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Non-invasive markers of hepatic fibrosis in chronic Hepatitis B: A review  [cached]
Al-Mahtab Mamun,Rahman Salimur,Khan Mobin
Hepatitis B Annual , 2007,
Abstract: Assessment of fibrosis is important in chronic hepatitis B for a number of reasons including decision-making regarding treatment and predicting prognosis.Currently liver biopsy is considered the gold standard for assessing liver histology. However, since liver biopsy has significant limitations,the quest for a non-invasive alternative to assess hepatic fibrosis continues. A review of published literature reveals that extensive research has been carried out in this field, and several simple to complicated alternatives to liver biopsy for assessing hepatic fibrosis have been evaluated. A few have shown promise too, but we are still short of an ideal alternative to liver biopsy. Despite the fact that much has been done, we still have a long way to go before we can finally say farewell to liver biopsy.
Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B
Ghodrat Montazeri, Arezoo Estakhri, Mehdi Mohamadnejad, Negin Nouri, Farhad Montazeri, Ashraf Mohammadkani, Mohammad Derakhshan, Farhad Zamani, Shahram Samiee, Reza Malekzadeh
BMC Gastroenterology , 2005, DOI: 10.1186/1471-230x-5-32
Abstract: 28 healthy volunteers and 65 patients with HBeAg negative chronic hepatitis B were enrolled. Liver biopsies scored according to Ishak system. Association of serum hyaloronate with liver fibrosis and inflammation were assessed, and cut off points for serum hyaluronate levels were identified by receiver operating characteristics (ROC) curves and their values for prediction of fibrosis and inflammation were assessed.In patients with CHB serum hyaluronate had the most significant correlation and predictive values for the liver fibrosis and inflammation comparing to the other variables. At the cut off point of 126.4 ngm/ml it could discriminate extensive fibrosis from milder ones with sensitivity of 90.9% and specificity of 98.1%. With the same value it could discriminate extensive inflammation from their milder counterparts with sensitivity of 63.6% and specificity of 92.6%.Serum hyaluronate was the best predictor of extensive liver fibrosis and inflammation and it could discriminate subgroups of patients with chronic hepatitis B. It could be used as a non-invasive test to monitor these patients more closely with developing anti viral agents in clinical trials.HBV infection is a serious global health problem. Of the 2 billions people who have been infected with HBV, more than 350 millions are chronically infected world wide [1,2]. Chronic HBV infection is the major cause of end stage liver disease, 25% of them will die prematurely of liver cirrhosis or hepatocellular carcinoma [3]. It is crucial to monitor the course of this disease more closely, especially with developing antiviral agents in clinical trials [4]. Liver biopsy is currently considered the gold standard for evaluation of liver fibrosis [5]. However it has several limitations like sampling error, post biopsy pain and death [6-9]. It is expensive procedure and could be exceedingly dangerous in cases of advanced liver disease with prolonged prothrombin time and low platelet count [10]. Liver function tests ar
Assessment of portal venous index as a non-invasive method for diagnosing liver fibrosis in patients with chronic hepatitis C
Rocha, Haroldo Luis Oliva Gomes;Diniz, Angélica Lemos Debs;Borges, Valéria Ferreira de Almeida e;Salom?o, Frederico Chaves;
Arquivos de Gastroenterologia , 2012, DOI: 10.1590/S0004-28032012000100004
Abstract: context: hepatitis c is an important cause of chronic liver disease worldwide. the grading of hepatic fibrosis in chronic hepatitis c is important for better clinical management. however, until now, liver biopsy is the only test accepted for this purpose, despite their contraindications and complications. new methods for non-invasive assessment of hepatic fibrosis are under investigation. one proposal is the doppler ultrasound, as a non-invasive, widely available and inexpensive. objective: to compare doppler parameters of portal vein in patients with chronic hepatitis c with a healthy control group and to correlate these parameters with fibrosis degree obtained by liver biopsy. methods: fifty patients with chronic hepatitis c submitted to liver biopsy and 44 healthy controls had doppler of the portal vein performed, with the calculation of the portal venous index. we conducted a comparison between the averages of the two groups of portal venous index. for the correlation between portal venous index and fibrosis was employed the spearman test. results: there was a difference between the average portal venous index between controls (0.33 ± 0.07) and patients (0.23 ± 0.09) with p<0.001. no difference was observed between the portal venous index in patients with chronic hepatitis c who have significant fibrosis or not. the correlation between the portal venous index and fibrosis degree was reverse and moderate (r =-0.448 p<0.001). the area under the roc curve was 78.4% (95% ci: 68.8% to 88%). the cutoff for the portal venous index was 0.28 with sensitivity of 73.5% and specificity of 71.1%. conclusion: the portal venous index was useful in distinguishing healthy patients from patients with chc. however, there was no significant difference in the quantification of degree of fibrosis.
Apoptosis and progression of hepatic fibrosis in hepatitis C patients
Schinoni, Maria Isabel;Paraná, Raymundo;Cavalcante, Daniel;
Brazilian Journal of Infectious Diseases , 2006, DOI: 10.1590/S1413-86702006000200009
Abstract: hepatitis c is a worldwide endemic disease, affecting roughly 200 million people. it has a variable prognosis, depending on the progression to fibrosis. during the last five years, the importance of apoptosis for the pathogenesis of various diseases, including hepatitis, has been recognized. it has been suggested that an increase in t cell-apoptosis during a hepatitis c virus infection is the cause of impaired regulation of the immune cellular response, helping to maintain infection. thus, the interest in discovering the probable mechanisms by which the hepatitis c virus perpetuates in the liver, and to determine the conditions that predispose for progression of this disease, makes investigation of apoptosis in hepatic injury of great interest. we have made an overview of the various mechanisms by which the cell, more specifically the hepatic cell, is affected by apoptosis, and how it interacts with the hepatitis c virus and the immune system.
The combination of endoglin and FIB-4 increases the accuracy of detection of hepatic fibrosis in chronic hepatitis C patients  [PDF]
Dawlat Salem, Magdy El-Serafy, Eman Obeida, Wafaa Al-Akel, Maissa El-Raziki, Dina Attia, Mostafa Hassan
Open Journal of Gastroenterology (OJGas) , 2012, DOI: 10.4236/ojgas.2012.22013
Abstract: Background and aim: In patients infected with chronic hepatitis C virus, liver biopsy is the gold standard method of staging fibrosis. Different combinations of serum markers attempted to correlate with hepatic fibrosis in place of liver biopsy and have shown encouraging results. The aim of our study is to evaluate the diagnostic value of endoglin and FIB-4 as non-invasive markers of hepatic fibrosis in HCV patients. Methods: We estimated serum endoglin & FIB-4 index in 40 infected chronic hepatitis C patients. Histological staging of hepatic fibrosis was done according to the METAVIR scoring system. Results: Both endoglin and FIB-4 index showed positive correlation with age and aspartate transaminase and inverse correlation with albumin. The diagnostic performance determined by AUROCs for early fibrosis (≤F2), was 0.868 for endoglin and 0.887 for FIB-4, at cut off va- lues of 5.5 & 0.98 with sensitivity of 64.3% & 82.1%, and specificity of 100% & 85% respectively. For ad-vanced fibrosis (>F2), the AUROC was 0.98 for endoglin and 0.967 for FIB-4, obtained at cut off values of 6.29 & 1.6, with sensitivity of 100% & 91.7%, and specificity of 89.3% & 92.9%, respectively. Conclusion: Both serum endoglin and FIB-4 index are fairly accurate in differentiating stages of hepatic fibrosis; their combination in a single equation enhanced the accuracy of fibrosis detection in chronic HCV patients.
Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients
Morais, Clarice Neuenschwander Lins de;Carvalho, Bruno de Melo;Melo, Wlademir Gomes de;Melo, Fábio Lopes de;Lopes, Edmundo Pessoa de Almeida;Domingues, Ana Lúcia Coutinho;Jucá, Norma;Martins, Jo?o Roberto Maciel;Diniz, George Tadeu Nunes;Montenegro, Silvia Maria Lucena;
Memórias do Instituto Oswaldo Cruz , 2010, DOI: 10.1590/S0074-02762010000400018
Abstract: liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. the main objective of this study was to evaluate biological markers, such as cytokines il-13, ifn-γ, tnf-α and tgf-β, platelets, bilirubins (bil), alanine aminotransferase (alt) and aspartate aminotransferase (ast), total proteins, γ-glutamil transferase (γ-gt) and alkaline phosphatase (ap), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis c (hc) as isolated diseases or co-infections. the following patient groups were selected: hc (n = 39), hc/hepatosplenic schistosomiasis (hss) (n = 19), hss (n = 22) and a control group (n = 13). anova and roc curves were used for statistical analysis. p < 0.05 was considered significant. with hc patients we showed that tnf-α (p = 0.020) and ap (p = 0.005) could differentiate mild and severe fibrosis. with regard to necroinflammatory activity, ast (p = 0.002), γ-gt (p = 0.034) and ap (p = 0.001) were the best markers to differentiate mild and severe activity. in hc + hss patients, total bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. in conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in hc and hc + hss.
Effects of liver inflammation on FibroScan diagnosis of hepatic fibrosis in patients with chronic hepatitis B  [cached]
LIU Zhiquan
Journal of Clinical Hepatology , 2013,
Abstract: ObjectiveTo investigate the influence of liver inflammation on the ability of the FibroScan non-invasive elastrography scanner to diagnose hepatic fibrosis in patients with chronic hepatitis B (CHB). MethodsA total of 124 CHB patients who received liver biopsy and concomitant liver stiffness measurement (LSM) by FibroScan between June 2011 and February 2012 were enrolled in the study. The liver puncture biopsies were subjected to histological analysis to determine fibrosis stage (S1 to S4, mild fibrosis to severe fibrosis or cirrhosis) and inflammation grade (G1 to G4, low to high extent of inflammation). Differences between groups were assessed by Kruskal-Wallis H test or Mann-Whitney U test. The correlations between LSM and fibrosis stages and inflammation grades were evaluated by Spearman’s rank correlation coefficient. Results The progressive fibrosis stages were accompanied by increased inflammatory grades, such that the significant majority of S1 samples showed G1 inflammation (81.8%, n=55; P<0.01), of S2 showed G2 inflammation (54.2%, n=13; P<0.01), of S3 showed G3 inflammation (47.4%, n=9; P<0.05), and of S4 showed G3 and G4 inflammation (40.0%, n=6 and 334%, n=5; both P<0.01). LSM and inflammation grade were positively correlated within each fibrosis stage group (P<0.01), suggesting that the degree of liver inflammation affects the FibroScan measured value. ConclusionLiver inflammation influences LSM by FibroScan and may impact the ability of this technology to diagnose hepatic fibrosis, with more severe inflammatory activity affecting the LSM to a greater extent.
Non-Invasive markers for hepatic fibrosis
Ancha Baranova, Priyanka Lal, Aybike Birerdinc, Zobair M Younossi
BMC Gastroenterology , 2011, DOI: 10.1186/1471-230x-11-91
Abstract: Liver fibrosis is defined as the building up of excessive amount of extracellular matrix, also known as scar tissue, in the liver parenchyma. While reviewing fibrosis as a component of the pathogenesis of a disease, it is important to remember that the process of fibrogenesis is also a component of the normal healing response to various kinds of injury. In the liver, this healing process normally involves the recruitment of immune and/or inflammatory cells to the site of injury, secretion of extracellular matrix (ECM) proteins, reorganization of the ECM and possible regeneration of the hepatic tissue. When the damage to the liver is chronic, excess fibrous connective tissue accumulates. In time, this process eventually distorts the normal parenchymal structure of the liver and impairs its function. As chronic liver disease progresses, hepatic fibrosis is accompanied by the formation of septae and nodules that intervene with the portal blood flow, leading to hypertension and formation of distinctive cirrhotic architecture. At all stages of the fibrogenesis, the stress exerted on the liver parenchyma is exemplified by subsequent activation of the immune system accompanied by increased levels of certain cytokines and growth factors, which augment fibrogenesis. In proinflammatory fibrotic microenvironment, constant stimulation of hepatocellular regeneration could predispose to the development of hepatocellular carcinoma (HCC). However disruptive, hepatic fibrosis even early cirrhosis can be reversed by suppression of the fibrotic response [1,2].The most important cellular player in the production of the extracellular matrix is the myofibroblast (MF). A wide array of cells of different origins can be converted into fibrogenic MFs, including portal MFs and bone marrow-derived mesenchymal stem cells. Some epithelial cells including hepatocytes and biliary epithelial cells (cholangiocytes) could be activated to function as myofibroblasts through the process of Epithelial-Me
APRI is not a Useful Predictor of Fibrosis for Patients with Chronic Hepatitis B
amun- Al-Mahtab,Ananta Shrestha,Salimur Rahman,Mobin Khan
Hepatitis Monthly , 2009,
Abstract: Background and Aims: Liver biopsy remains the gold standard to assess hepatic fibrosis, including for those with chronic hepatitis B. The search for a novel, non-invasive alternative to liver biopsy to assess hepatic fibrosis continues. The serum aspartate-aminotransferase-to-platelet ratio index (APRI) has been shown to correlate with the degree of hepatic fibrosis in patients chronically infected with hepatitis C virus (CHC). The aim of this study was to investigate whether the same also applies in cases of chronic hepatitis B (CHB). .Methods: One hundred and eleven consecutive patients who tested positive for hepatitis B surface antigen (HBsAg) for more than 6 months in our unit from July 2006 to June 2007 were included in the study. For all of the patients, platelet count, aspartate aminotransferase (AST), hepatitis B e antigen (HBeAg) by enzyme-linked immunosorbent assay (ELISA), hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR), and percutaneous liver biopsy were tested for. APRI was calculated for every patient using the formula, AST x UNL x 100 / platelet count x 109/L. Patient characteristics, including APRI, were compared between those with a fibrosis ? 2 and those having a fibrosis < 2..Results: AST level was found to be higher in those with significant fibrosis (HAI-F > 2) and the proportion of HBeAg-positive patients was higher in those with a fibrosis 3 2 (39%) compared to those with a fibrosis < 2. Only 3 patients out of 111 had an APRI > 1.5 and all of them had a fibrosis < 2..Conclusions: Liver biopsy remains the gold standard for assessment of fibrosis in chronic hepatitis and cirrhosis related to Hepatitis B infection. AST level was seen to differ among two groups, but no difference was seen for platelet counts. Although APRI has been shown to have good predictive value for significant fibrosis in patients with chronic hepatitis C infection, it does not appear to be of use in predicting fibrosis in patients with chronic hepatitis B infection.
Hepatic steatosis in patients with HIV-Hepatitis C Virus coinfection: is it associated with antiretroviral therapy and more advanced hepatic fibrosis?
Sumita Verma, Robert D Goldin, Janice Main
BMC Research Notes , 2008, DOI: 10.1186/1756-0500-1-46
Abstract: HIV-HCV coinfected patients were retrospectively identified from the HIV clinic. ART was classified as none, nucleoside reverse transcriptase inhibitors (NRTIs) only, highly active antiretroviral therapy (HAART) only, and sequential therapy (initial NRTIs followed by HAART). Fibrosis stage and necroinflammation grade were assessed by the modified HAI (Ishak) scoring method. Steatosis was graded as 0–3.Sixty patients were identified. The overall prevalence of hepatic steatosis was 58%. Those that received HAART only had a lower prevalence of steatosis (41%) compared to those on NRTIs only (70%) or sequential therapy (82%). Independent predictors of hepatic steatosis were absence of HAART only therapy, OR 2.9, p = 0.09, and presence of cirrhosis, OR 4.6, p = 0.044. Forty five percent of the patients had advanced fibrosis (fibrosis stage ≥ 3). NI grade (OR 1.9, p = 0.030), and steatosis grade (OR 3.6, p = 0.045), were independent predictors of advanced fibrosis.Hepatic steatosis is associated with more advanced hepatic fibrosis in the HIV-HCV coinfected population. HAART only therapy (rather than NRTIs only or sequential therapy) appears to be associated with a lower prevalence of hepatic steatosis. This may be one of the mechanisms by which HAART could attenuate hepatic fibrosis in such a cohort.Highly active antiretroviral therapy (HAART) has significantly improved survival in patients with human immunodeficiency virus (HIV) infection [1]. Increasing attention is now being focused on co infection with other viruses like hepatitis C (HCV). Because of similar routes of transmission, approximately 25–30% of patients with HIV are also coinfected with HCV [2]. Factors associated with more advanced hepatic fibrosis in HCV infection include HIV coinfection [3] and hepatic steatosis, (prevalence of 47%–79%) [4-6].Patients with HIV are also at increased risk of developing hepatic steatosis due to multiple factors including antiretroviral therapy (ART), obesity, hyperglycemia,
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