|
| ||
|
|
||
Bridging Fibrosis (bridging + fibrosis)
Selected AbstractsSerological markers of autoimmunity in patients infected with hepatitis C virus: impact of HIV co-infectionHIV MEDICINE, Issue 6 2005OM Adeyemi Objectives: We sought to evaluate the prevalence, predictors and significance of autoantibody expression in patients with chronic hepatitis C (CHC) with or without HIV co-infection. Methods: Retrospective review of laboratory and histologic data for all patients with CHC who had a liver biopsy available. HIV status was documented in all patients. Results analyzed in SPSS10, Chicago, IL, a p value <0.05 was considered significant. Results: 170 patients with hepatitis C viremia, including 107 (63%) HIV co-infection, who had testing for anti-nuclear antibody (ANA) or anti-smooth muscle antibody (ASMA) and anti-mitochondrial antibody (AMA) were included in the study. Overall, 63% (74/117) of patients were ASMA seropositive and 6% (9/153) were positive for ANA. All 117 patients tested for AMA were negative. HIV co-infected patients were significantly more likely to be ASMA positive 71% (53/75) compared to those with hepatitis C alone (50%) [P=0.026]. There were no significant differences in age, gender, race, risk group, alanine aminotransferase (ALT) levels or grade of inflammation on histology between autoantibody positive and negative patients. ASMA positive patients had significantly higher globulin levels (P=0.036) and a trend towards more bridging fibrosis or cirrhosis. Patients with autoantibody expression rarely had histologic features of AIH. Conclusion: We found a high rate of ASMA seropositivity in our cohort of patients with chronic hepatitis C, and HIV co-infection was associated with significantly higher rates of ASMA expression. Autoantibody expression was not associated with demographic or clinical characteristics and does not necessarily preclude antiviral therapy. [source] Meta-analysis: re-treatment of genotype I hepatitis C nonresponders and relapsers after failing interferon and ribavirin combination therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010A. G. Singal Aliment Pharmacol Ther 2010; 32: 969,983 Summary Background, The efficacy of re-treating genotype I hepatitis C virus (HCV) patients who failed combination therapy with interferon/pegylated interferon (PEG-IFN) and ribavirin remains unclear. Aims, To quantify sustained virological response (SVR) rates with different re-treatment regimens through meta-analysis of randomized controlled trials (RCTs). Methods, Randomized controlled trials of genotype I HCV treatment failure patients that compared currently available re-treatment regimens were selected. Two investigators independently extracted data on patient population, methods and results. The pooled relative risk of SVR for treatment regimens was computed using a random effects model. Results, Eighteen RCTs were included. In nonresponders to standard interferon/ribavirin, re-treatment with high-dose PEG-IFN combination therapy improved SVR compared with standard PEG-IFN combination therapy (RR = 1.49; 95% CI: 1.09,2.04), but SVR rates did not exceed 18% in most studies. In relapsers to standard interferon/ribavirin, re-treatment with high-dose PEG-IFN or prolonged CIFN improved SVR (RR = 1.57; 95% CI: 1.16,2.14) and achieved SVR rates of 43,69%. Conclusions, In genotype I HCV treatment failure patients who received combination therapy, re-treatment with high-dose PEG-IFN combination therapy is superior to re-treatment with standard combination therapy, although SVR rates are variable for nonresponders (,18%) and relapsers (43,69%). Re-treatment may be appropriate for select patients, especially relapsers and individuals with bridging fibrosis or compensated cirrhosis. [source] Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT-C trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009G. T. EVERSON Summary Backgroud, The impact of virologic response on hepatic function has not been previously defined. Aim, To determine the relationships of quantitative liver function tests (QLFTs) with virological responses to peginterferon (PEG) ± ribavirin (RBV) in patients with chronic hepatitis C and to use serial QLFTs to define the spectrum of hepatic improvement after sustained virological response (SVR). Methods, Participants (n = 232) were enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial, had failed prior therapy, had bridging fibrosis or cirrhosis and were retreated with PEG/RBV. All 232 patients had baseline QLFTs; 24 patients with SVR and 68 nonresponders had serial QLFTs. Lidocaine, [24- 13C]cholate, galactose and 99mTc-sulfur colloid were administered intravenously; [2,2,4,2- 2H]cholate, [1- 13C]methionine, caffeine and antipyrine were administered orally. Clearances (Cl), breath 13CO2, monoethylglycylxylidide (MEGX), perfused hepatic mass (PHM) and liver volume were measured. Results, Rates of SVR were 18,26% in patients with good function by QLFTs, but ,6% in patients with poor function. Hepatic metabolism, measured by caffeine kelim (P = 0.02), antipyrine kelim (P = 0.05) and antipyrine Cl (P = 0.02) and the portal circulation, measured by cholate Cloral (P = 0.0002) and cholate shunt (P = 0.0003) and PHM (P = 0.03) improved after SVR. Conclusion, Hepatic dysfunction impairs the virological response to PEG/RBV. SVR improves hepatic metabolism, the portal circulation and PHM. [source] Safety and efficacy of peginterferon plus ribavirin in patients with chronic hepatitis C and bridging fibrosis or cirrhosisJOURNAL OF VIRAL HEPATITIS, Issue 4 2005F. Marrache Summary., The combination of pegylated interferon and ribavirin is the most effective therapy in patients with chronic hepatitis C. We evaluated this combination in unselected patients with bridging fibrosis or cirrhosis. Eighty patients were treated with peginterferon alpha-2b plus ribavirin. Hepatitis C virus serum RNA was monitored. Tolerance and safety were evaluated by the rate of treatment's discontinuation for any reason, and occurrence of serious clinical adverse events, respectively. Sustained virologic response (SVR) rate was 36.3% overall, and was observed in every group of patients except those who had previously failed to respond to the combination of interferon and ribavirin. No serious clinical adverse event occurred. Treatment was withdrawn in 18.7% of patients. Variables associated with discontinuation of treatment were low prothrombin index [OR: 1.16 (1.05;1.27)] and low body mass index [OR: 1.47 (1.12;1.92)]. Initial blood count abnormalities were not associated with cessation of treatment. Furthermore, early virologic response at week 8 and week 12 of treatment had similar predictive value for SVR. Combination therapy with peginterferon plus ribavirin seems effective in this group of patients, except in those who had previously failed to respond to the combination of interferon and ribavirin. This therapy is safe with appropriate monitoring, but tolerance seems worse in patients with the most advanced liver disease. [source] Novel fibrinogen mutation ,314Thr,Pro (fibrinogen AI duPont) associated with hepatic fibrinogen storage disease and hypofibrinogenaemiaLIVER INTERNATIONAL, Issue 10 2010Stephen O. Brennan Abstract Mutation in fibrinogen genes may lead to quantitative or qualitative disorders that result in bleeding, thrombosis or hepatic fibrinogen storage disease. Only three mutations in the fibrinogen , gene have been identified that cause hepatic endoplasmic reticulum storage of mutant fibrinogen. To investigate the possibility of hepatic fibrinogen storage disease in a 4-year-old male with persistently elevated serum aminotransferases and preserved synthetic function except for a prolonged INR. After informed consent, liver and blood samples were obtained. Liver sections were examined by light microscopy, anti-fibrinogen immunolabelling and electron microscopy. Purified fibrinogen was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and reverse phase high performance liquid chromatography; DNA sequencing was performed using a BigDye Terminator (v. 3.1) cycle sequencing kit. Four-year-old male with persistently elevated transaminases with an INR 1.5 but otherwise normal synthetic function. Fibrinogen activity and thrombin clotting time were abnormal at 0.47 g/L and 46 s respectively. Hepatic histological examination revealed portal inflammatory infiltrates with bridging fibrosis. Clumped eosinophilic material was observed in hepatocytes that was immunoreactive to fibrinogen antisera. Ultrastructural examination showed cytoplasmic inclusions arrayed in fingerprint-like patterns. DNA sequence analysis revealed heterozygosity for a novel ,314Thr ,Pro mutation (fibrinogen AI duPont) in the fibrinogen , gene. Protein analyses showed normal patterns of A,, B, and , chains suggesting that the variant , allele was not expressed in plasma fibrinogen. We describe only the fourth mutation to be identified, ,314Thr,Pro (fibrinogen AI duPont), giving rise to hypofibrinogenaemia and hepatic fibrinogen storage disease. [source] Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in miceLIVER INTERNATIONAL, Issue 8 2009Wing-Kin Syn Abstract Objective: To determine how genetic factors might influence the progression of nonalcoholic fatty liver disease (NAFLD). Design/Intervention: Beginning in adolescence, male C57BL6 (BL6) and 129/SVJ mice were fed control (n=15/group) or high-fat (HF) diets (n=30/group) for 6 months. Main Outcome Measures: Assessed were body weight, insulin resistance, hepatic production of free radicals, expression of cytokines and fibrosis-related genes and severity of hepatic steatosis, injury and fibrosis. Results: High-fat diets induced comparable obesity, hepatic steatosis and insulin resistance in the two strains. Compared with BL6 mice, 129/SVJ mice had impaired induction of antioxidant genes, generated three- to four-fold more free radicals and exhibited two-fold greater induction of profibrogenic cytokines (interleukin-4 and transforming growth factor-,1) and fibrosis-related genes (fibronectin and tissue inhibitor of metalloproteinase-1) (all P<0.05 for 129 vs BL6). Surprisingly, however, induction of collagen I ,1 mRNA and accumulation of Sirius red-stained fibrils and hepatic hydroxyproline were similar in BL6 and 129/SVJ mice, and although patchy sinusoidal fibrosis emerged in both strains, neither developed bridging fibrosis. Conclusions: Although BL6 and 129/SVJ mice with diet-induced obesity, insulin resistance and steatosis differed with respect to several factors that are thought to influence human NAFLD progression, they developed comparable liver fibrosis. Moreover, none of the risk factors for NAFLD-related cirrhosis in humans, including obesity, insulin resistance, chronic inflammatory and oxidant stress, steatohepatitis or activation of fibrogenic genes, proved to be sufficient to cause cirrhosis in these mice, even when exposure to one or more of these insults was very prolonged. [source] Pretransplant MELD Score As a Predictor of Outcome After Liver Transplantation for Chronic Hepatitis CAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2003Nicholas N. Onaca The Model of End-Stage Liver Disease (MELD) score, an accurate predictor of mortality in patients awaiting liver transplantation (OLTX), did not predict graft or patient survival in the post-transplant setting. Our aim was to test the model in patients who underwent OLTX for chronic hepatitis C. Two hundred and eighty-seven adult patients who underwent primary OLTX for chronic hepatitis C between December 1993 and September 1999 were studied from a prospectively maintained database. The group was stratified by MELD scores of less than 15, 15,24, and greater than 24. Patient survival, graft survival, and interval liver biopsy pathology were reviewed. Both patient and graft survival at 3, 6, and 12 months were significantly lower in the higher MELD score groups, as was patient survival at 24 months (p-values, 0.01,0.05). The difference in survival between the low, medium, and high MELD score groups increases in time. The survival without bridging fibrosis in the allograft at 1 year post-transplant was significantly lower with higher MELD scores (p = 0.037). The decrease in survival seen in hepatitis C patients with MELD scores greater than 24 raises questions of transplant suitability for these patients. Therapeutic modalities to decrease post-transplant graft injury in these patients should be explored. [source] Bridging necrosis and reticulin bridging fibrosis induced by intrahepatic involvement of acute biphenotypic leukemia,APMIS, Issue 12 2006Case report A 47-year-old Japanese woman was diagnosed as having acute biphenotypic leukemia with association of t(9;22)(q34;q11). Cholestatic liver dysfunction arose, and she died of cachexia and intracranial hemorrhage. Autopsy showed unusual hepatic fibrosis. In the liver, bridging infiltration, bridging necrosis and bridging fibrosis by leukemic cells were seen. It seemed that the degree of fibrosis was associated with the number of aggregates of infiltrating leukemic cells. The fibrotic foci were predominantly composed of reticulin and collagen fibers, and distortion of the lobules was observed. Immunohistochemically, dense bundles of alpha-smooth muscle actin (ASMA)-positive stromal cells, namely activated hepatic stellate cells (HSCs), were observed in the immature fibrotic foci as well as along the sinusoids densely infiltrated by leukemic cells. No cells positive for TGF-,1 or PDGF-BB were identified. In conclusion, extensive intrahepatic involvement by neoplastic cells in adult acute biphenotypic leukemia may cause the unusual "disorganized" hepatic fibrosis. [source] Use of lidocaine metabolism to test liver function during the long-term follow-up of liver transplant recipientsCLINICAL TRANSPLANTATION, Issue 3 2004Filoména Conti Abstract:, Background/Aims:, The aim of this study was to assess the usefulness of the monoethylglycinexylidide (MEGX) test to monitoring the long-term function of liver allografts. Methods:, MEGX production was measured prospectively in 60 consecutive liver transplant recipients undergoing their annual review. Results:, Median MEGX values in liver recipients (54 ng/mL; range 10,146) were lower than those found in healthy controls (78 ng/mL; range 44,118). MEGX values correlated negatively with alanine aminotransferase (ALT) activity (p = 0.004) and with the overall histological score (p = 0.01), and positively with sulfobromophthalein (BSP) and indocyanine green (ICG) clearances (p = 0.0002 and p = 0.002, respectively). A stepwise decline was observed with worsening liver fibrosis, from 71 ± 5 ,g/L in patients with no fibrosis to 27 ± 9 ,g/L in patients with bridging fibrosis (p = 0.002). BSP and ICG clearances correlated more closely than the MEGX test with the overall histological score (p = 0.001 and p = 0.001, respectively) and portal fibrosis (p = 0.002 and p = 0.001). Conclusions:, The measurement of MEGX formation is a simple and non-invasive method to monitor liver graft function. It may constitute a valuable tool for assessing the degree of fibrosis. [source] | ||||||||||||||||||||||