Hepatitis: China

Fan JG, Farrell GC. · Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. · J Hepatol. · Pubmed #19014878 No free full text.

Abstract: Fatty liver (steatosis) is highly prevalent in China and is more often linked to obesity than to alcoholism. Among more affluent regions of China, the community prevalence of non-alcoholic fatty liver disease (NAFLD) is approximately 15%. With the increasing pandemic of obesity, the prevalence of NAFLD has approximately doubled in the past decade. The risk factors resemble those in other ethnic populations, but it is important to note that ethnic-specific definitions of central obesity, obesity and metabolic syndrome are more useful in assessment of Chinese people. The full range of histological manifestations of NAFLD has been demonstrated in Chinese patients, but to date hepatic severity is generally mild. In contrast to chronic hepatitis C, steatosis is less common in patients with chronic hepatitis B; it is associated with metabolic, and not viral factors and does not appear to affect disease severity. Although long-term outcomes of NAFLD in Chinese populations remain unclear, it may be a predictor of metabolic disorders, diabetes and cardiovascular disease. Public health interventions are therefore indicated to halt or reverse the national trend of obesity in China so as to improve liver as well as metabolic health.

Sun B, Karin M. · Liver Transplantation Center of the First Affiliated Hospital and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu Province, PR China. · Oncogene. · Pubmed #18931690 No free full text.

Abstract: The NF-kappaB signaling pathway has particular relevance to several liver diseases including hepatitis (liver infection by Helicobacter, viral hepatitis induced by HBV and HCV), liver fibrosis and cirrhosis and hepatocellular carcinoma. Furthermore, the NF-kappaB signaling pathway is a potential target for development of hepatoprotective agents. Several types of drugs including: selective estrogen receptor modulators (SERMs), antioxidants, proteasome inhibitors, IKK inhibitors and nucleic acid-based decoys have been shown to interfere with NF-kappaB activity at different levels and may be useful for the treatment of liver diseases. However, NF-kappaB also plays an important hepatoprotective function that needs to be taken into consideration during development of new therapeutic regimens.

Martin V, Chevalier V, Ceccato P, Anyamba A, De Simone L, Lubroth J, de La Rocque S, Domenech J. · Emergency Centre for the Control of Transboundary Animal Diseases (ECTAD), FAO, Beijing, China. · Rev Sci Tech. · Pubmed #18819669 No free full text.

Abstract: Climate change is likely to change the frequency of extreme weather events, such as tropical cyclones, floods, droughts and hurricanes, and may destabilise and weaken the ecosystem services upon which human society depends. Climate change is also expected to affect animal, human and plant health via indirect pathways: it is likely that the geography of infectious diseases and pests will be altered, including the distribution of vector-borne diseases, such as Rift Valley fever, yellow fever, malaria and dengue, which are highly sensitive to climatic conditions. Extreme weather events might then create the necessary conditions for Rift Valley fever to expand its geographical range northwards and cross the Mediterranean and Arabian seas, with an unexpected impact on the animal and human health of newly affected countries. Strengthening global, regional and national early warning systems is crucial, as are co-ordinated research programmes and subsequent prevention and intervention measures.

Fung J, Lai CL, Yuen MF. · The University of Hong Kong, Queen Mary Hospital, Department of Medicine, Pokfulam Road, Hong Kong. · Expert Opin Investig Drugs. · Pubmed #18808318 No free full text.

Abstract: Hepatitis B virus is a significant cause of liver cirrhosis and hepatocellular carcinoma in patients with chronic infection. Higher levels of viral load are associated with increased risk of developing liver-related complications. The current available oral therapies suppress viral replication through their action on the hepatitis B virus polymerase. As treatment with oral nucleoside/nucleotide analogues is associated with the development of drug-resistant mutations, there is continuing research for newer and more potent antiviral agents to reduce the chance of drug resistance. LB80380, a prodrug, is an oral nucleotide analogue that inhibits viral replication by incorporation into the viral DNA. Antiviral activity against wild-type virus and virus with drug-resistant mutations was demonstrated in Phase II trials, with significant reduction of viral load in patients treated with LB80380. LB80380 was also shown to be safe and well tolerated.

You JH, Chan FW. · The Chinese University of Hong Kong, Centre for Pharmacoeconomics Research, School of Pharmacy, Faculty of Medicine, Shatin, NT, Hong Kong. · Expert Opin Pharmacother. · Pubmed #18803453 No free full text.

Abstract: BACKGROUND: Entecavir is a new antiviral agent for chronic hepatitis B virus (HBV) infection with potent HBV suppression and a low rate of viral resistance. OBJECTIVE: To review published studies on the pharmacoeconomics of entecavir for treatment of chronic HBV. METHODS: A literature search on Medline and Embase over the period of 1998 - 2008 was performed in April 2008 using keywords 'entecavir' and 'cost'. RESULTS/CONCLUSION: Four studies comparing the cost effectiveness of entecavir with lamivudine and/or adefovir for treatment with chronic HBV infection using either decision tree or Markov modeling were reviewed. All four studies showed that entecavir was cost-effective in the treatment of chronic HBV with the incremental cost per QALY (quality-adjusted life-year) gained below the commonly accepted benchmark. The results are mainly due to the lower complication rates and better quality of life of patients using entecavir which can offset the higher acquisition cost of the drug. Patient characteristics, comparing agents and model assumptions were different among the four studies and they should be taken into account when applying the results to real life situations.

Lui YY, Chan HL. · The Chinese University of Hong Kong, Department of Medicine and Therapeutics and Institute of Digestive Disease, Hong Kong SAR, China. · Expert Opin Drug Metab Toxicol. · Pubmed #18798704 No free full text.

Abstract: BACKGROUND: 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. Telbivudine is a nucleoside analogue that has been approved for treatment of chronic hepatitis B. OBJECTIVE: This review article concentrates on the pharmacokinetics and therapeutic efficacy of telbivudine. The resistance and safety profiles are also addressed. METHODS: Relevant publications were identified from searches of MEDLINE (1996-June 2007), the Cochrane Library and BIOSIS (1993-June 2007). Search items included, but were not limited to, telbivudine, pharmacokinetics, hepatitis B, resistance and adverse events. CONCLUSIONS: Clinical trials demonstrated telbivudine to be a safe and potent antiviral agent for treatment of chronic hepatitis B. Telbivudine has superior efficacy compared to lamivudine and adefovir.

Yang J, Zeng XM, Men YL, Zhao LS. · Center of Infectious Diseases, National Key Laboratory of Biotherapy for Human Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, PR China. · Virol J. · Pubmed #18755018 links to  free full text

Abstract: BACKGROUND: Caesarean section before labor or before ruptured membranes ("elective caesarean section", or ECS) has been introduced as an intervention for preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Currently, no evidence that ECS versus vaginal delivery reduces the rate of MTCT of HBV has been generally provided. The aim of this review is to assess, from randomized control trails (RCTs), the efficacy and safety of ECS versus vaginal delivery in preventing mother-to-child HBV transmission. RESULTS: We searched Cochrane Pregnancy and Childbirth Group's Trials Register (January, 2008), the Cochrane Central Register of Controlled Trials (the Cochrane Library 2008, issue 1), PubMed (1950 to 2008), EMBASE (1974 to 2008), Chinese Biomedical Literature Database (CBM) (1975 to 2008), China National Knowledge Infrastructure (CNKI) (1979 to 2008), VIP database (1989 to 2008), as well as reference lists of relevant studies. Finally, four randomized trails involving 789 people were included. Based on meta-analysis, There was strong evidence that ECS versus vaginal delivery could effectively reduce the rate of MTCT of HBV (ECS: 10.5%; vaginal delivery: 28.0%). The difference between the two groups (ECS versus vaginal delivery) had statistical significance (RR 0.41, 95% CI 0.28 to 0.60, P < 0.000001). No data regarding maternal morbidity or infant morbidity according to mode of delivery were available. CONCLUSION: ECS appears to be effective in preventing MTCT of HBV and no postpartum morbidity (PPM) was reported. However, the conclusions of this review must be considered with great caution due to high risk of bias in each included study (graded C).

Sun F, Chen Y, Xiang Y, Zhan S. · Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China. · Int J Tuberc Lung Dis. · Pubmed #18713495 No free full text.

Abstract: BACKGROUND: Although some case-control studies have investigated the association between drug-metabolising enzyme (DME) gene polymorphisms and susceptibility to anti-tuberculosis drug-induced liver injury (ATLI), their results are conflicting, mainly due to limited power. OBJECTIVE: To review the literature systematically, by means of a meta-analytical review, to evaluate the putative association and provide a quantitative summary estimate on the association with ATLI. DESIGN: We searched the databases of MEDLINE, PubMed, EMBASE and CBMdisc from 1966 to May 2007 using 'DME', 'hepatotoxicity', 'genetic polymorphism', 'genetic susceptibility' in combination with 'antitubercular agents', performed a manual search of citations from relevant original studies and review articles, and corresponded with authors. RESULTS: Nine eligible articles were included in this meta-analysis, including five on N-acetyltransferase 2 (NAT2), four on cytochrome P450 2E1 (CYP2E1) and two on glutathione S-transferase (GST) studies, separately. The overall ORs of ATLI risk associated with NAT2 homozygous variant genotype (mt/mt), CYP2E1 homozygous wild genotype (*1A/*1A), GSTM1 homozygous null genotype (null/null) and GSTT1 homozygous null genotype (null/null) were respectively 1.93 (95%CI 0.81-4.62), 2.22 (95%CI 1.06-4.66), 2.62 (95%CI 1.45-4.75) and 1.18 (95%CI 0.61-2.29). In addition, the OR for Asian ATLI associated with the NAT2 homozygous variant (mt/mt) and the combined genotype (w/w + w/mt) was 2.52 (95%CI 1.49-4.26). CONCLUSIONS: NAT2 mt/mt, CYP2E1*1A/*1A and GSTM1 null/null were observed to increase the risk of ATLI in tuberculosis patients. Our results support the hypothesis that NAT2 mt, CYP2E1*1A and GSTM1 null have a modest effect on genetic susceptibility to ATLI, but no significant evidence for GSTT1 null/null.

Martin V, De Simone L, Lubroth J, Ceccato P, Chevalier V. · Emergency Centre for the Control of Transboundary Animal Diseases, FAO, Beijing, People's Republic of China. · Geospat Health. · Pubmed #18686251 links to  free full text

Abstract: Recent disease epidemics and their spread around the world have illustrated the weaknesses of disease surveillance and early warning systems (EWS), both at national and international levels. These diseases continuously threaten the livestock sector on a worldwide basis, some with major public health impact. EWS and accurate forecasting of new outbreaks of epidemic livestock diseases that may also affect wildlife, and the capacity for spread of such diseases to new areas is an essential pre-requisite to their effective containment and control. Because both the geographical and seasonal distribution of many infectious diseases are linked to climate, the possibility of using climaterelated environmental factors as predictive indicators, in association with regular disease surveillance activities, has proven to be relevant when establishing EWS for climate-related diseases. This article reviews the growing importance of using geographical information systems in predictive veterinary epidemiology and its integration into EWS, with a special focus on Rift Valley fever. It shows that, once fully validated in a country or region, this technology appears highly valuable and could play an increasing role in forecasting major epidemics, providing lead time to national veterinary services to take action to mitigate the impact of the disease in a cost-effective manner.

Xia X, Luo J, Bai J, Yu R. · Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 140, Hanzhong Road, Nanjing, Jiangsu 210029, PR China. · Public Health. · Pubmed #18486955 No free full text.

Abstract: OBJECTIVES: Injection drug use (IDU) is the predominant mode of hepatitis C virus (HCV) transmission in China. This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection in injection drug users (IDUs) in China to help inform prevention programmes and guide future research. STUDY DESIGN: Data from articles and reports according to pre-defined criteria on HCV infection rates among IDUs of different regions, genders, ethnic backgrounds and risk factors (injecting practice, needle sharing, long duration, sex behaviour and co-infection status) were abstracted and pooled by meta-analysis. A systematic review was constructed based on both pooled data and representative viewpoints. METHODS: Ninety-five percent confidence intervals (CI) of infection rates were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Publication bias was examined using Begg's test and Egger's test. Data manipulation and statistical analyses were undertaken using STATA 7.0 and RevMan 4.2. Epi Info 3.4.3 was used for map construction. RESULTS: The pooled prevalence of HCV infection among IDUs in China was 61.4% (95% CI 55.7-67.2%), and the epidemic was most severe in Hubei, Yunnan, Guangxi, Hunan and Xinjiang. No significant difference was found in HCV infection rates between male and female IDUs. A significant association was found between HCV infection and ethnic-minority status. IDUs were 9.24 times more likely to be infected with HCV than non-IDUs, while non-IDUs were more likely to be infected with HCV than members of the general population and other risk populations. There was no significant difference in the risk of HCV infection for needle-sharing IDUs and non-needle-sharing IDUs. A longer duration of IDU was associated with increased HCV prevalence. High-risk sexual practices were strongly associated with drug injection behaviours. Co-infection with human immunodeficiency virus (HIV) greatly increased the probability of HCV infection among IDUs, while the probability of hepatitis B virus infection remained similar for HCV-positive and HCV-negative IDUs in China. CONCLUSIONS: IDU continues to fuel the HCV/HIV epidemics spreading throughout China. Many pragmatic strategies are being implemented but need further evaluation.

But DY, Lai CL, Yuen MF. · Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China. · World J Gastroenterol. · Pubmed #18350595 links to  free full text

Abstract: Hepatocellular carcinoma (HCC) is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the disease. Hepatitis B and C infection are the most important risk factors. HCC incidence rates are higher but in decreasing trend in developing countries. However, the figures in the developed countries are contrary. Successful hepatitis B virus (HBV) vaccination programs, better food hygiene, increased global hepatitis C virus (HCV) prevalence and population migration are the possible explanations. A number of clinical and pathogenic differences exist between HBV- and HCV-related HCC. HBV infection leads to the development of HCC through direct and indirect pathways as it has the ability to integrate into the host genome affecting cellular signaling and growth control. HCV causes HCC mainly through indirect pathways: chronic inflammation, cell deaths and proliferation. As a result, HCC is almost exclusively found in cirrhotic HCV patients while HCC is sometimes found in HBV patients without significant liver cirrhosis. Due to the different severities of liver cirrhosis and HCC extent, therapeutic strategies from resection, liver transplantation to symptoms palliation are available. Poorly differentiated histology, lack of fibrous capsule, large tumour size, early vascular invasion and elevated serum levels of alpha fetoprotein (AFP) are the features for more aggressive disease. Combined with markers of liver reserve and performance status, accurate scoring systems and models have been developed to predict patients' survival and match best treatment option.

Wang SL, Yao NL, Lv WL. · Guang'an Men Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China. · Zhongguo Zhong Yao Za Zhi. · Pubmed #18330233 No free full text.

Abstract: Determination of treatment based in pathogenesis obtained through differentiation of symptoms and signs is the characteristic of traditional Chinese medicines' treatment on chronic hepatitis B. There are important effects and special superiorities for traditional Chinese medicines on resisting hepatic fibrosis, improving liver function, protecting liver cells and relieveing the symptoms. The therapeutic effects about the only traditional Chinese medicine and traditional Chinese medicine added western medicine compared with the only western medicine was reviewed in order to explain the traditional Chinese medicine' s therapeutic superiorities.

Au WY, Kwong YL. · Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China. · Acta Pharmacol Sin. · Pubmed #18298894 links to  free full text

Abstract: Arsenic trioxide (As2O3) has been used medicinally for thousands of years. Its therapeutic use in leukaemia was described a century ago. Recent rekindling in the interest of As2O3 is due to its high efficacy in acute promyelocytic leukaemia (APL). As2O3 has also been tested clinically in other blood and solid cancers. Most studies have used intravenous As2O3, although an oral As2O3 is equally efficacious. Side effects of As2O3 are usually minor, including skin reactions, gastrointestinal upset, and hepatitis. These respond to symptomatic treatment or temporary drug cessation, and do not compromise subsequent treatment with As2O3. During induction therapy in APL, a leucocytosis may occasionally occur, which can be associated with fluid accumulation and pulmonary infiltration. The condition is similar to the APL differentiation syndrome during treatment with all-trans retinoic acid, and responds to cytoreductive treatment and corticosteroids. Intravenous As2O3 treatment leads to QT prolongation. In the presence of underlying cardiopulmonary diseases or electrolyte disturbances, particularly hypokalaemia and hypomagnesaemia, serious arrhythmias may develop, with torsades du pointes reported in 1% of cases. This may be related to a dose-dependent arsenic-mediated inhibition of potassium ion channels that compromises cardiac repolarization. Because of slow intestinal absorption, oral-As2O3 gives a lower plasma arsenic concentration, which is associated with lesser QT prolongation and hence a more favorable cardiac safety profile. As2O3 does not appear to enter the central nervous system. However, if the blood brain barrier is breached, elemental arsenic may enter the cerebrospinal fluid. As2O3 is predominantly excreted in the kidneys, and dose adjustment is required when renal function is impaired.

Guan YS, He Q, Wang MQ, Li P. · West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China. · Expert Opin Ther Targets. · Pubmed #18269337 No free full text.

Abstract: BACKGROUND: Hepatitis can be caused by a number of viruses, which have similar clinical manifestations and render infected individuals at high risk of death from cirrhosis and liver cancer. Current therapies for hepatitis have limited effects and unsatisfactory patient outcomes. Nuclear factor kappa B (NF-kappaB) is critical for immune and inflammatory responses. During its lifetime the cell demands specific and highly regulated control of NF-kappaB activity. OBJECTIVE: To develop novel strategies to overcome various hepatitides and related liver cancer with NF-kappaB as the key point. METHODS: All aspects of NF-kappaB control with regard to hepatitis are covered. RESULTS/CONCLUSION: NF-kappaB plays an important role in the process of hepatitis and is hypothesized to be an anti-cancer factor in the subsequent inflammation-associated hepatocarcinogenesis.

Chan AO, Lau JS, Chan CH, Shek CC. · Department of Pathology, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong. · Hong Kong Med J. · Pubmed #18239245 links to  free full text

Abstract: Cryoglobulins are immunoglobulins that precipitate in the serum upon cooling to below core body temperature and re-dissolve at higher temperatures. Cryoglobulinaemia may be life-threatening. The three types of cryoglobulinaemia are associated with a wide spectrum of haematological, autoimmune, and chronic infectious diseases, especially hepatitis C infection. Our laboratory has received 378 requests for cryoglobulin testing over the past 5 years, with a detection rate of 4.8% in the 271 patients involved. Twelve per cent of the specimens were not processed due to being at an inappropriate temperature on arrival at the laboratory. Clinicians should be aware of temperature requirements when requesting cryoglobulin testing in suspected cases, and for all relevant protein tests in patients with cryoglobulinaemia. Handling specimens at inappropriate temperatures in the pre-analytical and analytical phases of the investigation might lead to cryoprecipitation and therefore false-negative results. The potential pitfalls encountered with specimen handling, analysis, and result interpretation are discussed in detail.

Pang RW, Joh JW, Johnson PJ, Monden M, Pawlik TM, Poon RT. · Centre for Cancer Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China. · Ann Surg Oncol. · Pubmed #18236113 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is a common cancer in the world due to high prevalence of hepatitis B or C virus infection. Research in recent years has uncovered important molecular pathways involved in development and progression of HCC. Several genetic aberrations and molecular mechanisms responsible for initiation of hepatocarcinogenesis have been identified. Novel biomarkers for HCC are being developed for better detection and prognostication. Alpha-fetoprotein, the conventional marker of HCC, has limited sensitivity and specificity. Serum levels of isoforms of AFP based on differential lectin binding of the glycan moiety appear to be more sensitive and specific than total AFP level in early detection of HCC. The clinical usefulness of other HCC biomarkers such as des-gamma-carboxy prothrombin and glypican-3 are under investigation. HCC is an aggressive tumor with early vascular invasion and metastasis. Studies over the past two decades have elucidated the clinical predictors of outcome, leading to several staging systems for HCC based on clinical parameters. However, the predictive accuracy of clinical staging systems is limited. Recent studies suggested that biological factors may provide additional prognostic information. In particular, gene expression profiling appears to be a promising approach. Study of tumor angiogenesis in HCC reveals that the expression of angiogenic factors such as vascular endothelial growth factor and angiopoietins may also predict prognosis. The elucidation of tumor biology of HCC is of particular importance in the current era of rapid development of anti-cancer molecular targeting agents, which provide hope for an effective systemic therapy for HCC.

Chen Y, Cheng G, Mahato RI. · Huai-An 4th People's Hospital, Jiangsu, China. · Pharm Res. · Pubmed #18074201 links to  free full text

Abstract: Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Current treatment strategies of HBV infection including the use of interferon (IFN)-alpha and nucleotide analogues such as lamivudine and adefovir have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. RNA interference (RNAi), by which a small interfering RNA (siRNA) induces the gene silence at a post-transcriptional level, has the potential of treating HBV infection. The successful use of chemically synthesized siRNA, endogenous expression of small hairpin RNA (shRNA) or microRNA (miRNA) to silence the target gene make this technology towards a potentially rational therapeutics for HBV infection. However, several challenges including poor siRNA stability, inefficient cellular uptake, widespread biodistribution and non-specific effects need to be overcome. In this review, we discuss several strategies for improving the anti-HBV therapeutic efficacy of siRNAs, while avoiding their off-target effects and immunostimulation. There is an in-depth discussion on the (1) mechanisms of RNAi, (2) methods for siRNA/shRNA production, (3) barriers to RNAi-based therapies, and (4) delivery strategies of siRNA for treating HBV infection.

Wong CM, Ng IO. · SH Ho Foundation Research Laboratory, Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. · Liver Int. · Pubmed #18069974 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Hepatocarcinogenesis is a multistep process evolving from normal through chronic hepatitis/cirrhosis and dysplastic nodules to HCC. With advances in molecular methods, there is a growing understanding of the molecular mechanisms in hepatocarcinogenesis. Hepatocarcinogenesis is strongly linked to increases in allelic losses, chromosomal changes, gene mutations, epigenetic alterations and alterations in molecular cellular pathways. Some of these alterations are accompanied by a stepwise increase in the different pathological disease stages in hepatocarcinogenesis. Overall, a detailed understanding of the underlying molecular mechanisms involved in the progression of HCC is of fundamental importance to the development of effective prevention and treatment regimes for HCC.

de Villa V, Lo CM. · Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. · Oncologist. · Pubmed #18055852 links to  free full text

Abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer death, particularly in Asia where the major etiology, chronic hepatitis B virus infection, is endemic. The tumor frequently develops in a background of cirrhosis, and liver transplantation offers a chance to cure both the tumor and the underlying cirrhosis. The Milan criteria based on tumor size and number as an estimate of tumor burden are conventionally the gold standard in determining eligibility for transplantation, and the outcome is excellent. The shortage of organs from deceased donors has curtailed the adoption of extended criteria and led to the problems of long waiting times and dropouts. Several measures have been taken to tackle these issues, including prioritization of patients with HCC, use of pretransplant adjuvant treatment to prevent tumor progression, and living donor liver transplantation (LDLT). With a high incidence of HCC and a low organ donation rate, Asia has developed a distinctive pattern of indication and strategy in the application of liver transplantation. Over the last decade, the number of liver transplants in Asia has increased rapidly, by 10-fold, largely as a result of the development of LDLT. The proportion of patients who undergo liver transplantation for HCC is increasing and HCC comprises one third of the indication for liver transplantation in Asia. LDLT is the dominant strategy, accounting for 96% of the liver transplants for HCC. Many transplant programs accept patients beyond the Milan criteria, and the reported 3-year survival rate is about 60%. With the promotion of organ donation, better quantification of the benefit of LDLT for extended indications, and identification of predictors for survival, the practice of liver transplantation for HCC in Asia will continue to evolve.

Lai CL, Yuen MF. · Department of Medicine, The University of Hong Kong, Hong Kong. · J Viral Hepat. · Pubmed #17958636 No free full text.

Abstract: The natural history of chronic hepatitis B is dependent on the age of acquiring the hepatitis B infection. Those who are infected at adolescence or adulthood (including most of the Caucasians) tend to have stable disease after hepatitis B e antigen seroconversion with normal serum alanine aminotransaminase (ALT) and hepatitis B virus (HBV) DNA levels <10(5) copies/mL (20 000 IU/mL). In contrast, those who are infected at birth or early childhood (including the majority of the world's hepatitis B carriers, i.e. Asians) have a prolonged immune tolerance phase followed by a prolonged immune clearance phase. A proportion of these patients have progressive disease after HBeAg seroconversion with HBV DNA <10(4) copies/mL (<2000 IU/mL) and ALT between 0.5 and 2x upper limit of normal. Core promoter mutations may play a part in the development of cirrhosis-related complications. However, continuing viral replication, even at a relatively low level of <10(4) copies/mL (<2000 IU/mL), is probably the most important factor for the development of complications.

Ma Y, Chan CY, He ML. · Stanley Ho Centre for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. · World J Gastroenterol. · Pubmed #17876887 links to  free full text

Abstract: RNA interference (RNAi) is an evolutionally conserved gene silencing mechanism present in a variety of eukaryotic species. RNAi uses short double-stranded RNA (dsRNA) to trigger degradation or translation repression of homologous RNA targets in a sequence-specific manner. This system can be induced effectively in vitro and in vivo by direct application of small interfering RNAs (siRNAs), or by expression of short hairpin RNA (shRNA) with non-viral and viral vectors. To date, RNAi has been extensively used as a novel and effective tool for functional genomic studies, and has displayed great potential in treating human diseases, including human genetic and acquired disorders such as cancer and viral infections. In the present review, we focus on the recent development in the use of RNAi in the prevention and treatment of viral infections. The mechanisms, strategies, hurdles and prospects of employing RNAi in the pharmaceutical industry are also discussed.

Dong Z, Wei H, Sun R, Tian Z. · Institute of Immunology, Hefei National Laboratory for Physical Materials at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China. · Cell Mol Immunol. · Pubmed #17764614 links to  free full text

Abstract: For predominant abundance with liver-specific Kupffer cells, natural killer (NK) cells, and natural killer T (NKT) cells and their rapid responses to several stimuli, the liver is considered as an organ with innate immune features. In contrast to their roles in the defense of many infectious agents like hepatitis viruses and parasites, hepatic innate immune cells are also involved in the immunopathogenesis of human clinical liver diseases and several murine hepatitis models such as concanavalin A (Con A), lipopolysaccharide (LPS), or polyinosinic-polycytidylic acid (Poly I:C)-induced liver injury. In this review, the destructive roles of NK cells, NKT cells and Kupffer cells in the processes of immune-mediated liver injury and regeneration will be discussed, and some putative mechanisms involving the impairment of liver regeneration caused by activated hepatic innate immune cells are also proposed.

Lai L, Hui CK, Leung N, Lau GK. · Department of Medicine, Caritas Medical Centre, Hong Kong SAR, China. · Int J Nanomedicine. · Pubmed #17717966 links to  free full text

Abstract: Chronic hepatitis B virus (HBV) is a serious and life-threatening disease afflicting 350 million of the world's population. So far, current monotherapy with conventional interferon-alpha, lamivudine, and adefovir dipivoxil remains unsatisfactory. In addition, the use of conventional interferon-alpha needs to be administered subcutaneously daily or thrice weekly and is associated with frequent adverse events. Although nucleoside-nucleotide analogs such as lamivudine and adefovir dipivoxil are well tolerated and can normalize serum alanine aminotransaminase rapidly, 1-year therapy with either lamivudine or adefovir dipivoxil results in low hepatitis B e antigen (HBeAg) seroconversion rates. In HBeAg negative patients, most of the patients would relapse after lamivudine has been discontinued. Pegylated interferon alpha-2a, an immunomodulatory agent, is a new drug that has just completed phase III clinical trials for the treatment of both HBeAg positive and HBeAg negative chronic HBV infection. The advantage of pegylated interferon alpha-2a in achieving sustained virological response over nucleoside-nucleotide analogs is particularly obvious in the HBeAg negative group. In both of these phase III studies, sustained off-treatment response is superior to the use of lamivudine. These recent data put pegylated interferon alpha-2a as the first choice of anti-HBV therapy, especially in young and motivated patients with chronic HBV infection.

Sun X, Qin WX, Li YP, Jiang XH. · Department of Clinical Epidemiology and Evidence-Based Medicine, Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China. · J Gastroenterol Hepatol. · Pubmed #17716343 No free full text.

Abstract: BACKGROUND AND AIM: Economic efficiency of the alternative antiviral therapies for chronic hepatitis B has not been systematically investigated and their quality remains unknown. The aim of the present study was to systematically overview economic evidence of antiviral therapies for chronic hepatitis B. METHODS: We searched six databases and eight major journals supplemented with screening references of eligible studies. Full economic evaluations comparing alternative antiviral therapies in patients with chronic hepatitis B virus infection were included. Two investigators assessed the study quality and transferability, independently. Data were analyzed qualitatively with adjustment when appropriate. RESULTS: Fourteen studies (six modeling vs eight trials and database analyses) were included. Quality was high in five studies, moderate in one US and five Chinese studies, and low in three Chinese studies. The major problems of quality are costing methods and analysis and the presentation of results. In Australia and Poland, lamivudine-preferred strategies dominated interferon (IFN)-alpha and its related strategy from the health-care sector perspective. In the US, adefovir salvage produced US$8446 per additional quality-adjusted life years (QALY) compared with IFN-alpha. In Spain, the cost of adefovir was US$34,840 for additional virological response. In Taiwan, the use of pegylated IFN-alpha (pegIFN-alpha) produced US$11,711.4 per additional QALY, compared with lamivudine. In China, the incremental cost-effectiveness ratios of combination therapy lamivudine ranged from US$2860 to US$22,160 per additional loss of hepatitis B e antigen (HBeAg), and IFN-alpha versus lamivudine ranged from US$2490 to US$8890 per additional loss of HBeAg. CONCLUSION: The cost-effectiveness frontiers of treatment alternatives vary and are influenced by the comparators and socioeconomic conditions of countries. Lamivudine-containing therapy is cost-effective when newer antiviral agents (e.g. adefovir/pegIFN-alpha) were not available. Economic methods should be further improved in studies, particularly in China.

Luk JM, Wang X, Liu P, Wong KF, Chan KL, Tong Y, Hui CK, Lau GK, Fan ST. · Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong. · Liver Int. · Pubmed #17696925 No free full text.

Abstract: Liver disease afflicts over 10% of the world population. This includes chronic hepatitis, alcoholic steatosis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC), which are the most health-threatening conditions drawing considerable attention from medical professionals and scientists. Patients with alcoholism or viral hepatitis are much more likely to have liver cell damage and cirrhosis, and some may eventually develop HCC, which is unfortunately, and very often, a fatal malignancy without cure. While liver surgery is not suitable in many of the HCC cases, patients are mostly given palliative support cares or transarterial chemoembolization or systemic chemotherapies. However, HCC is well known to be a highly chemoresistant tumour, and the response rate is <10-20%. To this end, alternative medicines are being actively sought from other sources with hopes to halt the disease's progression or even eliminate the tumours. Traditional Chinese herbal medicine has begun to gain popularity worldwide for promoting healthcare as well as disease prevention, and been used as conventional or complementary medicines for both treatable and incurable diseases in Asia and the West. In this article, we discuss the laboratory findings and clinical trial studies of Chinese herbal medicines (particularly small molecule compounds) for the treatment of liver disease ranging from fibrosis to liver cancer.