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Small molecule inhibitors of glycoconjugate metabolism are being exploited for therapeutic benefit in a number of human disorders. As examples of this class of compound, imino sugars, as monosaccharide mimics, have a number of advantages for compound design and synthesis to define biological activity. As polyhydroxylated molecules, each chiral centre offers manipulation to generate isomers with restricted or enhanced mimicry, and the endocyclic nitrogen atom is readily modified to gain selectivity, increase potency or improve pharmacodynamics. This review focuses on the discovery of imino sugars that have considerable potential for treating a diverse range of diseases, from lysosomal storage disorders diabetes and cystic fibrosis to viral pathogenesis, and addresses the mechanism of action that is dictated by structural modification.

Background: The association between domestic cat hepadnavirus (DCH) infection and feline chronic hepatitis and hepatocellular carcinoma has been suggested. However, studies focused on the association between DCH infection and clinicopathological changes consistent with liver disease in cats are not available. Methods: This retrospective investigation included sera obtained from 96 cats that had the serum activity of at least alanine aminotransferase or alkaline phosphatase measured during initial diagnostic work‐up. Based on these haematobiochemical results, cats were categorised according to their likelihood of having liver disease (absent, low, intermediate or high). DCH DNA was detected using real‐time PCR, nested PCR and sequencing. Results: Overall, potential liver damage was observed in 44 cats, including cats with low (n = 14), intermediate (n = 10) and high (n = 20) likelihood of liver disease. Four cats (4.2%) were DCH‐positive, with three positive cats belonging to the liver disease group (two with low and one with intermediate likelihood of liver disease). Conclusions: Although the pathogenic potential of DCH in cats still has to be clarified, these results suggest that DCH testing should not be based only on the presence of biochemical changes potentially consistent with liver disease. [ABSTRACT FROM AUTHOR]

The spread of viral hepatitis is the result of extensive and remarkable social changes that occurred in the last three decades of the twentieth century, especially in Western society. The emergence of viral hepatitis resulted in a significant reduction in quality of life and survival among those who contracted the infection. The impact of viral hepatitis varies with the different levels of socioeconomic development of populations and emerging factors in its transmission. Finally, important scientific and social advances have been achieved, but still insufficient to control these infections. The epidemiology of viral hepatitis in the XXI century reflects both the positive impact of preventive measures and the negative impact of historical and transmission emerging patterns. Viral hepatitis is a disease of two worlds, one where new infections are restricted to emerging patterns of transmission and treatment is available, another where both historical patterns and emerging new infections allow transmission and access to treatment is restricted. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study is the first attempt conducted to determine the co-infection rates of Hepatitis C virus among people living with HIV/AIDS (PLWHA) in our hospital. This is expected to lead to improvement in treatment protocols. Background: Co-infection of Hepatitis C virus infection and HIV (Human Immune Deficiency Virus) infection is not to be unexpected as they share routes of infection. The detection of such patients is particularly important as the treatment may involve life threatening drug interactions. This could result in shorter life expectancy of the patients. Materials and Methods: This is a prospective study. A total of 280 subjects living with HIV/AIDS were recruited into this study. Sera of the participants were subjected to anti-HCV antibody (IgG) screening using third generation ELISA kit from DIA.PRO, Italy. The prevalence of HCV was determined and bar charts and tables were utilised to depict the prevalence rates of various groups. Results: Sixty five (23.2%) of the participants were found to be co-infected. No association was established between age, sex, partners status, previous transfusion, and number of partners. Conclusion: The prevalence of 23.2% for HCV among PLWHA reported for this community is alarming. More focus should be directed on management of HCV component of coinfection than it is done now. Further studies are recommended employing molecular techniques to determine subtypes of HCV that may be predominant and why this figure of co-infection is so high in the study location. [Copyright &y& Elsevier]

Hemodialysis patients are at risk for hepatitis C and B virus infections. This study investigated the prevalences and risk factors of HCV and HBV infection and the distribution of HCV genotypes among hemodialysis patients and their spouses. From August to November 2011, a cross-sectional study was conducted on 20 hemodialysis units in Beijing to investigate prevalences and risk factors for markers of HCV and HBV among 2,120 patients and 409 spouses. In hemodialysis patients, prevalences of anti-HCV, HCV RNA, and hepatitis B surface antigen (HBsAg) were 6.1%, 4.6%, and 7.0%, respectively. The prevalence of HCV antibodies among spouses was 0.5%, of HCV RNA was 0.2%, and of HBsAg was 4.2%. Risk factors for HCV infection were dialysis duration, blood transfusion, and attending more than one dialysis unit. HBV infection was independently associated with age, family member with hepatitis infection, gender, and surgery. The predominant HCV genotypes were 1b (89.0%) and 2a (7.7%), and genotypes 3a, 3b, and 6a were each 1.1%. A significant decrease in HCV and HBV prevalences in Chinese dialysis units showed that infection control measures were effective. However, because nosocomial transmissions persist, strict adherence to infection control measures should be emphasized to reduce the risk of transmission. J. Med. Virol. 85:425-432, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background and Aim: A number of studies have shown that hepatitis virus infections may be associated with cholangiocarcinoma (CC). However, the relationship between hepatitis B virus (HBV) infection and CC, especially intrahepatic cholangiocarcinoma (ICC), is still controversial. Methods: Relevant studies were identified by searching PUBMED, EMBASE and Web of Science Datebases up to September 2011. Pooled risk estimates were calculated using a random-effects model. Potential sources of heterogeneity were performed by subgroup analyses. A total of 18 papers were included in this meta-analysis. Results: The pooled risk estimate of all studies showed a statistically significant increased risk of CC among individuals with HBV infection (rate ratio [RR]: 2.66; 95% confidence interval [CI]: 1.97, 3.60). Compared with those without HBV infection, persons with HBV infection had an increased risk of intra-CC (ICC) (RR: 3.42; 95% CI: 2.46, 43.74), extrahepatic CC (OR: 1.46; 95% CI: 0.98, 2.17), and CC (OR: 2.03; 95% CI: 1.15, 3.56). In a subgroup analysis of HBV infection and risk of ICC, the pooled risk estimate of studies in Asians (RR: 3.63; 95% CI: 2.56, 5.13) was higher than that in non-Asians (RR: 1.93; 95% CI: 0.78, 4.76). A Begg funnel plot and Egger test revealed no evidence for publication bias. Conclusions: This meta-analysis shows that HBV is associated with increased risk of CC, especially for ICC. Further investigation is needed to focus on the mechanism by which HBV may be involved in the pathogenesis of CC. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the present study was to develop a risk estimation model for the 10-year risk of hepatocellular carcinoma (HCC) that could be easily used in a general population to aid in the prevention of HCC. Methods: Our prediction model was derived from data obtained on 17,654 Japanese aged 40 to 69years who participated in health checkups (follow-up: 1993–2006). Cox proportional hazards regression was applied to obtain coefficients for each predictor. Results: During follow-up, a total of 104 cases of HCC were newly diagnosed. After checking the model fit, we incorporated age, sex, alcohol consumption, body mass index, diabetes, coffee consumption, and hepatitis B and C virus infection into the prediction model. The model showed satisfactory discrimination (Harrell''s c-index=0.94) and was well calibrated (the overall observed/expected ratio=1.03, 95% confidence interval=0.83–1.29). We also developed a simple risk scoring system. Those subjects with total scores of 17 or more under this system (score range: −1 to 19) had an estimated 10-year HCC risk of over 90%; those with 4 points or less had an estimated risk of less than 0.1%. Conclusion: We developed a simple 10-year risk prediction model for HCC in the Japanese general population as a public education tool. [Copyright &y& Elsevier]

Abstract: Non-coding RNA (ncRNA), a class of RNAs that do not code protein but have regulatory functions, can regulate gene expression and replication of hepatitis B virus or hepatitis C virus and play an important role in the virus–host interaction and the development of hepatocellular carcinoma (HCC). Deregulated ncRNAs in surgically removed hepatic tissues and circulation can be prognostic and diagnostic markers, respectively. ncRNAs functioning as either tumor suppressors or oncogenes can be therapeutic options. Here, we summarize the deregulated ncRNAs associated with the infections and HCC and focus on their roles on early diagnosis, prognosis prediction and therapeutic option of HCC. [Copyright &y& Elsevier]

Aim: The aim of this study was to evaluate the prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhotic patients with fasting plasma glucose (FPG) level of <126 mg/dL. Methods: A total of 263 patients with hepatitis C virus (HCV) or hepatitis B virus (HBV) positive liver cirrhosis, FPG level of <126 mg/dL, and had diabetes status evaluated by the use of 75-g oral glucose tolerance test (OGTT), were enrolled in this study. Plasma glucose and insulin levels were analyzed periodically for 3 h after oral glucose loading. Diabetes was defined as a 2-h post-load glucose on the OGTT of ≥200 mg/dL. The prevalence of diabetes by use of OGTT and predictive factors for diabetes were evaluated by the use of the Mann-Whitney U-test, Fisher's exact probability test or multivariate analysis by logistic regression. Hypoalbuminemia was defined as serum albumin level of <3.9 g/dL. Elevated indocyanine green retention rate at 15 min (ICG R15) was regarded as ≥ 25%. Results: Out of 263 patients, 44 (16.7%) were diagnosed as having diabetes. Multivariate analysis showed that diabetes occurred when patients had hypoalbuminemia of <3.9 g/dL (odds ratio [OR] 2.33; 95% confidential interval [CI] = 1.04-5.24; P = 0.040) and ICG R15 of <25% (OR 2.36; 95%CI = 1.01-5.58). Conclusions: Hypoalbuminemia and elevated ICG R15 in hepatitis virus related cirrhotic patients with FPG level of <126 mg/day enhance diabetes pattern after OGTT with significant difference. [ABSTRACT FROM AUTHOR]

Indolent lymphomas are malignant tumors of the cells of the immune system, located in different tissues. The clinical evolution is unpredictable, some cases going well beyond the average rate of survival of 8-10 years, and others with an increased probability of transforming into lymphomas with high malignancy. Based on the data provided in literature, we shall describe three cases diagnosed with indolent lymphomas focusing on the type of onset, evolution and treatment response. [ABSTRACT FROM AUTHOR]

Autophagy is a lysosomal pathway that degrades and recycles intracellular organelles and proteins to maintain energy homeostasis during times of nutrient deprivation and to remove damaged cell components. Recent studies have identified new functions for autophagy under basal and stressed conditions. In the liver and pancreas, autophagy performs the standard functions of degrading mitochondria and aggregated proteins and regulating cell death. In addition, autophagy functions in these organs to regulate lipid accumulation in hepatic steatosis, trypsinogen activation in pancreatitis, and hepatitis virus replication. This review discusses the effects of autophagy on hepatic and pancreatic physiology and the contribution of this degradative process to diseases of these organs. The discovery of novel functions for this lysosomal pathway has increased our understanding of the pathophysiology of diseases in the liver and pancreas and suggested new possibilities for their treatment. [Copyright &y& Elsevier]

Due to their high resistance to inactivation procedures, nonenveloped viruses such as parvovirus B19, human bocavirus (HBoV), human parvovirus 4 (PARV4), hepatitis A (HAV) and hepatitis E virus (HEV) pose a particular threat to blood products. Virus transmission to patients treated with blood products presents an additional burden to disease. We determined the frequency and the amount of nucleic acid specific for nonenveloped viruses in recently manufactured preparations of commercial coagulation factor concentrates. At least three different batches of each of 13 different plasma-derived and recombinant coagulation factor products were tested for the presence and the amount of nucleic acid for parvovirus B19, HBoV, human parvovirus 4, hepatitis A virus and HEV by using quantitative polymerase chain reaction. Whereas none of the recombinant products tested positive for any of these viruses, parvovirus B19 DNA with amounts ranging between 2 × 10 and 1.3 × 10 genome equivalents/ml was detected in five plasma-derived products. In addition to parvovirus B19 genotype 1, genotypes 2 and 3 were observed in two batches of a factor VIII/von-Willebrand factor product. In two products (one factor VIII concentrate and one activated prothrombin complex concentrate), a combination of both genotypes 1 and 2 of parvovirus B19 was detected. The data show that nucleic acids from several relevant nonenveloped viruses are not found at detectable levels in coagulation factor concentrates. In some cases, parvovirus B19 DNA was detectable at low levels. Testing of the plasma pools for the full range of parvovirus genotypes is advocated for ensuring product safety. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence, risk factors, and rate of vertical transmission of HBV and/or HCV infection among pregnant women in Upper Egypt, and assess the preventive efficacy of administering hepatitis B immunoglobulin and vaccine to newborns on their carrier status at 8 months.Methods: Five hundred pregnant women were screened for HCV and HBV serum markers by enzyme-linked immunoassay. Those testing positive had their status confirmed by polymerase chain reaction and their levels of liver enzymes and interferon gamma were evaluated. The newborns of HBV-positive women received hepatitis B immunoglobulin and vaccine and were followed up to assess the rates of vertical transmission and carrier status among the newborns.Results: Of the 500 pregnant women, 6.4% were HCV positive, 4.0% were HBV positive, and 1.0% were both. The vertical transmission rate was 3.1% for HCV, 30.0% for HBV, and 20.0% for a combined infection. The carrier rate of the infants at the end of their eighth month was 10.8% for those with HCV and 8% for those with HBV.Conclusion: Infection with HBV and/or HCV is highly prevalent among pregnant women in Upper Egypt. The rate of vertical transmission was also high. Administering hepatitis B vaccine and immunoglobulin resulted in a 92% reduction in carrier status among newborns. [ABSTRACT FROM AUTHOR]

Abstract: An integrated automatic electrochemical immunosensor array has been designed for the simultaneous detection of 5-type hepatitis virus antigens (i.e. hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E). Initially, 5-type hepatitis virus antibodies were immobilized onto a self-made electrochemical sensor array using nanogold particles and protein A as matrices, and the immunosensor array was then used to capture their corresponding antigens from sample solution with a 1-step capture format. The detection is based on the potential change before and after the antigen-antibody reaction by using a 2-electrode system. The developed immunosensor array with allowed simultaneous determination of 5-type hepatitis virus antigens in 5min. The detection limit of the sensor array was ≤1.0ng/mL for most analytes. The intra- and inter-assay imprecision (CVs) of the sensor array were ≤7.3% and 8.1%, respectively. No nonspecific adsorption was evaluated, and the crossing talk between neighboring sites was ≤7.5% (CV). The developed immunoassay system offers promise for label-free, simple, rapid, cost-effective analysis of multi-analyte. Importantly, the chip-based immunosensor array could open new opportunities for high-throughput multi-analyte immunoassays in point-of-care testing of miniaturized lab-on-a-chip devices. [Copyright &y& Elsevier]

Abstract: The human DEAD-box RNA helicase DDX3 has been implicated to play a role in the whole repertoire of processes regulating gene expression, including transcription, splicing, mRNA export and translation. It has also been suggested to be involved in cell cycle control and the regulation of apoptosis. In addition, DDX3 was recently shown to be part of innate immune signalling pathways and to contribute to the induction of anti-viral mediators, such as type I interferon. Interestingly, DDX3 appears to be a prime target for viral manipulation: at least four different viruses, namely Hepatitis C virus (HCV), Hepatitis B virus (HBV), Human Immunodeficiency Virus (HIV) and poxviruses, encode proteins that interact with DDX3 and modulate its function. HIV and HCV seem to co-opt DDX3 and require it for their replication. It has therefore been suggested that DDX3 could be a novel target for the development of drugs against these two viruses, both of which still pose major global health threats. However, in the light of the apparent multifunctionality of DDX3 in the cell, drug development strategies targeting DDX3 will have to be carefully evaluated. This review summarises the available data on the cellular functions of DDX3 and discusses their manipulation by the different viruses known to target DDX3. Understanding the viral strategies for manipulating or co-opting DDX3 in functional and molecular detail can provide valuable insights for the development of strategies to therapeutically target DDX3. [Copyright &y& Elsevier]

• CD133+ cells were increased in viral hepatitis-associated liver cirrhosis and HCC. • CD133 rs3130 TT, rs1029728 GG, and rs2240688 TT SNPs raised cirrhosis and HCC risk. • In HCV-HCC, rs3130, rs1029728, or rs2240688 increased number and size of lesions. • In HBV-HCC, rs3130 TT genotype was associated with higher lesion size. • rs3130 TT and rs1029728 GG genotypes had a higher percentage of CD133+ cells. CD133 has been postulated to identify cancer stem cells (CSCs) and to play a role in tumorigenesis and cancer progression. The purpose of this study was to explore the impact of CD133 polymorphisms on viral hepatitis-induced liver cirrhosis, as well as hepatocellular carcinoma (HCC) susceptibility and prognosis. CD133+ cells were counted and CD133 SNPs (rs3130, rs1029728, rs2240688, and rs2286455) were genotyped in HCV, HCV-liver cirrhosis, HCV-HCC, HBV, HBV-liver cirrhosis, and HBV-HCC patients and disease-free controls. The percentage of CD133+ cells was observed to be significantly higher in HCV- and HBV-associated liver cirrhosis and HCC. Also, the CD133 rs3130 (C > T) TT, rs1029728 (A > G) GG, and rs2240688 (G > T) SNP TT genotypes were associated with a greater risk of liver cirrhosis and HCC development in viral hepatitis patients. Furthermore, in HCV-related HCC, rs3130 TT, rs1029728 GG, or rs2240688 TT genotypes were significantly associated with an increased number and size of focal lesions, but only the rs3130 TT genotype was associated with higher lesion size in HBV-associated HCC. In addition, individuals having rs3130 TT and rs1029728 GG genotypes had a significantly higher percentage of CD133+ cells. However, only HCV-infected individuals, carrying rs2240688 TT genotype, had an elevated level of CD133+ cells. CD133 rs3130, rs1029728, and rs2240688 are genetic factors that can influence the susceptibility to liver cirrhosis and cancer, as well as the prognosis. As a result, CD133+ cells and CD133 polymorphisms might serve as potential predictors of these illnesses, laying the groundwork for the discovery of novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Viral infections or persistent alcohol or drug abuse, together with intrinsic factors, lead to hepatitis, which often ends in the development of liver cirrhosis or hepatocellular carcinoma (HCC). With this review, we describe inflammatory liver diseases, such as acute liver failure, virus-induced hepatitis, alcoholic- and non-alcoholic steatohepatitis, and autoimmune hepatitis, and highlight their driving mechanisms. These include external factors such as alcohol misuse, viral infection and supernutrition, as well as intrinsic parameters such as genetic disposition and failure, in immune tolerance. Additionally, we describe what is known about the translational machinery within all these diseases. Distinct eukaryotic translation initiation factors (eIFs) with specific functional roles and aberrant expression in HCC are reported. Many alterations to the translational machinery are already triggered in the precancerous lesions described in this review, highlighting mTOR pathway proteins and eIFs to emphasize their putative clinical relevance. Here, we identified a lack of knowledge regarding the roles of single eIF proteins. A closer investigation will help to understand and treat HCC as well as the antecedent diseases. [ABSTRACT FROM AUTHOR]

Hepatitis B (HBV) and hepatitis C (HCV) viruses are the two major causes of chronic liver inflammation worldwide. Despite distinct virologic features, both viruses are preferentially hepatotropic, not directly cytopathic, and elicit liver diseases that share several aspects of their natural history. HBV and HCV infections also share some important features of the adaptive antiviral immune response. We describe the innate immune response in the early phase following infection, and how these early events may influence the development of the adaptive immune response in these two important viral infections. The mechanisms by which high levels of viral antigens, liver immunological features, the presence of regulatory T cells and impaired dendritic cell functions may maintain the HBV- and HCV-specific immunological failure, characteristic of chronic hepatitis B and C patients, are also evaluated. [Copyright &y& Elsevier]

Abstract: Chronic hepatitis B virus (HBV) infection has been strongly associated with hepatocellular carcinoma (HCC) and the X protein (HBx) is thought to mediate the cellular changes associated with carcinogenesis. Recently, isolation of the hepatitis B virus integrants from HCC tissue by others have established the fact that the X gene is often truncated at its C-terminus. Expression of the GFP fusion proteins of HBx and its truncation mutants with a GFP tag in human liver cell-lines in this study revealed that the C-terminus of HBx is indispensable for its specific localization in the mitochondria. A crucial region of seven amino acids at the C-terminus has been mapped out in which the cysteine residue at position 115 serves as the most important residue for the subcellular localization. When cysteine 115 of HBx is mutated to alanine the mitochondria targeting property of HBx is abrogated. [Copyright &y& Elsevier]

The etiology of dermatomyositis is unknown, but immune mechanisms play an important role. Several dermatological manifestations have been reported among carriers of hepatitis B surface antigen, and after vaccination with the HBV vaccine. Almost all the skin reactions described were peculiar skin eruptions suggestive of an immune complex reaction. Some authors described the occurrence of dermatomyositis after BCG and influenza vaccination. We report a case of a 6-year-old child, who was vaccinated for hepatitis B virus and developed a flu-like disease accompanied by a skin rash, which had the typical features of dermatomyositis. The association of vaccination with autoimmunity is discussed. [ABSTRACT FROM AUTHOR]

Aim: Currently, approximately 44 000 hepatitis C virus (HCV), 11 000 hepatitis B virus (HBV), and 1600 hepatitis E virus (HEV) sequences are available at the International Nucleotide Sequence Database Collaboration (INSDC, previously known as DDBJ/EMBL/GenBank), and the number of these virus sequences is growing rapidly. However, since INDSC is not specialized to hepatitis viruses, it is difficult to retrieve information of virological or clinical interests from it. Thus, it is quite worthwhile to construct a specialized database for the hepatitis virus sequences and to make it accessible to researchers worldwide. Methods: We developed a WWW-based database hepatitis virus database (HVDB), which contains all the HCV, HBV, and HEV sequences available at INSDC. In the HVDB, all piece sequences obtained from INSDC are arranged to the genomesequence of each virus. Also given in the database are the phylogenetic relationships of each locus on the genome among variants for each virus. Results: Users of the database can easily retrieve entries (sequences with annotations) of the specific genotype by referring to the phylogenetic relationships or those of specific loci by referring to the genome map information. HVDB provides users with a tool for phylogenetic analysis that can be used in combination with the data retrieval tools. Conclusion: The latest release is publicly accessible at the HVDB website: . [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis virus replication in the liver is often accompanied by inflammation resulting in the formation of reactive oxygen species (ROS) and nitric oxide (NO) and these may induce cell death. We investigated whether the expression of HBx or HCV core protein in HepG2 cells has an influence on the sensitivity of these cells for oxidative radicals. Our previous study, using the inducible HBV model of HepAD38, revealed that oxidative-stress-related genes are upregulated by virus replication. In the present study, we examined the intracellular pro-oxidant status with dichlorofluorescein (DCF) in HepG2 cell lines transfected with HBx, HbsAg and HCV core. Baseline intracellular oxidative levels were not different in the cell lines expressing viral proteins as compared to control. However, when these cells were exposed to H2O2, the viral protein expressing cells, especially those expressing HBx, showed a reduced level of ROS. This suggests that HBx and HCV core transfected cells can convert H2O2 to less reactive compounds at a higher rate than the control cells. When HBx or HCV core expressing cells were exposed to peroxynitrite (a highly reactive product formed under physiological conditions through interaction of superoxide (O2 − ) these cells were less sensitive to induction of cell death. In addition, these cell lines were less prone to cell death when exposed to H2O2 directly. In conclusion, HBx and HCV core expression in HepG2 cells leads to a survival benefit under oxidative stress which in vivo can be induced during inflammation. [Copyright &y& Elsevier]

Mitochondrial antiviral signaling protein (MAVS) is an essential component of virus-activated signaling pathways that induce protective IFN responses. Its localization to the outer mitochondrial membrane suggests an important yet unexplained role for mitochondria in innate immunity. Here, we show that hepatitis A virus (HAV), a hepatotropic picornavirus, ablates type 1 IFN responses by targeting the 3ABC precursor of its 3Cpro cysteine protease to mitochondria where it colocalizes with and cleaves MAVS, thereby disrupting activation of IRF3 through the MDA5 pathway. The 3ABC cleavage of MAVS requires both the protease activity of 3Cpro and a transmembrane domain in 3A that directs 3ABC to mitochondria. Lacking this domain, mature 3Cpro protease is incapable of MAVS proteolysis. HAV thus disrupts host signaling by a mechanism that parallels that of the serine NS3/4A protease of hepatitis C virus, but differs in its use of a stable, catalytically active polyprotein processing intermediate. The unique requirement for mitochondrial localization of 3ABC underscores the importance of mitochondria to host control of virus infections within the liver. [ABSTRACT FROM AUTHOR]

The article reports on the involvement of oxidative stress in the development of liver cancer. An overview of the identified three distinct stages of the cancer initiation, promotion and progression, and the participation of oxidative stress in these stages are offered. It also mentions the treatments that are required to prevent the development this disease.

The tissue polypeptide-specific antigen (TPS, cytokeratin-18, a normal constituent of the hepatocyte cytoskeleton) is a standard tumour marker. This study aimed to evaluate serum TPS levels in patients with liver disease. Methods: Serum TPS was measured with a commercial immunoassay in 884 individuals (753 outpatients from a liver disease clinic, 131 patients admitted to the hospital with acute liver disease). Results: Abnormally high (>80 U/l) TPS levels were found in 57.7% (95% CI 54.0–61.3%) of outpatients with liver disease. Elevated TPS levels were observed for all liver diseases, including fatty liver, alcoholic disease, chronic viral hepatitis, autoimmune hepatitis, cholestasis, transplantation, and hepatocarcinoma. TPS levels correlated with liver markers, particularly serum AST. In addition, TPS levels correlated with Knodell's score in patients with chronic hepatitis. TPS was increased in one-third of patients with normal liver enzyme values. Serum TPS levels decreased after specific therapy in patients with hepatitis C and autoimmune hepatitis. Abnormally high TPS levels were found in the vast majority of patients admitted to the hospital, with markedly high (>800 U/l) values being observed in 47.5% (95% CI 36.1–55.7%) of patients with alcoholic liver disease and in 80.8% (95% CI 60.0–92.7%) of patients with acute hepatitis. Conclusions: Serum TPS (cytokeratin-18) is elevated in patients with non-malignant liver diseases, particularly in those with prominent cytolysis. Further studies are needed to evaluate the use of TPS as a marker of liver disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics of thalidomide in patients with advanced hepatocellular carcinoma (HCC). Methods: Patients with advanced HCC who were not feasible for definitive local therapy were eligible. Patients were enrolled in a cohort of three to receive thalidomide twice daily for 1 week to determine the MTD. Intra-patient dose escalation was permitted. Pharmacokinetic studies were performed at the first dose level and repeated at the second dose level of each patient. Results: Fifteen patients were accrued at four dose levels with the starting dose range 100–400 mg/day. Two patients at 400 mg/day experienced DLT (grade 3 angioedema and dyspnea, respectively). The MTD of twice-daily schedule was determined as 300 mg/day. The mean steady-state maximal blood concentration and mean steady-state area under the curve had a trend toward positive correlation, but non-linear proportionate, to the daily dose of thalidomide. Pharmacokinetic parameters are comparable for patients of Child-Pugh’s A and B. Apparent mild, transient drug-induced transaminitis was early onset, self-limited, which occurred in 30.7% of patients. Serum hepatitis B or C viral titers was largely not affected. Conclusion: The absorption and elimination of thalidomide are not significantly different in HCC patients with compensated or decompensated hepatic dysfunction. [ABSTRACT FROM AUTHOR]

Background: SouthernTaiwan is a hepatitis B and C viruses (HBV, HCV) endemic area. SEN virus (SENV) infection has been suggested as transfusion-related hepatitis. Two variants of SENV (SENV-D and SENV-H) have been studied in non-transfused children and transfusion-dependent thalassemia patients. Methods: Sera of 67 non-transfused children and 55 pediatric thalassemia patients with multiple transfusions were tested for SENV-D and SENV-H DNAs, liver function, iron status, HBV and HCV markers. Results: The prevalence of SENV (D or H), SENV-D, SENV-H infection, and SENV-D/H coinfection was significantly lower in nontransfused children than in thalassemia patients (22.4, 20.9, 5.0 and 1.5%, respectively, versus 67.3, 52.7, 40.0 and 25.5%, respectively, p < 0.001). The serum alanine aminotransferase (ALT) levels in thalassemia patients with SENV infection alone were significantly lower than levels in patients with SENV/HCV co-infection (p < 0.05), but not different when compared with those without SENV/HCV infection. SENV viremia was not associated with elevated ALT levels in thalassemia patients. SENV viremia did not increase the risk of HCV infection in thalassemia patients. Conclusions: SENV infection is high among non-transfused controls in Taiwan. Transfusion significantly increases the relevance of SENV infection. SENV viremia was not associated with the ALT levels in thalassemia patients. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To investigate the features of various hepatitis virus infection in intravenous drug users (IVDU), we conducted an epidemiological survey of hepatitis viruses including hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis G virus (HGV) in IVDU. The correlation of TH lymphocyte cytokine and hepatitis virus infection was examined. A study population of 406 IVDU consisted of 383 males and 23 females. HBV-DNA and HCV-RNA were detected by fluorescence quantitative polymerase chain reaction. HBsAg, HBeAg, anti-HBc, anti-HCV, HDV-Ag and anti-HGV were assayed by ELISA. The levels of cytokines of TH1 and TH2 were measured by ELISA. The similar indices taken from 102 hcalthy persons served as controls. The infection rate of cach virus among IVDU was 36. 45% for HBV, 69. 7% for HCV, 2.22% for HDV, and 1.97% for HGV, respectively. The co-infection rate of HBV and HCV was detected in 113 of 406 (27. 83%). In contrast, among controls. the infection rate was 17.65% for HBV and 0% for the other hepatitis viruses. The levels of PHA-induced cytokines (IFN-γ and IL-4) and the level of serum IL-2 were obviously decreased in IVDU. On the other hand, the level of serum IL-4 was increased. The IFN-γ level was continuously decreased when the IVDU was infected with HBV/HCV. In conclusion, HBV and HCV infection were common in this population of IVDU and they had led to a high incidence of impaired TH1 cytokine levels. [ABSTRACT FROM AUTHOR]

Background. The Japan integrated staging (JIS) score is recognized to be useful in managing hepatocellular carcinoma (HCC). We evaluated the effects of the causative virus in patients stratified by this system. Methods. We compared clinicopathologic features, cumulative and tumor-free survival rates, and causes of death between 301 hepatitis C virus-positive patients (HCV group) and 60 hepatitis B virus-positive patients (HBV group). Results. Among patients with low JIS scores (0 or 1), the proportions of patients with high aspartate and alanine aminotranferase activities, moderate-to-severe active hepatitis, and with cirrhosis were significantly higher in the HCV than in the HBV group. Among patients with high JIS scores (2 to 4), the proportion with moderate-to-severe active hepatitis was also significantly higher in the HCV group. In patients with low JIS scores, those in the HCV group had significantly lower tumor-free and cumulative survival rates than those in the HBV group. Although no patient in the HBV group died of causes other than liver disease (HCC or hepatic failure), some patients in the HCV group died of causes other than liver disease. The proportion of patients who died because of HCC recurrence tended to be higher among patients with high JIS scores than among patients with a low JIS score. Conclusions. The effects of viral status on survival outcomes are greatest in patients with JIS scores of 0 or 1. [ABSTRACT FROM AUTHOR]

A cross-sectional study was performed in 60 Cuban women of child-bearing age who were seropositive for human immunodeficiency virus (HIV) and 60 controls. Human papillomavirus (HPV) was identified most frequently, with oncogenic HPV serotypes 16, 33 and 58 detected in HIV-positive patients, and serotypes 11, 33 and 51 in the controls (relative risk 4.41; 95% CI 2.21–8.29). Syphilis and hepatitis B and C viruses were detected exclusively in HIV-seropositive women (p < 0.05). Sexually transmitted diseases (STDs) appeared to pose a substantial health problem, especially for HIV-positive women. Clinics should consider screening and treatment for STDs as part of their HIV prevention programmes. [ABSTRACT FROM AUTHOR]