Hepatitis: Asia

Zhang YY, Chen EQ, Yang J, Duan YR, Tang H. · Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China. · Virol J. · Pubmed #19467157 links to  free full text

Abstract: BACKGROUND: Currently, there is no evidence on the combination of lamivudine and thymosin alpha-1 on chronic hepatitis B patients. The aim of this study was to compare the effect of lamivudine monotherapy with that of lamivudine and thymosin alpha-1 combination therapy for the treatment of hepatitis B e antigen (HBeAg)-positive hepatitis B patients. RESULTS: We searched PUBMED (from 1966 onwards), EMBASE (from 1966), CBMdisk (Chinese Biomedical Database, from 1978), CNKI (National Knowledge Infrastructure, from 1980), the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Eight trials (583 patients in total) were identified. The lamivudine and thymosin alpha-1 combination treatment was significantly superior to lamivudine treatment in terms of ALT normalization rate (80.2% vs. 68.8%, P = 0.01), virological response rate (84.7% vs. 74.9%, P = 0.002), and HBeAg seroconversion rate (45.1% vs. 15.2%, P < 0.00001). CONCLUSION: Among HBeAg-positive patients, thymosin alpha-1 and lamivudine combination therapy may be more effective than lamivudine monotherapy, providing superior rates of biochemical response, virological response, and HBeAg seroconversion.

Bae K, Choi J, Jang Y, Ahn S, Hur B. · Vaccine Research Institute, CrucellBerna Biotech Korea, Yongin, 449-903, Korea. · Arch Pharm Res. · Pubmed #19407962 No free full text.

Abstract: This review paper provides an overview of innovative technologies designed to produce bacterial, viral, recombinant subunit, and polysaccharide vaccines, as well as combination vaccines. Advances in this field are illustrated by vaccines against DTP (diphtheria-tetanus-pertussis), influenza, hepatitis B (HepB) and typhoid fever. In addition, technological trends regarding antigens, adjuvants, and preservatives in vaccines are discussed. The progress achieved in vaccine production technologies is especially important for improving the protection of vulnerable populations against infectious diseases. These at-risk groups include infants, the elderly and immunocompromized individuals, as well as people living in developing countries or emerging economies.

Chang KY, Chang JY, Yen Y. · National Institute of Cancer Research, National Health Research Institute, Taiwan. · J Natl Compr Canc Netw. · Pubmed #19406042 No free full text.

Abstract: Primary liver cancer is the sixth most common cancer and third most common cause of cancer death worldwide. Cholangiocarcinoma is the second most common primary liver tumor after hepatocellular carcinoma. Because the incidence of intrahepatic cholangiocarcinoma is rising in most areas worldwide, identification of the main causes of this problem is urgently needed. Despite well-known risk factors in the development of intrahepatic cholangiocarcinoma, recent reports focus on chronic hepatitis B and C viral infections because an increasing number of studies have observed an association. The relationship, however, is still not conclusive because of the diversity in clinical reports and the lack of in vitro evidences. This issue should be emphasized and further investigation is required for clarification.

Hirata Y, Sudoh M, Kohara M. · Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan. · Uirusu. · Pubmed #19374199 links to  free full text

Abstract: Hepatitis C virus (HCV) develops persistent infection in most infected patients, and eventually cause chronic hepatitis, liver cirrhosis and then hepatocellular carcinoma. The combination therapy of PEG-IFN and ribavirin improves the efficacy in many patients, while it does not lead to sufficient achievements in genotype1b patients. To invent new anti-HCV reagent, we focused on host factors which HCV take advantage of in its life-cycle. We identified serine palmitoyltransferase inhibitor as anti-HCV reagent through high-through put screenig using HCV replicon cells. Moreover, we evaluate the anti-HCV effect of SPT-inhibitor in vivo with humanized chimeric mice. SPT-inhibitor led to rapid decline in serum HCV-RNA of about 1-2log within 8 day, futhermore the combination therapy of SPT-inhibitor and PEG-IFN achieved about 3log reduction in serum HCV-RNA. At last, we investigated the mechanism of anti-HCV effect of SPT-inhibitor. It has been reported that sphingolipids and cholesterol compose the lipid raft, in which the replication of HCV occur. We investigated the influence of SPT-inhibitor to lipid rafts by analysing the detergent resistant membrane (DRM). The analysis proved that SPT inhibitor got HCV RNA dependent RNA polymerase (NS5B) to move to detergent soluble fraction from DRM, and Biacore analysis indicated the binding of sphingomyelin to NS5B. These results suggested SPT inhibitor got NS5B to release from replication complex.

Suzuki T, Masaki T, Aizaki H. · National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo. · Uirusu. · Pubmed #19374198 links to  free full text

Abstract: A robust system for production of recombinant infectious hepatitis C virus (HCV) has been established in 2005 and classical virological techniques are now able to be applied to the HCV research, especially regarding molecular mechanisms on virion assembly and maturation. We recently demonstrated that the C-terminal serine cluster of NS5A is a determinant of NS5A interaction with Core and the subcellular localization of NSSA. Mutation of this cluster blocks the NS5A-Core interaction, resulting in perturbation of association between Core and HCV RNA. It is thus tempting to consider that NS5A plays a key role in transporting the viral genome RNA synthesized by the replication complex to the surface of lipid droplets (LDs) or LD-associated membranes, where Core localizes, leading to facilitation of nucleocapsid formation. We also demonstrated an important role of cholesterol and sphingolipid in HCV infection and virion maturation. Specifically, mature HCV particles are rich in cholesterol. Depletion of cholesterol from HCV or hydrolysis of virion-associated sphingomyelin results in a loss of infectivity, and the addition of exogenous cholesterol restores infectivity. In addition, cholesterol and sphingolipid on the HCV membrane play a key role in virus internalization. Finally, inhibitors of the sphingolipid biosynthetic pathway efficiently block virion production.

Kato N. · Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences. · Uirusu. · Pubmed #19374197 links to  free full text

Abstract: The studies on the mechanism of HCV replication proliferated after the development of cell culture based-subgenomic HCV replicon system and genome-length HCV RNA replication system. Furthermore, these RNA replication systems have been improved to be suitable systems for the screening of anti-HCV reagents by the introduction of reporter genes such as luciferase. Genetic analysis of HCV RNAs obtained in long-term cell culture of HCV replicon or genome-length HCV RNA-harboring cells revealed that genetic mutations in HCV RNAs accumulated in a time-dependent manner. The genetic diversity of HCVs was also enlarged in a time-dependent manner. The appearance of adaptive mutation in HCV replicon or genome-length HCV RNA is one of characteristic features of HCV RNA replication system. Although human hepatoma-derived HuH-7 cell line was mainly used for HCV RNA replication systems, a specific combination of adaptive mutations led to develop the HCV RNA replication systems using a new human hepatoma cell line other than HuH-7.

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.

Liu JP, Nikolova D, Fei Y. · Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, China, 100029. · Cochrane Database Syst Rev. · Pubmed #19370595 No free full text.

Abstract: BACKGROUND: Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention. OBJECTIVES: To assess the beneficial and harmful effects of the pre- and post-exposure prophylaxis with immunoglobulins for preventing hepatitis A. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, The Chinese Biomedical Database, and Science Citation Index Expanded for trials until October 2008. In addition, we read through reference lists of the identified publications and handsearched three journals. SELECTION CRITERIA: Randomised clinical trials on immunoglobulin prophylaxis for preventing hepatitis A, irrespective of blinding, publication status, or language. DATA COLLECTION AND ANALYSIS: Data were extracted by two authors and verified by a third author. Results were presented as relative risks (RR) with 95% confidence intervals (CI). The primary outcome was occurrence of hepatitis A (infectious hepatitis). MAIN RESULTS: We included 13 trials with 567,476 participants randomised to pre- or post-exposure prophylaxis. The trials had high risk of bias. The trials were heterogeneous in terms of study setting, participants, interventions, and outcome measures. Our meta-analysis with six randomised trials showed that immunoglobulins, when used for pre-exposure prophylaxis, significantly reduced the number of adult patients with hepatitis A at 6 to 12 months (1020/286503 versus 761/134529; RR 0.53; 95% CI 0.40 to 0.70; random-effects model) in comparison with no intervention or inactive control. Four trials showed a similar effect in children aged 3 to 17 at 6 to 12 months follow-up (917/210822 versus 677/78960; RR 0.45; 95% CI 0.34 to 0.59). Comparing different doses of immunoglobulins, higher dosage was generally more effective than lower dosage (1.5 ml better than 0.75 ml and 0.75 ml better than 0.1 ml) in preventing hepatitis A. No significant systemic adverse events were reported. One trial showed that immunoglobulin was more effective than placebo for post-exposure prophylaxis. It appeared that there was no significant difference between immunoglobulins and inactivated hepatitis A vaccine in seroconversion to hepatitis A vaccine antibodies at four weeks (RR 1.16; 95% CI 0.98 to 1.38), but immunoglobulins were significantly less effective than vaccine regarding antibody levels at 8, 12, or 24 weeks. AUTHORS' CONCLUSIONS: Immunoglobulins seem to be effective for pre-exposure and post-exposure prophylaxis of hepatitis A. However, caution is warranted for the positive findings due to the limited number of trials, year of conductance, and risk of bias. Conductance of rigorous trials will be justifiable.

Ueno Y, Sollano JD, Farrell GC. · Tohoku University Graduate School of Medicine, Division of Gastroenterology, 1-1 Seiryo, Aobaku, Sendai 980-8574, Japan. · J Gastroenterol Hepatol. · Pubmed #19368633 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection accounts for most cases of hepatocellular carcinoma (HCC) in Japan and is the second major cause in many other countries. Development of HCC takes a considerable time after onset of HCV infection, between 20-40 years in most cases, and usually develops after cirrhosis is established. Although only a minority of HCV infections reach this stage, the high prevalence of chronic HCV infection in many countries (1-3%) is such that HCC related to HCV infection poses a significant public health issue 20-50 years after the onset of HCV epidemics. Due to advances in testing, and accessibility of clean, disposable medical apparatus including syringes and needles, and particularly screening of donor blood for anti-HCV and by nucleic acid testing, new cases of HCV infection have decreased in most countries, except for continued transmission by injection drug users (IDU). A key difference between HBV and HCV infection is that HCV can be eradicated by effective antiviral treatment. Sustained eradication of HCV reverses hepatic fibrosis, thereby preventing progression to cirrhosis and risk of HCC. Further, it has been well demonstrated that interferon-based antiviral therapy suppresses development of HCC in high-risk patients, particularly when sustained viral response (SVR) is obtained. In summary, the two key approaches to prevent development of HCV-related HCC are primary prevention of HCV infection (adequate programs to screen donor blood, universal precautions to stop medical transmission of blood-borne viruses, curbing transmission by IDU) and potent antiviral therapy of chronic HCV infection.

Yam JW, Tse EY, Ng IO. · Liver Cancer and Hepatitis Research Laboratory, Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong. · J Gastroenterol Hepatol. · Pubmed #19368632 No free full text.

Abstract: Focal adhesions are structural links between the extracellular matrix and actin cytoskeleton. They are important sites where dynamic alterations of proteins in the focal contacts are involved during cell movement. Focal adhesions are composed of diverse molecules, for instance, receptors, structural proteins, adaptors, GTPase, kinases and phosphatases. These molecules play critical roles in normal physiological events such as cellular adhesion, movement, cytoskeletal structure and intracellular signaling pathways. In cancers, aberrant expression and altered functions of focal adhesion proteins contribute to adverse tumor behavior. It is evident that these proteins do not function alone, but rather associate and work together in the process of tumor development and cancer metastasis. Focal adhesion proteins have been shown to play critical roles in hepatocellular carcinoma. Understanding the molecular interactions and mechanisms of the interconnected focal adhesion proteins is of particular importance in understanding mechanisms underlying hepatocellular carcinoma progression and development of potential effective treatment.

Li M, Zhou Y, Feng G, Su SB. · Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou 515041, China. · Curr Mol Med. · Pubmed #19355917 No free full text.

Abstract: Toll-like receptors (TLRs) form a large family of pattern recognition receptors with at least 11 members in human and 13 in mouse. TLRs recognize a wide variety of microbial components and potential host-derived agonists that have emerged as key mediators of innate immunity. TLR signaling also plays an important role in the activation of the adaptive immune system by inducing proinflammatory cytokines and upregulating costimulatory molecules of antigen presenting cells. The dysregulation of TLR signaling may cause autoimmunity. This review discusses the contribution of TLR signaling to the initiation and progression of autoimmune diseases, such as rheumatoid arthritis, experimental autoimmune encephalitis, myocarditis, hepatitis, kidney disease, systemic lupus erythematosus, diabetes, obesity, and experimental autoimmune uveitis as well as aging. The involvement of TLR signaling in the pathogenesis of autoimmune diseases may provide novel targets for the development of therapeutics.

Chen TJ, Lai PC, Yang LC, Kuo TT, Hong HS. · Department of Dermatology, Wanfang Medical Center and Taipei Medical University, Taipei, Taiwan. · Am J Clin Dermatol. · Pubmed #19354335 No free full text.

Abstract: Bullous pemphigoid (BP) is an autoimmune disease with chronic, recurrent bullous eruptions. BP has been reported to be associated with drugs, physical stimuli, malignancies, and immune abnormalities. Its association with renal transplant is rare and only four cases have been reported. We present a case of BP in a 52-year-old man with chronic hepatitis B and C infection who underwent a cadaveric renal transplant 13 years earlier. His graft was still functioning well when BP appeared. The occurrence of BP in our patient might be a result of drugs (furosemide or tacrolimus), viruses, or renal allograft. As the patient was receiving regular T-cell immunosuppressant therapy, his BP lesions were recalcitrant to corticosteroid treatment. We discuss the pathogenesis and treatment of such patients.

Saito M, Kohno K. · · Tanpakushitsu Kakusan Koso. · Pubmed #19348256 No free full text.

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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.

This publication has no abstract.

Inoue K, Watanabe T, Yamada M, Yoshiba S. · Showa University Fujigaoka Hospital, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19346717 No free full text.

This publication has no abstract.

Koike K. · Department of Infectious Diseases, University of Tokyo, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19346715 No free full text.

This publication has no abstract.

Lui YY, Chan HL. · Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. · Expert Rev Anti Infect Ther. · Pubmed #19344240 No free full text.

Abstract: Chronic hepatitis B is a worldwide health problem. Research interests have focused on the development of potent and safe antiviral agents with low resistance rates. Among these, telbivudine is an oral nucleoside analogue with specific activity against hepatitis B virus DNA polymerase. Various prospective, randomized clinical trials have demonstrated the potent efficacy of telbivudine in suppressing viral replication and achieving hepatitis B e antigen seroconversion. Telbivudine was also proved to be superior to lamivudine and adefovir dipivoxil. This article provides an overview of the pharmacokinetics, clinical efficacies, resistance profile and safety of telbivudine. A comparison of telbivudine with other oral antiviral agents is also highlighted.

Saiki I, Yamazaki M, Matsumoto K. · Division of Pathogenic Biochemistry, Institute of Natural medicine, University of Toyama, Japan. · Yakugaku Zasshi. · Pubmed #19336991 links to  free full text

Abstract: The Core University Program provides a framework for international cooperative research in specifically designated fields and topics, centering around a core university in Japan and its counterpart university in other countries. In this program, individual scientists in the affiliated countries carry out cooperative research projects with sharply focused topics and explicitly delineated goals under leadership of the core universities. The Core University Program which we introduce here has been renewed since 2001 under the support of both the Japan Society for the Promotion of Science (JSPS) and the National Research Council of Thailand (NRCT). Our program aims to conduct cooperative researches particularly focusing on Natural Medicine in the field of Pharmaceutical Sciences. Institute of Natural Medicine at University of Toyama (Japan), Faculty of Pharmaceutical Sciences at Chulalongkorn University (Thailand), and Chulabhorn Research Institute (Thailand) have been taking part in this JSPS-NRCT Core University Program as core universities. The Program is also supported by the 20 institution members in both countries. This program is running the five research subject under a key word of natural medicine which are related to i) age-related diseases, ii) allergy and cancer, iii) hepatitis and infectious diseases, iv) structure, synthesis, and bioactivity of natural medicines, and v) molecular biology of Thai medicinal plant components and database assembling of Thai medicinal plants. The program also encourages university members to strengthen related research activities, to share advanced academic and scientific knowledge on natural medicines.

Yu ML, Chuang WL. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · J Gastroenterol Hepatol. · Pubmed #19335784 No free full text.

Abstract: The issue of best treatment for chronic hepatitis C virus (HCV) infection is in constant flux, not only in Western countries but also in Asia. Currently, pegylated-interferon plus ribavirin is the standard of care. Studies from Asia provide evidence to support the same broad treatment strategies for Asian patients as recommended in Western countries. Nevertheless, there is increasing evidence that Asians have a higher likelihood of achieving a sustained virological response (SVR) than their Caucasians counterparts when treated with the corresponding regimen. With the recommended 'standard dose and duration treatment regimens', SVR is achieved in Asia for around 70% of HCV genotype 1 (HCV-1) infected cases, approximately 90% of HCV-2/3, approximately 65% of HCV-4, and approximately 80% of HCV-6 patients. Difference of body weight in race might contribute the superior response in Asian patients. HCV genotype distribution in Asia also differs from North-America/Europe. HCV-6 and its variants, previously mistyped as HCV-1, needs accurate genotyping. Increasing data support the proposal that HCV genotype, baseline viral load and on-treatment virological response provide information for decision-making so that treatment can be individualized. Beyond the older recommendations, an abbreviated 24-week regimen could be suggested for HCV-1/4 patients with baseline viral loads < 400 000 IU/mL and a rapid virological response (RVR, HCV RNA undetectable at week 4), and an abbreviated 12-16 weeks of pegylated-interferon with weight-based doses of ribavirin could be suggested for HCV-2/3 patients with a RVR. Such tailored treatment regimens can reduce the costs of treatment and incidence of adverse events without compromising efficacy. Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis worldwide, and particularly in some countries of Asia (notably Japan) where it is now more prevalent than chronic hepatitis B virus infection. Hepatitis C virus infection can also lead to hepatocellular carcinoma (HCC). It is estimated that there are more than 170 million people chronically infected with HCV, and 3 to 4 million persons are newly infected each year. The risk for developing cirrhosis 20 years after initial HCV infection among those chronically infected varies between studies, but is estimated at around 10%-15% for men and 1-5% for women. Once cirrhosis is established, the rate of developing HCC is at 1%-4% per year. Approximately 280 000 deaths per year are related to HCV infection. Hepatitis C virus-related end-stage liver disease and HCC have become the leading cause for liver transplantation worldwide. In the Asia-Pacific area, the estimated prevalence of antibodies to HCV (anti-HCV) range from 0.3% in New Zealand to 5.6% in Thailand. In Japan, Middle East, Vietnam and Taiwan, several HCV hyper-endemic areas have been reported with an anti-HCV prevalence rate of 12% to as high as 58%. In addition to the well-known endemic status of HBV infection in most countries of the Asia-Pacific region, HCV infection presents another critical scenario of public health issue in this region, as outlined in Guidelines by the Asia-Pacific Association for Study of the Liver (APASL). Given the lack of an effective vaccine, optimal treatment of chronic HCV infection is now perceived as a 'must' in terms of public health strategies, as well as of the clinical setting for individual patients.

Hosseini-Moghaddam SM, Mousavi A, Alavian SM. · Urology and Nephrology Research Center, Shahid Beheshti University, M.C. (SBMU), Tehran, I.R. Iran. · J Antimicrob Chemother. · Pubmed #19329508 No free full text.

Abstract: Using interferon-alpha (IFN-alpha) as the conventional therapeutic antiviral drug, physicians generally achieve a treatment success of <50% in cases with chronic hepatitis C. Owing to the structural similarities between IFN-alpha and interferon-beta (IFN-beta), the latter is a candidate for obtaining sustained viral response. In this review, we have compiled the published information on the use of IFN-beta for the management of acute and chronic hepatitis C up to 2007. We have looked at the rates of success and side effects. IFN-beta might be helpful if IFN-alpha fails to achieve a favourable outcome. This antiviral drug may be helpful for the management of chronic hepatitis C in both age extremes, in case of a relapse after receiving IFN-alpha and for preventing the development of the carrier state after acute hepatitis C. Further studies are required on the efficacy of IFN-beta for the management of acute and chronic hepatitis C.

Yuen MF, Fung J, Wong DK, Lai CL. · Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong. · Lancet Infect Dis. · Pubmed #19324298 No free full text.

Abstract: Emergence of drug resistance in antiviral therapy for chronic hepatitis B negates treatment benefits. There is a lower chance for emergence of resistance for drugs with rapid and potent viral suppression and a high genetic barrier for resistant mutations. Measurement of viral load at 24 weeks' treatment to aid decision making is mandatory for patients receiving drugs that are associated with a higher resistance rate. Combination treatment with drugs that belong to different groups is associated with a lower chance of resistance. To ensure better control of viral replication in patients with drug resistance, the addition of another drug without an overlapping resistance profile should be given as early as possible, preferably at the time when genotypic resistance emerges. With such strategies, most patients can be maintained in clinical remission. However, because of the mechanism of viral persistence, research efforts should continue to anticipate and prevent the emergence of multidrug-resistant strains.

Jafri W, Subhan A. · Department of Medicine, Aga Khan University, P.O. Box 3500, Stadium Road, Karachi - 74800, Pakistan. · Trop Gastroenterol. · Pubmed #19323087 No free full text.

Abstract: Hepatitis C virus is one of the most common blood-borne viruses and is associated with significant morbidity and mortality. It affects 170 million people worldwide and 2.4%-6.5% people in Pakistan. Therapeutic injections by contaminated, re-used syringes, transfusion of unsafe blood and re-use of razors are major factors responsible for the spread of hepatitis C in the general population. Genotype 3 is the most common genotype in Pakistan and is most responsive to interferon and ribavirin combination therapy. HCV is the leading cause of chronic liver disease and hepatocellular carcinoma in Pakistan. Appropriate steps need to be taken in the country to control factors responsible for the spread of hepatitis C.

Tyagi P, Madan K. · Department of Gastroenterology, GB Pant Hospital, New Delhi. · Trop Gastroenterol. · Pubmed #19323086 No free full text.

Abstract: It is clear that the major indication for the use of hematopoietic growth factors in hepatology is to counteract the adverse effects of interferons (neutropenia and thrombocytopenia) and ribavirin (hemolytic anaemia) during the treatment of hepatitis C infection. This is important because the probability of SVR depends on proper adherence to therapy (at least 80% of the requisite dose maintained for at least 80% of the requisite duration) and proper adherence can only be achieved if the side effects are reduced to a minimum. Even though the studies have demonstrated beyond doubt that the use of hematopoietic growth factors does indeed reduce the incidence and severity of these adverse effects and helps the patients to complete the course of therapy, the data on improvement of SVR is still limited. There is only one study of darbepoetin and filgrastim showing the beneficial effect on SVR. Even among the hematological side effects, possibly the only significant effect which limits the use of optimal HCV therapy is the hemolytic anaemia induced by ribavirin. The other two main side effects, i.e. neutropenia and thrombocytopenia are not clinically problematic. The use of such growth factors would be particularly effective if patients who have advanced liver disease or cirrhosis are able to receive adequate anti-viral therapy as has been demonstrated in the study of eltrombopag among HCV cirrhotics. Apart from this, other indications of G-CSF or GM-CSF use are still in the experimental stage. So, as of now, apart from erythropoietic factors, the role played by other hematopoietic growth factors in hepatology is limited. But future research, especially in the areas of immunotherapy of liver cancers and stem cell therapy for endstage liver disease, is surely going to give these factors their due place in hepatology.

Liaw YF. · Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. · Antivir Ther. · Pubmed #19320233 No free full text.

Abstract: Studies published to date regarding on-treatment outcome prediction during chronic hepatitis B therapy were reviewed. Studies have shown that initial virological responses in terms of week 24 serum hepatitis B virus (HBV) DNA levels are associated with therapeutic outcomes of 1-year pegylated interferon-alpha and entecavir therapy, and weeks 52 or 104 of lamivudine and telbuvudine therapy. HBV DNA levels at week 48 are also associated with long-term adefovir therapy outcomes. Conceptual on-treatment adjustment and strategies have been proposed; however, this approach seems only necessary during therapy with nucleos(t)ide analogues with substantial risk of drug resistance. In addition, studies are needed to decide whether switching to or adding on a second drug, and with which drug, is the most cost-effective strategy.

Yamagiwa S, Kamimura H, Ichida T. · Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510, Japan. · Med Mol Morphol. · Pubmed #19294486 No free full text.

Abstract: The liver is a distinctive immune organ with predominant innate immunity, being rich in innate immune cells such as natural killer (NK) cells. In humans, NK cells comprise about 30%-50% of intrahepatic lymphocytes, whereas peripheral blood lymphocytes contain about 5%-20% NK cells. Accumulating evidence suggests that NK cells play an important role not only in host defense against invading microorganisms and tumor transformation in the liver but also in liver injury and repair. In recent years, significant progress has been made in terms of understanding how NK cells recognize their target cells and carry out their effector functions. It is now clear that NK cells are strictly regulated by numerous activating and inhibitory NK cell receptors that recognize various classes of cell surface ligands, some of which are expressed by normal healthy cells. Therefore, to further elucidate the involvement of NK cells in the pathogenesis of liver diseases, an understanding of recent advances in NK cell biology is crucial. This review provides an overview of recent advances in our knowledge of human NK cell receptors and their ligands in the context of liver diseases.