Home About us Contact
|
Home About us Contact | ||
|
|
||
Viral Hepatitis (viral + hepatitis)
Kinds of Viral Hepatitis Terms modified by Viral Hepatitis Selected AbstractsCharacterization of hepatitis A virus isolates from subgenotypes IA and IB in Rio de Janeiro, Brazil,JOURNAL OF MEDICAL VIROLOGY, Issue 1 2002Vanessa S. de Paula Abstract Hepatitis A virus (HAV) isolates from around the world have been classified into seven genotypes (I,VII). Most human strains belong to genotype I, which has been divided into two subgenotypes, A and B. South America has provided a small number of strains studied at the genome level. In the present study, IgM anti-HAV antibodies were detected in 116 out of 250 (46%) serum samples collected from consecutive patients with acute hepatitis referred to the Brazilian Reference Center for Viral Hepatitis, Rio de Janeiro. Viral RNA were extracted from all 250 samples and submitted to a reverse transcription-polymerase chain reaction (RT-PCR) assay designed to amplify a genome segment in the VP1/2A junction region. HAV RNA was detected in 54/116 (47%) and 17/134 (13%) IgM anti-HAV-positive and -negative sera, respectively. In addition, HAV RNA was detected in 17/35 (49%) IgM anti-HAV-positive sera that had been collected at a day care center where cases of acute hepatitis were being observed for 3 months. Nucleotide sequences (168 bp) of PCR products were determined for 30 HAV isolates. Phylogenetic analysis showed that 21 belonged to subgenotype IB, while 9 were of subgenotype IA. Interestingly, a concomitant circulation of isolates from subgenotypes IA and IB was observed in the day care center. J. Med. Virol. 66:22,27, 2002. © 2002 Wiley-Liss, Inc. [source] Risk of hepatitis A infection following travelJOURNAL OF VIRAL HEPATITIS, Issue 6 2002M. Ciccozzi summary.,Travel to endemic areas is one of the most frequently reported risk factors for infection with the hepatitis A virus (HAV). We evaluated the association between HAV infection and travel, by area of destination. We conducted a case,control study on all cases of HAV infection reported to the Italian National Surveillance System for Acute Viral Hepatitis in the period 1996,2000. The study population consisted of 9695 persons with HAV infection (cases) and 2590 with HBV infection (controls). The risk of acquiring HAV was highest for travel to Asia, Africa and Latin America [Odds Ratio=9.30 (95%CI=6.71,12.9)]; a three-fold statistically significant excess of risk was found for travel to southern Italy (OR=3.03) and to the Mediterranean Area and Eastern Europe (OR=3.15). Travel was implicated in 28% of the cases of HAV infection. When stratifying the analysis by area of residence (northern and central Italy vs southern Italy and the Islands), the above-mentioned risks were confirmed only for those residing in northern and central Italy, with no significant risk for those residing in southern Italy and the Islands. Travel to areas endemic for HAV infection constitutes a considerable risk. Our results highlight the importance of developing health policies for improving environmental and hygienic conditions, as well as the prevention of certain eating habits. Vaccination before travelling to a medium or high endemic area could be a safe and effective means of preventing travel-related HAV infection. [source] Viral Hepatitis in Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2009J. Levitsky First page of article [source] Review article: vaccination and viral hepatitis , current status and future prospectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2007R. S. KOFF Summary Background, Viral hepatitis is the most common cause of liver disease in the world. In the past 25 years, vaccines have become available for two of the five hepatitis viruses, and, where implemented, vaccination has become a key component of hepatitis prevention. Aims, To provide an update on recent advances in the use of current hepatitis vaccines and to examine progress in the development of vaccines for the remaining hepatitis viruses. Methods A Medline search was undertaken to identify the recent relevant literature. Search terms included hepatitis vaccines, hepatitis vaccination and hepatitis A,E vaccines. Results, Dramatic vaccine-induced declines in the incidence of both hepatitis A and B have occurred in the USA. Strategies to integrate hepatitis A vaccine into universal childhood immunization are being adopted. Similarly, strategies with the goal of eliminating transmission of hepatitis B have been promulgated. A vaccine for hepatitis E has been reported to be effective and safe, but progress in the development of vaccines for hepatitis C and D has been limited. Conclusion, During the next few decades, the goals of eliminating hepatitis A and B virus transmission may be reached in the USA and elsewhere. [source] Hepatitis viruses: live and let dieLIVER INTERNATIONAL, Issue 3 2007K. Herzer Abstract Viral hepatitis is a diffuse inflammatory reaction of the liver caused by hepatotropic viruses. Among the hepatitis viruses, only hepatitis B virus and hepatitis C virus are able to persist in the host and cause chronic hepatitis. In the course of persistent infection, inflammation forms the pathogenetic basis of chronic hepatitis that can lead to nodular fibrosis, which can progress to cirrhosis and, eventually, hepatocellular carcinoma (HCC). Of the different antiviral defense systems employed by the host, apoptosis significantly contributes to the prevention of viral replication, dissemination, and persistence. Pathomorphologic studies have shown acidophilic bodies and hepatocyte dropout, features that are compatible with apoptosis. The number of hepatocytes showing features of apoptosis in patients with chronic hepatitis B and C was found to be higher than in healthy subjects, indicating that apoptosis is involved in the pathogenesis of these diseases. There are various data suggesting that hepatitis B and C viral proteins may modulate apoptosis. Vice versa, mechanisms of apoptosis inhibition might represent central survival strategies employed by the virus which, in the end, may contribute to HCC development. While the expression and retention of viral proteins in hepatocytes may influence the severity and progression of liver disease, the mechanisms of liver injury in viral hepatitis are defined to be due not only to the direct cytopathic effects of viruses, but also to the host immune response to viral proteins expressed by infected hepatocytes. However, the exact role of these observations in relation to pathogenesis remains to be established. The mechanism and systems are complex. This report aims to provide an overview and intends to cite only a small number of pertinent references. [source] Peroxisome proliferator-activated receptor-, as emerging target in liver diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2010Bernd Schnabl Abstract Liver fibrosis is characterized by an excessive deposition of extracellular matrix (ECM) proteins that occurs in chronic liver disease of any origin, including nonalcoholic steatohepatitis (NASH), alcohol abuse, and viral hepatitis. Cirrhosis occurs with the development of regenerating nodules of hepatocytes and is a major health burden worldwide. Patients with decompensated liver cirrhosis have a poor prognosis, with liver transplantation often being necessary. The current treatment paradigm for patients with hepatic fibrosis is to treat the underlying liver disease. However, if this cannot be achieved, there are currently no effective antifibrotic treatments for patients with chronic liver diseases. With the advent of basic molecular technology providing insight into the mechanisms of the development of hepatic fibrosis, there is now an opportunity to develop therapeutic interventions for human clinical use. In this review, the function of peroxisome proliferator-activated receptor-, (PPAR ,) will be summarized with a special emphasis on ligand activation as potential use in liver disease. Drug Dev Res 2009. © 2009 Wiley-Liss, Inc. [source] The outcome of a rapid hepatitis B vaccination programme in a methadone treatment clinicADDICTION, Issue 2 2010Parameswaran Ramasamy ABSTRACT Aim Injecting drug users are a high-risk population for hepatitis B (HBV), but are difficult to engage in vaccination programmes. This study examines the completion rates of a HBV vaccination schedule and seroconversion in a group of patients in methadone maintenance treatment. Methods Patients at a public methadone maintenance programme in Sydney, Australia, were screened for viral hepatitis (hepatitis A, B and C) and offered a rapid HBV vaccination schedule (0, 1 and 2 months). Hepatitis B surface antibody (antiHBs) was retested on completion of the vaccination schedule. Results A total of 143 patients [71.3% male, mean age 33.1 (standard deviation ± 8.3)] enrolled in the project. Forty-nine per cent of patients were HAV antibody (Ab) positive, 81.1% hepatitis C virus (HCV) antibody (Ab) positive and 38.9% antiHBs positive. Exposure to multiple hepatitis viruses was common, with 24.5% testing positive for all three viruses. Seventy-three (83%) of the 88 antiHBs negative patients completed the vaccination schedule. Post-vaccination serology indicated a seroconversion rate of 75.4% (55 of 73) of completors, or 62.5% of eligible participants (55 of 88). Conclusion While there was a high rate of completion of the rapid vaccination schedule in this population, a moderate seroconversion rate was achieved. Further work is required to identify an optimal vaccination schedule in opioid substitution patients. [source] Natural killer cells in viral hepatitis: facts and controversiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2010Mario U. Mondelli Eur J Clin Invest 2010; 40 (9): 851,863 Abstract Background, Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human hepatotropic pathogens responsible for a large number of chronic infections worldwide. Their persistence is thought to result from inefficiencies of innate and adaptive immune responses; however, very little information is available on the former. Natural killer (NK) cells are a major component of innate immunity and their activity is tightly regulated by several inhibitory and activating receptors. Design, In this review, we examine controversial findings regarding the role of NK cells in the pathogenesis of acute and chronic liver disease caused by HCV and HBV. Results, Recent studies built up on technical advances to identify NK receptors and their functional correlates in this setting. While NK cells seem to behave correctly during acute hepatitis, it would appear that the NK cytotoxic potential is generally conserved in chronic hepatitis, if not increased in the case of HCV. In contrast, their ability to secrete antiviral cytokines such as interferon ex vivo or after cytokine stimulation is severely impaired. Conclusions, Current evidence suggests the existence of an NK cell functional dichotomy, which may contribute to virus persistence, while maintaining low-level chronic liver inflammation. The study of liver-infiltrating NK cells is still at the very beginning, but it is likely that it will shed more light on the role of this simple and at the same time complex innate immune cell in liver disease. [source] HEPATITIS C AND ADDICTION: Chronic viral hepatitis is a significant contributor to the immunosenescent phenotype of parenteral drug addictionADDICTION BIOLOGY, Issue 2 2009Albert S. Reece ABSTRACT Intravenous drug addiction is known to be associated with an inordinate morbidity and mortality. As our previous report had identified an immune phenotype consistent with accelerated ageing, we wished to investigate how much of this change may have been related to chronic viral hepatitis. A total of 12 409 clinical pathology results from the period 1995,2007 were reviewed. To control for the differences in age, only patients less than 48 years of age were considered. A total of 636 substance use disorder (SUD) and 6103 non-SUD (N-SUD) patients were studied. They had comparable ages (mean ± SD 31.32 ± 6.90 versus 31.57 ± 9.23, P -value not significant), but the SUD group had more males (74.37% versus 53.20%, P < 0.001). For most of the changes examined splitting the two SUD groups into hepatitis C positive (HCV+) and hepatitis C negative (HCV,) demonstrated that the majority of the described changes were most marked in the HCV+ group. The globulins were higher in the HCV+ group and the albumin was lower and fell more markedly with age than in N-SUD or HCV, (all P < 0.001). The globulin/albumin ratio was significantly higher in HCV+ than HCV, or N-SUD (both P < 0.0001) and rose more with age. These changes were paralleled by the ESR, elevations in the CRP and lymphocyte count. Transaminases were elevated in SUD and HCV+ groups compared with N-SUD (all P < 0.02). At multivariate analysis ESR, lymphocyte count, dual hepatitis B and C seropositivity, AST and HCVAb were significant predictors of the serum globulin level and accounted for 21% of the variance. These data extend our earlier report and show that much of the immunosenescent phenotype of SUD, encompassing the known immunosuppression and the observed immunostimulation, is statistically related to chronic viral hepatitis. Important theoretical and practical management (vaccination) implications ensue. [source] Naltrexone: report of lack of hepatotoxicity in acute viral hepatitis, with a review of the literatureADDICTION BIOLOGY, Issue 1 2004Colin Brewer Many clinicians appear to be concerned about the potential hepatotoxicity of the opiate antagonist naltrexone (NTX) and this may be one reason why it is not used more widely in treating both heroin and alcohol abusers. Some much-quoted early studies noted abnormalities in liver function tests (LFTs) in very obese patients taking high doses, although there was no evidence of clinically significant liver dysfunction. These concerns may be reinforced by advice in the UK product information sheet to perform LFTs before and during treatment, by high infection rates with hepatitis C virus (HCV) among injecting heroin addicts and by the frequency of abnormal LFTs in alcohol abusers. We describe a heroin abuser in whom clinical and laboratory manifestations of acute hepatitis B and C appeared a few days after the insertion of a subcutaneous naltrexone implant. A decision was made not to remove the implant but the hepatitis resolved completely and uneventfully well within the normal time-scale. A review of the literature indicates that even when given at much higher doses than are needed for treating heroin or alcohol abusers, there is no evidence that NTX causes clinically significant liver disease or exacerbates, even at high doses, serious pre-existing liver disease. During the past decade, NTX has been shown to be safe and effective in the treatment of pruritus associated with severe jaundice caused by severe and sometimes life-threatening cirrhosis and other liver diseases. Its safety, even in these extreme conditions, is particularly reassuring. We suggest that it may be more appropriate and economical to advise patients to report promptly any suspected side effects than to perform regular LFTs, which may be misleading. [source] Chronic viral hepatitis in hemodialysis patientsHEMODIALYSIS INTERNATIONAL, Issue 2 2005Sydney Tang Abstract Ever since the first outbreaks of hepatitis in hemodialysis units in the late 1960s, a number of hepatotropic viruses transmitted by blood and other body fluids have been identified. This review summarizes the current state of knowledge regarding these blood-borne agents from an epidemiologic and preventive perspective. Data source and study selection were obtained from research and review articles related to the epidemiology of viral hepatitis in hemodialysis and indexed on Medline and Embase from 1965 to 2004. Hepatitis B virus (HBV) was the first significant hepatotropic virus to be identified in hemodialysis centers. HBV infection has been effectively controlled by active vaccination, screening of blood donors, the use of erythropoietin, and segregation of HBV carriers. To date, HBV remains an important cause of morbidity in endemic areas. Hepatitis delta virus is a defective virus that can only infect HBV-positive individuals. Hepatitis C virus is the most significant cause of non-A, non-B hepatitis and is mainly transmitted by blood transfusion. The introduction in 1990 of routine screening of blood donors for HCV contributed significantly to the control of HCV transmission. An effective HCV vaccine remains an unsolved challenge, however. Pegylation of interferon-, has made it possible to treat HCV-positive dialysis patients. Unexplained sporadic outbreaks of hepatitis by the mid-1990s prompted the discovery of hepatitis G virus and hepatitis GB virus C in 1995 and the TT virus in 1997. Although epidemiologic analyses revealed high prevalence rates of both viruses in the hemodialysis population, their exact role in liver disease has yet to be determined. The vigilant observation of guidelines on universal precaution and regular virologic testing are the cornerstones of the effective control of chronic hepatitis in the setting of hemodialysis. [source] Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: A randomized 12-month trial,HEPATOLOGY, Issue 2 2008Lindsay D. Plank Patients with liver cirrhosis exhibit early onset of gluconeogenesis after short-term fasting. This accelerated metabolic reaction to starvation may underlie their increased protein requirements and muscle depletion. A randomized controlled trial was conducted to test the hypothesis that provision of a late-evening nutritional supplement over a 12-month period would improve body protein stores in patients with cirrhosis. A total of 103 patients (68 male, 35 female; median age 51, range 28,74; Child-Pugh grading: 52A, 31B, 20C) were randomized to receive either daytime (between 0900 and 1900 hours) or nighttime (between 2100 and 0700 hours) supplementary nutrition (710 kcal/day). Primary etiology of liver disease was chronic viral hepatitis (67), alcohol (15), cholestatic (6), and other (15). Total body protein (TBP) was measured by neutron activation analysis at baseline, 3, 6, and 12 months. Total daily energy and protein intakes were assessed at baseline and at 3 months by comprehensive dietary recall. As a percentage of values predicted when well, TBP at baseline was similar for the daytime (85 ± 2[standard error of the mean]%) and nighttime (84 ± 2%) groups. For the nighttime group, significant increases in TBP were measured at 3 (0.38 ± 0.10 kg, P = 0.0004), 6 (0.48 ± 0.13 kg, P = 0.0007), and 12 months (0.53 ± 0.17 kg, P = 0.003) compared to baseline. For the daytime group, no significant changes in TBP were seen. Daily energy and protein intakes at 3 months were higher than at baseline in both groups (P < 0.0001), and these changes did not differ between the groups. Conclusion: Provision of a nighttime feed to patients with cirrhosis results in body protein accretion equivalent to about 2 kg of lean tissue sustained over 12 months. This improved nutritional status may have important implications for the clinical course of these patients. (HEPATOLOGY 2008.) [source] Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytes,HEPATOLOGY, Issue 4 2006Sean E. Doyle Interleukin-28A (IL-28A), IL-28B and IL-29 are a family of class II cytokines that stimulate antiviral responses through a heterodimeric receptor that is distinct from the type I interferon (IFN) receptor. To better understand how this newly described family of cytokines regulates the antiviral state, we compared various cellular responses elicited by IL-29 and IFN-,. Here we show that these cytokines stimulate similar patterns of signal transducer and activator of transcription 1 (STAT-1), -2, -3, and -5 phosphorylation and nearly identical patterns of gene expression when analyzed in two distinct cell types by microarray analysis. Interestingly, the IL-29 receptor is preferentially expressed on primary hepatocytes within normal liver and pegylated forms of IL-29 and IFN-, induced equivalent 2,5, oligoadenylate synthetase (OAS) and MX1 gene expression in this cell type. Pegylated IL-29 also produced a significant reduction in human hepatitis B and hepatitis C viral load in vitro and reduced the cytopathic effect caused by the fully replicating flavivirus, West Nile virus. In conclusion, IL-29 and IFN-, stimulate identical antiviral responses despite their utilization of different receptors. This fact, combined with significant receptor expression in hepatitis virus-infected livers, suggests that IL-29 may have therapeutic value against chronic viral hepatitis in human patients. (HEPATOLOGY 2006;44:896,906.) [source] Non-invasive markers for the prediction of fibrosis in chronic hepatitis C infectionHEPATOLOGY RESEARCH, Issue 8 2008Timothy Cross Liver fibrosis occurs as a result of chronic liver injury and is the hallmark of chronic liver disease. The final stage of progressive liver fibrosis is cirrhosis, which is implicated in portal hypertension, end-stage liver disease and hepatocellular carcinoma. Liver biopsy has historically been the gold standard test for the assessment of liver fibrosis for liver diseases such as viral hepatitis, autoimmune hepatitis and primary biliary cirrhosis. Improved serological tests have enhanced the diagnosis of these conditions and reduced the need for liver biopsy. Liver biopsy is unpopular among patients and clinicians. It is associated with morbidity and mortality, and in addition is subject to sampling error, inter- and intra-observer variability. There is therefore a need for non-invasive markers of liver fibrosis that are accurate, reliable, cheap and easy to use. The aim of this review is to examine the different non-invasive methods that can be used to estimate the severity of fibrosis. The methods evaluated include clinical examination, routine laboratory investigations, imaging tests, specialized tests of liver function and finally serum extra-cellular matrix markers of fibrosis. The review mainly focuses on fibrogenesis in the context of chronic hepatitis C infection. [source] Sex- or gender-specific medicine in hepatologyHEPATOLOGY RESEARCH, Issue 3 2008Sumiko Nagoshi Sex- or gender-specific medicine is an up-to-date medical science in recent medical care. Medical doctors must offer better medical care and should understand and elucidate the mechanisms underlying the sex or gender differences regarding the incidence or etiology, clinical features, and natural history or response to therapies. Sex or gender differences are frequently seen among liver diseases, such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis and hepatocellular carcinoma. The mechanisms of sex or gender differences, however, are still unclear. Clinicians and basic scientists are required to cooperatively contribute to the development of sex- or gender-specific medicine to establish an accurate diagnosis and prophylaxis. [source] HFE C282Y gene variant is a risk factor for the progression to decompensated liver disease in chronic viral hepatitis C subjects in the Czech populationHEPATOLOGY RESEARCH, Issue 9 2007Pácal Aim:, To determine the prevalence of selected HFE polymorphisms (C282Y, H63D and S65C) among patients with chronic viral hepatitis B and C and to investigate their role in the progression of liver disease. Methods:, A total of 207 subjects with chronic B or C viral hepatitis and 243 healthy controls were enrolled in the case,control study. Cases were further classified into three groups according to the clinical stage of liver disease: (A) virus carriers; (B) compensated liver disease; and (C) decompensated liver disease. HFE polymorphisms were detected by polymerase chain reaction-based methodology. Fisher's exact test, ,2 and Kruskal,Wallis tests were used to test for differences in variables studied between groups. Haplotypes were inferred in silico and their distribution compared by permutation test. Modified survival (time-to-event) analysis was used to test for the differences in the progression to the decompensated liver disease in carriers of C282Y wild-type versus mutated genotypes. Results:, The frequency of HFE genotypes, alleles and haplotypes differed neither between HBV nor HCV patients versus controls. In HCV subjects: (i) the frequency of the 282Y allele was significantly higher in the (C) group compared to (B) group (12.5 vs 2.2%, respectively, P = 0.002, Fisher's exact test); and (ii) carriers of the 282Y mutation exhibited significantly faster progression to decompensated liver disease than wild-type carriers (P = 0.044, log,rank test). Conclusion:, Carriage of the minor HFE C282Y polymorphism is associated with decompensated liver disease and its earlier onset in the subjects with chronic viral hepatitis C in the Czech population. [source] Cocirculation of and coinfections with hepatitis A virus subgenotypes IIIA and IB in patients from Pune, western IndiaHEPATOLOGY RESEARCH, Issue 2 2007Shobha Chitambar Aim:, During the 1990s, a changing pattern of epidemiology of hepatitis A was reported in different populations of India. The present study was undertaken to investigate the molecular epidemiology of hepatitis A virus (HAV) strains over a period of 10 years. Methods:, Stool/serum samples were collected from hepatitis A patients clinically presenting acute viral hepatitis and hepatic encephalopathy. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect HAV-RNA. HAV genomes were examined by sequencing PCR products of VP1/2A junction (168 bp) and RNA polymerase (116 bp) regions. Results:, Subgenotype IIIA and IB were detected in 74.2% and 9.7% of specimens, respectively, while 16.1% of patients had mixed infections. Sewage samples also showed presence of both IIIA (9/10) and IB (1/10) subgenotypes. RNA polymerase region showed two clusters constituting 51.6% and 19.4% strains closer to Nor21 and HM175 strains, respectively, in clinical specimens. Three isolates appeared as discordant subgenotypes in VP1/2A and RNA polymerase regions. Conclusion:, The data revealed cocirculation of and coinfection with subgenotypes IIIA and IB, with predominance of IIIA and genetic heterogeneity of HAV strains in western India. [source] Hazardous drinking is associated with an elevated aspartate aminotransferase to platelet ratio index in an urban HIV-infected clinical cohortHIV MEDICINE, Issue 3 2009AA Chaudhry Objectives The aim of the study was to determine the relationship between alcohol consumption and liver fibrosis as assessed by aspartate aminotransferase to platelet ratio index (APRI) in HIV-infected adults and to explore the relative contributions of alcohol and hepatitis C virus (HCV) to APRI among HIV/HCV-coinfected adults. Methods We performed a cross-sectional analysis of data from an observational clinical cohort. Alcohol consumption was categorized according to National Institute on Alcohol Abuse and Alcoholism guidelines. We defined significant liver disease as APRI>1.5, and used multinomial logistic regression to identify correlates of increased APRI. Results Among 1358 participants, 10.4% reported hazardous drinking. It was found that 11.6% had APRI>1.5, indicating liver fibrosis. Hazardous drinking was associated with increased APRI [adjusted relative risk ratio (RRR) 2.30; 95% confidence interval (CI) 1.26,4.17]. Other factors associated with increased APRI were male gender, viral hepatitis, and HIV transmission category of injecting drug use. Among coinfected individuals, 18.3% had APRI>1.5, and hazardous drinking was not associated with APRI. Among non-HCV-infected individuals, 5.3% had APRI>1.5 and hazardous drinking was associated with increased APRI (adjusted RRR 3.72; 95% CI 1.40,9.87). Conclusions Hazardous drinking is an important modifiable risk factor for liver fibrosis, particularly among non-HCV-infected patients. Clinicians and researchers must address alcohol use as the burden of liver disease increases among HIV-positive individuals. [source] Acute hepatitis C in HIV-infected men who have sex with menHIV MEDICINE, Issue 4 2004J Ghosn Background Hepatitis C virus (HCV) is usually transmitted via the parenteral route, but there are widely discrepant findings on its possible sexual transmission. Thus there are no recommendations concerning protected sex for couples in which only one partner is HCV-infected. Whether HIV or other sexually transmitted diseases could favour HCV transmission remains unclear, but recent data suggesting an increasing incidence of acute HCV in HIV-infected men underline the major public health implications of this issue. Case reports Between June 2002 and July 2003, five HIV-infected homosexually active men presented with primary (n=4) and secondary (n=1) syphilis and concomitant abnormal liver function tests revealing acute asymptomatic HCV seroconversion. Other causes of acute viral hepatitis were inquired into and excluded. Highly at-risk sexual behaviour, including unprotected anal intercourse and unsafe oral sex, with concomitant syphilis, was found to be the only identifiable important risk factor for transmission of HCV. Conclusions Sexual transmission may be fuelling a significant increase in HCV seroconversions among HIV-infected men who have highly risky sexual behaviours. Given the recent data suggesting the spread of sexually transmitted infections among HIV-infected gay men, specific recommendations concerning safe sex are urgently needed. [source] Epidemiology, risk factors, and pathogenesis of cholangiocarcinomaHPB, Issue 2 2008S. A. KHAN Abstract Cholangiocarcinoma (CCA) is a fatal cancer of the biliary epithelium, arising either within the liver (intrahepatic, ICC) or in the extrahepatic bile ducts (extrahepatic ECC). Globally, CCA is the second most common primary hepatic malignancy. Several recent epidemiological studies have shown that the incidence and mortality rates of ICC are increasing. This review of the literature on the international epidemiological rates of CCA, both intra- and extrahepatic, explores possible explanations for the trends found. The possible role of epidemiological artifact in the findings is discussed and the known risk factors for CCA are summarized. These include primary sclerosing cholangitis, liver fluke infestation, congenital fibropolycystic liver, bile duct adenomas, and biliary papillomatosis, hepatolithiasis, chemical carcinogens such as nitrosamines, Thorotrast, chronic viral hepatitis, cirrhosis, chronic non-alcoholic liver disease and obesity. Potential pathways involved in the molecular pathogenesis of CCA are also summarized. [source] Hepatocellular carcinoma in Sydney South West: late symptomatic presentation and poor outcome for mostINTERNAL MEDICINE JOURNAL, Issue 8 2007L. Gellert Abstract Background: Hepatocellular cancer (HCC) is a serious complication of cirrhosis and chronic hepatitis B infection. The aim of the study was to determine the characteristics of patients with HCC presenting within the South West Sydney area, including an analysis of the rates and benefits of hepatocellular surveillance. Methods: Data from patients with HCC presenting to Liverpool and Bankstown Hospitals from July 1993 to June 2003 were analysed retrospectively, predominantly from hospital records. Results: Of the 151 HCC patients, 41% were Asian born. Most of the patients required an interpreter. Chronic viral hepatitis infection was present in 91 patients, of whom only 7% had previously received antiviral therapy. Alcohol alone was considered responsible in 31 patients. Cirrhosis could be documented in 58% of patients. Most of the patients (75%) presented symptomatically. The median survival was 5.1 months. When HCC was detected by surveillance, the tumours were slightly but not significantly more likely to be operable and the patients tended to be offered some form of active treatment more frequently. Multivariate analysis identified detection by surveillance, lower Child,Pugh score, smaller tumour size and eligibility for some form of treatment to be associated with a more favourable outcome. Conclusion: We observed low rates of surveillance for HCC, low recognition of cirrhosis before development of HCC and low rates of prior treatment of viral hepatitis. The poor outcome of HCC in the small group who had some sort of community surveillance is also a concern requiring further investigation. [source] Apoptosis in chronic viral hepatitis parallels histological activity: An immunohistochemical investigation using anti-activated caspase-3 and M30 Cytodeath antibodyINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2005Jo L. McPartland Summary Apoptosis is implicated as a major pathogenic mechanism in chronic hepatitis B and C. Previous studies of the relationship between apoptotic rates and histological necroinflammatory activity have produced conflicting results. Hepatocyte apoptosis was assessed in liver tissue from 32 cases of chronic viral hepatitis, seven cases of hepatocellular carcinoma (HCC) and six cases of steatohepatitis as non-viral disease controls and eight cases of control liver. Apoptotic rates were measured using H&E morphological assessment and immunohistochemical staining with antibodies to activated caspase-3 and M30. Histological necroinflammatory activity of viral hepatitis cases was scored using the Knodell scoring system, and the cases were divided according to their score into group 1 (mean 2.43 ± 0.48) and group 2 (mean 7.80 ± 0.49). Apoptotic indices were significantly higher in group 2 than group 1 using H&E (11.53 ± 2.70 vs. 0 ± 0, P = 0.015) and activated caspase-3 (22.01 ± 5.27 vs. 1.79 ± 1.79, P = 0.03) methods but were not significantly higher with M30 (3.80 ± 1.74 vs. 0 ± 0, P = 0.207). Apoptotic scores using an antibody to activated caspase-3 are significantly higher in cases of chronic viral hepatitis with greater histological necroinflammatory scores, supporting a central role for apoptosis in disease pathogenesis. This method offers an alternative to routine histological assessment for measuring disease activity. [source] TLRs antiviral effect on hepatitis B virus in HepG2 cellsJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2008C. Xia Abstract Aims:, A hepatoma cell line, HepG2, was used as a model system to detect Toll-like receptor (TLR) expression in hepatocytes and examine the antiviral effect on hepatitis B virus (HBV). Methods and Results:, Toll-like receptor expression was detected in HepG2 cells by RT-PCR. The TLRs, which were strongly expressed in HepG2 cells, were stimulated with specific ligands. Interferon (IFN) response was evaluated poststimulation with Western blotting for signal transduction and activators of transcription-1. Furthermore, HepG2 cells were transiently transfected with wild-type HBV 1·3-fold over-length plasmid and treated with specific ligands at indicated times. Replication of HBV DNA, transcription of HBV RNA intermediate and expression of HBV antigens were respectively detected by Southern blotting, real time PCR, ELISA and Western blotting. Activation of different TLRs induced antiviral effects on HBV to varying degrees. Conclusions:, The TLRs, which were strongly expressed in HepG2 cells, could be stimulated with specific ligands. Activation of TLRs induced apparent production of antiviral cytokines such as IFN-,/, and inhibited HBV lifecycle in the hepatocyte cell model. Significance and Impact of the Study:, Expression of TLRs in hepatocytes may be related to local immunity of liver and participate in the outcome of viral hepatitis. [source] Improved diagnoses of autoimmune hepatitis using an anti-actin ELISAJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2008Vincent Aubert Abstract The presence of antismooth muscle antibodies is one of the diagnostic criteria of autoimmune hepatitis. We evaluated a new anti-F-actin ELISA test and compared it with indirect immunofluorescence assay (IIFA) for antismooth muscle antibodies (ASMA). Two hundred and nine serum samples (35 autoimmune hepatitis, 174 other hepatopathies and control sera) were tested by IIFA on mouse stomach kidney sections for ASMA and by the Quanta Lite Actin ELISA for anti-F-actin antibodies. ASMA were detected in 26 of 35 sera from autoimmune hepatitis (74%) as compared with 25 (71%) with anti-actin antibodies, as well as in 25 of 49 (51%) samples from viral hepatitis as compared with 7 (14%) with anti-actin antibodies. With regards to autoimmune hepatitis, though sensitivity (74.3 vs 71.4%) and negative predictive value (93.5 vs 93.9%) of ASMA and anti-actin ELISA were comparable, anti-actin ELISA was significantly better than ASMA IIFA in terms of specificity (89.7 vs 74.7%), and positive predictive value (58.1 vs 37.1%). Although frequently positive in HCV samples, a comparable sensitivity but better specificity makes the anti-actin ELISA a useful tool in combination with ASMA IIFA for the screening and diagnosis of autoimmune hepatitis. J. Clin. Lab. Anal. 22:340,345, 2008. © 2008 Wiley-Liss, Inc. [source] Th17 cells: The emerging reciprocal partner of regulatory T cells in the liverJOURNAL OF DIGESTIVE DISEASES, Issue 3 2010Li ZHAO T helper cells that produce interleukin-17 (IL-17) (Th17 cells) have recently been identified as the third distinct subset of effector T cells, the differentiation of which depends on specific transcription nuclear factor retinoic acid-related orphan nuclear receptor-,t. Emerging data have suggested that Th17 cells play an important role in innate immunity, adaptive immunity and autoimmunity. Interestingly, there is a reciprocal relationship between Th17 cells and regulatory T cells (Treg), not only in development, but also in their effector function. Transforming growth factor (TGF)-, induces Treg-specific transcription factor Forkhead box P3(FOXP3), while the addition of IL-6 to TGF-, inhibits the generation of Treg cells and induces Th17 cells. It is proposed that the fine balance between Th17 and Treg cells is crucial for maintenance of immune homeostasis. In addition to IL-6, other factors such as retinoic acid, rapamycin, or cytokines (e.g., IL-2 and IL-27) could dictate the balance between Th17 and Treg cells. Since Treg cells play an important role in hepatic immunity with overregulation in chronic viral hepatitis and hepatic carcinoma, and inadequate inhibition in autoimmune liver diseases, graft rejection and acute liver failure, it is reasonable to assume that Th17 cells may play a reciprocal role in these diseases. Thus, future research on the Treg/Th17 balance may provide an opportunity to illustrate the pathogenesis of hepatic inflammation and to explore new therapeutic targets for immune-related liver diseases. [source] Major adverse events, pretransplant assessment and outcome predictionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2009Hui-Chun Huang Abstract Liver cirrhosis and portal hypertension pose enormous loss of lives and resources throughout the world, especially in endemic areas of chronic viral hepatitis. Although the pathophysiology of cirrhosis is not completely understood, the accumulating evidence has paved the way for better control of the complications, including gastroesophageal variceal bleeding, hepatic encephalopathy, ascites, hepatorenal syndrome, hepatopulmonary syndrome and portopulmonary hypertension. Modern pharmacological and interventional therapies have been designed to treat these complications. However, liver transplantation (LT) is the only definite treatment for patients with preterminal end-stage liver disease. To pursue successful LT, the meticulous evaluation of potential recipients and donors is pivotal, especially for living donor transplantation. The critical shortage of cadaveric donor livers is another concern. In many Asian countries, cultural and religious concerns further limit the number of the donors, which lags far behind that of the recipients. The model for end-stage liver disease (MELD) scoring system has recently become the prevailing criterion for organ allocation. Initial results showed clear benefits of moving from the Child,Turcotte,Pugh-based system toward the MELD-based organ allocation system. In addition to the MELD, serum sodium is another important prognostic predictor in patients with advanced cirrhosis. The incorporation of serum sodium into the MELD could enhance the performance of the MELD and could become an indispensable strategy in refining the priority for LT. However, the feasibility of the MELD in combination with sodium in predicting the outcome for patients on transplant waiting list awaits actual outcome data before this becomes standard practice in the Asia,Pacific region. [source] Toll-like receptors and their role in gastrointestinal diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2009Adam G Testro Abstract The innate immune response to invading pathogens is centred upon a family of non-clonal, germline-encoded pattern recognition receptors (PRRs), the Toll-like receptors (TLRs). These provide specificity for a vast range of microbial pathogens, and offer an immediate anti-microbial response system. Thirteen mammalian TLRs have been described; 10 are expressed in humans, each responsible for the recognition of distinct, invariant microbial structures originating from bacteria, viruses, fungi and protozoa. The two most thoroughly studied are TLR4 and TLR2, the PRRs for Gram-negative and Gram-positive bacterial products, respectively. TLR4 is also the major receptor recognising endogenous ligands released from damaged or dying cells. Activation of a TLR by its relevant ligand rapidly ignites a complex intracellular signaling cascade that ultimately results in upregulation of inflammatory genes and production of proinflammatory cytokines, interferons and recruitment of myeloid cells. It also stimulates expression, upon antigen presenting cells, of co-stimulatory molecules required to induce an adaptive immune response. Whilst a robust TLR response is critical for survival and defence against invading pathogens, inappropriate signaling in response to alterations in the local microflora environment can be detrimental. Such ,unhelpful TLR responses' could form the basis for a large number of gastrointestinal and liver disorders, including inflammatory bowel disease, viral hepatitis, autoimmune liver diseases and hepatic fibrosis. As our understanding of TLRs expands, the pathogenesis of a number of gastrointestinal disorders will be further elucidated, and this offers potential for specific therapies aimed directly at TLR signaling. [source] Des-,-carboxyprothrombin, ,-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinomaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2008Francisco A Durazo Abstract Background and Aim:, Hepatocellular carcinoma (HCC) is a common complication in patients with chronic viral hepatitis. Detection of HCC at an early stage is critical for a favorable clinical outcome. The study aim was to: (i) compare the levels of des-,-carboxyprothrombin (DCP), ,-fetoprotein (AFP) and AFP-L3 in HCC patients and in chronic viral hepatitis patients without HCC; (ii) define the level of each tumor marker with the best sensitivity and specificity for HCC diagnosis; and (iii) to correlate the levels of these markers with respect to size and tumor burden. Methods:, Two hundred and forty patients with either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection were studied. These included 144 with HCC, 47 with chronic hepatitis (fibrosis stage I,III on liver biopsy) and 49 with cirrhosis. Results:, Levels of DCP, AFP and AFP L-3 were significantly higher in patients with HCC than in those without HCC (P , 0.0001). Receiver,operating curves (ROC) indicated that the cut-off value with the best sensitivity and specificity for each test was ,84 mAU/mL for DCP, ,25 ng/mL for AFP and ,10% for AFP-L3. The sensitivity, specificity and positive predictive value (PPV) for DCP was 87%, 85% and 86.8%, for AFP 69%, 87% and 69.8%, and for AFP-L3 56%, 90% and 56.1%, respectively. DCP levels were below the ROC cut-off in all patients without HCC. In patients with single lesions, there was a direct correlation of DCP to tumor size. High levels of AFP correlated with diffuse type of HCC. All three markers were significantly elevated in the presence of metastatic HCC. No advantage was observed by combining two or three markers for HCC diagnosis. Conclusion:, DCP had the highest sensitivity and PPV for HCC diagnosis, had a direct correlation with tumor size, and was not elevated in any patients without HCC. DCP should be used as the main serum test for HCC detection. [source] Increasing trend of acute hepatitis A in north India: Need for identification of high-risk population for vaccinationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2006Zahid Hussain Abstract Background and Aims:, Hepatitis A (HAV) is endemic in India and most of the population is infected asymptomatically in early childhood with lifelong immunity. Because of altered epidemiology and decreasing endemicity, the pattern of acute HAV infection is changing from asymptomatic childhood infection to an increased incidence of symptomatic disease in the 18,40 age group. The aims of the present study were to assess whether the proportion of adults with acute HAV infection has been increasing over the years and to analyze the seroprevalence of immunoglobulin G (IgG) anti-HAV antibodies in young adults above the age of 15 years as well as in cases of chronic liver disease. Methods:, Sera collected from 3495 patients with acute (1932) and chronic (1563) liver disease attending the Medical Outpatient Department of Lok Nayak Hospital during the previous five years (1999,2003) were tested for various serological markers of acute (HBsAg, HBcIgM, anti-HCV, HEV-IgM, and HAV-IgM) and chronic (HBsAg, HBcIgG, HBeAg, and anti-HCV) hepatitis. In addition, 500 normal healthy attendants of the patients above the age of 15 years were tested for IgG anti-HAV as controls. Results:, Of 1932 patients with acute viral hepatitis, 221 (11.4%) were positive for immunoglobulin M (IgM) anti-HAV. The patients who were IgM anti-HAV negative included hepatitis B (321 patients), C (39 patients), E (507 patients) and unclassified (844 patients). Although the frequency of HAV infection among children had increased (10.6% to 22.0%) in the 5-year period, the frequency of HAV infection among adults had also increased (3.4% to 12.3%) during the same period. A total of 300 patients with chronic liver diseases that were etiologically related to hepatitis B (169), C (73) or dual infection (10) and alcoholic liver injury (48) were tested for the presence of IgG anti-HAV antibody; 98% (294/300) were positive for the antibody. Conclusions:, Although universal vaccination against HAV is not currently indicated, selective vaccination of the high-risk population, based on their serological evidence of HAV antibody, would be a rational and cost-effective approach. [source] Glucose-6-phosphate dehydrogenase deficiency is associated with increased initial clinical severity of acute viral hepatitis AJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2001Israel Gotsman Abstract Background and Aim: In glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme is deficient in liver cells as well as in erythrocytes. It has been suggested that this may be associated with a more severe clinical presentation of acute viral hepatitis A. The aim of this study is to determine the severity of liver disease in patients with viral hepatitis and G6PD deficiency. Methods: Eighteen patients with diagnosed G6PD deficiency and acute hepatitis A were compared with 18 matched control patients with hepatitis A in a university hospital for liver disease severity and clinical outcome. Results: Two of 18 patients with G6PD deficiency had neurological deterioration. Patients with G6PD deficiency had a mean peak prothrombin time (PT) that was significantly prolonged as compared with the control group (15.5 ± 3.7 vs 12.9 ± 2.0 s, respectively, P < 0.02), and a significantly higher proportion had an abnormal PT (PT > 13.3 s): 61 versus 11% (P < 0.0001). Hemolysis occurred in 44% of the G6PD deficiency patients. Total and direct bilirubin were significantly higher in all patients with G6PD deficiency, including patients without hemolysis. There was no significant difference in liver enzyme levels between the two groups. Patients with G6PD deficiency had a longer average hospital stay (9.5 ± 4.8 vs 3.4 ± 0.8 days, respectively, P < 0.001). There was no difference in the final clinical outcome between the two groups, and recovery of liver function was seen in all patients. Conclusions: Glucose-6-phosphate dehydrogenase deficiency in patients with hepatitis A causes a more severe initial clinical presentation, but does not alter the final clinical outcome. [source] | |||||||||||||||||||||||||||||||||||||