caused by only the repeated inflammations but also the biological activity of HCV proteins. HCV core protein has been reported as a component of the viral nucleocapsid as well as the pathogenic factor that could induce the production of oxidative stress and progression of cell growth. In this review, we summarize the current status of our knowledge regarding to the processing and pathogenicity of HCV core protein.

Kasuya T, Kuroda S. · Osaka University, Institute of Scientific and Industrial Research, Department of Structural Molecular Biology, Ibaraki, Japan. · Expert Opin Drug Deliv. · Pubmed #19236207 No free full text.

Abstract: A wide variety of nanoparticles (NPs) that can deliver incorporated therapeutic materials such as compounds, proteins, genes and siRNAs to the human liver have been developed to treat liver-related diseases. This review describes NP-based drug and gene delivery systems such as liposomes (including lipoplex), polymer micelles, polymers (including polyplex) and viral vectors. It focuses upon the modification of these NPs to enhance liver specificity or delivery efficiency in vitro and in vivo. We discuss recent advances in drug and gene delivery systems specific to the human liver utilizing bio-nanocapsules comprising hepatitis B virus (HBV) envelope L protein, which has a pivotal role in HBV infection. These NP-based medicines may offer novel strategies for the treatment of liver-related diseases and contribute to the development of nanomedicines targeting other tissues.

Kiuchi K, Kitagawa C, Miyashiro M. · Department of Ophthalmology, Osaka Saiseikai Izuo Hospital, Osaka, Japan. · Nippon Ganka Gakkai Zasshi. · Pubmed #19227928 No free full text.

Abstract: BACKGROUND: We treated a patient with anterior ischemic optic neuropathy caused by peginterferon. CASE: Upon medical examination of the eyes before starting interferon therapy for chronic hepatitis C at Saiseikai Izuo hospital, a 64-year-old man showed corrected visual acuity of 0.9 in the right eye and 1.0 in the left. No abnormality was visible in either eye except for mild cataracts. Six weeks after combination therapy with peginterferon alpha-2b and ribavirin was started, corrected visual acuity was found to have decreased in the right eye, and swelling of the optic nervehead in both eyes was evident. Bilateral anterior ischemic optic neuropathy caused by interferon therapy was diagnosed. Combination therapy with peginterferon alpha-2 b and ribavirin was discontinued, and administration of prednisolone was started at a dose of 60 mg. However, visual acuity declined in both eyes and the visual field defects worsend. At the most recent examination, visual acuity was 1.0 in the right eye and 0.01 in the left. The visual field included only the temporal periphery in the left eye, and part of the central and upper temporal periphery in the right. CONCLUSION: Since the outcome of visual acuity and visual fields in anterior ischemic optic neuropathy caused by interferon can be poor, an effective therapy for this complication needs to be developed.

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.

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.

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.

Iwai K. · Graduate School of Frontier Biosciences, Osaka University, Suita, Japan. · Rinsho Byori. · Pubmed #18646637 No free full text.

Abstract: Iron is an essential nutrient virtually almost all organisms including human, but at the same time, it is toxic because its high reactivity to molecular oxygen generates free radicals. Therefore, iron metabolism is tightly regulated. Recently, knowledge of roles that iron plays in our body as well as regulatory mechanism of iron metabolism in human body has been drastically expanded. Here I describe recent advance in our understanding on the regulation of iron metabolism and discuss its relationship to various diseases.

Kanto T. · Department of Gastroenterology, Osaka University Graduate School of Medicine, Suita, Japan. · Front Biosci. · Pubmed #18508652 No free full text.

Abstract: Dendritic cells (DCs) sense virus via toll-like receptors (TLR) or retinoic acid inducible gene-I (RIG-I) and evoke a cascade of immune reactions. In myeloid DC (MDC) from hepatitis C virus (HCV)-infected patients, the levels of TLR/RIG-I-mediated IFN-beta or TNF-alfa induction are lower than those in uninfected donors, suggesting that their signal transduction in MDC is impaired. Dendritic cells in HCV infection are unresponsive to interferon (IFN)-alfa, thus failing to enhance MHC class-I related chain A/B and subsequent NK cell activation. Alternatively, NK cells from the patients down-regulate DC in the presence of HLA-E-expressing hepatocytes by secreting IL-10 and TGF-beta1. Such functional alteration of NK cells in HCV infection is ascribed to the enhanced expression of NKG2A/CD94. Activated NKT cells from the patients produce higher levels of IL-13 but comparable IFN-gamma with those from controls, showing their bias to Th2-type. In pegylated IFN-alfa/ribavirin therapy for chronic hepatitis C, improved DC function is related with successful HCV eradication. In conclusion, cross-talks among DCs and innate lymphocytes are critical in shaping immune response against HCV, either spontaneously or therapeutically.

Moriishi K, Matsuura Y. · Department of Molecular Virology Research Institute for Microbial Diseases, Osaka University 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. · Uirusu. · Pubmed #18357752 links to  free full text

Abstract: Hepatitis C virus (HCV) infects approximately 170 million people worldwide including 2 million in Japan and induces serious chronic hepatitis that results in the development of steatosis, cirrhosis and ultimately hepatocellular carcinoma. The current combination therapy using pegylated interferon alpha and a nucleotide analogue ribavirin achieved a sustained virological response in about half population of individuals infected with HCV genotypes la and lb. More than two-thirds of the HCV-positive population has been chronically infected with genotype 1 in Western countries and Japan. Therefore, more effective therapeutics and preventative measures are needed for the treatment of hepatitis C patients who are not responsive to the current chemotherapy. HCV core protein is well known to be the viral capsid protein as well as the pathogenic factor that induces steatosis and hepatocellular carcinoma in the transgenic mice. In this review, we summarize the current status of our knowledge regarding the molecular mechanism by which HCV core protein induces liver steatosis and hepatocellular carcinoma and discuss on a future perspective for the development of novel therapeutics for chronic hepatitis C.

Mori Y, Moriishi K, Matsuura Y. · Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. · Int J Biochem Cell Biol. · Pubmed #18321762 No free full text.

Abstract: Hepatitis C virus (HCV) is a major cause of chronic liver diseases, including steatosis, cirrhosis and hepatocellular carcinoma, and epidemiological studies indicate that HCV is also associated with insulin resistance and type 2 diabetes mellitus. The HCV core protein is not only a viral structural component but also a pathogenic factor, since its expression leads to the development of liver steatosis, insulin resistance and hepatocellular carcinoma in mice. The nuclear proteasome activator PA28gamma/REGgamma, which specifically binds to the core protein, is required for the virulence of the core protein. Elucidation of the mechanisms by which HCV core protein participates in the above conditions may provide clues toward the development of novel therapeutic measures for chronic hepatitis C.

Hayashi N, Oze T, Hiramatsu N. · Department of Gastroenterology and Hepatology, Osaka University Graduate school of Medicine. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #18250587 No free full text.

This publication has no abstract.

Yagi K, Kojima M, Oyagi S, Ikeda E, Hirose M, Isoda K, Kawase M, Kondoh M, Ohgushi H. · Graduate School of Pharmaceutical Sciences, Osaka University, Suita City, Japan. · Yakugaku Zasshi. · Pubmed #18176050 links to  free full text

Abstract: Stem cell-based therapy has received attention as a possible alternative to organ transplantation, owing to the ability of stem cells to repopulate and differentiate at the engrafted site. We transplanted bone marrow-derived mesenchymal stem cells (BMSCs) into liver-injured rats to test the therapeutic effect. Rat bone marrow cells were cultured in the presence of hepatocyte growth factor (HGF). RT-PCR and immunocytochemical analysis indicated that the BMSCs expressed the albumin mRNA and the production of protein after cultivation with HGF for 2 weeks. The BMSCs appeared to differentiate into hepatocyte-like cells in response to the culture with HGF. After labeling with a fluorescent marker, the BMSCs were transplanted into CCl(4)-injured rats by injection through the caudal vein. The liver was excised and blood samples were collected 4 weeks later. Engraftment of the transplanted BMSCs was seen with significant fluorescence in the injured liver. Transplantation of the BMSCs into liver-injured rats restored their serum albumin level and suppressed transaminase activity and liver fibrosis. Therefore, BMSCs were shown to have a therapeutic effect on liver injury. Recently, we have been trying to use mesenchymal stem cells isolated from dental papilla of discarded human wisdom teeth. Autologous transplantation of mesenchymal stem cells from bone marrow and dental papilla could be ethically and functionally promising for stem cell-based therapy.

Iwai K, Ueta R. · Department of Molecular Cell Biology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. · Seikagaku. · Pubmed #18095456 No free full text.

This publication has no abstract.

Moriishi K, Matsuura Y. · Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita-shi, Osaka 565-0871, Japan. · Adv Drug Deliv Rev. · Pubmed #17720275 No free full text.

Abstract: Development of therapeutics for chronic hepatitis C has been hampered by the lack of an efficient cell culture system and a small animal model for the hepatitis C virus (HCV). An RNA replicon system, in which the HCV genome replicates autonomously in cells, and replication competent viruses derived from an HCV genotype 2a JFH1 strain efficiently propagating in Huh7 cells have been developed, and these systems have contributed to the evaluation of anti-HCV drugs targeted to viral and host proteins involved in the replication of HCV. Several compounds counteracting the viral enzymes, such as RNA polymerase and proteases, and host proteins involved in the lipid synthesis and protein folding are reported to have anti-HCV activities based on assessments using these in vitro systems. Furthermore, a mouse model transplanted with human liver fragments was shown to be capable of replicating HCV and has been used to evaluate the efficacy of antiviral drugs in vivo. In this review, we summarize information regarding systems for studying the HCV life cycle and potential new targets for therapeutic intervention for chronic hepatitis C.

Moriishi K, Matsuura Y. · Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. · Rev Med Virol. · Pubmed #17563922 No free full text.

Abstract: Hepatitis C virus (HCV) is the major causative agent of blood-borne hepatitis. The majority of HCV-infected individuals develop chronic hepatitis, which eventually progresses to liver cirrhosis, and hepatocellular carcinoma. Although the precise mechanisms of entry, replication, assembly, egress and pathogenesis of HCV are largely unknown, information about viral receptor candidates has accumulated by the development of pseudotype viruses and an in vitro replication system of the HCV JFH1 strain. Furthermore, the autonomous RNA replication system based on the artificial viral genome revealed that HCV replicates in the intracellular replication complex composed of viral and host proteins. Recently, an immunosuppress ant, cyclosporin A and inhibitors for sphingolipid synthesis and chaperon were reported to inhibit the replication of HCV by counteracting the interplay between host and viral proteins. This review considers the current knowledge of the host proteins that participate in HCV replication and the possibility of developing novel therapeutics intervention for chronic hepatitis C.

Jung J, Kasuya T, Tanizawa K, Kuroda S. · The Institute of Scientific and Industrial Research, Osaka University, Ibaraki City, Japan. · Yakugaku Zasshi. · Pubmed #17473521 links to  free full text

Abstract: To maximize the beneficial effects and minimize the side effect of drugs, DDS (drug delivery system) has been attracted many researchers in the recent drug development. Especially, the in vivo pinpoint delivery system for drugs is very important and key technology for developing the next generations of anti-cancer drugs and gene therapies. Bio-nanocapsule (BNC) is recombinant yeast-derived hepatitis B virus surface antigen particle, which has been used as a recombinant hepatitis B vaccine for the last 20 years in the world. BNC can incorporate various materials (chemical compounds, proteins, genes, siRNA, etc) by the fusion with liposome, and deliver them to the organs and tissues in vivo specifically by the action of bio-recognition molecules on the BNC's surface. The transfection efficiency is significantly higher than that of liposome, because BNC harbors the complete set of hepatitis B virus infection machinery. Recently, we succeeded in the in vivo retargeting of BNC by displaying either antibody or homing peptide, less than 10 amino acid residues for in vivo targeting. BNC is a hybrid of liposome and virus, and very flexible system for in vivo retargeting. BNC might be very promising carriers in the next generation of DDS.

Mizuno S, Nakamura T. · Division of Molecular Regenerative Medicine, Department of Biochemistry and Molecular Biology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan. · Regen Med. · Pubmed #17465748 No free full text.

Abstract: Liver cirrhosis is a major cause of morbidity worldwide and is characterized by the loss of hepatocytes with interstitial fibrosis. In this review, we discuss the potential uses of hepatocyte growth factor for treating hepatic diseases, focusing on the molecular mechanisms whereby hepatocyte growth factor reverses liver cirrhosis. Hepatic myofibroblasts play a central role in the development of liver cirrhosis, while myofibroblasts acquire c-Met. Using a rat model of liver cirrhosis, we recently delineated the direct effect of hepatocyte growth factor toward myofibroblasts: the induction of apoptotic cell death associated with matrix degradation, the inhibition of overproliferation and the suppression of transforming growth factor-beta1 production in myofibroblasts. Hepatocyte growth factor elicits mitogenic, anti-apoptotic and anti-inflammatory functions in hepatocytes, therefore contributing to reversing liver dysfunction. Considering the insufficient production of hepatocyte growth factor is responsible for the manifestation of chronic hepatitis, supplementation with or reinduction of hepatocyte growth factor represents a new strategy for attenuating intractable liver diseases.

Marubashi S, Dono K, Miyamoto A, Takeda Y, Nagano H, Umeshita K, Monden M. · Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. · J Hepatobiliary Pancreat Surg. · Pubmed #17013711 No free full text.

Abstract: Hepatitis C virus (HCV) infection is the leading cause of endstage liver disease in Western and Asian countries. However, after liver transplantation, HCV recurs in virtually all patients, and estimated HCV-related graft cirrhosis at 5-year follow-up is 30%. Although immunosuppression accounts for a major part of the accelerated progression of HCV in the transplant population, the best immunosuppression for recipients with HCV that could avoid such complication remains unknown at present. Combination therapy of interferon and ribavirin is thought to be the most effective for the treatment or prophylaxis of HCV infection. However, who should be treated, when treatment should be initiated, and with what agent should patients with HCV infection be treated are still unknown. The current data on HCV recurrence in patients who have received either living- or deceased-donor liver transplantation are controversial, but they are, presumably, similar. Thus, to avoid HCV recurrence in living-donor liver transplantation, we have to take approaches similar to those used for patients receiving deceased-donor liver transplantation. Based on reports from major transplant centers around the world, we consider the best strategy for liver transplantation-related HCV infection is steroid-free immunosuppression and preemptive low-dose interferon and ribavirin combination therapy. Here we describe our experience with living-donor liver transplantion for patients with hepatitis C at Osaka University. There is a need for standardizing the treatment for HCV infection. This can only be achieved through collaborative work between various liver transplant centers worldwide.

Kanto T, Hayashi N. · Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka. · Intern Med. · Pubmed #16543687 links to  free full text

Abstract: Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease worldwide. The critical role of innate as well as adaptive immunity has been reported in HCV persistence and liver injury. In the early phase of acute infection, HCV continues to replicate in the liver, suggesting the HCV capability of inhibiting innate immunity. The sustained, vigorous and multiepitope-specific CD4+ and CD8+ T cell responses are essential for spontaneous HCV clearance. HCV-specific CD8+ T cells are primary elements for HCV clearance by inducing hepatocyte apoptosis, in which Fas/CD95 is fundamentally involved. However, once HCV persistency develops, HCV utilizes multifaceted arms to subvert various immune effectors. During IFNalpha-based therapy, the enhancement of HCV-specific CD4+ T cell response followed by HCV eradication has been reported, however, it remains obscure whether the therapeutic HCV clearance is able to restore the durable immune competency to HCV. Further investigation is still warranted to establish the means to direct HCV-specific immune responses in the desired way.

Enomoto M, Tamori A, Nishiguchi S. · Department of Hepatology, Osaka City University Medical School, Osaka, Japan. · Clin Lab. · Pubmed #16506363 No free full text.

Abstract: Hepatitis B virus (HBV) infection is an important health problem worldwide. The virus has been classified according to 8 genotypes (A-H) based on sequence divergence. Most genotypes have specific geographic distributions; genotypes A and D are prevalent in Western Europe and North America, and genotypes B and C are prevalent in East Asia and Oceania. Currently accepted treatment for chronic hepatitis B includes interferon alpha, or the nucleoside/nucleotide analogues lamivudine and adefovir. The impact of HBV genotypes on response to antiviral therapy has been studied. HBV genotypes D and C are associated with a lower rate of favorable response to interferon alpha therapy than genotypes A and B, respectively. A study in Germany suggested that the rate of resistance to lamivudine was higher in patients with HBV genotype A infection than in patients with genotype D infection. No difference in the risk of lamivudine resistance is found between patients with genotype B and patients with genotype C. In patients with genotype C infection, however, virological response is worse during lamivudine therapy, and is also less durable after the discontinuation of therapy than in patients with genotype B infection. Determining the genotype could be helpful for predicting the outcome of antiviral therapy in patients with chronic hepatitis B.

Hayashi N, Takehara T. · Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, 565-0871, Japan. · J Gastroenterol. · Pubmed #16501853 No free full text.

Abstract: Antiviral therapy for chronic hepatitis C has dramatically advanced since the discovery of the hepatitis C virus (HCV) in 1989 and the introduction of interferon (IFN) monotherapy in the early 1990s. The current standard therapy uses a combination of pegylated IFN and ribavirin. The duration of therapy and response to therapy are HCV genotype-specific. Genotype 1 patients require 48 weeks of the combination therapy for 50% successful viral elimination, while genotype 2 patients require 24 weeks of therapy for 80% or 90% viral elimination. Early viral kinetics after the initiation of therapy is a useful predictor of the sustained virologic response (SVR), which is formally determined at 24 weeks after completion of the treatment. For example, an early virologic response, which is determined by a 2-log reduction of HCV RNA or viral elimination at 12 weeks after the initiation of therapy, is a strong negative predictor of SVR in genotype 1 patients. In contrast, a rapid virologic response of HCV RNA-negative at 4 weeks after the initiation of therapy identifies genotype 2 "super-responders," who may require a shorter period of therapy. Adherence to therapy is one of the most important factors for successful viral clearance. Hematopoietic growth factors such as epoetin and granulocyte-colony stimulating factor help reduce therapy-mediated cytopenia and improve patient compliance, thereby leading to better viral clearance. New types of anti-HCV agents such as HCV protease and polymerase inhibitors are needed for those patients that do not respond to combination therapy.

Kanazawa H. · Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Asahi-machi, Abenoku, Osaka, Japan. · Curr Opin Pulm Med. · Pubmed #16357581 No free full text.

Abstract: PURPOSE OF REVIEW: It is difficult to identify specific groups of asthmatic patients who may benefit from acute or chronic use of anticholinergic agents. Therefore, an important consideration is how anticholinergic agents can be used to achieve clinically effective treatment of asthma. RECENT FINDINGS: A genotype-stratified study revealed that greater bronchoprotective effect of anticholinergic agents was observed in asthmatic patients with the Arg/Arg genotype of the beta2-adrenergic receptor. Anticholinergic agents could add to the bronchodilation obtained with beta2-agonists on acute severe asthma. CD8+ T lymphocytes induced by chronic hepatitis C viral infection causes chronic obstructive pulmonary disease-like inflammation in asthma. Virus-specific CD8+ T lymphocytes may induce cholinergic activation in asthma through M2 receptor dysfunction. Therefore, anticholinergic agents are highly effective for asthma associated with chronic viral infection. In contrast, asthma with chronic obstructive pulmonary disease-like inflammation appears to be poorly responsive to beta2-agonists and can lead to partially irreversible airflow limitation. Moreover, a recent report suggested that treatment with inhaled tiotropium bromide markedly inhibited the increase in airway smooth muscle mass, myosin expression, and contractility in asthma. SUMMARY: Anticholinergic agents may benefit stable asthmatics, particularly those who have the Arg/Arg genotype. These agents have a demonstrated role in combination with beta2-agonists in the treatment of acute severe asthma, and may benefit asthmatics with chronic obstructive pulmonary disease-like inflammation. Moreover, these agents could be also beneficial in preventing airway remodeling in asthmatic airways.

Ohtani H, Yamazaki O, Matsuyama M, Horii K, Shimizu S, Oka H, Nebiki H, Kioka K, Kurai O, Kawasaki Y, Manabe T, Murata K, Matsuo R, Inoue T. · Department of Surgery, Osaka City General Hospital, 2-13-22 Miyakojimahondori, Japan. · Surg Today. · Pubmed #16341493 No free full text.

Abstract: A spontaneous regression of hepatocellular carcinoma is an extremely rare phenomenon. A 69-year-old Japanese man with hepatitis C virus-related chronic hepatitis presented with a liver tumor. We diagnosed the tumor to be hepatocellular carcinoma in the course of spontaneous regression, by imaging studies and changes in the tumor markers. Because the possible presence of viable cancer cells could not be ruled out, we recommended surgery. He refused all treatments at first, but finally agreed to undergo surgery about 10 months after presentation. A hepatectomy was performed. Histologically, no viable tumor cells were found. In our case, the vascularity of the tumor according to the imaging findings was followed up during the clinical course. The patient is now doing well and without any evidence of recurrence at 37 months after surgery.

Umeshita K, Monden M. · Department of Surgery, Osaka University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #16277259 No free full text.

Abstract: The outcome of liver transplantation for HBV-related liver disease has been dramatically improved by the introduction of hepatitis B immune globulin and antiviral drug such as lamivudine. On the other hand, prophylaxis against HCV recurrence has not been established. As for hepatocellular carcinoma, Milan criteria predict acceptable posttransplant outcome. MELD scores, calculated from serum creatinine, bilirubin, and PT-INR, have been shown to be effective in predicting patient survival 1) on the waiting list and 2) following transplantation. ABO-incompatible liver transplantation has been associated with poor patient survival, especially when the recipients are adults. Intraportal infusion of methylprednisolone, prostaglandin E1, and gabexate mesilate, however, has been reported to be effective. It has been reported that 12.4% of the living liver donor experienced postoperative complication, and therefore, more effort should be made to increase brain-dead donor.

Tsukuma H, Tanaka H, Ajiki W, Oshima A. · Department of Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3 Nakamichi 1-chome, Higashinari-ku, Osaka 537-8511, Japan. · Asian Pac J Cancer Prev. · Pubmed #16235981 No free full text.

Abstract: Liver cancer is one of the leading causes of cancer deaths in Asia and Africa. The epidemiology of liver cancer is distinctive in Japan, where chronic infection with hepatitis C virus (HCV) rather than hepatitis B virus (HBV) plays the major role in the etiology. In this paper, together with a brief review of the descriptive epidemiology of liver cancer and its prevention, Japanese experiences of liver cancer occurrence and some epidemiological studies are described, and Japanese national projects directed against hepatitis and liver cancer are presented. Distinctive time-trends have been observed for liver cancer incidence in Japan. The rates for over 55-59 year olds (both sexes) showed a peak in the birth cohort of 1931-1935, while the rates for less than 50-54 year old females indicate a decreasing trend. The extremely high incidences among birth cohorts around 1931-1935 seems to be related to endemic HCV infection in this generation in Japan. Follow-up studies not only of patients with chronic hepatitis C but also of apparently healthy carriers of HCV showed an increased risk of hepatocellular carcinoma (HCC). Cumulative risk of HCC (40-74 years of age) was estimated as reaching 21.6% (males) and 8.7% (females) among anti-HCV positive voluntary blood donors. Retrospective cohort studies indicated interferon (IFN), with or without ribavirin, to be effective for reducing the risk of HCC among patients with chronic hepatitis C. Periodic examination with ultrasonography and measurement of alpha-fetoprotein has become common practice for early detection of HCCs among patients with chronic hepatitis or liver cirrhosis in Japan. A non-randomized controlled study was conducted to evaluate the effect of periodic examination on mortality, but we failed to show any beneficial effects of screening for liver cancer. In the fiscal year 2002, Japanese National Projects directed against hepatitis and HCC were started, in which blood tests for HCV and HBsAg are offered just once at the age of 40, 45, 50, 55, 60, 65 or 70 for five years. Participants are categorized as either HCV carriers or non-carriers. HCV carriers are further examined by liver disease specialists, seeking indications for IFN therapy. Type C chronic hepatitis patients are recommended to receive IFN therapy with or without ribavirin. This project is expected to become a model of liver cancer control in HCV-endemic countries. Recently however, the US Preventive Service Task Force has recommended against routine screening for HCV infection in asymptomatic adults in the general population who are not at increased risk of infection. This divergence of views is also discussed.