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Chronic Viral Hepatitis (chronic + viral_hepatitis)
Terms modified by Chronic Viral Hepatitis Selected AbstractsHEPATITIS 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] 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] 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] 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] 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] 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] 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] 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] Optimal surveillance of hepatocellular carcinoma in patients with chronic viral hepatitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2001Deng-Yn Lin No abstract is available for this article. [source] Circulating soluble cytochrome c in liver disease as a marker of apoptosisJOURNAL OF INTERNAL MEDICINE, Issue 2 2003Z. Ben-Ari Abstract. Ben-Ari Z, Schmilovotz-Weiss H, Belinki A, Pappo O, Sulkes J, Neuman MG, Kaganovsky E, Kfir B, Tur-Kaspa R, Klein T (Beilinson and Golda Campuses, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and In Vitro Toxicology Laboratory, Sunnybrook Women's College, Toronto, Canada) Circulating soluble cytochrome c in liver disease as a marker of apoptosis. J Intern Med 2003; 254: 168,175. Objectives. To measure levels of soluble cytochrome c, a clinical marker of apoptosis in patients with liver disease; determine whether soluble cytochrome c is derived from the liver; and correlate soluble cytochrome c level with histology and disease activity. Design. Laboratory research study with comparison group. Setting. Liver Institute, at the Rabin Medical Center, Israel, and In Vitro Toxicology Laboratory, Canada. Subjects. A total of 108 patients with liver disease and 30 healthy controls. Interventions. Paired hepatic and portal vein samples were taken via the transjugular vein in patients after liver biopsy and transjugular intrahepatic portacaval shunt, and bile from patients with external biliary drainage. Soluble cytochrome c was measured with an enzyme-linked immunosorbent assay in peripheral blood. Apoptotic cells in liver tissue were identified by morphological criteria and quantitated with the dUTP nick-end-labelling (TUNEL) assay. Main outcome measures. Soluble cytochrome c level by type of liver disease by clinical and histological findings. Results. Soluble cytochrome c concentration (mean 187.1 ± 219.5 ng mL,1) was significantly higher in patients with liver disease than in controls (39.8 ± 35.1 ng mL,1; P = 0.0001), with highest levels in the primary sclerosing cholangitis group (mean 1041.0 ± 2844.8 ng mL,1; P = 0.001). Cytochrome c levels were correlated with serum bilirubin, alkaline phosphatase, creatinine levels, necroinflammatory score and apoptotic index, but not with serum alanine aminotransferase and synthetic liver function tests. In the 16 paired samples, soluble cytochrome c level was higher in the hepatic (mean 267.9 ± 297.0 ng mL,1) than the portal vein (mean 169.2 ± 143.3 ng mL,1), and it was highly detectable in bile (mean 2288.0 ±4596.0 ng mL,1) (P = 0.001). Untreated patients with chronic viral hepatitis (B and C) had significantly higher levels (mean 282.8 ±304.3 ng mL,1) than treated patients (77.9 ± 35.8 ng mL,1; P = 0.001). Conclusions. Soluble cytochrome c levels are increased in different types of liver disease. Soluble cytochrome c is probably derived from the liver and secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble cytochrome c may serve as a serum marker of apoptosis. [source] Safety and efficacy of pegylated interferon and ribavirin in adolescents with human immunodeficiency virus and hepatitis C virus acquired perinatallyJOURNAL OF MEDICAL VIROLOGY, Issue 7 2010Raffaella Rosso Abstract Limited evidence is available currently regarding the efficacy and safety of pegylated interferon (PEG-IFN) and ribavirin in patients co-infected perinatally with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). No information is available on whether or not these patients should be treated earlier for infection with HCV. This report describes four patients with HIV and HCV co-infection acquired perinatally, who were treated with PEG-IFN and ribavirin for chronic viral hepatitis caused by HCV. J. Med. Virol. 82: 1110,1114, 2010. © 2010 Wiley-Liss, Inc. [source] Intrahepatic long-term persistence of parvovirus B19 and its role in chronic viral hepatitis,JOURNAL OF MEDICAL VIROLOGY, Issue 12 2009Chun Wang Abstract Parvovirus B19 (B19V) has been detected in the liver of Asian patients infected with HBV and may contribute to acute and chronic liver disease. This study aimed to investigate the impact of B19V infection in European patients with viral hepatitis. B19V DNA was detected in 1/91 and 0/50 serum samples from patients with chronic hepatitis C and B, respectively. In contrast, B19V DNA was amplified frequently from explanted end-stage liver tissues (37/50, 74%) and from routine biopsy samples (14/32, 44%) (P,<,0.05). However, there was no significant difference in B19V copy number per cell between these two groups. B19V-specific CD4+ T-cell responses to two dominant MHC-class-restricted epitopes were detected in a similar frequency in healthy anti-B19V-positive individuals (3/19; 16%) and patients with chronic hepatitis C (3/13; 23%). These results indicate that B19V can persist in the liver. However, there is no evidence that B19V is a "hepatitis virus" worsening liver disease in European patients with chronic hepatitis C. J. Med. Virol. 81:2079,2088, 2009. © 2009 Wiley-Liss, Inc. [source] Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcomeJOURNAL OF VIRAL HEPATITIS, Issue 3 2008C. Castellares Summary., Liver disease is frequently seen in HIV+ patients as a result of coinfection with hepatitis B (HBV) or C (HCV) viruses, alcohol abuse and/or exposure to hepatotoxic drugs. The aim of this study was to assess the prevalence of liver cirrhosis, its main causes and clinical presentation in HIV+ patients. Observational, cross-sectional, retrospective study of all HIV+ individuals followed at one reference HIV outpatient clinic in Madrid. Liver fibrosis was measured in all cases using transient elastometry (FibroScan®). All 2168 HIV+ patients on regular follow-up (76% males, 46% injecting drug users) were successfully examined by FibroScan® between October 2004 and August 2006. Liver cirrhosis was recognized in 181 (overall prevalence, 8.3%), and the main aetiologies were HCV, 82.3%; HBV, 1.6%; dual HBV/HCV, 2.8%; and triple HBV/HCV/ hepatitis delta virus (HDV) infection, 6.6%. The prevalence of cirrhosis differed among patients with distinct chronic viral hepatitis: HCV, 19.2%; HBV, 6.1%; HBV/HCV, 41.7%; and HBV/HCV/HDV, 66.7%. In 12 patients with cirrhosis (6.7%), no definite aetiology was recognized. Overall, cirrhotics had lower mean CD4 counts than noncirrhotics (408 vs 528 cells/,L respectively; P = 0.02), despite similar proportion of subjects with undetectable viraemia on highly active antiretroviral therapy. Clinical manifestations of liver cirrhosis were: splenomegaly, 61.5%; oesophageal varices, 59.8%; ascites, 22.6%; encephalopathy, 12.1%; and variceal bleeding, 6.1%. Liver cirrhosis and hepatic decompensation events are relatively frequent in HIV+ individuals. Chronic HCV and alcohol abuse, but not chronic HBV, play a major role. Transient elastometry may allow the identification of a significant number of HIV+ individuals with asymptomatic liver cirrhosis. [source] Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendationsJOURNAL OF VIRAL HEPATITIS, Issue 1 2004V. Soriano Summary., Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients. [source] Surveillance programme for hepatocellular carcinoma improves the survival of patients with chronic viral hepatitisLIVER INTERNATIONAL, Issue 1 2008Grace Lai-Hung Wong Abstract Background: The survival benefit of surveillance for hepatocellular carcinoma (HCC) is controversial. Aim: We aimed to examine the survival benefit of HCC surveillance in chronic viral hepatitis. Methods: Survivals of HCC patients related to chronic viral hepatitis from the Hepatology Clinic (surveillance group) were compared with those referred from other hospitals/clinics (no-surveillance group). Lead-time and length-time biases were adjusted based on tumour volume doubling times. Results: Among 579 patients (91% hepatitis B), 472 (82%) patients had HCC and 79 (17%) of these patients were referred from the surveillance programme. HCC was smaller (4.2 vs. 7.7 cm; P<0.001) and fewer in numbers (2.6 vs. 3.8, P=0.03) in the surveillance group vs. the no-surveillance group. Treatment by surgery (20 vs. 10%, P=0.007) and local ablative therapy (46 vs. 19%, P<0.001) were more frequent in the surveillance group than that in the no-surveillance group. The median survival of the surveillance group (88 weeks) was significantly longer than that of the no-surveillance group (26 weeks) (P<0.001). The adjusted cumulative survival at 2 years was significantly longer in the surveillance group if the tumour volume doubling time was <90 days (P=0.0352). Conclusions: HCC surveillance can improve the survival of patients with chronic viral hepatitis B. [source] Expression of oxidative stress-related molecules in circulating leukocytes and urine in patients with chronic viral hepatitisLIVER INTERNATIONAL, Issue 2 2006Toshiya Saeki Abstract: Aims: Oxidative stress plays a role in pathogenesis of chronic viral hepatitis. Expression of oxidative stress-related molecules remains to be clarified. Methods: 4-hydroxy-2-nonenal (4-HNE), 4-hydroxy-2-hexenal (4-HHE), catalase, superoxide dismutase-1 (SOD-1), glutathione peroxidase-1, thioredoxin (TRX) in leukocytes and urinary 8-hydroxy-2,-deoxyguanosine (8-OHdG) were examined in 164 persons, including 130 chronic viral hepatitis patients and 34 normal individuals, by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Hepatic expression of these proteins was immunohistochemically examined in 12 patients with chronic viral hepatitis, compared with three persons without liver damage. Results: The 4-HNE/,-actin ratios in chronic viral hepatitis were significantly higher than those in normal individuals (P<0.01), and were significantly correlated with asparate aminotransferase (AST) and alanine aminotransferase (ALT) (P<0.01, each). The catalase/,-actin and SOD-1/,-actin ratios in chronic viral hepatitis were higher than those in normal individuals, and were significantly correlated with 4-HNE/,-actin ratios (P<0.01, each). Hepatic expression of 4-HNE, 4-HHE, catalase, SOD-1 and TRX in chronic viral hepatitis was higher than that without liver damage. Urinary excretion of 8-OHdG was not changed in chronic viral hepatitis. Conclusions: The results of the present study suggest that expression of oxidative stress-related molecules in leukocytes is upregulated in relation to serum aminotransferase levels. [source] Study of the effects of interferon a on several human hepatoma cell lines: analysis of the signalling pathway of the cytokine and of its effects on apoptosis and cell proliferationLIVER INTERNATIONAL, Issue 2 2004A. Legrand Background: Interferon , (IFN,), currently used for the treatment of chronic viral hepatitis, is also known to prevent the development of hepatocellular carcinoma (HCC), the mechanism of this action being still debatable. Aims: To study thoroughly in human hepatoma cell lines (HHL) , Hep3B, HepG2, HuH7, SKHep1, and Chang-Liver , submitted to rhIFN,, the signalling pathway of IFN,, the binding activity of the cytokine on specific gamma-activated sequence (GAS) and interferon-stimulated regulatory element (ISRE) nuclear sequences, and its effects on apoptosis and cell proliferation. Methods: The behaviour of signal transducer and activator of transcription (STAT)1, STAT2, p48IRF9 and the binding of nuclear proteins were investigated by immunoblot and electro-mobility shift assay. Expression of some IFN,-dependent proteins , p21/WAF1, inducible nitric oxide synthase, IRF1 and 2 , were studied by immunoblot. Apoptosis and the cell cycle were studied by morphological and biochemical methods. Results: Transduction of INF, was unaltered, although there were some variations in the different HHL. Nuclear protein binding to GAS or ISRE showed that ISRE was mainly involved. Apoptosis did not occur. The cell cycle was slightly modified in HuH7. Three GAS- and/or ISRE-dependent proteins increased, suggesting that IFN, may have some biological effects on HHL. Conclusions: The IFN, signalling pathway is functional in several HHL, but the cytokine has no apoptotic effect and a moderate anti-proliferative effect. This suggests that the preventive role of IFN, on HCC cannot be explained by an apoptotic and/or an anti-proliferative effect, but possibly by its action on several specific nuclear sequences that protect liver cells from transformation. [source] Expression of uncoupling protein-2 in biliary epithelial cells in primary biliary cirrhosisLIVER INTERNATIONAL, Issue 6 2002Eitaro Taniguchi Abstract:Background/Aims: Uncoupling proteins are thought to protect cells from oxidative stresses. Because uncoupling protein-2 is expressed in liver and reactive oxygen species are involved in pathogenesis of various liver diseases, this protein may protect liver cells from disease-associated oxidative stress. However, uncoupling protein-2 expression in human liver has not been examined. Methods: We investigated hepatic uncoupling protein-2 distribution in various liver diseases including primary biliary cirrhosis, autoimmune hepatitis, chronic viral hepatitis, and histologically normal liver by immunohistochemistry.Results: Uncoupling protein-2 was expressed in some hepatocytes, however, the degree of hepatocytic uncoupling protein-2 expression did not differ significantly among liver diseases and normal liver. Uncoupling protein-2 was abundant in biliary epithelial cells in primary biliary cirrhosis but not in other liver specimens. Enhanced uncoupling protein-2 expression in biliary epithelial cells was specific for primary biliary cirrhosis and did not result simply from cholestasis. The percentage of uncoupling protein-2 positive bile ducts in primary biliary cirrhosis patients treated with ursodeoxycholic acid was significantly lower than in untreated patients.Conclusions: These results suggest that uncoupling protein-2 is involved in the pathogenesis of primary biliary cirrhosis. [source] Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequencesLIVER INTERNATIONAL, Issue 4 2001Dimitrios-Petrou Bogdanos Abstract: The pathogenesis of autoimmune liver disease and autoimmunity associated with chronic viral hepatitis remains poorly understood. One of the major hurdles to a deeper understanding of these pathological processes is the absence of clearly defined inductive mechanisms, which, if identified and characterised, could guide clinical strategies for their prevention or allow therapeutic intervention. Molecular mimicry leading to crossreactive autoimmune responses has gained strong experimental support in the past decade. A fundamental premise of this hypothesis is the involvement of a mimicking environmental trigger. In view of the numerous viral and bacterial agents epidemiologically linked to autoimmune liver diseases, we and others have proposed molecular mimicry to be an important mechanism in these diseases. We also propose similar crossreactive mechanisms to operate in the generation of autoimmunity in viral hepatitis. This review focuses on molecular mimicry at the level of the B-cell, as few data on T-cell crossreactivity in liver disease are thus far available. [source] Expression of gap junction protein connexin 32 in chronic liver diseasesLIVER INTERNATIONAL, Issue 2 2000Kazuaki Yamaoka Abstract:Background: Gap junctions contain intercellular channels through which contacting cells communicate directly. The expression of connexin 32, a major gap junction protein in the liver, during the progression of chronic liver diseases has not yet been clarified. Methods: Immunohistochemical staining was performed using anti-connexin 32 antibody on 6 specimens of normal human liver, 7 of chronic viral hepatitis, and 7 of liver cirrhosis. Results: The number of gap junction plaques in chronic viral hepatitis and liver cirrhosis was significantly smaller than that in normal liver (10350±2180 and 7550±3040 vs 22560±3700 spots/mm2, p<0.01). The number of gap junction plaques tended to be lower in liver cirrhosis than in chronic viral hepatitis. Conclusion: These results suggest that in chronic liver diseases impaired intercellular communication between hepatocytes occurs. [source] Dysplastic nodules frequently develop into hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosisCANCER, Issue 3 2006Masahiro Kobayashi M.D. Abstract BACKGROUND Advances in imaging technology have enhanced the detection of small nodular lesions during the course of chronic liver disease. METHODS Between 1995 and 2002, the authors examined 154 consecutive patients with small hepatic nodules without hepatocellular carcinoma (HCC) over a median duration of 2.8 years. The median size of these nodules was 14 mm (range, 7,40 mm). The initial histopathologic diagnosis included high-grade dysplastic nodule (HGDN) (n = 13), low-grade dysplastic nodule (LGDN) (n = 42), and regenerative nodule (RN) (n = 99). RESULTS A total of 29 (18.8%) nodules developed into HCC during the observation period. Cumulative HCC development rates at the first, third, and fifth year were 46.2%, 61.5%, and 80.8% for HGDN; 2.6%, 30.2%, and 36.6% for LGDN; and 3.3%, 9.7%, and 12.4% for RN, respectively. The rate of HCC development was significantly higher in the HGDN group than for other types (P < 0.001). Multivariate analysis disclosed that histopathologic diagnosis (P < 0.001) and findings on computed tomographic arterial portography (CT-AP) (P = 0.004) were significantly associated with future HCC development. The hazard ratios of HGDN and LGDN were 16.8 (95% confidence interval [CI], 6.19,45.6) and 2.96 (95% CI, 1.20,7.31), respectively. A decrease in portal blood flow also showed a significantly high hazard ratio of 3.04 (95% CI, 1.42,6.50). Approximate annual development rate to HCC was 20% in patients with HGDN and 10% in LGDN. CONCLUSION HGDN should be considered a precancerous lesion when it appears during follow-up of chronic viral hepatitis or cirrhosis. Reduced portal blood flow in the nodule on computed tomography-AP is also an important predictor for development of hepatocellular carcinoma. Cancer 2006. © 2005 American Cancer Society. [source] | ||||||||||||||||||||||||||||